POSTGRADUATE PSYCHIATRY:
Clinical and Scientific Foundations
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POSTGRADUATE PSYCHIATRY:
Clinical and Scientific Foundations Second edition Edited by Louis Appleby MD FRCP FRCPsych Professor of Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, UK David M. Forshaw MB ChB MRCPsych DHMSA DPMSA Consultant in Forensic and Addiction Psychiatry, Forensic Addictive Behaviour Unit, Broadmoor Hospital, Crowthorne, UK Tim Amos MA(Oxon) MSc MB BS MRCPsych DPMSA Clinical Research Fellow, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, UK Helen Barker MB ChB MRCPsych Specialist Registrar in Psychotherapy, Manchester Royal Infirmary, Manchester, UK
A member of the Hodder Headline Group LONDON Co-published in the United States of America by Oxford University Press Inc., New York
First published in Great Britain in 1990 Second edition published in 2001 by Arnold, a member of the Hodder Headline Group, 338 Euston Road, London NW1 3BH
http://www.arnoldpublishers.com Co-published in the USA by Oxford University Press Inc., 198 Madison Avenue, New York, NY10016 Oxford is a registered trademark of Oxford University Press © 2001 Arnold All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronically or mechanically, including photocopying, recording or any information storage or retrieval system, without either prior permission in writing from the publisher or a licence permitting restricted copying. In the United Kingdom such licences are issued by the Copyright Licensing Agency: 90 Tottenham Court Road, London W1P OLP. Whilst the advice and information in this book are believed to be true and accurate at the date of going to press, neither the authors nor the publisher can accept any legal responsibility or liability for any errors or omissions that may be made. In particular (but without limiting the generality of the preceding disclaimer) every effort has been made to check drug dosages; however, it is still possible that errors have been missed. Furthermore, dosage schedules are constantly being revised and new side-effects recognized. For these reasons the reader is strongly urged to consult the drug companies' printed instructions before administering any of the drugs recommended in this book. British Library Cataloguing in Publication Data
A catalogue record for this book is available from the British Library Library of Congress Cataloging-in-Publication Data
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Contents
List of contributors Foreword Preface to the first edition Preface to the second edition
Part One 1 Psychopathology Helen Barker and Elspeth Guthrie 2 Clinical assessment Elizabeth Walsh and Thomas Fahy 3 Psychology and human development Helen Barker and Anthony Maden 4 Psychopharmacology Ian Anderson and Christopher Mortimore Part Two A 5 Neuroscience Eileen Joyce 6 Neurochemistry Robert Kerwin 7 Genetics Michael Owen and Kieran Murphy 8 Epidemiology, research methods and statistics Hollie Thomas and Glyn Lewis Part Two B 9 Schizophrenia Jane Shapleske and Anthony David 10 Affective disorders Simon Wessely and Anthony Cleare
vii xii xiv xv
1 3 29 40 60 81 83 119 136 145 167 169 186
vi 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27
Contents Neurotic and stress-related disorders Richard Gater and Richard Morgan Organic Psychiatry Maria Clarke and Simon Fleminger Epilepsy and the EEG in psychiatry Paul Chesterman Old-age psychiatry Alice Seabourne and Alistair Burns Personality disorders Kingsley Norton and Jonathan Vince Alcohol misuse Adam Winstock and Michael Farrell Substance misuse Adam Winstock and Andrew Johns Suicide and deliberate self-harm Tim Amos and Louis Appleby Eating disorders Frances Connan and Janet Treasure Postpartum and related disorders Mary Rowsell and Louis Appleby Sexual disorders Sue Smith and Alain Gregoire Disorders of childhood and adolescence Jane Whittaker and Richard Harrington Learning disability Robert Goodman and Therese Van Amelsvoort General hospital (liaison) psychiatry Chris Dickens and Francis Creed Social and community psychiatry Shailesh Kumar and Graham Thornicroft Transcultural psychiatry Cathy Shaw and Steven Reid Forensic psychiatry Tracey Heads and David Forshaw
209
231 267 284
302 313 331 347 358
370 382 396 424 436 451
469 477
Part Three 28 Psychological methods of treatment Nigel Pearson and Ulrike Schmidt 29 Pharmacological treatments in psychiatry Richard Drake and Shon Lewis 30 Physical methods of treatment Paul Cotter and Michael Philpot
505
Appendix
562
Index
The MRCPsych examination Tim Amos and Helen Barker
507 527 550
571
List of contributors
Tim Amos MA(Oxon) MSc MB BS MRCPsych DPMSA Clinical Research Fellow, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, Manchester Ian Anderson BA MB BS MA MRCP MRCPsych MD Senior Lecturer and Honorary Consultant Psychiatrist, School of Psychiatry and Behavioural Sciences, University of Manchester, Manchester Royal Infirmary, Manchester Louis Appleby MD FRCP FRCPsych Professor, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, Manchester Helen Barker MB ChB MRCPsych Specialist Registrar in Psychotherapy, Manchester Royal Infirmary, Manchester Alistair Burns MRCP DHMSA MRCPsych MPhil Professor of Old Age Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, Manchester Paul Chesterman MB BS BSc MRCP MRCPsych WLHCT Consultant Forensic Psychiatrist, North West Thames Forensic Psychiatry Service, Southhall, Middlesex Maria Clarke MB ChB MRCPsych MRCGP Specialist Registrar, Maudsley Hospital, London Anthony Cleare BSc MB BS MRCPsych Senior Clinical Research Fellow and Honorary Lecturer, Department of Psychological Medicine, King's College School of Medicine and Dentistry and The Institute of Psychiatry, London Frances Connan BSc(Hons) MB BS MRC Clinical Teaching Fellowship, Institute of Psychiatry, London
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List of contributors
Paul Cotter MB MRCP MRCPsych Consultant in General Psychiatry, Daisy Hill Hospital, Newry, Country Down Francis Creed MD FRCP FRCPsych Professor of Psychological Medicine, School of Psychiatry and Behavioural Sciences, University of Manchester, Manchester Royal Infirmary, Manchester Anthony David MD MSc FRCP MRCPsych Professor of Cognitive Neuropsychiatry, Institute of Psychiatry, London Chris Dickens MB BS MSc PhD MRCP MRCPsych Lecturer in Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Manchester Royal Infirmary, Manchester Richard Drake BSc MB ChB MRCPsych Clinical Research Fellow, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, Manchester Thomas Fahy MD MPhil MRCPsych Consultant Psychiatrist, Maudsley Hospital, London Michael Farrell MRCP MRCPsych Consultant Psychiatrist, Maudsley Hospital, London Simon Fleminger PhD MRCP MRCPsych Consultant Neuropsychiatrist, Maudsley Hospital, London David Forshaw MB ChB MRCPsych DHMSA DPMSA Consultant in Forensic and Addiction Psychiatry, Forensic Addictive Behaviour Unit, Broadmoor Hospital, Crowthorne Richard Gater MB ChB MRCPsych MSc MD Senior Lecturer and Honorary Consultant Psychiatrist, School of Psychiatry and Behavioural Sciences, University of Manchester, Manchester Royal Infirmary, Manchester Robert Goodman PhD FRCPsych MRCP Professor of Brain and Behavioural Medicine, Department of Child Psychiatry, Institute of Psychiatry, London Alain Gregoire DRCOG MRCPsych Consultant and Honorary Senior Lecturer in Psychiatry, The Old Manor Hospital, Salisbury Elspeth Guthrie MB ChB MRCPsych MSc MD Senior Lecturer in Liaison Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Royal Infirmary, Manchester
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Richard Harrington MB ChB FRCPsych MPhil MD Professor of Child and Adolescent Psychiatry, Honorary Consultant Child and Adolescent Psychiatrist, University of Manchester, Royal Manchester Children's Hospital, Manchester Tracey Heads MB ChB MD MRCPsych DFP Clinical Lecturer in Forensic Psychiatry, Institute of Psychiatry, London Andrew Johns BSc MB BS FRCPsych DFP Senior Lecturer and Honorary Consultant Psychiatrist, Broadmoor Hospital, Berkshire
Shailesh Kumar Senior Registrar in Psychiatry, King's College and Institute of Psychiatry, London Eileen Joyce MA PhD MRCP MRCPsych Senior Lecturer and Honorary Consultant Psychiatrist, Community Mental Health Team, Queen Mary's University Hospital, London Robert Kerwin MA PhD MB BChir DSc FRCPsych Professor of Clinical Neuropharmacology and Consultant Psychiatrist, Institute of Psychiatry, London Glyn Lewis PhD FRCPsych Professor of Community and Epidemiological Psychiatry, Division of Psychological Medicine, University of Wales College of Medicine, Cardiff Shon Lewis MA MSc FRCPsych Professor of Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, Manchester Anthony Maden BSc MRCPsych Senior Lecturer in Forensic Psychiatry, Institute of Psychiatry, London Richard Morgan MB ChB MRCP MRCPsych Senior Registar in Psychiatry, Manchester Royal Infirmary, Manchester Christopher Mortimore MA MB BChir MRCPsych Lecturer in Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Manchester Royal Infirmary, Manchester Kieran Murphy MRCPI MRCPsych MMedSci MRC Training Fellow, Neuropsychiatric Genetics Unit, University of Wales College of Medicine, Cardiff Kingsley Norton MA (Cantab) MD FRCPsych Clinical Director, Henderson Hospital, Sutton; Honorary Senior Lecturer, Forensic Section, Department of Mental Health Sciences, St George's Hospital Medical School, London
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List of contributors
Michael Owen PhD FRCPsych Professor of Psychological Medicine, University of Wales College of Medicine, Cardiff Nigel Pearson BA(Oxon) MB BS MRCP MRCPsych Specialist Registrar in General Adult Psychiatry, Maudsley Hospital, London Michael Philpot BSc MB BS FRCPsych Consultant in Old Age Psychiatry, Maudsley Hospital, London Steven Reid MRCPsych Senior Registrar in Psychiatry, Department of Psychological Medicine, King's College and Institute of Psychiatry, London Mary Rowsell MB ChB MRCPsych Specialist Registrar in Child and Adolescent Psychiatry, Royal Manchester Children's Hospital, Manchester Ulrike Schmidt PhD MRCPsych Consultant Psychiatrist, Maudsley Hospital, London Alice Seabourne MB ChB MRCPsych Senior Registrar in Old Age Psychiatry, School of Psychiatry and Behavioural Sciences, University of Manchester, Withington Hospital, Manchester Jane Shapleske MB ChB MRCPsych Honorary Lecturer, Institute of Psychiatry, London Cathy Shaw BA MSc MB BChir PhD MRCPsych Consultant Psychiatrist, Department of Mental Health, Tameside General Hospital, Ashton-under-Lyne Sue Smith MB BCh MRCPsych Senior Registrar in Psychiatry, Old Manor Hospital, Salisbury Hollie Thomas BSc DPhil Lecturer in Epidemiology, Division of Psychological Medicine, University of Wales College of Medicine, Cardiff Graham Thornicroft MA MSc(Epidem) MRCPsych PhD MFacPHM Professor of Community Psychiatry, King's College and Institute of Psychiatry, London Janet Treasure PhD FRCP FRCPsych Professor of Psychiatry, Maudsley Hospital, London Therese Van Amelsvoort MRCPsych Clinical Research Worker, Department of Psychological Medicine, Institute of Psychiatry, London
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Jonathan Vince MRCPsych Senior Registrar in Forensic Psychiatry, Shaftesbury Clinic, Springfield Hospital, Surrey Elizabeth Walsh MSc MRCPsych Wellcome Training Fellow, Division of Psychological Medicine, Institute of Psychiatry, London Simon Wessely MA MSc MD FRCP MRCPsych Academic Department of Psychological Medicine, King's College School of Medicine, Institute of Psychiatry, London Jane Whittaker BSc(Hons) MB ChB MRCPsych MSc Clinical Tutor and Honorary Senior Registrar, University Department of Child and Adolescent Psychiatry, University of Manchester, Royal Manchester Children's Hospital, Manchester Adam Winstock MRCP MRCPsych Clinical Lecturer in the Addictions, Institute of Psychiatry, London
Foreword
The study of mental disorders has been transformed since I qualified as a doctor over 40 years ago. At that time, we had descriptive psychopharmacology, and clinical know-how, but very few effective treatments. Much theoretical thinking was dominated by 'dynamic' concepts, which had a very poor evidence base and led to prolonged and largely ineffective treatments for those who could afford them. Today's young psychiatrist is expected to know a good deal more than we were. There are now highly effective pharmacological and psychological treatments of proven efficacy. These each necessitate a detailed knowledge of their theoretical underpinnings, and a clear statement of how they work. Our understanding of central neurotransmission, once pretty rudimentary, is now very much better, although there are still central problems which remain to be elucidated concerning the biological basis of both schizophrenia and depression. On the psychological front, cognitive behaviour therapy has extended the theoretical base of behaviour therapy, and is now applied to a wide range of mental disorders, both psychotic and non-psychotic. Behaviour therapy is a highly effective intervention in obsessional disorders, which were usually treated as a sort of damage limitation exercise in my early days. Sexual disorders are now not only better treated, but are very much better understood than they once were. Problem solving, family interventions and interpersonal psychotherapy are all effective tools in managing common mental disorders, and seem likely to displace 'dynamic' therapies in the coming century. These improved methods of management have been accompanied by an impressive development in the basic sciences and health technologies that are necessary to improve our understanding of the aetiology of mental disorders. Molecular genetics, brain imaging and advances in neurochemistry have all made enormous strides in recent years, and these topics are well covered in the book which follows. Techniques of
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investigation in social sciences and epidemiology have also advanced greatly since the days of my basic training, and these changes are also well covered here. If these are some aspects of a changed world, many of the things which clinicians had to know in the past, they still have to know today. The world of descriptive psychopathology, and the clinical descriptions of the many syndromes of mental disorder, may be superseded in the next century, but have not been superseded yet. They are all well covered in the present volume. Individual readers will each have their especial interests in what follows, and may be expected to read much more widely in these areas; but this book provides mental health workers with a basic knowledge covering a wide field. The book finishes with a really useful chapter on the MRCPsych Examination, which contains much excellent advice. Most importantly, a rapidly expanding field is well covered, and the reader can be assured of having information which is as up to date as one could hope for in a textbook. This book also marks the continued relationship between the Manchester Department of Psychiatry and Behavioural Science and the Maudsley Hospitals, which is as good an example of symbiosis as any that I know. Having made the journey from Maudsley to Manchester, and then back again, this has very special significance for me. Sir David Goldberg Professor Emeritus Institute of Psychiatry King's College, London
Preface to the first edition
The motivation behind this book came from two sources. First, there was the frequent complaint from postgraduate trainees in psychiatry that they needed a text which could provide a comprehensive account of the fundamentals of clinical and basic sciences while remaining concise enough to use for revision. Second, the postgraduate examinations of the Royal College of Psychiatrists and the Institute of Psychiatry were changed in 1987, which left many candidates uncertain as to what to study for each part of each examination. At the planning stage of this book it became clear that it was not only the exam candidate who needed a concise text. Such a book would also be useful to practising clinicians and teachers at any level of seniority. This book is, we hope, a concise and up-to-date text of psychiatric practice and related science topics. At the time of writing the book, each contributor was a member of the junior medical staff at the Maudsley Hospital, the Bethlem Royal Hospital or the Institute of Psychiatry. Some have moved on since then and their current posts are listed. We would particularly like to thank the following for their advice on individual chapters: Professor Griffith Edwards, Dr Gisli Gudjonnson, Dr Channi Kumar, Dr Colin Binnie, Professor Alywn Lishman, Dr Graham Robertson, Dr Janet Treasure and Dr Pauline Taylor. We would also like to thank Miss Joanne Crawford, who typed early drafts of some of the chapters. Louis Appleby and David M. Forshaw, 1989
Preface to the second edition
The practising clinician and the examination candidate both need information which is broad-ranging and concise, clinically and academically up-to-date, yet not skewed by individual opinion. With this ideal in mind, the content and contributors were selected. Each chapter has a senior author who is prominent in the subject and most chapters have a more junior who has taken the exam in the recent past. The structure of the book follows that of the MRCPsych examination. Chapters correspond to subjects specified as examinable by the Royal College of Psychiatrists, and the book's organization into Parts One to Three is intended to aid study. Part 1 of the MRCPsych examines the subjects described in Part One of the book: psychopathology, clinical assessment, psychopharmacology, psychology and human development. A knowledge of treatment is also required by Part 1 of the exam, although it does not demand a detailed understanding of clinical case management. For this reason we have included an additional treatment section to the book (Part Three), which should provide candidates for Parts 1 and 2 of the examination with the information on therapeutics. Practical case management of an individual disorder is outlined in the relevant chapter. Another area of overlap between the parts of the new examination is in clinical knowledge, in that basic knowledge of clinical syndromes and aetiology is tested in Part 1. Candidates for this exam should therefore read the clinical features and aetiology sections in the clinical chapters in Part Two B of the book, excluding those clinical sub-specialties which are not examined in Part 1 (Chapters 25-30). Part of the MRCPsych covers the basic sciences (Part Two A of the book) and clinical psychiatry (Parts Two B and Three of the book). Inevitably—in fact, intentionally—there are areas of overlap between the chapters, e.g., psychopharmacology with pharmacological treatments, and basic science chapters with the aetiology sections of clinical
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chapters. We hope these show where individual topics fit together and do not appear repetitive. The Appendix outlines the structure of the MRCPsych examination and makes suggestions on examination technique. We would like to thank Dr Eileen McGinley and Professor Conor Duggan who contributed to the first edition and have been kind enough to allow us to use some of their work in this edition. We would also like to thank Mrs Carol Rayegan for her assistance throughout the production of this book.
PART ONE
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1 Psychopathology HELEN BARKER and ELSPETH GUTHRIE
Psychopathology is the study of abnormal states of mind. It may be divided into descriptive and dynamic psychopathology. Both approaches involve the patient's description of mental experiences and the doctor's observation of and interaction with the patient. Descriptive psychopathology is confined to the definition and classification of psychic phenomena. In contrast, dynamic psychopathology seeks to provide explanations for the structure of the mind, personality development and symptom formation.
Descriptive psychopathology Descriptive psychopathology refers to the systematic study of abnormal behaviour and mental experiences without reference to any theoretical models of causation. Essentially it is a description of the symptoms and signs which may be associated with psychiatric disorders. Phenomenology, based on the philosophy of Edmund Husserl and Karl Jaspers, is an attempt to understand another person's state of mind and subjective experiences using empathy. There has been widespread disagreement concerning the precise definitions of many concepts. Over the past 30 years, several instruments have been developed to provide a more formal, internationally agreed method of assessing and classifying the psychopathology associated with the major psychiatric disorders, e.g. the Schedules for Clinical Assessment in Neuropsychiatry (SCAN). Disorders of movement and posture Mannerisms Mannerism are repeated, usually odd, goal-directed movements (e.g. eating, walking) or unusual postures. Verbal mannerisms are repeated
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odd uses of language not amounting to thought disorder. Mannerisms may be seen in schizophrenia, learning disability and in some normal individuals.
Stereotypies Stereotypies are repeated, non goal-directed movements (e.g. head banging, rocking). They can occur in schizophrenia and learning disability. Schnauzkrampf is a stereotypy seen in catatonia in which the lips are thrust forward like an animal's snout. Myoclonus
Myoclonus is a sudden shock-like movement of a muscle or muscle part seen in myoclonic epilepsy, Creutzfeldt-Jakob disease and in some normal individuals, especially during sleep. Tics Tics are repetitive, coordinated movements of small groups of muscles, occurring in organic disorders (e.g. encephalitis, Huntington's disease), emotional disorders (especially in childhood) and specific conditions such as Tourette's syndrome. Tremor
A tremor is a rhythmic, repetitive movement caused by alternating contractions of antagonist muscle groups. The fine tremor of anxiety or hyperthyroidism may be distinguished from the coarser tremors of alcohol withdrawal, lithium toxicity or cerebellar disorders. Intention tremors are seen in cerebellar lesions, whereas in Parkinsonism the tremor is worse at rest.
Spasmodic torticollis A spasm of the neck muscles pulls the head towards one side and twists the face in the opposite direction. Spasm usually lasts for a few minutes but may persist, with permanent disfigurement.
Chorea Chorea is the semipurposive, non-repetitive jerking movement of the muscle groups of the face, limbs or trunk. Athetosis
Athetosis is a slow writhing movement which is most marked peripherally.
Catatonia Catatonia is the collective term for the motor abnormalities classically seen in catatonic schizophrenia, although they may also be observed in
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dementia, learning disabilities and other organic brain disorders. In catatonia, bizarre, manneristic postures may be maintained for long periods and waxy flexibility (flexibilitas cerea or catalepsy) may be detected on passive movement of the patient's limbs. In automatic obedience the patient displays excessive compliance to commands. An apparently motiveless refusal to obey commands is termed negativism. When negativism alternates with automatic obedience this is known as ambitendency. Similar patterns of cooperation and opposition can be observed in the passive movement of the patient's limbs. In mitgehen the body can be moved into any position by the examiner. This occurs despite instructions to the patient to resist this movement. In gegenhalten there is active opposition to this passive movement and the patient's limbs cannot be moved by the examiner despite requests for cooperation. Echopraxia occurs when the patient automatically imitates the examiner's posture. Similar repetition phenomena may be observed in the patient's speech: echolalia is the repetition of a phrase or sentence; palilalia is the repetition of a word and logoclonia is the repetition of syllables only. Disorders of emotions An emotion is the positive or negative subjective reaction to an experience. A feeling is often used synonymously with emotion, but it also includes the notions of somatic sensations and personal convictions concerning the experience. An emotion is a transitory state, whereas mood describes the emotional state prevailing over a longer time period. Alexithymia is an impairment of the capacity to identify or verbalize subjective emotions. The examination of a patient's emotional state involves the psychiatrist's objective observation of facial expression, tone of voice, gesture and posture as well as the patient's subjective account. The overall observation of the doctor is usually termed affect.
Abnormal emotional states Abnormal emotional states are sometimes difficult to distinguish from normal states. Normal mood tends to show modulations or responsiveness to the external circumstances. Abnormal mood tends to be more pervasive and is often associated with other symptoms.
Depressed mood This is a feeling of misery or morbid sadness often associated with negative or self-critical preoccupations. There may be an inability to feel pleasure (anhedonia) and a loss of normal interests. Disturbances of sleep, appetite and concentration may occur. Depressed mood occurs in depressive disorders, dysthymia, organic states, schizophrenia and
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(briefly) in manic episodes. It may be considered normal following severe stress such as bereavement, unless it is prolonged, excessive or associated with other symptoms. Elation Elation is an elevation of mood which often has an infectious quality. In hypomanic states elation is commonly associated with overactivity, disinhibition and faulty judgement. The elation of hypomania may be interspersed with periods of irritability, labile and depressed mood. Elation also occurs in schizophrenia and organic states, such as frontal lobe disorders, hypothalamic lesions and general paralysis of the insane. Ecstasy is a state of elevated mood and extreme well-being which is usually kept private and lacks the infectious quality of elation. Anxiety Anxiety is a feeling of fear with no adequate cause. It is often associated with feelings of panic, dread, irritability and anxious anticipation. Commonly, there are somatic and autonomic symptoms such as sweating, tremor, palpitations and muscular tension. In free-floating anxiety the patient does not identify a particular object or situation as responsible. By contrast, phobias are recurrent, intrusive fears of specific objects or situations, often leading to avoidance. They are recognized by the patient as being irrational and the fear is out of proportion to any objective danger. Anxiety may occur in organic states, schizophrenia, affective disorders and in normal people under extreme stress as well as in the neurotic disorders. Perplexity Perplexity is an unpleasant emotional state of puzzled bewilderment. It can be observed in organic states and early schizophrenia. Apathy Apathy is a total absence of feeling, often associated with loss of drive and motivation. The patient is aware of the absence. This distinguishes apathy from alexithymia in which the patient is unaware of emotions. Blunted and flattened affect Blunted affect is a reduction in the usual modulation of emotions which is characteristically seen in chronic schizophrenia. Flattened affect is sometimes used to refer to depressed affect. Incongruous affect Incongruous affect is an emotional response which is inappropriate to the external events and not understandable to the observer. It is seen in schizophrenia.
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Emotional lability Emotional lability is the presence of rapid and excessive fluctuations of emotion seen in organic disorders, hypomania and some personality disorders. Emotional incontinence is an extreme form of lability when there is complete loss of emotional control. Cyclothymia refers to much slower and more persistent swings of mood between sadness and happiness. Disorders of thought and speech Abnormalities of thought and speech are considered together as there is considerable overlap between the two processes.
Disorders of thought content Delusion A delusion is a fixed, usually false belief which is held for the wrong reason. It is unshakeable and not modified by experience or counterargument. It is out of keeping with the patient's social and cultural norms. The content is often bizarre and infused with a sense of great personal significance. Delusions can occur in a wide range of organic disorders, schizophrenia, delusional disorders and affective disorders. Overvalued idea An overvalued idea is an understandable idea which is pursued by the patient beyond the bounds of reason but which lacks the unshakeable quality of a delusion. It often comes to dominate the individual's life and is associated with marked emotional investment. The presence of overvalued ideas is not necessarily indicative of illness, although they do commonly occur in eating disorders, somatoform disorders and psychosexual disorders. Types of delusions Delusional states can be classified according to their form (primary or secondary) or their content (persecutory, grandiose, etc.). Primary delusions arise fully formed without a preceding abnormal psychological event. They are autochthonous, that is they arise without external cause. Karl Jaspers noted the central importance of the ununderstandable in primary delusions. They may be further divided into sudden delusional ideas and delusional perception, both of which may develop from a delusional mood. A delusional perception is a two-stage process which occurs when a delusional meaning is attached to a normal perception with which it has no logical connection. A sudden delusional idea is the occurrence of a fully-formed delusion as in delusional perception but without the preceding perceptual experience. In delusional mood the patient feels that the environment has changed in an
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inexplicable, usually unpleasant and self-referential way. A delusional perception or delusional idea may then emerge after a period of days or weeks. Consequently, delusional mood is often only identified retrospectively, after the emergence of further abnormal phenomena. Secondary delusions arise from some other morbid process, e.g. from hallucinations, abnormal mood, abnormal personality or from primary delusions. Secondary delusions arising in affective disorders are usually mood congruent. Kretschmer described a particular type of secondary delusion (Sensitiver Beziehungswahn) which arises from a sensitive premorbid personality. In these patients sensitive ideas of reference become delusions following a disturbing, key experience. Delusions may be further classified according to their content, e.g. grandiose, nihilistic, hypochondriacal, religious. Delusions of reference are beliefs that remarks, events or objects have a personal, self-referential significance. These must be differentiated from simple ideas of reference which are found in many disorders as well as in abnormal personalities and normal people, particularly when under stress. Persecutory delusions are commonly beliefs that a person or organization is trying to inflict harm on the patient. They are often also known as paranoid delusions but, strictly speaking, paranoid means 'referring to the self and the term, therefore, encompasses many concepts in addition to persecutory. Delusions of control are also commonly part of passivity phenomena in which there is an experience of being under external control. This may apply to movements (motor passivity, made acts), sensations (somatic passivity, made sensations) or feelings (emotional passivity, made emotions). Passivity phenomena are often referred to as delusions of control, although strictly they are experiences which are explained in a delusional way. They are highly suggestive of schizophrenia. Other delusional states Delusions may arise singly or they may accumulate from a complex delusional system. Delusions may be held by one person or shared by another, usually someone of a suggestible nature who is in close contact with the patient. This is known as folie a deux. Delusional misidentification These are rare delusional syndromes which occur in schizophrenia and organic disorders. In the Capgras syndrome, the patient has the delusion that a close friend or relative has been replaced by a double or imposter. In the Fregoli syndrome, the patient believes that strangers are familiar people, often a persecutor, in disguise. The delusion that several familiar people have exchanged identities is known as intermetamorphosis. The delusion that the patient has a double occurs in the syndrome of subjective doubles.
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Preoccupations
Preoccupations are recurrent themes in thought content which are likely to be reflected in the content of speech. Many normal people have preoccupations which are appropriate to their circumstances. If themes become repetitive, unpleasant and are less dependent upon external circumstances, they are termed ruminations. These occur commonly in depressive disorders, anxiety disorders and obsessive-compulsive disorder. Obsessional thoughts
Obsessional thoughts are the persistent and recurrent intrusion into consciousness of unwanted and distressing ideas, images, impulses or doubts. They are seen as senseless and are usually resisted, although they are recognized as originating from within the individual (as opposed to passivity phenomena which are experienced as arising externally).
Disorders of the form of thought The term thought disorder refers to abnormalities of the process of thinking and the expression of thoughts in speech. Although it is the form of thought which is being examined, it is usual to include this under the heading of speech in the mental state examination. Formal thought disorder
Most authorities on thought disorder have recognized the same abnormalities but have used different terms to describe them. Formal thought disorder is highly suggestive of schizophrenia. Eugene Bleuler emphasized the lack of connection between the associations of ideas as the central abnormality in schizophrenia. This loosening of associations is greater than that commonly observed in hypomania and speech may become incomprehensible. Bleuler identified some underlying psychological processes, derived from Freud, which he believed contributed to the thought disorder: condensation, in which two associated ideas merge to form a false concept; displacement, in which an associated idea is wrongly used in place of a correct idea; and the misuse of symbols, in which only the concrete rather than the symbolic meaning of a symbol is used. Goldstein identified concrete thinking which is an impairment of abstract or symbolic thought. Cameron introduced the terms asyndesis, metonyms, overinclusivity and interpenetration of thoughts. Asyndesis is the lack of adequate connections between successive thoughts. Metonyms are personal idioms and imprecise expressions. In overinclusivity there is a lack of organized thinking with an inability to distinguish central themes from
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peripheral information. Interpenetration of thoughts occurs when the patient's attempt to consider one topic is confused by other themes. Carl Schneider described fusion, omission, derailment, substitution and drivelling. In fusion, separate thoughts are interwoven. In omission, major parts of a thought are simply missed out. Derailment refers to the shifting from one train of thought to another without connection. Substitution denotes the replacement of a thought by another, unconnected thought. Drivelling is the mixing of constituent parts of a complex thought. Schneider argued that healthy thinking has the properties of constancy, organization and continuity. In schizophrenic formal thought disorder each of these is disrupted, resulting in transitory thinking, drivelling and desultory thinking respectively. The term knight's move thinking approximates to the concepts of derailment and substitution. One thought is derailed and replaced by another with which it has no logical relationship. When this abnormality is extreme and the grammatical structure of speech is disrupted as well as the ideas expressed, it is called word salad. The term verbigeration refers to a senseless repetition of sounds, words or phrases. Neologisms are new words, distortions of other words or idiosyncratic uses of real words or word combinations.
Disorders of thought possession (thought alienation) These phenomena are disturbances of the experience of personal possession of thinking. They are experiences, not delusions, although delusional elaboration commonly occurs with each experience. They characteristically occur in schizophrenia. Thought insertion Thought insertion is the experience of having thoughts inserted into the mind, recognized as foreign and coming from outside. Thought withdrawal Thoughts suddenly disappear so that the patient's experience is that they have been removed by an outside influence. Thought broadcasting This is a passive process in which thoughts are made available to others by diffusing out of the confines of personal thinking. A comment that people can read the patient's thoughts is not in itself evidence of thought broadcasting.
Disorders of the stream of thought and speech Thought block Thought block is the experience of sudden interruption to the train of thoughts, leaving a mental blank before thoughts continue, often in a
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different direction. The patient describes thoughts stopping or drying up, but the experience is quite unlike an anxious patient losing the thread of his or her thoughts. It may be observed at interview. It occurs in schizophrenia. Persevemtion Perseveration is the repetition of an idea, thought, word or phrase beyond the point of relevance. For example, having given an appropriate answer, the patient may persist with the same response to unrelated questions. It occurs in organic disorders, notably frontal lobe lesions, but can occur in schizophrenia. Acceleration of thought There is an increase in the rate of thinking which manifests itself in speech as pressure of speech. A rapid succession of thoughts is known as flight of ideas. These ideas may have a tenuous logical connection or may be linked by alliteration, puns or clang associations. This is characteristic of hypomanic states but may be observed in organic disorders and schizophrenia. Retardation of thought There is a slowing of thinking, often accompanied by poverty of thought, poor concentration and poor memory. It is commonly observed in depression in association with motor slowing. It is said to occur rarely in a manic stupor. Thinking may also be slowed down by inclusion of trivial details. This is known as circumstantiality and occurs in many normal individuals as well as in the putative 'epileptic personality' (characterized by humourless sobriety, circumstantiality and religiosity). Talking past the point This is when a patient answers a question with a remark inappropriate to the actual question and obviously incorrect, but appropriate to the topic, thereby indicating an understanding of the question (e.g. 'A dog has five legs.'). It is also known as vorbeireden or approximate answers and it is traditionally said to occur in Ganser's syndrome. Disorders of the production of speech Disorders of speech produced by mechanical disorder of the anatomical structures necessary for the articulation of speech are called dysarthrias. Disorders of the understanding or expression of speech caused by focal neurological lesions are called dysphasias. Mutism is a total absence of speech. It can occur in organic disorders, schizophrenia, affective disorders and dissociative disorders. Elective
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mutism usually occurs in children and is characterized by an absence of speech in specific situations only. Disorders of perception These are commonly divided into sensory deceptions (illusions and hallucinations) and sensory distortions.
Illusions Illusions are misperceptions of stimuli. They are more likely to occur when the general level of sensory stimulation is reduced. The so-called illusion of doubles or Capgras syndrome is not an illusion but a form of delusional misidentification. Eidetic images are very vivid mental images. Pareidolia is the vivid perception of visual images in response to an indistinct stimulus, e.g. images in a coal fire.
Hallucinations A hallucination is a normal perception without an external stimulus. Hallucinations are perceived as having the same qualities as normal perceptions and they are located in the external world. They are classified according to their sensory modality and may be elementary or complex: e.g. auditory hallucinations may take the form of simple noises, such as banging or hissing, or may be complex in the form of voices. Hallucinations occur in many disorders, including organic disorders, schizophrenia and affective disorders, although they may rarely occur in normal people. The content tends to be related to the nature of the disorder, e.g. persecutory auditory hallucinations in schizophrenia or grandiose auditory hallucinations in hypomania. Auditory hallucinations These are commonly voices speaking to the patient or about the patient. These are described as second-person and third-person auditory hallucinations respectively. Third-person hallucinations are usually of two types: voices describing and commenting on the patient's actions (running commentary) and voices discussing or arguing about him or her. Sometimes a patient hears thoughts being spoken out loud, either as he or she is thinking them (Gedankenlautwerden) or with a slight delay (thought echo or echo de la pensee). Visual hallucinations These may occur in many disorders but are most strongly associated with acute organic disorders. In delirium tremens the patient sees miniature figures which are termed Lilliputian hallucinations. Visual hallucinations may also occur in disorders of the eye, e.g. Charles de Bonnet syndrome in the elderly.
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Gustatory/olfactory hallucinations These are most often reported in temporal lobe epilepsy but they may also occur in other organic and functional disorders. Tactile hallucinations These are also called haptic hallucinations and may take the form of being touched, painful or sexual sensations. Formication is the hallucinatory experience of feeling insects or small animals crawling on the skin. It occurs in drug and alcohol withdrawal, notably with the use of cocaine. Complex deep somatic hallucinations (coenestopathy) may occur as feelings of viscera being moved or distended. Special hallucinations These take several forms: • Functional hallucinations are provoked by a stimulus in the same modality, e.g. voices from a running tap. • Reflex hallucinations occur when a stimulus in one modality produces a hallucination in another. • Extracampine hallucinations are experience as located outside the sensory field of the modality of the hallucination, e.g. hearing someone talk on the other side of the world. • Hypnogogic and hypnopompic hallucinations may occur in normal people while falling asleep and waking up respectively. They may be visual or auditory (often a voice calling the person's name). • Dissociative hallucinations are usually intense feelings and knowledge of being in the presence of someone. The term can also be applied to hallucinations occurring in two sensory modalities, e.g. 'the vision that speaks'. They are normal in bereavement. • Autoscopic hallucinations (seeing the self) may be dissociative but may also occur in temporal lobe epilepsy, other organic states and in schizophrenia. Pseudohallucinations These are vivid perceptions which are experienced in inner, subjective space rather than in the external world. However, unlike ordinary mental imagery, there is no voluntary control over the pseudohallucination. The term has also been used to describe a perception arising in the external world but which has an 'as if quality and is lacking a sense of reality. Pseudohallucinations have little diagnostic specificity and may occur in any mental disorder as well as normal individuals. They are important as a failure to differentiate pseudohallucinations from hallucinations may result in the misdiagnosis of a psychotic disorder.
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Sensory distortions Changes in the intensity of perceptions may result from changes in physiological thresholds or mental state. Intensity of colour is enhanced in some drug-induced states, e.g. lysergic acid diethylamide (LSD) and in affective disorders, e.g. hypomania. A depressed patient may perceive the world as literally colourless. Changes in the spatial form of perceptions occur in organic disorders such as parietal lobe lesions, complex partial seizures or in drug use. In micropsia, objects appear smaller than they are, and in macropsia, they appear larger. In depersonalization, the self, and in derealization, the world, are perceived as being unreal. These experiences may occur in anxiety states, affective disorders, psychotic disorders and in states of extreme fatigue. Disorders of consciousness Consciousness is defined as a state of mental alertness and awareness of the self and the environment.
Reduced consciousness Clouding of consciousness occurs when there is disorientation in time, place and person, with disturbances of attention, perception and memory. It is usually associated with a certain level of drowsiness but the patient can be roused with stimulation. Further reductions of consciousness lead to a neurological stupor and then to coma, in which there is a profound decrease in conscious level with a greatly reduced or absent response to stimulation. It is important to note the different uses of the term stupor in neurology and psychiatry. In the psychiatric definition of stupor, consciousness is retained but there is a lack of response to external stimuli. It is a state of akinesis and mutism. The eyes may remain open and memory for the episode may be retained. It occurs in organic disorders, schizophrenia and affective disorders.
Restricted consciousness This is a state of narrowed awareness with only some lowering of conscious level, and apparently normal behaviour. Twilight states are seen in dissociative states and in organic disorders, particularly as postictal phenomena. In dissociative twilight states, the memory loss is usually associated with highly emotional events of personal significance. Fugue states are characterized by wandering, superficially normal behaviour and some loss of memory. These can occur in dissociative disorders, depressive disorders and as ictal phenomena.
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Delirium Delirium is a state of impaired consciousness associated with disorientation and abnormalities of perception and affect. The level of consciousness may fluctuate. Delirium is characteristic of acute and subacute organic disorders such as toxic states, delirium tremens (not alcoholic hallucinosis) and Wernicke's encephalopathy (not Korsakoff's syndrome). Delirium must be distinguished from dementia in which there is a global deterioration of intellect, memory and personality in the absence of any impairment of consciousness. Disorders of memory Memory has three components: registration, retention and recall. Registration may be impaired with alcohol, anxiety or after head injury. Retention is abnormal after head injury, in dementia, Korsakoff's syndrome or in any organic disorder causing bilateral hippocampal damage. Recall may be impaired in organic disorders but this is more typical of a psychogenic amnesia, e.g. anxiety, affective or dissociative disorders. Disorders of insight Insight is the individual's awareness and understanding of his or her own mental state. It is a matter of degree and is never fully present or fully absent. There are several components to insight, any of which may be impaired: • A recognition of the presence of mental phenomena. • A recognition that these mental phenomena are abnormal. • A recognition of how these phenomena cause problems for the individual or for others. • A recognition that the mental abnormalities are caused by a mental illness. • A recognition of the need for and role of treatment in this illness.
Dynamic psychopathoiogy Dynamic psychopathoiogy is principally concerned with theories derived from psychoanalysis, which attempt to explain the structure of the mind, the development of personality and the production of abnormal symptomatology. The theories emphasize the importance of childhood experience, particularly the quality of 'parental care giving' in the subsequent development of personality and an individual's capacity as an adult to make and sustain intimate relationships. Although there are many different schools of psychoanalysis, all of which adhere to a particular model or theory of development, they can
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be divided into two broad groups: the drive theorists and the object relations theorists. Drive theory In drive theory, it is postulated that human beings are subject to innate instinctual drives which need to be satiated or discharged to release inner tension and frustration. Within a civilized society, many instinctual needs cannot be fulfilled without harm to others. Thus conflict arises between the individual's unacceptable wishes and his or her need to resist them to maintain social order. The conflict is often repressed (pushed out of conscious awareness) but results in the development of physical or psychological symptoms. Drive theory was initially developed by Sigmund Freud, who described many different instinctual drives such as aggression, curiosity, hunger, etc., but who focused most of his attention upon sexual drives or libido. It is important to remember that Freud developed his ideas concerning drive theory approximately 100 years ago. He was influenced by concurrent developments in natural science and physics and his model has much in common with electrophysiological theories of the time. In addition, he was struck by the frequency of his patients' reports of childhood sexual abuse and the coexisting extreme social climate of sexual repression. Freud developed a whole series of interconnecting and related ideas based around the notion of drive theory. Many of these ideas were developed over a period of 40 years and they were revised several times during his life. They can be grouped into three main areas: depth psychology, developmental stages and the structural model of the mind.
Depth psychology and the topographical model Freud formulated his ideas relating to depth psychology as a result of material derived from his own self-analysis and treatment of patients. Freud argued that individuals behave in irrational ways which are motivated by feelings and ideas outside their conscious awareness. He suggested that in addition to the conscious mind, there are two other parallel levels or states of mind: the preconscious and the unconscious. The term 'topographical' refers to the distinction between these three states. Most subsequent writing has emphasized the role of the unconscious which Freud suggested operates by using what is called primary process thinking. The unconscious is governed by different laws from those of the conscious world, which can be summarized as follows: (a) there is no sense of time; (b) there is no sense of place; (c) there is no sense of person; (d) opposing and conflicting wishes can be held simultaneously without logical resolution. In addition, there is no
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Manifest content Latent content Symbolism Displacement Projection Condensation Secondary revision
Freudian dream terminology
The overt content of the dream The hidden meaning of the dream The visual expression of an idea or set of ideas that are hidden or secret The transference of emotions from the original object to a substitute person in the dream or to a symbolic representation of the original object The dreamer's unacceptable impulses or wishes are perceived as emanating from someone else Several unconscious wishes are combined or expressed as a single image Intellectual processes employed consciously by the dreamer to make sense of the dream
spoken language in the unconscious, but communication of ideas occurs through visual images and symbols. Freud postulated that through the study of patients' dreams, unconscious processes could be identified and be brought into conscious awareness. Dreams, he argued, were the 'Royal Road to the Unconscious'. He argued that the real meaning of dreams is often disguised and transformed into innocuous scenarios, but by analysing the dream, the patient's true wishes can be revealed. He called the overt dream material the manifest dream content. The unacceptable hidden meaning, was termed the latent dream content and the process by which latent material was transformed into manifest material was termed the dream censor. Other common terms concerning Freud's theories of dreams are summarized in Table 1.1. Freud also suggested that similar processes were occurring when individuals made mistakes or slips of the tongue. These 'parapraxes' often symbolize underlying repressed wishes.
Phases of psychosexual development Freud suggested that all individuals pass through stages of infantile psychosexual development. He suggested that failure to negotiate successfully a particular stage of development results in certain personality characteristics. The main stages of development are summarized in Table 1.2.
The structural model of the mind Freud proposed that the ego is that part of the individual which lies on the boundary between the inner and outer world. It has no energy of its own but acts as a mediator between inner conflicts and desires, and outer reality. It is therefore governed by the reality principle. The id is the repository of energy of the individual and is governed
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1. Oral stage (1-2 years)
- Erotic activity centres upon the mouth and lips - The psychological objective is to establish trusting dependence on a nurturing and sustaining parental object - Successful negotiation enables individuals to give and receive without excessive envy or dependency and to be able to trust others - Disturbance produces excessive optimism, demandingness, dependency, rage when dependency needs are not met. Such individuals need to be continually fed
2. Anal Stage (2-4 years)
- Erotic activity is centred on anal activity and the development of voluntary control over retention and expulsion of faeces - The psychological objective is to negotiate greater separation from a parent and develop self-control - Successful negotiation results in a capacity for independence, personal autonomy and self-control, and a capacity for cooperation without either excessive wilfulness or a sense of capitulation or defeat - Disturbance results in excessive rigidity, obstinacy, stubbornness, wilfulness, parsimony
3. Phallic or oedipal stage (3-5 years)
- Erotic activity focuses on sexual/genital activity - The psychological objective is formation of gender identity, the development of a conscience (superego) and the tolerance of three person relationships - Successful negotiation results in a stable sense of gender identity, mastery, confidence and the ability to compete with others - Disturbance results in difficulties with authority figures, inability to take control, problems with competitiveness. For men: a fear of women and difficulty in feeling close to women. For women: envy of men and excessive aggression towards men
4. Latency stage (5-13 years)
Quiescent phase
5. Genital stage (13-15 years)
Adolescent phase. Maturation of sexuality. Ultimate separation from parents
by the pleasure principle. It is the source of instinctual drives (for either good or bad). The superego is the conscience or moral agency of the mind. The superego develops as a result of the successful resolution of the oedipal complex. In the transition through the oedipal phase the boy, who is initially libidinally attached to his mother, begins to fear the power of his father with whom, he realizes, he is in competition for his mother's affections. Fearing castration, he controls his desire for his mother by incorporating his father's perceived hostile attitude into his own mind,
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resulting in a self-regulation of his incestuous impulses. Freud suggested that women's superegos were weak and inferior to men's because girls do not fear castration (like boys) as they imagine they have already been castrated.
Other drive theorists Adler Alfred Adler was a follower of Freud who split to form his own school of Individual Psychology. Adler placed less emphasis on sexual drives. Central to his theory was the concept of organ inferiority. Adler conceptualized the infant as a helpless being, unable to do anything for itself. He argued that this gave rise to deep-seated feelings of inferiority (an inferiority complex) which resulted in compensatory striving for superiority. He coined the term masculine protest which he described as a universal human tendency to move from a passive and feminine role to masculine and active role. He did not agree with Freud's theories concerning the inferiority of women and felt that many of the neurotic proclivities of women of that time were the natural reaction of anyone placed in a position of cultural inferiority.
Ferenczi Sandor Ferenczi was a close confidant of Freud. He was apparently a very gifted analyst who took on very difficult patients. He is credited with resurrecting the importance of real (as opposed to fantasized) psychic trauma in childhood being the seed for later adult disturbance.
Transition to object relations and interpersonal theories Later psychoanalytic theories began to emphasize the importance of interpersonal relationships in the development and maintenance of healthy psychic states. In particular, attention focused upon the very early mother-infant relationship. Melanie Klein, a Viennese analyst who moved to London in 1925, became central to the shift in thinking towards early infantile development. She developed a rather pessimistic view of the human psyche and suggested that the infant was born with innate aggressive and destructive impulses. Central to Klein's theory are the fear of annihilation and the use of powerful projective mechanisms. Klein used to the terms 'good breast' and 'bad breast' to symbolize the infant's primitive psychic experience. She suggested that when the infant feels satiated and comforted it creates a fantasy of a good breast. When comforts are denied, it creates the fantasy of a bad breast by projecting its inner distress into the fantasy breast which is perceived as not only bad, but persecutory. Thus, the world is perceived as a terrifying, persecuting place towards which the infant feels rage, anxiety and fear.
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This early phase of development, which Klein suggested lasted for the first 4 months of life, is called the paranoid-schizoid position. If the infant experiences sufficient nurturing it begins to be able to draw together its good and bad experiences of the world. Splitting occurs less frequently, and the infant begins to feel remorse and sadness as it realizes that it has been attacking its mother who is a whole person who cares about the infant. This stage of remorse and regret is called the depressive position. Failure to negotiate the depressive position results in a deep sense of insecurity, a tendency to view people as either all good or all bad, feelings of persecution, a sense of entitlement, inability to empathize with others, feelings of rage and primitive anxiety, and a tendency to project inner distress onto others. Many of Klein's ideas are particularly useful in understanding individuals with borderline or narcissistic personality disorders. Object relations theories In the 1930s, 1940s and 1950s a group of British analysts, including Fairburn, Guntrip and Winnicott began to develop a new psychoanalytic theory of psychological development and a model of the mind which came to be known as object relations theory. Essentially, 'internal objects' are mental representations of others which share some of the characteristics of the real person but are also distorted and primarily based upon perceptions of others. Psychic development occurs through the 'introjection' or incorporation of these mental representations into the person (ego or self, depending upon different theories). A satisfactory motherinfant relationship results in the systematic building up of good objects within the person, which is always balanced by the incorporation of some bad objects. Introjection of good objects results in a stable sense of one's own identity, positive self-esteem, confidence, independence and the ability to nurture, care for and trust others. A poor parental early relationship with abuse and neglect results in the incorporation of negative mental images of others. This leads to an inability to trust and nurture others, poor self-esteem, rage, dependency, and a fragile sense of identity making it difficult to distinguish fantasy from reality. Fairburn Ronald Fairburn, an influential Edinburgh analyst, rejected Klein's view of the infant as having innate aggression. He suggested that aggression was a reaction to frustration or deprivation. He went on to suggest that the ego is present from birth, and libido is a function of the ego, thus implying that there was no id. In his theory, the libido is fundamentally object seeking, as opposed to pleasure seeking as in Freudian theory. He postulated that the earliest anxiety experienced by the infant is separation anxiety. The infant introjects its experience of the mother but two
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aspects of the internalized object, its exciting and frustrating aspects, are split off from the main core of the object and repressed by the ego. The resulting internal structure has three parts: a conscious ego and two repressed other aspects. Winnicott Donald Winnicott was an English paediatrician and follower of Melanie Klein. He stressed the importance of the early mothering relationship in determining the child's development and sense of autonomy. He developed the concept 'good enough mothering', suggesting that frustration and disappointment in the infant with its mother is important in facilitating separation and independent mental life, provided that it occurs within a secure and loving relationship. He stressed the necessity for a degree of 'maternal preoccupation' with the infant for it to be able to thrive. He also observed that too much mothering or constant support could be harmful for the infant and prevent mature development. He introduced the term transitional object for toys or other possessions which the child imbued with characteristics of its mother. He observed that the child became able to tolerate separation from its mother by using an object (e.g. blanket) as an emotional substitute. He hypothesized that the object represented an area of intermediate experience between reality and mother. This process heralded the development of mental symbolizm and the capacity to contain distress through the use of fantasy and creative thought.
Other key psychodynamic theorists Sullivan Harry Stack Sullivan has had an enormous influence over American psychiatry. He more than anyone emphasized the importance of interpersonal relationships. He suggested that individuals can never be separated from the web of interpersonal relationships in which they live and operate. All knowledge of another person is mediated through interaction and can never be objective. Personality is not a firm concrete structure but is a creation of the individual and his or her interactions with others. Hence the same person can behave and appear differently with different people. Sullivan suggested that persons are motivated by needs: the need for all kinds of satisfaction (including food, warmth, but also emotional contact and warmth) and the need for security. Early on, these needs have to be met by the mother-infant dyad; later, they are met by adultto-adult dyads. The individual is never viewed as a separate entity.
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Mahler Margaret Mahler was another influential American analyst. She focused upon the first three years of the infant's life and devised another developmental schema, which is shown in Table 1.3. The main thrust of her ideas involved what she termed the separation-individuation process.
Kernberg Otto Kernberg reformulated Freud's structural model of the mind. Instead of three structures, the ego, id and superego, Kernberg suggested that there were four, the self, the ego, id and superego. Kernberg spent much of his time treating severely disturbed individuals with borderline personality disorder. He determined that the introjection of bad objects occurs, not only through abusive experiences, but also through neglect. He advocated a strong interpretational approach in which the patient is made to confront his or her perceptions of others and unreasonable anger and behaviour. Jung Carl Jung does not easily fit into either drive theories of psychoanalysis or object relation models. He developed his own, idiosyncratic theories Table 1.3 Mahler's stages of development 1. The normal autistic phase (0-4 months) - Infant sleeps most of time with relative lack of external stimuli - Main aim is the adjustment of the infant to the outside world as opposed to the prior environment of the womb 2. The symbiotic phase First subphase: hatching (4-10 months) - Infant develops greater awareness of the outside world - Differentiation and development of body image - Stranger anxiety Second subphase: practising (10-18 months) - Infant begins to explore the world - Concentration on practising and mastering skills Third subphase: rapprochement (18-24 months) - Oscillation between leaving the mother and going back to her when infant feels threatened - Mood swings and crises when mother is unavailable or child has ventured too far - Widening of emotional range and the beginning of empathy Fourth subphase: object constancy (24-36 months) - Consolidation of individuality and unification of good and bad into one whole representation - Development of a reliable internal image
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after initially being Freud's protege but then later splitting with him acrimoniously. Jung believed that all men had a common substrate and that this was inherited. This inheritance is shaped into a variety of symbolic images. Within what he termed the collective unconscious are unconscious images of basic instincts which he called archetypes. Archetypes are not true images, but are forms without content, representing the possibility of a certain type of perception and action. Archetypes become activated by the development of an external situation which corresponds to a particular archetype. Table 1.4 summarizes some of the key concepts and terminology developed by Jung.
Self-psychology Kohut Heinz Kohut developed a mixed model theory, attempting to combine instinctual and relational approaches. He postulated a psychic construction called 'the self which is responsible for functions previously ascribed to the activity of the ego, id and superego. In other words, the self is the main active psychic agency. Kohut described three strong Table 1.4 Jungian terminology 1. Psychological types Introversion: Refers to attitudes of individuals who derive motivations chiefly from within Extroversion: Individuals chiefly motivated from without 2. Structure of the human psyche Conscious ego: Situated at the junction of two worlds: exterior/spatial world and interior psychic world Around the ego gravitates a number of subpersonalities whose relationship to the ego are modified throughout the course of life: The persona: Animus: Anima: Archetypes: The shadow: 3. Individuation
The facade or social mask the person presents to the outside world The masculine aspects of a woman The feminine aspects of a man Inherited ideas or ways of thinking in an individual's unconscious which are transmitted from one generation to another Sum of the personal characteristics the individual wishes to hide from others and himself The process that normally leads a person to a unification of his or her personality. When individuation is completed the ego is no longer the centre of the personality but is like a planet revolving round an invisible inner sun: the self. Jung conceptualized the self as being the heart of the psyche
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developmental needs that must be fulfilled: the need to be 'mirrored', the need to idealize and the need to be like others (twinship needs). Mirroring is the safe and positive reflection of the infant's behaviour and feelings. If sufficient acceptable mirroring occurs early in the life the child introjects a positive and realistic view of himself. Minor failures in mirroring are important as they allow the infant to develop its internal mirror (transmuting internalization). A lack of mirroring results in the infant developing insecurity and feelings of worthlessness, compensated for by surges of unrealiztic grandiosity. Other important psychodynamic concepts
Transference and countertransference There are no agreed definitions of transference or countertransference. Loosely speaking, transference is the unconscious transferring of feelings from one or many key figures in an individual's previous or current life to another important figure. In the history of psychoanalysis, transference was first thought to be a hindrance to the patient's ability to freely associate. Freud later recognized that analysing the transference provided a key to understanding the root of the patient's difficulties. In dynamic psychotherapy, the patient's distorted perceptions of the therapist (the transference) are identified and brought into conscious awareness. The patient is then able to modify his or her behaviour both towards the therapist and important others. The term countertransference is also used in a number of different ways. It most commonly refers to the therapist's irrational feelings and reactions to the patient. Although some of the therapist's responses may be related to the therapist's own psychological conflicts, it has become recognized that often the therapist's irrational feelings provide valuable insights into the patient's unconscious feelings for the therapist. Countertransference, like transference, was originally thought to impede therapeutic progress. It is now however, considered a valuable therapeutic tool.
Defence mechanisms Defence mechanisms are habitual, unconscious mental processes that are employed to resolve conflict between instinctual needs, internalized prohibitions and external reality. They are a central feature of Freudian drive theory and are conceptualized as having two main functions: first, to keep affects within bearable limits during sudden alterations in an individual's emotional life; and second, to restore psychological homeostasis by postponing or deflecting sudden increases in biological
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drives. Anna Freud developed her father's work on defence mechanisms, describing and delineating a whole range of different psychological defensive strategies. Table 1.5 describes the main defence mechanisms and groups them into four subclassifications; narcissistic, immature, neurotic and mature. Table 1.5
Mechanisms of defence
1. Narcissistic/primitive defences Delusional projection: The projection of one's own feelings into another person who then identifies with that feeling Splitting: The division into good and bad. Results in intense but short-lived relationships as initially people are idealized and then denigrated Denial: Primitive denial is the denial of external reality. For example, the refusal to accept that someone has died 2. Immature defences Passive aggression:
Hypochondriasis: Schizoid fantasy: Projection: Acting out: 3. Neurotic defences Intellectualization: Repression: Displacement: Reaction-formation:
4. Mature defences Sublimation: Anticipation: Suppression: Altruism: Humour:
The expression of hostile and angry feelings through a passive gesture. For example, turning up late repeatedly, not eating a meal because one is angry with the person who has cooked it. The individual is unaware of own angry feelings Development of physical symptoms or preoccupation with disease Private fantasies of success to bolster low self-esteem or negative thoughts Putting onto another feelings which belong to oneself. For example, I'm not angry, you're the one who's angry' The expression of emotional distress through a maladaptive behaviour Avoidance of feelings through rational thought Putting out of conscious awareness Transfer of feelings from one individual to another. For example, kicking the cat Behaving in a way which is opposite to the fear which is being defended against. For example, denigration of homosexuals because of own homoerotic impulses Channelling of unacceptable drives or wishes into socially acceptable behaviour Reacting and responding emotionally to an event before it has occurred Temporarily putting painful feelings out of one's mind until they can be expressed at a more appropriate time Fulfilling one's own need to be looked after by caring for others Overt expression of feelings without personal discomfort or immobilization. Permits focusing upon issues difficult to tolerate
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Psychodynamic issues in common psychiatric syndromes Table 1.6 describes some of the main psychodynamic concepts used in relation to common psychiatric disorders. New directions in dynamic psychopathology In the last 20 years, new ways of approaching dynamic issues in therapy have been developed by psychotherapists in the USA and the UK. These approaches cut across traditional psychoanalytic perspectives, and provide innovative ways of understanding the dynamic process. New therapies have been developed all of which are underpinned by new approaches to psychodynamic theory.
The Core Conflictual Relationship Theme (CCRT) method The CCRT method is an assessment system developed by Luborsky for inferring the central relationship patterns that emerge from relationship Table 1.6 Psychodynamic concepts in relation to common psychiatric disorders Obsessive-compulsive disorder
Hysteria
Phobias
Depression:
Generalized anxiety disorder Post-traumatic stress disorder
Defensive strategies used: - reaction formation - displacement - magical undoing - substitution Defensive strategies include: - repression - dissociation - splitting - denial - projection - displacement Defensive strategies include: - repression - displacement - projection Depression linked to grief Vulnerability to loss highlighted Anger turned upon self Powerful sense of helplessness Collapse of false-self structures (object relations) Repressed or warded-off impulses converted into anxiety Small amount of anxiety from perceived danger signals ego to trigger defence mechanisms If defences fail, person is overwhelmed with anxiety Traumatic events lead to incessant incursion of stimuli so organism is flooded with impulses Regression occurs with repetition-compulsion Dissociation also used to ward off anxiety Current trauma revives infantile conflicts
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narratives in psychotherapy. Narratives are parts of sessions in which a patient spontaneously tells episodes about relationships, which are referred to as relationship episodes or REs. From each RE in a session, inferences are made about three types of components: types of wishes, responses from the other, and responses of self. The CCRT method is the combination of the most frequent types of wishes, responses from other and response from self across all the REs in a session or several sessions. The CCRT method has been used in many different psychodynamic models of therapy and by a wide range of psychotherapists from the USA and Europe. In addition, Luborsky has developed a form of psychoanalytic psychotherapy called supportive-expressive dynamic psychotherapy. In this therapy emphasis is placed upon the importance of developing a deep rapport with the patient and using interpretations which are based upon the CCRT method.
Interpersonal theories Interpersonal theoretical approaches have partially gained prominence in recent years due to the success of the Interpersonal Therapy (IPT) of Klerman and Weissman, which was originally specifically designed for the treatment of depression. It uses techniques derived from psychodynamically orientated therapies, but the focus is on the patient's current interpersonal functioning. There are three phases to the therapy. In the first phase, interpersonal problems associated with the onset of depression are identified; in the second phase, these problems are addressed; and in the third phase feelings about termination of therapy are discussed. In interpersonal therapy, unconscious mechanisms are accorded less importance than actual real interpersonal problems that the patient/client is facing. This approach signals a theoretical move back towards focusing upon conscious rather than unconscious processes.
The Conversational Model This approach to dynamic psychotherapy, by Hobson, emphasizes the importance of the development of the therapeutic relationship and advocates that the patient-therapist relationship is the main vehicle for providing change. It is an attempt to strip away complex dynamic theory and to provide a jargon-free approach to psychotherapy. Hobson argues that conventional psychodynamic interpretations can result in the patient either feeling that they are not understood by the therapist or, in the extreme, to a persecutory spiral. Hobson emphasizes the importance of developing a feeling language which grows through negotiation and subtle use of metaphor. Both the client and the therapist start from a position of not knowing, but through exploration, move towards something that is meaningful and new, something which has been
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created between them. Instead of formal interpretations, hypotheses are presented to the patient which can be accepted, modified or rejected. Hobson's theories are predominantly relational and are derived from Jungian psychoanalysis and the work of Harry Stack Sullivan.
Cognitive-analytic approaches Anthony Ryle has been one of the first theorists to incorporate both psychodynamic and cognitive theories in his approach to treatment, which he has termed Cognitive Analytic Therapy (CAT). Central to CAT is the Procedural Sequence Model (PSM). According to this model, intentional acts or the enactment of roles in relationships are maintained by repetitive sequences of mental, behavioural and environmental processes, as follows: (1) perception and (2) appraisal in terms of knowledge, values, other plans and predicted consequences; (3) enactment; (4) evaluation of the consequences of the enactment; (5) confirmation or revision of the aim and the means. In CAT therapy, target problems and underlying target problem procedures (so-called snags, traps and dilemmas) are identified during the first three to four weeks of therapy which are then drawn together in a reformulation which is shared with the patient in a collaborative manner. The remaining sessions are devoted to further recognition and modification of the target problem procedures.
References Hobson, R.F. (1985) Forms of Feeling. London: Tavistock. Jaspers, K. (1963) General Psychopathology (trans. J. Hoenig and M.W. Hamilton). Manchester: Manchester University Press. Klerman, G.L., Weissman, M.M., Rounsville, B.J. and Chevron, E.S. (1984) Interpersonal Psychotherapy of Depression. New York: Basic Books. Luborsky, L. (1984) Principles of Psychoanalytic Psychotherapy: A Manual for Supportive-Expressive (SE) Treatment. New York, Basic Books. Luborsky, L. (1990). A guide to the CCRT method. In Understanding Transference: The CCRT Method (eds L. Luborsky and P. Grits-Christoph). New York: Basic Books. Mahler, M.S., Pine, F. and Bergman, A. (1987). The Psychological Birth of the Human Infant: Symbiosis and Individuation. London: Maresfield Library. Ryle, A.(1995) Cognitive Analytic Therapy: Developments in Theory and Practice. New York: Wiley. Simms, A. (1988). Symptoms in the Mind. London: Bailliere Tindall.
2 Clinical assessment ELIZABETH WALSH and THOMAS FAHY
Interviewing technique The psychiatric interview provides an opportunity to do the following: • • • • •
obtain information; establish a therapeutic relationship; assess the patient's mental state; formulate a differential diagnosis; establish an assessment and treatment plan.
The structure and success of the interview will depend on several factors: 1. The purpose: everyday clinical interviewing will need to be approached in a more flexible way than interviews conducted in the MRCPsych examination. 2. The setting: a quiet room where the patient cannot be overheard and can speak confidentially should lead to a more fruitful interview. 3. Patient factors: the level of patient interaction in the process, the severity of their illness and mood will influence the interview. Even if a patient is fully cooperative, the severity of psychopathology and communication difficulties will have a bearing on the interviewer's ability to collect information and access the patient's mental state. 4. Interviewer skills: a balance of non-directive (open) and systematic probe (closed) questions increases the interviewer's ability to elicit relevant factual information. Attention should be paid to non-verbal cues, with the patient encouraged and given sufficient time to express feelings. Common deficiencies in interviewing technique include reluctance to encourage precision, failure to detect non verbal cues, inflexibility and acceptance of jargon from patients.
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The psychiatric history The order in which the findings of clinical assessment are presented is a matter of personal preference. Many clinicians prefer to begin with a brief description of the presenting problems, followed by a chronological review starting with the family history. The usual format for gathering information at interview is presented below. Presenting complaints Begin by obtaining a brief sketch of the presenting problems and the patient's views on when he/she was last well. A detailed account of the immediate reasons for referral and the method of referral should be noted. A list of the principal complaints, and possible precipitating factors, should be obtained and the course and severity of each should be systematically reviewed, with attention to the resulting impairment of function in work, relationships and social life. In this regard it is sometimes useful to ask the patient to describe how he/she spends an average day. Family psychiatric history As a significant genetic predisposition has been demonstrated in many psychiatric illnesses, it is important to elicit the psychiatric histories of biological relatives (first and second degree), as this can yield useful information. This can prove problematic, as patients may be only vaguely aware of events that occurred many years earlier. A patient may be aware of a relative being 'nervous', but specific enquiry about hospital admission or treatments received such as drugs or ECT may provide useful pointers to the possible diagnosis. Details are best obtained by naming and asking about each close relative individually. Information on the health, occupation and the life circumstances of parents and siblings helps to build up a picture of the individual's background. Past psychiatric and medical history Enquire about previous illnesses, admissions to hospital, outpatient attendance, treatment, legal status of admissions, degree of recovery and current contacts with the psychiatric services. If the patient took, or is currently taking, medication, the type and dosage should be recorded. If the name of the medication cannot be recalled, gentle prompting and enquiry about route and frequency of administration may provide useful clues. Any medical conditions and previous operations should be noted.
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Current social situation Provide a clear account of the patient's marital status, number of dependants, occupation, financial position, accommodation and social supports. Personal history This is usually the lengthiest part of the history, dealing with the patient's life from birth until the current day. It allows an evaluation of the patient's abilities. It may be divided into the following subheadings:
Birth and early development Information on duration of pregnancy and perinatal complications may be relevant to early developmental disorders and psychotic illness in later life. Achievement of developmental milestones, including speech and walking, are also recorded.
Childhood environment Records quality of emotional relationships within the family, loss of any significant figures, significant periods of separation from family, whether adopted or fostered, any changes in family structure and any psychological traumas. It is important to record experiences of childhood neglect or trauma. Enquiries about childhood sexual abuse should be handled sensitively; it may, on occasions, be best to wait until a trusting relationship has been established before making detailed enquiries.
Education and occupation Age of school entry and exit, any special educational needs, schooling difficulties, academic achievements and quality of relationships with peers are recorded. This is followed by a description of any higher education undertaken and then by a description of each period of employment, performance in the job and reasons for leaving. Periods of unemployment may have psychiatric significance or repercussions. It may be helpful to assess how realistic the patient's employment aims are.
Sexual and marital history A chronological record of significant sexual relationships, marriages and cohabitations should be obtained. The quality, duration and reasons for ending important sexual relationships may provide information on the patient's personality and emotional or sexual problems. Family disharmony, including a spouse's difficulty in coping with or accepting the patient's illness, may have an influence on the rate of relapse. A discreet enquiry should be made regarding the patients sexual orientation. In forensic assessments, a more detailed enquiry may be required
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into sexual deviations and fantasies. The names, ages and health of all children should be recorded. Personality An impression of the patient's enduring characteristics and behaviour may be gathered by asking about prevailing mood, attitudes to self and others, strengths and weaknesses, standards, hobbies and patterns of reaction to stress. Psychoactive substance use Specific enquiry about the patient's past and present use of alcohol, drugs and tobacco is vital, remembering that many patients underreport their use of these substances at interview. In the case of suspected alcohol abuse or dependence, it may be useful to run through the features of the alcohol dependence syndrome with the patient and enquire about additional features such as previous delirium tremens, attendances at Alcoholics Anonymous and physical complications. All illegal drugs previously used should be noted. It is important to enquire, in the case of drug abuse, about a history of intravenous abuse and other risk behaviours such as prostitution which may affect HIV status. HIV status should be established if possible. Abuse of prescribed medication often goes unnoted. Forensic history The nature and dates of charges, convictions, custodial sentences, probation orders, admissions to secure units or hospital orders should be recorded. It is worth while trying to ascertain whether offences may have been related to the patient's abnormal mental state at the time, secondary to substance abuse or non-compliance with medication. If there is a history of violent behaviour, risk assessment will form an important part of the interview (see below).
The mental state examination Appearance and behaviour Valuable information may be obtained by observing the patient's attitude and behaviour in the waiting area and reaction to the interviewer on introduction. The condition, colour and style of dress will provide information on self-care, self-image and mood state. Depression, anger, suspiciousness, perplexity, anxiety or hallucinatory experiences may be reflected in facial expression, amount of eye contact, physical demeanour, posture and general behaviour. The level of eye contact established,
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in addition to the quality of rapport between interviewer and patient are recorded. Speech Describe the spontaneity, rate, volume and intonation of speech. Difficulties in conducting the interview due to factors such as vagueness or over-precision should be noted. A brief summary of the content of speech should describe the patient's preoccupations at the time. Any abnormalities in the flow or content of speech should be recorded, e.g. neologisms, idiosyncratic use of words, clanging, perseveration and incoherence. Mood A direct enquiry should be made regarding subjective mood. This will provide information on which more detailed questioning can be based. Systematically probe for changes in the way the patient feels about him or herself, views of the future, changes in vegetative state, including sleep, appetite, libido, concentration, energy levels and diurnal variation in mood. An overall objective judgement of the patient's current mood state should be recorded. One of the most important parts of the mental state examination is assessment of suicide risk and a statement on this must always be included. Although not of concern in the majority of cases, it is prudent as a matter of routine to make a judgement on the patient's current dangerousness (for further information on risk assessment see below). Abnormalities of thought and passivity phenomena Abnormalities may occur in both the form and the content of thought. Disorders in the form of thought, such as loosening of associations and thought blocking, will have been noted during the previous part of the interview. It is helpful to provide some verbatim examples of these. Disorders of content of thought may be difficult to detect and may require probing questions. In psychotic disorders, ideas of reference and persecutory delusions may be revealed by asking about attitudes towards things such as neighbours, strangers, the government, being bugged and electrical appliances. Passivity phenomena should specifically be sought by enquiring into any experiences of thoughts, actions and perceptions being outside personal control. The appropriateness of abnormal beliefs to the patient's mood will provide important clues to the diagnosis, e.g. grandiose or nihilistic delusions in affective disturbance. Other abnormalities of thought such as the overvalued idea of body image disturbance in anorexia nervosa and the ruminations in obsessive and other disorders should be included here.
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Hallucinations The type, content and duration of hallucinations can provide useful diagnostic clues. Visual, olfactory, gustatory and tactile hallucinations are more common in organic states. Third-person auditory hallucinations are more commonly elicited in schizophrenia. Second-person auditory hallucinations may occur in affective, schizophrenic or organic psychoses. Auditory hallucinations experienced in affective disorder are generally more fleeting than those experienced in schizophrenia. Unpleasant, sometimes self-referential, olfactory hallucinations can occur in depression. Any illusions and pseudohallucinations should be recorded. Cognitive state The extent of the required cognitive assessment will vary. During the initial part of the interview, abnormalities of cognitive function may become obvious to the interviewer when, for example, a person has difficulties remembering what should be straightforward details. The detail of the cognitive assessment will therefore be dictated by this. If an elderly patient is referred because of failing memory or withdrawal, obviously a comprehensive cognitive assessment will be necessary. In the younger patient, it usually suffices to comment on orientation, attention, concentration, general knowledge, short-term and long-term memory. The following is a suggested format for a detailed cognitive assessment:
Level of consciousness This can be categorized as: comatose; impaired but responsive to physical stimuli; impaired but responsive to questions; alert; hyperalert.
Orientation Enquire about the approximate time of day, the day of week, date, and patient's name and address.
Attention and concentration Record the time taken and the number of errors made when the patient attempts to recite the months of the year backwards, or do a simple test of arithmetic, e.g. the serial sevens or threes. In the serial sevens the patient is asked to subtract seven from one hundred and to continue subtracting seven from each answer they get, aloud. It is important to give the patient clear instructions of how to proceed and not to interrupt during this process, as this will make the test inaccurate. Disturbances of attention and concentration occur in many psychiatric disorders in which anxiety and depression are present.
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Speech Note any dysarthria, dysphasia (see below) or unusual use of words. Verbal fluency is assessed by counting the number of words beginning with T' or the number of four-legged animals listed in 60 seconds.
General knowledge This is commonly assessed by asking questions about current world events or knowledge of the names of various heads of state.
Memory Assessment of short-term verbal memory can be made by giving the patient a name and address or a list of objects (e.g. fruit), ask them to repeat it to establish that they have registered the information and have intact immediate recall, and then ask them to repeat it again after 3 and 5 minutes. The remainder of the cognitive assessment can be conducted during the intervening time period. Visual memory can be tested the same way by substituting visual stimuli. Long-term memory can be assessed by asking the patient to recall significant dates from the past. Memory disturbance, typically global, often accompanied by varying degrees of disturbance of other intellectual functions, is a common early sign of chronic organic brain conditions. Other complicating neurological signs which may be detected in organic brain conditions include the following and should be noted if present during the mental state examination: Dysphasias • Nominal dysphasia: difficulty in naming familiar objects. In most cases this is a symptom of diffuse brain damage. • Sensory dysphasia: difficulty in comprehending sensory stimuli. This occurs following discrete lesions in the auditory association cortex in the temporal lobe (Wernicke's area). • Motor dysphasia: disturbance in motor speech. The patient knows what he/she wishes to say but is unable to do so. This is thought to be due to a lesion of the posterior two-thirds of the third frontal convolution (Broca's area). Agnosias Impaired recognition of familiar objects not due to primary sensory disturbance is known as agnosia. • Visual object agnosia: inability to identify a familiar visualized object implies occipital lobe damage. This is usually limited to small objects
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and can be revealed by asking the patient to name a number of small objects and asking what they are. • Proposagnosia: inability to recognize previously familiar and/or unfamiliar faces. Agnosia for familiar faces may extend to the subject's own face in a mirror or picture. It has been claimed that agnosia for familiar faces is associated with lesions in the right temporal lobe, while agnosia for unfamiliar faces is associated with right parietal lobe damage. • Topographical agnosia: inability to recognize familiar places and difficulty with route-finding. The patient may get lost travelling a previously well-known route. This is thought to be due to parietal lobe damage. Dyspraxias A dyspraxia is an inability to imitate actions or perform a complex action. • Constructional dyspraxia: inability to copy a series of line drawings of increasing complexity, draw a clock face or assemble a jigsaw puzzle. This is more common in damage to the non-dominant than the dominant parietal lobe. • Ideational dyspraxia: inability to carry out a complex sequence of motor tasks, e.g. dressing, combing hair. This is usually associated with diffuse brain damage or dominant temporoparietal lesions. Insight This is recorded verbatim from the patient's response to two questions. Do you think that you are unwell? Do you think you require treatment and, if so, would you be willing to accept it?
Physical examination and investigations A physical examination should be performed at all initial assessments. The extent of this should be judged on diagnostic possibilities in each case. Care should be taken not to miss physical disorders that may present with psychological symptoms, e.g. myxoedema in depressed patients. Routine physical investigations usually carried out on all admissions include: full blood count, urea and electrolytes, thyroid function tests and urinalysis. Urinary drug screens are useful if substance abuse is suspected. Other investigations may be required such as chest X-ray, electroencephalogram (EEG), lumbar puncture, skull X-ray, computerized tomography (CT) scan and magnetic resonance imaging (MRI) if there is a definite indication.
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Collateral history This is one of the most important aspects of the assessment. It may involve a discussion with a general practitioner, relative, employer or other suitable person who knows the patient well. With the patient's permission it is extremely useful to obtain information about their past and current life and any previous suicide attempts or forensic history, in order to clarify and expand on information already obtained. Others may have specific concerns about the patient's welfare which may not have been mentioned by the patient.
Summary and formulations A brief summary should outline the main presenting symptoms, any relevant past psychiatric history and other important factors obtained during the assessment. It is generally no longer than three sentences. This is followed by a list of possible differential diagnoses, starting with the most likely. It is useful to note beside these each differential, the reasons why this particular diagnosis is considered. Although a psychiatric assessment usually requires more than one interview, a management plan should be outlined, which can be updated if necessary at a later stage depending on progress.
Evaluating risk It is an integral part of a psychiatric assessment to assess the risk a patient poses to himself/herself (suicide risk) and to others (dangerousness). Suicide risk (see Chapter 18) This may involve assessing a patient who has already attempted suicide or a patient who has not. The skills required to make this assessment include: • evaluation of suicidal ideas; • detection of psychiatric disorder; • assessment of factors associated with an increased risk of suicide. It is useful to begin by asking whether the patient has thought that they can no longer go on with life. This can be followed by more direct enquiries about suicidal thoughts and specific plans. Any expression of intent should be taken seriously. Established risk factors for suicide include previous attempts, especially if violent and painful methods were used and the circumstances did not permit easy accessibility for rescue, being over 45 years of age, male, unemployed, living alone, recent bereavement or separation, poor physical health, psychiatric disorder and substance abuse. Among suicide attempters, the closer the
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individual resembles the typical completed suicide the greater the risk. A decision on the level of risk should only be made after examination of the patient and consideration of risk factors together with information from an informant. Assessing dangerousness (see Chapter 27) Risk cannot be eliminated. The very worst clinical practice does not involve making 'wrong' decisions, but the failure to collect relevant information and make a clear plan. Key decisions should be taken only after consultation with others involved in the patient's care. Following assessment, a comprehensive management plan should be formulated, recorded clearly, communicated to and discussed with team members, and all involved should be clear about what their exact role is. In assessing dangerousness it may be useful to divide the assessment into three sections.
Patient profile • Is there a history of violence? Previous violence has consistently been found to be the strongest predictor of future violence. Details of all previous episodes should be obtained. This will require information from other sources. This will identify precipitants or changes in mental state or behaviour that preceded prior violence, highlighting specific warning signs. • Is substance abuse a problem, or are there any other disinhibiting factors which may be important? • Does the patient comply with psychiatric treatment? Do they have insight into their condition or need for treatment? Is there any evidence of recent non-compliance with medication? Do they engage with psychiatric services? • Is there evidence of 'rootlesness'? Are there frequent changes of address or few social ties? • Does the person have a sociopathic disorder? • Have there been any recent stressors?
Mental state • Is there any evidence of threat, such as firmly-held beliefs of persecution by others or of control override symptoms, where the patient has firm beliefs of their mind or body being controlled or interfered with by external forces? • Does the patient display current emotions related to violence, e.g. irritability, anger, suspiciousness?
Environment • Has the patient identified a potential victim?
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• Does the patient have access to the identified potential victim? • Is the potential victim aware of the possible danger? The assessment of dangerousness should be based on the information obtained above, on other relevant items from the assessment and collateral information, e.g. family, probation officer, community psychiatric nurse, etc. It should specify factors likely to increase and decrease the chance of violence. It is useful to conclude by answering the following questions: • What is the seriousness of the risk? • How immediate is the risk? • What is the probability of the risk becoming actual?
Reading list Gelder, M., Gath, D. and Mayou, R. (1994) Concise Oxford Textbook of Psychiatry. Oxford: Oxford University Press. Holloway, F. (1997) The assessment and management of risk in psychiatry: can we do better? The Psychiatric Bulletin, 21, 283-85. Lishman, W.S. (1987) Organic Psychiatry: The Psychological Consequences of Cerebral Disorder. London: Blackwell. Royal College of Psychiatrists Special Working Party on Clinical Assessment and Management of Risk (1996) Assessment and Clinical Management of Risk of Harm to Other People. Council Report CR 53. London: Royal College of Psychiatrists.
3 Psychology and human development HELEN BARKER and ANTHONY MADEN
Basic Psychology Learning Learning is the production of relatively persistent changes in behaviour as a result of prior experience.
Associative learning Associative learning is the form of learning usually chosen for experimental study. It entails the formation of new associations between events and is traditionally divided into classical and operant conditioning. Classical conditioning Classical (or respondent) conditioning was described by Pavlov. He noted that a dog salivates (unconditioned response, UR) at the sight of food (unconditionedstimulus, US). Repeated pairing of a ringing bell (conditioned stimulus, CS) with the sight of food results in learning: the bell (CS) alone elicits salivation (conditioned response, CR). Classical conditioning pairs a new stimulus with an existing response; new responses cannot be produced and the responses concerned are often autonomic or emotional. The conditioned and unconditioned responses are basically the same, although the conditioned response is usually of a lesser magnitude. Classical conditioning can only occur if the stimulusresponse link exists already. Higher order conditioning is said to occur when a new CS is paired with the original CS which, therefore, acts as an US in its own right. Classical conditioning may be of clinical relevance in understanding the acquisition of phobias. Operant conditioning Operant (or instrumental) conditioning is concerned with the consequences of actions. A behavioural response (the operant) increases in
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frequency if followed by a reward (positive reinforcement). Ideally, reinforcers should occur immediately and be of a high incentive value. They may be primary (e.g food) or secondary (e.g. praise). The Premack principle refers to the observation that preferred activities may act as reinforcers to less preferred ones (e.g. a visit to the pub following a day of exam revision). The outcome of operant conditioning may depend on the reinforcement schedule used. If a behaviour is reinforced on every possible occasion, this is known as a continuous reinforcement schedule. This leads to fast acquisition and fast extinction. Alternatively, reinforcement may be intermittent, either fixed ratio (e.g. reinforcement every third time) or variable ratio (e.g. after the third, eighth and tenth responses). Intermittent reinforcement results in slower acquisition and extinction. Variable ratio reinforcement (e.g. in gambling) may be particularly resistant to extinction. In contrast to classical conditioning, operant conditioning is able to produce new behaviours and the learned responses are usually voluntary and may be complex. Further differences between classical and operant conditioning are summarized in Table 3.1. Terms used in associative learning These include: • Acquisition. The process by which a new association is formed. • Extinction. The diminishing of the learned response when the CS is presented repeatedly without the US or when the operant response is not rewarded. In classical conditioning the CR can be recovered if there is a repeated pairing with the US. Alternatively, there may be a spontaneous recovery if the subject is given a break when the CS is not presented. • Positive reinforcement. Any event which, when it follows a response, increases the probability of that response being repeated. • Negative reinforcement. Behaviour is reinforced by the termination of a noxious stimulus, e.g. rat presses lever to stop electric shock. A powerful variant of negative reinforcement is escape conditioning, in which the learned response provides a complete escape from the unpleasant situation. The subject learns to escape rather than stay Table 3.1
Further differences between classical and operant conditioning
Classical conditioning
Operant conditioning
Subject is passive Pairing between two stimuli Anticipation is learned The response is usually autonomic or emotional
Subject is active Pairing between stimulus and response A response is learned The response is usually behavioural
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• • •
• • •
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and alter the situation and, as such, the response is highly resistant to extinction. Punishment. A noxious stimulus is presented after a behaviour to diminish the likelihood of the behaviour's recurrence. Punishment will only be effective if it is immediate and is of sufficient intensity to prevent the behaviour on the first occasion. It is also preferable if the punishment makes sense to the subject and is associated with a positive reinforcement of a more desirable behaviour (differential reinforcement of other, DRO). The role of punishment in learning is complex and may lead to several undesirable consequences. It may result in behavioural rigidity and the inappropriate avoidance of other stimuli occurring at the time of punishment. Punishment may also act as an example of negative modelling and may elicit aggression towards the situation or person involved. Shaping. Production of new, often complex behaviours by reinforcement of natural responses which approximate to the desired one. Prompting. Verbal or physical guidance elicits the desired response which is then reinforced. Later, prompts are gradually withdrawn (fading), leaving the response to occur in their absence. Chaining. Teaching of complex behaviours by breaking them down into simple components. The first action in the sequence is reinforced; once acquired, reinforcement is given only following both the first and second components and so on until the complete sequence is established. Chaining, shaping and prompting are extensively used in teaching children with severe learning difficulties. Generalization. The process by which stimuli similar to an original CS will also evoke the CR. The tendency to evoke CR depends on degree of similarity. Discrimination. Learning to respond to only one stimulus. It is produced by the selective reinforcement of only the responses to the desired stimulus, extinguishing all others. Avoidance. Learning to respond by preventing contact with an unpleasant stimulus, e.g. rat jumps when bell sounds, in order to avoid electric shock. Avoidance is believed to be responsible for the maintenance of phobias. Once the phobic response is established, contact with the phobic stimulus is avoided and so there is little opportunity to learn more appropriate behaviour.
Other types of learning • Cognitive learning. This may be seen as complementary to associative learning. It is a process of taking in new information about the environment, relating it to existing knowledge and using it to formulate problem-solving strategies. • Observational learning (modelling). Behaviour is learned through the
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observation of others. This is most likely to occur when the model is of a high status, is highly competent, shows supportive or rewarding behaviour, and shares some features in common with the observer. • Insight learning. This occurs when the subject discovers a solution through a sudden insight rather than the slower process of trial and error. Once learned, this knowledge is easily transfered to other situations. • Social learning theory (Bandura). This theory attempts to integrate the principles of associative learning with the concepts of cognitive and observational learning. The main source of reinforcement of learned behaviours is seen as social rather than material, e.g. praise. Experiments designed to explore imitation in children often focus on aggressive behaviour, e.g. effects on a child of watching adults behave violently on television. The results are frequently ambiguous. In general, the tendency to imitate is less specific in younger children and, in older children, depends on the extent to which the model is seen as successful or powerful. Alternative explanations are often possible; seeing a violent adult may simply give the child permission to perform previously learned responses, rather than teach him or her new behaviour.
Ethology and learning Based on observations of animals in their natural habitat, ethology stresses the biological constraints on learning, in contrast to the 'blank slate' view held by traditional learning theorists. Rather than being able to learn anything at any time, animals show 'sensitive periods' when they are predisposed to learn certain responses quickly. Similarly, some responses are more easily learned than others, e.g. a conditioned fear response to spiders is far more common than to rabbits. Perception Perception is the selection, evaluation and organization of sensory input to produce a coherent and meaningful representation of the world. Selective attention is the process by which most sensory stimuli are ignored, in order to limit the amount of information to within the brain's processing capacity, and to ensure attention is focused appropriately. A filter theory proposes that many signals from different sense organs are simultaneously transmitted to the brain but, on arrival, only a fraction of the total input is passed through for further processing. Selection of signals may be based on physical characteristics (loudness, brightness) or meaning (a baby crying, one's own name). Perception entails further analysis of selected sensory input. Stimuli are organized into patterns which are related to information in memory stores in order to attach meaning to the percept. This is an active process.
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Rather than reflecting reality, sensory cues are used to construct a model, a hypothesis, that accounts for the data received by the senses. In this way, the brain is able to provide a consistent sensory experience. This is known as object constancy. However confusing or incomplete the sensory input, we usually experience objects to be constant in size, shape, brightness, colour and location. Ambiguous sensory input will be interpreted in the light of the subject's perceptual set, i.e. previous experience, physiological or emotional state, the presence of reward or punishment, and personality. The active nature of the perceptual process is shown by: • visual illusions: sensory cues lead the brain to produce an incorrect or inconsistent hypothesis; • hallucinations: the percept is produced in the absence of sensory input. Memory Memory includes the processes of registration, storage and retrieval of information. There are three memory stores: sensory information storage, short-term memory and long-term memory.
Sensory information storage Sensory information is stored in the peripheral sense organs for 0.5s before fading. This maintains a continuity of perception and may be considered as an extension of the registration process.
Short-term memory (primary or working memory) This store retains a limited amount of information (7 + 2 chunks) for a short time (approx. 30s). It functions as a 'working memory', allowing brief holding of information for use in problem-solving. Information is evaluated and a decision taken on whether to transfer it to long-term memory, but is quickly lost if no longer required. Impairment of shortterm memory may be assessed, provided that attention and perception are intact, by asking the patient to recall immediately a series of verballypresented digits, i.e. by testing digit span.
Long-term memory (secondary memory) This is a large-capacity store, capable of holding information for periods ranging from a few minutes to many years. Only a tiny proportion of the information passing through the short-term store is transferred to long-term memory. This transfer requires cognitive strategies, e.g. rehearsal/repetition or the relating of new information to that already stored. Long-term memory may be tested by asking a patient to remember a name and address for 5 minutes. Although this test is sometimes
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loosely, and incorrectly, termed a 'short-term memory test' it actually depends on the ability to store and retrieve information in long-term memory. Immediate repetition of the material tests attention and true short-term memory. Recall of distant events or dates tests the ability to recall previously stored information. This may remain intact when the ability to store new material has been lost, as in Korsakov's syndrome. Long-term memory may be subdivided into declarative and procedural memory. Declarative memory is further divided into episodic (or explicit) memory (autobiographical facts and events) and semantic (or implicit) memory (general knowledge facts). Procedural memory includes perceptual skills and motor skills, e.g. remembering how to ride a bicycle.
Forgetting Forgetting, or the loss of information, can occur at any of the stages described above, and in the following four modes: • Inattention. Only a fraction of total sensory input ever reaches the short-term store. Inattention is an important cause of 'poor memory' in many psychiatric disorders, e.g. depression. • Short-term memory. Information is rapidly lost from short-term memory unless it is repeated or rehearsed. Memory traces simply decay with time or the information is displaced by the arrival of new information, as short-term memory capacity is limited. • Long-term memory. This is vulnerable in the first few minutes after encoding of information, e.g. head injury with loss of consciousness commonly results in permanent loss of memory of events immediately prior to the incident. After this time, information is much more stable and may be retained for years. Forgetting may be due to decay over time, interference of new memories with recall of old ones, or a failure of retrieval. • Failure of retrieval. Recognition allows access to information not necessarily available to straight recall; presentation of the material acts as a prompt to aid retrieval. Multiple choice examination questions require recognition of correct responses rather than straight recall of information as required in many essay questions. Emotional factors can affect the retrieval process, e.g. examination stress. Retrieval may be improved if it occurs in the setting where the original learning took place (state-dependent learning). Personality and personality testing Personality comprises the characteristic patterns of thinking and behaviour by which individuals are distinguished. This assumes some consistency of behaviour across different situations, the emphasis being on internal determinants of behaviour rather than situational influences.
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This contrasts with the 'interactionist' view of behaviour which stresses the importance of the current environment.
General approaches to personality testing Three approaches are taken: • Observations and self-reports of behaviour in different settings. This is the basis of informal clinical assessment. Direct observation is often impractical and self-reports are unreliable. Observational methods have been standardized in the assessment of temperament in children. • Projective tests. Subjects are presented ambiguous stimuli and asked to report on their perceptions or give a meaning to the stimuli. The responses are said to reflect conscious and unconscious thinking. In the Thematic Apperception Test (TAT), subjects are asked to construct a story based on an ambiguous picture. In the Rorschach Test, subjects are asked to describe what they see when the ambiguous stimuli are ink blots. Results are often interesting but difficult to rate. They are unreliable and of dubious validity. • Self-report measures. Subjects indicate the degree of their agreement or disagreement with a series of statements about themselves and their attitudes. The results can be analysed statistically and reliability measured.
Idiographic theories of personality These are based on the study of individuals and are concerned with individual uniqueness. They include Kelly's personal construct theory, Rogers' self theory as well as the psychoanalytic theories (see Chapter 1). Kelly's personal construct theory The theory reflects a cognitive approach to personality, seeing man as a 'scientist' attempting to make sense of and manipulate the environment. The theory proposes that people use several personal bipolar concepts, or personal constructs, to make sense of the world. The nature of these constructs varies between individuals, but they are used to classify objects, events and people in meaningful ways, and so help determine reactions to situations. Bannister designed the repertory grid test to identify a person's constructs. The subject is asked to say how a series of named people on cards relate to each other. It is assumed that the terms used in the answers reflect personal constructs. The individual is therefore seen as unique, rather than assigned to a category or place on a dimension. A description of personality is provided. The theory is stated in such general terms that precise, testable hypotheses cannot be formulated, so validity is not easily established. The test is rarely used clinically.
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Rogers' self theory The theory assumes that individuals have a drive to fulfil themselves and to become their ideal self. To achieve this, it is considered essential to have had an experience of unconditional love and positive regard from another person. This results in healthy individuals who can achieve congruence between their self-concepts and their behaviour. These congruent individuals are then able to grow (self-actualize) and fulfil their potentials both internally and in society. Rogers' theory forms the basis of client-centred counselling and has links with Maslow's theories of motivation and self-actualization.
Nomothetic theories of personality These theories are based on the psychometric studies of populations rather than individuals. Eysenck's theory Eysenck's theory of personality suggests a biological basis for the dimensions of personality. Neuroticism is said to reflect lability of the autonomic nervous system, while extraversion/introversion reflects activity in the reticular activating system and relates to conditionability (the ease with which a person learns). At best, the evidence is contradictory and these ideas are not widely accepted. Eysenck developed the Eysenck Personality Questionnaire (EPQ) to replace his earlier questionnaires, the Maudsley Personality Inventory (MPI) and the Eysenck Personality Inventory (EPI). It produces a lie score, to detect those trying to present a good impression, and scores along three dimensions: (a) neuroticism: a measure of 'emotional stability'; (b) psychoticism: said to reflect 'longstanding personality features of psychotic patients' (a dubious concept which is often disregarded); (c) extraversion/introversion: relates to arousal - introverts have high levels of arousal, conditioned easily and are more prone to neurotic disorder. The EPQ is similar in principle to the earlier MPI but much shorter. It has been widely used in clinical and research settings and has generated a vast literature. Cattell's theory Cattell developed the 16PF personality questionnaire from a factor analysis of descriptive terms which resulted in 16 personality factors (e.g. stableemotional, imaginative-practical, dominant-submissive). Second-order factor analysis produces factors similar to the ones identified by Eysenck.
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Minnesota Multiphasic Personality Inventory (MMPI) The full MMPI is composed of over 500 statements but shorter versions are available. It gives a personality profile composed of ratings along several dimensions or traits such as depression, hypochondriasis and paranoia. It is not based upon a theory of personality, but is constructed empirically and validated by presentation of the items to defined groups so that statements which discriminated between the groups were retained. The large number of items makes it comprehensive. Though widely used in research, it does not assign subjects to clinical diagnostic categories.
Dimensional verses categorical approaches EPQ and MMPI rate personality along dimensions, while the Diagnostic and Statistical Manual (DSM) of the American Psychiatric Association and the International Classification of Disease (ICD) of the WHO use a categorical approach to classify extremes of personality as personality disorders. Full assessment would often allow a person to be placed in more than one category: using one only is an oversimplification. A dimensional descriptive approach is less convenient but often conveys more information. Motivation The study of motivation may be divided into extrinsic theories, intrinsic theories and the unified theory of Maslow.
Extrinsic motivation theories These state that internal, biological needs (e.g. hunger or thirst) activate drives and goal-seeking behaviour which restore the homeostasis and reduce the drive. Drives may be either primary (hunger and food-seeking behaviour) or more complex secondary drives which are acquired by learning (the wish to earn money or achieve status).
Intrinsic motivation theories These theories state that activity is intrinsically satisfying. They were developed following many criticisms of the extrinsic theories, e.g. their inability to account for curiosity and attachment, or the existence of behaviours that occur in the absence of drive reduction. Intrinsic theories propose that individuals are motivated to achieve an optimal level of arousal. When faced with boredom or sensory deprivation, individuals are prompted to seek out unusual and unfamiliar sources of stimulation. It is postulated that motivational drives are based on innate needs such as the need for novelty, the need for complexity, the need for affiliation and the need for achievement (nAch). These are more complex than
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the physiological needs central to the extrinsic theories and are strongly influenced by learning and experience.
Unified theory Maslow developed a unified theory of motivation which integrates the intrinsic and extrinsic theories and is also linked to humanistic theory and the concept of self-actualization. He proposes a hierarchy of needs which are ranked according to importance: f. 2. 3. 4. 5. 6.
Physical needs such as hunger and thirst. Need for personal safety and security. Social needs such as feelings of love and belonging. Need for self-esteem, achievement, approval and recognition. Need for autonomy. Need for self-actualization and a sense of self-fulfilment.
Only when the basic needs such as hunger and safety have been satisfied will the individual seek to meet needs which are further up the hierarchy. Emotion Emotion may be regarded as having two components, physiological (autonomic responses) and psychological. Early theories attempted to explain their interrelationship. The James-Lang theory saw the physiological response as primary and the psychological experience of emotion as based on the perception of bodily changes. The Cannon-Bard theory, however, proposed that the physiological changes are non-specific and could not be used to distinguish between a wide range of feeling states. It was concluded that physiological and psychological components of emotion appear to be simultaneous and of equal importance. For example, an injection of adrenaline mimics the physiological changes of fear but may not produce the emotional experience of fear. Similarly, beta-blockers may not block the feelings of anxiety despite their autonomic effects. Modern cognitive theories of emotion have built on these early ideas. Schachter showed that injection of adrenaline could produce feelings of anxiety or euphoria depending on the situation. A primary determinant of emotional experience was the subject's cognitive appraisal of himself/ herself and his/her circumstances. He concluded that physiological changes are integral to emotion but are interpreted in the light of cognitions. Environmental cues are used to 'label' the physiological arousal. This principle is central to cognitive therapy. Emotion can be seen as a prime motivation in much human behaviour; it increases arousal levels and stimulates action. However, high levels of arousal may be maladaptive, preventing effective action, e.g. in anxiety states.
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The Yerkes-Dodson law relates task performance to level of arousal. Performance gradually increases with increasing arousal until a peak performance is achieved; as arousal increases further performance declines. Stress and coping An individual experiences stress when the demands of a situation exceed the resources an individual has available to meet those demands. Events are likely to be perceived as stressful when they are experienced as being uncontrollable and unpredictable. Continued stress leads to anxiety, aggression, apathy, difficulties with clear thinking and a number of physical consequences such as chronic hypercortisolaemia, coronary heart disease and an impaired immune response. Those individuals who seem to thrive on stress have been found to be more actively involved in their work and social lives, more oriented towards challenge and change, and feel more in control of their lives.
Type A personality Friedman and Rosenman identified the type A personality. These are individuals who tend to deal with stressful situations by becoming hostile, aggressive and impatient. They show extreme competitiveness and are constantly striving for acheivement, while at the same time experiencing constant feelings of self-doubt. Having a type A personality has been shown to be associated with increased rates of coronary heart disease and myocardial infarction.
Coping When faced with stress, an individual will make repeated efforts to master the situation. There are two main strategies for coping: problemfocused strategies and emotion-focused strategies. Problem-focused coping concentrates on defining the problem and attempting to generate alternative solutions. Emotion-focused coping helps the individual manage the emotions associated with the stress rather than remove the source of stress itself. These include behavioural strategies (physical exercise or talking to friends), cognitive strategies (reappraisal or suppression) and distraction strategies (enjoyable alternative activities). Less helpful emotion-focused coping involves negative avoidant strategies (heavy drinking or reckless behaviour) and ruminative strategies (excessive worrying and concentrating on how bad the situation is).
Learned helplessness This was described by Seligman. Individuals under stress may make repeated unsuccessful attempts to master the situation before giving
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up. They believe that no action of their own can improve the situation and this leads to a withdrawn and negative state similar to depression. Even when the situation improves and a solution becomes available, individuals may continue to believe that they are helpless and fail to act to reduce the stress. This is linked with Rotter's concept of locus of control. If individuals have an external locus of control they may believe that they are at the mercy of their circumstances and tend to believe that their own actions will be ineffective.
Social Psychology Attitudes These are a sets of evaluated beliefs which reflect concepts of the self and others. Attitudes may strongly influence an individual's behaviour when faced with a certain situation. An attitude has three components: cognitive (a belief about something); affective (a feeling about something) and behavioural (a tendency to react in a certain way). Attitudes can be measured in three ways: • Thurstone scale. This is a range of different statements from which the subject chooses the one that most closely matches his/her own attitude. • Likert scale. The subject is presented with a statement and then asked to agree or disagree along a five-point scale. • Semantic differential. The subject is presented with two contrasting words at either end of a visual analogue scale. The subject places a mark on the line to indicate his attitude.
Cognitive dissonance Festinger developed this concept from the observation that individuals strive to achieve consistency in their attitudes. When an individual holds inconsistent or conflicting attitudes this is termed cognitive dissonance and results in discomfort or anxiety. The individual will attempt to reduce the dissonance by changing behaviour or reassessing the evidence underlying his attitudes.
Heider's attribution theory This states that individuals make judgements about the attitudes they hold which are based on their observations of their own behaviour. In other words, 'if we do something a lot then we tell ourselves that we must like it'.
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Attitudes and communication It is possible to change attitudes through persuasive communication. This is most likely to happen when the communicator is of high status, shows expertise, genuine motivation and appears to be attractive or likeable in some way to the recipient of the message.
Self-concept This is the set of attitudes which individuals hold about themselves. The concept may be further divided into concepts of self-image and selfesteem. Self-image is a description of the beliefs about oneself based on experiences of social behaviour and interactions. Self-esteem is the positive or negative evaluation of one's self-image. People with high self-esteem demonstrate increased social activity, warmer social relationships, less prejudice and more risk-taking behaviour. Leadership, groups and influence
Leadership Lewin identified three types of leaders: autocratic, democratic and laissezfaire. Autocratic leaders function well in groups where a task must be accomplished urgently but the group members tend to become aggressive towards each other and abandon the task in the absence of the leader. Democratic leaders function well in groups where greater productivity is required. A laissez-faire leader is associated with groups with lower productivity but higher creativity.
Social influence Being observed by others usually improves task performance (social facilitation). Latane developed social impact theory which states that the impact of any source of influence on a subject is dependent on the importance, immediacy and number of the sources.
Social power Raven and French described five types of social power: authority derived from status, power to allocate rewards, power to punish, power derived from charisma, and power derived from skills or knowledge.
Obedience Milgram studied obedience by conducting experiments in which subjects were instructed to administer electric shocks to stooges involved in learning tests. Sixty-five per cent of subjects complied with the instruction to deliver a potentially fatal shock. Factors increasing the subjects' compliance included close supervision by the experimenter, lack of
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physical proximity between subject and stooge, and the provision of an ideological justification.
Conformity Asch studied the pressures exerted on an individual to conform to a group's judgement, even when that judgement was clearly wrong. Conformity pressure increases with the status of other group members and decreases when just one other group member is prepared to dissent. These studies on obedience and conformity reveal that most people tend to underestimate the power that situational factors play in influencing behaviour.
Group decision-making When groups make decisions they tend to be riskier than an individual's decision (risky shift effect) and more extreme (group polarization). Groupthink occurs when group members suppress their own opinions in the interests of group consensus. This is more likely to occur when a group is cohesive, is isolated, has a directive leader, is faced with a stressful situation, and has no systematic procedures to consider alternative solutions.
Interpersonal attraction Attraction between two individuals is associated with close proximity, increasing exposure, increasing familiarity, mutual liking, mutual selfdisclosure and similarities in perceived attractiveness, competence and attitudes. Intelligence and psychological assessment
History and general principles Interest in individual differences first focused on physical characteristics, e.g. skull size. Attention later shifted to mental abilities and the possibility of measuring them. Early workers, such as Francis Galton, were often interested in racial differences and eugenics which in part explains the suspicion with which IQ tests are at times regarded. All cognitive tests measure performance in a particular situation; the extent to which this reflects underlying ability depends on many variables. Intelligence tests are constructed to measure the underlying intellectual ability and minimize the effects of past experience. The basic design is a collection of items covering verbal and non-verbal reasoning. Each test is standardized on a random sample of the population and individual scores are compared to these norms.
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Specific tests The Stanford-Binet test This is a revision of one of the earliest tests initially designed to detect children in need of remedial education. Items are age-graded so that the score yields a mental age. The Intelligence Quotient (IQ) is derived from the mental and actual ages of the tested subject:
The distribution of IQ in the general population is near normal, or Gaussian, but there is a significant excess of individuals with low IQs due to the various genetic and physical causes of mental impairment. Wechsler Adult Intelligence Scale (WAIS) Six verbal and five non-verbal items allow derivation of verbal, performance and combined IQ scores. Discrepancies in verbal and performance scores may indicate organic brain damage or dysfunction, in that a higher verbal score may suggest dysfunction acquired after the development of verbal skills and not involving language areas of the brain. The Wechsler Intelligence Scale for Children - Revised (WISC-R) and the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) are variants used for assessing children. The B! variant of the WAIS has been standardized for the elderly up to the age of 80 years.
Limitations of IQ testing The clinical use of IQ tests is limited for several reasons: • Ability is assessed by measuring performance, which will be affected by factors such as fatigue, prior experience, anxiety and psychiatric illness. • IQ takes no account of creativity, social skills, etc., which are crucial determinants of successful functioning. Intelligence tests are poor predictors of educational and vocational achievement. Occupational therapy (OT) assessment may give more information. • A test is valid only for the population on which it was standardized; results may be misleading in the elderly, people with different cultural backgrounds, the chronic mentally ill and those of low intelligence. Clinically useful information is more likely to be obtained from individual test items which may show specific deficits, e.g. localized brain damage or developmental delay. The main clinical use of IQ tests reflects this, identifying specific cognitive deficits and assessing progression over time. These tests cannot precisely localize cerebral dysfunction. Riegel
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and Riegel describe a sudden, terminal drop in the IQ of the elderly during the five years before their death.
The genetics of intelligence Familial studies reveal following correlations: Monozygotic twins: reared reared Non-twin siblings: reared reared Dizygotic twins: 0.53
together 0.87 apart 0.75 together 0.5 apart 0.25
Unrelated individuals have correlation coefficients of —0.01 (reared apart) and 0.23 (reared together). A significant genetic component is therefore apparent but environmental influence is also of great importance.
Human Development Many different theoretical approaches have been used to explain the acquisition and development of behaviours, attitudes, reasoning ability and language. Two fundamental issues are central to an understanding of development: heredity versus environment, and the question of sensitive periods or stages. The role of heredity versus that of environment Maturation is the expression of genetic information relatively independent of environmental influences. It accounts for the acquisition of simple motor skills, but most human behaviour is the product of an interaction between maturational and environmental factors; it is difficult, if not impossible, to establish their relative importance in any one instance. The significance of sensitive periods/stages Many theories of development propose that children learn certain things at specific ages, i.e. at sensitive periods or developmental stages, and that they progress through different stages in a fixed, genetically determined, sequence. If the pattern of behaviour to be learnt can only be acquired at a specific developmental stage, not before or after, then the stage is referred to as a critical period. Imprinting, described by ethologists, is an extreme example of this type of learning which is characterized by rapid acquisition and relative resistance to extinction of the learned pattern of behaviour. The role of imprinting in man is unclear.
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Theories of development Different theories often explain different aspects of development from different theoretical and experimental approaches. They are not necessarily mutually exclusive and may not even be comparable.
Ethological approaches and the question of attachment Emphasis is placed on the observation of behaviour in a natural setting which may be modified, in a controlled way, to perform experiments. Development is described rather than explained. A typical sequence of social behaviours in the newborn human is: 0-6 weeks - begins to produce aimless, random smiles; 6-12 weeks - indiscriminate smiling at faces; 3-5 months - selective smiling at familiar faces - an early sign of developing attachment; 6-9 months - separation reaction and fear of strangers. From these and similar observations, stages of social development may be described. Although the timing may vary, e.g. children with multiple caretakers are slower in developing selective smiling, there does appear to be a sequence to general social development: up to 6-12 weeks - asocial stage; 3-6 months - stage of indiscriminate attachment; 6-9 months - true social attachments to specific individuals develop. This fixed sequence suggests a large maturational influence. Bowlby clarified the concept of attachment and stressed its biologically adaptive function. He noted that a child's first social relationship, usually with its mother, may profoundly influence subsequent relationships. He suggested, on the basis that a child's development went through sensitive periods, that continuous child-mother contact during early life was essential for healthy emotional development; anything less constituted maternal deprivation. This was an oversimplification and the concept of maternal deprivation is now seen as too general and abstract. Rutter stresses the importance of specific aspects of the parent-child relationship in influencing development and argues against an all-or-none phenomenon. Studies of extreme deprivation have demonstrated the resilience of the developing mind. Development does not completely cease after an early sensitive period and later positive events are able to change many effects of deprivation. The ethological approach now stresses the reciprocity within parentchild relationships; from birth, babies differ in temperament and tend to elicit different responses from the caretaker.
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Piaget's theory of intellectual development Intellectual development occurs in four stages which are characterized by qualitative changes in the nature of thinking: 1. Sensorimotor stage (0-2 years). The child develops the concept of object permanence and an awareness of himself as a distinct being. 2. Preoperational stage (2-7 years). The child develops use of symbols. Thinking is egocentric and often magical. Rules are considered to be inviolable (moral realism). Certain belief patterns are characteristic, including syncretism (everything is interconnected), animism (objects have feelings) and finalism (everything has a purpose). 3. Concrete operational stage (7-14 years). The child develops concepts of conservation of number, volume, etc. There is greater flexibility of thought, with a capacity to use classifications and make use of reasoning. 4. Formal operational stage (14 years onwards). The adolescent now has the capacity for systematic hypothesis testing and problem-solving. Abstract thinking becomes possible, as well as the capacity to think about one's own thinking (reflective or recursive thinking). Criticism of Piaget's work has focused on: • Piaget's own evidence for qualitatively different stages is sometimes equivocal; • other researchers have been unable to repeat some of Piaget's observations; • alternative explanations of Piaget's findings are often possible.
Kohlberg's theory of moral development Kohlberg extended Piaget's ideas on moral reasoning and studied how this develops throughout childhood and adolescence. He identified three levels, each with two stages: Level 1. Preconventional morality (less than 10 years): Stage 1. Punishment orientation. Rules are obeyed to avoid punishment. Stage 2. Reward orientation. Rules are obeyed to receive a reward. Level 2. Conventional morality (10-13 years): Stage 3. Good-boy/good-girl orientation. Rules are obeyed to receive the approval of others. Stage 4. Authority orientation. Rules are obeyed to avoid censure from authority figures and to avoid feeling guilty. Level 3. Postconventional morality (13 years onwards). Stage 5. Social contract orientation. Actions are guided by commonly-held principles related to public welfare and the good of society.
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Stage 6. Ethical principle orientation. Actions are guided by personally-held principles usually related to concepts such as justice, equality and dignity.
Erikson's stages of psychosocial development Progression occurs through stages marked by conflict. However, account is taken of social influences from outside the family and development is seen as a lifelong process in which different relationships have priority at different ages. He proposed eight stages which are shown in Table 3.2. Table 3.2 Age
Erikson's eight stages of psychosocial development Stage
0-1 years 1-2 years 3-5 years 6 years-puberty Adolescence Early adulthood Middle adulthood
i ii iii iv v vi vii
Old age
viii
Conflict Trust v. mistrust Autonomy v. doubt Initiative v. guilt Industry v. inferiority Identity v. confusion Intimacy v. isolation Generativity v. selfabsorption Integrity v. despair
Important relationships Mother Parents Family Friends Peer group Family and own children Family and own children Mankind
Development of language The development of language is closely related to the development of thinking; as concepts develop so do the words denoting them. Observed sequence of development 12-18 months: few isolated words. short 2-3-word sentences. 2 years: The child has three types of word: (a) open-class words which may be positioned anywhere in a sentence (e.g. mummy); (b) left-pivot words which occur as first word of a sentence (e.g. bye bye); (c) right-pivot words which occur at the end of a sentence (e.g. gone). Right-pivot words are not placed alone with left-pivot words. sentences more grammatically correct, 3 years: simple, but essentially adult form of speech. 4 years:
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Suggested mechanisms of development These have included: • Imitation. Little evidence exists to support this mechanism as the mainstay of language acquisition. Individual words may be learnt by imitation, but their correct grammatical use is probably acquired by other mechanisms. A young child's speech errors often reflect their use of inadequate grammatical rules rather than incorrect imitation of words. • Conditioning. Adults tend to reinforce comprehensibility, rather than correct grammar, in young children's speech. When grammar is experimentally reinforced, the response is too slow to account for the rapid acquisition of language. • Rule learning. Good evidence for this mechanism is provided by errors resulting from inappropriate generalizations of rules. For example, 'I goed out' may be said instead of 'I went out' because of the inappropriate use of the rule 'add -ed to a word to form the past tense'. This error is unlikely to have resulted from imitation or conditioning. Some workers have claimed that the generation of grammatical rules is genetically influenced. Naom Chomsky maintains people have an innate deep structure language which underlies the superficial language of their everyday spoken and written national language. Language development offers the best evidence of sensitive periods in man: severe deprivation at the critical time produces lasting impairment of function despite some catching up.
Reading List Atkinson, R.L., Atkinson, R.C., Smith, E.E. and Bern, D.J. (1993) Introduction to Psychology, 11th edn. New York: Harcourt Brace Jovanovich. Bandura, A. and Walters, R.H. (1963) Social Learning and Personality Development. London: Holt Rinehart & Winston. Bowlby, J. (1969) Attachment and Loss, Vol. 1 Attachment. London: Hogarth Press and Institute of Psychoanalysis, London. Brown, J.A.C. (1974) Freud and the Post-Freudians. London: Pelican. Erickson, E.H. (1950) Childhood and Society. New York: Norton. Hobson, R.P. (1985) Piaget: on the ways of knowing in childhood. In Child and Adolescent Psychiatry, 2nd edn. (eds M. Rutter and L. Hesov). London: Blackwell. Rutter, M. (1981) Maternal Deprivation Reassessed, 2nd edn. London: Penguin. Schaffer, H.R. (1971) The Growth of Sociability. London: Penguin.
4
Psychopharmacology IAN ANDERSON and CHRISTOPHER MORTIMORE
Psychopharmacology is concerned with the effect of drugs on behaviour and mental functioning. Modern clinical psychopharmacology, the use of drugs to treat psychiatric disorders, effectively began with the discovery of the antipsychotic properties of chlorpromazine by Delay and Deniker in 1952, followed shortly in 1957-58 by the recognition of the antidepressant actions of imipramine by Kuhn and iproniazid by Crane and Kline independently. The 1950s also saw the development of the first relatively safe benzodiazepine anxiolytic, chlordiazepoxide, as well as the beginning of the use of lithium for its mood-stabilizing properties. These discoveries came from clinical observation. Progress in the subsequent 40 years has mainly involved understanding and developing the pharmacology of the initial drugs, recognizing their limitations and widening their use, rather than true innovation. Drugs designed with specific pharmacological properties and with new mechanisms of action have recently begun to appear, suggesting that the territory mapped out in this chapter may radically change in coming years.
From laboratory to patient Only 1 in 10000 chemicals considered for therapeutic use reach the market, at a cost of £120 million and taking over 12 years. Promising compounds enter preclinical testing which involves further elucidation of pharmacology, likely efficacy based on animal models and toxicity profile. Development for human use involves four phases: • Phase 1, usually in normal volunteers, determines a drug's safety, side effects and gives initial information about pharmacokinetics. • Phase 2 initially involves open studies in patients for a particular indication, progressing to small randomized double-blind studies. • Phase 3 is the period of clinical development with larger double-blind studies controlled against standard treatment and placebo. Information
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about the safety and tolerability of extended treatment and drug interactions is gathered, leading to submission for registration of the drug with regulatory authorities. • Phase 4 involves post-marketing surveillance (see Adverse effects, below) which has led to the withdrawal from the market of a number of new psychotropic drugs in recent years (zimeldine - Guillain-Barre syndrome; nomifensine - hepatotoxicity; remoxipride - blood dyscrasia). The development of the drug for other indications is explored.
Pharmacokinetics Drugs are intended to act on target organs but usually have to be given systematically. Pharmacokinetics is concerned with the time course and disposition of drugs in the body ('what the body does to drugs'). Drugs are absorbed, distributed in the body and finally eliminated (metabolized and/or excreted) (Figure 4.1). There is a dynamic interplay between
Figure 4.1 Plasma drug concentration showing the phases of absorption, distribution and elimination after a single dose of a drug following first-order kinetics. Cmax is the maximum drug concentration and f1/2 is the elimination half-life
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these processes which determine how much of an administered drug reaches its target (its bio availability). The law of mass action states that 'the rate of a reaction is proportional to the active masses of the reacting substances'. For non-reversible reactions such as absorption and elimination the rate therefore is usually directly proportional to the amount of drug remaining to be absorbed or eliminated; this is calledfirst-orderkinetics and results in an exponential shape to the absorption or elimination curve (Figure 4.1). In situations where there is some other rate-limiting factor, the process becomes independent of drug concentration and follows zero-order kinetics, resulting in a fixed amount of drug being absorbed or eliminated for each unit of time. Most drugs used in psychiatry obey first-order kinetics. Notable exceptions where zero-order kinetics tend to apply are absorption from slow-release tablets (e.g. some lithium preparations) and depot intramuscular preparations (e.g. antipsychotics) and the elimination of drugs which rapidly saturate their metabolizing enzymes (e.g. alcohol and phenytoin).
Route of administration and absorption The route of administration determines how rapidly a drug reaches its site of action. Intravenous injection is the most rapid method of systemic administration. Intramuscular injection usually results in absorption over 10-30 min, with the rate dependent on the blood flow to the muscle and aqueous solubility. Formulations of drugs dissolved in inert oil may be absorbed very slowly and this forms the basis of 'depot' antipsychotic preparations. Oral administration is the most common route but absorption may be erratic and drugs are subject to metabolism by the liver (first-pass effect) before entering the systemic circulation, leading to variable plasma concentrations for many drugs. To be effectively absorbed the drug must be soluble in gastrointestinal fluids (delayed by slow-release preparations), acid resistant and able to pass across the gut wall. Absorption occurs by passive diffusion across cell membranes, the rate of which depends on the drug's molecular shape and weight, its lipid solubility and degree of ionization. Membranes have a high lipid content and the more lipid soluble a drug is (measured by its partition coefficient between oil and water), the more readily it will be absorbed. Weak acids are readily absorbed as they are un-ionized in the acid gastric juice (pH 2-3), while the opposite is true of weak alkalis (bases). Antacids reduce the gastric absorption of weak acids such as aspirin. The small intestine is less acidic (pH 5.0-6.6), but the large surface area and long transit times means that much of the absorption even of weak acids takes place here. Other methods of administration (e.g. subcutaneous, inhalation, topical) are not generally important for psychotropic drugs.
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Distribution Once absorbed into the plasma the drug is distributed to the various tissues in the body. This depends on tissue perfusion, binding to plasma proteins and the permeability of tissue membranes (see above). The body consists of a number of different tissues, or compartments, into which the drug is distributed. An approximation is the two-compartment model: a central compartment (plasma) from which drugs are distributed to a peripheral compartment (tissues). Drugs may become bound to sites in muscle, bone, fat and plasma where they exert no effect. This binding influences the distribution of drugs in the body and can reduce or prolong drug action, metabolism and excretion. Plasma protein binding, particularly to albumin, is an important factor in reducing the distribution of drugs to the brain, as only unbound drug is available to cross the blood-brain barrier. Highly plasma protein bound drugs (e.g. many antidepressants, anticonvulsants and warfarin) may displace each other from binding sites, leading to increased free plasma concentrations and potentially greater therapeutic or toxic effects. The blood-brain barrier, a consequence of the special structure of capillaries in the brain, acts like an extreme form of lipid membrane, allowing only lipid-soluble molecules to diffuse into the brain. Most psychotropic drugs are lipid soluble and passively diffuse in and out of the brain. Exceptions are L-tryptophan and L-dopa which are actively transported. Some areas of the brain are not protected by the bloodbrain barrier (e.g. the hypothalamic median eminence and part of the brainstem next to the vomiting centre). Elimination Elimination for most drugs follows first-order kinetics so that the time taken for the plasma concentration to fall by one half is constant (elimination half-life or t l / 2 .) This is useful in predicting the duration of action of a drug. A longer half-life allows therapeutic drug concentrations to be achieved with once-daily dosage. While metabolism may occur in plasma, lung and kidney, the liver is the most important site. Hepatic microenzymes are subject to genetic variation, resulting in large inter-individual variation, with some individuals or ethnic groups having reduced or inactive specific enzymes. The major metabolic routes are (i) non-synthetic reactions such as oxidation, reduction and hydrolysis which may produce active or inactive compounds, and (ii) synthetic reactions or conjugation (usually with glucuronic acid) which produces inactive, water-soluble compounds. The cytochrome P450 family of enzymes are responsible for non-synthetic oxidative metabolism of the majority of psychotropic drugs, in particular the antidepressants and antipsychotics. Drugs may induce or inhibit the activity of microsomal enzymes, leading to increased or decreased drug
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metabolism respectively. They may also compete with each other for the same metabolic pathway (e.g. haloperidol and tricyclic antidepressants). These effects form the basis for many drug interactions and may also cause tolerance (a reduced effect with repeated administration of the drug) if the drug induces its own metabolism (e.g. carbamazepine). Excretion can occur through the lungs or in bile, sweat, milk and saliva, but the most important route is through the kidney. This may be of the active drug or its metabolites. Metabolism of the parent drug to ionized and non-lipid-soluble compounds enhances renal excretion as these products are not reabsorbed across the lipid membrane of the distal tubule. Lithium is eliminated primarily by renal excretion and important increases in plasma lithium concentration can occur as a consequence of decreases in renal blood flow (e.g. non-steroidal antiflammatory drugs, angiotensin-converting enzyme inhibitors, dehydration), renal impairment and reduction of lithium reabsorption (e.g. thiazide diuretics, low plasma sodium). Manipulation of urine pH can sometimes be useful in hastening excretion (e.g. alkaline diuresis for aspirin and phenobarbitone overdose).
Steady-state concentration and therapeutic index With repeated doses of a drug an equilibrium is achieved in plasma between absorption and elimination, the steady-state concentration, which is dependent on dose administered, time between doses and half-life. The time to steady-state concentration is between four and five halflives. Large initial doses (loading doses) may be given to achieve therapeutic plasma concentrations more rapidly. When doses are administered at greater intervals than the half-life there are likely to be significant fluctuations in plasma concentration of that drug. For some drugs there is a recognized range of plasma concentrations required for therapeutic effect while minimizing adverse or toxic effects, the therapeutic range (e.g. lithium, carbamazepine, phenytoin). The therapeutic index is the ratio of the minimum plasma drug concentration causing toxic effects to that causing a therapeutic effect. Drugs with a low therapeutic index (e.g. lithium, phenytoin) usually require monitoring of plasma/serum concentrations.
Pharmacodynamics Pharmacodynamics is the study of the mechanism of drug action ('what drugs do to the body'). Most psychoactive drugs used in psychiatry affect the function of neurotransmitters. Traditionally drugs affecting monoamine neurotransmitters (dopamine, noradrenaline and 5-hydroxytryptamine (5-HT; serotonin)) have been important in the treatment of psychotic and affective disorders and those acting on gamma-
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aminobutyric acid (GABA) in the treatment of anxiety disorders and epilepsy. There is increasing interest in drugs acting on other neurotransmitters (e.g. peptides). Alteration of neurotransmitter function is also commonly responsible for side effects (unwanted or adverse effects). Drugs may influence neurotransmitter function at the level of: • synthesis (e.g. L-tryptophan is the precursor of 5-HT); • storage (e.g. reserpine depletes noradrenaline and dopamine stores in nerve terminals); • release (e.g. amphetamine releases noradrenaline and dopamine into the synapse); • reuptake (e.g. tricyclic antidepressants (TCAs) inhibit monoamine reuptake into the presynaptic neuron and so increase neurotransmitter concentration in the synapse); • degradation (e.g. monoamine oxidase inhibitors (MAOIs) prevent the breakdown of monoamine neurotransmitters); • receptors (e.g. antipsychotics antagonize dopamine receptors); • postsynapticmechanisms (e.g. lithium inhibits second messenger function). Receptors A receptor is a molecule, usually a protein, which binds to a drug with a high degree of selectivity (sometimes described as a 'lock and key'). The drug-receptor combination (complex) produces changes in the cell leading to a response. Receptors are found in two main sites: 1. On the surface of cells. These membrane receptors bind neurotransmitters and bring about cellular responses by directly affecting ion channels or second-messenger systems (see Chapter 5). They can be situated on a different neuron from the one releasing the neurotransmitter (postsynaptically] or on the same neuron (presynaptically). Presynaptic receptors (autoreceptors) are part of a negative feedback system regulating neurotransmitter release. Drugs binding to receptors can mimic or block the actions of endogenous neurotransmitters. 2. Within the cytoplasm or nucleus. These receptors usually bind hormones (e.g. thyroxine, glucocorticoids) and alter neuronal function by influencing gene transcription or protein synthesis. Agonists are drugs which mimic endogenous neurotransmitters, whereas antagonists block their effects. Most drugs bind reversibly to receptors and in the simplest case the response is proportional to the fraction of receptors occupied (law of mass action). As the concentration of drug increases, the response increases until all the receptors are occupied. This can be illustrated graphically as a dose-response curve (Figure 4.2). While two drugs may be able to bring about the same maximum
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Figure 4.2 Dose-response curves for three drugs. Drug A is a potent agonist with greater affinity for the receptor than drugs B and C. It elicits a full response at a concentration that produces about a half-maximal response with drug C and nearly no response with drug B. However drug C is a partial agonist and cannot elicit a maximal effect, whereas drug B is a full agonist and can do so if the concentration is high enough (concentration X)
response, one may do so at a much lower concentration because it has a greater affinity for the receptor. Some drugs cannot bring about a maximum response even when all receptors are occupied and are called partial agonists (e.g. buspirone, buprenorphine). Partial agonists are said to have lower efficacy than (full) agonists. The potency of a drug is determined by the proportion of the drug reaching the receptor, its affinity for the receptor and its efficacy. Not all drugs bind reversibly to their target site; traditional MAOIs are irreversible antagonists so that restoration of function can only occur by the synthesis of new monoamine oxidase which takes 2-3 weeks. The acute pharmacology of psychoactive drugs is usually responsible for side effects (Table 4.1) and sometimes for therapeutic effects (e.g. the sedative and anxiolytic effects of benzodiazepines). More commonly, there is a delay in the therapeutic effect of days to weeks (e.g. antidepressant or antipsychotic actions) believed to be due to secondary adaptive changes. One mechanism by which this occurs is an alteration in the sensitivity or number (up- or downregulation] of receptors. This is another mechanism by which tolerance can occur.
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Side effects of psychotropic drugs related to pharmacological actions
Pharmacological action Acetylcholine Muscarinic blockade
Noradrenaline Increased neurotransmission
a1 antagonism
5-Hydroxytryptamine Increased neurotransmission
5-HT2 antagonism
Side effects
Drugs
Dry mouth Blurred vision due to mydriasis Constipation Glaucoma Urinary retention Confusion (in elderly)
TCAs Antipsychotics - phenothiazines Anticholinergics - procyclidine, benzhexol
Arousal Insomnia
Non-sedative noradrenaline reuptake inhibitors MAOIs Psychostimulants - amphetamine, cocaine
Tremor Sweating Mild anticholinergic side effects due to functional opposition
Noradrenaline reuptake inhibitors MAOIs
Sedation Postural hypotension
Amitriptyline, amoxapine, trazodone, mirtazapine Chlorpromazine, thioridazine, clozapine, quetiapine
Miosis (if not counteracted by muscarinic blockade)
Thioridazione, clozapine
Priapism
Trazodone
Agitation Serotonin syndrome
MAOIs, SSRIs, L-tryptophan (rare outside combination treatment)
Extrapyramidal side effects (functional dopamine antagonism)
SSRIs
Nausea (probably mediated by HT3 receptors)
SSRIs, Venlafaxine
Increased appetite and weight gain
Amitriptyline, trazodone, nefazodone, mirtazapine Lithium (second messenger inhibition) Antipsychotics - phenothiazines, atypical antipsychotics
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Table 4.1 Pharmacological action Histamine H1 receptor antagonism
Dopamine D2 receptor antagonism
(Continued)
Side effects
Drugs
Sedation
Sedative TCAs - amitriptyline, dothiepin, trimipramine Maprotiline Mianserin
Extrapyramidal sideeffects Pseudoparkinsonism Acute dystonia Akathisia 'Rabbit syndrome' perioral tremor Tardive dyskinesia
Antipsychotics (less/absent with atypical drugs) Amoxapine Metoclopramide
Antipsychotics (less/absent with Neuroleptic malignant atypical drugs) syndrome Hyperprolactinaemia Depression/deficit syndrome (controversial)
Principles of prescribing The basic principle is that the likely therapeutic effects should outweigh the harmful effects of the drug. Patients should be given information about the likely effects of drugs (therapeutic and adverse) so that they give informed consent to treatment. Physical treatments for severe mental illness may be given without consent in certain circumstances under the provision of the Mental Health Act 1983. Compliance with treatment is enhanced by a good therapeutic relationship, proper explanation of treatment, well-tolerated and simple drug regimens, and monitoring. Not all the effects of a drug are due to its pharmacological actions and placebo responses are common. These are due to non-specific factors in treatment such as the therapeutic relationship and the patient's beliefs. While placebo effects may be frequent (e.g. accounting for 30 per cent of the response to antidepressant treatment in depression) it is not possible to harness them consistently; they are often transient, and ethically there is conflict with the principle of informed consent. 'Negative placebo' effects may also occur. Prescribing in special situations Pregnancy Medication is best avoided, especially in the first trimester, although more severe psychiatric disorders may require drug treatment. Preference
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should be given to drugs with which there is extensive experience, e.g. older TCAs and antipsychotics, although neonatal withdrawal symptoms may occur with the former and extrapyramidal effects with the latter. Some drugs are teratogenic, for example lithium, and therefore in general contraindicated or require special monitoring. (See Chapter 20 for further details.) Breastfeeding Psychotropic drugs are best avoided, although most are excreted in too small an amount in breast milk to have significant effects. (See Chapter 20 for further details.) Elderly There is increased risk of adverse events due to altered pharmacokinetics (reduced body weight, plasma protein binding, hepatic metabolism and renal elimination) and increased sensitivity to drugs. Lower doses and caution with compounds with long elimination half-lives is recommended to avoid accumulation and toxicity. Interactions with other drugs or coexisting physical illness should be considered. Children The use of psychotropic drugs is controversial. Psychotherapeutic and social measures are generally used as first-line treatments. Physical illness In liver disease the dose of any drug with hepatic metabolism should be reduced; benzodiazepines and antipsychotics can precipitate coma and MAOIs, lofepramine and phenothiazines can be hepatotoxic and are best avoided. In renal impairment there may be increased cerebral sensitivity to antipsychotics and benzodiazepines; lithium should be avoided if possible or carefully monitored if used.
Adverse effects • Type A: dose-related side effects that can be predicted from the receptor profile of the compound. Common type A adverse effects are summarized in Table 4.1. • Type B: idiosyncratic adverse effects. They are relatively uncommon, and are not predictable from the pharmacology of the drug although the mechanism may be known. In the UK, adverse drug reactions should be reported to the Committee on Safety of Medicines using yellow cards (these may be found in the British National Formulary - BNF). All suspected adverse events and drug interactions should be reported for newer agents (indicated by a
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black triangle in the BNF) and more serious drug reactions for older agents, irrespective of whether the effect is well recognized. Psychiatric symptoms caused by drugs The following drugs have been reported to cause psychiatric symptoms. In many cases the association appears understandable on a pharmacological basis (e.g. depletion or blockade of monoamines causing depression). In some cases the evidence for an association is anecdotal. Depression • chronic use of substances that deplete monoamines such as reserpine, tetrabenazine, amphetamine, cocaine; • cardiovascular drugs such as diltiazem, nifedipine, propranolol, clonidine, alpha-methyldopa; • psychotropic and neurological agents such as antipsychotics and benzodiazepines (controversial), amantadine, L-dopa, sodium dantroline, phenytoin, vigabatrin, alcohol; • miscellaneous compounds such as clomiphene, buserelin and glucocorticoids. Psychotic reactions • hallucinogens and stimulants such as LSD, psilocybin, phencyclidine, amphetamine, cocaine; • withdrawal from central nervous system (CNS) depressants such as benzodiazepines and alcohol; • anti-Parkinsonian agents such as antimuscarinics and dopamine agonists such as L-dopa and bromocriptine; • psychotropic and neurological drugs including MAOIs, appetite suppresants (e.g. fenfluramine), vigabatrin; • anti-infectious agents such as chloroquine, acyclovir, cycloserine; • other miscellaneous compounds such as glucocorticoids, ketamine, baclofen, digoxin, pentazocine, disulfiram.
Classes of psychotropic drugs The major groups of drugs in psychiatry are classified according to the disorders which they were originally developed to treat: antipsychotics or neuroleptics; antidepressants; anxiolytics and hypnotics; mood stabilizers; and anticonvulsants or anti-epileptic drugs. Other drugs Anticholinergic (antimuscarinic) drugs are used to reduce the extrapyramidal side effects of antipsychotics.
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Drugs for alcohol dependence: disulfiram, an aldehyde dehydrogenase inhibitor, causes an unpleasant and potentially dangerous systemic reaction if alcohol is consumed and is used as an adjunctive treatment to prevent relapse. Acamprosate, related to amino acid neurotransmitters, is thought to reduce craving for alcohol. Drugs for opioid dependence: methadone, an opioid agonist, acts as a substitute for diamorphine (heroin). Naltrexone, an opioid antagonist, prevents the psychological effects of taking opioids. Lofexidine and clonidine reduce the sympathetic overactivity that occurs during opioid withdrawal. Antidementia drugs: donepezil, an acetylcholinesterase inhibitor, is indicated for symptomatic treatment of mild to moderate Alzheimer's disease. Antipsychotics Phenothiazines were first synthesized in the nineteenth century and were used as veterinary antihelminthics and sedatives in the 1930s. Following the discovery of chlorpromazine's antipsychotic effect, other drugs were soon developed, such as haloperidol in 1957. Antipsychotics have a calming or tranquillizing effect which starts within a few hours, and an antipsychotic action which is delayed in onset by days or weeks. The major indication for antipsychotics is the treatment of psychotic illness, particularly schizophrenia, but also acute mania, psychotic depression and organic psychoses. Other psychiatric uses include the treatment of behavioural disturbance, severe or intractable anxiety and depression (controversial). Non-psychiatric uses are as antiemetics, anaesthetics (premedication and 'neuroleptanalgesia' combined with an opioid analgesic), intractable hiccough and as adjucts to analgesics in the terminally ill. Antipsychotics are rapidly absorbed orally. Some can also be administered by intramuscular injection. First-pass metabolism is particularly high with phenothiazines (about 80 per cent for chlorpromazine) but lower for other compounds. All antipsychotics are highly protein bound and are widely distributed. They pass freely across the blood-brain barrier with the exception of sulpiride. Chlorpromazine has a t 1 / 2 of 16-30h but has over 100 metabolites, many of which are active. Butyrophenones and thioxanthines have less complex metabolism and few if any active metabolites. Evidence accumulated during the 1970s that the therapeutic effect of antipsychotics was related to antagonism of dopamine D2 receptors. For example, clinically effective doses correlate with potency at inhibiting D2 receptors and an important study compared two isomers of flupenthixol which only differ substantially in D2 receptor antagonism; a-flupenthixol (a D2 antagonist) showed antipsychotic properties whereas b-flupenthixol (lacking D2 activity) did not. This evidence led to the dopamine
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hypothesis of schizophrenia which holds that dopamine systems are overactive in the condition. Although this is no longer accepted as sufficient to account for schizophrenia, dopamine antagonist action in mesolimbic/ mesocortical pathways is still thought to underlie the action of typical antipsychotics. However, the importance of other mechanisms was indicated by the important discovery that the atypical antipsychotic, clozapine, possessed superior efficacy to chlorpromazine in spite of being a relatively weak D2 antagonist. Candidates for the pharmacological basis of clozapine's action include antagonism at other dopamine receptors (Dj or D 4 ), 5-HT2 receptors or a particular combination of actions. New 'atypical' antipsychotics are being developed based on clozapine's pharmacology. Antagonism of D2 receptors also accounts for other effects of antipsychotics such as their antiemetic effect and, most importantly, for certain adverse effects (see Table 4.1). Dopamine blockade in the nigrostriatal pathway causes extrapyramidal side effects (see Chapter 29 for details) which can be functionally antagonized by muscarinic blockade and 5-HT2 receptor blockade; the latter may account, in part, for the reduced propensity to cause extrapyramidal side effects possessed by atypical antipsychotics (e.g. clozapine, risperidone). D2 blockade in the anterior pituitary (tuberoinfundibular tract) results in hyperprolactinaemia which can cause galactorrhoea and amenorrhoea. Other side effects of antipsychotics largely follow from their actions at other receptors (see Table 4.1), with different classes of drugs having a different receptor binding profile. Some antipsychotics (e.g. thioridazine) increase the Q-T interval, causing the potential for fatal tachyarrhythmias.
Classification of antipsychotics Classification has traditionally been according to chemical structure. Phenothiazines are tricyclic structures with antagonist properties at a large number of receptors. They are subdivided according to the nature of their side chain: (a) aliphatic (e.g. chlorpromazine, promazine): low potency and strongly sedative. Chlorpromazine in particular has been associated with hepatotoxicity. (b) piperidine: more antimuscarinic and hence a lower tendency to cause extrapyramidal side effects. Thoridazine may cause retinitis pigmentosa at higher doses. (c) piperazine (e.g. trifluoperazine, fluphenazine): more potent and selective D2 antagonists which are less sedative but more prone to cause extrapyramidal side effects. Thioxanthines are phenothiazine derivatives. Flupenthixol is relatively activating. Zuclopenthixol is sedating and is available as a short-acting depot (zuclopenthixol acetate) to treat severe behavioural disturbance.
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Butyrophenones (e.g. haloperidol, droperidol): relatively selective D2 antagonists and hence more prone to cause extrapyramidal side effects but fewer other side effects. Droperidol is sedative with a very short half-life. Diphenylbutylpipemdines are butyrophenone derivatives which are potent highly selective D2 antagonists with long half-lives. Pimozide may cause cardiac arrhythmias at higher doses. Substituted benzamides. Sulpiride is a low-potency, highly selective, D2 antagonist which is relatively free of extrapyramidal side effects but causes hyperprolactinaemia. Dibenzodiazepines. Clozapine is the prototypical atypical antipsychotic which antagonizes D2 receptors weakly, but a wide variety of other receptors more strongly. Haematological monitoring is required because it causes neutropenia leading to agranulocytosis in up to 1 per cent of patients which restricts its use to those unresponsive to, or intolerant of, typical antipsychotics. Olanzapine is a recently introduced analogue of clozapine which does not cause agranulocytosis. Other atypical antipsychotics (e.g. risperidone, quetiapine) are relatively selective dopamine and 5-HT2 antagonists which do not fit into this structural classification. Apart from risperidone they are more potent in antagonizing mesolimbic than nigrostriatal and tuberoinfundibular D2 receptors, resulting in an improved side effect profile. Antidepressants Antidepressants drugs were developed to treat depressive disorders, but many are also effective in other conditions such as anxiety disorders, obsessive compulsive disorder and bulimia nervosa. Nearly all antidepressants acutely modulate noradrenaline and/or 5HT function. The original monoamine hypothesis of depression postulated a deficit in function of these monoamines in depression. However, the delay in onset of action of antidepressants has led to the search for common longer-term effects. Recent interest has focused on the ability of antidepressants to increase 5-HT1A neurotransmission and on combined noradrenaline and 5-HT effects. Antidepressants have been confusingly classified according to structure (e.g. tricyclic, tetracyclic), pharmacology (e.g. MAOIs, SSRIs) or history (e.g. first-generation, second-generation). A classification based on pharmacology is used here.
Monoamine reuptake inhibitors These drugs inhibit the noradrenaline and/or 5-HT transporter on the presynaptic neuron and therefore acutely increase synaptic monoamine concentrations.
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Tricyclic antidepressants (TCAs) These are highly lipid soluble, readily absorbed from the gut and have a high degree of plasma protein binding. They bind to a variety of receptors, but their antidepressant effect is believed to be primarily due to monoamine reuptake inhibition (although trimipramine is only a weak inhibitor). Tertiary amines (e.g. imipramine, amitriptyline, clomipramine) tend to inhibit both noradrenaline and 5-HT reuptake. These are demethylated in the liver to secondary amines (desipramine, nortriptyline and desmethylclomipramine, respectively) which are more selective for noradrenaline reuptake. In general there is no clear relationship between plasma concentration of TCA and clinical effectiveness, although an optimal range (therapeutic window) has been suggested for nortriptyline and imipramine. The side effects are mostly predicted by increased monoamine function and receptor binding (see Table 4.1). Sedative TCAs (amitriptyline, dothiepin, trimipramine) are more potent antihistamines than less sedative ones (imipramine, clomipramine, nortriptyline, desipramine). TCAs have epileptogenic potential and are toxic in overdose owing to effects on cardiac conduction. Lofepramine, a newer TCA which is selective for noradrenaline reuptake, has fewer side effects and is relatively safe in overdose. Acute withdrawal of TCAs can cause insomnia, nightmares and agitation. Selective serotonin reuptake inhibitors (SSRIs) (citalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) These differ from one another in their structure and pharmacokinetics, but share the property of selective inhibition of 5-HT reuptake with mnimal binding to other receptors. Citalopram is the most selective and paroxetine the most potent. They are lipid soluble and well absorbed from the gut, with high plasma protein binding apart from citalopram. Citalopram and sertraline have less effect on liver cytochrome P450 enzymes than other SSRIs and less potential for drug interactions at this site. The active metabolite of fluoxetine, norfluoxetine, has a half-life of about a week. Side effects are related to increased 5-HT neurotransmission (see Table 4.1). Differences between SSRIs are subtle; fluvoxamine has the reputation for causing the most nausea and fluoxetine the most agitation. Epileptogenic potential is probably less than the TCAs and they are relatively safe in overdose. Withdrawal symptoms of dizziness, ataxia, gastrointestinal upset, influenza-like symptoms and sensory and sleep disturbance may occur. Other reuptake inhibitors Maprotiline, viloxazine and reboxetine are non-tricyclic selective noradrenaline reuptake inhibitors with relatively low anticholinergic side
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effects. Maprotiline is more epileptogenic than TCAs. Venlafaxine inhibits 5-HT reuptake, with weaker effects on noradrenaline reuptake. It lacks significant affinity at other receptors, has a side effect profile similar to the SSRIs and is relatively safe in overdose.
Monoamine oxidase inhibitors (MAOIs) Monoamine oxidase (MAO) exists in two forms, MAO-A which metabolizes noradrenaline and 5-HT and MAO-B which metabolizes phenylethylamine. Dopamine and tyramine (an indirect sympathomimetic present in some foods) are metabolized by both forms. Older MAOIs (phenelzine, tranylcypromine and isocarboxazid) are non-selective and irreversible and require a two-week wash-out period before interacting drugs are started. Moclobemide is a reversible inhibitor of MAO-A (RIMA) with a short half-life. Selegeline (L-deprenyl), an irreversible inhibitor more selective for MAO-B than MAO-A, is anti-Parkinsonian but lacks antidepressant effects at low doses. Antidepressant efficacy is said to require 80 per cent inhibition of plasma MAO. MAOIs lack receptor binding and side effects are generally related to increased monoamine function (see Table 4.1). Other adverse effects include postural hypotension, weight gain, sexual dysfunction and a potentially fatal hypertensive crisis with tyramine-containing foods (cheese reaction - see Chapter 29 for details). MAOIs potentiate the effects of sympathomimetics (particularly indirect) and combination with monoamine reuptake inhibitors may be dangerous (notably tranylcypromine with clomipramine).
Drugs acting at monoamine receptors Trazodone and nefazodone are only weak inhibitors of 5-HT reuptake but antagonize 5-HT2 receptors. Trazodone can cause priapism possibly related to a1 receptor antagonism (see Table 4.1). Mianserin antagonizes a2, 5-HT2 and H1 histamine receptors, although it lacks significant antimuscarinic properties. It may cause blood dyscrasias at higher doses. Mirtazapine is an antagonist at a1, a2, 5-HT2 and 5-HT3 receptors. It causes increased noradrenaline and 5-HT release through antagonism of autoreceptors. Other drugs L-tryptophan, the 5-HT precursor, is a weak antidepressant on its own but may augment the action of reuptake inhibitors and MAOIs in resistant depression. It is sedative and may cause side effects related to excessive 5-HT stimulation (serotonin syndrome) when combined with SSRIs or MAOIs. Other augmenting agents include lithium, thyroid hormones and pindolol, a b-blocker which antagonizes 5-HT1A receptors.
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Anxiolytics and hypnotics Alcohol and opioids have been used as anxiolytics and hypnotics since antiquity. Barbiturates were synthesized at the turn of this century and used as hypnotics and anxiolytics until they were replaced by benzodiazepines in the 1960s. Suggestions that abnormalities in a number of neurotransmitters, particularly GABA but also 5-HT and noradrenaline, cause anxiety disorders are unproven, but drugs acting on these systems are effective anxiolytics and hypnotics.
Drugs increasing GABA function GABA is the main inhibitory neurotransmitter in the CNS acting principally through the GABAA-benzodiazepine receptor complex which also has binding sites for barbiturates, benzodiazepines and neurosteroids. Inhibitory effects following stimulation of this receptor complex result from the opening of an associated chloride ion channel. Barbiturates Barbiturates directly open the chloride channel, which accounts for their danger in overdose. They are no longer indicated for the treatment of anxiety or insomnia. Drugs with a long elimination half-life are still used as second-line anticonvulsants and very short-acting drugs are used as anaesthetic agents (e.g. thiopentone, methohexitone). Barbiturates are potent hepatic enzyme inducers, have a low therapeutic index and addiction and tolerance are common. They cause sedation, cognitive impairment and respiratory depression. There is less tolerance to respiratory depression than other effects, making them particularly dangerous in overdose. Benzodiazepines The benzodiazepine receptor modulates the GABAA receptor and is unusual in that it binds to one group of compounds to increase the action of GABA (agonists such as benzodiazepines) and to another group that decrease GABA's effect (called inverse agonists) which are anxiogenic and proconvulsive. Flumazenil acts as an antagonist to both groups. Benzodiazepines are highly selective agonists which enhance the action of endogenous GABA but lack direct action on the chloride channel, giving them a high therapeutic index unless combined with other CNS depressants (e.g. alcohol which acts at the same complex). The medical use of benzodiazepines reflects their properties: sedation (use as hypnotics, the treatment of behavioural disturbance, minor operative procedures), anxiolysis, increased seizure threshold (use as anticonvulsants), muscle relaxation (treatment of muscle spasm) and amnesia (useful for minor operative procedures). Unwanted sedation and amnesia are experienced as side effects and ataxia can occur at higher doses.
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Benzodiazepines are rapidly absorbed and quickly distributed. They are highly protein bound and almost entirely metabolized in the liver. Many benzodiazepines have active metabolites with longer plasma elimination half-lives than the parent compound (e.g. diazepam, tl/2 32 h, is metabolized to desmethyldiazepam, tl/2 65h). Compounds with a short half-life without active metabolites are useful as hypnotics (e.g. temazepam), whereas compounds with longer half-lives (e.g. diazepam) are more appropriately used as anxiolytics and anticonvulsants. Tolerance to the sedative effects of benzodiazepines develops with chronic dosing, whereas this is less apparent for the anxiolytic effects. A withdrawal syndrome may occur, characterized by anxiety, rebound insomnia, somatic symptoms, perceptual disturbance and seizures, and hence a duration of treatment of less than 4 weeks is generally recommended. Non-benzodiazepine hypnotics Zopiclone and zolpidem are short half-life hypnotics that are structurally unrelated to the benzodiazepines. They have selectivity for subtypes of the benzodiazepine receptor and can be antagonized by flumazenil. At clinically used doses, the other properties of benzodiazepines are less apparent and they may be less prone to cause physical dependence.
Drugs acting on monoamine neurotransmitters Buspirone is a partial agonist at 5-HT1A receptors which are sited preand postsynaptically. It lacks immediate anxiolytic effects which develop over 2-3 weeks. It does not interact with CNS depressants and is not physically addictive. It appears effective in generalized anxiety but not panic disorder and also has antidepressant properties. Propranolol is a b-adrenoceptor antagonist which decreases peripheral anxiety symptoms caused by sympathetic overactivity. Antidepressants are also effective anxiolytics and are the drug treatment of choice for chronic anxiety. Mood stabilizers This group of drugs is primarily used for the prophylactic treatment of bipolar affective disorder, with evidence for efficacy in the acute treatment of mania. Lithium is used in the prophylaxis of recurrent depressive illness and as an augmenting agent in acute depressive illness not responding to antidepressants alone. Lithium and carbamazepine have also been used to treat impulsive and aggressive behaviour with limited success. Lithium Lithium was used in the nineteenth century to treat 'gout' which probably included melancholy or depression. In 1949 John Cade first
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described its use in manic patients and Mogens Schou developed a technique for accurate measurement of plasma levels in the 1950s which paved the way for routine clinical use. The quality of the evidence for lithium's effectiveness has been questioned and the recognition that withdrawal of lithium can precipitate mania may account for the widespread use of lithium not reducing admission for manic relapse. Lithium (available as the carbonate or citrate) is a monovalent cation which is counter-transported across membranes in a non-energy dependent way in exchange for sodium. It is not protein bound and is excreted unchanged by the kidneys. Oral absorption is rapid and slowrelease preparations have been introduced to reduce the plasma peak and related side effects. Lithium is slowly distributed in body water. Regular monitoring of serum lithium is required to maintain a therapeutic concentration in the range 0.5-1.2 mmol/1, but the lower half of the range is usually used because side effects increase above about 0.8 mmol/1 (gastrointestinal symptoms, tremor, polyuria and polydipsia, concentration difficulties). In addition the low therapeutic ratio means that toxic effects (vomiting, diarrhoea, polydipsia, ataxia, irritability, seizures and coma) begin between 1.5 and 2.0 mmol/1, with death supervening at 4.0 mmol/1. Enhanced risk of neurotoxicity at serum levels in the therapeutic range has been reported with a number of drugs including carbamazepine, SSRIs and haloperidol. The tl/2 is about 12 h but is increased if renal elimination is reduced. The mode of action of lithium is not known, partly because of its widespread effects. It interacts with sodium and potassium ions affecting neuronal membrane excitability and with calcium ions implicated in neurotransmitter release. It influences monoamine neurotransmission, increasing some aspects of 5-HT function. It inhibits second messenger systems, notably phosphotidyl inositol (linked to 5-HT2 receptors which may account for weight gain and possibly some of the therapeutic effects) and cyclic AMP (thought to be responsible for impaired renal concentrating ability and hypothyroidism). Finally it alters the gene expression of G-proteins which link receptors to their second messengers. Anticonvulsants as mood stabilizers Carbamazepine is widely used as an alternative to lithium for the prophylaxis of bipolar affective disorder since reports from Japan in the 1960s. It is believed to be useful for rapid cycling and non-psychotic illness, but there is less evidence for its use as an acute treatment for mania or depression. The therapeutic range is less clear than for its use as an anticonvulsant. Sodium valproate is effective in acute mania and is mainly used as a prophylactic agent in lithium-refractory patients. Bipolar affective dis-
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order which is non-psychotic or secondary to head injury is said to respond best. The therapeutic dose and plasma range is not established.
Anticonvulsants Anticonvulsants act by decreasing neuronal excitability and suppressing seizure activity. Bromides were used in the nineteenth century but were replaced by barbiturates and phenytoin in the early twentieth century. Traditional first-line drugs are carbamazepine, phenytoin, sodium valproate and ethosuximide. There is no standard classification, but it is possible to group anticonvulsants by putative mechanism of action. Enhancement of GABA function This group includes the barbiturates (phenobarbitone and primidone which is metabolized to phenobarbitone), benzodiazepines (e.g. clonazepam), possibily sodium valproate (unknown mechanism) and newer drugs such as vigabatrin (inhibition of GABA transaminase) and tiagabin (inhibition of GABA uptake). Barbiturates are no longer first-line anticonvulsants. Cognitive impairment and behavioural disturbance can occur in children with sedation in adults. Sodium valproate is well absorbed and highly plasma protein bound. It inhibits hepatic enzymes and increases the plasma concentration of other anticonvulsants. Hepatoxicity is a rare serious adverse effect. Gastrointestinal irritation, hair loss and rash can occur as can irritability, confusion and tremor at high doses. Ion channel antagonists Phenytoin and carbamazepine may act by inhibiting sodium channels, ethosuximide and sodium valproate, calcium channels, and acetazolamide, chloride/bicarbonate channels. Phenytoin is a hepatic enzyme inducer. It has saturable metabolism leading to zero-order kinetics. Drug interactions due to displacement from protein binding sites (e.g. valproate, salicylates) or enzyme inhibition (e.g. valproate, imipramine, phenothiazines) can cause toxicity. Neurological side effects include cognitive impairment, irritability and peripheral neuropathy. Gum hyperplasia, hirsutism, blood dyscrasias, rashes and folate and calcium deficiency may also occur. Carbamazepine is a hepatic enzyme inducer which induces its own metabolism. It is relatively free from cognitive side effects but causes sedation and ataxia at high doses. Rashes are not uncommon and blood dyscrasias can occur. Ethosuximide, used for absence seizures, does not induce hepatic enzymes. Side effects include CNS and gastrointestinal disturbance, blood dyscrasias and rashes.
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Inhibition of excitatory amino acid release Lamotrigine is an add-on drug that inhibits glutamate release. Unknown mechanism The mechanisms of action of piracetam, topiramate and gabapentin (although an analogue of GABA) are unknown.
Reading list Feldman, R.S., Meyer, J.S. and Quenzer, L.F. (1997) Principles of Neuropsychopharmacology. Sunderland, Massachusetts: Sinauer Associates. King, D.J. (ed.) (1995) Seminars in Clinical Psychopharmacology. London: Gaskell.
PART TWO A
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5 Neuroscience EILEEN JOYCE
Neuroanatomy Neurons and neuroglia Neurons or nerve cells are specialized for electrical and chemical transmission of information. Each neuron consists of a cell body with several branching dendrites and a single axon. Along the length of each dendrite are spinous processes or dendritic spines. Axons terminate in the form of branching processes, each ending with a terminal button. A synapse is the gap or cleft between neurons. A synapse is formed by a terminal button presynaptically and either a dendritic spine or an area of the neuron cell body membrane postsynaptically. Neuroglia or glia are the supporting and protecting cells of the CNS. There are several types. Astrocytes Large star-shaped cells which have several functions: • They form the greater part of the supportive matrix holding neurons in place. • They form the blood-brain barrier. Astrocytes near the surface of the brain send foot processes to the surface where adjacent processes abut against each other, essentially forming a limiting membrane. This glial capsule fuses with the inner layer of pia mater to form the pial-glial membrane which completely surrounds the brain and spinal cord. Blood vessels entering the brain invaginate the pial-glial membrane and therefore never have direct contact with neurons. Blood constituents leaving capillaries need to pass through this pial glial membrane or blood-brain barrier. • They react to local brain damage by increasing in size and dividing to form scar tissue or gliosis.
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• They straddle the space between blood vessels and neurons and their processes are in close contact with both. This suggests that they exchange metabolites and nutrients between the blood and neurons. • Synapses are surounded by astrocytic processes, suggesting that they act to prevent diffusion of neurotransmitters outside the synapse Oligodendroglia Round cells which send out protrusions which wrap around the axon to form the myelin sheath. Gaps in the myelin sheath between adjacent oligodendroglia are the nodes of Ranvier. Microglia Small cells which respond to pathological insults by changing into phagocytes which ingest microbes and products of tissue breakdown. Grey/white matter Grey matter is an area of the CNS composed of neuronal cell bodies. White matter is formed by axons travelling to and from areas of grey matter as white matter tracts or pathways. Functional neuroanatomy of the central nervous system
The telencephalon (cerebral hemispheres, cerebrum) The cerebral hemispheres are composed of an outer layer of grey matter (the cerebral cortex), an inner core of white matter (the centrum semiovale) and discrete masses of subcortical grey matter or nuclei which form the basal ganglia and the amygdala. The undulating surface is made up of convolutions or gyri, grooves or sulci and deeper infoldings or fissures. The telencephalon is separated into right and left hemispheres by the longitudinal fissure. Communication between the hemispheres is afforded by fibre bridges or commissures, the largest of which is the corpus callosum. Each hemisphere is composed of four lobes. The frontal lobe occupies the anterior part and is bounded posteriorly by the central sulcus separating it from the parietal lobe and inferolaterally by the Sylvian fissure (or lateral sulcus), separating it from the temporal lobe. The occipital lobe lies most posteriorly, separated from the parietal lobe by the parietooccipital sulcus. There are no clear anatomical landmarks delineating the temporal lobe from either the parietal or the occipital lobes.
The cortex There are two phylogenetically distinct types of cortex: allocortex and neocortex.
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Neocortex (new cortex) is differentiated into six layers and forms the major portion of the cortex, occupying most of the visible surface of the hemisphere. It can be further classified into primary and association cortex. Primary cortex is concerned with either the execution of voluntary movement or the analysis of sensory information as follows: Primary motor cortex is located as a coronal strip anterior to the central sulcus, in the precentral gyrus of the frontal lobe. Parts of the body are represented somatotopically to form the motor homunculus. Primary sensory cortex receives input from peripheral sense organs. Somatosensory cortex, subserving touch, pain, temperature and proprioception, is located as a sensory homunculus posterior to the central sulcus, in the postcentral gyrus of the parietal lobe. Visual cortex is located around the calcarine fissure of the occipital lobe. Auditory cortex lies deep within the Sylvian fissure in the temporal lobe. Olfactory cortex, subserving taste and smell, is found in the uncus and parahippocampal gyrus of the temporal lobe and so strictly is allocortical rather than neocortical. Association cortex forms the major portion of the neocortex (75 per cent) and is concerned with higher mental function. Association cortex, depending on the level of complexity, receives input from primary sensory cortex or from other areas of association cortex. Specific cognitive functions can in general be localized according to lobar divisions. Parietal lobe association cortex is concerned with visuospatial and tactile perception. Temporal lobe association cortex is concerned with visual perception and memory. Frontal association cortex is concerned with executive function. The edge or rim of the cerebral cortex is composed of allocortex (old cortex) which is poorly differentiated in that it does not have a distinct layered internal structure. The edge of the cerebral cortex is infolded to form a ring of allocortex on the medial face of the hemisphere. This is the limbic lobe (or rhinencephalon) and is part of the limbic system. The major constituents are the hippocampal formation and the cingulate gyrus. The principal source of input to both of these structures is association neocortex. The hippocampal formation consists of hippocampus, dentate gyrus and hippocampal gyrus. The dendate and hippocampal gyri are visible on the medial aspect of the cerebral hemispheres. The hippocampus is rolled inwards to occupy the floor of the ventral horn of the lateral ventricle and is therefore not visible on the surface of the brain.
The limbic system This consists of areas of allocortex as described above, discrete subcortical structures within the telencephalon and diencephalon and interconnecting fibre pathways. Neuroanatomical circuits are thus formed which
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subserve emotional behaviour and memory (see Neurophysiology, below). The exact components of the limbic system vary according to different opinion. However, central to the concept is the Papez circuit formed by: • in the telencephalon: cingulate cortex, hippocampal formation; • in the diencephalon: mamillary body of the hypothalamus, anterior nucleus of the thalamus; • connecting pathways: fornix (hippocampus to mamillary bodies); mamillothalamic tract (mamillary body to anterior nucleus of thalamus); gyrus fornicatus (anterior nucleus to cingulate gyrus); cingulate fasciculus (cingulate gyrus to parahippocampal gyrus). The amygdala consists of several groups of nuclei: corticomedial, central and basolateral.The latter two groups are part of the limbic system. The amygdala receives inputs from many diverse areas of the brain including a prominent neocortical input. The main output pathway is the stria terminalis which projects to the septum and the anterior part of the hypothalamus. Another important output is to the dorsomedial nucleus of the thalamus. Other structures often included in the definition of the limbic system include: • in the telencephalon: septum, olfactory bulbs, uncus, entorhinal cortex; • in the diencephalon: hypothalamus (i.e. areas in addition to mamillary bodies), habenular nucleus; • connecting pathways: stria medullaris (between several limbic structures and habenula). The basal ganglia (corpus striatum) Three masses of grey matter, congregated centrally in the midline of the hemispheres, form the basal ganglia and are concerned with the initiation and performance of voluntary movement - caudate; putamen and globus pallidus. The neostriatum is a collective term for the caudate and putamen. The kntiform nucleus is a collective term for the putamen and globus pallidus. The corpus striatum is a collective term for the caudate and lentiform nucleus.
The diencephalon This is a midline forebrain structure separating the telencephalon rostrally from the brain stem caudally. The bulk is made up of the thalamus and the hypothalamus; other structures are the epithalamus (pineal body and habenular nucleus), the subthalamus and the optic chiasma.
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The thalamus A large ovoid structure, occupying the upper half of the diencephalon, and composed of many groups of nuclei named according to their anatomical position. These nuclei are better considered with respect to function as follows. The cortical relay nuclei are situated ventrolaterally and receive the terminals of either motor or sensory fibres. The signal they convey undergoes complex transformations before being transmitted to specific areas of ipsilateral primary cortex: • visual pathway lateral geniculate nucleus visual cortex; • auditory pathway medial geniculate nucleus auditory cortex; • general sensory pathways ventral posterior nucleus somatosensory cortex; • cerebellum and basal ganglia ventrolateral and ventroanterior nuclei motor cortex. The thalamic syndrome is a peculiarly unpleasant pain sensation which can be experienced spontaneously and is secondary to disease, usually vascular, of the sensory relay nuclei. Intractable Parkinsonian tremor can sometimes be alleviated by neurosurgical ablation of motor relay nuclei. The association nuclei have reciprocal connections to areas of association cortex and, depending on the nucleus, with limbic structures and the hypothalamus, e.g. the dorsomedial nucleus projects to frontal cortex damage here can mimic the effect of frontal lobe lesions. The anterior nuclei are included in the limbic system and are integral part of the Papez circuit. The lateral nuclei, e.g. pulvinar nucleus, project to parietal and temporal association cortex, suggesting a role in the integration of sensory information. The nonspecific nuclei appear to be involved in arousal and form an integral part of the reticular activating system. They receive inputs from the reticular formation of the brain stem and project diffusely and bilaterally to the entire cortical mantle. Impulses from these nuclei, e.g. reticular nucleus and midline nuclei, are thought to regulate and maintain normal EEG rhythms. The hypothalamus Below the thalamus is a collection of nuclei collectively known as the hypothalamus; these nuclei are named according to either their anatomical position or their relation to the optic chiasma which lies just anterior. There are three regions as follows: • The mamillary region. This contains the large mamillary body, which forms one structure in the limbic circuit. • The tuberal region. At the base of the tuberal region is the median
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eminence, containing the arcuate nucleus. From the median eminence arises the infundibular stalk, which expands at the bottom to form the posterior lobe of the pituitary gland (or pars nervosa). Together the median eminence, the infundibular stalk and the posterior lobe of the pituitary gland are termed the neurohypophysis. • The suprachiasmatic region. Within this region, which lies above the optic chiasma, lie two nuclei, supraoptic and paraventricular. Axons from the cells in these nuclei pass downwards in the infundibular stem to terminate in the posterior lobe of the pituitary. Relations of the hypothalamus to the pituitary
There are two types of anatomical connection between the hypothalamus and pituitary, the hypothalamohypophyseal tract and the pituitary portal system. Hypothalamohypophyseal
tract
Axons from cells in the supraoptic and paraventricular nuclei (see above) terminate on capillaries in the posterior lobe of the pituitary. The cells manufacture the neurohormones oxytocin and vasopressin, which are packaged in secretory granules and transported down the axon to be released into the blood stream. Pituitary portal system
Arterioles derived from the carotid arteries form a network of capillaries that penetrates the median eminence and drains into vessels travelling down the infundibular stem into the anterior pituitary. Cells within the median eminence secrete hormones (releasing and release-inhibiting) into this vascular system to influence the function of anterior pituitary cells. Other connections of the hypothalamus
The hypothalamus receives sensory input conveying visceral and gustatory information from the brain stem and spinal cord and also input from the limbic system. It can also detect certain properties of circulating blood, such as temperature, osmotic pressure and hormonal levels. In turn, it influences autonomic nuclei in the brain stem and spinal cord and sends reciprocal connections to the limbic system. Thus the hypothalamus is poised to control homeostatic mechanisms in response to received information concerning the internal milieu and emotional state. Consequently it has been termed (by Sherrington) the 'head ganglion of the autonomic nervous system'. A separate and important connection is between the hippocampus and the mamillary body (the fornix), and between the mamillary body and the anterior nuclei of the thalamus (mamillothalamic tract), forming an important link in the Papez circuit of the limbic system.
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The brain stem The midbrain, pons and medulla oblongata constitute the brain stem.
The midbrain The superior part, the tectum, consists of the superior and inferior colliculi, which form part of the visual and auditory pathways, respectively. Ventral to this lie the cerebral peduncles composed of the substantia nigra, tegmentum and basis pedunculi. The substantia nigra is the important source of dopamine-containing neurons, which ascend to innervate the basal ganglia and other forebrain structures. Cell death here is the cause of Parkinson's disease. Within the tectum lies the red nucleus, part of the motor system and the nuclei of two cranial nerves: oculomotor (II) and trochlear (IV), both in the grey matter around the cerebral aqueduct (periaqueductal grey). The basis pedunculi, or crus cerebri, consist of corticospinal and corticopontine fibres.
The pons and medulla The important structures here are grouped below as follows. Motor pathways These travel in the most ventral portion of the brain stem and consist of the corticospinal tract, which in the medulla forms the pyramids, and the corticobulbar tracts, terminating on cranial nerve nuclei controlling musculature of the face and throat. Sensory pathways Running in a layer above the motor tracts, fibres of the dorsal column of the spinal cord synapse in the gracile and cuneate nuclei of the medulla and then travel forwards in the medial lemniscus. Fibres of the spinothalamic tracts of the spinal cord continue as the spinal leminscus within the brain stem.
Cranial nerve nuclei These occupy the most dorsal layer of the brain stem. Nuclei V-VII are in the pons and VIII-XIII are in the medulla.
The reticular formation Throughout the medulla, pons and midbrain is a central core of groups of cell bodies and fibres forming a reticular network. Within this are centres controlling such vegetative functions as the sleep/wake cycle, arousal, respiration, blood pressure and heart rate.
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The cerebellum Located above the pons and medulla, the cerebellum is composed of an outer cortex arranged as transverse folds of folia and a medullary centre of white matter, embedded in which are four pairs of central nuclei: fastigial, globose, emboliform and dentate. The cerebellum is divided into two hemispheres with a central uniting vermis. Each hemisphere has three lobes: flocculonodular, anterior and posterior. Fibres enter the cerebellum via the inferior and middle cerebellar peduncles and originate in the olives of the medulla and the pontine nuclei, respectively; fibres leave the cerebellum via the superior cerebellar peduncle. The cerebellum is a motor structure concerned with the coordination of movement and the maintenance of equilibrium. This is reflected in the nature of the input from sensory pathways, basal ganglia, motor cortex and the vestibular apparatus. The spinal cord The spinal cord is continuous with the medulla and extends caudally to the level of the first lumbar vertebra. Grey matter occupies a central Hshaped core and contains the cell bodies of lower motor neurons. The outer white matter consists of groups of fibre pathways or columns: these carry efferent motor fibres and afferent sensory fibres which leave and enter the spinal cord at different levels via spinal nerves. The tracts of the spinal cord are: • dorsal columns, consisting of the cuneate and gracile tracts and conveying sensory fibres mediating fine touch, pressure and proprioception; • ventral and lateral spinothalamic tracts, conveying pain, temperature and coarse touch fibres. • lateral columns (pyramidal or corticospinal tracts), carrying motor fibres from the cortex to the anterior horn of the spinal cord; • ventral and dorsal spinocerebellar tracts, carrying touch, pressure and proprioceptive fibres to the cerebellum. The meninges Investing the brain and spinal cord are three connective tissue membranes (meninges). The outer layer is the dura mater, a vascular fibrous layer. Dural reflections occur where it dips down between parts of the brain to make septa, such as the falx cerebri between the cerebral hemisperes, and the tentorium cerebelli between the cerebellum and cerebral hemispheres. The gaps formed between the inner periostium of the skull and the dural reflections accommodate dural venous sinuses. Beneath the dura lies the avascular arachnoid mater, which projects into the dural venous sinuses as arachnoid granulations. Here, cerebrospinal fluid present in the subarachnoid space diffuses across the arachnoid
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into venous blood. The innermost layer, the pia mater, is thin and vascular and closely follows the contours of the brain. It diverges from the arachnoid around the base of the brain to form cisterns, e.g. the cisterna magna between the posterior cerebellum and the medulla.
Cerebrospinal fluid (CSF) The ventricles are lined by a layer of epithelium, the ependyma. On the medial surface of the lateral ventricles and the roof of the third and fourth ventricles, the ependyma comes into contact with pia mater to form choroid plexuses, which have a highly folded surface. The choroid plexuses are the source of the CSF, which is formed by a mixture of diffusion and active transport of substances within the blood vessels of the pia mater into the ventricular space. The flow of CSF is from the lateral ventricles downwards through the third ventricle and cerebral aqueduct to the fourth ventricle. From here, CSF enters the subarachnoid space via apertures, the foramina of Magendie and Luschka. CSF travels up over the surface of the brain to be reabsorbed into the venous sinuses via the arachnoid granulations. It is not clear whether spinal CSF has any active circulation. Blood supply to the CNS The blood supply to the brain is derived from the vertebral and internal carotid arteries.
The vertebral artery system The two vertebral arteries travel forward on the underside of the medulla and each gives off a branch to the cerebellum (posterior inferior cerebellar). They unite to form the basilar artery, which gives off bilateral branches to the cerebellum (anterior inferior and superior cerebellar) and two bilateral pontine arteries. At the level of the midbrain it divides to give bilateral posterior cerebral arteries. These supply the medial aspects, and a narrow lateral strip, of the hemisphere - namely the occipital lobe and medial temporal lobe.
The internal carotid system The carotid arteries travel upward in the neck to terminate at the underside of the midbrain where they divide into anterior and middle cerebral arteries. The smaller anterior artery supplies the medial part of the hemisphere not supplied by the posterior artery, i.e. the medial aspect of the frontal and parietal lobes. The large middle cerebral artery supplies most of the outer part of the hemisphere.
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The circle of Willis This is a complex anastomosis of arteries on the underside of the midbrain formed by: the junction of the basilar artery and the posterior cerebral arteries; the junction of the internal carotid arteries and the middle cerebral arteries; the anterior cerebral arteries; the anterior communicating arteries, which link the anterior cerebral arteries; and the posterior communicating arteries, which link the internal carotid arteries with the posterior cerebral arteries. This serves to provide alternative routes for blood when one of the major arteries leading into it are occluded. Central arteries arise at various points from the circle of Willis to supply midline structures such as the basal ganglia, diencephalon and midbrain. Spinal blood supply The spinal cord is supplied at various levels by spinal arteries arising from the vertebral artery to supply the upper region, and from the descending aorta to supply the rest.
Venous drainage of the CNS The brain stem and cerebellum drain directly into the nearby dural venous sinuses. The cerebral hemispheres drain via either the subarachnoid veins or the deep venous system into the dural venous sinuses. The peripheral nervous system The peripheral nervous system consists of lower motor neurons, which directly innervate voluntary muscles, sensory fibres from all structures in the body and autonomic fibres innervating involuntary muscle, including that of blood vessels and glands. The cell bodies of lower motor neurons are located in the grey matter of the brain (cranial nerve nuclei) and spinal cord (ventral horn). Sensory neurons have cell bodies located in ganglia, close to the central nervous system, which send a long axon process to the periphery and a short process into the CNS. The autonomic nervous system requires two neurons for transmission. Cell bodies of preganglionic neurons arise within the CNS and synapse in autonomic ganglia from which postganglionic neurons send axons to the target site. Cranial nerves The cranial nerves carry motor efferents, sensory afferents and parasympathetic efferents to the head and neck. Three of these nerves, olfactory (1), optic (II) and acoustic (VIII) are adapted to convey special senses.
Oculomotor (III) Motor fibres arise from the oculomotor nucleus in the periaqueductal grey matter of the midbrain. It supplies the external ocular muscles (medial,
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superior, inferior recti and interior oblique) and levator palpebrae. Parasympathetic fibres arise from the Edinger-Westphal nucelus in the midbrain and synapse in the ciliary ganglion, which supplies the ciliary muscle that contracts to thicken the lens and the iris, so constricting the pupil. A Illrd nerve lesion causes diplopia (because the eye is deviated 'down and out'), fixed dilatation of the pupil and ptosis.
Trochlear (IV) Motor fibres arise from its midbrain nucleus to innervate the superior oblique muscle. A lesion of this nerve, which rotates and depresses the eyeball, causes diplopia that is maximal on looking down and in, e.g. on walking downstairs.
Abducens (VI) Motor fibres arise from the nucleus on the floor of the fourth ventricle and innervate the lateral rectus muscle. A lesion of this nerve causes medial deviation of the eye and diplopia.
Trigeminal (V) The motor nucleus is situated in the pons and innervates the muscles of mastication, several small muscles in the neck and the tensor tympani muscle, which dampens vibration of the tympanic membrane caused by loud sound. Motor fibres travel in the mandibular division of the trigeminal nerve. The sensory component serves the skin of the face, forehead and scalp in front of the vertex, the lining of the mouth, nose and sinuses, the teeth and the dura mater. These fibres travel in all three divisions (mandibular, maxillary and ophthalmic) and have their cell bodies in the trigeminal ganglion. From here, fibres pass into the substance of the brain to terminate in one of two nuclei: the main sensory nucleus in the pons, subserving mainly touch, or the spinal nucleus, which extends from the pons down to the upper cervical segment of the spinal cord and mediates pain, temperature and light touch. Proprioceptive fibres from the muscles of mastication have their cell bodies in the mesencephalic nucleus of the midbrain. Trigeminal neuralgia is a condition consisting of paroxysms of pain in the distribution of one of the divisions of the trigeminal nerve, triggered by minor irritation of the skin, e.g. pressure or cold.
Facial (VII) The facial motor nucleus lies in the pons and innervates the muscles of facial expression and several other muscles in the neck. The sensory component mediates taste from the anterior two-thirds of the tongue and general sensation from the parotid gland and skin around the ear.
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The cell bodies lie in the geniculate ganglion and from here fibres pass into the brain to terminate in the nucleus of the tractus solitarius in the pons. Parasympathetic fibres arise in the superior salivatory and lacrimal nuclei of the pons and innervate the glands of the mucous membranes and the submaxillary and sublingual salivary glands. Bell's palsy is caused by a lesion of the Vllth nerve as it traverses the facial canal in the petrous temporal bone, and is usually caused by inflammation. This produces paralysis of the facial muscles on one side, so that the face drops on that side and the eye cannot close or blink. Depending on the exact location of the lesion, hyperacusis, loss of taste and reduced salivation can also occur. Herpes zoster infection of the geniculate ganglion can cause a painful form of Bell's palsy known as the Ramsay Hunt syndrome. Upper motor-neuron Vllth nerve lesions cause paralysis of the lower two-thirds of the contralateral facial muscles. Glossopharyngeal (IX) Motor fibres arise in the nucleus ambiguus of the medulla and innervate the stylopharyngeus muscle. Parasympathetic fibres arise from the inferior salivatory nuclei of the medulla and innervate the parotid gland. The sensory component mediates general sensation from the posterior one-third of the tongue, pharynx and soft palate; taste from the posterior one-third of the tongue; and special receptors in the carotid sinus and carotid body concerned with the reflex control of blood pressure, heart rate and respiration. Vagus (X) Motor fibres arise in the nucleus ambiguus and innervate the muscles of the soft palate, pharynx and larynx. Parasympathetic fibres from the dorsal motor nucleus of the vagus in the medulla innervate the viscera of the thorax and abdomen and serve to inhibit heart rate and adrenal secretion, as well as to stimulate peristalsis of the gut and secretion in the liver, pancreas and stomach. Accessory (XI) Motor fibres leave the accessory nucleus lying in the upper cervical spinal cord and lower medulla to innervate trapezius and sternomastoid muscles. Hypoglossal (XII) The hypoglossal nucleus lies in the medulla and supplies motor fibres to the tongue. Lesions of the last four cranial nerves are most often due to brain stem strokes and can result in, for example, ipsilateral paralysis of the soft
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palate and pharynx, causing difficulty in swallowing, breathing and phonation (bulbar palsy). The tongue becomes atrophic ipsilaterally and deviates to the side of the lesion. Speech becomes dysarthric ('Donald Duck' speech). Spinal nerves There are 31 pairs of spinal cord: eight cervical, 12 thoracic, five lumbar, five sacral and one coccygeal. Each spinal nerve arises from the spinal cord as two roots - ventral and dorsal. The ventral root conveys motor efferents; the dorsal root carries sensory afferents, which have their cell bodies in the dorsal root ganglia. These roots merge, close to the spinal cord, and leave the vertebral column as spinal nerves. The sympathetic division of the autonomic nervous system arises from cell bodies in the 12 thoracic and upper four lumbar segments of the spinal cord. The axons join the spinal nerves via the ventral root but soon exit, via white rami communicantes, to enter the sympathetic ganglia. These ganglia form a communicating chain, parallel to the spinal cord, and lying on the lateral sides of the vertebral bodies. Once inside the ganglion, sympathetic fibres can synapse there, travel upwards or downwards to synapse in ganglia at other levels or pass through without synapsing. Fibres leave the sympathetic chain via grey rami communicantes to rejoin the spinal nerves. Postganglionic fibres then travel directly to the target organ. Preganglionic fibres synapse in ganglia close to the target organ. The parasympathetic division of the autonomic nervous system arises from the brain stem (cranial nerve nucle III, VII and IX supplying the head, and X supplying the thorax and abdomen) and spinal cord (sacral segments 2, 3 and 4 supply the lower abdomen and pelvis). These mostly travel directly to the target site without synapsing.
Neurophysiology Somatosensory systems Sensory receptors are the nerve endings of sensory neurons located throughout the skin, musculoskeletal system and viscera. In general, these are naked nerve endings, which mediate aspects of touch, pain and temperature sensation. Some nerve endings have become modified to mediate specific sensations: Skin 1. Fine touch 2. Vibration 3. Pressure
Meisner's corpuscle Merkel's disc Paccinian corpuscle Ruffini's endings
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Muscle
1. Proprioception
Neuromuscular spindle
Tendons
1. Proprioception
Golgi tendon organ
Sensory information from the face, oral and nasal cavities and skin over the anterior part of the head travels in the sensory component of cranial nerves V, VII and IX. The sensory component of spinal nerves enters the spinal column via the dorsal roots. There are two main sensory tracts in the spinal cord, the spinothalamic tract and the dorsal column. Nerve fibres subserving pain, temperature and coarse touch enter the dorsal horn and synapse with cell bodies of spinothalamic fibres. Their axons then cross to the opposite half of the spinal cord to travel upwards to the brain stem where they progress uninterrupted, in the spinal lemniscus, to synapse in two thalamic areas: • Ventroposterior nucleus. Here a great deal of perceptual processing occurs before impulses are relayed to the somatosensory cortex of the parietal lobe. For example, perception of pain and temperature can occur without the somatosensory cortex but cannot be accurately localized. • Nonspecific nuclei. These project diffusely to both sides of the neocortex and are concerned with arousal. The dorsal columns carry sensory fibres mediating fine touch, vibration and proprioception (joint position sense). After entering the spinal cord via the dorsal roots they turn upwards on the same side. The dorsal columns consist of a medial, gracile tract carrying fibres from the lower limbs and abdomen and a lateral, cuneate tract carrying fibres from the thorax and upper limbs. These synapse in the gracile and cuneate nuclei in the medulla. From here they decussate and travel in the medial lemniscus to the cortical relay nuclei of the thalamus where they synpase and are relayed to the somatosensory cortex of the parietal lobe. In addition, collaterals from fibres in the medial lemniscus subserving proprioception pass into the cerebellum.
Pain Unlike other sensory modalities, pain perception is a complex interaction between physiological and psychological processes. The degree to which pain is perceived differs between individuals because of differences in the affective response to pain sensation. Pain peception and pain tolerance are mediated by different neural systems: the intralaminar and parafascicular nuclei of the thalamus are involved in pain perception, whereas the dorsomedial and anterior thalamic nuclei and their connection to the limbic system and prefrontal cortex mediate the emotional response to pain.
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Endogenous opioid peptides Enkephalins and endorphins are intrinsic peptide neurotransmitters which have analgesic properties akin to morphine and other opiates. Opioid systems lie at different levels in the CNS. For example, within the substantia gelatinosa of the dorsal horn of the spinal cord are enkephalin interneurons which synpase on the endings of pain fibres carrying pain sensation from the periphery. They act to inhibit the release of the neurotransmitter substance P in the dorsal horn. This dampens down or gates the transmission of pain impulses (the gate theory of pain). Release of enkephalin in the spinal cord is triggered by serotinergic input from descending fibres originating in the raphe nuclei of the medulla. The raphe nuclei, in turn, are activated by input from the periaqueductal grey matter containing the peptide neurotransmitter neurotensin. Within the periaqueductal grey, there are enkephalin interneurons, which when stimulated set off the cascade of events resulting in enkephalin release in the dorsal horn. The periaqueductal grey receives input from frontal cortex, amygdala and hypothalamus, providing a route by which emotional and cognitive responses to pain can actually modulate pain transmission in the spinal cord. Finally, enkephalins and endorphins are also prominent in the amygdala, suggesting that the emotional response to pain is also modulated by these opioid neurotransmitters.
Perception of somatosensory information Ventroposterior nucleus projects to the primary somatosensory cortex of the anterior parietal cortex. The contralateral half of the the body surface is somatotopically mapped onto each hemisphere (sensory homunculus). Lesions here produces selective impairment in cortical sensations such as two-point discrimination, touch localization, position sense and stereognosis (perception of two stimuli simultaneously). Touch, pain and temperature sensation remain preserved. Integration of somatosensory information in parietal association cortex (praxis). In the posterior parietal cortex, visual and somatosensory information converge. This is essential for visuospatial orientation and for carrying out actions such as dressing, sitting in a chair, getting into bed, etc. Lesions here produce ideomotor, ideational and constructional apraxias.
Vision The visual receptors of the retina are specialized cells: rods, mediating light and dark, and cones, mediating colour. These contain photosensitive pigments that are activated by light and begin the process of transduction of light energy into electrical action potentials. Impulses from rods and
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cones converge on bipolar cells which, in turn, converge on ganglion cells. Ganglion cells are the cell bodies of visual neurons. Axons from these congregate at the optic disc and leave the eye as the optic nerve (cranial nerve II). There are no receptor cells overlying the optic disc, hence the blind spot on visual field testing. Lateral to the optic disc is the macula, which contains the fovea, an area containing a high density of cones and conferring the highest degree of visual acuity. Retinogeniculostriate pathway The optic nerve terminates at the optic chiasma, which lies in relation to the hypothalamus, behind and above, and the pituitary gland, below. Fibres from the nasal half of both retinae decussate here, so that fibres leaving the optic chiasma on the right carry neurons from the left nasal and right temporal parts of the retinae, and on the left carry neurons from the right nasal and left temporal retinae. These fibres form the optic tracts; thus the right optic tract corresponds to the left visual field and vice versa. The optic tract synapses in the dorsal lateral geniculate nucleus (LGN) of the thalamus. This structure has six layers, each receiving input from one eye only (2, 3 and 5 from ipsilateral eye and 1, 4 and 6 from contralateral eye), and each containing a complete map of the retina. In the LGN, the signal is modified before being relayed to the primary visual cortex of the occiptal lobe, via the geniculocalcarine tract. The entire visual field is mapped onto the primary visual cortex (striate cortex, area VI), each hemisphere receiving input from the contralateral visual field. Visual field defects A knowledge of the retinogeniculostriate pathway is important in appreciating the effect of lesions at different levels, which are listed below: • Optic nerve - monocular blindness at same side as lesion. • Optic chiasma - bitemporal hemianopia usually resulting from a pituitary tumour compressing the midline. • Optic tract - homonymous hemianopia. • Geniculocalcarine tract and visual cortex - homonymous hemianopia with macula sparing, - upper homonymous quadrantanopia if fibres in temporal lobe are specifically affected, - lower homonymous quadrantanopia if fibres in parietal lobe are specifically affected. Visual perception This is the analysis and understanding of incoming visual information. Coding of visual information begins at the retina:
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• place coding, with repect to which ganglion cells are stimulated; • temporal coding, with respect to the rate of firing of ganglion cells. Further analysis occurs in the LGN of the thalamus: • magnocellular system (layers 1 and 2), detection of form, movement and depth; • parvocellular system (layers 3-6), detection of colour and fine detail. Primary visual cortex consists of columns of cells perpendicular to the surface. Each analyses a particular portion of the visual field with respect to lines, edges, movement and colour. Within each column cells are specialized for feature detection: • simple cells - line orientation and edge detection; • complex cells - movement of lines, texture; • hypercomplex cells - movement of lines of specific length. Some cells are binocular in that they respond most vigorously when each eye sees a stimulus at slightly different locations. This is stereopsis or depth perception. Visual association cortex Primary visual cortex ( V I ) projects to prestriate cortex (peristriate cortex) which contains several functionally distinct areas involved in the processing of visual information across the visual field: V2 V3 V4 V5 -
orientation, depth; form; colour; movement.
Prestriate cortex then projects to inferior temporal and parietal cortex. Inferior temporal cortex Visual perception occurs here, i.e. the identification of objects. This involves a combination of information processed in areas V2-5. Neural circuits learn to detect stimuli with particular shapes. Cells respond best to three-dimensional objects rather than simple stimuli. Parietal cortex Spatial perception occurs here, i.e. where things are. In addition, visual infomation converges with somatosensory information to allow coordination of movement and manipulation of objects (praxis). Lesions in the visual association cortex result in visual agnosias, prospopagnosia, simultanagnosia, constructional apraxia, visual disorientation and visual neglect.
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Other visual pathways These involve projections from the retina to: • suprachiasmatic nucleus of hypothalamus (via ventral LGN), involved in synchronizing circadian rhythms; • accessory optic nucleus, involved in coordinating eye movements that compensate for head movements; • pretectum (via ventral LGN), involved in control of pupillary size; • superior colliculus (via ventral LGN), projects onto visual cortex and is involved in attention to visual stimuli and control of eye movements. Pupillary reflexes The pathway for constriction of the pupil in response to light involves afferents from the retina to the pretectal region of the midbrain. From here, impulses pass to the Edinger-Westphal nucleus on both sides and then to the pupil via parasympathetic efferents travelling in the oculomotor nerve (cranial nerve III). Thus when light is shone into one eye there is a direct and consensual contraction of the pupils. Convergence of the eyes also causes reflex contraction of both pupils (accommodation reflex). The efferent pathway is the same as for the light reflex, but the afferent pathway originates in visual association cortex and travels first to the superior colliculus. From here, impulses are relayed to cranial nerve nuclei to produce the eye movement and to the Edinger-Westphal nucleus to initiate pupillary contaction. The Argyll Robertson pupil, seen in tertiary syphilis, demonstrates the different afferent pathways because the pupil responds normally to accommodation but not to light. Dilatation of the pupils is mediated by sympathetic efferents from the superior cervical ganglion. This occurs in response to pain or emotional states, indicating the origin of impulses in the thalamic or limbic nuclei that project to the hypothalamus and then to the spinal cord. Eye movements Coordination of eye movements is via internuclear neurons travelling in the medial longitudinal fasciculus, providing communication between the three cranial nerve nuclei III, IV and VI and between both halves of the brain. Conjugate eye movements are initiated in the superior colliculus, which receives the command to move from the frontal eye fields of the frontal lobe (for voluntary movement) or visual cortex (for reflex movement).
Auditory system Sound waves travel along the external auditory canal and set into vibration the tympanic membrane. This vibration is transmitted across the
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chamber of the middle ear via three ossicles: malleus, incus and stapes. The stapes abuts on the oval window, a membrane at the interface between the middle ear and cochlea of the inner ear. The cochlea is a fluid-filled, spiral-shaped organ. Movement of the oval window sets into motion the fluid of the cochlea, causing the basilar membrane, which travels the length of the cochlea, to vibrate. The sensory receptors, specialized hair cells, are situated on the basilar membrane and are responsible for transduction of sound energy, as vibration, into electrical action potentials. Processes of sensory nerve cells, situated in the nearby cochlear ganglion, innervate these hair cells and convey impulses down long axons of the cochlear nerve (part of cranial nerve VIII), which synapse in two cochlear nuclei in the medulla. From here, auditory impulses travel via a polysynaptic pathway to the medial geniculate nucleus (MGN) of the thalamus where they synapse before being relayed to the primary auditory cortex. Deafness may be due to either impaired transmission in the external or middle ear (conduction deafness) or to neural pathway damage (nerve deafness). These can be distinguished by Rinne's test and Weber's test, utilizing a vibrating tuning fork. Auditory perception Primary auditory cortex is situated on Heschl's gyrus (posterior superior temporal cortex). It receives input from the medial geniculate nucleus. Neurons here identify the location of sound in the contralateral hemispace. Auditory association cortex is located in the superior temporal gyrus. This receives projections from the primary auditory cortex and the MGN. Wernicke's area This is an area of auditory association cortex in the caudal part of the left superior temporal gyrus which is specialized for the reception of language, whether spoken or written. Lesions here result in auditory agnosias. The vestibular system Detection of head movement and position relies in part on the vestibular apparatus of the inner ears and contributes to the control of posture. This apparatus consists of the utricle and saccule, for the detection of head position, and the semicircular canals for the detection of movement. All are fluid-filled and contain specialized hair cells, the receptors, which sense displacement of the fluid. Processes from the cell bodies of vestibular neurons, which have cell bodies in the nearby vestibular ganglion, innervate these hair cells and transmit action potentials along long axons into the brain stem to terminate in four vestibular nuclei
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(part of cranial nerve VIII). From these nuclei, impulses are relayed to the spinal cord in the vestibulospinal tract, the cerebellum, and the cranial nerve nuclei controlling eye movements. The latter connection allows fixation of an object despite movement of the head. This is illustrated by the phenomenon of nystagmus. After a period of rotation, the eyes show jerky movements consisting of a slow component in the opposite direction to the rotation followed by a fast movement jerking the eyes back to the midpoint. Conventionally the direction of the nystagmus is named according to the fast movement. Disease of the vestibular apparatus as in Meniere's disease can produce paroxysms of nystagmus.
Olfactory system Olfactory sensory receptors are modified nerve endings of olfactory neurons, which have their cell bodies buried within the nasal mucosa. From here, long axons (forming the first cranial nerve) enter the olfactory bulbs by piercing the cribriform plate of the ethmoid bone. Within the olfactory bulbs, olfactory neurons synapse with cell bodies which send axons directly to olfactory cortex. Unlike auditory, visual, gustatory and somatosensory modalities, there is no thalamic relay nucleus involved and the primary cortex is allocortical, with affiliation to the limbic system, rather than neocortical. Because the olfactory bulbs lie directly below the frontal lobes, anosmia is an early sign of an expanding frontal lobe tumour.
Gustatory system Taste sensation is transmitted via cranial nerves VII, IX and X. These neurons synapse in the nucleus of the solitary tract of the medulla. This area projects to the ventroposterior nucleus of the thalamus. Thalamic taste-sensitive neurons then project to the primary gustatory cortex in the anterior insular cortex and the adjacent frontal operculum. Unlike other sensory modalities, taste sensation is represented ipsilaterally. This area of cortex is in close connection to limbic areas such as amygdala and hypothalamus which presumably mediates the reinforcing value of tastes. Motor systems Four parts of the nervous system act together to control movement: lower and upper motor neurons, the extrapyramidal system, the cerebellum and motor association cortex.
Lower motor neurons These have their cell bodies in the ventral horn of the spinal cord. Axons leave via the ventral root and travel in spinal nerves to innervate
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skeletal musculature. These neurons form the final common pathway for all descending influences on motor function from the brain. Lower motor neuron lesions have the following effects on the muscles of innervation: • • • •
flaccid paralysis (decreased tone); muscle atrophy; muscle fasciculation; loss of tendon reflexes
Upper motor neurons These constitute all of the neurons originating in the brain that make connection with lower motor neurons in the ventral horn of the spinal cord. This is often referred to as the pyramidal system, although only the corticospinal tracts form the pyramids. In fact, several descending pathways form the upper motor neuron system as follows. The corticospinal tract This pathway stems from cell bodies in the motor cortex and travels uninterrupted to the spinal cord. From the cortex axons travel in the internal capsule of the hemispheres and then ventrally in the brain stem. In the medulla this system forms the pyramidal tract. When it meets the spinal cord most fibres decussate to form the lateral corticospinal tract and the rest descend ipsilaterally in the ventral corticospinal tract. This system controls the precision and speed of highly skilled movements. The rubrospinal tract This orginates in the red nucleus of the midbrain and is influenced by descending inputs from motor cortex and cerebellum. The reticulospinal tract This descending pathway originates in the nuclei of the pons and medulla reticular formation and is influenced by inputs from the motor and sensory cortices. The vestibulospinal tract This originates in the vestibular nuclei of the medulla and receives inputs from the vestibular neurons subserving information about the orientation of the head, and the cerebellum. Together the last three systems connect with lower motor neurons and govern gross movement and coordination of the trunk and limbs. The primary motor cortex is the source of upper motor neurons. This is
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located in the precentral gyrus and contains a representation of the body (motor homunculus). Effects of upper motor neuron lesions In general, upper motor neuron lesions produce the following effects on the muscles they control: • • • •
spastic paralysis (increased tone - clasp-knife rigidity); clonus of the muscles when stretched; increased tendon reflexes; upgoing plantar responses (Babinski's sign)
Extrapyrarnidal system This term suggests that it refers to all motor influences other than the pyramidal, i.e. corticospinal tract. In practice it refers to two intrinsic systems of the brain which influence the ouput of all upper motor neurons - the basal ganglia and cerebellum. Basal ganglia Afferents to the basal ganglia are from the neocortex, the substantia nigra and the thalamus. The main efferent pathway is to the motor cortex, synapsing once in the thalamus. The basal ganglia are crucially concerned with the initiation of movement and with its smooth execution. Thus, the basal ganglia can be thought of as a store of plans for motor action. Lesions of the basal ganglia can cause: 1. Akinesia. 2. Increased muscle tone: - cogwheel rigidity; - lead-pipe rigidity. 3. Involuntary movements: - tremor; - chorea; - athetosis; - dystonia.
Cerebellum The cerebellum receives input from the neocortex via pontine nuclei (corticopontocerebellar fibres), from proprioceptors via the spinocerebellar tracts, and from the vestibular apparatus. In turn, the cerebellum projects to motor cortex via the thalamus and to the brain stem nuclei, which form the origin of many motor tracts. The cerebellum receives information concerning orientation of the head, trunk and limbs, and also sensory processing from the cortex. It
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can influence all motor output pathways. It is crucially concerned with the coordination of motor activities. Cerebellar lesions can cause: 1. Ataxia: - of gait; - on fmger-to-nose test. 2. Intention tremor. 3. Dysdiadochokinesis (poor rapid alternating movements). 4. Dysarthria. 5. Nystagmus.
Motor association cortex (premotor cortex) Motor association cortex lies anterior to the primary motor cortex. This receives information being processed in temporoparietal association cortex and itself projects to primary motor cortex. In this way, motor function can be regulated by sensory information. Lesions in these pathways produce apraxia, which is the inability to execute purposive coordinated movement despite intact sensory and motor function. This premotor cortex is involved in the planning and initiation of complex movement guided by sensory information. This area is also involved in learning of complex movements. Broca's area is an area of premotor cortex in the left frontal lobe specialized for the production of speech. Executive function The prefrontal association cortex of the frontal lobes are thought to be involved in executive function. Executive function refers to those mechanisms by which performance is optimized in situations requiring the operation of a number of cognitive processes. In other words, the prefrontal cortex acts as a supervisor which channels cognitive resources into the performance of the most appropriate cognitive processes in times when there is heavy demand on these resources. This occurs, for example, when the action required is novel as opposed to routine or prepotent, when complex sequences of behaviour need to be planned and when strategies need to be adopted. The dorsolateral prefrontal cortex has been particularly implicated in executive function. Lesions here produce difficulties in abstraction, planning and short-term memory (working memory). The latter deficit is due the failure of the executive system to keep memories active in the mind for short periods of time while other cognitive operations are being performed. Cerebral dominance It is an oversimplification to regard one cerebral hemisphere as dominant over the other. Rather the hemispheres are functionally asymmetrical
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(lateralization). The term dominant is applied to the hemisphere determining language and preferred hand, foot and eye use. Language is almost entirely restricted to the dominant hemisphere. Handedness refers to preferred hand use: 90 per cent of the population are lefthemisphere dominant and right-handed; 30 per cent of lefthanders are right-hemisphere dominant and the rest are left-hemisphere dominant. The nondominant hemisphere in general mediates visuospatial function. Neurosurgeons wishing to avoid postoperative aphasia by operating on deep structures through the nondominant hemisphere, and psychiatrists wishing to minimize verbal memory impairment after electroconvulsive therapy (ECT) by giving unilateral ECT, need to determine dominance. Tests for dominance include the following: • Electroencephalogram (EEG) techniques - alpha rhythm shows greater suppression in the dominant hemisphere during verbal thought. • Dichotic listening and visual techniques - simultaneous presentation of different, neutral information to both ears or visual fields (using appropriate equipment) results in the information presented on the contralateral side of the dominant hemisphere being better perceived. • Wada technique - injections of sodium amytal into alternate carotid arteries produce temporary speech loss on injection on the side of the dominant hemisphere. • Unilateral ECT - administration of first treatments of a course of unilateral ECT to alternate sides and testing for verbal difficulties immediately after recovery is an adequate technique for determining dominance in preparation for further ECT. Verbal difficulties are less pronounced on the nondominant side. Language Language encompasses the abilities to speak and write grammatically, and to understand both the spoken and written word. These individual aspects of language are mediated by different, though connected, parts of the cortex within the dominant hemisphere. A disorder of language can arise from damage to the specialized areas themselves or the pathways linking them together (a disconnection syndrome). Production of speech is a function of Broca's area in the frontal cortex. Lesions here produce an expressive or motor aphasia, which can vary from complete mutism to mild word-finding difficulty. The ability to comprehend language, whether spoken or written, is a function of Wernicke's area, which spans temporal and parietal cortex just posterior to the medial end of the Sylvian fissure. Patients with lesions here are unable to execute commands, read (alexia), write (agraphia) or communicate thoughts. They are, however, able to speak, often fluently, although the
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content is meaningless (jargon aphasia) and may contain neologisms and paraphasias. Nominal aphasia is the inability to name objects: other words sounding like the intended word may be produced or phrases conveying a similar meaning may be used instead. A variety of lesions to language structures can produce this deficit, which is therefore of no localizing value. Emotional behaviour
Physiological correlates of emotions The experience of emotion produces characteristic bodily responses mediated by the sympathetic nervous system and neuroendocrine system. In acute stress these responses serve to prepare the individual for 'flight, fight or negotiation': • • • •
increased heart rate and blood pressure; increased sweating (reflected in the galvanic skin response); dilatation of pupils; diversion of blood from skin (pallor) and viscera to muscle and brain tissue; • increased cortisol secretion to elevate blood sugar. In addition to the above, chronic stress can have profound effects on the release of anterior pituitary hormones so that growth can be retarded and sexual function impaired (impotence, amenorrhoea, etc.). This is thought to be a means of conserving energy for action.
CNS control of emotion The above physiological reactions are normally governed in a reflex manner via brain stem and hypothalamic homeostatic mechanisms. When occurring in response to emotion, they are governed by higher cerebral structures - the limbic system and frontal cortex. Within the limbic systyem, the amygdala has been implicated as mediating learning about stimuli that have an emotional significance. Aggression The neurophysiology of aggressive behaviour shows how emotional behaviour is integrated at increasingly sophisticated levels within the CNS. Motor structures for the production of aggressive behaviour lie in the periventricular grey matter of the midbrain. Electrical stimulation here produces ill-directed uncoordinated behaviour known as sham rage. Descending input from the hypothalamus to this midbrain area serves to control this behaviour in a more coordinated fashion. In turn, the initiation of aggressive behaviour via the hypothalamic/
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midbrain system is modulated by descending pathways from the limbic system and prefrontal cortex. For example, the septum is inhibitory to the hypothalamus. In animals, septal lesions lower the threshold for eliciting aggressive responses. Similarly, the amygdala, when stimulated, facilitates aggression elicited by hypothalamic stimulation. Furthermore, bilateral lesions of the cingulate cortex have been used in man as a treatment for uncontrollable aggression. The EEG Characteristic variations in electrical potential can be recorded from the brain using surface or scalp electrodes - the electroencephalogram (EEG).
Alpha rhythm This is the dominant rhythm recorded during relaxed wakefulness with the eyes closed. It is prominent over the parieto-occipital region and consists of 50 mV waves at 8-12 c/s. The frequency of alpha waves is increased by low blood sugar, low body temperature and high arterial CO2 concentration. Forced overbreathing decreases arterial CO2 concentration and decreases the frequency of alpha waves, which may bring out latent EEG abnormalities. Alpha block (desynchronization) Alpha block occurs when the eyes are opened. Alpha waves are replaced by fast, irregular, low-voltage waves. This phenomenon reflects arousal. Beta rhythm This is seen in addition to alpha waves, especially over the frontal region; it is low voltage and at 18-30 c/s. Theta rhythm This rhythm consists of large waves of 4-7 c/s and in adults is present only in sleep. Delta rhythm Large slow waves of less than 4 c/s, seen during sleep. In childhood the EEG is slower and less regular, and theta and delta waves can be recorded during the waking state. Alpha rhythm becomes prominent in adolescence. A slowing of the alpha occurs in old age.
Arousal and sleep The recording from each EEG electrode represents net potential changes in cortical neurons located beneath that electrode. These are not action
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potentials propagated along long axons, but local inhibitory postsynaptic potentials (IPSPs) and excitatory postsynaptic potentials (EPSPs) on the dendrites of cell bodies. The rhythms are generated by ascending inputs from the reticular activating system.
The EEG in sleep The EEG changes according to the phases of sleep. There are two types of sleep, that accompanied by rapid eye movements (REM sleep) and that without rapid eye movements (nonREM sleep). NonREM sleep has four stages with progressive slowing and synchronization of the EEG: Stage 1. Onset of sleep, low-amplitude, fast-frequency EEG, vertex v waves. Stage 2. Appearance of k waves and sleep spindles, i.e. bursts of alphalike activity. Stage 3. Large slow waves appear in EEG ( < 60 per cent delta waves). Stage 4. Delta waves predominate - deep sleep (> 60 per cent delta waves). During REM sleep the EEG is desynchronized, as if awake, and REM sleep is therefore sometimes referred to as paradoxical sleep. During one night there are 4-6 cycles consisting of rapid passage through stages 1 and 2, 70-100 min in stages 3 and 4 and a period of REM sleep; 25 per cent of total sleep time is in REM. Children have more stage 3 and 4 sleep, while the elderly have less. NonREM sleep is not merely due to the withdrawal of external sensory stimuli but is an active process involving cortical synchronization. Desynchronization of the EEG is the physiological correlate of arousal. This represents a tonic activation of the cortex which facilitates sensory processing and enhances the readiness for motor activity. Activity in these systems is reflected in mood, e.g. in anxiety or hypomania there is often a concomitant heightened sensory awareness and overactivity or agitation. The autonomic nervous system (ANS) The ANS is a motor system controlling involuntary activity. Its principal neurotransmitters are noradrenaline and acetylcholine, distributed as follows: 1. Cholinergic neurons: - all preganglionic fibres; - parasympathetic postganglionic fibres; - sympathetic postganglionic fibres innervating sweat glands, blood vessels in skeletal muscle causing vasodilation. 2. Nomdrenergic neurons: - all remaining postganglionic sympathetic fibres.
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The adrenal medulla is essentially a modified sympathetic ganglion the cells of which have lost their axons so that noradrenaline is secreted into the blood stream. In general, the parasympathetic division is concerned with day-today vegetative function such as increased gastric acid secretion, increased intestinal motility, etc. Conversely, the sympathetic division is called into action in emergency situations when the body needs to be prepared for 'flight, fight or negotiation'.
Neuroendocrinology The pituitary gland Many of the endocrine functions of the body are under the control of the hypothalamus and the pituitary gland. The pituitary secretes hormones into the blood stream, which have either a direct action on target organs or an indirect action via the stimulation of other endocrine glands to release hormones with a direct action on target organs. The pituitary gland has two lobes; their hormones are listed below: Anterior lobe hormones • growth hormone (GH); • prolactin; • follicule-stimulating hormone (FSH); • adrenocorticotrophic hormone (ACTH); • thyroid-stimulating hormone (TSH). Posterior lobe hormones • Oxytocin; • Vasopressin/antidiuretic hormone (ADH). Hypothalamic control of the pituitary gland
Posterior pituitary secretion Oxytocin and vasopressin are synthesized in the supmoptic and paraventricular nuclei of the hypothalamus. They are transported as secretory granules down the axons that innervate the posterior lobe. Vasopressin release is stimulated by osmoreceptors in the anterior hypothalamus. These respond when the osmotic pressure of the blood is increased. Oxytocin is released by a reflex pathway from the nipple or genital tract to the hypothalamus.
Anterior pituitary secretion These hormones are under the control of releasing or inhibiting hormones secreted from the pituitary into the portal system. These are:
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corticotrophin-releasing hormone (CRH); thyrotrophin-releasing hormone (TRH); growth hormone-releasing hormone (GHRH); growth hormone-inhibiting hormone (somatostatin or GIH); luteinizing hormone-releasing hormone (LHRH); prolactin-releasing hormone (PRH); prolactin-inhibiting hormone (dopamine or PIH). In general, release of anterior lobe pituitary hormones is controlled by feedback inhibition of either the hormones themselves or the secondary hormones they stimulate, e.g. T4, cortisol, etc. Other factors can also influence their release, e.g. stress, temperature, starvation, etc., brought about by central mechanisms acting on the hypothalamus.
Psychoneuroendocrinology Neuroendocrine changes in endogenous depression Several neuroendocrine disturbances have been found in patients with endogenous or biological depression, such as diurnal variation, early morning waking or weight loss. However, these are of limited diagnostic value since they are not seen in all such patients and since other forms of psychiatric illness or physiological state can produce the same effects. The more distinct change are now considered.
The hypothalamic-pituitary-adrenal axis (HPA) Activity in this axis is increased in endogenous depression as shown by increased urinary, plasma and CSF levels of cortisol. The normal diurnal rhythm may be maintained, i.e. high in the morning and low in the evening, but the actual levels are higher than normal. In 50 per cent of depressives the normal inhibition of cortisol production by the exogenously administered glucocorticoid, dexamethasone, is not found. This failure to suppress cortisol production may be demonstrated by the dexamethasone suppression test (DST), in which 1 mg of dexamethasone is administered at 11 p.m. and plasma cortisol is measured the following day at 8a.m., 4p.m. and llp.m. Normally, plasma cortisol production is suppressed to less than 6 ng/ml. However, there are other causes of failure to suppress, thus limiting the value of the DST as a diagnostic tool. These include: 1. Psychiatric disorders: - anorexia nervosa; - alcoholism; - schizoaffective disorder. 2. Pregnancy. 3. Recent weight loss.
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4. Diabetes mellitus. 5. Any physical illness. 6. Drugs: - reserpine; - oestrogens; - opiates; - hepatic enzyme inducers. 7. 10 per cent of normal people. It has been shown that failure to suppress may be an artefact of weight loss or sleep disturbance associated with depression rather than depressed mood per se. Normal volunteers subjected to dietary restriction and sleep interruption (onset of sleep delayed and then woken 2 h earlier than normal) showed failure to suppress cortisol production in response to the DST.
Growth hormone (GH) response Normally, GH release is under the influence of dopamine and noradrenergic innervation of the hypothalamus. Hence, the dopamine receptor agonist apomorphine, the adrenergic alpha-2-receptor agonist clonidine and the indirect adrenergic agonist desmethylimipramine all induce release of GH. In some endogenously depressed patients, this response is normal to apomorphine but impaired to clonidine, so it has been argued that in depression, there is a downregulation of adrenergic alpha2-receptors in the forebrain.
Hypothalamic-pituitary-thyroid axis Although levels of thyroid hormones are normal in depressed subjects, a flattened response of TSH release to TRH stimulation can often be found. It has been suggested that these subjects have a normal response to DST, whereas nonsuppressors have a normal TSH response to TRH.
Melatonin secretion In animals and man there is an endogenous rhythmic secretion of melatonin from the pineal gland. Light inhibits the release of melatonin and so it is highest at night and lowest during the day. It has been reported that in depression and mania this cyclic fluctuation of melatonin secretion is altered; in depression it is 'phase advanced', i.e. the rise and fall of secretion is several hours ahead of normal, and in mania it is 'phase delayed'. This has been proposed to explain the variations in mood and sleep seen in mania and depression. Interest in melatonin secretion has also been generated by the observation that 85 per cent of subjects who tend to become depressed in the winter months (seasonal affective disorder - SAD) respond to bright
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light given for up to 6 h a day. This has been compared to hibernation in animals, which is regulated by the effect of daylight length on melatonin secretion. There is also a pathway by which light can affect the pineal gland: the retina sends projections to the suprachiasmatic nucleus of the hypothalamus which controls melatonin secretion via descending pathways to the superior cervical ganglion; from there is direct sympathetic innervation of the pineal gland. However, it has not been demonstrated that light therapy, in addition to improving mood, causes suppression of melatonin release. Neuropathology
Primary degenerative diseases
Alzheimer's disease Macroscopic changes Generalized brain atrophy. Frontal and temporal lobes, especially the medial temporal lobes, are more severely affected than occipital and parietal lobes. Histology 1. Neuronal degeneration, involving mainly pyramidal cells. 2. Glial proliferation. 3. Extracellular neuritic plaques. A central core of beta-amyloid is surrounded by a halo of degenerating neurons and glia. Beta-amyloid is a protein of 40-42 amino acids derived from a larger transmembrane protein known as amyloid precursor protein (APP). APP is metabolized or processed by two pathways. One pathway involves cleavage within the amyloid protein domain resulting in a soluble protein. The other pathway involves cleavage of APP at two sites at either end of the beta-amyloid sequence, thus releasing beta-amyloid 40-42 into the extracellular space. Deposition of beta-amyloid 42 appears to be the earliest event in the formation of neuritic plaques. Molecules of betaamyloid then coalesce and condense into beta-pleated sheets to form the core of a neuritic plaque. Beta-amyloid is thought to be neurotoxic on neighbouring cells, thus degenerating cells and glial proliferation are also found within the zone of a plaque. 4. Neurofibrillary tangles. These are intracellular paired helical filaments composed of abnormally phophorylated tau protein (a normal component of the intracellular microtubular system).
Plaques and tangles are most densely deposited in the hippocampus and amygdala, followed by areas of association cortex. Areas of primary cortex (e.g. visual, motor, somatosensory) have a more sparse distribution of
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plaques and tangles. Plaques and tangles also occur in the cholinergic subcortical nuclei of the basal forebrain, the serotoninergic raphe nuclei and noradrenergic locus coeruleus. Inflammation Inflammatory processes may be involved in the neurodegenerative processes, since alpha antichymotrypsin (an acute phase protein) is found in plaques and there is an increase in microglial cells in the brain which stain for interleukins. Thus there has been some success in slowing the course of Alzheimer's disease with nonsteroidal anti-inflammatory drugs.
Lewy body dementia Macroscopic changes 1. Mild brain atrophy. 2. Pallor of substantia nigra and locus coeruleus. Histology 1. Cortical Lewy bodies are present most frequently in the limbic areas, parahippocampal gyrus, cingulate cortex and insula, followed by frontal and temporal neocortex. The hippocampus is not affected. Subcortical areas involved include the substantia nigra and cholinergic basal forebrain nuclei. Lewy bodies are rounded filamentous eosinophilic intraneuronal inclusion bodies which contain the protein ubiquitin. 2. There is usually associated beta-amyloid plaque formation, but neurofibrillary tangles are not common. 3. Cell loss in cortex, substantia nigra and basal forebrain nuclei. 4. Spongiform degeneration of medial temporal lobe in many cases.
Pick's disease Macroscopic changes 1. Atrophy of frontal lobes, temporal lobes or both. The gyri have a 'knife-edge' appearance. 2. Atrophy of basal ganglia and thalamus. Histology 1. Balloon cells are swollen oval-shaped neurons present in 60 per cent. 2. Intraneuronal Pick bodies. These displace the nucleus to the side and consist of tau- and ubiquitin-containing protein filaments. Present in 20 per cent of cases. 3. Dense astrocyte proliferation and prominent gliosis of underlying white matter. Spongiform degeneration may be present.
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4. Cell loss in affected lobe. It has been suggestsed that there are two neuropathological types of Pick's disease. Type I is characterized by balloon cells and Pick bodies in the cortex. Type II has subcortical gliosis as the prominent feature involving white matter, nuclei of forebrain and brain stem and ventral columns of spinal cord.
Frontal lobe dementia Macroscopic changes 1. Mild atrophy of frontotemporal regions. Histology 1. Loss of pyramidal neurons. 2. Spongiform changes of frontotemporal neocortex and limbic cortex varying from mild to severe. Not present in all cases. 3. Mild to severe gliosis. Prion diseases (spongiform encephalopathies, slow virus diseases)
Creutzfeldt-Jakob Disease (CJD) Macroscopic changes 1. Generalized atrophy often apparent but the brain can also appear normal. In severe cases spongiform changes (see below) are apparent macroscopically. Histology 1. Spongiform neuronal degeneration of cortex, basal ganglia, thalamus and cerebellum. Intracellular vacuoles develop mainly in dendritic processes and coalesce to form microcysts. 2. Extracellular prion protein (PrP) plaque formation in 5-10 per cent of cases (positive staining for PrP by immunocytochemistry). N.B. Those cases without evident plaques also show positive tissue staining for PrP. 3. Dense astrocyte proliferation.
New variant CJD Spongiform degeneration and astrocytosis are present as in classical cases. The difference lies in the increased amount of PrP deposited throughout grey matter regions and the presence of PrP plaques in all cases which are extensively distributed throughout the cortex and cerebellum.
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Huntington's disease (HD)
Macroscopic changes 1. Marked atrophy of the basal ganglia, especially head of caudate nucleus. This causes the loss of the normal concave appearance of the lateral wall of the anterior horn of the lateral ventricles. 2. Variable atrophy of cortex, maximum in frontal lobes.
Histology 1. Relatively specific loss of medium spiny neurons in basal ganglia. 2. This neuronal loss can be seen in cortex, especially frontal cortex, but to a lesser degree. 3. Astrocyte proliferation. Parkinson's disease
Macroscopic changes 1. Depigmentation of the substantia nigra. 2. Variable atrophy of the frontal lobe.
Histology 1. The substantia nigra and ventral tegmental area show cell loss, Lewy bodies in surviving neurons and glial proliferation. 2. Lewy bodies are found to a lesser extent in locus coeruleus (noradrenaline), raphe nuclei (serotonin) and basal forebrain nuclei (acetylcholine). Progressive supranuclear palsy (Steele-Richardson syndrome)
Histology 1. Cell loss and gliosis in the basal ganglia, brain stem and cerebellar nuclei. 2. Neurofibrillary tangles in affected areas; these are different to those of Alzheimer's disease, consisting of straight tubules. Cerebrovascular disease
Multi-infarct dementia Infarcts within the brain tissue are the result of ischaemia secondary to arterioscelerotic changes in the arteries of supply. To a lesser extent, other pathophysiological mechanisms are involved, namely, thromboembolism from distal arteries and localized haemorrhage. The distribution of lesions depends upon the vessels affected. Circum-
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scribed cortical infarcts are produced by disease in a single large artery and result in a well-defined cortical syndrome. If several large arteries are involved, then multiple cortical infarcts can be seen, often accompanied by cortical atrophy, resulting in clinical dementia. Occlusion of smaller arteries supplying subcortical structures can also produce dementia, the so-called lacune state. Predominant sites of involvement are the internal capsule, basal ganglia and thalamus. Within the infarct, the histological changes are of neuronal cell death, demyelination, reactive gliosis, and sometimes cystic softening.
Subcortical arteriosclerotic encephalopathy (Binswanger's disease) This is a variant of cerebrovascular disease that can also be associated with cognitive impairment. The periventricular white matter shows diffuse demyelination and arterioscerotic changes are found in nearby nutrient arterioles. Metabolic and toxic CNS disorders
The Wernicke-Korsakoff syndrome The acute pathological changes are small, punctate haemorrhages within the periventricular grey matter of the brain stem. Two structures around the third ventricle are particularly affected, the mamillary body and the dorsomedial nucleus of the thalamus. These account for the memory deficit. The chronic lesions consist of cell loss, reactive gliosis and vascular proliferation.
Vitamin B12 deficiency As well as producing pernicious anaemia, vitamin B12 deficiency causes demyelination within the brain, spinal cord and peripheral nerves. The neurological manifestation of subacute combined degeneration of the cord and peripheral neuropathy can be accompanied by dementia.
Carbon monoxide poisoning The predominant lesions are patchy cell loss in the globus pallidus, hippocampus and cerebral cortex. There may also be confluent areas of demyelination in the deep white matter of the cerebral hemispheres. CNS infections
Acquired immune deficiency syndrome (AIDS) CNS complications of AIDS occur in two ways. First, opportunistic infections, secondary to immune deficiency. Second, the AIDS virus
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(human immunodeficiency virus; HIV) itself can directly invade the CNS and the virus is found in microglia and their activated forms, macrophages and giant cells. Direct infection of the CNS can produce several pathological types: 1. HIV encephalitis - foci of inflammation (microglia, macrophages, giant cells) throughout the grey and white matter. 2. HIV leukencephalopathy - diffuse white matter demyelination with reactive astrocytosis and macrophage accumulation. 3. Vacuolar myelopathy - vacuolar lesions of myelin in spinal cord.
Herpes encephalitis The herpes simplex virus has a predilection for the cortex of the medial temporal lobes and orbitofrontal cortex, causing massive destruction of all cell types.
General paralysis of the insane Cortical atrophy affects mainly the frontal and temporal lobes. Microscopically there is disturbance of cortical cell organization with cell death, glial proliferation, iron deposition and inflammatory infiltrates. Treponema pallidum can be recovered from these lesions. Multiple sclerosis
Macroscopic changes 1. Grey translucent plaques distributed throughout the white matter of the brain and spinal cord. The most common sites are around the lateral ventricles and in the cerebellum.
Histology 1. Acute lesions show degenerating myelin sheaths, glial proliferation and infiltration with lymphoctyes and macrophages. 2. Chronic lesions show prominent glial scarring and secondary degeneration of axons.
Reading list Brodal, A. (1981) Neurological Anatomy, 3rd edn. New York: Oxford University Press. Carlson, N.R. (1996) Physiology and Behaviour, 4th edn. Boston: Allyn and Bacon. Lishman, W.A. (1998) Organic Psychiatry, 3rd edn. Oxford: Blackwell Science.
6
Neurochemistry ROBERT KERWIN
Research methods in psychopharmacology Methods of studying neurotransmitters in animals Animal studies can give useful insights into neurotransmitter activity. Several different laboratory animals may be used, serving as behavioural, biochemical or psychological models. A brief account of some of the techniques, usually used in combination, is now given.
Empirical behavioural models Some aspect of animal behaviour may be observed empirically to correspond to a behaviour in man. This animal behaviour may be used to examine drug action, though a knowledge of the mechanism of action is not required. For example, a drug's ability to reverse the reserpine-induced hypothermia in an experimental animal predicts its possible antidepressant activity in man.
Specific behavioural models These behavioural models are predictive of specific neurotransmitter activity or represent models of clinical disorder. Some knowledge of the mechanism of action is therefore required.
Lesion studies Transmitter pathways may be anatomically and functionally characterized by studying the consequences of localized lesions. Interruption of a pathway allows subsequent behavioural and biochemical studies to elucidate their functional role and their relationship with other systems. Localized lesions may be produced by:
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electrolytic lesions; stereotactic knife cuts; focused ultrasound; focal injection of a selective neurotoxin such as 6-hydroxydopamine, which destroys dopamine (DA) and noradrenaline (NA) neurons, or 5, 7-dihydroxytryptamine, which destroys 5-hydroxytryptamine (5-HT) neurons.
Biochemical methods To follow lesions or drug studies, various methods of biochemically assessing neurotransmitter function in vitro are available: • Steady-state measurement of neurotransmitter levels. • Turnover studies of the rate of production of neurotransmitter, disappearance of a precursor, or the formation of metabolite give information on the activity of a pathway. • Enzyme studies give indirect information on the formation and breakdown of neurotransmitters and on their presynaptic and postsynaptic regulation. Enzymes often measured include: (a) tyrosine hydroxylase and catechol-orthomethyl transferase (COMT) to study DA pathways; (b) glutamate decarboxylase and GABA-transaminase to study gammaaminobutyric acid (GABA) pathways; (c) choline acetyl transferase and acetyl cholinesterase to study acetylcholine (Ach) pathways.
Receptor binding techniques The main use of these techniques is to measure in vitro the number and affinity of receptors in a tissue following an experimental manipulation. Samples of the tissue under study are incubated with a range of low concentrations of a ligand (a compound that binds with the receptors) labelled most often with a radioactive isotope. After an interval, the amounts of bound and free ligand, for each of the different concentrations, is determined. As the binding might be both specific (to the receptor) and nonspecific (to sites other than the receptors), the nonspecific binding is determined and the estimations of the amount of ligand binding to receptors corrected accordingly. A Scatchard plot (Figure 6.1) is produced by plotting bound/free (along the y-axis) against bound (along the x-axis). For a single receptor population, a straight-line plot is obtained where the slope gives a value of the binding affinity (the negative reciprocal of which is the dissociation constant) and the intercept with the bound axis gives the maximum number of receptor sites. The Scatchard plot assumes that the degree of binding is dosedependent, specific and saturable, i.e. the kinetics of the binding follow Michaelis-Menton kinetics.
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Idealized Scatchard plot for single receptor population
The Hill plot, first used to study the oxygen-haemoglobin interaction, can be used to determine the number of molecules per binding site and to study cooperativity. Carbamylcholine and decamethonium are both choline agonists, which when applied together are not merely additive, but potentiate each other's effects, i.e. they are mutually cooperative (or synergistic). Binding studies can be performed ex vivo (injecting label, then post mortem assay) or in vitro (incubating in test tube). Preparations of membranes can be used or receptor maps can be imaged by performing the binding study on histological sections placed against photographic film sensitive to the radioactive label used in the ligand (autoradiography).
Immunohistochemistry The ultrastructure of a nerve terminal can be studied by visualizing its neurotransmitters on histological sections. This is usually done by incubating a sample of the appropriate neural tissue with antibodies to the neurotransmitter. The antibody is then made to fluoresce by a fluoroscein key or stained using the peroxidase-antiperoxidase method. Sections are then examined by microscopy.
Release and uptake studies Presynaptic mechanisms of transmitter release can be studied by labelling brain slice preparations or synaptosomes with radioactive transmitter and following the efflux of radioactivity. Endogenous release can be measured with the help of electrochemical detectors or high-performance liquid chromatography. Inactivations systems, such as high-affinity reuptake systems, can be studied by following the rate of accumulation of radioactivity in the
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brain tissue from radiolabelled neurotransmitters when these systems are inhibited.
Gene expression studies In the previous 10 years it has been possible to monitor the processes of gene expression within cells by measurement of mRNA production within the CNS either following a drug intervention or brain lesions/ stimulation, etc. Four broad methods are available, as described below. In situ hybridization histochemistry This involves the use of radiolabelled or fluorescent probes of DNA in various forms which are complementary to the endogenous DNA. When specific sequences or genes are incubated with brain slices, this can provide an anatomical image of mRNA activity for a particular gene, e.g. a neurotransmitter receptor. Northern blot analysis This is a semiquantitative measure of mRNA formation following hybridization with a probe and the products are separated by molecular weight on a gel. Reverse and transcriptase polymerase chain reaction This involves the direct measurement of mRNA from brain tissue for specific genes, using a multistep approach to be able to amplify RNA directly by the polymerase chain reaction. Again, quantification of gene expression is from the products of gel electrophoresis. Ribonuclease protection assay This is a very sensitive technique for measuring gene expression by destroying all RNA within a specimen, except the gene of interest which is 'protected' by hybridization to a complementary probe.
Early immediate gene activity The gene products cfos and cjun and some others are the very first products of any gene activation and their production is often monitored as a worker for general neuronal activation, cfos and cjun are proteins and are therefore amenable to immunocytochemical analysis. Typical experiments would be to use this method to pinpoint specific regions in the brain where highly selective drugs may be acting.
Cerebrospinal fluid (CSF) examination Neurotransmitters, and their metabolites, are often estimated in CSF. However, this does not reflect CNS activity accurately because of the
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slow rate at which these substances are transported from the brain into the CSF.
Blood estimations Measurements of receptors on, and levels of, 5-HT, DA, NA and GABA in blood platelets, red cells and white cells are often claimed to reflect CNS states. Much of this work is inconclusive.
Focal (stereotactic) intracerebral injections The role of a specific neurotransmitter in a particular brain region can be elucidated by its localized injection into that region. For example, hyperactivity is evoked by injecting dopaminergic drugs into the nucleus accumbens, stereotypy is evoked by injecting dopaminergic drugs into the striatum, and increased behavioural activity is provoked by injecting substance P into the substantia nigra.
Electrical stimulation Behavioural responses may be studied through electrical stimulation of brain nuclei by permanently implanted electrodes. The classical example is the repetitive bar pressing seen in animals with electrodes implanted in the median forebrain bundle. Method of studying neurotransmitters in man Many of the techniques applied to animal studies may be adapted for use in human studies, as described below.
Post mortem brain tissue Post mortem specimens can be used to study: membrane receptor binding; transmitter levels; transmitter enzyme activity; immunohistochemical visualization; transmitter uptake and release; gene expression. The delay between death and the study, and the final mode of death (agonal status), critically influence the findings in the above studies. Only a small number of neurotransmitter systems, enzymes and receptors are stable enough to allow accurate characterization in post mortem studies.
Functional neuroimaging Recent advances in positron emission tomography (PET), single photon emission tomography (SPET), including functional magnetic resonance imaging
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(fMRI) have improved the correlation between clinical and neuroscientific variables. Regional blood flow, oxygen and glucose metabolic studies have been possible for some time using PET. It is now possible to label neurotransmitter precursors, receptor ligands and enzyme inhibitors to give in vivo maps of neurotransmitter pathways, receptors and regulatory enzymes. Examples include 18F-fluorodopa to study DA terminals, 187N-methylspiperone and 11C-raclopride for studying DA receptors, 11 C-flunitrazepam for benzodiazepine receptors, and 11 C-etorphine for opiate receptors. The clearest value of these techniques in psychiatry has been to use receptor ligands to monitor drug occupancy such as clozapine at D2 receptors or to test fundamental hypotheses such as dopamine theories of schizophrenia or GABA theories of anxiety. Although results are conflicting, some studies claim an increase in basal ganglia DA receptors (see next section) in schizophrenia. MRI imaging has chiefly found use as a structural scanner; however, it is now possible to measure small molecules by MR spectroscopy in vivo and to use NMR to monitor blood flow by rapidly measuring ratios of oxygenated versus deoxygenated haemoglobin (fMRI).
Individual neurotransmitters Dopamine (DA)
Chemical class Phenylethylamine (catecholamine). Synthesis Substrates: tyrosine and dihydroxyphenylalanine (DOPA). Enzymes: tyrosine hydroxylase and DOPA-decarboxylase. Breakdown Monoamine oxidase (MAO) and COMT; end-products include homovanillic acid (HVA). Method of inactivation High affinity reuptake. Receptor types according to genetic classification Dj - postsynaptic, linked to adenyl cyclase. D2 - postsynaptic, not linked to adenyl cyclase. D3 - limbic frontal/high affinity for atypical antipsychotic drugs. D4 - limbic frontal/high affinity for atypical antipsychotic drugs. D5 - 'D1 like'.
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Action Complex, modulatory. Distribution Ascending from the central midbrain to form two broad systems: the nigrostriatal and ventral tegmental limbic (mesolimbic) systems. Also major contributions to the incertohypothalamic system (diencephalic interneurons) and the tuberohypophyseal system (from arcuate nucleus to pars intermedia of the pituitary), and the periglomerular cells of the olfactory bulb. Pharmacology of the DA synapse Releaser - amphetamine, amantidine. Agonist - apomorphine, bromocriptine. Antagonist - haloperidol, chlorpromazine. Uptake inhibitor - nomifensine. MAO inhibitor - deprenyl (MAOI-B). Noradrenaline (NA) Chemical class Phenylethylamine (catecholamine). Synthesis Substrate: dopamine. Enzyme: dopamine beta-hydroxylase. Breakdown MAO and COMT; end-products include vanilmandelic acid (VMA). Method of inactivation High-affinity reuptake. Receptor types Alpha-1 - Postsynaptic. Alpha-2 - presynaptic (autoreceptors). Alpha-3 - postsynaptic. Beta-1 and beta-2. Alpha-1 and presynaptic alpha-2 receptors may be regulated by antidepressant treatment.
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Action Complex, modulatory. Distribution Majority arise from the locus coeruleus, but also some from the cell bodies in the lateral tegmentum and dorsal medulla. There are projections to the cortex, hippocampus, fornix, olfactory nuclei, septal nuclei, anterior thalamus, amygdala, piriform lobe, ventral thalamus, cerebellum and hypothalamus. There is a contribution to the descending bulbospinal noradrenergic system in the sympathetic lateral column. Pharmacology of the NA synapse Releaser - amphetamine. Agonist - phenylephrine. Alpha agonist - clonidine. Beta agonist - isoprenaline. Alpha antagonist - phentolamine, phenoxybenzamine. Beta antagonist - propranolol, pindolol, acebutalol. Uptake inhibitor - amitriptyline, imipramine. MAO inhibitor - phenelzine, tranylcypromine, mocobemide. 5-hydroxytryptamine, serotonin (5-HT) Chemical class Indole amine. Synthesis Substrates: tryptophan and 5-hydroxytryptophan (5-HTP). Enzymes: tryptophan hydroxylase and 5-HTP decarboxylase. Breakdown MAO and aldehyde dehydrogenase to give 5-hydroxyindole acetic acid. Method of inactivation High-affinity reuptake. Receptor types Central 5-HT1 (subdivided into 1A-1D). Central 5-HT2 (possible autoreceptor). Central 5-HT3 (only 5-HTla and 5-HT2 are thought to be important in depression). Peripheral vascular (M). Peripheral neuronal (D).
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Action Mostly inhibitory, but also facilitation of some excitatory responses. Distribution Dorsal raphe and median raphe midbrain nuclei - projections to basal ganglia, amygdala, accumbens, cortex, septum, hippocampus, hypothalamus and olfactory nuclei. Pharmacology of the 5-HT synapse Releaser - fenfluramine, reserpine, tetrabenazine. Agonist - LSD, mescaline, methyltryptamine. Antagonist - methysergide, cinnanserine, cyproheptadine, metergolide, risperidone, sertindole. Uptake blacker - chlorimipramine, nortriptyline, fluoxetine. MAO inhibitor - clorgyline, tranylcypromine. Acetylcholine (Ach) Chemical class Quarternary amine. Synthesis Substrates: acetyl co-enzyme-A and choline to form acetylcholine and co-enzyme-A. Enzyme: choline acetylase. Breakdown Acetylcholinesterase. Method of inactivation Acetylcholinesterase (hydrolysis of ester). Receptor types Nicotinic and muscarinic. Action Nicotinic: low dose - excitatory; high dose - depolarizing blockade. Muscarinic: inhibitory. Distribution Many systems including interneuronal in the basal ganglia and several long pathways such as pontine reticular formation to cerebellum, septohippocampal pathway, and ventral and dorsal tegmental pathways.
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Pharmacology of the acetylcholine synapse Nicotinic agonist - nicotine. Nicotinic antagonist - D-tubocurarine, gallamine, hexamethonium, suxamethonium. Muscarinic agonist - muscarine, carbachol, methacholine, pilocarpine. Muscarinic antagonist - atropine, hyoscine, benzotropine, procyclidine. Inhibition of release - botulinus toxin. Facilitation of release - black-widow spider venom. Cholinesterase inhibitor - physostigmine, neostigmine, edrophonium, donepezil. Gamma-aminobutyric acid (GABA) Chemical class Neutral amino acid. Synthesis Substrate: glutamate. Enzyme: glutamic acid decarboxylase. Breakdown GABA transaminase and succinic semialdehyde dehydrogenase. Method of inactivation High-affinity reuptake. Receptor types GABAa - baclofen-insensitive. GABAb - baclofen-sensitive, present peripherally. Action Inhibitory. Distribution Ubiquitous interneuronal inhibitory neurotransmitter - contribution to many long pathways including the descending striatonigral pathway, descending striatopallidal pathway, descending pathway from the limbic regions to the ventral tegmental region, and the cerebellar Purkinje cell output to the midbrain cerebellar nuclei. Pharmacology of the GABA synapse Releaser - none. Agonist- 3-aminopropane sulphonic acid, muscimol, baclofen (GABAb). Antagonist - bicuculline, picrotoxin.
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Uptake inhibitor - nipecotic acid, 4-methyl-GABA. Breakdown inhibitor -amino-oxyacetic acid, acetylenic GABA, gabaculine. Glycine This is the other major inhibitory amino acid neurotransmitter. It is located principally in the spinal cord. Glycine receptors are also present as part of a regulatory mechanism on excitatory NMDA receptors. Peptides Various peptides may act as neurotransmitters or neuromodulators. These include the five amino-acid encephalins, the related larger molecules, endorphins, the neurohypophyseal hormones, oxytocin and vasopressin, and the neurotransmitter substance P. Neuropeptides of neuralcrest gut origin, such as vasoactive intestinalpolypeptide (VIP) and chokcystokinin (CCK), currently arouse interest.
Encephalins and endorphins These were discovered after the recognition of highly specific opiate receptors and endogenous opioids. There is a large family of related molecules - lipotrophin, endorphin, alpha-endorphin, gamma-endorphin, encephalins. The encephalins are usually inhibitory and all produce analgesia in animal models. They delay extinction of active and passive avoidance behaviour and often produce catatonia-like states. All neuronal response to encephalins is naloxone-sensitive. Although widely distributed, particularly high concentrations are found in the dorsal horn, periaqueductal grey matter and basal ganglia.
Substance P This neurotransmitter was discovered in 1931 when Gaddum and von Euler found pharmacological activity in powdered extract of hypothalamus. This 11 amino-acid peptide is located in pain-conveying sensory afferents to the substantia gelatinosa of the dorsal horn, where it is a potent slow-onset depolarizing (excitatory) agent. The brain is rich in substance P, highest levels being in the substantia nigra. The best characterized pathway is a descending striatonigral system, but high concentrations also occur in the amygdala, hypothalamus and cerebral cortex. It is always excitatory. Substance P is dramatically reduced in the striatonigral pathway in Huntington's chorea. The physiological actions of the neurotransmitters may be deduced from their distribution and action. For example, the dopamine contributions to the nigrostriatal and tuberohypophyseal systems reflect its roles in sensorimotor coordination and hormone release respectively.
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Neurotransmitter theories of some major psychiatric disorders Dopamine and schizophrenia The dopamine hypothesis rests on the following facts: • amphetamine (DA releaser), lisuride, bromocriptine (DA agonists), Ldopa (DA precursor) can provoke some psychotic symptoms (typically paranoid); • current antipsychotic drugs are antidopaminergic and their clinical potency is correlated linearly with their ability to block D2-receptors; • drugs with geometrical isomers (e.g. alpha- and beta-flupenthixol) possess antischizophrenic activity only in the isomer that has antidopaminergic activity; • some important pathways, thought to control mood, behaviour, cognition and thought processing, utilize dopamine as a neurotransmitter, e.g. mesolimbic and mesocortical systems.
The current status of the dopamine theory Post-mortem studies of DA levels and receptors and CSF studies of DA and metabolites have given conflicting results. However, the majority show increased numbers of DA receptors in some brain regions (notably the striatum) in schizophrenia. This may be neuroleptic-induced. One finding independent of drug treatment is an apparent increase of dopamine in the left amygdala. Initially some PET studies showed raised spiperone binding (DA antagonist tracer) in schizophrenic brains but this has not been confirmed. In schizophrenia, degenerative changes are seen in temporal lobe structures, notably the hippocampus, but these regions have no dopamine input.
Pharmacology of antischizophrenic drugs Although antipsychotic agents have a wide spectrum of activity, they share the ability to block DA receptors, making it likely that this is their mechanism of action. DA blockade in man (as gauged by elevation of prolactin) occurs immediately, but there may be an irreducible delay of up to 6 weeks before antipsychotic efficacy is achieved. Thus, there may be some secondary or transynaptic mechanism which changes as a consequence of DA blockade and which is required for antipsychotic activity. The side effects strongly support DA receptors as the site of action. Parkinson's disease is produced by a loss of DA-containing nigrostriatal neurons and blockade of DA receptors produces analogous symptoms. Also, there are experimental reasons to suppose that tardive dyskinesia is produced by DA receptor supersensitivity, and the more pure and potent the DA-blocking action of a neuroleptic, the more likely it is to produce tardive dyskinesia (e.g. haloperidol trifluoperazine^
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pimozide). The most important revision to the dopamine hypothesis has come with the advent of functional receptor imaging. It has proved difficult to demonstrate elevations in dopamine receptors using PET or SPET. In addition, drug occupancy studies show it is possible to achieve good antipsychotic effect with atypical antipsychotics such as clozapine and olanzapine without blocking dopamine receptors. Serotonin and schizophrenia A role for serotonin in schizophrenia has been suggested by a number of findings: • there are reproducible abnormalities in 5HT2 receptors in schizophrenia; • some atypical antipsychotics have particularly high affinities for 5HT2 receptors; • highly selective 5HT2 blockers may act against negative symptoms; • a 5HT2a genetic variant may be present in excess in schizophrenia; • response to novel antipsychotics seems to vary with differences in receptor genes for 5HT2 receptors. Glutamate and schizophrenia A glutamate hypothesis for schizophrenia has also arisen because: • there is a fundamental interaction between glutamate and dopamine in limbic basic ganglia; • drugs like phencyclidine and ketamine which produce very characteristic schizophreniform states act at some glutatmate receptor subtypes (called the NMDA receptors); • there is a variety of consistent post-mortem studies in schizophrenia which show elevations in glutamate markers in frontal regions and decreases in temporal regions. The cholinergic hypothesis of Alzheimer's disease A cholinergic deficit for Alzheimer's disease has been hypothesized because of the following observations: • lesions to cholinergic systems in animals produce cognitive impairment; • anticholinergics given to man cause cognitive and memory impairment as side effects; • there is a loss of the cholinergic enzymes choline acetyl transferase and acetylcholinesterase in post-mortem material of patients who had suffered from Alzheimer's disease; • basal forebrain nuclei, where ascending cholinergic neurons arise, are degenerate at post-mortem (notably the basal nucleus of Meynert or nucleus gigantocellularis).
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Until recently, attempts to replace the deficient acetylcholine have produced various results. Therapeutic interventions have included precursor administration of choline or lecithin or agents such as pralidoxime which, via a metabolic action, accelerates the release of acetylcholine. With these agents, formal cognitive testing may reveal improvements, but the patients are often agitated and overactive and more difficult to manage. Acetylcholinesterase inhibition with physostigmine and tetrahydroamino acridine may be effective. However, tacrine was a successful orally active cholinesterase inhibitor but its use was limited by hepatoxicity. A new drug donepezil is now available and seems to be useful in early disease. The most recent pharmacological interest lies in the action of nerve growth factors (NGFs). NGF is responsible for the integrity of ascending cholinergic neurons. In animals, antibody to NGF provokes degeneration of these pathways and cognitive impairment. Subsequent NGF administration provokes regrowth of the cholinergic neurons and reversal of the impairments. Many groups are now attempting to synthesize active fragments of NGF that will cross the blood-brain barrier. Deficits in several other neurotransmitters are also apparent in postmortem brain, notably 5-HT, glutamate and sonlatostatin. Depression A series of observations from the 1950s led to the monoaminergic theories of depression. The main theories were based on either decreased function of the catecholamines (particularly NA) or decreased function of 5-HT. Monoaminergic theories received support from the following observations: • LSD and 5-HT share a similar structure and the former has a profound effect on mood (as well as other aspects of mental state); • reserpine, which depletes 5-HT, can precipitate severe depression; • iproniazid and isoniazid, used to treat tuberculosis, can induce euphoria and inhibit degradation of rnonoamines (MAOs); • tryptophan, precursor of 5-HT, is believed to have an antidepressant effect; • MAOIs have antidepressant effects; • reductions in serotonin, NA and DA metabolites in the CSF of depressed patients have been claimed by some studies; • low concentrations of 5-HT and metabolites have been reported in suicide victims at autopsy; • tricyclic antidepressants block reuptake of 5-HT. The evidence against the monoaminergic theories is as follows: • absence of unequivocal change in levels of metabolites in urine/CSF (with the exception of a link between low CSF 5-HIAA and suicidal behaviour);
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• not all drugs that deplete amine synthesis cause depression; • recent studies using improved methodology have failed to show any change in brain NA or 5-HT; • antidepressants block monamine reuptake or oxidation immediately, but clinical improvement may not occur for weeks; • alterations in DA function appear to be related solely to motor activity; • drugs that selectively block either NA reuptake (e.g. maprotilene) or 5-HT uptake (the SSRIs) have equivalent antidepressant potency. Research has concentrated on receptor function, following these observations: • Growth hormone release is mediated by central alpha-adrenoreceptors. Certain stimuli, such as insulin-induced hypoglycaemia, or clonidine, cause receptor stimulation and growth hormone release in normals, but not in some depressives. This is taken as evidence of a deficit in postsynaptic alpha-2-adrenoreceptors. • Reduced 5-HT uptake and reduced numbers of imipramine receptors have been found in the platelets of depressives, suggesting presynaptic receptor dysfunction. • Antidepressants paradoxically increase transmission at alphaadrenergic receptors. The significance of this is unknown. Many recent reports claim changes in both pre- (affecting autoregulation) and postsynaptic receptor sensitivities. Downregulation of postsynaptic beta-receptors is one of the most consistent findings after antidepressant treatment and has been reported after ECT and sleep deprivation. However, not all antidepressants produce this effect. The role of alpha-f- and alpha-2-receptors is unclear. 5-HT2 receptors also appear to be downregulated by antidepressant therapy and similar effects on 5-HTla have been reported. Some researchers have implicated the other neurotransmitter systems, such as the neuropeptides, GABA and endogenous benzodiazepine-like ligands. The picture is far from clear. Anxiety Because of the autonomic concomitants of anxiety and the role of ascending noradrenergic systems in animal models, early interest focused on noradrenergic abnormalities in anxiety. This situation was transformed by the discovery of the specific benzodiazepine receptor. Most interest is now focused on GABA, since the benzodiazepine receptor is an integral part of the GABA receptor. The possible role of hitherto uncharacterized endogenous ligands for the benzodiazepine receptors also needs to be considered, as does the role of a possible abnormal anxiety peptide.
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Drug development research Stage of drug development Preclinical phases (animal studies) These include: (a) synthesis of candidate molecules according to known activity of chemically related molecules; (b) screening for biological activity: (i) empirical, e.g. behavioural screen, (ii) specific, e.g. DA receptor assays, amine uptake assay, anticonvulsant activity; (c) full characterization of pharmacological activity, including the potential drug's potency, affinity, and range of activity in other systems; (d) assessment of a promising molecule for: (i) acute toxicity, (ii) carcinogenicity, (iii) teratogenicity, (iv) pharmacokinetic profile; (e) assessment of long-term toxicity and carcinogenicity - often run concurrently with early human studies.
Clinical phases Phase I. Young healthy volunteers receive a fraction (l/30th) of the predicted effective dose. This is gradually increased in subsequent and different volunteers until the effective dose is reached. The effect and side-effect of a single dose is carefully monitored before careful subchronic dosage (usually 14 days) is administered. Phase II. A small number of carefully selected (named) patients at independent centres receive the drug. Approval is required by the local ethical committee and the Committee on Safety of Medicines (CSM). Phase III. The clinical trial begins (see below). Information from longterm animal studies is usually incorporated at this stage. The drug company redesigns synthesis from small-scale laboratory to large-scale manufacture. Pharmaceutical research produces the best formulation (e.g. slow-release, enteric-coated, etc.). If all is well, an application is submitted to the CSM for a product licence and distribution. A data sheet is then distributed to all registered medical practitioners. Phase IV. Postmarketing surveillance addresses: (a) patient acceptability; (b) Long-term side effects; (c) rare side effects;
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(d) the overall place of the drug alongside other pharmacological and therapeutic options.
The clinical trial: principles and terminology 1. Objective. Clinical assessment of a drug usually attempts to answer one of these questions: (a) (b) (c) (d)
is it effective? is it better than a standard active drug? is it better than placebo? does it have fewer side effects?
2. Exclusion. It is important that criteria are preset to allow patients to be removed from the trial if it is to their benefit, e.g. deterioration or urgent requirement for other forms of treatment. 3. A run-in period on placebo should eliminate likely defaulters. 4. Comparison can be made between subjects or with the same subject at different times. 5. Removal of bias. Thirty to fifty per cent of patients are placebo responders. However, control patients often know when they are on an active drug, e.g. headache with nitrates, slow pulse with betablockers, characteristic taste of aspirin, stiffness with neuroleptics. The usual design is randomized double-blind crossover, ensuring match of colour, taste and appearance. 6. Carry-over effects. These are very important in psychiatry. Many drugs take several weeks to wear off and may carry over to contaminate the standard or placebo arm of a crossover trial.
Reading list Bjorklund, A. and Hokfelt, T. (1983) Methods in Chemical Neuroanatomy (4 vols). Amsterdam: Elsevier. Cooper, J.R., Bloom, F.E. and Roth, R.H. (1987) The Biochemical Basis of Neuropharmacology, 5th edn. Oxford: Oxford University Press. Green, A.R. and Costain, D.W. (1981) Pharmacology and Biochemistry of Psychiatric Disorders. Chichester, Wiley. Heiss, W.D. and Phelps, M.E. (eds) (1983) Positron Emission Tomography of the Brain. Berlin: Springer Verlag. Iversen L.L., Iversen, S. and Synder, S.H. (1977-84) The Handbook of Psycho pharmacology, Vols 1-18. New York: Plenum Press.
7 Genetics MICHAEL OWEN and KIERAN MURPHY
Basic genetics Genes and chromosomes Genetic information is stored in the nucleus of human cells as deoxyribonucleic add (DNA), which is arranged into 23 pairs of chromosomes. One member of each pair is derived from each parent. Genes are lengths of DNA that specify the structure of a protein product. They are situated at specific sites (loci) on the chromosomes. Since chromosomes exist in homologous pairs, so also do genes. Individual genes may exist in several forms, termed alleles, only two of which can be present in any single individual, with one being derived from each parent. Individuals with two different alleles are heterozygous, while those in whom they are the same are homozygous. Usually, cells divide by a process called mitosis, which involves doubling of each pair of chromosomes such that both daughter cells acquire an identical set to the parents, in which both members of each pair are present (diploid). In contrast, gametes are formed by a type of cell division known as meiosis, in which homologous pairs of chromosomes separate (segregate) to give daughter cells with only one member of each pair (haploid). The union of gametes at fertilization usually restores the diploid state. The normal complement of human chromosomes, or karyotype, consists of 22 pairs of autosomes and one pair of sex chromosomes. Females have two X chromosomes and males have one X and one Y. Sexual development in the embryo depends upon whether or not a Y chromosome is present. In the female, each cell contains only one active X chromosome. The inactivated X chromosome can be revealed as a densely staining area, the Ban body, in cells from a buccal smear. It is conventional to indicate the total number of chromosomes per cell by an Arabic numeral and, if
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relevant, the constitution of sex chromosomes by one X and/or Y for each chromosome. Thus, the normal male and female karyotypes are written as 46XY and 46XX, respectively. Chromosomal abnormalities Chromosomal abnormalities fall into three categories (below). Those most relevant to psychiatrists are those which are associated with learning disability. Abnormal number of autosomes For example, Down's syndrome usually reflects trisomy 21, i.e. the presence of an extra chromosome 21 resulting from a failure of segregation (nondysjunction) during meiosis. Other examples include trisomy 18 (Edward's syndrome) and trisomy 13 (Patau syndrome). Abnormal number of sex chromosomes For example, Turner's syndrome (45 XO) and Kleinfelter's syndrome (47 XXY). Cells from a buccal smear have up to a maximum of (n — 1) Barr bodies, where n = number of X chromosomes. Chromosomal rearrangements For example, translocation where a portion of one chromosome becomes attached to another. The offspring of phenotypically normal carriers of translocations are at risk of having a 'partial trisomy' for the former chromosome (this is known as an unbalanced translocation). Five per cent of cases of Down's syndrome result from translocations of a portion of chromosome 21. Deletions Deletions of small chromosomal regions can also occur. Deletions near the ends of chromosomes (telomeres) are associated with learning disability. Deletions of the long arm of chromosome 22 are associated with velocardiofacial syndrome, a disorder with characteristic dysmorphology, abnormalities of the palate and heart and a high prevalence of psychosis. Mendelian inheritance Mendel's laws describe the inheritance of discrete (i.e. present or absent) characteristics. Law 1. Alleles segregate Members of the same pairs of genes (alleles) are never present in the same gamete but always segregate and pass to different gametes. For example:
138 Parents Offspring
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Two parents, both heterozygotes, give rise to three possible types of offspring with a probability of occurrence of 1:2:1. Law 2. Independent assortment of non-alleles Members of different gene pairs move to gametes independently of each other. For example: Parents Offspring
AaBb x aabb AaBb aaBb Aabb aabb
One locus has alleles A and a and another has B and b. One parent is a double heterozygote and the other is a double homozygote. There are four possible types of offspring with equal probability of occurrence.
Gene characteristics Disease genes are described as dominant or recessive. A dominant allele manifests its overt, or phenotypic, effect in heterozygotes, whereas a recessive allele must be present in the homozygous state to do so. There are three main ways in which Mendelian transmission of single gene disorders can occur, as follows. Autosomal dominant The parents are usually an affected heterozygote and an unaffected homozygote. In this case, the average ratio of affected offspring is 1:1. These disorders do not skip generations. If parents are unaffected, then this suggests a new mutation. However, one must bear in mind that the parent carrier may have died before the onset of the disease or paternity may have been incorrectly assigned. Autosomal recessive Both parents are usually unaffected heterozygous carriers of an abnormal gene. The average ratio of unaffected to affected offspring will then be 3:1. Two-thirds of normal offspring will be carriers. Parental consanguinity should raise a suspicion of autosomal recessive inheritance. X-linked Most X-linked characters are recessive in that heterozygous females are unaffected. However, 50 per cent of their sons will be affected and 50 per cent of daughters will be carriers. Father-to-son transmission does not take place.
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Table 7.1 summarizes the Mendelian inheritance of single gene disorders relevant to psychiatry. Non-Mendelian inheritance Like other common diseases, most psychiatric disorders show patterns of inheritance that are complex. That is, in spite of evidence for the involvement of genes from family, twin and adoption studies (see below), inheritance does not follow simple Mendelian patterns. Complex disorders have traditionally been attributed to a combination of multiple additive genetic effects (polygenes) and environmental factors which together determine an individual's liability to disease. Illness then occurs when a threshold of liability is exceeded (so-called multifactorial liabilitythreshold models). Such mathematical models were proposed at a time when it was not possible to identify the genes involved. However, now that the identification of susceptibility genes is becoming feasible, the term quantitative trait locus (QTL) is often used to describe genes which contribute to continuously distributed traits and the term oligogenic inheritance to describe the situation in which susceptibility alleles at relatively few genetic loci confer increased risk to a disorder but are individually insufficient to cause disease. An example of this is the e4 allele of ApoE in Alzheimer's disease. Table 7.1
Mendelian inheritance of single gene disorders
Inheritance
Examples relevant to psychiatry
Autosomal dominant Parents: aa aa
Offspring: aa aa aa aa Autosomal recessive Parents: aa aa
Offspring: aa aaaa aa X-linked recessive Parents: XY _XX Offspring: X X _ X X X Y X Y Denotes Denotes Denotes Denotes
disease allele normal allele affected individual unaffected carrier
Huntington's disease Acute intermittent porphyria Neurofibromatosis Tuberous sclerosis Sturge-Weber syndrome Wilson's disease Galactosaemia Tay-Sachs disease Mucopolysaccharidoses (except Hunter's syndrome) X-linked mental retardation Lesch-Nyhan syndrome Hunter's syndrome
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Molecular genetics has in recent years revealed other mechanisms that can lead to departures from classical Mendelian patterns of transmission and which may play a role in psychiatric disorders. They include: • Mitochondrial mutation. If a disease mutation lies within the mitochondrial genome rather than the nuclear genome, a maternal pattern of transmission is seen as mitochondria are inherited only from the mother. • Genomic imprinting - where there is differential expression of genes depending on whether the chromosomes are maternally or paternally derived. • Dynamic mutation - where unstable DNA sequences in the form of expanded trinucleotide repeats occur, which mutate when transmitted from one generation to another. This can be associated with the phenomenon of anticipation, whereby disease severity increases and/ or age of onset decreases from generation to generation. Claims have been made that anticipation can be observed in both bipolar disorder and schizophrenia and this has prompted the search for dynamic mutations in these disorders.
Classical genetic approaches Family studies The frequency of a disorder is measured in the relatives of index cases (often referred to as probands) who have the disorder and compared with that in the general population or in relatives of control probands. In the family history method, information is obtained from the proband and/or relative. However, this tends to lack sensitivity. The family study method, in which the mental health of all available relatives is assessed from personal interview, is much more satisfactory but requires considerable investment of time and resources. Rates of illness in relatives are often expressed as morbid risk (also called lifetime expectancy or lifetime incidence). By correcting this for age, this takes into account the fact that, for most psychiatric disorders, there are specific periods of risk in a lifetime. Familial aggregation alone does not necessarily indicate genetic transmission. Twin and adoption studies are required to determine the relative importance of genetic and environmental effects. Twin studies Monozygotic (MZ) twins have all their genes in common, whereas dizygotic (DZ) twins are like other siblings and share, on average, 50 per cent of their genes. The main assumption underlying twin studies is that both types of twin share common environmental effects to an
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approximately equal extent. Therefore, if MZ twins are more alike than DZs for a particular trait, then this must reflect genetic influences. Where we are concerned with discrete traits, such as psychiatric diagnosis, similarity within pairs is expressed as a concordance rate (CR). This may be calculated from two perspectives: Pairwise CR =
Number of twin pairs in which both are affected Total number of pairs
Probandwise CR =
Number of affected co-twins Total number of co-twins
The main methodological problems associated with twin studies are: • Ascertainment bias. Nonsystematic ascertainment leads to overrepresentation of concordance MZ pairs. Therefore, pairs should be systematically obtained from twin registers. • Misspecification of zygosity. Objective measures of zygosity, such as molecular genetic markers, should be used. • Shared microenvironment. MZ pairs may be treated more similarly and share their microenvironment to a greater extent than DZ pairs. This problem can be partially overcome by studying MZ twins reared apart. Unfortunately, these are rare and ascertainment is often unsystematic. • Twins are unusual. MZ twinning itself is an error of development and a number of defects appear to be more common in MZ twins than in DZs or singletons, e.g. congenital heart disease. Birth complications, which have been implicated in the aetiology of some psychiatric illnesses, are also more common in twins. Adoption studies There are three common designs: • Adoptee study. The rates of illness in the adopted away offspring of affected parents are studied and compared with those in control adoptees. • Adoptee's family study. Adopted individuals with the disorder in question are ascertained. The rates of illness in their biological and adoptive relatives are then compared. • Crossfostering study. The rates of illness in adoptees who have affected biological parents but unaffected adoptive parents are compared with those in adoptees whose adoptive but not biological parents are affected. When interpreting the results of adoption studies, the following should be taken into account:
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• Adoption is an abnormal event - there is probably a higher rate of psychopathology in adoptees than in the general population. • Placement is rarely random. Molecular genetic approaches Molecular genetic techniques
Restriction enzymes Restriction enzymes (restriction endonucleases) cut DNA at sites where specific base sequences occur. Each restriction enzyme recognizes a different sequence of bases and enzyme digestion results in fragments of easily manageable size (usually 103-104 base pairs). This size is of the order of that expected for many genes, thereby enabling genes to be examined individually. Molecular cloning
Specific pieces of DNA can be purified, enabling them to be studied further and, in particular, to be used as DNA probes. There are two main types of DNA probe: 1. Those made from genomic DNA extracted and digested with restriction enzymes. 2. Those made from complementary DNA (cDNA), which is synthesized from mRNA by the action of an enzyme called reverse transcriptase. Following restriction enzyme digestion, these segments of DNA can be inserted into the genome of vectors such as bacterial plasmids or bacteriophages (recombinant DNA molecules). Individual bacteria will give rise to bacterial colonies, each containing many copies of the DNA fragment that was inserted into the founder. The collection of bacterial colonies from a particular source is termed a library.
Southern blotting Initially, genomic DNA is cut with a restriction enzyme. This produces a large number of different-sized DNA fragments which can then be separated by electrophoresis according to their size. After transfer to a membrane sheet, the blot is then exposed to a radioactively labelled DNA probe. Sometimes the sizes of the fragments detected by a probe will vary from individual to individual, owing to variation in the DNA sequence creating restriction enzyme cut sites. Such restriction-fragment-lengthpolymorphisms (RFLPs) can be used for genetic mapping.
DNA sequencing Techniques are available to determine the base sequence of any purified segment of DNA by either chemical or enzymatic means.
Polymerase chain reaction This allows a sequence of interest to be amplified selectively against a background of a large excess of irrelevant DNA.
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Molecular genetic studies Genetic markers are reliably measured DNA sequences which have a simple mode of transmission and are polymorphic, i.e. there are two or more alleles with a gene frequency of at least 1 per cent. Early molecular genetic studies used RFLPs as markers. Currently, most molecular studies are based on polymorphisms in simple repetitive sequences such as (CA) n . These are highly polymorphic and are readily detectable using PCR. Several thousand have been discovered and mapped which allows investigation of the entire human genome. The two main strategies adopted to investigate the relationship between genetic markers and disease are linkage studies and association studies, as described below. Linkage studies In this approach, evidence for linkage is sought between a genetic marker and a disease gene. Linkage occurs when a genetic marker and a disease gene lie close together on the same chromosome. Linkage studies are performed on families containing multiple members affected by the disease under investigation. Linkage is said to occur when marker alleles tend to segregate with the disease in affected family members. This is because the marker and the disease gene recombine during meiosis less than the expected rate of 50 per cent, producing a deviation from Mendel's law of independent assortment. Linkage studies in multiply affected families are powerful ways of locating genes for Mendelian disorders. In disorders exhibiting complex inheritance where Mendelian subforms do not exist, linkage is best studied by testing for excess allelesharing in large numbers of affected relative pairs (e.g. sib-pairs). In general, there are two strategies that can be used to guide linkage studies: 1. The candidate gene approach. This approach targets known genes coding proteins which may plausibly be involved in the pathogenesis of the disease, e.g. the Amyloid Precursor Protein gene in Alzheimer's disease. 2. The positional cloning approach. Disease genes are identified through their position in the genome rather than through their function. This approach often relies upon a systematic search of the genome for linkage. Occasionally a clue to the location of a disease gene comes from the co-occurrence of a cytogenetic abnormality with the disease. The great advantage of the positional cloning strategy is that it allows disease genes to be identified in the absence of detailed understanding of pathogenesis. Once linkage has been detected, the chromosomal region containing the disease gene can be progressively refined prior to employing a range
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of molecular techniques to identify genes and search for mutation in them. Unfortunately, in complex disorders it is more difficult to narrow down the region containing a gene. Here, the favoured approach is increasingly to rely upon the analysis of plausible genes known to map to the region of interest. This positional candidate approach is based firmly upon access to data from the Human Genome Project.
Association studies In linkage studies, different alleles will cosegregate with the disease in different families. By contrast, association studies seek to detect an association between a particular marker allele and the disease in a population sample. The frequency of particular marker alleles in unrelated patients is compared to ethnically matched controls. Allelic association occurs either when the marker itself has some direct influence on susceptibility to the disease or when the marker allele is very closely linked (i.e. in linkage disequilibrium) with the disease allele. This means that at the present time association studies are best applied to the study of candidate genes. Allelic association studies can detect genes of small effect, unlike linkage studies, and are becoming increasingly used in psychiatric genetics.
Animal studies Animal models can be important in facilitating an examination of the role of genetic factors in the aetiology of human disease. In addition, they allow an examination of the pathophysiological basis of disease by investigating the function of disease genes that have been cloned. In the past, there were few good animal models of psychiatric disorders but recently, selective breeding experiments have produced models for alcohol dependence, depression and personality traits. Gene targeting and transgenic technologies have provided more direct methods of obtaining animal models of single gene disorders such as Huntington's disease. Exogenous genes can be inserted into the genome of totipotent animal cells to generate so-called transgenic animals. The expression of this foreign gene can then be studied in a variety of different cellular environments within the animal. In gene targeting, a mutation is introduced into a preselected endogenous gene that 'knocks out' gene function and the effects of this mutation can then be studied in the animal.
Reading list McGuffin, P., Owen, M., O'Donovan, M., Thapar, A. and Gottesman, I.I. (1994) Seminars in Psychiatric Genetics. Gaskell: London. Owen, M.J. and Cardno, A.G. (1999) Psychiatric Genetics: Progress, Problems and Potential. Lancet 354, 11-14. Owen, M.J., Cardno, A.G. and O'Donovan, M.C. (2000) Psychiatric Genetics; Back to the Future. Molecular Psychiatry 5, 22-31.
8
Epidemiology, research methods and statistics HOLLIE THOMAS and GLYN LEWIS
Epidemiology Epidemiology is the quantitative study of the distribution and determinants of disease in human populations. Descriptive epidemiology refers to the description of the distribution of a particular disease by time, place or person. Routinely collected data are often used to describe individuals with the disease with reference to the population from which they come. In analytical epidemiology, hypotheses on the aetiology of a disease are often tested or generated by comparing the actual characteristics of individuals with the disease with those of the population in which the patient would normally live. Intervention studies aim to provide absolute proof of causality by determining whether the incidence of a disease is altered when a risk factor is modified. Systematic reviews aim to generalize the results from a number of individual intervention studies. Sampling It is usually impossible to examine every individual in the population of interest; instead one is limited to examining a random sample of n individuals from this population in the hope it is representative of the complete population. If the study sample is small, random sampling may yield an unrepresentative group of individuals. Random stratified sampling can be used to improve the representation. For example, the sampling frame (the total study population) could be divided into age groups before randomly selecting the sample from within each group to ensure all age groups are represented. Many large household surveys use random clustered sampling in which individuals are selected at random from within small geographical areas which themselves have been selected randomly.
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Definition and classification of cases Epidemiological research relies on the clear definition of what is meant by a case, i.e. an individual in a population who has the disease or suffers the event of interest. However in psychiatric research, as in many areas of medicine, the unequivocal definition and identification of those who do and do not have a certain condition is frequently problematic. For example, many assessments of neurotic disorder lead to a score that has a continuous distribution. Cases are then defined by a cut-off point at which the severity is great enough to arouse clinical concern. There are four main methods for assessing psychiatric disorder: 1. Rating scales and checklists. Rating scales provide guidance about the symptoms that need to be enquired about but do not specify the actual questions that are to be used. These are left up to the investigator who therefore usually requires some clinical training, e.g. the Hamilton Rating Scale for Depression. 2. Semi-structured interviews. These provide some guidance on which questions to use and give more information on when to rate psychopathology as present or absent. However, they are intended to mimic the clinical examination and require clinicians to administer them, e.g. the Schedule for Clinical Assessment in Neuropsychiatry (SCAN). 3. Structured interviews. Structured interviews provide all the questions that should be asked, together with detailed guidance on how responses should be coded. They are suitable for social survey interviewers and can also be administered by computer. Most clinicians regard these as unsuitable for the assessment of psychotic illness or illnesses when there is lack of insight, e.g. Revised Clinical Interview Schedule (CIS-R), Composite International Diagnostic Interview (CIDI). 4. Self-administered questionnaires. Brief self-administered or 'paper and pencil' questionnaires are frequently used to assess neurotic disorders. They have sensitivities and specificities of around 75-80 per cent when compared with the more detailed assessments, e.g. General Health Questionnaire (GHQ), Beck Depression Inventory (BDI). Once the psychopathology has been identified by one of the methods described above, it may be possible to apply diagnostic criteria and place people in hierarchies. The two most widely used classification systems are the 1 Oth edition of the World Health Organization International Classification of Diseases (ICD-10) and the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) of the American Psychiatric Association. In almost all respects these two systems have identical diagnostic criteria, though previous editions did not show agreement.
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Validity and reliability of data The validity of a diagnostic test refers to the ability of that test to measure what it claims to measure. Validity can only be determined if there is a reference or gold standard for comparison. In psychiatry, gold standards do not exist and the unreliability of the reference measure effectively puts an upper limit on two important aspects of the validity of a test: its sensitivity (the proportion of true positives that are correctly identified) and its specificity (the proportion of true negatives that are correctly identified). An ideal test has both high sensitivity and specificity, although this can be difficult to obtain. In contrast to the validity of a test, the reliability or repeatability of a test concerns whether a test will give the same result if it were applied twice in the same circumstances. It therefore refers to error of measurement. It is often wise to include a check of the reliability or repeatability of measurements of the important variables in an epidemiological study. The kappa statistic (K) is a measure of agreement which takes into account the agreement expected by chance alone. A K value of 1.0 indicates perfect agreement and a value of zero indicates no agreement better than chance. Generally any value of K below 0.5 will indicate poor agreement. Predictive value The predictive value of a positive test result is the likelihood that someone with a positive result has the disease. This is usually the characteristic that is of most interest to clinicians and patients. The predictive value of a negative result is the likelihood that someone with a negative result does not have the disease. The predictive value of a test depends on the prevalence of the disease. The lower the prevalence, the lower the predictive value of a positive test result because of the increase in the number of false positives when there are few positives in the population. For example, a screening questionnaire used to estimate the prevalence of psychosis could have a high specificity and sensitivity in a validity study, but if applied to a household survey where the prevalence of psychosis would be much lower in comparison, the predictive value of a positive test result could drop dramatically.
Statistical analyses Variables Quantitative variables can take any numerical value along a continuous scale of measurement. Examples include age, height, blood pressure, duration of symptoms in weeks. In contrast, the values of categorical variables represent labels indicating different categories rather than actual
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measurements of a quantity. Examples include marital status and socioeconomic status. Binary variables are categorical variables that can only exist as two different categories, e.g. sex, presence or absence of disease of interest. Ordinal variables are ranked, but equal differences between values along the scale do not correspond to equal differences in what is measured. Most psychological and psychiatric data from rating scales and questionnaires are ordinal. Variables can also be classified in terms of their purpose in the statistical analysis, as either explanatory (independent) or response (dependent) variables. The response variable is the outcome of interest, while the explanatory variables are the characteristics of the subjects (i.e. the potential risk factors) that are thought to explain some of the variability in the response variable. Descriptive statistics Data analysis should always start with an exploration of the data using simple tabulations, graphs and basic summary measures. Quantitative variables and categorical variables need to be summarized in different ways.
Distributions The distribution of values for a variable describes the data and determines the statistical tests that are to be used. The normal distribution is a continuous and symmetrical distribution of data in which most values are concentrated around the mean (average) value. The frequency distribution is bell-shaped. Many biological variables (e.g. weight and height) are distributed similarly to a normal distribution and most statistical tests assume this distribution. If a distribution is close to normal but the data are skewed, the data can be transformed by taking logarithms which results in a better approximation to the normal distribution and allows the use of statistical tests based on this distribution. The binomial distribution is concerned with binary variables. The Poisson distribution is concerned with events that are distributed randomly in time. It is used to describe the number of events that occur in a given time period. When presenting the frequency distribution of a quantitative variable, the large number of distinct values are first grouped and the number of subjects who fall within each group are then reported as a percentage of the total number of subjects in the sample. A histogram presents this distribution in a graphical manner (Figure 8.1). Categorical variables can also be presented in the form of a frequency distribution, with the number of subjects who fall within each labelled category reported as a percentage of the total number of subjects in the sample. Bar charts are often used to display the distribution of a categorical variable.
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Figure 8.1
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Frequency distribution of height, showing histogram and normal curve
Measures of central position The arithmetic mean (x) is the most commonly used measure of the central value of a continuous distribution. It is equal to the sum of all observations divided by the number of observations (n). Since the mean takes into account every observation, it can be affected by outliers, i.e. single observations which are very extreme in comparison with the majority of observations and whose exclusion from statistical analysis alter the reported results. The median is the middle observation if all the observations are listed in order of increasing magnitude. This is a particularly useful measure when the presence of outliers renders the mean unrepresentative of the majority of the data and for data that is not symmetrically distributed. The mode is the single value in the data that occurs most frequently. Categorical variables cannot be summarized by the mean or median; only the frequency distribution can be presented.
Measures of variation The investigator will also want to know over what values the data is spread, or how it varies. The range is the interval between the largest and smallest values. This is based only on these two observations and gives no feel of how the observations between them are arranged. The standard deviation (sd) measures, on average, how far each observation deviates from the mean value. The equation is given below:
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The more the values in a population vary, the greater the standard deviation. For a normal distribution, one standard deviation either side of the mean includes approximately 70 per cent of the distribution and two standard deviations include about 95 per cent. The variance is the square of the standard deviation. Inferential statistics Statistical inference is the process by which one draws conclusions about a large study population from the results observed in a small random sample of the study population. If random samples are repeatedly selected from the study population, the means (or proportions) in the sample would vary between the samples. This variation would be larger if small samples were being selected. The standard error (SE) indicates how precisely the sample mean estimates the true mean in the study population. The standard error of a mean can be estimated by dividing the standard deviation of the sample by the square root of the sample size. The central limit theorem states that sample means will tend to be normally distributed even when the distribution from which the sample has been drawn is non-normal. For any symmetrical distribution it is therefore reasonable to assume that sample means are normally distributed, but if the study population distribution is markedly nonnormal other statistical approaches may be needed.
The estimation approach - confidence intervals In a normally distributed study population, there is a 95 per cent chance that the study population mean will be within 1.96 standard errors of the sample mean. This range is known as the 95 per cent confidence interval (95% CI). Thus a confidence interval provides an estimate of the range of values that is likely to cover the true population mean with a given accuracy (e.g. 90%, 95% or 99% CI).
Hypothesis testing The other approach towards statistical inference is known as hypothesis testing. It assumes that an investigator has an a priori hypothesis (i.e. before the study is carried out). The first step is to declare the null hypothesis, i.e. that there is no true difference between groups in the study population and any difference observed is a result of random variation usually because of sampling error. The null hypothesis is effectively the reverse of the study hypothesis. The next step is to calculate the probability of getting as big a difference or greater as that observed if the null hypothesis were true. This probability, denoted by P, is determined by applying the appropriate statistical test. It is important to emphasize that the null hypothesis (or for that
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matter the study hypothesis) cannot be proved correct. The odds of winning the lottery are over 107 to 1 but even though that is extremely unlikely, enough people buy tickets for someone to win almost every week. It has become common practice to consider P < 0.05 as indicating 'statistical significance', i.e. that there is enough evidence that the null hypothesis is untrue and the study hypothesis is true. This indicates that the results would occur by chance 5 per cent of the time (or 1 in 20 occasions). However, this is an arbitrary cut-off point and its emphasis is not recommended. It is far better to report the actual value of P, as computer programs can easily calculate this value. A type 1 error occurs when the investigator rejects the null hypothesis because the P value is 'significant' (i.e. <0.05) but there was no true difference in the study population. In other words, the finding was a result of chance. This is more likely if there the investigator has carried out multiple hypothesis tests. This commonly occurs when studies have not stated an a priori hypothesis and have merely 'dredged' their data for 'significant' findings. If an investigator collected 100 variables, 5 per cent of them would be significantly associated with the outcome by chance. This illustrates that P values are difficult to interpret in the absence of a clearly stated hypothesis formulated before the study begins. A type 2 error occurs when there was a true difference in the study population but the P value is not significant. This usually occurs when the sample size is too small to detect important differences. The statistical power of a study is the probability that a type 2 error will not occur in a study. The power depends upon the significance level (usually 0.05), the size of difference the investigator expects to discover or is important to find, and the sample size. Power increases as sample size increases. It is important to distinguish between the size of the effect (e.g. the difference in means) and the statistical significance of the result. The magnitude of the P value depends on both the size of effect and on the sample size. Thus, in a small sample a P value might not be significant despite a large difference, while in a large enough sample small irrelevant differences can achieve statistical significance.
Parametric and non-parametric statistics Significance tests can be divided into parametric tests and nonparametric tests (Table 8.1). Parametric tests assume the sample has been drawn from a defined population with a known statistical distribution such as the normal distribution. Non-parametric tests make no assumption about the sample population and can be used for data that are not normally distributed. They often require data to be ranked in order of increasing magnitude. Non-parametric tests do not allow estimation of confidence limits.
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Table 8.1 Commonly used significance tests No. of samples Two
Matching
Type
Matched Unmatched
Interval Interval Categorical
Three or more Unmatched
Nonparametric
Wilcoxon's Mann-Whitney U-test x2 test
Interval Categorical x2 test
Parametric Matched pairs t test nest z test for two proportions Analysis of variance
Parametric tests The Student's t test is used for comparing the means of two groups when the outcome variable is a continuous measure:
where x 1 =mean of sample 1, x2 = mean of sample 2, sd1 and sd2 = standard deviations of the two samples, and nl and n2 = number of cases in each of the two samples. The value t derived from the above formula is then converted to a probability by using the appropriate conversion table from a standard book of statistical tables. If the study design involves matching, a matched t test is used. The means of three or more groups can be compared by the technique known as analysis of variance.
Non-parametric tests The Mann-Whitney U-test is the non-parametric equivalent of the t test and is used for comparing two groups of unmatched continuous data that do not follow a normal distribution. The chi square test ( x 2 ) is used with categorical data to compare the difference in a proportion between two or more groups of individuals (e.g. the proportion of each sex who are depressed). The data are presented in a cross-tabulation table giving the numbers and proportions (or percentages) in each combination (or cell of the table). Large values of x2 suggest that there is an association between the two categorical variables. The P value is obtained by referring the calculated value of y2 to tables of the chi square distribution.
Measures of disease frequency In addition to needing information on the number of cases that occurred in a particular population, it is necessary to know both the size of the
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population from which the cases originated and the time period during which the data were collected. This knowledge can be used to measure disease frequency. There are two measures of disease frequency: prevalence and incidence. Nomenclature It is customary in epidemiology to use the terms disease to refer to the outcome or response variable of interest and exposure to refer to the explanatory variables or potential risk factors. This is a shorthand to enable the more succinct discussion of study designs. Prevalence Prevalence is defined as the number of cases of disease in a population at one point in time as a proportion of the total number of persons in that population. It is estimated using a cross-sectional survey. The point in time to which it refers should always be stated. Point prevalence is based on a single measurement, while period prevalence is the prevalence during a specified short period. Lifetime prevalence considers all the individuals who have ever had an episode of the illness of interest. Prevalence depends on the frequency with which new cases occur and are diagnosed, and on the average duration of the disease. The sample of subjects obtained in a prevalence estimate will include a higher proportion of subjects with chronic disease than in a sample of new cases. An association found between an exposure and a prevalent sample of cases may be an association with increased incidence or a factor associated with long duration. For aetiological research it is therefore necessary to identify new cases of a disease. Incidence Cumulative incidence is the proportion of new cases of disease that develop in a population at risk during a specified time interval. Cumulative incidence can be misleading if there is attrition from the population or if the incidence of disease is high. Subjects who have left the population or who have the disease are no longer at risk. Calculating the incidence rate avoids this difficulty by calculating the person-time at risk for each individual in the population. The incidence rate is then equal to the number of persons who become cases in a given time period divided by the total person-time at risk during that period. The time period and relevant person-time units must be specified, e.g. the suicide rate in the UK is 8 per 100000 person-years. Odds and probability Epidemiologists often use odds rather than probability when calculating prevalence or cumulative incidence. This is done because it is easier to
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mathematically manipulate odds. If there are X cases of disease and F non-cases of disease the probability (or risk) of disease is X divided by (X+Y). The odds of disease is X divided by Y. The odds tends to be larger than the probability, but for low probabilities (<0.05) there is little difference in the value of odds and probability. Measures of association Epidemiological research investigates aetiology by estimating the association between exposure to a possible risk factor and the occurrence of the disease. Relative measures of association These are calculated by comparing the incidence or prevalence of disease in a group exposed to the possible risk factor with the incidence or prevalence in the unexposed. Thus three types of relative measure of association can be calculated: the risk ratio, the rate ratio and the odds ratio. These three ratios are numerically very similar for rare diseases so are often loosely called relative risk, although it is probably better practice to specify the exact measure for reference. These ratios of the measures of disease frequency for the two groups estimate how much more likely the exposed group is to develop the disease then the unexposed group. A value of 1.0 indicates that the incidence of disease is identical in both the exposed and unexposed groups and infers that there is no association in the data between the exposure and the disease. A value greater than 1.0 indicates an increased risk among those exposed to the factor, while a value less than 1.0 indicates a decreased risk amongst the exposed group. For example, cigarette smokers are 10 times more likely to develop lung cancer than those who have never smoked. Those exposed to a threatening life event are 4 times more likely to develop depression. Those born in the winter are 1.1 times more likely to develop schizophrenia. Relative risks are useful in studying the cause of disease. Absolute measures of association These are calculated as the differences in risks or incidence rates between the exposed and unexposed groups: the risk difference is defined as the risk in the exposed minus the risk in the unexposed; the rate difference is defined as the incidence rate in the exposed minus the incidence rate in the unexposed. These two absolute measures of association are known as attributable risk. Attributable risk is useful in trying to estimate the size of effect of a treatment difference and to help clinicians and patients to decide on what to do. Assuming that the relationship between exposure and disease is
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causal, then the attributable risk indicates the number of cases of the disease among the exposed that could be prevented if the exposure were completely removed. The attributable risk depends on the baseline incidence in the non-exposed group, which can vary between populations. An alternative measure to attributable risk is known as the number needed to treat (NNT) to avoid one adverse outcome. This measure is useful for clinicians who must make decisions about treatment. It is the inverse of the absolute risk difference. For example, in a randomized trial 40 per cent of depressed subjects recover spontaneously within 6 weeks and 60 per cent recover during the same period when on antidepressant medication. The NNT is 5 (1 divided by 0.2). This means that a clinician needs to treat about 5 patients with antidepressants for 1 additional patient to recover within 6 weeks who would not have recovered if they had been untreated. Correlation and regression The relationship between two quantitative variables can be illustrated and explored initially by a scatter diagram. Usually the response variable is plotted on the vertical axis and the explanatory variable on the horizontal axis. Linear regression summarizes the linear relationship between two continuous variables and allows the prediction of the value of one variable if the value of the second variable is known for an individual. The regression line can be drawn through the scatter diagram by using the method of least squares, which minimizes the vertical distances of the points in the scatter diagram to the straight line. The data can be summarized by the equation y = a + bx
where y = response variable, x = explanatory variable, a = intercept on x axis, and b = slope of the regression line. From this equation the average value of y for a given value of x can be estimated, provided that the value of x lies within the range of values in the observed data. It is important to remember that although the existence of a linear association demonstrates an association between two variables, it does not in any way establish a causal relationship between them. The possible strength of association between two continuous variables can be examined by calculating the (Pearson) correlation coefficient. The correlation coefficient, r, always lies between — 1 and + 1, with a value close to 1 indicating relatively little scatter. If r = 0 there is no linear relationship between the two variables, but this does not rule out the possibility of the existence of a strong nonlinear or curved relationship.
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The squared correlation coefficient measures the proportion of the variability in the response variable that can be accounted for by the linear relationship with the explanatory variable.
Causal inference An association between an exposure and a disease can be explained by chance, bias, confounding, reverse causality or causation. Epidemiologists are usually interested in whether an exposure is a cause for the disease. Chance An observed association between an exposure variable and disease outcome could be explained by chance. Significance testing and estimation of confidence limits assess the likelihood that chance alone can explain the findings. A type 1 error occurs when a statistically significant result occurs by chance. It is a particular problem when many statistical tests are conducted within a single study in the absence of a clearly stated prior hypothesis. A type 2 error occurs when a real result is obscured by chance or random error. Bias Systematic error or bias can distort an association in any direction, either increasing or decreasing the association. Bias is a result of defects in the design or execution of a study and the two main types in epidemiological studies are selection bias and information bias. Selection bias is a particular problem in case-control studies. It arises if the sampling method used to identify cases and controls results in a poor representation of the diseased and non-diseased individuals in the same population. An example is seen in the study of Brown and Harris (1978) who identified community cases of depression using a crosssectional survey and patient cases of depression by contact with psychiatric services. When the community cases were compared with community controls there was an association between depression and having a young family (odds ratio 3.77), but this association was absent when comparing the patient cases and community controls. Selection bias is acting here because, for someone who is depressed, having young children might reduce the likelihood of receiving treatment from psychiatrists. Since the majority of cases of depression never get referred to a psychiatrist, a community sample would not be an appropriate control group for cases seen in psychiatric services. Information bias in an analytical study occurs when subjects are misclassified according to their exposure status, disease status or both. Non-differential or random misclassification occurs when errors in classi-
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fication of exposure status affect cases and non-cases equally (or when errors in classification of disease status affect exposed and unexposed individuals equally). This type of misclassification always underestimates the true strength of association between exposure and disease. Random misclassification therefore cannot create a spurious association but can reduce or eliminate an association. Differential misclassification occurs when errors in classification of disease status are dependent on exposure status and vice versa and can result in biased estimates of association in either direction. Types of differential misclassification include recall bias, reporting bias and observer bias. Recall bias occurs especially in case-control studies and crosssectional surveys when individuals with the disease may be asked about the exposure retrospectively. In cohort studies, exposure is determined before onset of the disease and so it is less likely to be biased by the presence of disease. Case-control studies may also be able to use exposure information collected before the onset of disease. Observer bias occurs when the observer is aware of the hypothesis and the measurement of exposure or disease is biased. Keeping the assessments blind to disease or exposure can reduce the chance of this happening. Reverse causality This is the possibility that the exposure is the result rather than the cause of the disease. This is more likely to occur in case-control studies and cross-sectional surveys that assess exposure after the onset of disease. Cohort studies usually eliminate this possibility by selecting those without the disease at the beginning of the study. Causation An association may indicate that the exposure causes the disease. Trying to infer causation is a difficult task. It is usually helpful to review the epidemiological literature to decide whether there is a consistent finding, irrespective of the population or study design. When there is a strong association, then the likelihood that the relationship is causal is increased. For example, for relative risks over 3 or 4 then confounding and bias has to be quite marked to explain the findings. However, there is generally little confidence in findings when the relative risk is 1.5 or below. A dose-response relationship can also provide additional evidence for causality, depending upon the hypothesized mechanism of action. For example, one would expect that more severe obstetric complications would lead to higher rates of schizophrenia than milder forms if that were a causal agent. Finally, the scientific plausibility of the findings has to be considered. Epidemiology, when it is investigating cause, is interested in biological and psychological relationships.
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Confounding Confounding occurs when an estimate of the association between an exposure and disease is mingled with the real effect of another exposure on the same disease due to the two exposures being correlated. If an association results from confounding it does not mean this association is wrong but that there is an alternative explanation for it. An epidemiologist should identify potential confounders at the design stage of the study and collect information on them, otherwise at the time of analysis it will be difficult to reject alternative explanations for any associations found in the data. A variable is said to be a confounder if the analysis which controls for this variable produces results which are markedly different from the crude or uncontrolled analysis.
Adjusting for confounding Confounding can be controlled for in the design of a study, but more usually it is controlled for in the analysis, provided that sufficient information on possible confounding variables has been collected. In the design - restriction Only those individuals who are not exposed to the confounding variable are included in the study. In the design - matching The groups to be compared are often matched on potential confounding variables (e.g. age, sex) particularly in case-control studies. Matching on confounding variables that are difficult to measure (e.g. neighbourhood) is particularly useful since it would be difficult to accurately adjust for these variables in the statistical analysis of a study. Matching on variables that are not potentially important confounders is bad practice, since the researcher cannot later investigate any association between the disease and exposure to the matching variables. The disadvantages of matching are the increase in administrative effort required and the slightly more complex analysis that is required in case-control studies to take into account the matching factors and to prevent the results from the study being biased. Overmatching can also occur in case-control studies when there is inadvertent matching on the exposure variable and the power of the study is reduced. In the design - randomization This is the most powerful method of controlling for confounders that can be used. Random allocation of subjects from a sufficiently large sample into groups receiving different preventive or therapeutic treatments should eradicate any other underlying differences between the
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groups except those arising by chance. Of course, it is usually impossible to investigate aetiological agents using randomization. In the analysis - stratification The association between the disease and exposure of interest is analysed according to different levels or strata of the confounding variable. The true relationship between disease and exposure is revealed within each stratum of the confounding variable. A weighted average or summary estimate can then be calculated across the strata of the confounding variable. The Mantel-Haenszel odds ratio gives a weighted average of the odds ratios in the different strata, the odds ratios from larger strata being given more weight. Standardized mortality ratios are a way of adjusting for the confounding effects of age and sex using a stratified analysis. In the design - multivariate analysis As the number of confounders increases, stratified analyses - such as the Mantel-Haenszel method - become impractical. Instead, multivariate modelling techniques are used to adjust for confounding by a large number of variables. Logistic regression analysis is used when studying binary outcomes (e.g. diseased versus well) to estimate odds ratios that are simultaneously adjusted for several confounders. Similar modelling techniques include conditional logistic regression, which estimates adjusted odds ratios in a matched case-control study, and Poisson regression which estimates adjusted rate ratios using persontime data from cohort studies. Least squares regression is used to model continuous outcomes (e.g. scores on a depression test) and assumes that the dependent variable is normally distributed; this is often not the case with many outcomes in psychiatry.
Epidemiological study designs The main study designs used in epidemiological research can be described as either observational (ecological, cross-sectional, case-control and cohort), experimental (randomized controlled trial), or summary in nature (systematic reviews), as listed below: ecological or aggregate; cross-sectional survey; case-control; cohort or longitudinalrandomized controlled trials; systematic reviews.
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Ecological or aggregate studies Ecological studies examine the association between disease and the characteristics of an aggregation of people, rather than the characteristics of individuals. The main difficulty with this design is that the association between exposure and disease at an aggregate level may be highly susceptible to confounding and may not be reflected in an association at the individual level. This is termed the ecological fallacy. The advantages of using aggregate data are that long-term differences in lifestyle (e.g. diet) can be detected and some community variables can only be thought of in ecological terms. For example, Sainsbury (1955) found an association between area suicide rates and the population turnover in those areas. He explained these results by suggesting that alienation in an area might increase suicide rates. Cross-sectional surveys This type of descriptive study relates to a single point in time and can therefore report on prevalence of a disease but is adversely affected by the duration of illness. A cross-sectional survey is often quick and cheap. It eliminates the problems of selection bias and has been frequently used for the study of depression and other neurotic conditions. However, any association found in a cross-sectional survey could either be with incidence or duration. Case-control studies In a case-control study, individuals with the disease are compared with a comparison group of controls. If the prevalence of exposure is higher in the cases than in the controls the exposure might be a risk factor for the disease, and if lower the exposure might be protective. Case-control studies are relatively cheap and quick and can be used to study rare diseases. However, great care is needed in the design of the study in order to minimize selection bias. The validity of case-control studies does not depend upon matching but upon ensuring that the case and controls come from the same population. A useful rule is to ensure that controls, if they developed the disease, should be included in the sampling frame for your cases. The importance of this rule can be illustrated by the case-control study of O'Callaghan et al. (1992) which examined the association between abnormalities in pregnancy and childbirth and the development of schizophrenia. Obstetric notes were traced for 65 schizophrenics attending a psychiatric hospital in Dublin, and the next birth in the Dublin obstetric hospital was used as the control. The odds ratio for schizophrenia in relation to an obstetric complication was about 2.4 (95% CI 1.1-6.0). Since the study design did not dictate that control
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subjects must still be resident in Dublin at the time of the study it is likely that some controls might have moved away. Therefore, even if they had developed schizophrenia they would not have been eligible as cases. A design in which the investigators had only included cases who still lived in Dublin would have reduced the chance of a selection bias. For a case-control study of schizophrenia, the cases could be new presentations to a service in a defined catchment area. If we assume that all cases of schizophrenia attend psychiatric services, then the appropriate control group would be general population controls. For hospital cases of depression, general population controls would be a poor choice of controls because very few cases of depression reach specialist services, so selection into treatment would be important (see example of selection bias under Bias, above). A matched case-control study involves one or more controls being selected for each case, owing to their similarity for a number of characteristics that are thought to be potential important cofounders. Common matching variables are age and sex. A nested case-control study is one based within a cohort study or sometimes a cross-sectional survey. The cases are those which arise as the cohort is followed prospectively and the controls are a sample of the non-diseased members of the cohort. The analysis of case-control studies results in the reporting of odds ratios; case-control studies cannot directly estimate disease incidence rates. If the study is matched, a more complex matched analysis needs to be performed (conditional logistic regression). Cohort or longitudinal studies A cohort (or longitudinal or follow-up) study is an observational study in which a group of persons who are exposed to a potential cause of disease, together with a group who are unexposed, are followed up over a period of time and the incidence of the disease in the two groups is compared. Ideally, the exposed and unexposed groups should be chosen to be virtually identical with the exception of the exposure. Often the exposure of interest is a continuous variable which can be subdivided into grades of exposure and a trend of increasing disease with increasing exposure can be examined. The ability of a cohort study to rule out reverse causality as a reason for an observed association is of great benefit. For example, Lewis et al. (1992) studied a cohort of 50 000 Swedish male conscripts. The incidence of schizophrenia was 1.65 times higher in those brought up in cities compared to those brought up in country areas. These results could not have occurred because of the 'geographical drift' hypothesis. This suggests that schizophrenics tend to drift into city areas because of the presence of their illness. Since this cohort study asked about upbringing
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before the onset of disease, the authors concluded that environmental factors found in cities increase the risk of the disorder, though drift into cities could also occur. Exposure definition is linked to the timing of the study. Cohort studies always look forward from the exposure to disease development; however they can sometimes be termed 'retrospective' when they use historical data on exposure. Historical cohort studies have the major advantage of offering a short-cut to studying diseases with a long interval between exposure and disease. The disadvantage of these studies is that exposure measurement is dependent on the historical record that is available and exposure measurement may have been more inaccurate in the past. A particularly useful historical method is where some type of biological sample has been stored which can be measured as an index of exposure at the present time. The completeness of follow-up is particularly important in cohort studies. It is essential that as high a proportion of people in the cohort as possible are followed up and those who migrate, die or leave the cohort for any reason should be recorded. These reasons for leaving the cohort may be influenced by the exposure, and incomplete follow-up can therefore introduce bias. The analysis of cohort studies involves calculation of either the incidence rate or risk of disease in the exposed cohort compared with that in the unexposed cohort. Measures of relative and absolute measures of effect can then be calculated. A summary comparison of the advantages and disadvantages of casecontrol and cohort study designs is shown in Table 8.2. Randomized controlled trials Randomized controlled trials (RCTs) are usually used (when possible) to investigate the effectiveness of medical interventions. They are the strongest design to investigate causality between an intervention and outcome because confounders are randomly allocated between the Table 8.2 Comparison of case-control and cohort study designs Advantages
Case-control
Cohort
Cheap and quick
Prospective definition of risk factors and disease Incidence rates can be calculated Expensive and time-consuming Losses to follow-up must be allowed for Not well suited for investigating rare diseases
Useful if disease is rare Disadvantages
Careful selection of controls Retrospective ascertainment can lead to recall bias Incident rates cannot be calculated
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groups. The study population should ideally be representative of the population to which the results will apply. However, since trials are often comprised of volunteers this is rarely the case. The subjects are then randomly allocated into the control group who receive the standard or placebo treatment and the intervention group who receive the new treatment. This random allocation aims to prevent any underlying differences between the two groups being responsible for any differences in outcome. Even random allocation can fail in this, especially if the number of subjects being assorted is relatively small. Therefore it is important to collect baseline information on factors that affect outcome for all subjects and to check the similarity of the randomized groups in these baseline variables. Finally, measurement bias should be minimized in the assessment of the outcome of the study by a standardized method of assessment which should be blind to the study group to which a subject belongs. Bias can still be introduced if subjects who are lost to follow-up are different in their outcome to those who have complete follow-up and there is differential drop-out between the randomized groups. Therefore it is important to minimize the non-compliance rate and loss to followup rate. An 'intention to treat' analysis should be carried out which includes the outcomes of all randomized subjects, including those who were lost to follow-up during the study. Systematic reviews and meta-analyses Secondary research aims to summarize and draw conclusions from all the known primary studies on a particular topic (i.e. those which report results at first hand). The main advantage of these studies is the resulting increase in the combined sample size. A problem of secondary research is the presence of publication bias, i.e. small negative results are less likely to be published. Therefore, ideally one should attempt a comprehensive search strategy which includes not only published results but also results reported in abstracts, personal communications and the like. Meta-analyses are a type of secondary research tool which integrate the numerical data from more than one study and then statistically reanalyse these pooled data. In comparison, a systematic review simply summarizes (sometimes quantitatively) the results of primary studies using a predefined methodology. When pooling or comparing data from different studies, a researcher should check that the comparison is indeed valid by testing for heterogeneity between studies. Individual studies can vary in methodological quality of the research and there are concerns about giving equal weighting to studies of different qualities.
Evidence-based medicine This is the name given to the transfer of the best epidemiological evidence from quantitative clinical and health care research to the
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clinician who can then apply this knowledge in the surgery, health clinic and the community. The results from those studies which are judged to be suitable for informing medical practice are either used to draw guidelines for clinical treatment and management, or to indicate a preferable use of economic resources. Randomized controlled trials provide the best evidence for clinical effectiveness, but there are always difficulties in generalizing the results from a single trial. Systematic reviews and meta-analyses of RCTs are often used to provide guidelines for optimum practice. The term pragmatic RCTs is used to describe RCTs that are designed to directly inform clinical practice. They therefore intend to mimic real life practice in the health service. A checklist of the important features to watch for is included in Table 8.3. One of the important points is to investigate a clinical dilemma faced frequently by clinicians. The health service also has to make decisions about the relative cost of interventions to compare with their potential benefits. An economic assessment that includes consideration of costs that are not directly related to treatment is also needed to inform clinical practice. Quality of life measures assess important outcomes affected by the intervention that are not directly reflected in symptomatology. For example, a person might be feeling less depressed but still has not returned to work. Critical appraisal Critical appraisal of a research paper involves the assessment of its methodological quality. When assessing the value of a research paper it Table 8.3
Checklist for assessing pragmatic randomized controlled trials
Aims • Has the trial included subjects who would normally be given the treatment? • Was the intervention one that is readily available (or potentially available) in the Health Service? Design • What method of randomization was used and how did the investigators ensure that it was adhered to? • Who and what was blind to the randomized allocation - patient, physican, outcome measurement, analysis? • Were 'quality of life' and the costs of health and social care assessed? Analysis • Was the randomization successful in producing groups with the same characteristics? • Was an 'intention to treat' strategy used in the analysis? • Was the main outcome specified before the trial was started? Were multiple statistical tests used? • If a negative result, how large are the confidence intervals? Was the trial too small to find a clinically important effect of treatment?
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is useful to follow a structured checklist to help in deciding what a paper is actually reporting. A published paper should be able to provide answers to the following questions. Why was the study done and what was the specific clinical question or hypothesis that was addressed? What study design was used and was it appropriate to the research question? What sources of bias were there in the study and were these discussed by the authors? What are the main potential confounders? What design or statistical methods were used to adjust for confounding? Finally, one needs to assess the possible direction of causality and any other features such as a dose-response relation that might support a causal relationship.
References Brown, G.W. and Harris, T. (1978) Social Origins of Depression. London: Tavistock. O'Callaghan, E., Gibson, T., Colohan, H.A., Buckley, P., Walshe, D.G., Larkin, C. and Waddington, J.L. (1992) Risk of schizophrenia in adults born after obstetric complications and their association with early onset of illness: a controlled study. British Medical Journal, 305, 1256-59. Lewis, G., David, A., Andreasson, S. and Allebeck, P. (1992) Schizophrenia and city life. Lancet, 340, 137-40. Sainsbury, P. (1955) Suicide in London. London: Chapman and Hall.
Reading list Beaglehole, R., Bonita, R. and Kjellstrom, T. (1993) Basic Epidemiology. Geneva: World Health Organization. Chalmers, I. and Altman, D.G. (1995) Systematic Reviews. London: BMJ Publishing Group. Crombie, I.K. (1996) The Pocket Guide to Critical Appraisal: A Handbook for Health Care Professionals. London: BMJ Publishing Group. Hennekens, C.H. and Buring, J.E. (1987) Epidemiology in Medicine. Boston: Little Brown. Lewis, G., Churchill, R. and Hotopf, M. (1997) Systematic reviews and metaanalysis. Psychological Medicine, 27, 3-7. Lewis, G. and Pelosi, A.J. (1990) The case-control study in psychiatry (review). British Journal of Psychiatry, 157, 197-207 Pocock, S.J. (1983) Clinical Trials: A Practical Approach. Chichester: Wiley.
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PART TWO B
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9
Schizophrenia JANE SHAPLESKE and ANTHONY DAVID
Historical background Descriptions of mental disorders date back to antiquity. Clearly recognizable accounts of schizophrenia emerged in the nineteenth century. Below is a list of important historical contributions to the concept of schizophrenia: 1852 Morel applied the term demence precoce to a condition marked by intellectual deterioration starting in adolescence. 1871 Hecker described hebephrenia, a condition occurring in puberty with gradual deterioration and a tendency to 'silly' behaviour. 1874 Kahlbaum described catatonia, or tension insanity, a cyclical condition with prominent motor disturbances, particularly stupor, in the absence of neurological disorder. 1896 Kraepelin grouped catatonia, hebephrenia and paranoia together as a degenerative disease and used the name dementia praecox. 1911 Eugen Bleuler introduced the term schizophrenia, meaning splitting of psychic functions, and added the simple type. He described four psychological mechanisms which he believed to be 'primary': ambivalence, autism, loosening of associations and flattening of affect. These are often referred to as the Tour As'. 1939 Kurt Schneider proposed first-rank symptoms, in the absence of evidence of an organic disorder, to be highly suggestive of schizophrenia. 1980 Tim Crow proposed two types of schizophrenia (which to some extent drew on older notions of 'process' - chronic and deteriorating versus 'reactive' - relapsing and remitting). The innovation was to link this with proposed differences in dopamine hyperactivity (type I), associated with positive symptoms and good response to dopamine antagonist drugs; and neurological damage (type II), associated with chronicity, poor premorbid functioning and response to treatment.
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Clinical Features Characteristically, schizophrenia is a condition of relapse and relative remission superimposed on chronic deterioration of thinking and behaviour. The onset may be abrupt with florid psychotic phenomena, gradual deterioration in performance, or non-specific with low mood, anxiety or even obsessions (4 per cent) and no typical features. Behaviour may be odd, disruptive, suspicious, or at times aggressive. The premorbid personality is typically described as emotionally and socially detached. Such people have few friends are often cold and aloof and engage in solitary occupations. Their behaviour may be eccentric and they are indifferent to praise or criticism. Recent studies, including UK National cohort studies and a Swedish Conscript cohort study indicate that children who later develop schizophrenia are more likely to have lower IQs and educational achievements than other children. They are also more likely to have interpersonal and behavioural difficulties. Mothers recognize 'pre-schizophrenic' children as being different from their other siblings. Positive symptoms Most of the so-called positive symptoms are seen in acute episodes of illness, though they may also occur in chronic cases. The seven important groups of symptoms are considered next.
Delusions These are most commonly persecutory, though many other types occur (e.g. reference, grandiose), some with bizarre content. Characteristically they are linked to each other in a delusional system, which may preoccupy the patient. Primary delusions are most likely to occur at the onset of the illness and may take the form of delusional perception, sudden delusional idea or delusional mood.
Passivity phenomena These experiences of outside influence, which may be motor (made acts), sensory, or in the form of made feelings or impulses. The patient's belief in external interference is often described as a delusion of control.
Hallucinations These are characteristically auditory (70 per cent) but can occur in all sensory modalities (visual 30 per cent), including touch, as in the feeling of being stabbed or penetrated in some way. Hallucinatory voices refer to the patient in the second (most common) or third person and are usually derogatory, but can be complimentary or reassuring. They may be discussing or arguing about the patient or keeping up a running
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commentary as an hallucination. Chronic patients may develop a relationship with 'the voices' and find it hard to distinguish whether they occur inside or outside the head.
Abnormal mood states Anxiety and depression are common. Less common, but more specific, is incongruous or blunted affect.
Motor disorder Stereotypies and mannerisms are often present, particularly in the chronic disorder. A variety of motor disturbances is seen in catatonia.
Formal thought disorder This is chiefly a disorder of language, ranging from vague discourse that is difficult to follow (loosening of associations) to fragmented speech with neologisms which is incomprehensible (word salad).
Thought alienation This is the experience of external interference or access to thinking such as thought insertion, thought withdrawal and thought broadcasting. Thought block may be reported or observed. Schneider's first-rank symptoms These were said to indicate schizophrenia in the absence of organic disease, although they were not essential for the diagnosis. They are: • • • •
delusional perception; thought insertion, withdrawal and broadcasting; thought echo; third-person auditory hallucinations - discussions or running commentary; • passivity phenomena - motor or sensory passivity and made feelings or impulses. It has been reported that nearly 20 per cent of chronic schizophrenics have never had these symptoms. The negative syndrome The onset is usually gradual (process schizophrenia; Langfeldt; type II, Crow) or can follow repeated relapses with incomplete recovery. Features are flattening of affect, social withdrawal, lack of motivation and interest, poverty of thought and speech. It must be distinguished from depression, parkinsonism and frontal lobe syndromes. A newer more refined description calls this the 'deficit syndrome'.
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Schizophrenic deterioration In this state, noted by Kraepelin, there is a fall in intellectual ability, loss of skill, socially inappropriate behaviour and decline in independence. It represents an interaction between premorbid functioning, effects of illness and effects of institutional care. It tends to reach a plateau in mid-life, unlike true dementing conditions.
Classification and diagnosis Most classificatory systems are based on a combination of psychopathology with onset and course.
International Classification of Diseases (ICD 10) The WHO 1992 ICD 10 has retained the following categories: 1. Paranoid. 2. Hebephrenic. 3. Catatonia. 4. Undifferentiated. 5. Post-schizophrenic depression. 6. Residual. 7. Simple. 8. Other 9. Schizophrenia other specified. ICD 10 specifies a minimum duration of 1 month. Within the stated subtypes, there is a separate designation according to course, e.g. paranoid schizophrenia - episodic, stable, etc.
Diagnostic and Statistical Manual (DSM IV) The DSM IV criteria require two or more of delusions, hallucinations, disorganized speech, grossly disorganized (or catatonic) behaviour, and negative symptoms for at least 1 month, social/occupations dysfunction and a duration of disturbance totalling at least 6 months. Shorter episodes are called 'Schizophreniform'. There are paranoid, disorganized, catatonic, undifferentiated and residual subtypes. Exclusions include effects caused by drugs or medical conditions and other (affective disorder) diagnoses. Differential Diagnosis
Schizoaffective psychosis It is difficult to demonstrate a 'point of rarity' between the distribution of symptoms of schizophrenia and those of affective disorders, i.e. overlap is common. Furthermore, many schizophrenics are depressed
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and some patients (up to 15 per cent) with affective psychosis have Schneiderian first-rank symptoms. When schizophrenic and affective features are present with equal prominence, schizoaffective psychosis may be diagnosed. Clinical features include episodic, recurrent psychosis in which schizophrenic symptoms occur against a background of elevated, depressed or labile mood. Prognosis is intermediate between manic-depressive psychosis and schizophrenia proper. Evidence from family studies is inconclusive, but there is a demonstrable genetic link to the affective disorders. Lithium prophylaxis is effective in a proportion of cases. It is classified under 'Schizophrenia and other psychotic disorders' in DSM IV, with depressive and bipolar types, and classified within the schizophrenia, schizotypal and delusional group of disorders in ICD 10. This is then divided into depressive, manic and mixed types. Many cases go on to have a clear affective illness or schizophrenia on future relapse.
Manic-depressive psychosis Some illnesses that are initially affective can recur with more schizophrenic symptoms.
Cycloid psychosis The nosological status of Leonhard's cycloid psychosis is uncertain. It appears to be a schizophrenia-like condition, commoner in females, with prominent affective change and good prognosis. It is subdivided into anxiety-happiness psychosis, confusion psychosis, and motility psychosis.
Reactive psychoses (psychogenic psychosis) Transient psychotic episodes of less than 1 month may follow stressful events. First-rank symptoms and other schizophrenic symptoms can occur. Bouffee delirante is a similar diagnosis, used in France.
Paranoid psychoses Other delusional conditions can resemble or lead to schizophrenia. Often they occur in middle age, in paranoid personalities and have little or no hallucinations. For example, in Kretschmer's sensitiver Beziehungswahn sensitive personalities develop paranoid psychoses with delusions of self-reference following key experiences. Monosymptomatic hypochondrical psychosis is a condition in which delusion of illness exists without hallucinations (although somatic sensations may receive delusional interpretations). It sometimes leads to further delusions. In Ekbom's syndrome, the delusion is specifically of infestation. In morbid jealousy (Othello syndrome), one partner believes the other
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to be sexually unfaithful, going to considerable lengths to prove the suspicion correct and at times using threats to extract a confession. The delusional condition may be part of a broader psychosis, such as schizophrenia, or may be a monosymptomatic state. Alcohol (10 per cent) and some drugs (e.g. cocaine) predispose. It occurs twice as commonly in men. Sometimes the delusion becomes self-fulfilling, as the accused partner seeks refuge with another person. On occasions it can lead the patient to kill or seriously injure his/her partner. De Clemmbault's syndrome (erotomania) is a delusional condition in which the patient believes another individual, usually someone of higher status, or in some other way unattainable, to be in love with them. This leads to persistent attempts to contact the 'lover', which are 'inexplicably' rebuffed. It may occur in isolation or as part of a psychotic disorder such as schizophrenia.
Alcoholic hallucinosis See Chapter 16.
Drug-induced psychosis See Chapter 17.
Acute toxic confusional state Fluctuating confusion plus prominent visual hallucinations and misinterpretations dominate the clinical picture.
Epileptic psychosis See Chapter 13.
Other CNS disorders A variety of organic conditions may (rarely) resemble schizophrenia in producing deteriorating mental function with delusions and hallucinations, e.g. Wilson's disease, Huntington's disease, metachromatic leukodystrophy, cerebral tumours (especially temporal or frontal lobe), etc.
Personality disorder Long-standing social withdrawal, aloof or eccentric attitudes and poor social adjustment may be features of personality or part of a schizophrenic defect state.
Epidemiology The lifetime risk of schizophrenia is approximately 1 per cent. The incidence is 15-20 per 100 000 population per year. The usual age of
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onset is 15-45 years, though it can occur at any age from 8 to 80. In males, the onset is on average 5 years earlier than females, and more males are hospitalized. The incidence of schizophrenia is equal in females and males. Fertility is now approaching normal levels with improved treatment and community care. Marriage is still uncommon in males. The increased prevalence in urban areas and low social class is probably due largely to downward social drift. Comparisons of fathers' occupations with those of controls shows no difference. However, recent work has pointed to urban birth and upbringing as weak but significant risk factors for schizophrenia. This may relate to increased exposure to pre- or perinatal viral infection (e.g. influenza) or other environmental stressors. The relationship between the incidence and prevalence of schizophrenia and migration is complex. The higher incidence in Norwegian Americans compared to Norwegian residents may have been due to immigration of predisposed individuals. However, this seems an unlikely explanation for the increased morbid risk of schizophrenia, which is 47 times greater in second-generation African Caribbeans in the UK, compared to their white counterparts. The incidence of schizophrenia in a similar ethnic population in Trinidad is no higher than elsewhere in the world. Asians who have migrated at the same time as African Caribbeans do not show this increased incidence. It appears that environmental factors may operate selectively on second-generation African Caribbeans. High rates of psychosis have been claimed to occur in Croatia, the Irish Republic and Northern Sweden, with low rates in Tonga, Papua New Guinea and the Islands of Indonesia. Estimates may differ due to differing diagnostic criteria, inbreeding or unidentified environmental factors. First-rank symptoms are found in a variety of cultures. The World Health Organization studies show similar incidences of narrowly defined schizophrenia in many international centres throughout the developed and less developed world. Less narrowly defined schizophrenia shows considerable variation. There is an unexplained negative association with rheumatoid arthritis. Mortality is higher than in the general population.
Aetiology Biological factors Genetic Family studies show the risk in first-degree relatives of schizophrenics to be around 10 per cent, but less in parents due to selection factors, i.e. ill parents are less likely to reproduce. The risk for second-degree
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relatives is 3-4 per cent; with an affected sibling and parent the figure is 16 per cent, while the child with both parents schizophrenic carries a 40 per cent risk. Modern studies using standardized or operationalized diagnostic criteria give the morbid risk of schizophrenia in first-degree relatives as between 5.5 and 3.7 per cent, which is still significantly higher than in other relatives and controls. Twin studies give concordance rates of monozygotic (MZ) twins 47 per cent and dizygotic (DZ) twins 12 per cent. Adoption studies show that the children of schizophrenic mothers are more likely to develop the disorder: 5 out of 47 cases against 0 out of 50 controls in Heston's study. Approximately 20 per cent of the biological relatives of adopted schizophrenics suffer from some form of the disorder compared to 6 per cent of the adopting relatives. Using DSM III criteria, the figures are 13 and 1.6 per cent, respectively. The mode of inheritance is likely to be multifactorial-polygenic, i.e. multiple genes plus environmental effects acting additively. Alternative proposals are a single dominant gene with impaired penetrance and multiple disorders, each with its own inheritance. This latter model is finding support in some molecular genetics studies of certain kindreds. Linkage to sites on the long arms (q) of chromosomes 5, 11 and 18 and the short arm (p) of 19 and the X chromosome are the most commonly reported associations. Recent genome-wide scans focusing on large samples of systematically ascertained pedigrees, rather than looking for a single major gene to explain most cases of schizophrenia, have suggested a multilocus model of schizophrenia genetics, focusing on the short arm of 6, 22 and the long arm of 8, 3, 20 and 9. Biochemical
Dopamine The dopamine theory is based on the response to dopamine blocking drugs, and the clinical similarity to amphetamine psychosis, which entails increased dopamine release. The D2 receptor was always thought to be the most important dopamine receptor in the aetiology of schizophrenia. However, the advent of atypical antipsychotic medications with equal potency, but with low D2 receptor occupancy has indicated that other dopamine receptor subtypes may have an equal or possibly more important role in the aetiology and treatment of schizophrenia.
Serotonin (5-HT) The 5-HT2A and C receptors appear to play a role in the negative symptoms of schizophrenia and protection against the long-term sequelae of neuroleptic use (e.g. tardive dyskinesia, TD). Antipsychotics with
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high-affinity antagonistic activity at the 5-HT2A receptors (atypical antipsychotics) have been shown to be more efficacious in the treatment of negative symptom schizophrenia than typical antipsychotics and produce fewer motor side effects (e.g. parkinsonism) with a similar level of dopamine blockade. Recent post-mortem studies of schizophrenics suggest decreased 5-HT receptor density in the frontal cortices of schizophrenics. This agrees with the fact that drugs which act on 5-HT receptors such as LSD are psychomimetic and some effective antipsychotics appear to have a primary effect on 5-HT receptors. Molecular genetic association studies have identified subgroups who may respond differently to typical and atypical antipsychotic drugs.
Gamma-aminobutyric acid (GABA) There are three areas where GABA has been implicated in schizophrenia. First there are non-specific post-mortem changes in GABA receptors in schizophrenia; second, benzodiazepines have some antipsychotic effect; and third anticonvulsants which act on the GABA receptor may be psychotogenic. Recent studies of GABA receptor density using SPET have shown an inverse correlation with positive symptoms.
Glutamate The non-NMDA receptors which are acted upon by glutamate are abnormal in post-mortem studies of schizophrenic brains. Recent work has suggested a modulatory link between the dopaminergic and NMDA systems. This together with the fact that drugs like phencyclidine (PCP) which act on the NMDA receptor are psychomimetic has led to some authors proposing a role for glutamate in the pathophysiology of schizophrenia. Anatomical A wide range of organic conditions may mimic schizophrenia, especially where left temporal lobe-limbic structures are involved, e.g. after head injury. An increased incidence of obstetric complications in the birth records of schizophrenics supports the developmental hypothesis (relative risk approximately 2.0). The main positive findings in gross pathology involve changes in the medial temporal lobe, with reduction in parahippocampal gyral volume in most studies, and reduction in hippocampal volume in some studies. The histological changes also occur in the medial temporal lobe. There are inconsistencies in the literature, but currently the main findings involve hippocampal neuronal disarray, reduced hippocampal cell size and increase in the number of cells in the hippocampus. The latter may represent a lack of pruning. Disorganization of parahippocampal cells
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and a deficit in small interneurons in the prefrontal and cingulate cortices have also been reported. The most consistent finding in structural imaging studies in schizophrenia is that of lateral ventricular increase and cortical volume decrease, found both in CT and MRI studies. Increased third and fourth ventricle size has also been demonstrated in schizophrenia. Generally, ventricular enlargement is more pronounced in male rather than female schizophrenics. The range of ventricular size is usually greater in schizophrenics than in control groups. The distribution of ventricular size is shifted in a downward direction relative to controls; that is, there is no identifiable subgroup of patients with particularly large ventricles. Affected MZ twins have larger ventricles than non-affected co-twins, possibly due to obstetric complications. However, the atrophy is nonspecific, being found in some people with bipolar affective disorder, alcohol dependence, anorexia, etc. The recent burgeoning of structural MRI studies has produced many results, not infrequently at variance with each other. Despite this, some general conclusions can be drawn, and some consistency with neuropathological studies is apparent. Reduced volumes and loss of asymmetry of the structures surrounding the ventricles have been demonstrated but with little correlation with symptoms. These include the amygdala, hippocampus and parahippocampal gyrus. The loss of asymmetry is most marked in an area known as the planum temporale which includes the auditory association cortex (Wernicke's area). These areas combined are concerned with selection, association and integration of sensory information, memory and the control of basic drives and emotions, all of which may be disrupted in schizophrenia. There is no relationship, however, between duration of illness and response to treatment, and structural brain abnormalities. Correlations with poor premorbid adjustment, neuropsychological impairment and negative symptoms have been found in some studies. These abnormalities appear to be present at the onset of illness and do not progress. This, in addition to the absence of gliosis on microscopy, gives further support to the notion that schizophrenia is a developmental disorder. This implies that incomplete or aberrant brain development (which may be focal or generalized) is present at or before birth, but that the recognized symptoms of psychosis occur after a delay perhaps because abnormal areas need to be fully innervated to have an effect or because of distant disruptions in neurotransmitter balance. This is referred to as the neurodevelopmental hypothesis.
Functional MRI (fMRI) and MR spectroscopy (MRS) Functional magnetic resonance imaging (fMRI) is a new way of measuring changes in regional blood flow and is still in its infancy as a tool in
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psychiatric research. Recent studies have concentrated on eliciting the difference in patterns in cortical activation under various cognitive activation tasks in schizophrenics. Magnetic resonance spectroscopy (MRS) uses a combination of radiofrequency pulses to make various nuclei absorb and emit energy. The results of this are represented in graphical form, giving a series of peaks or 'spectra'. The x-axis is the 'chemical shift' and allows the identification of the nucleus of the chemical element, and on the y-axis the height of the peaks gives quantitative information about the nucleus of interest. Consequently a series of peaks for a given nucleus provides information about the exact quantity of a particular molecule in a given volume of tissue. The use of proton MRS has allowed investigation of regional neuronal density. It is apparent that the decrease in mesial temporal volumes seen particularly in male schizophrenics is most likely due to decreased neuronal number. Phosphorus MRS, which gives an estimate of membrane and cell metabolism, has been used more extensively. Early studies have indicated decreased synthesis and increased breakdown of membrane phospholipids in the dorsolateral prefrontal cortex of schizophrenic patients. MRS can also be used to investigate the regional concentrations of medications.
Positron emission tomography (PET) and single photon emission tomography (SPET) Both PET and SPET can be used to measure regional cerebral blood flow and metabolism and estimate receptor density and function. A large number of studies have been conducted investigating the regional cerebral blood flow (rCBF) and metabolism in schizophrenic patients. It was previously thought that a decrease in frontal blood flow and metabolism ('hypofrontality') was indicative of schizophrenia, but the finding is not consistent. Correlating symptoms with functional imaging findings has proved productive. For example, psychomotor poverty has correlated with reduced rCBF in the left and medial prefrontal cortex. Estimations of receptor density and activity using PET and SPET techniques have to date focused mainly on the dopaminergic system. Emission tomography studies have found no clear striatal dopamine receptor differences between drug-naive patients and normal controls. Subtle alterations, including asymmetry of binding, have been noted but have not been fully confirmed. In studies of patients on medication, radioactive labelled ligands have been used to determine the in vivo receptor occupancy of both typical and atypical antipsychotics, relating these to clinical state. In contrast to the findings in drug-naive patients, emission tomography has partially reinforced the accepted theory that antipsychotic efficacy is related to D2 blockade. Nevertheless, nonresponders to antipsychotics still show high levels of striatal D2 blockade.
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Furthermore the highly effective atypical antipsychotic, clozapine, produces far less striatal D2 blockade than typical antipsychotics.
Neurophysiology Neurological soft signs are common, occurring in up to 60 per cent. These mainly involve increased prevalence of problems with sensory integration and motor coordination, and primitive reflexes. Smooth pursuit eye movements are abnormal in a proportion of schizophrenics and unaffected relatives. Event-related evoked potentials such as the P300 (evoked by the detection of novel stimuli) and N400 (detection of semantic anomaly) show reduced amplitude and increased latency in some studies. Psychological factors
Neuropsychology There has been increasing interest by psychologists and psychiatrists in using neuropsychology, which seeks to understand the relationship between brain function and behaviour, in the study of schizophrenia. The most robust findings indicate impairment in both verbal and visuospatial working memory, that is, the ability to use and manipulate information on line. It is yet unclear, but probable, that these deficits are due to malfunctioning of the 'central executive' - a proposed cognitive module thought to reside in the prefrontal cortex. Its function is to coordinate and integrate simpler processes, direct and maintain attention to task, and inhibit irrelevant inputs. Deficits in the central executive lead to planning difficulties and poor 'set-shifting' skills, found to be impaired in schizophrenia and tapped by tasks such as the Wisconsin Card Sorting test. The same sorts of problems are also observed in patients with frontal lobe lesions. Some subtle changes in semantic memory have also been noted and these involve abnormalities in categorizing objects or words and defining the meaning of words and phrases. These deficits are not seen in all people with schizophrenia. The disorder is heterogeneous and as a consequence researchers have started to study subgroups of schizophrenics with a particular symptom in common such as auditory hallucinations or delusions. Studies of deluded subjects have revealed that they display an attentional bias towards material sensitive to the patient's delusions, thereby continually reinforcing their delusions. Neuropsychological deficits are present at an early stage of the illness and do not show marked deterioration as the illness progresses. It seems that negative symptoms and an earlier age of onset are associated with worse cognitive performance.
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Reality monitoring This applies to the memory of the source of information rather than its content. Hence if a person cannot determine reliably whether he/she heard, thought or spoke an utterance, he/she may, for example, attribute a thought to an hallucination. Failure of one part of the brain to anticipate input from another because of a lack of feedforward information could lead to abnormal experiences (e.g. thought insertion).
Theory of mind This is a topic derived from studies of infantile autism. Human beings are adept in working out the thoughts and intentions of others (we understand that other people have minds like us). A defect in this ability could lead to, for example, misreading the intentions of others (persecutory delusions).
Attention and arousal Early, intuitively-satisfying theories stressed a breakdown of a sensory filter or gate which limits sensory input or the intrusion of preconscious cognitive processing and helps the person to select appropriate responses. Psychophysiological techniques utilizing early potentials such as the P50 and the pre-pulse inhibition learning paradigm offer support for this model. Venables proposed a disorder of arousal mechanisms. Chronic schizophrenics may be over-aroused on testing despite appearing apathetic. Social withdrawal may thus be adaptive.
Psychodynamic theories Symptoms represent the intrusion of primary process thinking and the use of defence mechanisms such as projection. This is the basis of persecutory delusions and pathological narcissism.
Social factors The association with social deprivation is probably effect rather than cause, although the effects of famine on early development are being studied. However, socially impoverished environments correlate with negative symptoms as in institutionalization. Life events, both positive and negative, in the preceding 3 weeks to 3 months, may precipitate onset. Analytically-based theories of abnormality within families (the double bind theory, etc.), particularly the mother-infant relationship, are unsupported by evidence. Some objective evidence of abnormal parental use of language was found in the 1960s and 1970s. There is weak evidence that communication deviance or affective style may be aetiological in high-risk individuals but equally, it could reflect shared genetic factors.
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Stronger evidence exists that criticism, hostility and over-involvement (expressed emotion - EE) within the family increases the chance of relapse of an established schizophrenic illness, although it does not cause it initially. Cultural factors modify the effect of EE.
Management Pharmacotherapy The efficacy of chlorpromazine and the other antipsychotic drugs developed subsequently has been proved beyond doubt in numerous double blind, randomized controlled clinical trials. They are predominantly used to treat 'positive' symptoms, but are less effective in treating 'negative' symptoms or preventing deterioration. They are used to treat acute psychosis, although their peak antipsychotic effect is delayed for approximately 2 weeks; however, they can act non-specifically to reduce agitation. Antipsychotics can also be used prophylactically. The therapeutic effect of typical antipsychotics, e.g. haloperidol, is thought to be related to their ability to block dopamine (primarily D2) receptors. It has been postulated that there is a 'dopamine window' whereby between 65 and 85 per cent dopamine receptors have to be occupied before a therapeutic effect is observed. Above 85 per cent, extrapyramidal symptoms appear. Using greater than 500 mg of chlorpromazine equivalents per day has no further antipsychotic effect. Any greater dose is essentially being used to sedate the patient. Typical antipsychotics are also available in depot preparations which can improve compliance and allow regular contact with community psychiatric nurses and clinics. Relapse occurs around 3 months after stopping drugs. Long-term treatment carries the risk of tardive dyskinesia. Approximately one-third of patients do not respond well to typical antipsychotics. Medication compliance may be poor in 50 per cent or more patients. The development of newer atypical (defined as not inducing extra pyramidal side effects in animal behavioural models) antipsychotic drugs (e.g. clozapine, risperidone, olanzepine, sertindole) which do not have high activity at the D2 receptor, but are still clinically efficacious, has challenged the dopamine hypothesis. Glozapine has been used since the 1960s for treatment of schizophrenia; however, after reports of several deaths from neutropenia, its use has become restricted. In the UK it can only be used for patients unresponsive to two other neuroleptics, or those with TD or severe extrapyramidal symptoms and only with blood monitoring. The risk of neutropenia is 1-2 per cent, and in most cases is reversible. Important aspects of clozapine's pharmacology include its low affinity for the D2 receptor, with higher affinity at the Dl and D4 receptors. Clozapine also has antagonistic activity at the 5-HT2 receptor, and this may underlie its clinical efficacy in improving positive and (possibly) negative symptomatology. Olanzepine is a similar drug, but
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does not cause blood dyscrasias. Both risperidone (which has moderate D2 affinity) and sertindole also act at the 5HT receptor sites. Lithium is used in schizoaffective psychosis and there is some evidence for a therapeutic effect. Benzodiazepines have been used but are not conventional treatment, though they can be given intravenously as non-specific treatment of acute serious disturbance. Psychological therapies General long-term support and counselling is desirable. Social skills training during remission can also be valuable. More recently, a cognitive behavioural approach has been used to challenge the assumptions underlying delusions, with some success. This can be helpful, provided that a therapeutic alliance is formed, where challenging the basis for delusions is carried out in a non-confrontational style and the patient is willing to engage in dialogue. Cognitive techniques can also be used to reduce the intrusiveness of symptoms such as auditory hallucinations. These treatments are complementary to pharmacotherapy, rather than an alternative. Practical treatments such as planning new activities in a graded hierarchy or carefully titrating exposure to novel situations can be devised to overcome cognitive deficits. Cognitive-behavioural techniques aimed at improving treatment compliance have been shown to improve outcome and reduce readmission rates. Social interventions Admission to hospital prevents the consequences of disordered behaviour, reduces psychological precipitants and allows the initiation of treatment. There is evidence that targeted community support may reduce the need for respite, crisis and compulsory admissions, although increased community outreach services also uncover previously unmet needs. There will always be a need for inpatient beds, particularly where social deprivation is high in the inner cities. Up to 40 per cent of patients live with parents. It is therefore essential to include the family in the management of patients, through educating, to improve problem-solving and to reduce abnormal closeness and the tendency to criticize. Adverse family and other stress effects may be mediated through increasing arousal. Social interventions are intended to reduce stress including expressed emotion thereby preventing relapse, reducing the burden on family or other care-givers and improving patient compliance. A key worker can help coordinate treatment, disability benefits and housing needs. Hostels or group homes vary in structure and support, from high-dependence units that provide 24-hour care, to the semiindependence of a supported flat with someone visiting daily. Rehabilitation is aimed at preventing overdependence, loss of skills,
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loss of dignity, and apathy. Abilities are initially assessed by occupational therapists. Latent abilities are fostered, developing job skills through industrial therapy, as well as simply providing low-key activities at day centres which help to improve social functioning. This may also have the added benefit of reducing contact with high EE relatives. There is evidence that carefully structured rehabilitation programmes improve patients' clinical state and social performance concurrently. Rapid change, however, including abrupt discharge, may precipitate relapse. Overall progress, including drug compliance, should be monitored by a community psychiatric nurse and/or regular outpatient clinics. This is usually carried out as part of the Care Programme approach (CPA) of patient care. This approach attempts to coordinate the various strands of care patients may require through a designated key worker, by first carrying out a needs-led assessment, which includes assessing social requirements such as housing, money, social contacts as well as psychological and medical care. Other physical therapies ECT still has a place in the management of catatonic schizophrenia, schizophrenia with a marked affective component (schizoaffective disorder) and in some cases of resistant schizophrenia. The short-lived improvement (weeks) is probably unrelated to improvement in underlying depression. Prognosis
Average outcome rates are 25 per cent - good, 50 per cent - chronic fluctuating course, 15 per cent - continuous symptoms requiring longterm care, 10 per cent - severe incapacity. The course of schizophrenia is the most stormy at its onset and early on, plateauing thereafter. The first readmission or relapse is most likely to happen within 5 years of the first episode. There was no evidence to suggest that schizophrenia undergoes progressive amelioration or deterioration in one 13-year follow-up study. A better prognosis is found in the developing world. This may be due to accepting attitudes, lack of responsibility or a more supportive family and social structure. Clinical features indicating a good prognosis are normal premorbid personality (one-third of patients), acute onset, a clear precipitant, older at age of onset (over 25 years), positive symptoms, paranoid subtype, prominent mood disturbance and good response to low doses of medication. Normal CT scan and higher IQ are also said to be associated with good outcome. First-rank symptoms do not carry any prognostic significance. Post-illness adjustment, i.e. work, relationships, etc., is most closely related to premorbid adjustment.
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Deliberate self-harm is much commoner than in normals, and the suicide rate is 10 per cent. Suicide risk is increased in young male patients with persistent delusions or hallucinations, particularly shortly before or in the first 3 months after discharge, especially early in the course of their illness when insight is highest. Very elderly patients may appear to gradually deteriorate but their 'dementia' is unlike Alzheimer's disease, pathologically.
Reading list Andreasen, N.C. and Olsen, S. (1982) Negative v. positive schizophrenia: definition and validation. Archives of General Psychiatry, 39, 789-94. Bebbington, P. and Kuipers, L. (1988) Social influences on schizophrenia. In Schizophrenia: The Major Issues (eds P. Bebbington and P. McGuffin). Oxford: Heinemann/Mental Health Foundation. Brockington, I.R, Kendell, R.E., Wainwright, S., Hillier, V.F. et al. (1979) The distinction between the affective psychoses and schizophrenia. British Journal Psychiatry, 135, 243-48. Brown, G.W. and Birley, J.L.T. (1968) Crises and life changes and the onset of schizophrenia. Journal Health and Social Behaviour, 9, 203-14. Cloninger, C.R., Martin, R.L., Guze, S.B. and Clayton, P.J. (1985) Diagnosis and prognosis in schizophrenia. Archives General Psychiatry, 42, 15-25. Crow, T.J. (1980) Molecular pathology of schizophrenia: more than one disease process? British Medical Journal, 280, 1-9. Crow, T.J. (1987) Recurrent and chronic psychoses. British Medical Bulletin, 43, 479-773. Cutting, J.C (1985) The Psychology of Schizophrenia. Edinburgh: Churchill Livingstone. Cutting, J. and Shepherd, M. (eds) (1987) The Clinical Roots of the Schizophrenia Concept. Cambridge: Cambridge University Press. David, A.S. and Cutting, J.C. (eds) (1994) The Neuropsychology of Schizophrenia, 1st edn. Lawrence Erlbaum Associates. Frith, C.D. and Done, C.J. (1988) Towards a neuropsychology of schizophrenia. British Journal Psychiatry, 153, 437-43. Gottesman, I.I. and Shields, J. (1982) Schizophrenia, the Epigenetic Puzzle. Cambridge: Cambridge University Press. Jones, P. (1997) The early origins of schizophrenia. British Medical Bulletin, 53, 135-55. Kendler, K.S., Gruenberg, A.M. and Tsuang, M.T. (1985) Psychiatric illness in first-degree relatives of schizophrenic and surgical control patients. Archives of General Psychiatry, 42, 770-79. Laing, R.D. (1959) The Divided Self. London: Tavistock. McKenna, P.J. (1994) Schizophrenia and Related Syndromes. Oxford University Press. Murray, R.M., Lewis, S.W. and Reveley, A.M. (1985) Towards an aetiological classification of schizophrenia. Lancet, 1, 1023-26. Weinberger, D.R. (1987) Implications of normal brain development for the prognosis of schizophrenia. Archives of General Psychiatry, 44, 660-9.
10
Affective disorders SIMON WESSELY and ANTHONY CLEARE
Clinical features Depressive disorder Depression is a clinical syndrome consisting of a core feature of low mood and/or anhedonia together with numerous behavioural, emotional, cognitive and biological features. Severe cases are associated with the development of psychotic features.
Appearance and behaviour • Psychomotor retardation or agitation. • Altered facial expression such as mouth turned down, exaggerated facial lines, lack of facial expressivity. • Self neglect and social withdrawal.
Emotional features • Low mood, distinct from ordinary unhappiness qualitatively (pervasiveness) and quantitatively (>2 weeks). • Loss of interest in anything that would normally have given pleasure, and an inability to feel pleasure (anhedonia). This is particularly relevant in assessing depression in the physically ill. • Lack of reactivity of mood to external events. • Tearfulness. • Irritability. • Anxiety: psychological symptoms such as dread, phobic anxiety or panic attacks, and physical symptoms such as tension, pains and autonomic arousal.
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Biological features Biological (somatic or vegetative) symptoms include: diurnal variation of mood, usually worse on awakening; sleep disturbance, with early morning waking; anorexia leading to weight loss; loss of libido; fatigue and generalized lassitude (anergia); constipation; amenorrhoea. Reversed biological features may be present, i.e. hypersomnia (increased sleep), increased appetite and weight gain. Atypical depression is a syndrome with reversed biological features, extreme (leaden) anergia, and interpersonal rejection sensitivity.
Cognitive changes Form Cognitive slowing is reflected in speech which becomes retarded and monotonous. Generalized cognitive impairment occurs with subjective and objective evidence of difficulties in concentration, registration and recall. Memory disturbance may be severe and resemble dementia (depressive pseudodementia). Content Thought content reflects the abnormality in mood, shown by the negative views of self (self-blame], the world (negativism] and the future (pessimism). Milder forms include a vague pessimistic outlook and a tendency to worry unnecessarily. Cognitive distortions include selective recall of unpleasant experiences. Moderate cases may show hopelessness, worthlessness and excessive guilt. Worries may amount to depressive ruminations. In severe depression, cognitive distortions give way to full delusions which reflect the mood state, i.e. they are mood congruent. Themes include guilt, poverty and hypochondriasis. The patient may feel he/she is being persecuted, which sometimes, but not always, is viewed as deserved. Auditory and other hallucinations may occur. Cotard's syndrome characteristically occurs in elderly patients, where severe depression results in nihilistic delusions, often with hypochondriacal content. Distorted views of the future may lead to predictions of disaster and suicidal thoughts or behaviour. Bipolar affective disorder (mania) Mania is a syndrome where the core feature is elated mood. Again, the syndrome includes behavioural, emotional, biological and cognitive features, and in severe cases, psychosis.
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Appearance and behaviour • • • •
Overactivity. Distractibility. Disinhibition of behaviour, dress, social contact and sexuality. Lack of judgement in social, sexual and financial affairs.
Emotional • Elevated mood: euphoria (normal, infectious mood) gives way to elation (abnormal, not infectious) and, in extreme, ecstasy. • Irritability, particularly in older patients. • Hostility, particularly when the patient's wishes are opposed. • Lability of mood is common: short episodes of depression, often intense, occur in many severe manic episodes.
Biological • Increased food intake, although excitement may lead to decreased intake. • Excessive energy (but rarely may get a manic stupor). • Increased libido. • Decreased need for sleep.
Cognitive changes Form • Pressure of speech and flight of ideas, leading to incoherence in severe cases. Content Grandiose ideas and delusions (80 per cent). Ideas or delusions of reference (40 per cent) Persecutory delusions (40 per cent). Auditory hallucinations (20-40 per cent). Visual hallucinations (10-25 per cent). First-rank schizophrenic symptoms (10-15 per cent). Most, but not all, psychotic features in mania are mood-congruent. A definite diagnosis of mania is often easier retrospectively. However, some clear-cut episodes of mania are succeeded by equally clear-cut episodes of schizophrenia. Mixed states The relationship between mania, depression and schizophrenia is a complex one:
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• Symptoms of mania and depression can coexist in the same patient at the same time (Kraepelin: mixed affective disorder}. • Symptoms of both mania and depression can coincide with those of schizophrenia in the same patient at the same time (Kasanin: schizoaffective psychosis}. • Patients with schizoaffective psychosis can be divided into a group that appears close to mania (schizomanic}, which respond to lithium, and a group with symptoms of schizophrenia and depression that respond to phenothiazines and ECT but not tricyclics (schizodepressive}. Some clinicians, such as Griesinger in the nineteenth century, consider all psychotic illnesses as representations of the same basic disorder ('unitary psychosis'). Other clinical presentations
Masked or atypical depression The usual symptoms of mood disorder are not prominent or are overlooked. Presentations include: Physical symptoms. Hypochondriasis. Impaired social functioning, especially in the elderly. Histrionic behaviour. Hypersomnia and fatigue. Most studies emphasize the importance of physical symptoms in the presentation of depression, i.e. the process of somatization. Feelings of fatigue and weakness are the most important, followed by headache, gastrointestinal disturbance, chest symptoms and dizziness. Longitudinal studies show that these often precede the affective symptoms.
Abnormal grief reactions Symptoms of a normal reaction to bereavement are similar to those of typical depression. Initially there is a stunned phase lasting for a few days, followed by misery and searching behaviour persisting for up to 6 months. However, grief reactions may merge into depressive illnesses. Murray-Parkes classifies abnormal grief into: • unexpected grief, when the death occurred unexpectedly and often in a horrifying way; • ambivalent grief occurs after relationships characterized by discord; • chronic grief is normal in form, but persistent - it particularly occurs following a dependent relationship with the deceased; • delayed or absent grief is a failure to pass through the normal stages of bereavement.
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Other features of abnormal grief reactions include intense anger and feelings of betrayal persisting beyond 6 weeks (Paykel). In some cases an anxiety state or psychosis may occur. Features increasing the risk of abnormal grief reactions include: sudden death; death where the survivor is blamed in some way; a dependent relationship with the deceased; personality characteristics (inability to express grief, insecurity); person still adjusting to previous losses; isolated social circumstances.
Classification A multitude of overlapping classifications coexist. Classification by course Affective disorders may be divided into those which involve only depression (unipolar illness) and those in which both episodes of mania and depression occur (bipolar). This division was clearly propounded by Leonhard, but refined by Angst and Ferris. Several observations are in its favour: • differing age of onset: bipolar 20-30 years, unipolar 30-45 years; • genetic evidence: first-degree relatives of bipolar probands (20 per cent) are more likely to be affectively ill than those of unipolar probands (10-15 per cent), and relatives of bipolar probands are much more likely than those of unipolar probands to have a bipolar course; • differing treatment response: although lithium is effective in the prophylaxis of both bipolar and unipolar illness, tricylics are effective only in unipolar. However, the division is not quite so clear. The relatives of bipolar probands have a higher rate of bipolar illness, but an even higher rate of unipolar illness. Furthermore, no differences can be found on symptomatology or acute treatment between the two groups. Finally, an unequivocal diagnosis of unipolar illness can never be made with certainty, as a subsequent episode may be of mania. Classification by aetiology • Reactive/endogenous. • Primary/secondary. Classification by symptomatology Common to all nosological studies of depression is a group characterized by certain symptoms: early morning waking, weight loss, poor appetite,
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anhedonia and agitation. This grouping has emerged from a variety of statistical analyses, using both factor and cluster techniques, and has been variously labelled as endogenous, nuclear, and melancholic depression. This symptom group is also associated with a specific treatment response and positive family history. There is less agreement as to what constitutes the rest. They are most often grouped together by the absence of the above symptoms. Contrasted with nuclear depression is a group characterized by milder symptoms, day-to-day fluctuation of mood, initial insomnia and prominent features of anxiety. Unlike the nuclear grouping, neither factor nor cluster analysis has given consistent results. The principal argument is whether the two groups represent distinct illnesses or lie at either end of a continuous spectrum. The Newcastle school (Roth) supported the former position, using multiple regression analysis to demonstrate two groups. However, Kendell was unable to demonstrate that a point of rarity exists between the two forms and proposed that depression represented a continuum. Paykel separated four groups of patients based upon cluster analysis: psychotic depressives (i.e. melancholic), anxious depressives (middle-aged, moderate depressive symptoms plus anxiety), hostile depressives (young, hostile) and younger with personality disorders. The classification into psychotic and neurotic depression is confusing, because the term psychotic was often used to imply severe depression rather than the presence of psychotic features. Modern usage restricts psychotic depression to those patients who have delusions and hallucinations.
International classifications DSM-IV The major division of mood disorders is into bipolar and depressive disorders:
Bipolar disorders • Bipolar I disorder. Episodes of mania alternating with depression. • Bipolar II disorder. Episodes of hypomania alternating with depression. • Cyclothymic disorder - a chronic mood disorder including both hypomanic and depressive symptoms, but insufficient to meet criteria for bipolar disorder.
Depressive disorders • Major depression, single episode. • Major depressive disorder, recurrent.
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• Dysthymic disorder - 2 years of depressive symptoms most days insufficient to meet criteria for major depression. • Depressive disorder NOS - including recurrent brief depressive disorder, premenstrual dysphoric disorder, minor depressive disorder, postpsychotic depression. In addition, mood disorders should be specified with regard to: • severity (mild, moderate, severe, severe with psychosis); • features (melancholic, catatonic, atypical); • pattern - post-partum onset, seasonal pattern, rapid cycling (at least four episodes per year). Depression may also be classified elsewhere, e.g. as part of an organic disorder or as an adjustment reaction. Schizoaffective psychosis is not listed under mood disorder.
ICD-10 Like DSM-IV, the clinical descriptions are claimed to carry no theoretical implications. Mood disorders • Depressive episode - mild, moderate, severe, severe with psychotic features. • Manic episode - hypomania, mania, mania with psychotic features. • Recurrent depressive disorder. • Bipolar affective disorder refers to any affective illness occurring in a subject with a previous or current manic episode. Persistent affective states • Cyclothymia: a persistent instability of mood involving mild depression and mild elation not sufficient to meet criteria for bipolar affective disorder. • Dysthymia: a chronic syndrome of low mood and associated symptoms never or rarely severe enough to meet criteria for a depressive episode. Depression is also encountered in other settings, e.g. organic (organic depressive state), other anxiety disorders (mixed anxiety and depressive disorder), or adjustment disorder which includes brief or prolonged depressive reactions. Schizoaffective disorder and post-schizophrenic depression are classified under the psychoses. Clinical description A full description of a mood disorder is not obtained simply by using the modern classification systems, though they have become closer
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with recent modifications. A full clinical summary would include the following:
Cross-sectional description • Clinical syndrome: mania, depression or mixed. • Symptomatic description: melancholic (endogenous/biological), psychotic or atypical depression features. • Behavioural description: retarded, agitated, catatonic. • Assessment of severity: mild, moderate or severe.
Longitudinal description • Unipolar or bipolar. If bipolar, presence of rapid cycling. • Seasonal pattern.
Aetiological description • Predisposing factors: these may be remote, such as childhood experiences or a family history, or more recent, such as chronic vulnerability or persistent stress. • Recent precipitants: these may be social, e.g. life events, or biological, e.g. physical illness, drugs, childbirth.
Differential diagnoses Differential diagnosis of mild/moderate depression
1. Normal sadness/bereavement Normal sadness lacks the other features of the syndrome. Bereavement may have many features of the syndrome, but is regarded as normal unless prolonged (>2 months in DSM-IV) or unusually severe, with e.g. profound retardation, suicidal ideas or psychosis (though transient hallucinations of dead person's voice occur normally in about 10 per cent).
2. Anxiety neurosis and phobias There is debate about the distinction between anxiety and depression. It is probably impossible to differentiate between the two either by symptoms or syndromes in mild cases. In neurotic outpatients, a Northwick Park study showed identical response to amitriptyline in both groups. Depression is a frequent occurrence in the natural history of agoraphobia, but less so in social and specific phobias. However, behaviour therapy appears to be a specific treatment for phobias.
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3. Obsessive-compulsive disorder Obsessional personality is a risk factor for depression. Obsessional symptoms occur in 20-30 per cent of depressive illnesses. Most of such patients do not have premorbid obsessional symptoms. Thirty-five per cent of those with typical obsessive-compulsive disorder will also meet criteria for major depression.
4. Dysthymia or cyclothymia 5. Personality disorder It is important to remember that patients with premorbid personality disorder have an increased, rather than decreased, likelihood of current depression. Differential diagnosis of moderate/severe depression or psychotic depression
1. Schizophrenia Depressive symptoms are common in schizophrenia, so accurate diagnosis is not always possible. Assessment of the mood congruency of psychotic features is important. Post-schizophrenic depression may respond to antidepressants or antipsychotics.
2. Delusional disorder (paranoid psychosis) The relative contribution of mood disorder must be determined in anyone presenting with predominantly paranoid features.
3. Dementia In favour of depression, and depressive pseudodementia, is: (a) (b) (c) (d) (e)
rapid onset, distressed affect, fluctuating cognitive deficit and patient's complaint of this, islands of normality, with no dyspraxia or dysphasia, past or family history of affective disorder.
In favour of dementia is: (a) normal sleep/wake cycle, (b) no diurnal variation in symptoms, (c) gradual onset, with prominent memory disturbance, and focal features, such as apraxia, agnosia and dysphasia. Modern concepts of dementia (e.g. Lishman) do not require progression or exclude reversibility. Furthermore, there is a subgroup of elderly depressives with enlarged ventricles. A clear-cut separation between
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dementia and pseudodementia is probably over-simple. If in doubt, the patient should be treated as depressed.
4. Physical disorders A variety of biological agents may underlie mood change, including: (a) endocrine: e.g. disorders of cortisol, thyroxine or parathormone production; (b) infections: e.g. glandular fever, syphilis; (c) CNS damage: e.g. strokes, Parkinson's disease, multiple sclerosis, meningioma; (d) carcinoma: e.g. a non-metastatic manifestation, especially pancreatic carcinoma which may otherwise remain occult. (e) Drugs: (i) cardiovascular - methyl-dopa, reserpine, beta-blockers, calcium channel blockers, digoxin. (ii) endocrine - steroids, (iii) others - L-DOPA, pentazocine, indomethacin, diuretics, clonidine, psychostimulants, alcohol, (iv) on withdrawal - amphetamines, benzodiazepines, cocaine. Although fluphenazine is said to lower mood, it is debated whether antipsychotic drugs cause clinical depression. Instead, depression may be either part of the psychotic process, a reaction to the social and personal disruption or a misdiagnosis of akinesia. Some antipsychotics have antidepressant properties (flupenthixol, thioridazine). The Royal College of General Practitioners' prospective contraception study suggests a small increase in risk of depression with oestrogen doses greater than 35 ^g daily. Kendler's twin study suggested that the tendency to develop depressive symptoms on the oral contraceptive was strongly genetic, but different from the genes controlling baseline morbidity. Differential diagnosis of mania
1. Cyclothymia 2. Schizophrenia and schizoaffective psychosis The best pointers to a diagnosis of mania often lie in a history of previous episodes of depression or mania, or a family history. Otherwise it is difficult to differentiate reliably between the two. Thought disorder or first-rank symptoms can occur in both, although personality deterioration, but not chronicity, is suggestive of schizophrenia. 3. Organic disorders In any case of mania it is important to search for cognitive disturbance.
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4. Secondary mania A variety of drugs may precipitate mania, e.g. amphetamines, steroids, L-DOPA, isoniazid, amantadine. Note that although exogenous steroids are more likely to cause mania than endogenous steroids, depression is still more commonly caused by both. Many CNS diseases may also present with mania, especially infectious or space-occupying lesions.
Epidemiology All surveys must be evaluated according to the diagnostic system employed, sample investigated, screening instrument used and case definition chosen. The point prevalence of major depression varies from 4 per cent to 7 per cent. The point prevalence of depressive symptoms is 16-20 per cent in most studies. The lifetime risk is around 20 per cent for depression, 0.75 per cent for mania. The National Co-morbidity Study in the USA represents a landmark study. A structured interview was administered to 8000 individuals in the community representative of the general population. The 12-month prevalence of depression was 10 per cent (M 8 per cent, F 13 per cent) and the lifetime prevalence 17 per cent (M 13 per cent, F 21 per cent) using DSM-IIIR criteria. Dysthymia was diagnosable in 6 per cent of the population (M 5 per cent, F 8 per cent). The peak age of onset is 50-70 years for psychotic depression, 30-40 years for unipolar depression and 20-30 years for bipolar illness. There is a female predominance of approximately 2:1 in unipolar depression, but equal sex incidence in bipolar disorder. Fifteen per cent of Camberwell (inner city London) women are depressed on Present State Examination (PSE), compared to 8 per cent in the Hebrides. There appears to have been a real rise in both the incidence and prevalence of depression during the last three decades, believed to be a cohort effect. This is true for both men and women.
Aetiology Aetiological factors have been extensively discussed in earlier sections of this book, but are summarized and, where appropriate, extended here for convenience. Biological
Genetics • Twin studies. In bipolar illness, concordance rates are 60-70 per cent monozygotic (MZ): 20 per cent dizygotic (DZ). Concordance rates are
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also 60-70 per cent in MZ twins reared apart. In unipolar depression, concordance rates are less, approximately 40-50 per cent MZ: 25 per cent DZ. MZ rates are even lower in 'neurotic' depression/community samples. • Adoption studies. In both bipolar and unipolar illness, there are increased rates of illness in biological relatives compared with adopted relatives of probands. • Family studies show increased familial risk (see above). The earlier the age of onset the higher the familial risk; late onset affective disorder has a lower genetic loading. No evidence exists for true Mendelian inheritance. The best current model is of polygenic/multifactorial inheritance. Recent linkage and association studies seem to confirm genetic heterogenicity. The few studies finding linkage (e.g. the X-chromosome and number 11) have not been replicated. There is no inverse relationship between genetic loading and the degree of environmental stress required to precipitate an episode. Thus a propensity to develop depression in response to life events is inherited. Also, recent family and twin studies show a clear genetic component to life events themselves. Both the tendency to suffer adversity and to respond by becoming depressed have genetic components.
Endocrine Hypothalamo-pituitary-adrenal axis Many depressed (and manic) patients have high levels of cortisol in plasma and urine. The normal diurnal variation in cortisol production may be reduced or phase shifted forward. There is an increased central drive to the axis shown by high CSF corticotrophin-releasing hormone (CRH) levels, and depressed patients show increased adrenal gland size on CT/MRI. Cortisol is the main stress hormone, and may act as a link between life events and biological changes in depression. High cortisol levels may cause: • impairment of neuronal 5-HT neurotransmission (relating to monoamine hypothesis of depression); • neurotoxicity - hippocampal cell death and shrinkage; • osteoporosis - women with recurrent depression have lower bone densities than controls. Lowering cortisol levels by giving cortisol synthesis inhibitors results in a resolution of depression in many cases.
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Dexamethasone suppression test (DST) Dexamethasone suppresses hypothalamic CRH and pituitary adrenocorticotrophic hormone (ACTH) release and hence plasma cortisol in normals. In a proportion of depressed individuals such suppression fails to occur. This observation has led to the development of the dexamethasone suppression test (DST). Dexamethasone 1 mg is given at 11 p.m., and plasma cortisol measured at 8 a.m., 4p.m. or 11 p.m. the following day. Non-suppression of cortisol on these measurements equals a positive test. Rates of non-suppression are: • • • •
endogenous/melancholic depression 60-70 per cent; mania 60-70 per cent; neurotic depression 40 per cent; schizophrenia 20 per cent.
There are also increased rates of non-suppression in old age, Alzheimer's Disease, weight loss (including anorexia nervosa), and with a number of drugs e.g. anticonvulsants. Non-suppression occurs across cultures. There is little difference in antidepressant response between DST positive and DST negative cases, though placebo response may be less in DST positive. However, if clinical response to treatment is associated with a continued positive test, there is a four-fold increase in the risk of short-term relapse or suicide attempt. One study found that DST non-suppression predicted a poor response to cognitive therapy. Hypothalamo-pituitary-thyroid axis Clinical disorders of thyroid function (hypo- and hyper-) are known to cause alteration in mood. In depression, several abnormalities in thyroid function have been described: • The TSH response to TRH (TRH test) is abnormally low in 30 per cent of depressives. • 8-17 per cent of depressed patients have subclinical hypothyroidism (high TSH but normal T4 levels, or an enhanced response to the TRH test). This rises to over 50 per cent in those refractory to initial treatment, compared with 5 per cent of the normal population. • Antithyroid antibodies are present in 9-20 per cent of depression. T3 or T4 supplementation potentiates both speed and efficacy of antidepressant medication, and may be particularly useful in resistant depression or rapid cycling bipolar disorder. T3 has the advantage of being more physiologically active and having a shorter half life. In mania, there is also a raised incidence of blunted TRH tests and antithyroid antibodies: subclinical hypothyroidism is very common in resistant/rapid cycling mania, and T3 supplementation is a treatment for refractory mania.
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Biochemistry Neurotransmitters The original monoamine hypothesis of depression proposed deficiency of noradrenaline (NA) and serotonin (5-HT) at monoaminergic synapses. Current theories are more complex. For example, behavioural pharmacology suggests that rewarding behaviour is potentiated by NA systems, and inhibited following unpleasant experiences by 5-HT systems. Also, lowered CSF 5-HIAA is more strongly associated with aggression and suicide than depression per se. Refinements of monoamine theories of depression include hypotheses about alterations in the balance of activity between the different neurotransmitter systems, receptor changes, postreceptor second-messenger system changes and attempts to relate monoamines to dimensional psychopathology rather than syndromal. Neuropharmacological challenge tests • 5-HT neurotransmission: prolactin response to fenfluramine or Ltryptophan is reduced in depression and mania. • Noradrenaline activity: GH response to clonidine (alpha-2 agonist) reduced in depression. • Dopamine activity: reduced GH response to apomorphine (DA agonist) in depression - inconsistent. • Acetyl choline activity: enhanced GH response to pyridostigmine (anti-cholinesterase) in depression. • GABA-ergic activity: reduced GH response to baclofen in depression.
Other studies CSF examination shows reduced 5-HIAA in depression, though possibly with a bimodal distribution. HVA and 3-methoxy-4-hydroxyphenylglycol (MHPG) are also reduced, suggesting reduced dopamine and noradrenaline turnover. Post-mortem brains from depressed suicide victims show decreased 5-HT content and increased 5-HT2 receptors, especially in frontal cortex. Depression is associated with reduced REM latency and increased REM sleep (and therefore dreaming/nightmares). These effects may represent increased cholinergic activity. Depressed patients show supersensitivity to REM sleep effects of cholinergics and serotonergics. There is an increased intracellular sodium in depression and mania. Studies of the activity of Na/K ATP-ase are inconclusive.
Cerebral pathophysiology Neuroimaging - structural Elderly depressives have features of cerebral atrophy (sulcal widening and ventricular enlargement) midway between that in depression and
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dementia. Patients with pseudodementia have more abnormalities than those without. Few differences demonstrated in younger patients with affective disorder, though possibly increased white matter lesions in bipolar patients. Neuroimaging-functional Functional neuroimaging uses SPET, PET or fMRI to measure brain activity, either via cerebral glucose metabolism or regional cerebral blood flow (rCBF). There is a consistent decrease seen in rCBF in the prefrontal cortex in depression. However, this is not a rinding specific to depression, and may instead be related to features such as psychomotor retardation, rather than diagnosis. Treatment of depression results in a normalization of this deficit. Changes in rCBF are impaired in response to serotonergic challenge with fenfluramine in depression, suggesting downregulated central 5-HT receptors. Kindling Neurons which are repeatedly subjected to convulsions or electrical stimuli show a process of kindling, whereby the fit threshold is gradually lowered, and the cells eventually become autonomously firing. Post has suggested that this phenomenon might underlie the tendency for some bipolar patients to suffer increasingly severe or refractory episodes of mania and depression, or to require fewer provoking life events, with passing time, eventually becoming rapid or ultra-rapid cycling. He proposes that anticonvulsants prevent this progression by preventing kindling. Psychological
Psychodynamic The psychoanalytic view of depression emphasizes the importance of loss, as in bereavement or separation. However, self-esteem and selfimage are equally relevant, whether lost or under threat. Psychoanalytic theory also views depression as a turning inward of aggression and hostility.
Cognitive Cognitive psychology places great emphasis on the cognitive distortions and errors that accompany depression. The cognitive theory of depression suggests that such changes are not just reflections of the lowered mood, but are instrumental in the origin and persistence of the disorder. For example, depressed people have substantial distortions of memory, with access to pleasant memories reduced and to unpleasant memories
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facilitated. Such distortions serve to amplify low mood. Cognitive theorists identify several specific errors in the thinking of depressed patients: 1. Automatic negative thoughts: regarding past, present and future (the cognitive triad - worthlessness, helplessness and hopelessness). 2. Negative expectations. 3. Cognitive distortions. (a) arbitrary inference - assuming events to have negative implications, (b) selective abstraction - concentrating on only the negative aspects of events, (c) magnification - attaching undue importance to insignificant matters, (d) minimization - underestimating good performance or events, (e) overgeneralization - extensive conclusions drawn from single incidents, (f) personalization. In addition, Beck theorized that people develop schema - characteristic ways of interpreting and looking at the world, based upon development, learning, genetics, etc. These are then instrumental in bringing about cognitive distortions and hence depression.
Behavioural Some animals, subjected to chronic stress, lose their capacity to act and avoid the stress. They also show a variety of other behavioural changes found in depressed people, as well as similar changes in endocrine, noradrenergic and cholinergic systems. This was called learned helplessness by Seligman. In a cognitive-behavioural formulation, Lewinsohn has proposed that normal mood state depends upon positive behavioural rewards, which may result from job or marital satisfaction, whereas distressing experiences are associated with negative rewards, and hence depression.
Social Predisposing factors (vulnerability) Bowlby proposed that people have an innate tendency to seek attachments, and that failure to do so leads to a failure of individual satisfaction (attachment theory}. Depression is viewed as the end result of disruption of these bonds. The study of Brown and Harris was carried out in two samples of depressed women, one in the community, the other known depressed psychiatric patients. First, they demonstrated the relationship between life events or severe long-term difficulties and depression in both
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samples. They then studied what factors made depression more likely after such events, remembering that only the minority of events are succeeded by illness. The following factors were reported as significant: • • • •
lack of a confiding relationship; unemployment; three or more children under the age of 14 at home; loss of mother before age of 11.
Others have hypothesized that low self-esteem as a result of these factors may be the important mediator. Tennant and his co-workers suggested that it is not the loss of, or separation from, the mother per se that is important, but subsequent events consequent on that loss. Death of a parent may lead to a variety of negative experiences and increased likelihood of other stressors. It is now accepted that there is a relationship between poor parenting and adult depression irrespective of whether that care was provided by the biological parent. The effects of childhood loss are not specific for depression. Similar claims have been made for adult anxiety disorder, schizophrenia, antisocial personality disorder and drug dependence. Social isolation is a powerful risk factor for depression, especially in the elderly.
Precipitating factors (life events) In the 6-month period following a life event, the chance of an episode of depression is increased five or six times. This is even more pronounced in parasuicide. These may be exit events, such as bereavement or separation, or undesirable events, such as mugging, redundancy. However, less than 10 per cent of exit events are followed by depression. Using the concept of brought-forward time, Brown calculated that threatening life events advanced an episode of depression by 2 years. The most commonly recorded event in a women's life in the 6 months prior to onset of depression is marital discord. Recent work suggests that the highest risk is posed by events which involve loss, which are independent of a person's control, or which are threatening or entrapping. People in hospital with a variety of medical illnesses also have an excess of life events prior to admission. It is possible that life events are associated with the decision to seek help rather than the actual illness itself. A similar role in the creation of illness behaviour rather than illness has been suggested for early loss of a parent.
Social networks Research by Henderson suggests that depressed persons do not actually lack social networks, but rather that the social bonds within such networks are weaker and provide less support.
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Management Physical treatment - pharmacological Indications, contraindications, side effects, therapeutic effects and drug interactions of the various drugs that may be used in the treatment and prophylaxis of affective disorders are discussed in detail elsewhere in this book. The general principles behind drug treatment strategies are summarized:
Pharmacological treatment of depression In mild depression, most patients do not require medication. Several general practice studies have shown that a variety of simple psychotherapies, such as problem-solving, are as effective as drugs. If drugs are to be prescribed, the following principles should be observed: • In view of the risk of overdose, outpatients should be assessed frequently and short supplies of drugs prescribed. Tricyclic antidepressants are fatal in overdose, and newer drugs may be preferred where there is concern. • Patients (and their relatives) should be warned about the delay in treatment response, otherwise they may stop the treatment as ineffective. • Likely side effects should be described to aid compliance. Also, if sedative tricyclics are to be used, the effects on driving and the sedative interaction with alcohol should be explained. Some measures show amitriptyline to be as cognitively impairing as alcohol above the legal limit. • The non-addictive nature of antidepressants should be stressed, as patients will frequently harbour a fear of addiction and subsequently not comply.
Treatment in special groups • The elderly may be more prone to anticholinergic and hypotensive effects of tricyclics. Thus SSRIs may be preferred • In the medically ill, many antidepressants are contraindicated in heart disease, epilepsy, etc. Also, most SSRIs inhibit cytochrome P450 liver enzymes and may interact with many liver metabolized drugs. • Patients who operate machinery or drive should not be given sedative drugs. • In patients with agitated depression, anxiety or agitation within depression responds to antidepressant treatment. It is not necessary to give sedative drugs in most cases, as sedative and anxiolytic effects are pharmacologically distinct. • In patients with psychotic depression, the combination of antipsychotic and antidepressant may be needed.
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• In pregnancy, if drugs are necessary, older tricyclics are preferred as there is more experience with their use. • Patients with atypical depression may respond preferentially to MAOIs.
General management Tricyclics or SSRIs are considered first-line treatments for depression, but ECT should be considered if rapid improvement is needed because of high suicide risk or depressive stupor. Suicidal patients with affective disorder should be admitted.
Pharmacological treatment of mania In mania, most cases will require admission, as deterioration can be rapid, and behaviour can have far-reaching consequences. Lithium is the first-line treatment and is an effective antimanic, but takes 7 days to be effective and is not sedative. Alternatives include carbamazepine and sodium valproate, both of which are effective acutely. The latter are more efficacious for rapid cycling mania and mixed affective disorder. Abnormal behaviour should be controlled in the meantime using either benzodiazepines in mild to moderate cases, or antipsychotics in severe and psychotic cases. ECT is probably effective, but is seldom used. As important is good nursing and the provision of space.
Continuation and prophylactic treatment In depressive disorder many studies have now demonstrated the necessity for adequate continuation treatment to prevent early relapse. Current recommendations are for a period of treatment of 4-6 months after resolution of the depression. Recurrent unipolar depression where there have been 3 or more episodes, or where episodes have been particularly treatment resistant or disabling, should be considered for long-term prophylactic treatment. The issue of full versus reduced dose has not been resolved, though most placebo-controlled evidence for efficacy comes from studies employing full doses of SSRIs or tricyclics. Lithium is also effective, but has too many drawbacks to be used, except for cases that are difficult to treat. In bipolar disorder, lithium is the treatment of choice for prophylaxis. However, there is a rebound effect when withdrawing lithium, with higher rates of relapse than if not treated. Therefore, patients should only take lithium if likely to comply. Carbamazepine and sodium valproate are also effective in the prophylaxis of bipolar illness.
Predictors of treatment response There are no clear predictors of treatment response, but it is believed that dexamethasone non-suppression and/or shortened REM latency
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may be associated with response to physical rather than psychological treatments. Several studies show that low urinary MHPG predict response to tricyclics, but variability is high, limiting clinical utility.
Biological effects of antidepressants There have been various demonstrations that antidepressants: • downregulate 5-HT2 receptors; • upregulate 5-HT,a receptors; • downregulate beta-adrenergic receptors and presynaptic alpha-2 autoreceptors; • have no effect on clonidine/GH response. Tryptophan depletion is a technique that rapidly lowers plasma tryptophan, and hence availability of tryptophan in the brain for resynthesis of 5-HT. Performing this procedure in remitted depressed patients causes a rapid relapse in symptoms in SSRI-treated patients, but not patients treated with desipramine, a noradrenergic specific tricyclic. The reverse is true if noradrenaline synthesis is inhibited: desipramine-treated patients relapse, while SSRI-treated patients do not. Antidepressant efficacy may depend upon differing biochemical mechanisms. Physical treatment - other
ECT ECT is discussed in detail in Chapter 30. Unlike antidepressants, ECT causes upregulation of postsynaptic 5-HT2 receptors. Other effects (e.g. prolactin response to fenfluramine) are the same.
Sleep deprivation REM latency, the period between the onset of sleep and the start of REM sleep, is decreased by around 50 per cent in endogenous depression, returning to normal on recovery. Antidepressants suppress REM sleep. Deprivation of sleep, and particular REM sleep, is associated with substantial improvement in mood, although it may not be sustained.
Psychosurgery See Chapter 30. Psychological treatment Cognitive therapy aims to alter the disturbed cognitions discussed above. Trials in outpatients have shown it to be as effective for mild to moderate depression in the short term as antidepressants. Other studies have suggested it may reduce relapse in outpatients. The combination of
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antidepressants and cognitive therapy affords a slight benefit over either alone. Supportive psychotherapy should be part of the treatment of all depressed patients, with the following aims: • • • •
an empathic, supporting relationship; ventilation of distress; education about nature of disorder; general semi-directive counselling.
Brief focused psychodynamic therapies (e.g. Malan) maybe useful. Dynamic psychotherapy, aiming for the development of insight by self-examination, may be inappropriate for acute cases, but can help selected patients subject to non-psychotic depressions. In interpersonal therapy, depression is viewed as a disorder of interpersonal relationships, regardless of aetiology. Therapy aims at symptom relief and a more effective approach to relationships. Reduced frequency therapy is effective at reducing relapse. Social Effective treatment of depression is impossible without attention to social factors. Counselling and family therapy may reduce social and psychological distress. Patients may benefit from advice on, or help with, changing adverse social situations such as financial, housing and employment difficulties. The meaning of a social situation may be modified by cognitive therapy. The decision to admit to hospital may be influenced by social factors such as: • In favour: • Against:
allowing patient and family a breathing space, danger of suicide, inadequate nutrition and lack of self-care. stigma of hospitalization, undermining of ability to cope.
Resistance to treatment Commonest causes are: non-compliance; inadequate dosage; insufficient time; wrong diagnosis (including missed physical illness); unaddressed psychiatric comorbidity; drug interactions; inadequate account taken of social, family and personal factors.
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Strategies in treatment failure Check for any of the above causes and take appropriate action. Pharmacological strategies include an increased dose, a change in drug class, adding lithium, combining antidepressants, adding T3 or L-tryptophan. Other strategies include the use of psychotherapy, ECT or psychosurgery.
Outcome and prognosis Short-term prognosis There is great individual variation. Episodes of mania are usually shorter than depression. Recovery of melancholic depression (26 weeks) takes longer than other depressions (16 weeks). About 10 per cent do not achieve full remission, remaining continuously ill. Long-term prognosis A meta-analysis of outcome in depression by Piccinelli and Wilkinson in 1994 showed that 50 per cent recover in 6 months, 25 per cent relapse in 1 year, 75 per cent relapse in 10 years and 10 per cent have persistent unresponsive depression. An 18-year follow-up by Lee and Murray of the cohort originally described by Kendell showed that psychotic depression responded better in the short term, but worse in the long term with a 75 per cent readmission rate and the majority suffering severe, long-term handicap. Ten per cent of unipolars became bipolars, and the suicide rate was 10 per cent. Bipolar illness is more likely to relapse than unipolar. In distress and disability, manic depression is probably as serious as schizophrenia. Of the 'new long-stay' patients described by Mann and Cree, 15 per cent had affective disorder.
Reading list Akisthal, H., Bitar, A.M., Puzantian, V.R., Rosenthal, T.L. and Walker, P.W. (1978) The nosological status of neurotic depression: a prospective three- to four-year follow-up examination in light of the primary-secondary and unipolar-bipolar dichotomies. Archives of General Psychiatry, 35, 756-66. American Psychiatric Association (1993) Practice guideline for major depressive disorder in adults. American Journal of Psychiatry, 150, 1-26. American Psychiatric Association (1994) Practice guideline for the treatment of patients with bipolar disorder. American Journal of Psychiatry, 151, 1-36. American Psychiatric Association Task Force on Laboratory Tests in Psychiatry
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(1987) The dexamethasone suppression test: an overview of its current status in psychiatry. American Journal of Psychiatry, 144, 1253-62. Bench, C.J., Frackowiak, R.S. and Dolan, R.J. (1995) Changes in regional cerebral blood flow on recovery from depression. Psychological Medicine, 25, 247-61. Charney, D. and Nelson, J. (1981) Delusional and non-delusional unipolar depression: further evidence for distinct subtypes. American Journal of Psychiatry, 138, 328-33. Dinan, T.G. (1994) Glucocorticoids and the genesis of depressive illness. A psychobiological model. British Journal of Psychiatry, 164, 365-71. Glen, A., Johnson, A. and Shepherd, M. (1984) Continuation therapy with lithium and amitriptyline in unipolar depressive illness: a randomised double blind, controlled trial. Psychological Medicine, 14, 37-50. Goodwin, G.M. (1994) Recurrence of mania after lithium withdrawal. Implications for the use of lithium in the treatment of bipolar affective disorder. British Journal of Psychiatry, 164, 149-152. Grove, W., Andreasen, N.C., Young, M., et al. (1987) Isolation and characterization of a nuclear depressive syndrome. Psychological Medicine, 17, 471-84. Hirschfeld, R. (1981) Situational Depression: Validity of the Concept. British Journal of Psychiatry, 139, 297-305. Kendell, R. (1976) The Classification of Depressions: A Review of Contemporary Confusion. British Journal of Psychiatry, 129, 15-28. Kessler, R.C., McGonagle, K.A., Zhao, S., et al (1994) Lifetime and 12 month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Archives of General Psychiatry, 51, 8-19. Maes, M. and Meltzer, H. (1995) The serotonin hypothesis of major depression. In Psychopharmacology. Fourth Generation of Progress (eds F.E. Bloom and DJ. Kupfer). New York: Raven Press. Paykel, E.S. (ed.) (1992) Handbook of Affective Disorders, 2nd edn. Edinburgh: Churchill Livingstone. Paykel, E.S., Scott, L. and Teasdale, J.D., et al. (1999) Prevention of relapse in residual depression by cognitive therapy: a controlled trial. Archives of General Psychiatry 56, 829-35. Piccinelli, M. and Wilkinson, G. (1994) Outcome of depression in psychiatric settings. British Journal of Psychiatry, 164, 297-304. Post, R.M. and Weiss, S.R.B. (1995) The neurobiology of treatment-resistant mood disorders. In Psychopharmacology. Fourth Generation of Progress (eds F.E. Bloom and DJ. Kupfer). New York: Raven Press. Schatzberg, A.F. and Nemeroff, C.B. (1995) Textbook of Psychopharmacology. Washington DC: American Psychiatric Press. Schou, M. (1986) Lithium treatment: a refresher course. British Journal of Psychiatry, 149, 541-7. Stavrakaki, C. and Vargo, B. (1986) The relationship of anxiety and depression: a review of the literature. British Journal of Psychiatry, 149, 716. Taylor, M. and Abrams, R. (1973) The phenomenology of mania. Archives of General Psychiatry, 56, 520-2. Thase, M.E., Greenhouse, J.B., Frank, E., et al. (1997) Treatment of major depression with psychotherapy or psychotherapy-pharmacotherapy combinations. Archives of General Psychiatry, 54, 1009-15.
11 Neurotic and stress-related disorders RICHARD GATER and RICHARD MORGAN
Despite its important place in the history of psychiatry and common use by mental health professionals, the term neurosis has been gradually disappearing from the major diagnostic classifications, to be replaced by more specific diagnoses. The term neurosis was proposed in 1776 by William Cullen to describe 'all those preternatural affections of sense or motion which are without pyrexia'. These included a wide range of disorders, some of which have subsequently been classified elsewhere (e.g. epilepsy, diabetes and chorea). Neurosis has continued to refer to a collection of functional mental disorders that do not involve hallucinations, delusions or loss of insight, and that are not caused by organic pathology. These disorders make up the vast majority of mental disorders in the community. In most community or primary care based research, a psychiatric 'case' usually corresponds with a diagnosis of neurotic disorder, and several near synonymous terms have come into widespread use, such as: the common mental disorders, minor affective disorders and minor psychiatric morbidity.
Current classification of neurotic disorders The process of refining the classification of neurotic disorders has continued with the latest revisions to the World Health Organization's International Classification of Diseases. ICD-10 does not identify neurotic disorders alone as a main class of mental disorders. Instead, neurotic disorders are classified with stress-related and somatoform disorders, owing to their common historical backgrounds and associations with psychological stress. The main disorders in this group are: phobic anxiety disorders, other anxiety disorders (including panic disorder, generalized anxiety disorder, and mixed anxiety and depressive disorder), obsessivecompulsive disorder, reaction to severe stress, adjustment disorders,
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dissociative (conversion) disorders, somatoform disorders and other neurotic disorders (including neurasthenia and depersonalizationderealization syndrome). Depressive states are classified separately from neurotic disorders under mood disorders. The American Psychiatric Association's Diagnostic and Statistical Manual (4th edn) has been more radical in dealing with neurosis than ICD-10. Since the development of DSM-III, the American diagnostic system has aimed to be an explicit and reliable system of classification based on criteria without any unproved aetiological assumptions. The concept of neurosis has no place in such a system, because neuroses were grouped together on the assumption of a common aetiological process of intrapsychic conflict, not on the basis of shared phenomenological characteristics. Therefore, diagnostic groups of neurosis or neurotic disorder do not appear in DSM-IV, but are superseded by anxiety disorders and dissociative disorders. This chapter will consider most of the ICD-10 neurotic and stressrelated disorders. Dissociative disorders, somatoform disorders and neurasthenia are covered separately in Chapter 24.
Problems with the categorical classification of neurotic disorders The individual neurotic disorders do not fit comfortably into a categorical system of classification that is reliable, mutually exclusive and jointly exhaustive. Anxiety and depression merge into each other with overlapping symptoms. The specific categories of neurotic disorder are not stable over time. Even within a single episode, anxiety symptoms may predominate at one time while depressive symptoms are stronger at another. There is evidence for a common cause to some (but not all) neuroses, in that genetic factors appear to generally predispose to depression and anxiety disorder. Similarly, the response to treatment of neuroses is largely similar irrespective of the specific diagnosis.
Dimensional models and latent trait analysis An alternative approach is a multidimensional model in which symptoms can be simultaneously rated on several different dimensions. Latent trait analysis is one method of dimensional modelling which has identified, in primary care attenders, three major dimensions corresponding with anxiety, depression and phobic anxiety/avoidance.
Anxiety - the core symptom of neurotic disorders Anxiety is the common feature of the neurotic and stress-related disorders. However, at subpathological levels it is a useful drive that
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maximizes performance. The Yerkes-Dodson curve illustrates that within the normal range of anxiety, performance improves to a plateau as the level of anxiety rises. However, when anxiety rises further and becomes pathological, attention to the task is lost and performance falls rapidly. The subjective experience of anxiety varies from person to person. Some people find brief high levels of anxiety thrilling. They seek out situations where they can experience a rush of anxiety. Others find almost any symptom of anxiety distressing and debilitating. For many people the experience of anxiety is predominantly physical, whereas others recognize the mental symptoms above the physical manifestations. When anxiety is pathological, it is usually experienced as an unpleasant emotional state of fear, often of an imminent threat or disastrous event such as death or collapse. These fears are recognized as being out of proportion to the real danger. Physical symptoms and signs of autonomic arousal, muscular tension and hypervigilance accompany the mental symptoms.
Differential diagnosis of anxiety symptoms Anxiety is a common feature of the disorders that are above the neurotic disorders in the diagnostic hierarchy. Therefore, it is important to exclude organic psychosis, which in early or mild stages may present with anxiety and impaired concentration; functional psychoses such as schizophrenia and affective psychosis, and alcohol, benzodiazepine or barbiturate withdrawal. Physical disorders, including thyrotoxicosis, hypoglycaemia and phaeochromocytoma, may present with anxietylike symptoms. Stimulants such as caffeine or methyl phenidate, and sympathomimetics such as salbutamol can mimic symptoms of anxiety.
Epidemiology Neurotic symptoms and disorders are common in the general population. Studies from different parts of the world have found community prevalence rates between 7 and 26 per cent per month. The most frequently reported neurotic symptoms are fatigue (27 per cent), sleep problems (25 per cent), irritability (22 per cent), worry (20 per cent), depression (10 per cent) and anxiety (10 per cent). The one-week prevalence of neurotic health problems identified in the OPCS survey of psychiatric morbidity among adults in Great Britain was 14 per cent. The prevalence of specific neurotic disorders reported from the OPCS survey were: mixed anxiety and depressive disorder (7.1 per cent), generalized anxiety disorder (3.0 per cent), phobias (1.7 per cent), depressive disorder (1.7 per cent), obsessive-compulsive disorder (1.3 per cent) and panic disorder (0.8 per cent). The high rate of mixed
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anxiety and depressive disorder may be inflated because it was used to classify people who were identified as cases but did not meet diagnostic criteria for any other diagnosis. Nevertheless, its high prevalence confirms the overlap in anxiety and depressive symptomatology in the general population. Two landmark studies from the United States have been the Epidemiological Catchment Area (EGA) Study and the National Comorbidity Survey. The EGA Study found one-month prevalence rates for DSM-III disorders of: phobia (6.2 per cent), major depressive episode (2.2 per cent), obsessive-compulsive disorder (1.3 per cent) and panic disorder (0.5 per cent). The National Comorbidity Survey reported that almost 1 in 5 adults aged between 15 and 54 years suffers an anxiety disorder in a year, and this rose to 1 in 4 when lifetime diagnosis were considered. The most common anxiety disorders were social phobia (13.3 per cent) and simple phobia (11.3 per cent), followed by agoraphobia (5.3 per cent), generalized anxiety disorder (5.1 per cent), and panic disorder (3.5 per cent).
Prevalence in primary care and specialist mental illness services Between 12 and 23 per cent of primary care attenders have mental disorder. One-third are anxiety disorders and most of the remainder are depressive disorders. General practitioners treat the vast majority (~90 per cent) without referral to specialist mental illness services. Of patients seen in psychiatric outpatient clinics, just over 10 per cent have anxiety disorders, though this falls to about 5 per cent of those admitted to psychiatric inpatient care.
Gender The rates of neurotic disorders are higher in women than men, with a gender ratio approaching 2:1. However, some studies report an approximately equal number of women and men in social phobias and obsessive-compulsive disorder.
Age Most community studies have shown that the prevalence of neurotic disorder has its peak in middle age. Among women, generalized anxiety disorder progressively increases with age, whereas phobias are most prevalent among young women. Rates of panic disorder are higher in people aged 25-44, and lower in those aged over 65.
Other sociodemographic factors Higher rates of neurotic disorder are linked with social disadvantage, such as: lower social class; unemployment; living in a poor housing
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environment; overcrowding; and being divorced, separated or cohabiting. Anxiety states are more common than depressive illness among women in rural areas.
Culture Surveys of neurotic disorders in different countries have shown intriguing differences in their prevalence. The difficulty in interpreting these differences is that some variation can be attributed to the different methodologies used to identify and define cases. Depression and generalized anxiety disorders show wide ranges of prevalence rates across countries. This suggests that different cultural or risk factors influence the expression of these disorders in different countries. In contrast, prevalence rates of agoraphobia, panic disorder, obsessive-compulsive disorder and social phobia are generally confined within low ranges across countries. Anxiety and depressive disorders show culture-specific variations in their presentations; for example Koro and Dhat (see Chapter 26 for further information).
Birth cohort effects During the past 15 years there has been concern that rates of major depression have increased dramatically through the past 70 years. Similar trends have been reported for panic disorder and agoraphobia. These observations are based on findings using lifetime diagnostic interviews, but longitudinal data on rates of depression do not confirm a marked increase in rates. It is possible that the apparent increase in rates is an artefact of the method of lifetime diagnostic interviews. Resolution of this problem will have to await further epidemiological surveys.
Co-occurrence of neurotic disorders The introduction of explicit diagnostic criteria has stimulated the investigation of co-morbidity, or the presence of more than one disorder over a period of time. Co-morbidity can arise for several reasons: one disorder may predispose to another; there may be a common aetiological basis for the two disorders; or it may be an artefact due to the method of assessment. When clear diagnostic criteria are applied, almost half of the cases of anxiety disorder also have current depressive disorder, and vice versa. The development of lifetime diagnostic assessments has allowed investigation of the consistency of neurotic diagnosis over time. A single neurotic diagnosis throughout a lifetime is the exception rather than the rule, except perhaps for generalized anxiety disorder. Among people given a lifetime diagnosis of major depressive episode without psychosis and melancholia, 84 per cent have lifetime co-occurrence of another
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neurotic disorder. The lifetime co-occurrence rate for dysthymia is 83 per cent; obsessive-compulsive disorder 67 per cent; social phobia 73 per cent; panic/agoraphobia excluding agoraphobia without panic 76 per cent; and generalized anxiety disorder 40 per cent.
The social impact of neurotic disorder Anxiety disorders are associated with a substantial social cost, including increased use of general medical care, and increased rates of drug or alcohol abuse and dependence. Men with panic disorder, phobias or obsessive-compulsive disorder are more likely to be chronically unemployed, to receive benefits and to be financially dependent than those with no mental disorder. These associations are strongest with panic disorder, and the degree of disability is greater for people with comorbid disorders than for those with a single neurotic disorder. The economic costs of neurotic illness are substantial. These include the direct costs such as the costs of the individual seeking care and the health or social services providing care; and the indirect costs of lost productivity. The total costs of neurotic disorders in UK general practice for 1985 was estimated to be £373 million, two-thirds of which was due to lost productivity.
Aetiology The aetiology of neurotic disorders is multifactorial. Predisposing factors include biological constitutional factors such as genetic liability and neurochemistry, adverse experiences in childhood, personality and temperamental coping strategies, and chronic social adversity. Precipitating factors that trigger an episode of anxiety disorder are usually associated with threat or danger.
Genetic factors Genetic factors play an important role in the development of neurotic disorders. For example, recent studies have concluded that the heritability of generalized anxiety disorder is 30 per cent. Other research has confirmed a shared genetic liability to anxiety and depression, and that environmental experiences determine the specific type of neurosis. The exception is panic disorder which aggregates in families, and does not show family associations with other mental disorders apart from social phobia.
Neurochemistry Ascending noradrenaline (NA) and 5-hydroxytryptamine (5-HT) neuron pathways terminating in the limbic lobe and neocortex have been implicated in anxiety. Enhanced NA function is involved in producing
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symptoms of increased arousal, while increased 5-HT2 receptor function leads to pathological levels of fear and avoidance. Other neurotransmitter pathways are important mediators of anxiety. Pharmacologically the most important of these are the inhibitory gamma-amino butyric acid (GABA) neurons that decrease the activity of other neurons including those in the monoamine system. Benzodiazepines enhance GABA transmission (and consequently reduce monoamine activity) by binding to specific receptors that are part of the post-synaptic GABAA receptor complexes in the limbic lobe and neocortex.
Childhood experiences Associations between childhood adversity and depression in adult life have frequently been reported. There are fewer reports of similar links for anxiety disorders. Parental separation, maternal death and traumatic events in childhood are associated with agoraphobia and panic. Women who experienced neglect, or physical or sexual abuse in childhood, are more vulnerable to both depression and anxiety as adults.
Personality People with anxiety disorders may have almost any premorbid personality, but those with personality disorder are far more likely to have a lifetime diagnosis of mental disorder than those who do not have a personality disorder. Certain personality features predispose to individuals showing a neurotic response to stressors. These include neuroticism, external locus of control, a defensive style and high levels of trait anxiety. Personality profiles of people suffering from generalized anxiety disorder and panic disorder are associated with high scores on the personality dimension of harm avoidance.
Learning theory Learning theory has offered explanatory models for some aspects of neurotic disorders, particularly phobic and obsessional phenomena. Normally, neutral thoughts or stimuli become associated with anxiety either by classical conditioning or indirectly learned from others. The individual develops neurotic responses to avoid or end exposure to the stimulus and so reduces anxiety. Anxiety reduction reinforces and perpetuates the neurotic response.
Social support In the presence of social adversity, those who feel they have inadequate support are more likely to develop neurotic symptoms than those with good support.
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Life events Neurotic disorders usually occur in the understandable context of stressful life events. There is some evidence that anxiety and depressive disorders follow different types of events. Events that pose a threat or danger tend to trigger anxiety disorders, for example the threat of the loss of important relationships, physical illness, or job threats such as possible loss of employment or an increase in responsibility. Compared with those suffering with depression, people with anxiety disorders have experienced fewer loss or undesirable events.
Treatment strategies The main treatment strategies for the neurotic disorders are pharmacological and psychological. The different categories of neurotic disorder show a generally similar response to treatment. For example, tricyclic antidepressants and behaviour therapy have a similar effect for generalized anxiety disorder, obsessive-compulsive disorder and panic disorder. The choice of treatment should take account of the nature and duration of the symptoms, previous treatment response, and the health-related attitudes of the patient. General measures Appropriate reassurance, education and supportive therapy are important initially and at relapse. This may involve the patient and their family. For patients who develop chronic disorder, the option of long-term support aimed at maintaining and improving social adjustment may be considered. Patients with chronic disorder value a consistent and reliable supportive contact. In considering general measures, it is worth taking account of factors that have been shown to predict recovery, such as reduction of difficulties, resolution of problems, positive life changes and good social support. Pharmacological treatments Benzodiazepines are rapidly effective and well tolerated in the treatment of anxiety. However, fast-acting high-potency benzodiazepines which carry a risk of dependence should generally be avoided unless the symptoms are severe and debilitating or the treatment will be short term. Special caution needs to be taken if there is a previous history of drug abuse or dependency. Gradual withdrawal will be necessary if use has continued for more than 1 month to minimize withdrawal symptoms and rebound anxiety. Side effects of sedation, impaired cognitive function and ataxia may be problematic during use. Tricyclic antidepressants and serotonin reuptake inhibitors have a
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slower onset of action. They are effective in generalized anxiety disorder, panic disorder and possibly post-traumatic stress disorder, and do not carry the same risk of tolerance and abuse as benzodiazepines. Discontinuation may be associated with relapse. Even those who initially respond well may stop therapy due to lack of complete response or side effects. Therefore, full information about the effects of medication and monitoring of response is important. Azapirones (e.g. buspirone) have anxiolytic effects after several days or weeks of use, and do not carry the same risk of dependence as benzodiazepines. Buspirone is effective in generalized anxiety disorder but not panic disorder. Buspirone is less effective in people who have previously taken benzodiazepines, and is not particularly useful for benzodiazepine withdrawal. Buspirone should not be prescribed with monoamine oxidase inhibitors (MAOIs) as the combination may produce hypertension. MAOIs tend not to be used as first-line treatment because of the dangers of the tyramine food and drug interaction. Nevertheless, MAOIs have useful anxiolytic properties that are effective in the treatment of phobic anxiety, panic disorder, social phobia and possibly generalized anxiety disorder. Reversible MAOIs (e.g. moclobemide) are safer but have been less widely investigated. Beta-blockers are helpful for the symptoms of anxiety mediated through beta-adrenoceptors, such as palpitations, tremor and flushing. Psychological treatments Behavioural or cognitive approaches are generally preferred in the treatment of anxiety and panic unless the severity of anxiety is so great that it impairs the ability of the patient to work with the treatment. Psychological therapy may include education about bodily and psychological aspects of anxiety, training in managing somatic symptoms by relaxation techniques and breathing exercises, systematic desensitization, cognitive restructuring, modelling and exposure therapy. More specific techniques may be employed in particular circumstances, such as response prevention and thought-stopping in obsessive-compulsive disorder, and social skills training for social phobia. Cognitive behaviour therapy is at least as effective as pharmacotherapy and has the advantages of lower drop-out rates and the potential for long-term benefit following withdrawal. Combination of pharmacological and psychological treatments Pharmacological and psychological treatments can be combined to good effect. An anxiolytic drug can produce rapid improvement in symptoms that allows the patient to build confidence in their ability to cope, so they are more likely to persevere successfully with psychological
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treatment. Psychological treatments may reduce the risk of relapse when drug treatment is withdrawn.
Course and prognosis The prognosis of neurotic disorder varies according to the population studied. About half the people with a neurotic disorder in the community recover in 3 months. Of those seen in primary care, one-quarter recover in a year, half have a variable course through the year, and one-quarter have a chronic course. For those referred to specialist mental illness services, half recover in 4 years. Factors associated with a worse prognosis are older age, longer duration of illness, co-morbidity, physical illness, persistent social problems, lack of social support, and personality disorder. The course of neurotic disorders may be adversely affected by the use of dangerous coping strategies such as alcohol or drug abuse, and by vicarious gains to the patient or others which reinforce illness behaviour. Factors associated with a better outlook are reduction of difficulties, resolution of problems, positive life changes and good social support. Several studies in the 1960s and 1970s showed that the relative risk of death for patients with neurotic illness compared with a normal sample was raised to between 1.4 and 2.0. This was due to a marked increase in risk of death due to suicide and accident during the first 2 years, but there was also an increase in deaths due to physical illness following 3 to 4 years later.
The individual neurotic and stress-related disorders Phobic anxiety disorders Phobic anxiety disorders are characterized by anxiety specific to welldefined situations, which the sufferer consequently tries to avoid. Merely contemplating their presence in the phobic situation can induce anticipatory anxiety. The distinction from normal fears can be made as the fear persists, even though the patient recognizes that the fear is excessive and unreasonable. For an ICD-10 diagnosis, at least one autonomic symptom of arousal must be present which may be accompanied by other somatic symptoms. In addition, the patient suffers significant emotional distress either through the anxiety symptoms or avoidance behaviour. Phobias are divided, in ICD-10, into agoraphobia, social phobia and specific phobias which encompass acrophobia, animal phobias, claustrophobia and simple phobias. Phobias to disease or disfigurement are classified, in ICD-10, under hypochondriacal disorder.
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Agoraphobia Clinical features • fear of open spaces (when originally introduced); • a consistent fear in, or avoidance of, at least two of the following situations: crowds, public places, and travelling alone or away from home (current specific characteristics described by ICD-10); • panic attacks, if severe, or alternatively individual may avoid the precipitating circumstances sufficiently to experience little anxiety.
Differential diagnosis The main differentiation is from other phobias - see differential diagnosis under social phobia below, for main differences.
Epidemiology The age of onset is typically between 15 and the mid-thirties.
Aetiology A precipitating event may be identified. There is also evidence to support the view that agoraphobia and panic disorder are part of the same spectrum. In DSM-IV it is considered to be part of a panic disorderagoraphobia spectrum in which patients with panic disorder are further described by the presence or absence of agoraphobia which is believed to reflect severity.
Course and prognosis Agoraphobia tends to be a lifelong disorder with a fluctuating course.
Social phobia Clinical features • characteristic fear is of scrutiny by others with the anticipation of humiliation; • most common phobic situations reported are: fear of speaking in social groups, fear of meeting new people and fear of eating in public places; • specific symptoms such as blushing or shaking, fear of vomiting, urgency or a fear of micturition or defaecation in the feared situation; • anxiety symptoms - any two of symptons 5-14 from Table 11.1 required by ICD-10 for diagnosis.
Differential diagnosis The primary differentiation is from other phobias, particularly agoraphobia and panic disorder. Agoraphobic patients fear that their next panic attack will occur in a setting from which escape is difficult, and
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Table 11.1
Symptoms used in the ICD-10 Diagnostic Criteria for neurotic and stress-related disorders*
At least one symptom of autonomic arousal 1. Palpitations or pounding heart, or accelerated heart rate 2. Sweating 3. Trembling or shaking 4. Dry mouth (not due to medication or dehydration) Symptoms involving the chest or abdomen 5. Difficulty breathing 6. Feeling of choking 7. Chest pain or discomfort 8. Nausea or abdominal distress (e.g. churning in stomach) Symptoms involving mental state 9. Feeling dizzy, unsteady, faint or light-headed 10. Feelings that objects are unreal (derealization) or that the self is distant or 'not really here' (depersonalization) 11. Fear of losing control, 'going crazy' or passing out 12. Fear of dying General symptoms 13. Hot flushes or cold chills 14. Numbness or tingling sensations 15. 16. 17. 18.
Muscle tension or aches and pains Restlessness and inability to relax Feeling keyed up, on edge or mentally tense A sensation of a lump in the throat, or difficulty in swallowing
Other non-specific symptoms 19. Exaggerated response to minor surprises or being startled 20. Difficulty in concentrating, or mind 'going blank', because of worry or anxiety 21. Persistent irritability 22. Difficulty getting to sleep because of worrying These include: agoraphobia, social phobia, specific phobia, panic disorder, generalized anxiety disorder and acute stress reaction (symptoms 15-22 are used only in the criteria for generalized anxiety disorder and acute stress reaction)
this lacks the crucial fear of humiliating scrutiny. Somatic symptoms vary slightly between the two disorders, thus social phobias are more likely to note blushing and twitching muscles whereas agoraphobic patients frequently experience dyspnoea, dizziness or faintness. The core phobic anxiety also helps differentiation from shyness and those with an avoidant personality. Epidemiology The mean age of onset is 11-15 years, with few new cases occurring beyond 25. Unlike most phobias, social phobias are equally common in women and men.
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Aetiology Parental behaviour, life experiences, genetic and developmental factors, as well as a negative cognitive appraisal of social situations, have all been considered as aetiologically relevant to social phobia, although the first two of these are present in other neuroses. There appears to be some continuity between the presence of childhood behavioural inhibition at 21-31 months with later childhood anxiety disorders and adult phobic or panic disorders. Familial studies have shown that 16 per cent of first-degree relatives of social phobias also had the condition, compared with only 5 per cent of controls. Biological studies have yet to demonstrate consistent abnormalities. Of interest, however, is a blunted growth hormone response to the alpha-2 agonist clonidine. Course and prognosis The course tends to be chronic and continuous, and as with other neuroses many do not present for many years. Co-morbidity is common and carries a worse prognosis. The reported suicide rate increases from population levels in those with simple phobias to rates of 15.7 per cent in those with comorbid conditions.
Specific phobias Specific phobias comprise phobic responses to very specific situations with little generalization beyond. ICD-10 further divides these phobias into phobias of animals, natural phenomena, blood injury or injection, and situational phobias such as fear of tunnels and so forth. This group differs from the others by virtue of relatively low levels of co-morbidity. The aetiology is not clear. Classical conditioning is unlikely to fully account for these phobias as many cannot recall a precipitating event. Most cases arise in childhood, a pattern particularly seen in animal phobias which also have a much greater female excess by adulthood. Certain fears are considerably more common than others, and the age of onset varies with particular fears. The prognosis for childhood phobias is generally good but that for adult phobias considerably worse, often with ongoing or even deteriorating symptoms. Nevertheless, the specific phobias respond well to desensitization.
Panic disorder Clinical features • panic attacks, which occur unpredictably, and are discrete episodes of intense fear or discomfort of abrupt onset that rapidly reaches a peak and which lasts at least several minutes and can be up to 1 hour;
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• signs of autonomic arousal and at least three other symptoms, from 5-14 in Table 11.1, during a panic attack - such symptoms must be out of proportion to the situation; • a persisting fear of further attacks; concerns about the consequences of further attacks; or major behavioural changes associated with the attacks (these features are required for diagnosis with DSM-IV but notICD-10). Differential diagnosis Differentiation from other psychiatric conditions requires the exclusion of psychotic experiences giving rise to panic symptoms, exclusion of a pre-existing depressive disorder (50 per cent of patients with panic disorder will at some stage experience an episode of major depression), and consideration of a somatoform disorder or hypochondriasis. The unpredictable nature of the attacks differentiates panic disorder from phobias which are situation or circumstance specific. Physical disorders such as hyperthyroidism, cardiac ischaemia, chronic obstructive airways disease, and cardiac dysrhythmias, may mimic panic disorder and must be excluded. Other conditions which should be considered are phaeochromocytoma, pulmonary embolus, hypoglycaemia, Cushing's disease and temporal lobe epilepsy. Epidemiology and co-morbidity The prevalence of panic disorder varies according to the population studied. People with panic disorder often interpret their symptoms as signs of a physical disorder. As a result, they frequently first present to medical settings, and are over-represented among primary care attenders, medical outpatients and accident and emergency departments. High rates of panic disorder have been reported in patients with airways disease, cardiovascular disease, migraine and irritable bowel syndrome. Aetiology Two studies have identified asymmetry in the parahippocampal gyral metabolism, but thus far few consistent findings have arisen. The main areas of interest in the search for a unitary neurochemical explanation of panic disorder have concerned the role of lactate, respiratory and blood gas effects, noradrenergic and 5-HT theories, the role of GAB A receptors and CCK. Lactate, carbon dioxide, hyperventilation, yohimbine (an alpha-2 antagonist), 5-HT agonists and flumazenil which blocks the GABAA receptor site all are anxiogenic. Clonidine (an alpha-2 agonist), the benzodiazepines and SSRIs can alleviate. The number of differing proposed mechanisms suggest that the neurochemistry is complex and a unitary model may be inadequate. Twin and family studies provide some evidence for a genetic contribution to the aetiology of this disorder with up to one fifth of first
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degree relatives of sufferers, compared to under 2 per cent of controls, having panic attacks. Cognitive models have also provided a partial explanation for panic symptoms. It has been proposed that panic symptoms arise as a conditioned association of the bodily symptoms of anxiety. The patient makes catastrophic misinterpretations of sensations, such as interpreting a slight increase in heart rate as a sign of imminent heart attack. This increases arousal and anxiety and fuels a rapidly escalating cycle. There is good evidence of the presence of such cognitions, and for the efficacy of treatment in altering this pathway. However, several findings indicate that this is unlikely to be the whole explanation: mood changes can precede physical symptoms in induced panic attacks; beta-blockers reduce physical symptoms but are not effective in preventing panic; panic can be pharmacologically induced despite prior knowledge that the physical symptoms will be brief and harmless; and conscious evaluation of sensations is not required as panic can start during non REM sleep. Course and prognosis One-third of patients experience sustained remission, half have a recurrent course and 20 per cent a chronic course. Between 73 per cent and 93 per cent are symptomatic after 20 years. Sufferers can be profoundly affected, with associated adverse effects on their social, physical and mental health, including an increased rate of suicide, myocardial infarction and cerebrovascular disease. Patients who fear further bodily symptoms or have phobic avoidance, particularly social phobia, have a poorer prognosis as do those with other co-morbidity. Childhood anxiety is not a predictor of poor outcome.
Obsessive-compulsive disorder (OCD) Clinical features • Obsessional thoughts, which are repetitious, unwelcome and intrusive. They may be ideas, images or impulses but despite their nature and content they are recognized by the patient as products of their own mind. Obsessions concerning contamination, pathological doubt, the body, a need for symmetry or of an aggressive or sexual nature are most common. • Compulsive acts, which tend to be secondary to the thoughts. They are repetitive and voluntary but are not pleasurable and the person realizes that they are senseless. Frequently reported compulsions include checking, washing, counting, a need to ask or confess, a need for symmetry or hoarding.
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• Resistance is a key feature, although this may have dissipated in those with long-standing symptoms. • Anxiety and depressive symptoms may also be present. Differential diagnosis The differential diagnosis of OCD includes the anxiety disorders, depression, schizophrenia, obsessive-compulsive personality disorder, organic conditions and the so-called OCD-spectrum disorders. Obsessional thoughts may occur in the course of a depressive episode, while those with OCD may consequently develop depressive symptoms. Timing of the relative onset of symptoms may help to distinguish which is the primary diagnosis. Approximately one-third of OCD sufferers have comorbid depressive disorder, while a lifetime risk of two-thirds has been reported. Various organic disorders, including post-encephalitic Parkinson's disease, Huntington's chorea, Sydenham's chorea and degenerative dementias, are traditionally included in the differential diagnosis, largely based on the presence of repetitive stereotyped movements. There is evidence from genetic and phenomenological studies, as well as from differences in treatment response, to support the view that OCD may be a heterogeneous condition, possibly with subtypes such as those with associated tic disorders. Similarly, the concept OCD-spectrum disorders has arisen owing to shared clinical features. Body dysmorphic disorder, anorexia nervosa, trichotillomania, sexual compulsions and Tourette's syndrome have all been proposed to belong in this group. In childhood OCD co-morbidity with tic, attention deficit, anxiety and affective disorders have been reported. Epidemiology OCD has been a hidden illness because patients present late, and early hospital-based studies missed those with less severe or transient disorders who had not sought care. There is a bimodal onset peak at 12-14 and 20-24 years with the mean being 20, and less than 15 per cent have an onset beyond 35 years. However, presentation is typically delayed and thus the mean age for this is 27 years. Most childhood onset cases are male. Aetiology A neurobiological view has increasingly come to the fore based on some clinical similarities with conditions affecting the frontal cortex and basal ganglia, imaging studies, neuropharmacology and genetics. The precise pathophysiology, however, remains elusive. PET scans have fairly consistently shown increased metabolic activity in the inferior prefrontal cortex, anterior cingulate and striatal regions. These changes decrease following treatment alongside clinical improvement.
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The biochemical correlates of the above findings are unclear. A major pathophysiological role for 5-HT has been proposed, largely due to a clear response to clomipramine and SSRIs. This response is independent of the presence or severity of depressive symptoms. Conflicting results from 5-HT receptor and provocation studies show that any aetiological role if present is complex. Family studies have shown a slight increased risk in first-degree relatives, although there have been insufficient systematic twin studies to confirm an increased incidence in concordant twins. An interesting genetic link has been found with Gilles de la Tourette syndrome, in which 11 per cent of those with this condition have family members with OCD, and OCD patients have an increased incidence of tic disorders. Management Pharmacotherapy using SSRIs or clomipramine is effective in approximately 50 per cent of patients. The addition of neuroleptics to treatmentresistant patients (particularly those with co-morbid tic disorder) has been advocated. Cognitive and behavioural therapies, particularly exposure and response prevention, considerably help at least 50 per cent of sufferers. Initial pharmacotherapy may alleviate symptoms in those severely affected, sufficiently to allow the addition of cognitive behavioural therapy thereafter. Owing to the chronic nature of the condition, supportive therapy is often required. Finally stereotactic cingulotomy or subcaudate tractotomy have been used, with claims from uncontrolled series of improvement in about one-third of patients. This form of treatment should only be considered when the condition is debilitating and has proved unremittingly unresponsive to all other therapy. Course and prognosis If the patient reaches psychiatric care the condition tends to be continuous rather than episodic, although recovery rates of up to 70 per cent at 1 year have been found in community surveys. Poor prognosis has been associated with male sex, early age of onset, longer duration of illness and obsessions of symmetry or exactness.
Generalized anxiety disorder Clinical features • persistent anxiety that is free-floating - this means that the anxiety is not restricted to specific situations but occurs generally across a variety of circumstances; • tension, worry and apprehension about everyday events persisting for at least 6 months; • four other symptoms from the list shown in Table 11.1.
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Differential diagnosis The main differential diagnoses of generalized anxiety disorder are the other neurotic disorders. Before making a diagnosis of generalized anxiety disorder it is therefore important to check for other neurotic symptoms and depression. A diagnosis of generalized anxiety disorder is not made if the disorder meets the criteria for phobic anxiety, panic disorder, obsessive-compulsive disorder or hypochondriacal disorder. Generalized anxiety disorder is left as a residual category that captures the substantial group of people in the population with high levels of trait anxiety who under conditions of stress experience persistent freefloating anxiety.
Mixed anxiety and depressive disorder As reported in the OPCS survey, mixed anxiety and depressive disorder is the most common neurotic disorder in the community. Symptoms of anxiety and depression are both present, but neither predominate and neither are sufficient to justify a separate diagnosis. Along with generalized anxiety disorder, mixed anxiety and depressive disorder correspond with the general concept of neurotic disorder discussed earlier in this chapter. Stress-related disorders The stress-related disorders arise primarily as a direct consequence of a stressful event or change of circumstances. They are maladaptive responses to stress or change. There are three stress-related disorders defined according to their symptoms and time course in relation to the stressor: acute stress reaction, post-traumatic stress disorder and adjustment disorders.
Acute stress reaction An acute stress reaction starts immediately (within 1 h) following the experience of an exceptional physical or mental stress. Initially the person is dazed, with impaired concentration and difficulty comprehending what has happened. In extreme cases they may appear disorientated. Over the following hours this symptom pattern may change to include symptoms of autonomic arousal, social withdrawal, anger, despair, purposeless overactivity or uncontrollable grief. However, these are short-lived and the symptoms of acute stress reaction disappear within a few hours or days.
Post-traumatic stress disorder Post-traumatic stress disorder (PTSD) is a more severe reaction following a threatening or catastrophic event. The term PTSD recently entered the
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major diagnostic classifications, but the concept has long been recognized as shell-shock, combat neurosis or battle fatigue. Clinical features • Traumatic event which involves the threat or witnessing of serious injury or death, and is of a severity that would cause major distress in almost everyone. • 'Latent' period of a few weeks to 6 months following the event before the onset of PTSD. • Specific symptoms, often prominent and distressing, relating to memories, thoughts and feelings about the event. They include fear, helplessness or horror. The event is relived in repeated 'flashbacks', strong memories or recurrent nightmares. Intense distress is triggered by cues resembling the event, and there is persistent avoidance of such situations. This may include avoiding thinking, remembering or talking about the event, and avoiding the people or places that trigger memories of the event. There may be inability to recall certain important aspects of the event. • Non-specific hyperarousal symptoms including hypervigilance, an increased startle response, difficulty in falling asleep or staying asleep, irritability or anger, and impaired concentration. Epidemiology The prevalence of PTSD varies according to the exposure to traumatic events of the population studied. General population rates are around 1 per cent. In subgroups, such as young adults in the city, this may rise to 9 per cent. Typically, a significant minority of people experience PTSD following a major traumatic event, with reported rates ranging between 3 per cent and 58 per cent. Some types of event carry greater risk. About half the survivors of concentration camps have persistent PTSD. Reported rates among crime victims are between 19 per cent and 75 per cent, and rates as high as 80 per cent have been reported following rape. Aetiology The stressful event is a necessary factor but family history, premorbid neuroticism, previous experience and perceptions of traumatic events, social support and the presence of other psychiatric disorders have also been implicated in the development or maintenance of PTSD. These are the same factors that are important in the development of neurotic illness generally, and it is not yet clear whether there is a specific predisposition to PTSD. Complex cognitive and neurochemical models of PTSD have been formulated. These include fear conditioning, sensitization, alterations in the speed, accuracy and depth of information processing, kindling and
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alterations in neurochemical systems involving noradrenaline, dopamine, endogenous opiates and corticoreleasing factors. Patients with PTSD have multiple exaggerated neurochemical responses to reminders of the traumatic event. Management Assessment should consider the effects of the trauma in the context of premorbid functioning and previous experience of trauma. It is important to check for the presence of other mental disorders or substance abuse, and the possibility of secondary gains or related litigation. If there was a possible head injury during the traumatic event, then a neurological examination should be carried out. Early cases have a relatively good prognosis. Simple support, ventilation and encouragement to resume normal activities may be sufficient. If symptoms persist beyond 3-6 months then more specific intervention is required. Pharmacological and psychological approaches are useful, and if combined these should be used in an integrated and flexible way. The non-specific symptoms of arousal may be helped by conventional psychological intervention such as anxiety management. Cognitivebehavioural techniques such as containment, desensitization, and cognitive restructuring, are useful for the specific symptoms. Problemsolving or assertiveness training may be helpful in particular cases. The results of pharmacological interventions are not consistent, but in persistent PTSD there do appear to be benefits from tricyclic, SSRI and monoamine oxidase inhibiting antidepressants. Eye movement desensitization has been rapidly effective in case studies of PTSD, but full evaluation is awaited. There have been mixed results from preventive measures using early critical incident debriefing. It is important to be flexible to the needs of the individual and not to force debriefing too hard or too soon after the event. Working with patients with PTSD can be demanding. They may be ambivalent about embarking on therapy, and angry or taking legal action against the cause of their stress. The therapist should ensure their own support and supervision, because the need to work through the stressful events with the patient may also be traumatic for the therapist. Course and prognosis In about half the cases, PTSD is an acute disorder followed by recovery within 3 months. Others go on to suffer persistent and disabling symptoms, often accompanied by other psychiatric disorders such as major depression, anxiety and substance abuse.
Adjustment disorders Adjustment disorders manifest as a state of anxiety, depressed mood, worry or inability to cope, accompanied by impaired function in daily
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activities at the time of adaptation to a significant life change or event. In the general approach to neurotic disorder, adjustment disorders occupy the part of the continuum between normal and the neurotic disorders. The symptoms are the same as those found in the affective disorders (except for delusions and hallucinations), neurotic disorders or conduct disorders, but at a severity falling short of that required for those specific diagnoses. In ICD-10, several subtypes of adjustment disorder are described according to their symptoms and time relation to the stressful event: • brief depressive reaction: mild depressive state lasting less than 1 month; • prolonged depressive reaction: mild depressive state lasting less than 2 years, related to a prolonged stressful situation; • mixed anxiety and depressive reaction: mild mixed state of anxiety and depression lasting less than 6 months after a stressful event; • adjustment disorder with predominant disturbance of other emotions: mild mixed state of anxiety, depression, worry, tension and anger lasting less than 6 months after a stressful event; • adjustment disorder with predominant disturbance of conduct: disturbance of conduct lasting less than 6 months after a stressful event; • adjustment disorder with mixed disturbance of emotions and conduct: mild emotional symptoms and conduct disturbance lasting less than 6 months after a stressful event.
Reading list Baldwin, D. (1997) Understanding obsessive-compulsive disorder: is it a class of its own? Progress in Neurology and Psychiatry, 1, 18-21. Goldberg, D. and Huxley, P. (1992) Common Mental Disorders: A Bio-Social Model. London: Routledge. Hohagen, F. (1998) New perspectives in research and treatment of obsessivecompulsive disorder. British Journal of Psychiatry 17 (suppl. 35). Judd, L. (1994) Social phobia: a clinical overview. Journal of Clinical Psychiatry, 55 (Suppl. 6). Marks I.M. (1987) Fears, Phobias and Rituals: Panic, Anxiety and their Disorders. Oxford: Oxford University Press. Office of Population Censuses and Surveys (1994) OPCS Surveys of Psychiatric Morbidity in Great Britain: Bulletin No. 1. The Prevalence of Psychiatric Morbidity Among Adults aged 16-64 Living in Private Households in Great Britain. London: OPCS. Regier, D.A., Boyd, J.H., Burke, J.D., Rae, D.S., et al. (1988) One-month prevalence of mental disorders in the United States. Archives of General Psychiatry, 45, 977-86. Snaith, P. (1981) Clinical Neurosis. Oxford: Oxford University Press. Tyrer, P. (1989) Classification of Neurosis. Chichester: Wiley.
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Ustun, T.B. and Sartorius, N. (eds) (1995) Mental Illness in General Health Care: An International Study. New York: Wiley. Wittchen, H-U. (ed.) (1996) Comorbidity of mood disorders. British Journal of Psychiatry, 168 (Suppl. 30). See also review articles on aspects of panic disorder in Journal of Clinical Psychiatry (1997) 58 (Suppl. 2).
12
Organic Psychiatry MARIA CLARKE and SIMON FLEMINGER
Delirium Delirium is an acute organic mental syndrome with a relatively constant clinical picture despite the wide variety of different causes. It is a common condition, with up to 15 per cent of patients over 65 being delirious on admission to hospital. Known risk factors include increasing age, underlying dementia and physical illness. Full recovery is the usual outcome of delirium, but there is a significant morbidity and mortality associated with this condition. The diagnosis of delirium is a two-stage process involving primarily recognition of the clinical features of the syndrome and then identification of the underlying cause. The clinical features of delirium are: • Impairment of consciousness and attention. • Global disturbance of cognition. The main cognitive functions of thinking, perception and memory are all impaired. Impairment of perception leads to illusions and hallucinations, often visual. Delusions may occur which are often fragmentary and fleeting. Immediate memory is impaired leading to secondary anterograde short-term memory deficits. Generally there is preservation of long-term memory. On recovery there is an amnesic gap for the period of delirium. Poor attention and memory leads to disorientation in time, place and, in severe cases, person. • Psychomotor disturbance. There may be under- or overactivity. • Disturbance of sleep-wake cycle. The patient is often drowsy during the day and shows broken night-time sleep. • Emotional disturbance. Mood disturbance is common, often fear, anxiety, perplexity or suspiciousness. Mixed states are frequent, giving an overall picture of mood lability. There may be a prodromal period of nonspecific symptoms, e.g. irritability, insomnia, but typically the onset is sudden over hours or days. The
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clinical picture varies, lucid intervals occurring usually during the day with nocturnal worsening. The duration is generally determined by the duration of the underlying cause. Common causes of delirium are: • infections - urinary tract infection, chest infection, or intracranial infection, e.g. meningitis; • cardiovascular causes - MI, congestive cardiac failure, arrythmias; • metabolic; • endocrine; • alcohol - Wernicke's/delirium tremens; • illicit drugs; • prescribed drugs-psychotropics, steroids, anticholinergics, digoxin; • head injury; • epilepsy - ictal, postictal; • cerebrovascular - stroke, transient ischaemic attack, etc.; • neoplasm - intracranial or remote effects; • other causes - vitamin B 12 /folate deficiency, SLE, porphyrias.
Investigations FBC, ESR, U + E, liver function tests, thyroid function tests, urinalysis, mid stream urine, EGG and chest X-ray. EEC usually shows generalized slowing, but in delirium associated with alcohol or benzodiazepines the EEG may show fast wave activity.
Management Management consists of treatment of the underlying condition and general supportive measures. General measures include nursing in a well-lit quiet room. Nursing care should involve regular orientation and reassurance. Antipsychotics should be used with caution; benzodiazepines may be required in cases of alcohol/benzodiazepine dependence.
Stupor Defined as a syndrome of akinesis and mutism with relative preservation of consciousness.
Aetiology Organic • Presenile/senile dementia. • Confusional state. • Cerebral tumour/cyst - commonest site for brain lesion is upper brain stem/mesencephalon.
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• Neurosyphilis. • Postepileptic. • Postencephalitic. Functional • Schizophrenic. • Depressive. • Manic. • Hysterical/psychogenic.
Clinical features In stupor due to functional illness the patient is less likely to be dependent on others for toileting and feeding. Facial expression and posture may give indications of the underlying mood state. On recovery there is likely to be recall for events during the period of mutism, in contrast to the amnesia for events in stupor of organic aetiology. Depressive stupor may develop from severe psychomotor retardation. Facial expression of sadness and a past history of depression may give further clues to the diagnosis. In manic stupor there may be periods of hyperactivity and facial expression of elation. Schizophrenics may adopt bizarre postures during the period of stupor. In stupor of organic origin there are usually abnormalities on neurological examination, e.g. abnormal pupils, roving eye movements. In these cases the distinction between stupor and other states of reduced consciousness or loss of consciousness may be very difficult.
Dementia Dementia is an acquired impairment of multiple areas of cognitive functioning occurring in clear consciousness. The cognitive impairments are often accompanied by deterioration in social behaviours, emotional control and acquired skills. Alzheimer's disease See Chapter 14. Lewy body disease See Chapter 14. Vascular dementia A clinical syndrome which can be caused by different vascular lesions (haemorrhagic, infarction, ischaemia). Males are more commonly affected. The clinical presentation can vary from a sudden onset post-stroke or show a step wise progression with a fluctuating course. The cognitive
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deficits commonly fluctuate and there may be focal neurological signs. There is often preservation of personality and insight until late in the course of disease. Depression and emotional lability may be prominent. By definition vascular dementia must show: • a decline in memory and at least two other cognitive functions, e.g. language, attention, visuospatial abilities; • evidence of cerebrovascular disease; • a temporal relationship between items 1 and 2. Clinical subtypes of vascular dementia include the following.
Multi-infarct disease Multiple infarcts cause a stepwise decline in cognitive function. There are often focal neurological signs and a history of hypertension.
Binswanger's disease This is commoner in males of age group 60-70 years. There is often a history of stroke-like episodes and chronic hypertension. Chronic hypertension causes arteriolar narrowing which causes ischaemic demyelination of periventricular subcortical white matter and lacunar infarction. Clinically there is a dementia of subcortical type, often with focal neurological deficits, especially motor deficits, clumsiness and gait abnormalities. Psychiatric symptoms include depression, apathy, psychomotor retardation, hallucinations and delusions. Patients with Binswanger's disease often show poor judgement and lack of insight. CT scan shows leukoaraiosis - low-density changes in white matter often in a periventricular distribution.
Strategic single infarct dementia A focal stroke causes a dementia syndrome, e.g. Angular gyrus syndrome aphasia, alexia with agraphia and spatial disorders. In suspected cases of vascular dementia on examination - check BP, examination of cardiovascular system (atrial fibrillation, carotid stenosis etc). Neurological system - focal deficits; fundi-arteriolar disease. Alcohol See Chapter 16. HIV
See later in chapter. Dementia of the frontal lobe type (DFT) This disorder has an average age of onset in the mid-50s and the average time to death is 8 years. Fifty per cent have a family history.
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DFT is a clinical syndrome of progressive personality and behaviour changes associated with frontal lobar atrophy. There is often loss of judgement and social awareness, lability of mood, disinhibition with lack of insight. Later there may be apathy, mutism, echopraxia and stereotyped speech. Psychiatric disorders are varied, including depression, persecutory ideation and mania. The psychiatric features may precede the personality changes. Physical examination is normal, as is, generally, the EEC. SPET scan shows anterior perfusion deficits. The underlying pathology of DFT is heterogeneous, including Pick's disease, atypical Alzheimer's and a nonspecific subgroup with neuronal loss and gliosis. DFT may be linked to Diogenes' syndrome - a disorder of self-neglect in the absence of psychiatric illness or cognitive deficits. There is also an association between frontal lobe dementia and motor neuron disease. Pick's disease This disease occurs more commonly in women than men and has a peak age of onset of 50-60 years.
Clinical features It presents with a dementia of the frontal lobe type but accounts for only a minority of DFT. In addition a Kluver-Bucy-like syndrome may be seen, with excessive oral activity and indiscriminate sexual behaviour, suggesting temporal lobe involvement. Progression of the disease leads to intellectual impairment, memory deficits and neurological abnormalities. Perseverative and iterative phenomena are characteristic. Incontinence occurs early. CT scan may show selective atrophy of frontal or temporal lobes. Neuronal argentophilic inclusion bodies (Pick's bodies) are seen at postmortem.
Prognosis The course is slower than Alzheimer's. Death occurs some 2-10 years after onset. Huntington's chorea Huntington's chorea is an autosomal dominant disorder with complete penetrance. Prevalence in the UK is 4-9 cases per 100000 and the mean age of onset is 35-45 years. The responsible gene has been located to the short arm of chromosome 4. Huntington's disease is an example of an unstable trinucleotide repeat disorder (GAG), the length of repeat bearing an inverse relationship to
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the age of onset of disorder. Offspring of affected fathers have an earlier age of onset, a phenomenon known as genetic anticipation. One-third of patients present with mental changes and two-thirds with chorea. The dementia is subcortical in type with a gradual onset of apathy, impaired concentration, attention and visuospatial skills. Insight is retained late into the illness. Other psychiatric disorders include: major affective disorder, paranoid and schizophreniform psychoses, behaviour and personality changes. Chorea consists of brief, unpredictable, abnormal movements affecting all parts of the body. The chorea tends to plateau late in the course of the disease. CT scan shows atrophy of the caudate nucleus and putamen with cortical atrophy. Treatment is symptomatic and genetic counselling should be offered if desired.
Prion diseases
Prion diseases are neurodegenerative diseases in which there is an accumulation of an abnormal form (PrPsc) of prion protein. Normal prion protein (PrPc) is a cell membrane bound glycoprotein. PrPsc differs from host protein by a post-translational conformational change into an insoluble form. This is an autocatalytic process. All prion diseases share a common neuropathology: • spongiform degeneration of areas of brain; • neuronal cell loss; • astrocytic gliosis. Prion diseases affecting man are as follows.
1. Kuru Kuru occurs solely in the Fore people of Papua New Guinea. It is transmitted during funereal rituals involving cannibalism and peaked in incidence in the 1950s. Clinically it has a long incubation period, presenting initially with cerebellar ataxia, dementia occurring late. Average time to death is 12 months.
2. Gerstmann-Straussler disease An autosomal dominant inherited form of prion disease with early ataxia and late dementia.
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3. Fatal familial insomnia Fatal familial insomnia presents with a picture of insomnia, motor signs and dysautonomia. Histopathology demonstrates degeneration of the thalamus and hypothalamus. 4. Creutzfeldt-Jakob disease (CJD) A rare disease with a worldwide incidence of 1 per million and approximately 50 cases a year in the UK. It has a peak incidence between 50 and 70 years of age. Classically CJD presents as a rapidly progressive dementia with myoclonus, ataxia and, at a late stage, akinetic mutism. Cortical blindness due to involvement of the occipital cortex may be seen. Five to ten per cent are familial with autosomal dominant inheritance. Transmission has also occurred during neurosurgery, depth electrodes, corneal transplants and human pituitary-derived growth hormone; EEG classically shows triphasic sharp wave complexes.
New variant CJD Since 1995 there has been an emergence of a new form of CJD with, to the present date nearly 100 cases in the UK. These cases tend to present at an earlier age with psychiatric symptoms - anxiety, depression, behavioural changes or withdrawal - with progression to neurological abnormalities. Typical EEG changes are often absent. Neuropathology demonstrates numerous kuru-type plaques. Diagnosis of prion diseases is commonly confirmed by brain biopsy or at necropsy. The emergence of a new variant has led to a search for early diagnostic markers in vivo, including the development of tests on CSF fluid and tonsillar biopsy.
Subcortical dementia This term has been introduced to highlight the distinct clinical features that result from damage to subcortical regions of the brain rather than the cortex, as in Parkinson's disease, Huntington's disease, progressive supranuclear palsy and AIDS-dementia complex. Clinical features • Psychomotor retardation with slowed thought processes. Performance improves if sufficient time is allowed. • Short-term memory is impaired - recall facilitated by prompting and cues. • Apathy and inertia are prominent. Depression is common. • Visuospatial skills may be impaired.
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• Movements are slow, often with flexed posture. • Cortical deficits not prominent (aphasia, agnosia, apraxia). The validity of the concept of subcortical dementia is not universally recognized: in Parkinson's disease there are neuropathological changes also seen in the cortex; in Alzheimer's disease (a cortical dementia) neuropathology indicates involvement of subcortical structures. Hydrocephalus Hydrocephalus is usually classified as follows: 1. Non-obstructive/communicating - secondary to atrophy of brain tissue, e.g. Alzheimer's. 2. Obstructive/non-communicating - due to obstruction of CSF outflow, leading to ventricular enlargement, e.g. tumour in the aqueduct. 3. Normal pressure hydrocephalus (NPHC) (obstructive and communicating). This third type of hydrocephalus is important as it is a potentially treatable cause of dementia.
Aetiology Fifty per cent of NPHC is idiopathic. Secondary causes include subarachnoid haemorrhage, head injury, meningitis and intracranial surgery.
Clinical features Hakim's triad of:
• Mental impairment - the mental changes usually appear first. Forgetfulness, inattention, slowing of complex information processing and aspontaneity are common features. Progression to a global dementia may occur late. • Gait disturbance. This is the symptom most to likely to improve after shunting. The gait is typically wide-based, with difficulty in turning and initiating movements (magnetic phenomenon). There is often a history of falls. Hyperreflexia of lower limbs with extensor plantars may be present. • Urinary incontinence. This is a late sign but urgency is often present from an early stage. Relative to the degree of dementia, urinary incontinence appears early which should lead to the suspicion of this diagnosis. In untreated cases there is a progressive deterioration in mental and neurological symptoms. Some cases may plateau at a fixed level, others progressing to coma and death. Sucking and grasping reflexes may appear late.
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Investigations and diagnosis • CT scan shows enlarged ventricles with little or no cortical atrophy. • LP - normal pressure lumbar CSF. A CSF tap test involves removing 40-50 ml CSF and noting if there is any clinical improvement. A positive tap test suggests a good response to a shunt, but the predictive accuracy of the test is limited by the high rate of false negative results. • Continuous lumbar drainage - sometimes used if the CSF tap test is negative to try to predict the outcome of a shunt. The test involves noting the effect of draining of CSF (100-150ml) for 3-5 days. • Cisternography - isotope cisternography shows disturbance in CSF flow with failure of lumbar CSF to spread over the surface of the brain despite entering the ventricles. Metabolic See later in chapter. Endocrine See later in chapter.
Other causes of dementia Metachromatic leucodystrophy An autosomal recessive lysomal storage disease with reduction in arylsulphatase A (measured in leucocytes). The majority of cases present in childhood, but 25 per cent manifest symptoms after 21 years. Men are more commonly affected than women (2:1). The onset is insidious and often protracted. Mental symptoms include behavioural disorders, psychosis with complex auditory hallucinations and bizarre delusions, personality change and progressive cognitive impairment. Neuropathy with CNS involvement leading to cerebellar and long tract signs. Diagnosis is by low level of leucocyte arylsulphatase A, high urinary sulphatide level, CT and MRI findings. Bone marrow transplant is used therapeutically to replace deficient enzyme and halt/slow progression of disease. Adrenocortical leucodystrophy X-linked, unknown cause. Cerebral symptoms (personality change, cognitive impairments, long tract signs) plus adrenal insufficiency.
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Kuf's disease Adult-onset cerebral ceroid lipofuscinosis; lipofuscin is deposited in neurons. Myoclonus, cerebellar or extrapyramidal signs occur in association with dementia. Gaucher's disease Glucocerebrosidase deficiency; accumulation of glucocerebroside occurs in reticuloendothelial cells and CNS. Adult-onset cases may present with motor incoordination. Mental disorders include behavioural disorder, psychosis and dementia. Investigation of dementia • Routine blood tests - FBC, U/E, calcium level, blood glucose, LFT, TFT, vitamin B12 and red cell folate, syphilis serology. • Neuropsychological assessment - to determine nature and extent of cognitive deficits. • CXR. • Neuroimaging - CT/MRI to exclude space-occupying lesions, hydrocephalus, may also demonstrate white matter changes. • EEG. • If suspect vascular dementia, may need - echocardiography, Doppler ultrasonography of the carotid arteries, EGG including 24 h monitoring. • Non-routine investigations include: (a) screen for metabolic disorders, e.g. Wilson's disease, (b) HIV test especially in young patients, (c) CSF if suspect vasculitis (raised protein or cell count), chronic meningitis, (d) Genetic screening, e.g. Huntington's disease. Management • Treatment as appropriate for reversible dementias (e.g. hydrocephalus, hypothyroid). • Donepezil may be of benefit in early Alzheimer's disease (acetylcholinesterase inhibitor). • Vascular dementia - reduce risk factors, e.g. hypertension, smoking, hyperlipidaemia. Aspirin or warfarin if embolic aetiology. • Multidisciplinary assessment as appropriate - physiotherapy, occupational therapist, etc. • Early discussion of diagnosis, prognosis and management with patient and carers. • Organize a supportive network within the community (e.g. GP, community nurse, social worker).
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• Consider day-centre attendance and respite care. • Plan for the patient's future need for long-term institutional care if appropriate.
The amnesic syndrome In the amnesic syndrome there is a disproportionate impairment of recent memory relative to other cognitive functions. There is a severe and permanent learning deficit (anterograde amnesia) in addition to a variable retrograde amnesia. These deficits occur in the presence of preserved intelligence and intact immediate recall (e.g. as measured by digit span recall). There are a variety of causes of the amnesic syndrome and attempts have been made to develop a classification system. Subgroups include those syndromes with predominantly diencephalic damage (WernickeKorsakoff 's, tumours of third ventricle), amnesics with medial temporal damage (herpes simplex encephalitis, anoxic brain injury, post-surgery) and amnesics with frontal lobe damage (e.g. post-anterior communicating artery aneursym). There are multiple aetiologies of the amnesic syndrome and prognosis depends on the underlying cause. Wernicke-Korsakoff syndrome Wernicke-Korsakoff syndrome is an amnesic syndrome resulting from thiamine depletion. The commonest cause of this syndrome is chronic alcohol abuse; other causes include persistent vomiting of hyperemesis gravidarum, neoplasm, e.g. carcinoma stomach, and toxic poisoning (carbon monoxide). Wernicke's syndrome is the acute phase of Vitamin B1 deficiency characterized by ophthalmoplegia, ataxia, confusion and peripheral neuropathy. Korsakoff's syndrome may have an acute or insidious onset. In addition to memory deficits there may be impaired performance on tests of frontal lobe function and visuospatial skills. Pathological lesions occur in periaqueductal grey matter, the walls of the third ventricle, floor of the fourth ventricle and the mamillary bodies. Herpes simplex encephalitis (HSE) HSE shows a predilection for the medial temporal lobes. In the acute phase there is rapid onset of pyrexia, delirium and focal neurological signs. The illness is frequently fatal (approximately 70 per cent). Survivors of the illness may show an amnesic syndrome in the chronic phase.
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Subarachnoid haemorrhage An amnesic syndrome may occur following rupture and repair of anterior communicating artery aneurysms as a result of subarachnoid haemorrhage. These patients have basal forebrain and striatal lesions. Post head injury The amnesic syndrome occurs as a sequela of head injury, possibly from damage to the medial temporal areas. Anoxic damage The temporal lobes are particularly sensitive to anoxic damage and after a period of reduced oxygen perfusion of the brain an isolated amnesic syndrome can occur. Causes of anoxic encephalopathy include cardiac arrest, carbon monoxide poisoning and strangulation. Transient global amnesia (TGA) TGA is defined as a sudden onset of amnesia occurring in clear consciousness with preservation of higher cognitive functions and absence of focal neurological signs lasting less than 24 h. During an attack the patient remains aware of personal identity but appears perplexed and may ask the same question repeatedly. After an attack there is a total (rarely partial) amnesia for events that occurred during the attack. A single attack is the most common pattern, although recurrent attacks can occur (< 20 per cent). Aetiology is disputed but a vascular origin is probable - ischaemia in the posterior cerebral artery circulation. Some studies have shown an increased incidence of migraine. Epilepsy may mimic these episodes.
Cerebral trauma Head injury Neuropsychiatric problems are the commonest cause of disability after a head injury. Head injury is common, with an incidence of 200 per 100 000 patients attending A&E departments in the UK per annum. Of these, 80 per cent are mild head injuries, 10 per cent moderate and 10 per cent severe; 1 per cent will go on to have considerable disability. Males outnumber females by more than 2 to 1 and peak incidence is in young males (15-24 years). Injuries may be either open or closed. Open head injuries are those in which the skull and dura are penetrated. Brain damage is usually focal.
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The vast majority of head injuries are closed, occurring as a result of road traffic accidents. In this type of injury the brain damage is more diffuse and typically there are contusions at the site of injury and at the opposite pole - 'contrecoup' injury.
Neuropathology Brain injury is usually classified in terms of pattern, i.e. focal or diffuse, and time course - primary or secondary. Primary injuries occur at the time of impact and secondary damage occurs post-injury as a consequence of complications which are either intracranial (e.g. hydrocephalus, haematoma) or extracranial (hypoxia, infection). Closed head injury 1. Diffuse axonal injury Diffuse axonal injury (DAI) involves scattered damage in the white matter, particularly occurring in the brain stem, around the basal ganglia and hippocampus and inter/intrahemispheric cortical connections. The injury consists of twisting and shearing of axons and when axon rupture occurs a 'retraction ball' develops. CT is poor at detecting DAI, but on MRI bright signals are seen in the white matter. DAI is associated with loss of consciousness in acute head injury and is also thought to account for much of long-term disability. 2. Contusions These occur in situations where soft brain is traumatized on rough bone. Contusions occur especially on the tips of the temporal lobes and the basal surface of the frontal lobes. 3. Diffuse small focal haemorrhages These occur typically in the brain stem. There may also be anoxic damage, oedema with raised intracranial pressure and subarachnoid haemorrhage.
Open head injury Skull and dura are perforated, encouraging infection. Brain damage may be localized precisely and there is relatively little diffuse damage.
Severity of head injury A classification of severity is useful both in management of the acute stage and as a guide to potential for recovery. Three indicators of severity of head injury are commonly used as follows: • Glasgow Coma Scale. This is a composite score of best verbal, motor and eye movement performance on admission. The coma score ranges
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from 3-15. A severe head injury is defined as those with a score of GCS < 9, moderate 9-12 and mild 13-15. • Duration of coma - a long duration suggesting a poor prognosis. • Post-traumatic amnesia (PTA). This is defined as the time from injury to the time of resumption of normal continuous memory. PTA is the best predictor of behavioural and cognitive problems.
Chronic sequelae Cognitive deficits Following head injury there is often rapid recovery of cognitive deficits in the first 6 months, with a slower rate of recovery occurring in the next 24 months. A chronic subdural haematoma, hydrocephalus or coincident dementing process should be excluded as a cause of cognitive deficits, particularly if there is deterioration. Global cognitive deficits occur post head injury. A common pattern is reduced speed of information processing, distractibility, reduced attention and problems with short-term memory. Naming and word-finding difficulties may also occur and in some cases difficulty in recognition of non-verbal cues of emotional expression.
Personality change Personality change post head injury is common. Changes include apathy, low frustration tolerance and impulsivity. Mood is often labile with marked instability. The patient is often described as self-centred and with no insight. Aggression may be a problem.
Neuroses Many clinical features can occur, the most common being depression. Anxiety with reduced self-esteem post injury is also common. Post traumatic stress disorder may occur without memory of the injury (although amnesia tends to protect). OCD has an association with frontal lobe injury.
Post-concussional syndrome This cluster of complaints occurs commonly following both minor and severe head injury. The syndrome consists of multiple complaints including dizziness, fatigue, irritability, poor concentration, insomnia and reduced tolerance to alcohol. The aetiology of post-concussional syndrome is poorly understood but there is evidence for organic factors in the early stages - EEG changes and altered brain stem evoked potentials. With persistence of symptoms for months, psychological and social factors become more important in causation.
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Suicide There is a 2 to 3 fold increased risk of suicide post head injury.
Psychoses Affective psychoses are usually depressive. There is also an increased prevalence of schizophrenia-like psychosis after traumatic brain injury, particularly in association with temporal lobe damage. Epilepsy The risk of epilepsy occurring, other than in the first week post head injury, is 5 per cent in closed head injury and up to 30 per cent in penetrating injuries. All the psychiatric sequelae of epilepsy may then follow. Aetiology of neuropsychiatric sequelae of head injury The following factors should be considered: • pretmuma factors - premorbid personality, past psychiatric history, family history, past history of head injury and alcohol history; • trauma factors - amount and localization of brain injury, cause and nature of injury (meaning for the patient); • post-trauma factors - development of epilepsy, convalescent environment particularly noting family support or conflict; financial consequences of disability - particularly compensation or litigation. Management Acute On emergence from coma there is often a period of confusion, disorientation and alteration in psychomotor activity lasting minutes to months. The patient should be nursed in a well-lit room. Care should be taken with medication. Psychotropic drugs should be avoided if feasible, but if this is not possible lower doses should be employed. People with traumatic brain injury appear to be particularly sensitive to the side effects of psychotropics and these drugs may slow recovery of neurocognitive function. When assessing these patients it is important to look for other causes of the confusional state, e.g. other complications of trauma, e.g. fat embolus, and head injury, e.g. subdural haematoma; drug and alcohol withdrawal; other causes of delirium - metabolic/ endocrine. Chronic stage • Assess physical disability.
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• Multidisciplinary assessment to determine nature and extent of cognitive and behavioural deficits. • Evaluate any psychogenic causes of symptoms and treat accordingly. • following full assessment, rehabilitation/convalescent care as appropriate. • Support for family - family therapy or meetings may be required. • Referral to specialist agencies, e.g. HEADWAY, may help. Prognosis Poor prognostic factors are left hemispheric damage, previous alcohol use, older age, post-traumatic epilepsy, inadequate compensation or unresolved litigation.
Medicolegal aspects of assessment Assessment should include the degree of disability, prognosis, and the impact on the quality of life. The relationship of the disability to the injury must be judged, noting whether symptoms might have occurred even if there had been no injury. Being involved in litigation may result in worse symptoms. Boxing and head injury Dementia pugilistica - 'punch-drunk syndrome' - is a traumatic encephalopathy caused by repeated blows to the head during a boxing career. Neuropathology shows atrophy, occasionally perforation of septum pellucidum and loss of cells with neurofibrillary tangles, particularly involving the hippocampic-limbic system and upper brain stem. Neurological features are of pyramidal, extrapyramidal and cerebellar disorder, especially dysarthria, slowed movements, ataxic gait and tremor. Psychiatric features occur in 50 per cent and include global cognitive impairment, personality change with irritability and apathy, chronic amnesic states and morbid jealousy. Impairments are often static, and may improve.
Dysexecutive syndrome Executive functions include self-regulation and monitoring, goalorientated behaviour, planning, motivation, response to changing environmental stimuli and creative problem-solving. Previously the term 'frontal lobe syndrome' was applied to patients with deficits in executive functions, as lesions in the prefrontal cortex were known to produce these deficits. The frontal cortex has extensive connections with other cortical and
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subcortical sites, and lesions distant from the frontal cortex are known to produce similar cognitive deficits. The term dysexecutive syndrome, a clinical description without any anatomical implications, is therefore now the preferred term for patients with loss of executive functions, i.e. lack of ability to plan ahead, poor self-monitoring, poor problem-solving and difficulties carrying out two tasks at once.
Cerebrovascular disorder This is a frequent cause of severe disability. The ratio of infarction to haemorrhage is 3:1.
Syndromes • middle cerebral artery - contralateral hemiparesis, sensory loss, dysphasias (dominant hemisphere), body-image disturbances (non-dominant) and contralateral homonymous hemianopia. • anterior cerebral artery - contralateral hemiparesis, with leg more affected than arm; incontinence; prominent personality change • posterior cerebral artery - contralateral homonymous hemianopia, visual agnosia, spatial disorientation; memory loss as a result of ischaemia of inferomedial temporal lobe • vertebrobasilar system - various neurological syndromes with cranial nerve, motor and sensory disorder: A. 1. 2. 3.
Posterior inferior cerebellar artery syndrome (PICA) Ipsilateral Horner's syndrome. Ataxia. Dissociated sensory loss - analgesia ipsilateral face and contralateral trunk and limbs. 4. Ipsilateral paralysis soft palate. 5. Nystagmus. B. Locked-in syndrome Complete motor paralysis plus aphonia but with normal consciousness and eye movements owing to severe damage to motor pathways in pons.
Psychiatric sequelae Cognitive impairment In general, a single stroke will not produce global impairment but patients with severe dysphasia may be difficult to assess. A variety of focal cortical syndromes are seen - anosognosia, contralateral neglect or inattention (especially with right-sided lesions).
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Personality change
Ability to deal with novel tasks may be reduced so the patient restricts him/herself to routines. He/she may be apathetic or irritable. A catastrophic reaction may be seen if the patient is overstressed, especially with left frontal damage. Affective disturbance
Depression is common, especially with left anterior hemisphere involvement, usually as a reaction to disability. It may exacerbate cognitive disability. Hypochondriasis is seen. Emotional incontinence may be due to bilateral lesions of the corticospinal tract (producing pseudobulbar palsy) from lacunar infarcts, but is seen following many different causes of brain injury. Exaggerated weeping and laughing follow trivial emotional stimuli.
Management • Medical - control risk factors, e.g. hypertension, consider aspirin or warfarin if embolic or patient has chronic atrial fibrillation. • Rehabilitation should pay particular attention to unilateral neglect, communication disorder and motivation. • Treat depression and emotional incontinence with antidepressants. • Involve family - facilitate social interaction to prevent social isolation.
Prognosis Major recovery from cognitive/neurological disability is usually complete at about 1 year, but may improve over many years, especially in the young. Patients are at risk of further cerebrevascular accident. Subarachnoid haemorrhage This is bleeding into the subarachnoid space and may be due to haemorrhage from a ruptured cerebral aneursym, arteriovenous malformation or secondary to trauma. Clinically there is a sudden severe headache with vomiting and faintness. Organic personality change occurs in at least 20 per cent, often related to cognitive impairment (especially after middle cerebral artery aneurysms). Anterior artery aneurysms produce personality change (due to frontal lobe damage) and amnesic syndromes, rather than global cognitive impairment. A 'leucotomy effect' may rarely produce improvement in premorbid personality. Anxiety is common, with fear of recurrent haemorrhage. Hydrocephalus may produce symptoms after a long latent period.
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Chronic subdural haematoma The head injury, often trivial and forgotten, may antedate symptoms by many months. Fifty per cent of adults with this condition give no history of trauma. It is more common in alcoholics (up to 50 per cent of cases) and the elderly. Classically there is vague headache, fluctuating conscious level and mild oculomotor signs, but the more common presentation is poor memory, difficulty in concentration and confusion or dementia. Surgical evacuation produces improvement in about 50 per cent. Systemic lupus erythematosus (SLE) SLE is a multisystem autoimmune disease occurring more frequently in women (9:1). The CNS is affected in 75 per cent of cases. Affective disorders and neurotic reactions are more common than in the general medical population. Schizophrenic and affective psychoses (usually depressive) are seen. Organic mental psychoses, usually delirium, are seen in 30 per cent of patients at some time. It is important to consider the possible effects of drug treatment, e.g. steroids, or metabolic disturbances as a cause of symptoms.
Intracranial infection Encephalitis Encephalitis, a primary cerebral infection, is often thought to be due to a virus although a viral aetiology is not demonstrated in every case. The virus may have a direct neurotoxic effect or cause immune destruction of nervous tissue. The illness usually presents as an acute febrile illness with impaired consciousness, drowsiness, headache, focal neurological signs, fits and evidence of systemic infection. In some cases all of these signs are absent and odd behavioural changes in a patient have been attributed to hysteria. Psychosis may be present. Encephalitis should be considered in the differential diagnosis of delirium and dementia.
Herpes simplex encephalitis This is the commonest cause of severe encephalitis in the UK. The virus causes a necrotizing encephalitis with a predilection for the medial temporal and inferior frontal lobes. CSF shows raised protein and cells but may be normal. Diffuse slow waves appear on the EEG. Brain imaging may show abnormalities over affected areas but can be normal. Brain biopsy was previously used to confirm the diagnosis but is now rarely performed. Polymerase chain reaction (PCR) assays of CSF are
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used in diagnosis. Despite treatment with the antiviral agent, acyclovir, the morbidity and mortality from HSV encephalitis remains high. Chronic sequelae include amnesic syndrome and dementia.
Rabies Rabies has a long incubation period of up to many years following inoculation. Early clinical features include restlessness and overactivity. There may be seizures and neurological signs of severe laryngeal and diaphragmatic spasms. These spasms produce hydrophobia - intense fear of water. The disease is usually fatal within a few days. Treatment after exposure to a suspected rabid animal includes local wound toilet, passive immunization and vaccination.
Encephalitis lethargica This disease occurred in epidemics in the early part of this century, but few well-documented cases have appeared in recent years. Clinically there is often an influenza-like prodromal phase followed by lethargy and sleep disturbance, ophthalmoplegia and various mental abnormalities. Residual difficulties include postencephalitic Parkinsonism with oculogyric crises, tics and compulsive behaviour.
Subacute sclerosing panencephalitis This affects mainly children and adolescents, males more frequently than females. The pathogen is thought to be the measles virus, possibly provoking an unusual immune reaction. Symptoms may first occur up to 6 years after the original measles infection. Early features are behaviour changes, temper outbursts, sleeplessness and hallucinations. Later there is a progressive intellectual deterioration associated with myoclonus and epilepsy. The EEC is characteristic, with high-voltage slow-wave complexes. Death usually occurs within a few days.
Progressive multifocal leucoencephalopathy This is due to infection with a papova virus. The infection occurs in immunocompromised groups, e.g. HIV, lymphoma, leukaemia. Clinically there is a progressive dementia with focal neurological signs, e.g. ataxia, aphasia, hemiparesis. There is usually a rapid deterioration, with death within a few months to years. Meningitis Meningitis is an infection of the pia mater and arachnoid. It is often fatal unless promptly treated with antibiotics.
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Pyogenic In adults the common organisms are meningococcus and Streptococcus pneumoniae. Tuberculous Gram-negative organisms and cryptococcus are more common in the immunocompromised. In the past, neurological complications including severe cognitive impairment, deafness and epilepsy were common post infection. Nowadays death, or recovery, is the rule often complicated by mild prolonged depression during convalescence.
Aseptic Mainly due to viral causes, enduring sequelae are rare.
Tuberculous meningitis The onset of this infection is insidious and commonly presents with illdefined mental changes, typically apathy, irritability and subtle changes in personality. Pyrexia is low grade and neck stiffness may be only slight until late, making diagnosis difficult. Cranial neuropathies may persist post infection. Neurosyphilis Caused by Treponema pallidum. Classical forms of illness are now rare. Neurosyphilis may present with any form of psychiatric illness.
Cerebral gurnma Resembles any other space-occupying lesion in presentation.
Meningovascular Usually occurs 1-5 years after primary infection with few spirochaetes present. The infection involves the meninges and superficial vessels of the cortex and spinal cord (endarteritis obliterans). Clinical features include headache, general malaise, lethargy, irritability, focal neurological signs, e.g. dysphasia, cranial nerve palsies. The course may be relapsing and remitting and response to treatment is good.
Tabes dorsalis Usually occurs 8-12 years after primary infection, rarely seen these days. Involvement of dorsal root ganglia and columns produces loss of sensation and joint position sense, ataxia, high-stepping gait, Charcot joints, loss of reflexes and Argyll-Robertson pupils (small, irregular, accommodate but no reaction to light). Lightning pains due to dorsal nerve root involvement occur.
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General paralysis of the insane (GPI) Occurs 5-25 years after primary infection. In the early stages may produce personality changes - irritability, emotional lability. Classically GPI produces grandiose expansive mood and delusions but now more frequently presents with depression, psychosis or dementia. Argyll Robertson pupils are present in 60 per cent and reflex changes in 50 per cent.
Serology Antibodies are formed against two different antigens: 1. Treponeme specific antigen - positive during disease and remains so despite treatment, e.g. TPHA, FTA, TPI. These tests do not distinguish syphilis from the non-venereal jaws, pinta, etc. CSF serology is required to rule out neurosyphilis as yaws causes antibody conversion in serum but not in CSF. 2. Wassermann reaction antigen (cardiolipin antibody). Indicates active infection, e.g. VDRL. Reverts to normal after treatment. False positive, e.g. pregnancy, pneumonia, SLE, etc. Note if HIV-positive, serology may be negative during syphilis reactivation. HIV may also modify the course and presentation of syphilis.
Treatment Procaine penicillin in high dosages (600mg-1.2g per 24 h) for 14 days. Herxheimer reaction occurs in 5-10 per cent. Treat with steroids. Follow-up is carried out at 2 and 6 months, then yearly for 5 years. Neuropsychiatric aspects of HIV infection HIV infection produces a wide variety of neuropsychiatric disorders. These complications may be due to: Direct invasion of the CNS by the HIV virus; secondary to cerebral opportunistic infection; primary CNS lymphoma; secondary to drug treatment; metabolic/endocrine secondary to disease. Common psychiatric disorders include adjustment reaction, depression, anxiety, substance abuse, psychosis, delirium, and dementia. AIDS dementia complex HIV dementia occurs late in the course of illness and is a rapidly progressive dementia with survival time of 3-6 months. The early symptoms are non-specific lethargy, depression. The cognitive deficits are typical of a subcortical dementia, with slowing of
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thought processes, poor memory, motor slowing, poor concentration and incoordination. There may be emotional lability. Later there is severe psychomotor retardation, word-finding difficulties, incontinence, myoclonus, and seizures. On examination there is increased tone, especially in the lower limbs, tremor, clonus and frontal release signs. CT scan shows cortical atrophy with ventricular enlargement, MRI periventricular white matter changes. Treatment with acyclovir may slow the progression of HIV dementia.
Space-occupying lesions Cerebral tumours Fifty per cent of cerebral tumours will produce mental symptoms at some time and can produce many different psychiatric syndromes. The prevalence of meningiomas in institutionalized psychiatric patients is increased two-fold above normal. Perhaps 1 in 500 patients presenting to the psychiatrist has an undiagnosed tumour. Symptoms are due to: • increased intracranial pressure leading to difficulty in concentration, impairment of consciousness, drowsiness, apathy, emotional flatness; • local effects of the lesion, though mental symptoms are poorly localized; • epilepsy. Individual factors such as genetic predisposition and premorbid personality may determine the individual's reaction to disability. Psychosocial effects may determine the nature and severity of neurotic symptoms. The type and location of tumour affects the production of psychiatric symptoms. Slow-growing tumours may produce mental symptoms in the absence of neurological signs and may therefore be difficult to diagnose. There is a higher incidence of psychiatric symptoms if tumours are: • • • •
supratentorial; malignant; metastatic; gliomas.
Meningiomas show a predilection for silent parts of the brain.
Clinical features Usually there is a progressive downhill course, but symptoms may be present over many years. Personality change is an early sign of tumour. Psychotic illness, schizophrenic and affective, may occur. Affective or neurotic symptoms are seen commonly; these may be an
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exacerbation of previous personality traits or a reaction to disabling and life-threatening illness. Mental symptoms may be related to the location of the tumour as follows: • frontal - common, especially frontal lobe personality change; relatively silent neurologically; • temporal - common with personality change, early cognitive deficits and complex visual hallucinations. There is an association with schizophreniform psychosis. Temporal lobe epilepsy occurs in 50 per cent; • posterior hypothalamic/upper midbrain - akinetic mutism; • pituitary - patients are often slow, passive, dull with increased sleep and appetite; • posterior fossa - early behavioural disturbance in children.
Management • Establish the nature of the tumour to establish prognosis and management. • Ensure that patient and family have access to detailed information about medical aspects of tumour, in particular the prognosis. • Treat psychiatric symptoms as appropriate. • Support the patient, family and carers. Other space-occupying lesions (SOLs) Brain abscess may follow middle ear infection or open head injury, though often no cause is found. Usually no systemic signs are seen. Early treatment may effect a cure with no residual symptoms. The organism is usually bacterial but in some patients e.g. with HIV, opportunistic infections are now seen (fungal and parasitic). Tuberculoma is an important SOL in India, but very rare in the West. Chronic subdural haematoma may lead to an SOL.
Endocrine disorders Hyperthyroidism Symptoms include restlessness, irritability, dysphoria, emotional lability, anxiety and poor concentration. The picture may mimic mania, although hyperthyroid patients have reduced energy. Affective (especially manic) and schizophrenic psychoses are probably seen more frequently than by chance association. Delirium occurs in thyroid crisis. In the elderly, hyperthyroidism may present with apathy and lethargy and may be detected, for example, when a tachyarrhythmia is noted on examination. Symptoms usually respond to medical treatment.
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Hypothyroidism This often has an insidious onset with ill-defined complaints - apathy, poor concentration and attention, fatigue, psychomotor slowing and poor memory. Severe cases may present with delirium, functional psychosis with paranoid features or dementia. EEG changes are common with slowing and flattening of alpha waves. Response to medical treatment is good unless symptoms are severe and greater than 2 years' duration. Hypercortisolism (Cushing's syndrome or exogenous steroids) This presents with behavioural/mental symptoms in up to 50 per cent of hospitalized patients with this syndrome. The most common symptom is depression; other features include anxiety, agitation, irritability, loss of energy and panic attacks. Psychosis may occur and memory impairment in older patients. The response to medical treatment is good. Addison's disease Apathy, fatigue and depression are commonly seen. Delirium occurs at times of metabolic crisis. There may be hypotension, and blood tests show hyponatraemia and hyperkalaemia. Hyperparathyroidism This may result in years of morbidity before the diagnosis is made. The commonest cause is a benign parathyroid adenoma. The main symptoms are physical 'bones, stones and abdominal groans', referring to bone pain, renal stones and abdominal pain due to various causes including pancreatitis and constipation. Psychiatric features are also common, especially depression, anergia and irritability. Mental slowing or memory impairment occur in 10 per cent. Delirium can accompany parathyroid crisis. Symptoms respond well to surgical treatment. Hypoparathyroidism This commonly follows thyroidectomy. In acute hypocalcaemic crisis, organic psychiatric syndromes are seen (e.g. delirium). The serum calcium level correlates with the mental state. Borderline low calcium levels result in neurotic symptoms, e.g. depression, tension and irritability. These may respond to oral calcium. With lower levels, acute confusion occurs which if severe requires treatment with intravenous calcium gluconate. Chronic symptoms include poor memory and concentration.
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Patients may be left with permanent cognitive deficits after normalization of serum calcium level. Hypopituitarism Secondary to tumour or planned destruction of the gland by surgery or irradiation. Apathy, depression and irritability are common. Delirium occurs and, in severe cases, coma. There is pallor of the skin, amenorrhoea in women and impotence in males with loss of axillary and pubic hair. It can also present as a slowly progressive dementia. Phaeochromocytoma Usually a benign tumour. 90 per cent are found in the adrenal medulla, producing catecholamines. Periods of crisis, usually lasting up to 15 min, occur with palpitations, sweating, nausea, tremor, headache and panic. Excitement may follow. Treatment is surgical. Hypoglycaemia Hypoglycaemic attacks (plasma glucose <2.5mM) may result from insulinoma, treatment of diabetes, liver disease or alcohol. A common cause is deliberate self-harm with self-injection of insulin. During an episode there is odd, often aggressive, behaviour with sweating, pallor, anxiety and, on occasions, depersonalization. There may be transient focal neurological signs and amnesia for the event. With an insulinoma, typically the episodes occur before breakfast or after exercise late morning. Chronic hypoglycaemia can lead to progressive dementia.
Metabolic disorders Hepatic disease Neuropsychiatric disturbance is common and may be the presenting feature of liver disease. Typically there is a fluctuating course with acute episodes which remit and recur. Clinically there is impaired consciousness, somnolence, slow monotonous speech and psychomotor retardation. The impaired consciousness may be associated with visual hallucinations. Personality change with features of frontal lobe disorder and abrupt changes in mood are seen. Dyspraxia, dysphasia and visual agnosias can occur. If encephalopathy progresses on physical examination there is asterixis (motor disturbance with intermittent lapses of postural tone producing,
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for example, a flapping tremor) and in the final stages hyperreflexia, extensor plantars and coma. EEG changes correlate more closely with psychiatric disturbance. In the early stages with personality changes theta waves appear; in the final stages EEG shows delta waves of low amplitude. Uraemia Fatigue, depression and somnolence are commonly seen. There may be difficulty in concentration often episodic, episodes of delirium (30 per cent) and seizures (30 per cent). On examination, muscle twitching, tremor and peripheral neuropathy are noted. EEG roughly correlates with the severity of the clinical picture. Dialysis may be associated with psychiatric disturbance: • Depression and anxiety - possibly reflecting the stress of repeated dialysis and the impact of this on daily living. Sexual problems also occur with increased frequency in this group. • Disequilibrium syndrome - Too rapid dialysis may produce muscle twitching, fits, confusion and occasionally coma. • Dementia - associated with dysarthria, myoclonus and seizures; this may be due to CNS accumulation of aluminium during dialysis. Electrolyte disturbance Electrolyte disturbances are likely to produce acute organic reactions often associated with muscle cramps and seizures. Hyponatmemia Associated with weakness, irritability, depression and anxiety or delirium. Hypokalaemia Depression, anxiety, paranoid ideation and muscle weakness may occur. Tendon reflexes are often present until very low K+ levels are reached. Hypokalaemic muscle weakness may be diagnosed as hysteria, especially in patients with familial periodic paralysis in which hypokalaemia may be triggered by emotional stress. Diabetes insipidus Polyuria and polydypsia may result from lack of antidiuretic hormone production or renal insensitivity to ADH (nephrogenic). Head injury may produce the former, lithium the latter.
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Compulsive water drinking Psychogenic polydypsia can be associated with neurosis, personality disorder or psychosis. It can be difficult to distinguish from diabetes insipidus, especially as prolonged excessive water intake may lead to the secondary nephrogenic form. The resultant hyponatraemia may present with vomiting, impairment of consciousness or fits. Carcinoid syndrome The symptoms are ascribed to excess secretion of serotonin, although serotonin levels in the brain are probably low. Psychiatric symptoms such as depression, anxiety, sleeping difficulties and confusion occur in 75 per cent. Porphyria Porphyria has been described as the 'little imitator'. Three subtypes may cause neuropsychiatric disorders: • acute intermittent porphyria; • variegate porphyria; • coproporphyria. Porphyrias may be inherited or acquired. A partial enzyme deficiency leads to overproduction of haem precursors which may produce symptoms by acting as false neurotransmitters. Clinical attacks may be acute or chronic. Psychiatric symptoms of any description can occur - depression, anxiety, restlessness, insomnia and psychosis. These symptoms may accompany multiple somatic complaints, especially abdominal pain. Precipitants include starvation, infection, pregnancy, luteal phase of the menstrual cycle and many drugs, e.g. sulphonamides, barbiturates, benzodiazepines, sulpiride, oral contraceptive pill, antiepileptic drugs - carbamazepine and phenytoin. Diagnosis is by demonstrating raised levels of haem precursors in urine or faeces. Treatment is by a high-carbohydrate diet and treatment of any intercurrent infection. Carcinoma Carcinoma may produce effects either due to direct spread of tumour to the brain or remote effects (non-metastatic). Tumours metastasizing to the brain include lung, breast, GI, prostate and pancreas. Remote neurological effects include neuropathy, cerebellar degeneration, lymphocytic infiltration of the cortex, neuronal loss and gliosis of the limbic grey matter (limbic encephalitis). These may result in cognitive and memory impairments, often with anxiety, depression or clouding of consciousness.
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Vitamin deficiency syndromes Nicotinic acid deficiency Pellagra is a triad of diarrhoea, dementia and dermatitis. Early symptoms resemble neurasthenia; other symptoms include tremor, ataxia and fits. An acute confusional state may rarely present. More severe disease presents with evidence of organic impairment. Pellagra may occur in the carcinoid syndrome. Pyridoxine deficiency This may result from inborn errors of metabolism, as well as from drugs or poor diet. Depression may result. In infancy, mental retardation is associated; organic brain syndromes may be seen in adults. S12 deficiency
This may result from pernicious anaemia, post-gastrectomy, poor diet, disease of the terminal ileum, e.g. Crohn's. There is a macrocytic anaemia and bone marrow shows a megaloblastic picture. Clinically there is: • peripheral neuropathy; • Subacute combined degeneration of the cord (SACD) - with absent vibration sense, extensor plantars and spasticity; • psychosis (10 per cent); • depression and apathy; • if untreated there may be confusional states and dementia. Rarely, CNS involvement occurs in the absence of anaemia or abnormal bone marrow. Treatment results in considerable improvement if symptoms have lasted less than 2 years. Folic acid deficiency This is commonly seen in the elderly and is due to poor dietary intake; it is also seen secondary to drug therapy (phenytoin and trimethoprim). Other causes include malabsorption and increased need, e.g. pregnancy, haemodialysis. In general, a low serum folate is of little clinical significance but if severe and prolonged, apathy, depression and ultimately dementia may follow. Folate deficiency is treated cautiously in those on anticonvulsants (may make seizures worse) or if B12 is also deficient (may precipitate SACD).
Drugs and toxins Prescribed or illicit drugs should enter into the differential diagnosis of many psychiatric disorders, especially delirium and acute psychotic
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reactions. Psychotropic medications, sedatives, stimulants, hallucinogens and anticholinergics are particularly potent. The following groups can also cause psychiatric disturbance. Cholinergics These include, for example, organophosphate fertilizers or physostigmine. Early symptoms include depression, fatigue and irritability. Later there are seizures with myoclonus and acute organic reactions. Anticholinergics may cause confusion and memory impairment and exacerbate visual hallucinations. Steroids Mental symptoms are seen in 5 per cent of patients on steroids. Often the effect is euphoric but labile affect, depression and depersonalization also occur. Other presentations include psychosis with auditory hallucinations and persecutory delusions. Symptoms may occur after several months on a stable dose. Oral contraceptives may be associated with depression. Anticonvulsants These may cause a toxic confusional state with ataxia and nystagmus. Behavioural and cognitive effects without confusion are also seen, particularly with phenytoin and phenobarbitone. Reduced libido is partly due to increased metabolism of sex hormones by induced liver enzymes. Cardiovascular medication Cardiac glycosides, e.g. digoxin in toxic doses, cause altered visual perception, hallucinations, mania or delirium. Beta-blockers may cause depression, vivid nightmares and visual hallucinations. Antineoplastic drugs Several of these produce an encephalopathy, the alkaloids being potentially neurotoxic. CNS radiotherapy exacerbates the effects which may be delayed and result in personality change and dementia. Antibiotics Delirium has been reported with chloramphenicol, rifampicin, nitrofurantoin, gentamicin, cefalexin and sulphonamides. Sulphonamides may also cause dizziness, headache, mood changes and drowsiness. Penicillin allergy may be accompanied by apprehension, restlessness and confusion. Intramuscular procaine penicillin has been reported to
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produce sensations of impending death, anxiety, hallucinations and psychomotor activity, possibly the effects of procaine on the CNS. Volatile substance abuse Toluene abuse - 'glue-sniffing' - produces a euphoric state with exhilaration and agitation. If abuse is prolonged, toluene can produce cortical atrophy, cognitive impairment and cerebellar emotional lability. Heavy metals
Mercury Mercury poisoning occurs with both organic and inorganic mercury sources. Common symptoms of poisoning are depression, irritability and mild cognitive impairment. Neurological signs also occur, including tremor, cerebellar ataxia, slurred speech and neuropathy.
Lead Lead poisoning may occur as a result of occupational exposure, secondary to intake of contaminated illicit whisky or from accidental ingestion. Systemic effects include gastrointestinal symptoms (especially anorexia, colic) and peripheral neuropathy. Encephalopathy is more common in children, often with permanent brain damage. Early symptoms are irritability, restlessness, insomnia, ataxia and headache. Chronic low-dose poisoning produces dullness and poor memory.
Manganese After continued exposure, manganese may cause emotional lability, gait disturbance, slowness of movements and speech disorder.
Neurological disorders Parkinson's disease This is a common disease affecting 1 in 1000 of the population and 1 per cent of the population over 70 years of age. Peak incidence is in the sixth decade of life. Parkinsonism is the clinical syndrome of tremor, rigidity and bradykinesia. This syndrome is seen in those on neuroleptic drugs, in Wilson's disease, following cerebral anoxia or associated with other neurological conditions, e.g. Shy-Drager syndrome. Parkinson's disease refers to the clinical syndrome of idiopathic
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Parkinsonism caused by degeneration of dopaminergic striatonigral neurons.
Clinical features The classical features are akinesia, rigidity, pill-rolling tremor and postural abnormalities. Early presenting complaints may be of difficulty in handwriting or walking. Evidence exists for premorbid personality traits of rigidity and obsessionality. Depression is generally of a neurotic type and is clinically significant in one-third and is often associated with anxiety. There is no good correlation with duration of illness or disability. Dementia affects 20 per cent of patients late in the illness. Bradyphrenia, slowed thinking, is prominent. A proportion of untreated patients at presentation show evidence of cognitive impairment. The 'on-off effect consists of swings in motor function sometimes associated with pronounced changes in affect (depressed/anxious when 'off, aroused/hypomanic when 'on'). It is seen after treatment with Ldopa for many years, the fluctuations being related to duration and dosage. Most patients will have fluctuations within 5 years of commencing treatment with L-dopa.
Aetiology Aetiology of Parkinson's disease remains unclear. It is occasionally familial.
Neuropathology There is cell loss in the substantia nigra; similar changes are seen in some other basal or brain stem nuclei. Depletion of dopamine is greater than 90 per cent in the striatum with lesser reductions in the nucleus accumbens, frontal cortex or hypothalamus. Reductions in 5-HT, noradrenaline, and choline acetyl transferase can be detected.
Management • Drug treatment includes L-dopa, selegiline (a monoamine oxidase B), directly acting dopamine agonists (Bromocriptine). • Neurosurgery. There is a renewed interest in surgical treatments for Parkinson's disease, in part due to the limitations of long-term pharmacological treatments. Operations include thalamotomy, pallidotomy, and striatal grafting of dopaminergic fetal tissue. • Support for the family/patient. Open discussion about the disease, with explanation that current treatment is symptomatic not curative and that life expectancy is near to normal. The Parkinson's Disease Society can provide further support. • Referral to physiotherapist, speech therapist/social worker as necessary.
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Multiple sclerosis (MS) Prevalence of psychiatric disorder is raised in MS, partly reflecting the psychological reaction to chronic disabling disease with uncertain prognosis. Affective disorders are common - depression and anxiety. Brief schizophreniform psychoses also occur. Cognitive impairment affects 40-65 per cent. Slowing of thought processes, which may be seen in the late stages, and memory impairment are related to brain damage, as are euphoria and elation. Emotional incontinence occurs. Occasionally dementia (subcortical) supervenes. Wilson's disease This is an autosomal recessive disorder of copper metabolism leading to deposition of copper in the liver and brain. This is as a result of lowered caeruloplasmin, the plasma protein which binds copper. Onset is usually in the first two decades of life but may be delayed as late as the fifth.
Clinical features One-quarter present with psychiatric symptoms. In children there may be behavioural changes or school performance may fall. Adults may show personality change, psychosis, anxiety and depression. Early neurological symptoms include incoordination, tremor and dysarthria. Late in the course, disabling parkinsonism and dystonia are found. Other patients present with liver failure.
Investigations • Kayser-Fleischer rings around the iris may be detected on slit-lamp examination. • Liver function tests. • Twenty-four hour urinary copper excretion is raised. • Serum copper and caeruloplasmin are decreased. • Liver biopsy shows copper deposition.
Management Penicillamine is used to chelate copper. Screen relatives.
Prognosis Reversal of neurological and cognitive disability may follow treatment. Untreated there is a steady decline until death after several years. Myasthenia gravis This is an autoimmune disorder in which antibodies are produced against the acetylcholine receptor of the neuromuscular junction. Ptosis,
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diplopia and weakness of the legs are early symptoms. Often the initial diagnosis is hysteria, since emotional upset may exacerbate the disease. Tensilon test: intravenous edrophonium produces a rapid increase in muscle strength. Movement disorders
Idiopathic torsion dystonia This is a disorder of the basal ganglia. Intellect is preserved; dystonia is generalized. With onset in childhood, severe disability develops within 10 years. The adult onset condition rarely progresses to severe disability.
Focal dystonias These have been regarded as psychogenic but are now usually regarded as neurological disorders. Dystonia is localized to one area of the body. Psychotropic drugs (especially anticholinergic) may be effective but are generally unsuccessful. In spasmodic torticollis, spasms of the sternomastoid and other neck muscles produce turning or flexion/extension of the head. Usually the presentation is in middle age, only rarely with remission, and occasionally dystonia develops elsewhere. Sometimes there is a psychological precipitant. In addition, the disorder is socially disabling and may result in mental symptoms. Surgery to cut the nerve supply is used if severe. In writer's cramp there is abnormal posture of the hand and increased pressure on the paper, with the pen gripped with force and held at an abnormal angle. It is often associated with mild neurotic symptoms, in particular anxiety; it is likely that some cases are largely psychogenic. Blepharospasm is spasm of eye closure and oromandibular dystonia is spasms around the mouth, producing facial grimacing. Depression and psychological stress are associated with both conditions. Injection of botulinum toxin into affected muscles is now the treatment of choice for blepharospasm and may be used in all the focal dystonias.
Paroxysmal choreoathetosis These are rare disorders, usually familial, and often diagnosed as hysteria because of their bizarre, intermittent picture in which the patient suddenly goes into writhing spasms involving the whole body. Consciousness is not affected.
Sydenham's chorea Seventy-five per cent of cases occur at 7-12 years of age; in only 33 per cent is there a history of rheumatic fever. Neuropathology is a diffuse inflammatory encephalitis. Mental symptoms are common - agitation,
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irritability, disobedience and inattention. Both the chorea and mental symptoms recover slowly over several months and may recur.
Benign essential tremor Postural tremor affects the arms and head, causing a slowly progressive mild disability. The tremor is suppressed by alcohol and exacerbated by stress. Propanolol may be helpful. Inheritance is often autosomal dominant. Friedreich's ataxia This is the commonest inherited spinocerebellar degeneration. The onset is in childhood, with cerebellar and corticospinal tract signs. Tendon reflexes are depressed due to a peripheral neuropathy. There may be associated delinquent personality change. The intellect is impaired in 25 per cent with long-term illness. The progressive course is over 10-20 years.
Reading list Baldwin, B. and Forstl, H. (1993) Tick's disease' - 101 years on still there, but in need of reform. British Journal of Psychiatry, 163, 100-4. Bendixen, B. (1993) Vascular dementia: a concept in flux. Current Opinion in Neurology and Neurosurgery, 6, 107-12. Collis, I. and Lloyd, G. (1992) Psychiatric aspects of liver disease. British Journal of Psychiatry, 161, 12-22. Conway, A. (1993) Difficulties in managing a case of stupor. British Journal of Psychiatry, 162, 826-8. Crimlisk, H.L. (1997) The little imitator - porphyria; a neuropsychiatric disorder. Journal of Neurology, Neurosurgery and Psychiatry, 62, 319-28. Cummings, J.L. (1995) Anatomical and behavioural aspects of fronto-subcortical circuits. Annals of the New York Academy of Science, 769, 1-13. Feinstein, A. and Ron, M.A. (1990) Psychosis associated with demonstrable brain disease. Psychological Medicine, 20, 793-803. House, A. (1991) Mood disorders in the first year after stroke. British Journal of Psychiatry, 158, 83-92. Johnson, J. (1993) Catatonia: the tension insanity. British Journal of Psychiatry, 162, 733-78. Johnstone, E.G., Cooling, N.J., Frith, C.D., Crow, T.F. and Owens, D.G.C. (1988) Phenomenology of organic and functional psychosis and the overlap between them. British Journal of Psychiatry, 153, 770-6. Kopelman, M.K. (1995) The Korsakoff syndrome. British Journal of Psychiatry, 166, 154-73. Mallucci, G.R. and Collinge, J. (1997) Neuropsychiatric manifestations of prion disease. Current Opinion in Psychiatry, 10, 59-62. Marsden, C.D. (1994) Parkinson's disease. Journal of Neurology, Neurosurgery and Psychiatry, 57, 672-8.
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McAllister, T. (1992) Neuropsychiatric sequelae of head injuries. Psychiatric Clinics of North America, 15, 395-413. McPherson, S.E. and Cummings, J.L. (1996) Neuropsychological aspects of vascular dementia. Brain and Cognition, 31, 269-82. Pantoni, L. and Garcia, J.H. (1995) The significance of cerebral white matter abnormalities 100 years after Binswanger's report. A review. Stroke, 26, 1293-301. Rao, S.M. (1996) White matter disease and dementia. Brain and Cognition, 31, 250-68. Rossor, M. (1994) Management of neurological disorders: dementia. Journal of Neurology, Neuropsychiatry and Psychiatry, 57, 1451-6. Taylor, D. and Lewis, S. (1993) Delirium. Journal of Neurology, Neuropsychiatry and Psychiatry, 56, 742-51 (review). Van Duijn, C.M. (1996) Epidemiology of the dementias: recent developments and new approaches. Journal of Neurology, Neurosurgery and Psychiatry, 60, 478-86. Vanneste, J.A.L. (1994) Three decades of normal pressure hydrocephalus: are we wiser now? Journal of Neurology, Neurosurgery and Psychiatry, 57, 1021-5.
13
Epilepsy and the EEG in psychiatry PAUL CHESTERMAN
Epilepsy and clinical electrophysiology Definition The Gould Medical Dictionary defines epilepsy as: A disorder of the brain characterised by a recurring excessive neuronal discharge, manifested by transient episodes of motor, sensory, or psychic dysfunction, with or without unconsciousness or convulsive movements. The seizure is associated with marked changes in recorded electrical brain activity.
However, no current definition of epilepsy is entirely satisfactory. A seizure is a symptom rather than a diagnosis. All brains will convulse if given sufficient provocation, as in electroconvulsive therapy (ECT). Perhaps the best definition is the tendency to recurrent fits. This excludes an isolated seizure due to, for example, hypoglycaemia. A frequently used diagnostic criterion for epilepsy is two or more seizures within a year. Classification Seizures can be classified in several different ways: • by phenomenology; • by the site of origin within the brain; • by the underlying aetiology. The International League Against Epilepsy has attempted to produce an agreed classification based on clinical description and EEG localization: 1. PARTIAL (FOCAL, LOCAL) SEIZURES:
In partial seizures, the epileptic episode originates in a localized area of cortex or subcortical region.
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Simple partial seizures. Seizures are marked by simple motor or sensory symptoms and consciousness is not impaired: (i) with motor signs (e.g. Jacksonian march); (ii) with somatosensory or elementary hallucinations (a) somatosensory, (b) visual, (c) auditory, (d) olfactory, (e) gustatory, (f) vertiginous; (iii) with autonomic symptoms, e.g. sweating or flushing. Complex partial seizures. Seizures are marked by disturbance of higher functions and consciousness is impaired. Usually temporal lobe in origin, but occasionally similar phenomena are seen in fits of frontal lobe origin. Symptoms may include: (a) (b) (c) (d) (e)
dysphasia; dysmnesia, e.g. deja-vu; cognition, e.g. distortion of time sense; affective, e.g. ictal fear; structured hallucinations, e.g. hearing music.
There are two main presentations: (i) simple partial onset (with symptoms as above) followed by impairment of consciousness; (ii) impaired consciousness at onset. In either type, automatisms, either simple (e.g. lip smacking) or more complex (e.g. undressing) may be present. Secondarily generalized seizures. Partial seizures may evolve to generalized tonic-clonic seizures. 2. GENERALIZED SEIZURES:
In primary generalized seizures, the seizure is generalized from the onset. Absence seizures (petit mal). Transient loss of consciousness with retention of postural tone, lasting a few seconds, and occurring predominantly in childhood. Automatic behaviour or movements may be seen in cases where the seizures are prolonged (petit mal automatism). Tonic-clonic seizures (grand mal). Either phase can occur alone. In the tonic phase respiratory arrest, tongue biting and bladder emptying can occur. There is usually some degree of postictal confusion and drowsiness. Myoclonic Atonic 3. UNCLASSIFIED
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Differential diagnosis A number of alternative diagnoses need to be considered with each seizure type: for generalized seizures, cardiac arrhythmias and other causes of syncope; in simple focal seizures, migraine and transient ischaemic attacks. Complex partial seizures are of particular psychiatric interest and the differential diagnosis is discussed below. Aetiology The epilepsies are a heterogeneous group of disorders. In each condition there is an interaction between genetic factors and damaged neurons. There is a spectrum of disorders with predominantly genetic factors at one end, and structural or physiological lesions at the other. These lesions may result from trauma, infections, toxins, cerebral degenerative disorders, cerebrovascular disorders, metabolic and endocrine disorders. Metrakos and Metrakos in 1960 demonstrated an autosomal dominant condition that produced a 3 per second spike and wave on the EEG. This EEG abnormality, which is not necessarily associated with seizures, had a penetrance that was age dependent, reaching a maximum between the ages of41/2and161/2.Whether this results in clinical seizures depends on other factors such as minor birth injuries. In many cases of epilepsy the size of the lesions will be too small to be detected by current techniques of brain imaging. The most likely neuropathological change in epilepsy varies with the age of onset, e.g. congenital abnormalities and CNS infections in infancy, trauma in adolescence, and in old age tumours and cerebrovascular disease. Febrile complex seizures at age 6 months to 5 years and lasting more than 10 minutes are associated with later temporal epilepsy as these may produce mesial temporal sclerosis. Epidemiology Figures for incidence and prevalence vary considerably; 5 per cent of the population experience one fit in their lifetime. One in eight of these go on to develop epilepsy, with an onset before the age 20 in 75 per cent of cases. The prevalence in Britain is of the order 3-8/1000 with an annual incidence of 30-50/100 000. Recent evidence has shown that the prognosis is much better than originally thought. When onset occurs in adult life, 80 per cent will become seizure free.
Psychiatric aspects of epilepsy One study, of 14 general practices, identified 245 epileptic patients. There was a 30 per cent prevalence of psychiatric disorder; 7 per cent required psychiatric treatment as an inpatient. These were mainly mild affective disorders in adults and conduct disorders in children. The Isle
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of Wight study of children found a 30 per cent prevalence of psychiatric disorder in uncomplicated epilepsy, but 70 per cent in cases of epilepsy associated with a structural lesion of the brain. The majority of people with epilepsy have no psychiatric disorder. Psychiatric concomitants of epilepsy are usually discussed under two categories - peri-ictal and interictal - as follows. Peri-ictal
Precipitation of seizures In a number of patients, clear precipitants can be recognized. These may be external events as in reflex epilepsy where, for example, hearing a particular piece of music may induce a fit. Photic stimulation can be responsible, fits being induced by the flicker from a television set or light passing through trees while driving. Some children learn to induce fits by waving their fingers in front of their faces. Fenwick has shown that internal events can have the same effect; a particular thought, emotion or cognitive activity are all recognized possibilities. Interpersonal difficulties, problems with employment and other environmental stressors can increase seizure frequency. Acute anxiety accompanied by hyperventilation in some epileptics will precipitate a seizure. Fatigue, sleep loss, alcohol and the use of certain drugs are important, especially the withdrawal of barbiturates and benzodiazepines.
Prodrome These symptoms appear minutes to days before a seizure. They are incompletely understood and are not directly related to the seizure activity itself. Changes in mood, particularly dysphoria and irritability, are common.
Auras These represent the initial focal onset of the seizure. They last from a few seconds to a minute and may have a stereotyped form. They have an abrupt onset and termination. Of most psychiatric interest are those arising from the temporal lobe, the features of which have been outlined above. If seizures arrest at this stage, and do not progress to full fits, then diagnostic difficulties can occur. Acute panic attacks last longer and are often situation dependent. There are similarities with episodic dyscontrol (see below). All of the positive symptoms of schizophrenia can occur as focal seizure phenomena.
Ictal If the seizure starts in the peri-amygdaloid region and spreads bilaterally to involve mesial temporal structures, automatisms can occur. Control
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of posture and muscle tone is maintained and actions of some complexity can be carried out, but these are never entirely appropriate to the surroundings and the patient will display evidence of confusion during the episode and amnesia for the event. Eighty per cent last less than 5 min; ictal automatism never lasts more than 1 hr. More protracted automatisms can occur, owing to continuing seizure activity in the conditions of petit mal and complex partial status. Seventy-five per cent of cases of petit mal status occur before the age of 20, but it can appear for the first time in middle age. Again, amnesia for the episode is seen with abrupt onset and termination. Fugue is a term sometimes used to describe longer lasting periods of automatic behaviour associated with wandering away from the patient's usual environment. Epileptic fugues can last up to several days. Although behaviour can be relatively complex, if the patient is examined during the episode some degree of confusion will be apparent. A history of typical seizures will aid in differentiating from depressive or hysterical fugue.
Postictal Some degree of postictal confusion is common after any generalized seizure. This is usually brief but occasionally can be protracted and the patient may carry out complex behaviour before full consciousness returns. Examination during this time will reveal confusion, reduced attention, disorientation and incoordination. The term twilight state is sometimes used to describe this phenomenon but has also been used for other forms of epileptic automatism, and to refer to a postictal state that shares some features of the functional psychoses such as poorly systematized delusions, hallucinations and affective features. A twilight state can last up to several days and there may be a lucid interval after the preceding seizure. Interictal
Schizophreniform psychosis of epilepsy In the early part of this century it was thought that epilepsy and schizophrenia were biologically antagonistic. This led to the introduction of cardiazol-induced seizures in schizophrenia in the 1930s. Hill, and later Pond, described a paranoid psychosis in association with temporal lobe epilepsy in the 1950s. Relative preservation of affect and personality were noted. In the early 1960s, Slater collected from two hospitals 69 patients with epilepsy who had subsequently developed schizophrenia and argued that this number would not be expected by chance based on the known incidence of the two conditions. The mean age of onset was 30 years with the mean duration of epilepsy before the onset of
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psychosis of 14 years. Eighty per cent showed an insidious onset with a generally poor prognosis, resulting in an organic defect state. Although individual cases could not be distinguished from schizophrenia, the group as a whole showed certain differences. Affect and personality were particularly well preserved. Visual hallucinations occurred more often than in schizophrenia, although auditory hallucinations remained the most common. Forty-six per cent displayed a psychosis typical of paranoid schizophrenia and 8 per cent a hebephrenic picture. The epilepsy in 67 per cent was of temporal lobe origin. The actual incidence of this disorder in epileptics remains disputed. Flor-Henry estimated an incidence of approximately 2 per cent and noted that the majority occurred in epilepsy due to left-sided lesions. Falconer noted an unusually high proportion of hamartomas in temporal lobectomy material. It has been argued that the condition may be a nonspecific effect of underlying brain damage rather than being directly due to seizure activity. This was supported by Flor-Henry who showed that those who developed psychosis had fewer seizures than those who did not and by Stevens who demonstrated a 7-15 per cent incidence of psychosis in post-temporal lobectomy cases.
Affective psychosis Flor-Henry's claim that epileptics with non-dominant lesions were prone to develop affective psychoses has been refuted by several investigators. Toone and colleagues concluded in 1982 that there was a chance association only. Even in the absence of major depression there is a high risk of suicide in epilepsy with a five-fold increase in the risk of suicide overall and a 2 5-fold increase in temporal lobe epilepsy.
Neurotic conditions These make up the bulk of the psychiatric morbidity of epilepsy. A number of factors are likely to be important, including: risk of injury; social prejudice, overprotective parental attitudes; employment problems and the effects of medication. The majority of pseudoseizures probably occur in patients who have epilepsy, whether continuing or remitted. A number of features help to distinguish them: the rarity of injuries or incontinence, the often flamboyant abnormal movements that are non-symmetrical and semi-purposeful, and the circumstances in which they occur (e.g. during the day, in front of others). An association with stress or secondary gain may be detected, as may previous personal or family patterns of abnormal illness behaviour. Serum prolactin and growth hormone rise sharply after generalized seizures but not after focal or pseudoseizures. If an EEG can be obtained during an attack, this will be useful. Prolonged EEG recordings using telemetry may be necessary. Occasionally, differentiation can be difficult.
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Disorders of cognitive function It was originally believed that epilepsy was associated with low intelligence. Where this occurs it has been shown to be due to underlying brain damage. Institutionalized epileptics do have below average intelligence but epileptics in the community have a relatively normal IQ distribution. The association with brain damage is said to explain why patients with temporal lobe epilepsy, in which underlying structural lesions are more common, are more likely to have impaired intelligence. Also, because their seizures are more difficult to control, they are frequently taking multiple and large amounts of anticonvulsants. These drugs have been shown recently to have a greater effect on cognition than was previously suspected. Epileptic dementia, a progressive cognitive decline seen in a very small proportion of epileptic patients, is now thought not to be due to the epilepsy itself. Some cases are due to a progressive cerebral disorder giving rise to both fits and dementia. Reversible causes, especially drug intoxication, must be considered.
Personality problems In the early part of the century, deterioration of the personality was seen as integral to epilepsy. Indeed, certain forms of personality change permitted a diagnosis in the absence of clinical seizures. In the 1940s Lennox emphasized the normality of patients with epilepsy when chronically institutionalized patients with severe underlying brain damage were excluded. The characterization of temporal lobe epilepsy in the 1960s resulted in a number of personality traits being suggested as specific associations. Bear and Fedio extracted 18 personality traits from the literature and compared patients with temporal lobe epilepsy to normal controls. The majority of these traits were found to occur significantly more frequently in the epileptic group, particularly humourless sobriety, dependence, sense of personal destiny, circumstantiality and preoccupation with philosophical and religious interests. The validity and reliability of this study have been criticized and subsequent studies controlling for brain damage and the presence of psychiatric disorder have failed to support a specific temporal lobe personality disorder, although ponderousness, circumstantiality and irritability are recognized associations of brain damage of whatever cause. In some epileptic patients, surgical treatment is said to result in changed behaviour, aggression being particularly likely to respond favourably.
Sexual disorders The most common problem is hyposexuality. Recent evidence suggests that the effects of anticonvulsants on sex hormone function may be of considerable importance. Hypersexuality is rare. Of interest are claims
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of cases of sexually deviant behaviour relieved by surgical treatment of the epilepsy. Epilepsy and the law Aggressive behaviour is more common in patients with epilepsy. One retrospective study found that 33 per cent (mostly temporal lobe epilepsy) had childhood rages associated with psychiatric morbidity as adults. Further studies have replicated this, but if such confounding variables as brain damage, parental psychopathology and effects of medication are taken into account, the specific association with temporal lobe epilepsy is lost. Ictal or postictal violence, i.e. during an automatism, is rare. Gunn, in 1969, found a prevalence of epilepsy in prisoners of 7.2/1000, almost twice the estimate for the general population. In only 2 of 158 epileptic prisoners was their crime related to a seizure. In 1981, Delgardo-Escuata and colleagues collected 5400 videotapes of seizures and found only 13 cases of violence. Most were postictal, coordinated behaviour was not seen, weapons were not used and the episodes lasted only 1-2 mins. In English law, disease of the mind, as defined by the McNaughton Rules (see Chapter 27), would apply to offences committed during postictal or interictal states of epilepsy. A defence of absence of mind is divided into sane automatisms, due to external factors such as a blow to the head, in which cases the defendant goes free, and insane automatisms, due to intrinsic factors liable to recur, in which cases the defendant may be committed to a special hospital. The latter applies to epileptic automatisms. Epileptic automatism is more likely in the following circumstances: • patient known to have epilepsy; • offence out of character and inappropriate to circumstances; • no premeditation or concealment; • disorder of consciousness observed by witness; • some degree of memory impairment; • a diagnosis of epilepsy can be made clinically. The differential diagnosis of epileptic automatism includes alcoholic blackouts, dissociative states, malingering and the episodic dyscontrol syndrome, a disputed clinical entity referring to brief episodes of violence after minimal provocation. Before the episode, experiences similar to auras are reported and the episode is followed by headache and drowsiness. Considerable remorse is seen. Management Seizures Maximum seizure control is important. Studies suggest little difference in efficacy between phenobarbitone, phenytoin, carbamazepine and
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sodium valproate, the only drug that is effective in patients with mixed seizure types that include petit mal. Choice of drug depends largely on minimizing side effects. A number of relatively new drugs are now available including lamotrigine, vigabatrin and gabapentin. Phenobarbitone is the most sedative and can cause behavioural disturbances in children. Carbamazepine is the least sedative and may have a positive psychotropic effect as a mood stabilizer. Side effects are additive and multiple drug regimens should be avoided where possible. Avoidance of toxicity is facilitated by monitoring serum levels. Status epileticus may be treated by various drugs including i.v. diazepam, chlormethiazole or phenytoin. Paraldehyde (i.m. or very slow i.v.) and phenobarbitone (i.m.) may also be useful. In suitable cases of localized epilepsy, surgery (most commonly temporal lobectomy) can be of benefit. Psychiatric abnormalities Treatment of specific psychiatric conditions in the presence of epilepsy will not differ significantly from standard practice. When a tricyclic is required, trazodone is probably the least epileptogenic. Neuroleptics will be required in some cases of psychosis when chlorpromazine should be avoided in favour of haloperidol. There is no contraindication to ECT in an associated affective psychosis. Behaviour therapy has been used where specific precipitants of seizures have been identified. Opportunities to receive education and ventilate feelings about epilepsy should be provided. Young people with epilepsy are often deficient in self-care and social skills and can be helped by a suitable milieu or outpatient group. Vocational guidance is often useful. Patients should be advised about how their illness affects their ability to drive a motor vehicle.
The EEG and psychiatry Background Electroencephalography was first described in humans by Berger in 1929. Rhythmic changes of potential are seen of approximately 20-40 millionths of a volt. These are produced by the inhibitory and excitatory postsynaptic potentials in the dendrites and the soma of neurons close to the surface of the brain and orientated perpendicularly to the surface, principally the pyramidal cells. The surface EEG detects activity from only about 3 per cent of the neurons of the brain. Activity within the thalamic nonspecific and specific nuclei, modulated by the activity of the reticular activating system (RAS) generates the rhythmic activity of the cortical neurons which is largely responsible for the EEG signal. Hence, pathology leading to anatomical or physiological disturbance of the RAS and thalamic nuclei, such as trauma or metabolic disorders,
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produces generalized abnormalities in the EEC, whereas discrete cortical lesions tend to produce localized abnormalities of the EEG. Technique By convention EEG recordings are arranged so that negative potentials cause an upward deflection. Usually 22 electrodes are placed according to the International 10/20 System, which refers to the percentages of distance of the electrodes between certain bony landmarks on the skull. Electrodes are of two types: • bipolar - recording the potential between two electrodes; • unipolar - the potential is recorded between an active electrode and either an electrically neutral site, such as the nose, or the combination of all the the electrodes (common reference). The electrodes are connected together in a variety of montages, such as anteroposterior or transverse sequentially connected bipolar electrode to maximize the possibility of detecting any abnormalities. The montages used in recording a particular EEG should be shown diagramatically. Frequencies of the rhythms recorded are classified as: • • • •
delta < 3.5 Hz; theta 4-7 Hz; alpha 8-13 Hz; beta > 13 Hz.
Normal EEG activity In the resting state, the prominent rhythm is alpha, maximal over the occipital lobes and abolished by opening the eyes or by cognitive activity. It is often asymmetrically increased on the dominant side. Frontal and Rolandic low-amplitude beta is also seen which is unaffected by eye opening. In infancy, rhythms are slower and amplitudes higher and asynchronous. The adult pattern is not fully established until late adolescence. In old age, alpha frequency declines. In young adults, frontal theta and posterior temporal delta are normal findings and if these persist they are termed maturational phenomena. Abnormal EEG activity
Non-paroxysmal • diffuse slow activity - theta or delta - seen in metabolic conditions or in the acute phase of brain trauma; • focal slow activity - can be evidence of a space-occupy ing lesion such as an abscess or tumour; • diffuse fast activity - produced by benzodiazepenes and barbiturates;
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• reduction of normal activity - either diffusely as in Huntington's chorea or focally after a traumatic brain insult or with attenuation of the EEG signal as with a subdural haematoma.
Paroxysmal Includes epileptiform abnormalities which can be generalized or focal: • sharp waves 70-200 ms in duration; • spikes 20-70 ms in duration; • spike or sharp and slow wave complexes. Other forms of paroxysmal activity include bursts of slow or sharp waves against a background of low-amplitude slow activity seen in subacute sclerosing panencephalitis and Creutzfeldt-Jakob disease. Specific conditions
Epilepsy Spikes or sharp waves or spike/sharp wave complexes in the interictal record strongly support a diagnosis of epilepsy, though these abnormalities can be seen in non-epileptic patients. Generalized spike and wave with a frequency of 3 Hz is seen in petit mal epilepsy. In 50 per cent of cases of epilepsy, a routine EEG will fail to detect any interictal abnormality. The chance of detecting epileptic activity is increased by the use of activating techniques such as hyperventilation, photic stimulation and sleep induction or deprivation. When these procedures are used interictal abnormalities will be found in 90 per cent of cases. The changes seen during a seizure depend on the seizure type. In grand mal, bursts of polyspikes are followed by a run of spike/wave complexes. In petit mal, bursts of spike wave discharges are seen. In focal sezures there may be no surface changes or a focal reduced amplitude.
Acute organic psychosis Focal slow waves and slowing of background rhythms are common, assisting differentiation from functional psychiatric disorders.
Dementia The EEG can assist in the diagnosis of: • Huntington's disease. Alpha rhythm is greatly reduced with very lowamplitude background rhythms. • Alzheimer's disease. Alpha rhythm is reduced with some theta disorganization.
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• Creutzfeldt-Jakob disease. Characteristic periodic discharges are seen against reduced background rhythms. • Pick's disease. Little abnormality of the EEC is seen. • Lewy body disease. There is a varyingly abnormal EEC depending on the extent of cortical involvement. A cerebral tumour or abscess may be revealed.
CNS infections Herpes simplex encephalitis, periodic slow, sharp and triphasic waves against a background of slow activity with no alpha rhythm is characteristic. Neurosyphilis, an excess of theta with a slowed alpha rhythm is seen. AIDS, may have focal or generalized slow activity.
Mental handicap The EEG does not usually provide evidence of a specific aetiology, but most severe cases have generalized slow activity and epileptiform activity with or without clinical seizures is seen in up to one-third. In infants with severe mental handicap, a chaotic EEG with mixed slow and spike wave activity called hypsarrhythmia which is associated with salaam attacks may be found.
Brain trauma • Acute stages. The relative amounts of alpha versus theta and delta activity are indicative of severity. Early seizure activity indicates poor prognosis. • Chronic. Can see localized reduction of amplitude of background rhythms indicative of cortical damage. In cases of repeated head trauma, as in dementia pugilistica, a normal EEG does not exclude the diagnosis.
Effects of treatment • ECT. The EEG is increasingly used to measure duration of seizure, optimal 25-90s. Following ECT treatment, there can be generalized irregular slow activity and bilateral synchronous bursts of slow activity for up to 4 months • Barbiturates. Excess fast activity and EEG changes of drowsiness can be seen. • Benzodiazepenes. Excess fast activity can persist for up to 2 weeks after cessation. • Tricyclics. slow the alpha rhythm; can see paroxysmal spike/sharp and slow complexes. • Lithium. EEG changes common; can see focal slow activity. • Neuroleptics. At therapeutic doses, minor degrees of background
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slowing with slowing of the alpha rhythm; at high doses, can see paroxysmal activity.
Personality disorder Nonspecific EEC abnormalities, often referred to as evidence of immaturity, have been reported in personality disorder.
Schizophrenia Nonspecific abnormalities are often found.
Affective disorders Generally no specific EEG changes, but in one study by Small et al. (1975) 43 per cent of patients with manic-depressive psychosis had diffuse small sharp spikes. The EEG may indicate an organic aetiology for an affective disorder, particularly in the elderly.
Sleep and its disorders Five stages of sleep are recognized; these are defined using EEG criteria: • Stage 1. Low-voltage mixed theta and faster frequencies dominate. Roving eye movement are seen. • Stage 2. Increased theta, vertex sharp waves, sleep spindles (11-15 Hz bursts) and K complexes (slow waves with spindle) are seen. • Stage 3. Slow waves appear and 20-30 per cent of activity is delta. • Stage 4. Sixty per cent delta. • Rapid eye movement (REM) stage. Similar to stage 1, but sporadic irregular eye movements occur. This normally occurs 4-5 times per night, the first episode ocurring 1-1.5 h after falling asleep. This is the stage of sleep usually associated with dreaming, although dreaming does occur in other stages. There is evidence of physiological arousal with tachycardia, rapid breathing, pupil dilatation and penile erection. REM constitutes 50 per cent of sleep in infants and 25 per cent in adults, declining further in old age. Polysomnography - the simultaneous recording of EEG, eye movements, muscle activity and other physiological parameters such as respiration rate and oxygen saturation - is being increasingly used, often in dedicated sleep laboratories, to facilitate the diagnosis of a variety of sleep disorders. The International Classification of Sleep Disorders (ICSD) includes four main categories:
1. Dyssomnias (insomnia and excessive daytime drowsiness) These can be due to: (A) Intrinsic causes such as:
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Physiological - the expectation of not sleeping, treated with behavioural techniques. The sleep EEC often demonstrates that the insomnia is not as severe as the patient reports. Sleep apnoea - obstructive sleep apnoea is associated with obesity, hypertension and cardiac disease. It is treated by weight loss and the use of continuous positive airways pressure (CPAP). Central sleep apnoea also occurs. Narcolepsy - which affects 0.05-0.6 per cent of the population - is characterized by episodes of uncontrollable somnolence in the daytime, usually associated with one or more of: cataplexy (abrupt loss of muscle tone), sleep paralysis (transient paralysis with spontaneous recovery) and/or hypnagogic hallucinations. REM stage sleep is seen at the onset of sleep and its early appearance is described as short REM latency. Narcolepsy has a strong association with certain HLA subtypes. Treatment is with methylphenidate or amphetamines. Cataplexy responds to clomipramine. Sleep paralysis can occur either on falling asleep (predomital paralysis) or on awakening (postdormital paralysis). Klein-Levin syndrome - characterized by episodes of hypersomnia lasting several days, accompanied by compulsive eating, irritability, confusion and visual or auditory hallucinations. Bursts of high-amplitude delta activity have been described in the waking EEG during an attack. (B) Extrinsic causes, including drugs such as nicotine, caffeine, cocaine, cannabis and heroin. (C) Circadian rhythm disturbance such as jet-lag and shift-work.
2. Parasomnias (disorders of arousal and partial arousal) These are characterized by autonomic and skeletal muscle activity. Four types have been described: (A) Arousal disorders, which typically occur in stage 4 and therefore most often in the first third of the night. These include confusional arousals, night terrors, most common in children associated with extreme autonomic arousal which are not usually remembered, and sleep walking. Sleep walking is also more common in childhood but affects up to 1.4 per cent of the adult population. Behaviour, for which there is usually amnesia, can be complex and include acts of violence, even homicide. (B) Sleep wake transition disorders, including hypnogogic hallucinations and sleep paralysis. (C) Parasomnias, usually associated with REM sleep. These include nightmares and REM sleep behaviour disorder where there is a failure of the normal paralysis of REM sleep allowing dreams to be acted out. It is more common in males over 60 years, is usually idiopathic but
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has been associated with a variety of neurological disorders and drug withdrawal. (D) Other pamsomnias, including sleep bruxism, enuresis and nocturnal death syndrome.
3. Sleep disorders associated with medical or psychiatric illness These include: (A) Depression. One in five suffer from daytime drowsiness. Early morning wakening, short REM latency and an abnormal distribution of slow wave and REM sleep is seen which can be exacerbated by fluoxetine. (B) Alcoholism, associated with increased snoring and sleep apnoea, decreased latency sleep onset with increased sleep efficiency first half of night and decreased efficiency in the second, with fragmentation and arousals. On withdrawal, sleep architecture may not return to normal for up to 2 years.
4. Proposed sleep disorders These include short and long sleeper and sleep-related laryngeal spasm.
Event-related potentials The conventional EEG records spontaneous brain activity. If a stimulus is presented to the brain, and a suitable epoch is chosen, changes in the EEG produced by the stimulus can be detected with the use of averaging techniques, as the potential changes are of the order of microvolts compared to the tens of microvolts of the spontaneous EEG. The most readily identified components are labelled with a P for positive peaks or n for negative, followed by the latency in milliseconds, e.g. P300. These potential changes can divided into: 1. Event-preceding potentials These include: (A) In the 1000ms preceding a voluntary movement, the readiness potential can be detected in the precentral area. (B) The contingent negative variation (CNV). This is seen when a stimulus is presented ( S I ) followed by an interval, usually 1 s, when a second stimulus is presented (S2) to which the subject has to respond. During the interval a slow-rising potential can be detected. The CNV is reduced in schizophrenia and psychopathic disorder.
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2. Event-following potentials In the 100ms following a suitable stimulus, the EEC response is largely dependent on the physical properties of the stimulus and these are referred to as exogenous or evoked potentials and can be used to determine the integrity of sensory pathways. Evoked potentials include: (A) The visual evoked potential (VEP). In multiple sclerosis the arrival of the stimulus response in the visual cortex is delayed. In hysterical blindness a normal is found. (B) Auditory evoked potential (BSAEP). A number of peaks reflects activity within the brain stem auditory pathways (far-field potentials). The BSAEP can localize the cause of deafness. (C) Somatosensory evoked potentials (SEP). This can be used to test the integrity of peripheral sensory systems and can be useful in excluding organic disorders in suspected hysterical sensory loss. In cases of dementia due to degenerative disorders, evoked potentials can be used to indicate specific disorders. Endogenous potentials refer to changes in the EEC recorded after the first 100ms following a stimulus. These responses are modified by attention, arousal and motivation and other psychological variables. A number of different waveforms have been identified including P300, which is seen after a rare stimulus is presented in a series of stimuli such as a tone of a different frequency, and is maximal over the central parietal area and is reduced in schizophrenia.
Reading list Bear, D. and Fedio, P. (1977) Quantitative analysis of inter-ictal behaviour in temporal lobe epilepsy. Archives of Neurology, 34, 454-67. Binnie, C. (1989) The monitoring of chronic epilepsy. In The Chronic Epilepsy, Its Prognosis and Management (ed. M. Trimble). Chichester: Wiley. Delgardo-Escuata, A., Mattson, R. and King, L. (1981) The nature of aggression during epileptic seizures. New England Journal of Medicine, 305, 711-16. Fenton, G. (1983) Epilepsy. In: Mental Disorders and Somatic Illness, Handbook of Psychiatry, Vol. 2 (ed. M. Lader). Cambridge: Cambridge University Press. Flor-Henry, P. (1969) Psychoses and temporal lobe epilepsy. Epilepsia, 10, 363-95. Gunn, J. and Fenton, G. (1969) Epilepsy in prisons - a diagnostic survey. British Medical Journal, 4, 326-8. Halliday, A.M., Butler, S.R. and Paul, R. (eds) (1987) A Textbook of Clinical Neurophysiology. New York: Wiley. Hill, D. (1953) Psychiatric disorders of epilepsy. The Medical Press, 229, 473-5. Lishman, W.A. (1987) Organic Psychiatry: The Psychological Consequences of Cerebral Disorder. Oxford: Blackwell.
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Pond, D.A. (1962) The schizophrenia like psychoses of epilepsy - discussion. Proceedings of the Royal Society of Medicine, 55, 311. Pond, D.A. and Bidwell, B. (1960) A survey of epilepsy in 14 general practises: social and psychological aspects. Epilepsia, 1, 285-99. Reynolds, E.H. and Trimble, M.R. (Editors) (1981) Epilepsy and Psychiatry. Edinburgh: Churchill Livingstone. Rugg, M.D. and Coles, M.G.H. (eds) (1995) Electrophysiology of Mind, Eventrelated Brain Potentials and Cognition. Oxford: Oxford University Press. Rutter, M. Graham, P. and Yule, W. (1970) A neuropsychiatric study in childhood. Clinics in Developmental Medicine 35/36. Shapiro, C. and McCall Smith, A. (1997) Forensic Aspects of Sleep. New York: Wiley. Slater, E. and Beard, A.W. (1963) The schizophrenic-like psychoses of epilepsy. British Journal of Psychiatry, 109, 95-150. Small, J., Small, I. and Milstein, V. (1975) Familial associations with EEG variants in manic-depressive disease. Archives of General Psychiatry, 32, 43-8. Stevens, J.R. (1980) Biological background of psychoses in epilepsy. In Advances in Epileptology: Xlth Epilepsy International Symposium (eds R. Ganger et al.}. New York: Raven Press. Thorpy, M.J. (Chair) (1990) International Classification of Sleep Disorders, Diagnostic and Coding Manual. Rochester, Minnesota MN: American Sleep Disorders Association. Toone, B.K. Garralda, M.E. and Ron, M.A. (1982) The psychoses of epilepsy and functional psychoses - a clinical and phenomenological comparison. British Journal of Psychiatry, 141, 256-61. Trimble, M.R. (1983) Interictal behaviour and temporal lobe epilepsy. In Recent Advances in Epilepsy (eds T. A. Pedley and B.S. Meldrum). Edinburgh: Churchill Livingstone. Livingstone, M.R. and Bolwig, T.G. (eds) (1986) Aspects of Epilepsy and Psychiatry. Chichester: Wiley.
14
Old-age psychiatry ALICE SEABOURNE and ALISTAIR BURNS
Old-age psychiatry is both continuous with and discrete from general psychiatry: patients graduate from generic services or are newly referred with the onset of disorders associated with ageing. Pre-existing disorders may be modified by the changes of ageing and previous therapies may need to be modified due to intercurrent physical problems or therapies. Ageing itself brings psychological changes. Individuals must adapt to altered social, work and family roles. They may be confronted with losses of spouses, friends, physical health, financial and physical security, routine, dignity, privacy and independence. Finally, the individual must come to terms with the loss of their own life. The old-age psychiatrist functions within a multidisciplinary, multiagency team which is predominantly community based. There should be good liaison with colleagues in geriatric medicine, social services and voluntary agencies supporting the elderly in the community. The service should have a range of resources available to assess, treat and support patients and relatives. These may be organized in conjunction with social services centres and should involve home-based assessments and treatments, day hospitals, acute assessment in patient units, respite admission beds and long-stay beds for those meeting criteria for longstay NHS care.
History and examination Site of assessment Ideally the old-age psychiatrist assesses the patient in his/her own home. This has the advantage that the patient is on his/her own territory and is therefore more likely to be relaxed. It allows the psychiatrist to glean information about the patient's past from photographs and objects around the house which can provide a focus for discussion. In addition,
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the psychiatrist can observe the current home situation, looking for selfneglect or risks in the home. It is not always possible to assess the patient in their own home, for example when individuals are inpatients on geriatric wards. In these cases it is important to optimize conditions for assessment, taking the patient off the busy, noisy ward to a quiet, well-lit side room. The interview Hearing and visual impairments may hamper communication and the psychiatrist should make sure that these are reversed as well as possible prior to conducting the interview. Check that the patient has his/her glasses on, find out if they have better hearing on one side and make sure that his/her hearing aid is switched on. However, do not assume deafness and shout at everyone. Mumbling speech in Parkinson's disease and absent or poorly fitting dentures mean that the psychiatrist may need to listen very carefully to grasp what the patient is saying. The psychiatrist must explain clearly and sometimes repeatedly who they are and the purpose of the assessment. If the assessment is being conducted at home, it is particularly important to have official identification. It may be necessary to conduct the interview over a number of occasions, particularly when the patient is physically unwell and easily fatigued. Be sensitive to distress that the cognitively impaired patient may be experiencing when his/her memory is being tested. In these cases it is necessary to be flexible and change the subject to and talk about something less distressing for a time. Patients may feel more at ease in the presence of the informant or may find this inhibiting. It is important to check which they would prefer before the interview, not assuming that if their spouse is in the room they want to be seen with them. Cognitive assessment Structured instruments are useful as screening instruments to ensure that the clinician has tested all domains of cognitive function. The most frequently used instrument in clinical practice is the Mini Mental State examination. This includes tests for amnesia, apraxia and orientation. The shorter Abbreviated Mental Test Score is also used. Abnormalities on these screening instruments should be explored more fully by further clinical testing. In severe cognitive impairment behaviour, rating scales (e.g. the Crichton Behaviour Rating Scale) may be used to describe the extent of a patient's impairment and behavioural disturbance. This may be useful in monitoring decline of cognitive function and the need for care.
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The informant interview The patient may not be able to give a clear and coherent picture of his/ her problems and past. Even if they appear to be able to do so, it is often useful to get a corroborative history. The informant interview is therefore a vital part of assessment. Useful sources of information range from family and friends to home care workers, neighbours and local shopkeepers. Informants may provide important information about personality change, memory dysfunction, wandering at night and dangerous behaviour at home that the demented individual may have forgotten. They can also provide important information about the rate of progression of a disorder, whether the patient was normal last week or was getting gradually more impaired over months or years. If the informant is the carer it is also important to assess the impact that the disorder has had on them as this is likely to influence future management. The carer themselves may need education and support. Physical examination Physical examination in individuals with cognitive impairment may reveal signs suggestive of acute physical illness causing delirium. Primitive reflexes may be present in Alzheimer's disease and the presence of focal neurological symptoms and signs in a cognitively impaired individual would suggest vascular dementia. Physical examination in other disorders will reveal organic disorders causing symptomatic psychiatric illnesses. It may also reveal physical illnesses that are independent of the psychiatric illness. Physical investigations • Full blood count may reveal anaemia which presents as fatigue or depression • Erythrocyte sedimentation rate will be elevated in acute illnesses. A raised ESR in dementia would suggest that a screen for systemic lupus erythematosus should be performed. • Serum B12 and folate - low levels may cause a reversible dementia. • Urea and electrolytes may be abnormal in acute illness in delirium, and show dehydration in the severely depressed with poor fluid intake or in the demented self-neglected individual. • Liver function tests may be abnormal in delirium and an elevated gamma-GT might indicate alcohol withdrawal as a cause of delirium. • Syphilis serology, to exclude neurosyphyllis as a cause of dementia. • Thyroid function tests to exclude hypothyroidism as a cause of dementia or depression. • ECG to establish if arrhythmias may be causing cerebrovascular disease.
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• Chest X-ray in delirium. • EEC to differentiate between dementia and delirium and may suggest causes of dementia. • CT brain scan in cognitive impairment to determine if there are focal lesions, infarcts or lobar atrophy. • SPECT scanning to determine if there are abnormalities in regional blood flow which may be suggestive of particular dementias. • Neuropsychological testing may be particularly useful in determining between normal ageing and early dementias and may aid differentiation between different dementias.
Dementia Dementia is a syndrome due to disease of the brain, usually of a chronic or progressive nature, in which there is disturbance of multiple higher cortical functions, including memory, thinking, orientation, comprehension, calculation, learning capacity, language and judgement. Consciousness is not clouded. Impairments of cognitive function are commonly accompanied, and occasionally preceded, by deterioration in emotional control, social behaviour or motivation. The prevalence of moderate and severe dementia in the over 65s is 5 per cent increasing to 25 per cent over 75 and 60 per cent over 85. The annual incidence in those over 65 is between 1 per cent and 1.5 per cent and age-specific prevalence rates double every 5 years. There are many pathological causes of the dementia syndrome. The most important causes are listed below. Early clinical presentation is determined by the cortical and subcortical areas involved. Diagnosis Diagnosis of dementia involves excluding the differential diagnoses and then establishing which of the many pathologies is responsible for causing the dementia in the patient. The differential diagnosis includes delirium and pseudodementia due to functional psychiatric illness. Clinical features of dementia These comprise the 'five As', outlined below.
Amnesia The most common early sign is loss of memory, predominantly learning of new material. The individual has difficulty recalling recent events but can describe past events relatively well. As the disorder progresses the individual develops deficits in long-term memory. Onset of memory
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disorder is gradual in Alzheimer's disease but sudden in vascular dementia.
Aphasia Initially in Alzheimer's disease there may be a mild nominal dysphasia which is apparent only on testing, but this gradually progresses to a mixed expressive and receptive dysphasia and then to complete aphasia. In vascular dementia, dysphasia may be prominent from the early stages. Dysphasia may severely impair performance on cognitive testing when the individual is not severely amnesic because of comprehension difficulties
Apraxia This may lead to problems with self-care; the patient may not be able to dress or feed him/herself properly. They may be unable to write or draw.
Agnosia The individual may fail to recognize others, objects, faces (prosopagnosia), themselves or their body parts (autopagnosia).
Associated symptoms Depressive symptoms may be present in 10-50 per cent of patients. While the individual with an early dementia may complain of depressed mood, in the later stages the only signs of depression may be behavioural or neurovegetative changes. Anxiety and agitation are not uncommon but may be associated with depression, psychotic symptoms or intercurrent physical illness. Personality change, including disinhibition, may be particularly troublesome for carers Psychotic symptoms include delusions and hallucinations in 10-20 per cent of those with AD. Again it is important to rule out other aetiologies of psychotic symptoms. Psychotic symptoms, mood disorder and behavioural disturbances are significantly associated with strain on carers. Primitive reflexes may re-emerge, urinary incontinence is common and a small proportion of individuals develop seizures. Causes of dementia
Alzheimer's disease (AD) This, the commonest cause of the dementia syndrome, is rare in those under 65 years, occurring in less than 1 per cent of the population but
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increasing in prevalence with increasing age. It accounts for 50-60 per cent of all cases of dementia. It is commoner in women than men, with an average age of onset in the mid-70s. Clinically the earliest sign in AD is usually short-term memory disorder. Progression of the disease is gradual and global. A possible or probable diagnosis of AD may be established using the NINCDS/ADRDA criteria. Definite diagnosis can only be established after histological confirmation on biopsy or post-mortem brain samples.
Pathology of AD Post-mortem examination shows cortical atrophy with the earliest changes in the temporal lobe, in particular the hippocampus. Sulci are wide with increased ventricular volume. The characteristic neuropathological lesions are extracellular senile plaques and cytoplasmic neurofibrillary tangles in the cerebral cortex (predominantly in the outer three layers). This is associated with cortical neuronal loss and a decrease in dendritic tree branching. Several neurotransmitter abnormalities have been described; the most consistent finding has been diminished levels of acetylcholine and its metabolic enzymes, acetylcholinesterase and choline acetyl transferase. Both CT and MRI imaging in vivo show cortical atrophy with temperoparietal emphasis. SPECT scans show decreased cerebral blood flow and PET scanning shows decreased cerebral metabolism in a similar distribution.
Aetiology of AD Down's syndrome and AD. The observation that individuals with Down's syndrome develop Alzheimer-type pathology at an early age had long suggested a link with chromosome 21. Genetic. Having a first-degree relative with AD is a robust risk factor for developing AD. In less than 1 per cent of cases of AD there is autosomal dominant inheritance of this disorder and a number of single gene mutations have been discovered in these families. Gene mutations have been found on chromosome 21 in the amyloid precursor protein gene and on chromosomes 19 and 14. As single gene mutations account for the minority of cases of AD a multifactorial aetiology is suspected. The apolipoprotein E4 allele incidence is increased in individuals with AD (48 per cent) when compared with the general population (13 per cent). Individuals who are homozygous for ApoE4 are at increased risk of developing AD but do not inevitably develop AD and 40-50 per cent of individuals with late onset AD do not have an ApoE4 allele.
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Aluminium hypothesis. It has been suggested that aluminium ingestion may be a cause of AD as aluminium has been found in post-mortem brains of AD patients and renal dialysis causes a dementia due to high aluminium levels. Current research is inconclusive. Prognosis of AD This is poor, individuals dying in 5-8 years of onset, usually of intervening physical illness.
Vascular dementia This, the second most common cause of dementia, accounts for about 20 per cent of all cases. Individuals show cognitive decline which is patchy and progresses in a stepwise manner. The age of onset is younger than in AD and the sex ratio is reversed with significantly more men than women diagnosed as having vascular dementia. Aetiology is multifactorial. It is associated with risk factors for cerebrovascular and cardiovascular disease, incuding hypertension, carotid artery atherosclerosis and cardiac arrhythmias. Rarely, it is associated with a single genetic disorder. Information from the history and examination may aid differentiation between AD and vascular dementia (Table 14.1). The modified Hachinski Ischaemia Score may also give an Table 14.1
Factors aiding differentiation of Alzheimer's disease and vascular dementia
Factor
AD
Vascular dementia
Onset Progression
Insidious Gradual
May be sudden Stepwise
Sex
F >M
M >F
Age onset
Mid-70s
Late 60s
Mental state Somatic complaints Cognitive impairment Insight Affect
Rare Global Early loss Blunted
Personality
Early changes
Common Patchy Early preservation Affective symptoms common, including labile mood May be preserved
Physical signs Seizures Neurological signs Hypertension Atherosclerosis Pseudobulbar palsy CT scans
Rare Primitive reflexes Rare Rarer Rare Atrophy
Epidemiology
Common Focal neurological signs Common Common May be present Infarcts, subcortical white matter changes
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indication that an individual is more likely to have a vascular dementia or AD. Vascular dementias may present suddenly with cognitive impairment after a stroke, as a gradually progressive memory disorder after small asymptomatic infarcts or with both cognitive decline and neurological signs of gradual onset. Cognitive symptoms depend on the cortical and subcortical structures which have been damaged. There is no treatment for vascular dementia, but investigation of individuals with vascular dementia would aim to identify and control the risk factors for cerebrovascular disease which might then slow disease progression. The average time from diagnosis of vascular dementia to death is 5 years, at least half of individuals dying of ischaemic heart disease.
Diffuse Lewy body dementia This dementia, associated with Parkinson's disease, is probably the third most common cause of the dementia syndrome. It is characterized by fluctuating memory and higher cortical function impairment associated with an episodic delirium-like state, auditory and visual hallucinations and altered consciousness. There may be mild spontaneous extrapyramidal symptoms or neuroleptic hypersensitivity syndrome.
Frontal lobe dementia This uncommon dementia is characterized by insidious onset over many years of: • personality change with development of obsessional traits and rituals and loss of insight; • behaviour disturbance including disinhibition, loss of normal social behaviour, planning and judgement, hyperorality, stereotyped and perseverative behaviour; • affective disorder - the individual may be labile, apathetic and lacking in spontaneity with emotional unconcern, anxious, depressed with hypochondriasis or fatuous; • language disorder with low-volume speech, lack of spontaneity in speech, verbal stereotypies, echolalia, perseveration and finally mutism. Spatial orientation, memory and praxis are preserved until late in the disease. Primitive reflexes and urinary incontinence may be early signs. It is of unknown aetiology, although as there is an increased incidence in first-degree relatives a genetic contribution is implicated. CT scans will show preferential atrophy of the frontal and anterior temporal lobes whereas the EEG may be normal. Neuropsychiatric testing shows profound failure on frontal lobe tasks.
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Progression is slow and the individual may live for up to 20 years from onset.
Spongiform encephalopathies In the UK the commonest of these rare dementias is Creutzfeldt-Jakob disease. This is a rapidly progressive disorder, usually presenting in the sixth decade, in individuals with no family history of the disorder. Presentation is usually with mood and personality change associated with cognitive failure, cortical blindness and myoclonus. The EEG characteristically shows triphasic discharges, with a frequency of 1-2 Hz. Survival from onset is usually less than 2 years.
Reversible dementias It is important to exclude these in assessment of an individual with dementia: • intracerebral disorders including subdural haematoma, tumour or other space-occupying lesion, normal pressure hydrocephalus and neurosyphylis; vitamin B12 or folate deficiencies; hypothyroidism; other physical illnesses including renal, hepatic or respiratory failure; dementia due to prolonged alcohol abuse; pseudodementia due to functional psychiatric illness.
Normal pressure hydrocephalus The individual has a triad of ataxia, urinary incontinence and subcortical dementia. The CT scan shows hydrocephalus without obstruction in the ventricular system. Ventriculocaval shunt insertion may reverse the disorder.
Subcortical dementias Due to involvement of subcortical structures rather than cerebral cortex these disorders present with a clinical picture of minimal memory loss with marked psychosocial impairment. The individual with a subcortical dementia is apathetic, slowed in thoughts and actions with early motor abnormalities including extrapyramidal and pseudobulbar signs. They tend not to have language disorder early in the disease and although they appear to have a memory disorder on testing, their performance is improved by giving cues unlike in cortical dementias. Causes of subcortical dementia include Lewy body dementia, Huntington's disease, progressive supranuclear palsy, subcortical vascular dementia, Wilson's disease and normal pressure hydrocephalus.
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Investigating dementia History from patient and informant will reveal the extent of interference with activities of daily living and cognitive assessment of the level of cognitive dysfunction. It may be necessary to carry out specific occupational therapy functional assessments to outline problems at home in detail. Physical examination, haematological, radiological and neuropsychological assessments will aid differentiation between different causes of dementia. Management of dementia
Social Management is predominantly social, ensuring that the patient is in an appropriate environment where his/her safety and care needs can be met. Carers should be supported, particularly where there is behavioural disturbance, as this is associated with carer distress. Individual carers and patients have different needs but care may involve home-based support from social or health services, attendance at day centres, respite care, rest home or nursing home long-term care.
Psychological This includes reminiscence therapy with individuals, and family therapies with the patient and their carers.
Pharmacotherapy Psychotic symptoms may respond to neuroleptics in small doses. Aggressive behaviour may also be treated with neuroleptics, but it is important to monitor the need for continuing these prescriptions given the risk of extrapyramidal side effects and the transient nature of symptoms. Neuroleptics should be avoided and used only with extreme caution in individuals with Lewy body dementia. Depressive episodes respond well to antidepressants, as in the nondemented. Although there is no cure for Alzheimer's disease, the anticholinesterases donepezil hydrochloride and rivastigmine have been shown to be of moderate benefit in improving symptoms for up to six months in some individuals with mild to moderate AD. Pseudodementia
This refers to functional illnesses presenting with cognitive impairments resembling dementia. In the elderly this is commonly associated with depression, although it may be a presentation of schizophrenia, other psychotic illness or hysteria.
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Depressive pseudodementia should be suspected if: • the disorder has been relatively acute in onset with variable symptoms unlike the gradual decline in dementia; • there is a personal or family history of depressive episodes; • there are neurovegetative symptoms suggestive of depression; • despite complaints of poor memory there is evidence of ability to learn new information, performance on psychological testing is variable and the individual often gives 'don't know' answers without appearing to attempt to find the answer; • behaviour is not consistent with progressive dementia; • there is a good response to antidepressant therapy.
Delirium Delirium is a temporary syndrome of fluctuating intellectual impairment with some or all of disorientation in time or space, impaired consciousness, concentration and attention, inability to register new memories and inability to understand surrounding events accompanied by intrusive abnormalities derived from fields of perception and affect. It is associated with physical illness, metabolic upset, alcohol or drug intoxication or withdrawal. Delirium is underdiagnosed and is relatively common in general hospital inpatients, particularly after hip or cardiac surgery, where up to 60 per cent of individuals may have symptoms of delirium at some stage. Careful history-taking from an informant will reveal that symptoms are of acute onset and will be related to onset of physical illness. Other symptoms differentiating between delirium and dementia are outlined in Table 14.2. Treatment is of the underlying disorder with reassurance, consistent nursing and neuroleptics to relieve the psychotic symptoms and agitation. Mortality is high (between 15 per cent and 40 per cent) but almost all of those who do not die are left with no increased cognitive dysfunction.
Depression 'Depression is depression at any age.' Unfortunately in the elderly it is underdetected and undertreated. There is no evidence that the prevalence of depressive disorder is any different in the elderly and the young. Prevalence rates are equal across all age groups in the elderly, except in the very elderly who may have lower prevalence rates. The prevalence of severe depression in the elderly is 1-3 per cent and of moderate severity is 10-15 per cent. Depressive symptoms without the full
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Factors aiding differentiation between delirium and dementia
Factor
Delirium
Dementia
Onset Duration Course
Rapid over hours or days Hours to weeks Fluctuates - worse at night, lucid intervals Always impaired Fluctuates Always impaired Mistake unfamiliar for familiar
Insidious over months Months to years Relatively stable
Awareness Alertness Orientation
Usually normal Usually normal May be intact Little tendency to confabulate Recent and remote impaired Some loss of general knowledge Poor in abstraction Misperceptions often absent Fragmented
Memory
Recent and immediate impaired General knowledge intact
Thought Perceptions
Slow or accelerated, dreamlike Misinterpretations, especially visual
Sleep-wake cycle
Always disrupted Drowsy during day Insomnia at night Usually Incoherent Agitation/fear Common
Often absent Aphasia common Apathy/disinhibition Rare
Common
Rare
Physical illness Language Mood Autonomic disturbance Psychomotor change
depressive disorder are even more common. It is more common in women, in those with serious physical illnesses. Aetiology Ageing itself does not predispose to development of depression but physical, social and psychological changes associated with ageing may.
Genetic Depression in old age is significantly associated with a family history of depression, although it is not clear whether this is significantly different from the association in younger individuals with depression.
Physical illness This is significant in over half of cases. Depression may be symptomatic of physical illness, including hypothyroidism, anaemia, occult cancer, hypercalcaemia, Cushing's syndrome, alcohol dependency or be induced
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by prescribed medication. Physical illness may also precipitate depression by being a loss event. Social Loss life events including bereavement are associated with about half of all depressive episodes in the elderly, as losses are common in this group. Other factors are important in determining who develops depression. These include chronic social difficulties, social isolation and lack of a confiding relationship
Differences from depression in younger individuals Classical features of depression are less reliable in diagnosing depression in the elderly. Depressed mood may be less overt and the severely depressed may fail to describe themselves as such or deny adamantly that they are depressed. It is therefore important to check carefully for associated biological symptoms and cognitions of hopelessness, guilt, burden and feelings that life is not worth living. The elderly are less likely to admit to lowered libido or suicidal thoughts, but more likely to complain of disturbed sleep which should be distinguished from the normal decline in sleep of old age. The elderly are more likely to complain of physical ailments and have hypochondriacal worries. They may present solely with physical problems, for example pain out of proportion to physical pathology. Anxiety is commonly associated with depression in the elderly and in fact may be the major symptom. As anxiety disorders of late onset are relatively rare, a depressive disorder should always be suspected. The elderly may present with a subjective memory complaint or pseudodementia. They are more likely to have psychotic symptoms with nihilistic or paranoid delusions. Investigation of depression • History and mental state examination, including establishing suicidal intention. • Physical examination and investigations to rule out symptomatic depression. • Screening questionnaires may be helpful, e.g. the Geriatric Depression Scale. Management Antidepressants have similar efficacy in elderly and younger individuals, but they may take longer to be effective in the elderly. Choice of antidepressant is guided by concurrent medication, physical illnesses
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and presence or absence of agitation or sleep disturbance. The elderly often require smaller antidepressant doses. ECT may be used for depression that is severe, life-threatening or failing to respond to pharmacotherapy. The elderly are more likely to develop transient post-ECT confusional states and if this occurs it is sometimes worthwhile using unilateral ECT on the nondominant hemisphere. Social interventions and supportive psychotherapies may be helpful. Prognosis Most individuals have a good outcome when treated, but there is a high risk of relapse. Relapse rates are significantly decreased by continuing to take therapeutic doses of antidepressants for over 2 years. Poor outcome is associated with chronic episodes, physical ill health and the presence of psychotic symptoms.
Suicide Twenty to thirty per cent of suicides are in the elderly, despite the elderly only accounting for 15 per cent of the population. Predictors of suicide in the elderly are male sex (twice the rate of women), increasing age (in men), alcohol dependency, physical ill health, hopelessness, agitation, insomnia, hypochondriasis, social isolation, and mental illness especially depression which has been partially treated. Deliberate self-harm without mental illness is rare in the elderly. Any elderly individual presenting after an overdose or other attempted selfharm, however medically trivial, should be assessed carefully for signs of mental illness, as there is no correlation with the medical severity of an overdose and the presence of suicidal intention
Other conditions Late paraphrenia This psychotic illness presents for the first time in old age and is characterized by persecutory delusions and auditory hallucinations. The presentation may vary from a pure delusional disorder to one indistinguishable from paranoid schizophrenia in a young person.
Epidemiology The prevalence is between 0.3 per cent and 1 per cent of the elderly population and accounts for at least 5 per cent of first psychiatric admissions in the elderly. It is much more common in women, with a female to male ratio of around 7:1.
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Aetiology Individuals are more likely to have premorbid paranoid and schizoid personality traits A genetic contribution is likely; the frequency of schizophrenia in first-degree relatives is midway between that of the general population and younger schizophrenics. It is significantly associated with deafness and other sensory impairments.
Differential diagnosis This includes paranoid states in depression, delirium, other organic disorders, dementia, mania and paranoid psychoses with onset before old age. History, examination, cognitive assessment and mood assessment should distinguish between these causes.
Management Developing a relationship with a nonthreatening and nonjudgmental therapist is important in ensuring compliance with treatment. Improving sensory impairments may be of benefit. Psychotic symptoms should be treated with neuroleptics either in oral or, if continued compliance is problematic, parenteral form.
Prognosis This is variable: 20 per cent may recover fully with neuroleptics but 10 per cent may fail to show any recovery with drug treatment. Personality disorder In general, personality disorders tend to become less troublesome as people become older. The presence of a pre-existing personality disorder may, however, colour an individual's presentation of mental illness, even in old age. Personality traits may be accentuated by development of organic disorders (e.g. frontal lobe syndromes) and it is important to investigate such. Alcohol and drug misuse Alcohol and drug dependency should not be ignored as it is not uncommon. In general, women tend to abuse prescribed hypnotics and men alcohol. This may only be detected on admission to hospital when they develop withdrawal symptoms. Dependency may be long-standing or of recent onset. If of recent onset, alcohol or hypnotic use may be a means of self-medicating depressive or anxiety symptoms or may be secondary to loneliness or personality changes related to dementia.
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Neuroses Individuals may present with lifelong neurotic disorders or, more rarely, with late onset neuroses. The annual incidence of neurotic disorders, in those over 60 years of age is less than 0.6 per cent. Individuals with late onset neuroses tend to be more physically unwell, have a lower income and are less able to look after themselves than those with long-standing neuroses. Unlike individuals with longstanding disorders they tend to have had good relationships with parents, no neurotic personality traits as children and have anankastic or anxious personality traits. Neurotic disorders may be precipitated by losses or physical illnesses. Phobic anxiety or panic symptoms are often associated with physical illness. Hysteria does not begin in old age and a physical explanation should be sought for all symptoms. Investigation of neurotic disorders aims to exclude the differential diagnosis which includes depression and early dementia (where up to 50 per cent of patients may have anxiety symptoms). Treatment includes that of underlying disorders, social and psychotherapeutic support, and cognitive and behavioural approaches to anxiety management.
Ethical and legal aspects Testamentary capacity To execute a will an individual must be of sound disposing mind, understanding and remembering the extent of his/her property, the individuals to whom he/she might reasonably leave his/her property and his/her relative claims upon him/her. Dementia or other mental illness per se does not make making a will invalid. Guardianship An order for guardianship under the Mental Health Act 1983 may be applied for by an approved social worker or nearest relative, supported by two medial recommendations. The patient should be suffering from mental disorder of a nature or degree warranting their reception into guardianship and it should be in the interests of the patient's welfare or the protection of others. Guardianship requires the patient to live in a specified place, to attend specified places for education, treatment, occupation or training and to allow access to doctor, approved social worker or other specified individual. It does not give the guardian power to use force to ensure attendance, gain access or convey the patient to their place of residence. In the elderly it is generally used to place elderly individuals in residential care homes when they are incapable of giving informed consent.
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Power of Attorney and Enduring Power of Attorney An individual (the donor) may use Power of Attorney to allow another individual (the attorney) to act in a specified capacity to deal with their finances or property. This power, however, becomes invalid once the donor becomes so mentally disordered that they are incapable of managing his/her own affairs. Enduring Power of Attorney (EPA) is anticipatory, allowing the attorney to continue managing the donor's affairs once the donor is incapable. When registering the EPA, the donor must be mentally capable of managing his/her own affairs and therefore allows the donor to determine his/herself who will manage their affairs when they do become incapacitated. Court of Protection If an individual is already incapable of managing his/her affairs, an EPA cannot be implemented. In such cases application for Receivership under the Court of Protection may be made. The Court of Protection, an office of the Supreme Court, manages the affairs and property of individuals with mental disorder (within the meaning of the Mental Health Act) who are incapable of managing his/her own financial affairs. One medical certificate is required. A receiver, usually a relative or friend, although sometimes a solicitor, bank manager or Public Trustee, is appointed by the court to manage the individual's affairs. The receiver is charged with using the patient's money for his/her benefit and must keep accounts which are monitored through the Public Trust Office Receivership Directorate. Driving and Dementia Psychiatric disorder, including dementia, does not necessarily preclude individuals from driving and in the early stages of dementia an individual's driving capabilities may be relatively unimpaired. The doctor who is concerned about the patient's ability to drive should inform the patient that they, the patient have a legal obligation to inform the Driver and Vehicle Licensing Authority (DVLA) of their medical condition. If the patient fails to do this, and continues to drive, the doctor is entitled to inform the DVLA in confidence who may then ask for further information from the patient's GP or ask the patient to undergo further medical assessment by an appointed doctor. If the licence is revoked and the patient continues to drive, it may be necessary to resort to removal of, or disabling, the car.
Reading list Benbow, S.M. (1987) The use of electroconvulsive therapy in old age psychiatry. International Journal of Geriatric Psychiatry, 2, 25-30.
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Burns, A., Jacoby, R. and Levy, R. (1990) Psychiatric phenomena in Alzheimer's disease II: disorders of perception. British Journal of Psychiatry, 157, 76-81. Burns, A., Russell, E. and Page, S. (1999) New drugs for Alzheimer's disease. British Journal of Psychiatry, 174, 476-9. Byrne, E.J. (1987) Reversible dementia. International Journal of Geriatric Psychiatry, 2, 73-81. Folstein, M., Folstein, S. and McHugh, P.R. (1975) Mini-mental state: a practical method of grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12, 189-98. Howard, R., Almeida, O. and Levy, R. (1994) Phenomenology, demography and diagnosis in late paraphrenia. Psychological Medicine, 24, 397-410. Lindesay, J., Briggs, K. and Murphy, E. (1989) The Guy's/Age Concern Survey: prevalence rates of cognitive assessment, depression and anxiety in an urban elderly community. British Journal of Psychiatry, 155, 317-29. Murphy, E. (1982) Social origins of depression in old age. British Journal of Psychiatry, 141, 135-42. Murphy, E. (1982) The prognosis of depression in old age. British Journal of Psychiatry, 142, 111-19. Yesavage, J. (1993) Differential diagnosis between depression and dementia. American Journal of Medicine, 94, 23S-28S.
15
Personality disorders KINGSLEY NORTON and JONATHAN VINCE
Debate continues over the validity of the concept of personality disorder (PD) and its subcategories. Validating studies, however, do not relate equally to all PD subcategories and aetiological and treatment outcome data do not adequately refer to the entire range of subcategories. The most thoroughly researched subcategories are antisocial and borderline PD. Studies of co-morbidity among PD subcategories reveal it to be common, especially in borderline PD. There appears to be no simple relationship between PD subcategories or the severity of PD and the relevant therapeutic strategies. For the most part, therefore, PD will be considered as a unitary syndrome and of equal severity. However, the reader will need to recognize the inevitable bias towards DSM-IV, cluster 'B' PD subcategory diagnoses - antisocial, borderline, histrionic and narcissistic - or, where they exist, their equivalents within ICD-10.
History of the PD concept The concept of PD shares a common ancestry with that of 'psychopathic personality'. The latter is conventionally viewed as arising in the early nineteenth century, following the identification of patients who were prone to outbursts of rage and violence but who were not deluded 'manie sans delire'. Shortly thereafter, others identified broadly similar patients but labelled them as suffering from 'moral derangement' or 'moral insanity'. By the late nineteenth century there was a growing realization that a whole range of mentally disturbed patients existed who were not deluded. Consequently, dissatisfaction with the category of 'moral insanity' grew but it nevertheless persisted. The concept of 'psychopathic infirmity' brought greater clarity with its narrower description of a behavioural abnormality in the absence of psychotic illness or intellectual impairment.
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The first half of the twentieth century saw further attempts, notably by Kraepelin, to classify 'psychopathic personality'. The concept of psychopathic personality was later expanded to include, as part of its definition, the personal suffering of the patient and the term 'personality disorder' was introduced. Until then, abnormal personalities had been identified mainly through their effect on others or on society. Considerable conceptual, terminological and diagnostic confusion still remains.
Current definition Diagnosis of PD requires knowledge and skill to distinguish between normal and abnormal personality, to elicit the pertinent PD psychopathology and to recognize the limits of the patient's ability to access information about their personal, interpersonal and social functioning. Only then is it possible for the psychiatrist to apply reliably the definitions of PD in ICD-10 and DSM-IV. These classifications use broadly similar definitions but different language and style. A diagnosis of PD may be unreliable for many reasons. Commonly, however, there are problems in the interaction of PD patient and clinician, partly reflecting the former's interpersonal difficulties, which impair the reliability of the diagnostic process. To maximize the quality of diagnostically relevant information, attention needs to be paid to the interaction during the assessment interview itself and, specifically, to the manner in which the patient's PD may be enacted interpersonally. Since the patient does not always provide accurate or full information, especially regarding interpersonal and social functioning, it is usually necessary to obtain collateral information about this from other informants and sources before making the diagnosis of PD. This is to identify an enduring pattern of disharmonious attitudes and behaviour, not limited to episodes of illness, clearly maladaptive to a range of personal and social situations and often resulting in considerable personal distress. PD subtypes A single patient may fit more than one personality disorder subcategory and whereas structured assessments of patients reveal an average of between 3.75 and 4.6 PD per patient, practising clinicians rarely diagnose more than 1 PD. Table 15.1, which lists the PD subcategories of ICD-10 and DSM-IV, displays summaries of each and allows a comparison within and between the two. There is substantial overlap between the supposedly separate PD subcategories. In clinical practice, since the presence of PD worsens the prognosis of other disorders, it is more important to establish accurately the presence of PD than to designate a subcategory.
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Comparison of classification of personality disorder subcategories (after Tyrer) DSM-IV
ICD-10 Code
Description
Code
Description
F60.0
Paranoid - excessive sensitivity, suspiciousness, preoccupation with conspiratorial explanation Schizoid- emotional coldness, detachment, lack of interest in other people, eccentricity and introspective fantasy (No equivalent)
301.00
Paranoid- interpretation of people's actions as deliberately demeaning or threatening Schizoid- indifference to relationships and restricted range of emotional experience and expression Schizotypal - deficit in interpersonal relatedness with peculiarities of ideation, appearance and behaviour Obsessive-compulsive pervasive perfectionism and inflexibility
F60.1
F60.5
F60.4
F60.7
F60.2
F60.6
F60.30
F30.31
Anankastic- indecisiveness, doubt, excessive caution, pedantry, rigidity and need to plan in immaculate detail Histrionic- self-dramatization, shallow mood, egocentricity and craving for excitement with persistent manipulative behaviour Dependent- failure to take responsibility for actions, with subordination of personal needs to those of others, excessive dependence with need for constant reassurance and feelings of helplessness when a close relationship ends Dissocial- callous unconcern for others, with irresponsibility, irritability and aggression, and incapacity to maintain enduring relationships (No equivalent)
Anxious- persistent tension, self-consciousness, exaggeration of risks and dangers, hypersensitivity to rejection, and restricted lifestyle because of insecurity Impulsive - inability to control anger, to plan ahead, or to think before acts, with unpredictable mood and quarrelsome behaviour Borderline- unclear self-image, involvement in intense and unstable relationships
301.20
302.22
301.40
301.50
Histrionic - excessive emotionality and attention seeking
301.60
Dependent - persistent dependent and submissive behaviour
301.70
Antisocial - evidence of repeated conduct disorder before the age of 15 years.
301.81
Narcissistic - pervasive grandiosity, lack of empathy and hypersensitivity to the evaluation of others Avoidant- pervasive social discomfort, fear of negative evaluation of others
301.82
301.83
Borderline - pervasive instability of mood and self-image
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PD severity There are many scales with which to rate the presence of PD, but only inadequate measures of its severity. Frequently, even in research studies of treatment outcome, change in severity is measured solely by the presence or absence of PD-associated features, such as parasuicide, rather than by changes to core features of the PD itself or those features to which treatment was actually addressed, such as affective instability. Until relevant measures of severity are developed, the number of PD subcategory diagnoses or of PD 'clusters' provides the best estimate of severity. An assessment of the PD patient's personality organization, which can be used alongside a psychiatric diagnosis of PD, has implications for prognosis and treatment and can also contribute to the measurement of severity. It is a more sensitive indicator of severity than a psychiatric diagnosis, which is simply recorded as absent or present. However, it requires the clinician to carry out a so-called 'structural interview', which includes the recognition of the psychological defence mechanisms of splitting, denial, primitive projection and projective identification. A self-assessment scale, incorporating aspects of borderline personality disorder and borderline personality organization, has been developed which is sensitive to therapeutic change in a PD population.
Prevalence Community surveys of the general adult population suggest that approximately 1 in 10 suffers from PD. Roughly, 20 per cent of patients attending their GP and 30 per cent of those patients attending psychiatric outpatient clinics have a PD. Interpersonal aspects, within the relationship between GP and PD patient, may trigger the referral to secondary services and hence account for the prevalence gradient. Psychiatric inpatient populations show a still greater proportion of personality disorder.
Aetiology Genes Twin and adoption studies, which are required to distinguish genetic from environmental factors in PD, are rare. One study, involving 69 PD patients, did not support a genetic aetiology. However, there is some evidence for a distinct genetic component to aetiology in some PD subcategories, especially for antisocial and schizotypal PD. Psychosocial environment High levels of PD are found in the family members of patients suffering from PD, although the predicted specific association between PD and
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the mothers of PD patients is not always borne out. Research findings reveal a range of disorders in family members, including substance abuse and alcoholism, but no specific associations between particular symptom disorders and PD. The hypothesis that early, prolonged and traumatic separations or losses are sufficient or necessary for the development of later PD has been refuted. A family atmosphere which is marked by angry conflict with poor organization and low supportive cohesion, especially when coupled with little opportunity to express feelings and expectations of normal independence, achievement and morality, is aetiologically potent. The absence of protective factors, such as a stable family structure or capable substitute carers within the family network, however, may be just as important as trauma in the development of PD. Sexual and physical abuse frequently appear in the personal histories of PD patients. It has also been suggested that the prognosis of PD is worsened by a history of abuse. Many PD patients have been exposed to considerable impulsive and aggressive behaviour from parents who thus provide maladaptive role models. The existence of past abuse is important to uncover in the history-taking. This often requires the questioning to be sensitive and the patient to be engaged, at least to an extent, in a therapeutic alliance. Early separations, the modelling effects of emotionally and impulsively disturbed parents and the effects of sustained abuse, all appear to play a part in the genesis of PD. There is some evidence for an association between early styles of attachment and maladaptation later in childhood, which has been inferred to develop into PD in adulthood. A formulation of a particular patient's personality development and difficulties should make reference to such aetiological factors and their potential for interaction and hence for protection or summation. It should also take into account the presence and timing of the usual developmental tasks confronting the individual patient (e.g. puberty), since these represent opportunities for solving personal and interpersonal problems as well as posing threats to later psychosocial adaptation.
Clinical management PD and the therapeutic alliance Psychiatrists may feel professionally disempowered by many PD patients who, in effect, present only themselves rather than a clear treatable symptom. The clinical encounter can thus fail even before relevant symptoms are presented, leading to or reinforcing therapeutic pessimism in some clinicians. Successful engagement of the PD patient requires the establishment of sufficient mutual trust and respect. Thus it may be important to acknowledge at interview that these are likely to be absent initially.
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Asking for help often induces feelings of vulnerability or humiliation in the PD patient and associated fears of abuse or neglect, hence it can be useful to discuss the patient's likely ambivalence about seeking help. Furthermore, the patient's fragile self-esteem may mean that the psychiatrist's care and attention is felt to be undeserved and, confusingly, misfortune or illness to be merited. Such vulnerability is often marked by aggressive or passive-aggressive interpersonal styles. Sensitively acknowledging the potential presence of mistrust, ambivalence and fragile self-esteem, and their combined effect as an obstacle to appropriate care-seeking, may aid the patient to acknowledge personal difficulties rather than to reject or deny them in favour of a maladaptive interpersonal enactment with the diagnosing or treating psychiatrist. A therapeutic alliance, essential as a vehicle for change, may thus begin to develop. Its continuing presence, however, should not be assumed. General points about treatment Maximizing the success of any PD treatment includes: the identification and effective treatment of any co-morbid disorder; stressing the collaborative nature of the therapeutic enterprise; agreeing realistic goals for treatment; attending particularly to hatred in the countertransference; and maintaining a low threshold for seeking consultation. Nevertheless, many PD patients still terminate treatment prematurely, often feeling misunderstood or badly treated by their therapist. Knowing which PD patient is best suited to which treatment, and for how long it should last, are far from being fully understood. Those patients referred to psychiatrists are likely to require long-term clinical management and thus to receive a range of different approaches. This fact also compromises an accurate assessment of the success rate of any particular treatment ingredient. In view of this, the treatments described below will be discussed without reference to their specific efficacy. Supportive psychotherapy Most PD patients receive supportive psychotherapy focusing on the reality problems of daily life for the patient. Frequently treatment is longterm, lasting between 3 and 5 years, with continuing supportive psychotherapy on an 'as required' basis beyond this. It requires skill and training. The overall aim is to improve adaptation in the PD patient, through diminishing self-destructive responses to predictable interpersonal frustrations. Although the aim is not to change the patient's personality, there is some evidence that support may facilitate personality change. Starting with a supportive approach may prepare some patients for more intensive psychotherapies. Repeated 'doses' of shortterm therapy, the so-called 'short-term intermittent therapy', on a longterm basis, has also been advocated.
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Psychoanalytic psychotherapy Psychoanalytic psychotherapy for selected PD patients may also need to last for years and can be intensive - two or more sessions per week. The aim is personality reorganization, through the resolution of intrapsychic structural conflicts and/or deficits thought to be at the heart of the disorder. In order to achieve this aim, controversy remains over the usefulness of interpretation early in treatment and over how to manage the patient's negative transference. Since the PD patient often experiences interpretations as critical, some therapists argue for a supportive modification which anticipates such a reaction, as part of the interpretation itself. This approach may be particularly relevant to PD patients with abusive histories. Thus, the abused patient's aggressive and manipulative behaviour may be both interpreted (e.g. as a defence against feelings of vulnerability and depression) and discussed as having been of adaptive value to earlier abusive situations. Few now recommend unmodified psychoanalysis for PD patients. Family therapy Family therapy has been used with families marked by over-involvement or abuse and neglect. Usually this is to maintain outpatient psychotherapy with the individual PD patient, especially when it is likely to fail because of the adverse effect of the family network on the treatment. It is seldom advocated as sufficient in itself but can be a useful adjunct, usually on an 'as required' basis. Some also use conjoint sessions, involving both the individual and family therapists, where therapists for each treatment ingredient are different. Group therapy Group therapy has been regarded as useful for PD patients, especially those showing prominent demanding behaviour, egocentrism, social isolation or withdrawal, and socially deviant behaviour. The claimed advantage, over individual or family therapy, is that the PD patient's peer group (not necessarily themselves suffering from PD) potentially provides: enhanced confronting of maladaptive behaviour; better identification of dependent and manipulative gratifications; greater success in recognizing such behaviours as personal problems; providing a field of study of others' maladaptive coping strategies (more easily identified by the PD patient than are their own strategies); and the provision of support for new and better relationships, both in and out of the group. Controversy remains, however, over whether it is advisable to have more than one PD patient in an outpatient psychotherapy group and whether concurrent individual psychotherapy is superior to group therapy alone.
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Behaviour therapy Behaviour therapy is not often advocated, even though it can address relevant therapeutic targets, namely, impulsivity, self-destructiveness and maladaptive modes of expressing aggression. A behavioural assessment can also aid an understanding of both positive and negative reinforcers, so that any necessary treatment can at least avoid perpetuating the PD patient's destructive behaviours. Linehan's behavioural treatment incorporates cognitive strategies, particularly to deal with selfdestructiveness. This important approach includes a mixture of weekly individual and twice-weekly group treatment over 1 year, with treatment goals broken down into their component tasks in order to facilitate their achievement. It is highly structured and seeks to teach the PD patient general problem-solving skills, emotional regulation strategies, interpersonal skills and distress tolerance. Cognitive psychotherapy Cognitive psychotherapy focuses on identifying the patient's major cognitive distortions or schemas and the way in which these are reiterated and maintained in everyday life. Discussion of such self-defeating and maladaptive strategies is aimed at atrophying their use and replacing them with more self-affirming and adaptive cognitive strategies, linked with appropriate affect. Traditional cognitive therapy methods are applied, such as daily thought record, as well as more advanced techniques, for example schema identification or the eliciting of the patient's personal constructs. The importance of understanding the patient's personal history in the formulation of their problems, the collaboration between therapist and patient, and dealing with transference-countertransference (i.e. interpersonal) aspects are increasingly stressed. Pharmacotherapy In view of the PD patient's interpersonal difficulties, there is a need to engage the PD patient as an ally who will study, along with the prescribing psychiatrist, his or her responses to the various pharmacological agents. Such a constructive approach has the potential advantage of curbing unrealistic expectations of the drug effect, facilitating patients to step back and identify their own behaviour and symptom patterns, and helping them to avoid an adversarial relationship with the psychiatrist. A drug treatment may be used in combination with psychological interventions including inpatient admission. However, the possibility of the PD patient's self-destructive use of any medication should always be remembered. Dispensing small amounts of medication, especially to those with a history of parasuicide or addiction, should thus form part of any treatment regimen.
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Neurochemical models of behaviour and empirical pharmacotherapy trials have identified aspects of the PD patient's psychopathology as targets for drug treatment. Each may involve a different neurotransmitter and hence be potentially susceptible to an appropriate pharmacological agent. The PD patient's symptoms of depersonalization, derealization, illusions, ideas of reference and brief paranoid states may respond to low-dose neuroleptics. Where intense anger and hostility are prominent, low-dose neuroleptics are probably also the drugs of choice, since benzodiazepines may disinhibit the PD patient and thereby increase hostility, self-destructiveness and assaultiveness. In managing impulsiveness, there may be a role for SSRIs, neuroleptics, carbamazepine and lithium carbonate, although a controlled study of the last found it to be only slightly superior to placebo. Treatment contract Some clinicians find that a formal treatment contract fosters a therapeutic alliance, helps address unrealistic fears or phobias about treatment, contains dangerous behaviour and protects the integrity of treatment. However, the contract needs to be frequently updated in accordance with any clinical change, whether improvement or deterioration, and it should be remembered that treatment contracts with PD patients are not a panacea. Many fail through being unduly restrictive, becoming a substitute for psychotherapy or being used by the clinician, unwittingly, as a means of defence or punishment. Inpatient treatment The long-term management of most PD patients is eclectic and many require inpatient treatment at some time. The latter is often occasioned by clinical deterioration and/or the breakdown of existing therapy. Inpatient PD research has lagged behind that of outpatient treatment, hence there is a lack of consensus on both indications for admission and duration of treatment. Long- versus short-term hospitalization often hinges on the likelihood of an unhelpful regression, which may be induced by admission. Those aiming only for stabilization and attachment favour a short admission to avoid regression, while those aiming for the internalization of new psychic structures (i.e. personality change) argue for long-term admission, usually to a specialist PD unit. Duration is often not defined in the available literature; however, the suggestion of 'short' (less than 60 days), 'intermediate' (60 days to 6 months) and 'long' (over 6 months) may prove to be useful. Some advocate a strictly time-limited admission to diagnose accurately and plan treatment, while adhering rigidly to a discharge date which is fixed soon after admission. Others stress the establishing of clear and limited goals, a firm treatment alliance or the fostering of realistic
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expectations of treatment. The last emphasizes the importance of staff providing a consistent set of responses within the hospital setting, since inconsistent treatment has dangers even with short-term inpatient treatment. In planning the hospitalization of PD patients, it is important to consider all the risks inherent in carrying out such a decision. These pertain not only to the patient but to staff, the hospital unit, other patients and to the treatment milieu as a whole.
Specialist inpatient psychotherapy Specialist settings are able to operate selection criteria. They can thus choose PD patients who display, at least, some genuine motivation for change, psychological mindedness and a degree of interpersonal stability. Such settings are also better placed to deliver an integrated and consistent treatment package, since they can concentrate on the PD aspects of their patients. Two relatively distinct models of specialist inpatient psychotherapy are recognized. The first incorporates psychotherapy as the main ingredient of treatment within a setting specifically set up to support it. In the second model, the supportive environment itself shares an equal therapeutic status with that of the inpatient psychotherapy sometimes known as the therapeutic community. Prognosis A study by Stone of 206 PD patients, at 10-2 5-year follow-up, found over 50 per cent had clinically recovered but that there was a suicide rate (3-9 per cent) which was vastly inflated compared with that of the general population. Adequate prospective and long-term treatment outcome studies, however, are both rare and inconclusive. Reading list Dolan, B., Warren, F. and Norton, K. (1997) Change in borderline symptoms one year after therapeutic community treatment for severe personality disorder. British Journal of Psychiatry, 171, 274-9. Gunderson, J. and Sabo, A.N. (1993) Treatment of borderline personality disorder: a critical review. In Borderline Personality Disorder: Etiology and Treatment (ed. J. Paris), Washington, DC: American Psychiatric Press. Hinshelwood, R. (1988) Psychotherapy in an inpatient setting. Current Opinion in Psychiatry, 1, 304-8. Johansen, K. (1983) The impact of patients with chronic character pathology on a hospital inpatient unit. Hospital and Community Psychiatry, 34, 842-8. Kernberg, O. (1984) Severe Personality Disorders: Psychotherapeutic Strategies. New Haven, CT: Yale University Press.
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Koch, J.L. (1891) Die Psychopathischen Minderwertigkeiten. Ravensburg, Germany: Maier. Linehan, M.M. (1992) Cognitive-behavioural Treatment for Borderline Personality Disorder: The Dialectics of Effective Treatment. New York: Guilford. Links, P.S., Steiner, M., Boiago, I., et al. (1990) Lithium therapy for borderline patients: preliminary findings. Journal of Personality Disorders, 4, 173-81. Pinel, P. (1801) Traite Medicophilosophique sur I'alienation mentale, ou la manie. Paris: Richard, Caille et Ravier. Prichard, J.C. (1835) A Treatise on Insanity and Other Disorders Affecting the Mind. Philadelphia: Haswell, Harrington and Haswell. Rush, B. (1812) Medical Enquiries and Observations upon the Diseases of the Mind. Philadelphia: Kimber and Richardson. Schneider, K. (1950) Psycho lop athic Personalities. London: Cassel. Sederer, L. and Thorbeck, J. (1990) Borderline character disorder. In Inpatient Psychiatry: Diagnosis and Treatment (3rd edn.). Baltimore: Williams and Wilkins. Silver, D. (1985) Psychodynamics and psychotherapeutic management of the self-destructive character-disordered patient. Psychiatric Clinics of North America, 8, 357-75. Skodol, A.E., Rosnick, L., Kellman, D., et al. (1988) Validating structured DSMIIIR personality disorder assessment with longitudinal data. America Journal of Psychiatry, 145, 1297-9. Stone, M.H. (1990a) Abuse and abusiveness in borderline personality disorder. In Family Environment and Borderline Personality Disorder (ed. P.S. Links). Washington D.C.: American Psychiatric Association. Stone, M.H. (1990b) The Fate of Borderline Patients: Successful Outcome and Psychiatric Practice. New York: Guilford. Torgesen, S. (1984) Genetic and nosological aspects of schizotypal and borderline personality disorders. Archives of General Psychiatry, 41, 546-54. Tyrer, P. (1991) Neuroses and personality disorders. In Concepts of Mental Disorder: A Continuing Debate (eds A. Kervy and H. McClelland). London: Gaskell. Widiger, T., Trull, T., Hurt, St., et al. (1986) Diagnostic criteria for the borderline and schizotypal personality disorders. Journal of Abnormal Psychology, 95, 43-51.
16
Alcohol misuse ADAM WINSTOCK and MICHAEL FARRELL
Alcohol is still the most widely used and abused mood-altering substance in our society. About 90 per cent of the population drink alcohol at some time, with American studies reporting a lifetime prevalence of an alcohol dependency syndrome as 9 per cent. In the UK, the social cost of alcohol misuse in the UK is estimated at £4 billion/year. The Royal Colleges recommend a maximum weekly intake of 21 units of alcohol for men and 14 for women. Recently government advisers have suggested that on occasions men may drink 3-4 units in a night (women 2-3) without serious risk of physical damage. Paradoxically, reducing alcohol consumption in that large number who drink just in excess of recommended levels, through public education and brief interventions, may be a more cost- and health-effective option than highlighting the treatment for the smaller number of dependent users whose individual consumption of resources is enormous.
Definition The clinical syndrome was described by Edwards and Gross, who noted the following: • narrowing of drinking repertoire (loss of variation in pattern of intake); the salience (primacy) of drink-seeking behaviour; increased tolerance to alcohol; repeated attempts at withdrawal from alcohol; relief or avoidance of withdrawal symptoms by further drinking; subjective awareness of compulsion to drink; reinstatement of dependent drinking after a period of abstinence. Classification in ICD-10 is under 'Disorders due to psychoactive substance abuse'.
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Metabolism Ethanol (ethyl alcohol), is chiefly metabolized by the liver. The ratelimiting enzyme is alcohol dehydrogenase, which is saturable when intake is above about lOmg pure alcohol per hour. Once this is exceeded, a rapid rise in alcohol levels occurs. Induction of hepatic enzymes is the major mechanism in the development of tolerance. Epidemiology of alcohol misuse Consumption Per capita consumption is the principal measure of alcohol consumption in society. There is good correlation between per capita consumption and death rate from cirrhosis of the liver and, within countries, fluctuations in consumption over time are positively correlated with changes in the rate of cirrhosis. Prevalence About one-third of men and 10 per cent of women drink above the recommended levels for a prolonged period. The average UK per capita consumption is however much lower at under 10 units a week. Approximately one-quarter of men will be problem drinkers at some time in their lives and the EGA study in the USA reported a 14 per cent lifetime prevalence of alcohol dependency, higher in men than women. Prevalence studies in the UK give dependence rates in the year prior to interview as 7.5 per cent for men and 2 per cent for women (4.9 per cent overall). Age Adults drink less with advancing age. The heaviest drinking occurs in the late teens and early 20s when the sex differences in consumption are least evident.
Sex Men drink about three times as much as women. In Asian and Hispanic cultures, the male to female ratio for consumption is nearer 10. Religion and culture The role of culture and religion upon consumption is complex, with highly prohibitive rules perhaps making binge-drinking more likely. However, the effect of global marketing and homogenization of social behaviours may diminish such effects in years to come. In Europe the highest per capita consumption (12-15 units/week) is in France and Spain.
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Occupation Jobs permitting access to cheap, easily available sources of alcohol or those where consumption is regularly seen as 'part of the job' increase the risk of drinking. Factors such as unsociable hours, shiftwork or time away from the family add to the risk. People in unskilled manual occupations, publicans, travelling salesmen, journalists and doctors are at particular risk. Thirty per cent of the working population drink above recommended levels. Marital status Alcoholics are more likely to be divorced, separated or never married. Socioeconomic class Wine is more commonly consumed by social classes 1 and 2, beer among social classes 4 and 5, with heavy spirit consumption most common among the higher classes. In the Whitehall II of UK civil servants study the most striking difference between the classes was the increase in the prevalence of nondrinkers with progressively lower grades. The lowest rate of drinking problems is in the 'middle classes', whereas one-half of the UK's homeless are thought to have alcohol-related disorders. Economic cost There are costs to NHS and to industry (absenteeism, reduced productivity), and costs arising from accidental injury (including road traffic accidents), legal and police work, social work involvement and loss of person-years. Co-morbidity The American EGA study suggested high rates of substance misuse among those with serious mental illness, giving an odds ratio of 4 and 8 for schizophrenia and bipolar disorder respectively. However, the most likely co-morbid diagnosis in someone with alcohol dependency is dependence upon another substance. The combination of diagnoses increases the likelihood of violence and suicide.
Identification of cases This may take a number of forms, from drinking diaries and questionnaires to biochemical and physical examination. Questionnaires: the CAGE comprising four simple questions (Cutdown, Angry, Guilt and Eye opener), the MAST (Michigan Alcohol Screening Test) and the
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AUDIT (Alcohol Use Disorders Identification Test) are sensitive (> 80 per cent) instruments. The latter, devised for the WHO, is designed to identify harmful drinking and consists of 10 items. The use of screening instruments in primary care can markedly improve identification of alcohol problems with an 80 per cent increase reported in one GP study. Useful measures of alcohol-related problems (which correlate with severity of dependence) include - self reporting Alcohol Problems Questionnaire (APQ) and the Severity of Alcohol Dependence (SADQ). Biochemical investigations such as gamma-GT (50-60 per cent sensitive), MCV (30-40 per cent sensitive) and most specifically and recently carbohydrate deficient transferrin (80 per cent) screens are also useful in identification as well as in monitoring relapse. Taking a drinking history Presentation of a drinking history must demonstrate the evolution, development and nature of the drinking problem. Salient points in the diagnosis of alcohol dependency should be highlighted. The following is a suggested scheme of enquiry and presentation: 1. Current level of intake: volume, type (per cent alcohol), duration of abuse at this level. 2. Typical day: symptoms of withdrawal on waking, relief drinking, social and nutritional activities; place of drinking and antisocial behaviours. 3. Alcohol-related problems, especially physical/psychological. Enquire specifically for GI symptoms, withdrawal fits, DTs, head injuries and blackouts. 4. Previous treatments and length and pattern of abstinent periods. 5. Circumstances surrounding relapse. 6. Drinking history. Age first used alcohol. Age first consumed at regular level (note quantities to assess development of tolerance). Development of the salience of drink-seeking behaviour and narrowing of drinking repertoire. Age first experienced withdrawal and institution of relief drinking. Note the changing social circumstances especially with respect to family, social and employment. 7. Family history of substance abuse. Aetiology
This is multifactorial, with constitutional and environmental influences as outlined next. Genetic Twin studies give concordance rates of 70 per cent (MZ) : 43 per cent (DZ) for men and 47 per cent (MZ) : 32 per cent (DZ) for females. The
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evidence for a genetic contribution in women, however, is less consistent than in men. Adoption studies demonstrate a four-fold increase in the incidence of alcoholism among male adoptees adopted away from their alcoholic parent(s). Averaging-out studies would suggest that the incidence in first-degree relatives is raised by about 2.5 times. The genetic component of aetiology is mediated in a number of ways. In relation to consumption, those with a positive family history (PFH) experience a less intense reaction such that vulnerable individuals 'need' to drink more to experience intoxication. Alternatively, alcohol consumption in some may be normalizing, as is suggested by the apparent corrective effect of alcohol on the baseline low levels of alpha activity seen in alcoholics. In a third group-genetic variation in the activity of aldehyde dehydrogenase may be protective against the development of alcohol dependency. Thus about half of 'normal' Chinese and Japanese subjects are deficient in the active mitochondrial form of AID 2 (compared with 2 per cent of Japanese alcoholics) and experience 'flushing' (tachycardia, hypertension, a facial flush and weakness) on ingestion of small amounts of alcohol. Acetaldehyde may also combine with neurotransmitters to form tetrahydroisoquinolines, substances with opiate-like qualities, explaining the sometimes useful administration of naloxone to those with severe alcohol intoxication. Genetic effects also determine the susceptibility to alcohol-associated physical damage, for example in the development of cirrhosis, haemachromatosis and brain damage. Dependence is likely to be in part genetic. Recent studies showing a strong association between alcohol dependency and a genetic marker, the Al allele of the dopamine D2 receptor gene, though replication studies have been inconsistent. Cloniger hypothesizes two types of genetic transmission. (Table 16.1).
Table 16.1
Cloniger subtypes of alcoholism
Type 1 (milieu limited)
Type 2 (male limited) Less likely to achieve abstinence
Sex Family history
Loss of control with high psychological dependency and guilt M and F Parents mild/non-abusers
Age of onset Violence and crime
Usually > 25 years No association
M High genetic component for alcohol and antisocial behaviour Usually < 25 years Increased
Personality
Traits of dependency and harm avoidance
Impulsive and antisocial traits.
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Biological markers The growth of molecular genetics in the last decade has raised the possibility of identifying genetic loci that may confer a predisposition to the development of alcohol dependence. (Table 16.2). Table 16.2 Biological markers for alcoholism Lower alpha activity on the EEG Reduced platelet MAO activity Decreased subjective intoxication Transketolase Km higher Blunted prolactin response to ethanol challenge
Reduced amplitude and increased latency of the P300 (not specific) Increased static ataxia in first-degree relatives Autonomic stress response increased A1 allele of D2 receptor? Blunted cortisol response to ACTH especially in family positive
Biochemical Dopamine is probably central to the development of dependence (alcohol releases DA in the nucleus accumbens) and is also thought to underlie craving. However, other neurotransmitters including 5-HT and GAB A are also proposed to play a role (see Neurobiology of ethanol dependence, below). Psychological Freud would point to the concept of the death instinct to explain the self-destructive consumptive process. More likely explanations are given by classical and operant learning theories, with relief drinking and cued response/relapse being two examples often cited. The two main dimensions of the condition within this framework are seen as withdrawal avoidance and reward, with the latter seemingly the more important. Such explanations have an important role in directing some therapeutic interventions such as relapse prevention. Modelling (vicarious learning) and social learning are also proposed aetiological theories. Personality traits Half a century of research has failed to identify the alcoholic or addictive personality, however attractive the idea may sound. Of the many traits associated with alcoholism (Table 16.3), only antisocial ones stand up Table 16.3 Childhood Locus of control Emotional
Predisposing personality traits and alcoholism
Aggression, inattention, hyperactivity, antisocial behaviours External Dependency, anxiety and alexithymia. Higher neuroticism scores on EPQ
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confidently. Note, however, that antisocial personality and alcoholism are inherited independently. Neurobiology of ethanol tolerance, dependence and withdrawal Ethanol is thought to act by interfering with the lipid integrity of the neuronal membrane and consequently neurotransmission. Its anxiolytic activity is probably mediated through the potentiation of the inhibitory effects of GABA at GABAA receptors. Ethanol sensitivity is specifically controlled by part of the gamma subunit containing a phosphorylation site. More recently it has been acknowledged that alcohol may cause stimulation and euphoria, most notably when there is a rapid increase in blood alcohol levels, and these effects may be highly reinforcing. Its anaesthetic qualities are mediated through NMDA receptor inhibition and the resulting disruption of long-term potentiation is thought to underlie its amnestic effects. The acute administration of alcohol leads to reduced activation of the NMDA receptor by the excitatory transmitter glutamate. With chronic administration upregulation occurs and the associated toxicity may result in increased neuronal excitability on withdrawal. Alcohol acutely potentiates the effect of GABA, but chronically leads to downregulation through reduced receptor sensitivity. The precise neurochemical basis for withdrawal phenomena is difficult to ascertain, though withdrawal seizures are thought to be due to changes in unopposed GABA and NMDA activity, reflecting the general increase in neuronal excitability that is seen on withdrawal. This explains the rationale for using benzodiazepines in the management of alcohol withdrawal. Alcohol-related physical problems Those who consume alcohol at or below recommended levels show lower mortality than either lifelong abstainers and heavy users (Jshaped curve), with consumption of between 1 and 3 units per day protective against coronary heart disease (effect mediated through increased levels of HDL). Susceptibility increases with age, female sex, total consumption and pattern of use (constant heavy drinking > binge drinking). Acute intoxication Initially associated with mild euphoria, increasing doses lead to sedation and incoordination, with risk of accidental injury. In some, intoxication precipitates hypoglycaemia and may cause metabolic acidosis. Death
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from alcohol poisoning is rare and tends to occur in compromised individuals or those who have taken other substances concurrently. Methanol poisoning Fortunately methanol is rarely ingested, because methanol poisoning has a mortality rate of 20 per cent mediated through its metabolites, formaldehyde and formate. It causes confusion, ataxia and visual disturbance and may cause optic atrophy and necrosis of the putamen. Ethyl alcohol is used therapeutically in its treatment. Gastrointestinal tract Oesophagitis and reflux. Gastritis and ulceration anywhere in tract. Mallory-Weiss tears (causes haematemesis on retching). Oesphageal varices (15-20 per cent mortality). Pancreatitis (may be chronic with malabsorption). Portal hypertension. Carcinoma of tongue, pharynx, larynx, oesophagus, colon, rectum and liver. Liver • Alcoholic hepatitis. Acute inflammation consequent upon heavy drinking. Reversible with abstinence. Mortality of 10 per cent. Fatty liver. Alcoholic hepatitis. Alcoholic cirrhosis (in 10-20 per cent). Haemachromatosis in those with genetic susceptibility. Hepatic encephalopathy. Cardiovascular • Arrhythmias: atrialfibrillationand ventricular extrasystoles. • Dilated cardiomyopathy. • Coronary and cerebrovascular disease • Hypertension, important especially in young males. Metabolic Hypoglycaemia (fasting or reactive). Ketoacidosis. Hypertriglyceridaemia. Hypomagnesiumaemia. Hyperuricaemia.
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Endocrine and reproductive • Hypercortisolaemia with non-suppression on the dexamethasone suppression test. A 'pseudo-Cushings' picture may be seen, though it tends to resolve on abstinence. • Hypogonadism with testicular atrophy, infertility, decrease libido and impotence. Musculoskeletal • Muscular: proximal myopathy with or without myositis, Dupytren's contracture, gout. • Bony: avascular necrosis, osteoporosis. Healed rib fractures on X-ray are a marker for alcoholism. Haematological • Anaemia - iron, B12 or folate deficient. • Thrombocytopenia. • Disordered clotting. Respiratory • Tuberculosis. • Pneumonia. • Bronchiectasis. Dermatological Spider naevi. Palmar erythema. Acne rosacea. Discoid eczema. Worsening of psoriasis. Neurological
Wernicke-Korsakoff syndrome This is characterized by persistent, prominent impairment of recent memory and thus new learning (may affect remote as well), while immediate recall and procedural memory are preserved. Disturbances in time sense and ordering are common, though other cognitive functions are unimpaired. The main feature is that memory loss is out of proportion to cognitive loss and new learning is impaired.
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Pathology Alcohol reduces the absorption of thiamine and th6.activity of the enzyme that converts it to an active form. The subsequent neurological damage is focused in the brain stem, wall of the third and floor of the fourth ventricle, periaqeductal grey, part of the thalamus, the mammillary bodies, the terminal portion of the fornices and the anterior lobe and superior vermis of the cerebellum. Microscopically, myelinated fibres are affected more than neurons, and petechial haemorrhages, with astrocytic and histiocytic proliferation, dominate the microscopic picture. Clinical features ofWernicke's encephalopathy Acute onset (may be over days). Prodromal nausea, anorexia, vomiting. Nystagmus. Abducens and conjugate gaze palsies (90 per cent). Ataxia of gait (90 per cent). Peripheral neuropathy (80 per cent). Clouding of consciousness with disorientation. Lethargy and hypotension. Misidentification. Decreased spontaneous activity and speech. Memory problems (confabulation usually occurs later). Emotional lability. Anxiety, insomnia, fear of the dark. Signs of malnutrition: angular stomatitis, glossitis, dry skin, etc. Abstinence syndrome occurs in 15 per cent with fits and DTs. EEC shows diffuse slowing. CSF: mild rise in protein. Pyruvate levels raised in blood. Clinical features of Korsakoff's syndrome Korsakoff's syndrome may be defined as 'an abnormal mental state in which memory and learning are affected out of all proportion to other cognitive functions, in an otherwise alert and responsive subject'. It is differentiated from bilateral temporal lobe excision by the absence of disturbed social behaviour and emotional and intellectual decline, that characterizes Korsakoff's. Features include: Apathy and reduced initiative. Loss of interest in alcohol. Thinking is stereotyped, perseverative and facile. Reduced ability to categorize and form concepts. Visuospatial impairment is common. Underestimate age and time in hospital. Reduced insight and confabulation.
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• Impairment of new learning. • Variable retrograde amnesia. • Procedural memory and digit span intact. Causes of Korsakoff's syndrome are as follows: cancer of the upper gastrointestinal tract; malabsorption or malnutrition; heavy metal poisoning; carbon monoxide poisoning; tumours of the third ventricle; head injury; bilateral hippocampal destruction; anaesthetic agents. Imaging in Korsakoff's syndrome CT shows frontal lobe atrophy in one-third and convolutional atrophy in quarter of cases. The EEG shows diffuse slowing (in contrast to DTs).
Prognosis In Victor's classic 1971 study of 245 patients, the following conclusions were reached: 17 per cent died in the acute phase; 16 per cent presented with Korsakoff's syndrome; sixth nerve palsies always recovered; 66 per cent had residual horizontal nystagmus; of the 186 who were followed up, a quarter showed a complete recovery, half showed a partial recovery and a quarter showed no recovery; • women had a better prognosis.
Cerebellar degeneration The anterior lobe and superior vermis demonstrate Purkinje cell loss leading to ataxia of stance and gait.
Amblyopia With an onset over a matter of weeks, this retrobulbar neuritis, which is associated with peripheral neuropathy, rarely leads to blindness.
Marchiofava-Bignami syndrome This is characterized by ataxia, epilepsy, dysarthria and severely impaired consciousness. A slowly progressive form involves dementia and spastic paresis. The neuropathology is demyelination of the corpus callosum, optic tract and cerebellar peduncles.
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Central pontine myelinosis Clinically there is pseudobulbar palsy, quadriplegia and loss of pain sensation in the limbs and trunk. Acutely there may be nausea, vomiting, confusion and coma. Neuropathologically there is demyelination of pyramidal neurons in the pons.
Epilepsy This a common sequela of chronic alcohol abuse. The occurrence of seizures may arise consequent upon head injury or subdural or direct neurotoxicity with alcohol, itself being epileptogenic.
Dementia Mild cognitive deficits are common in alcoholics, particularly visuospatial, frontal and memory. Damage may be due to direct neurotoxicity, head trauma or nutritional deficiency and it would appear that women are more susceptible than men. CT and MRI studies show ventricular enlargement and cortical atrophy with some suggesting an association between degree of atrophy, and cognitive impairment. Abstinence may be associated with some reversibility in these structural changes. Alcohol-related psychological disorders The co-morbidity of alcohol misuse and other psychiatric syndromes is common, present in over two-thirds of dependents. The reasons for misuse often provide a clue to underlying psychopathology, most commonly depression and anxiety. Alcoholic hallucinosis These are auditory hallucinations, often in the third person, characteristically derogatory or command, that occur in clear consciousness. They may also take the form of fragments of conversation or music and there may be secondary delusions or perseveration. The symptoms may be highly distressing and may result in violent suicide. The onset is often associated with a reduction in dose or the precipitation of withdrawal and hallucinosis must be differentiated from delirium tremens, though they may appear as a continuation of hallucinations first experienced during this state. They may, however, arise in the current drinker. Visual hallucinations, although not typical, may occur. Affective disorders Up to 70 per cent of alcoholics complain of dysphoria during heavy drinking, with depression occurring in about 20 per cent. 80-90 per cent of depression was formerly thought to be secondary to alcohol use,
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with the diagnosis of alcoholism antedating that of affective disorder. However, recent large epidemiological studies suggested that a diagnosis of depression or anxiety was as likely to precede, as follow, the diagnosis of alcohol dependency. Certainly the incidence of depressive symptoms falls with abstinence, but careful assessment is required and treatment should be instituted if a primary diagnosis of depression is made, since untreated this may precipitate relapse. Alcohol may interfere with treatment efficacy and compliance, and consumption may rise during a manic episode in some with bipolar affective disorder. Depression may occur as a direct result of the pharmacological effects of alcohol as well as in response to the complications of alcohol use. Reasons for the association between alcohol dependence and depression may include common genetic factors especially in women, shared family environment, poverty, social isolation and unemployment or both conditions may develop as secondary features of other disorders such as personality disorder, polysubstance abuse and Briquet's syndrome. Suicide About a quarter of alcoholics attempt suicide, with a rate that is fourfold increased in men and 20-fold in women. Recent studies suggest a lifetime risk of suicide in alcoholics of 2-4 per cent (down from earlier reports of levels of 10-15 per cent). Pathological jealousy (Othello syndrome) This is characterized by the abnormal belief (delusion or overvalued idea) of infidelity of the sexual partner and is twice as common in men than women with alcohol problems. Anxiety states According to the 'anxiety reduction' theory, alcoholics self-medicate what otherwise might be disabling anxiety. One review concludes that 'anxiety traits do not appear to be an important causal factor in alcoholism.' However, in combination with learning theory it may be regarded as one route to alcohol abuse. Other neurotic disorders such as social phobia also predispose to alcohol abuse, although, as with anxiety, often alcohol is the cause of the problem, with prolonged abstinence often leading to symptom resolution. Eating disorders Up to 30 per cent of young women with a serious drinking problem have a significant eating disorder, while among those attending eating disorder clinics heavy drinking is overrepresented.
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Other drug use Dependence upon another drug is the commonest co-morbid disorder in someone with an existing dependence syndrome. Many alcoholics abuse other drugs, frequently prescribed sedatives such as benzodiazepines and chlormethiazole.
Alcohol-related social damage Family Heavy drinking imposes considerable strain on finances and is associated with increased rates of physical and sexual abuse. Children are at increased risk of juvenile delinquency and conduct disorder. The stability of marriage and family life is a predictor of a good outcome. Employment Absenteeism or turning up late may indicate alcohol problems. There is an increased risk of accidental injury as well as reduced productivity. Unemployment is high in this group and many workplaces provide education and screening of employees. Crime About two-thirds of male and one-fifth of female prisoners have serious drinking problems. About 70 per cent of habitual community criminals have drink problems, with legal problems most commonly for affray, driving offences and theft. Alcohol is also implicated in rapists (40-70 per cent), paedophile offences and in over half of both victims and perpetrators of violence. Drinking and driving Over three-quarters of fatal road traffic accidents involve alcohol. The peak age for drink-driving convictions is 21 years, with one-third of convictions in those aged 25 or under. The legal limit is 80 mg/100 ml, with urinary concentration 1.3 times that of blood.
Alcohol withdrawal This occurs following cessation (or reduction) of use in the dependent drinker. It usually begins between 6-24 hours after last use, peaks at days 2-3, with the highest risk of fits in the first 24-36 h (Table 16.4). Delirium tremens (DTs) occurs in about 5 per cent of withdrawals. It remains potentially fatal, although mortality rates are unclear, perhaps up to 10 per cent. Historically known as 'the horrors', the DTs peak on days 3-4 of withdrawal. Characterized by a dramatic and rapidly changing picture, the following may be seen:
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Early (12h) Middle (12-60h) Late (72h)
Sweating, tachycardia, tremor, nausea, anorexia and vomiting, anxiety and panic, insomnia and restlessness, transient auditory hallucinations Grand mal seizures (associated with low K+ and Mg2+, delirium tremens with misperception and hallucination Persistent insomnia and nightmares, tremor and confusion, hallucinosis
confusion and disorientation; clouding of consciousness; delusions and hallucinations; psychomotor agitation and autonomic dysfunction; perceptual disturbance and fear; insomnia and truncal ataxia electrolyte imbalance and dehydration are common; laboratory tests reveal leucocytosis and disordered LFTs; the EEG shows an increase in fast activity. Treatment regimen for medically-assisted withdrawal After a full history and examination, treatment of withdrawal should be implemented at the earliest point to minimize the risk of fits. Recommended are chlordiazepoxide (librium) and diazepam, with recent recommendations suggesting avoidance of chlormethiazole because of the risk of severe interactions (respiratory depression in overdose) and abuse liability. A starting dose of 40 mg chlordiazepoxide 6-hourly, in combination with close physical monitoring, allows for titration of dosage. Doses may need to be as high as 300 mg/day, but undertreatment of withdrawal is potentially more problematic than oversedation. Reduction in dose over 5-10 days is usually sufficient, although those with concurrrent benzodiazepine dependence will need longer. The concurrent administration of anticonvulsants in those prone to fits (history of epilepsy, withdrawal seizures, head injury) is used in some units, though drugs such as carbamazepine are unlikely to reach therapeutic levels during the peak time for fits. All patients should be given an intramuscular multivitamin preparation on admission and oral supplements, especially of the B group. Observation for intercurrent infection, dehydration and suicidal behaviour are important, especially in those with DTs, in whom low but adequate levels of stimulation should be given in a side room with frequent review. Indications for inpatient detoxification are as follows: • past history of withdrawal seizures or epilepsy;
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co-morbid severe mental or physical illness; elderly/frail; intercurrent acute illness; failed outpatient attempts.
Post-detoxification Detoxification is a prerequisite for abstinence. Only a careful psychosocial history with informant corroboration can allow suitable aftercare provision. The assessment and provision of care should be multidisciplinary with continued liaison between referrer, aftercare providers and GPs. Pharmacotherapy Drug treatments have been diverse and even bizarre at times, with LSD once a highly regarded candidate. The main drugs currently in use are disulfiram, naltrexone and acamprosate. The effects of disulfiram (Antabuse) may be explained by both classical and operant learning theories as well as cue exposure with response prevention. Starting with 3 or 4 days' loading dose of about 600800mg/day, the usual maintenance dose is 200 mg. Consumption of alcohol by the client will lead to the dilsulfiram-ethanol reaction, with flushing, tachycardia, dyspnoea, headaches, nausea and vomiting, owing to the accumulation of acetaldehyde. Provided that consumption ceases these symptoms will abate. Continued consumption may, however, lead to hypotensive episodes and even myocardial infarction. Prescription should not be unsupervised and regular review in clinic is mandatory to assess progress and occurrence of side effects. It is generally most useful in highly motivated groups and where administration may be assisted by a wife or friend. The most favourable outcome is seen in those who are male, older, have severe dependence, and have fewer psychological problems and stable social support. Continued compliance may be a problem, but attempts in some centres to use implants have been unsuccessful. Naltrexone and acamprosate are so-called 'anti-craving' drugs. High dropout rates, recruitment bias, difficulty in the double blind as well as different outcome criteria and length of follow-up make research into these drugs very difficult. Naltrexone is an opiate receptor antagonist and is thought to negate the euphoria associated with alcohol and is als'o thought to reduce craving. Studies have found a positive effect: in one study the relapse at 12 weeks was 23 per cent in the active group and 54 per cent in the placebo arm. Another found that, although effects on abstinence continued for only 2 months once off treatment,
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there were further reductions in symptoms of dependence and heavy episodes of drinking. Acamprosate (calcium bis acetyl homotaurine) is a synthetic GAB A analogue. Trials suggest a small but positive effect, with evidence of a dose-related response.
Psychological interventions Relapse prevention, motivational interviewing, cue-exposure with response prevention, social skills training, relaxation techniques and cognitive behavioural therapy (CBT) are all used in various form. Family therapy can be useful, especially in the supervision of drug administration.
Brief interventions Consisting of an empathic assessment of alcohol intake and pattern of use, feedback about personal risk and advice to reduce consumption with a menu of options for changing patterns of use, brief motivational interventions have consistently been shown to reduce intake in those drinking at harmful levels by 25 per cent. Further evidence suggests that brief interventions are as effective as more expensive specialist treatments. One study demonstrated no difference in abstinence rates at 2 years between groups receiving minimal intervention and those receiving more costly intensive therapies. However, the more intensive group did suffer less alcohol-related harm, especially regarding the family.
Alcoholics Anonymous Founded by recovering alcoholics 'Dr Bob' and 'Bill W in 1935, AA now represents the largest self-help group in the world, with 5-10 per cent of treatment-enlisted alcoholics attending. Based on 12 steps and the premise that alcoholism is a disease without cure that can only be held at bay a day at a time, AA provides friendship, advice and support; meetings are characterized by a diverse clientele and diverse locations. AA remains a cheap, widely available form of support. Residential rehabilitation houses are a popular though expensive means of consolidating upon initial abstinence. Often based on the 'Minnesota model' (first 5 steps of the 12 AA steps), additional interventions provided may include social skills training, relaxation techniques, anxiety management and structured relapse prevention programmes.
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Provision of service Services should be integrated and multimodal. Assessment of catchment area needs by case register or audit studies allow service providers and purchasers to have at least some common ground in the fraught issue of resource allocation for specialist services. Liaison with liver and obstetric units may prove particularly useful.
Prognosis A poor prognosis is associated with alcoholic brain damage, comorbid psychiatric disorder, divorced status, criminal record, low IQ and poor support and motivation. One multicentre trial, with an 18-month follow-up, showed that only a quarter of patients remained abstinent for 6 months, and less than 10 per cent for 18 months. However, there was a persistent reduction in consumption in over 70 per cent at followup. One follow-up of alcoholics over 10 years found that 25 per cent had continued troubled drinking and 12 per cent were abstinent. The remaining had a patchwork of abstinence and troubled drinking.
Reading list Besson, J.A.O. (1993) Structural and functional brain imaging in alcoholism and drug use. Current Opinion in Psychiatry, 6, 403-10. Edwards, Marshall, E.J. and Cook, C.C. (1998) The Treatment of Drinking Problems: A Guide for the Helping Professions. Cambridge: Cambridge University Press. Goddard, E. (1991) Drinking in England and Wales in the late 1980s. London: HMSO. Hall, W. and Farrell, M. (1997) Comorbidity of mental disorders with substance abuse. British Journal of Psychiatry, 171, 4-5. Litten, R.Z. and Allen, J.P. (1999) Medications for alcohol, illicit drug, and tobacco dependence. Journal of Substance Abuse and Treatment, 16, 105-12. Littleton, J. and Little, H. (1994) Current concepts of ethanol dependence. Addiction, 89, 1397-412. Miller, W.R. (1992) Effectiveness of treatment for substance abuse: reasons for optimism. Journal of Substance Abuse Treatment, 9, 93-102. Moncrieff, J. and Drummond, C. (1997) New treatments for alcohol problems: a critical appraisal. Addiction, 92, 939-47. Reiger, D.A., Farmer, M.E., Rae, D.S. et al. (1991) Co-morbidity of mental disorders with alcohol and other drug abuse: results from the epidemiological catchment area (EGA) study. Journal of the American Medical Association, 264, 5-11. Wallace, P. and Haines, A. (1985) The use of a questionnaire in general practice to increase the recognition of patients with excessive alcohol use. British Medical Journal, 290, 1949-53.
17
Substance misuse ADAM WINSTOCK and ANDREW JOHNS
Definitions Problems associated with substance abuse are categorized in ICD-10 under the heading 'Mental and behavioural disorders due to psychoactive substance abuse'. Categories include acute intoxication, harmful use, dependence syndrome, psychotic state, amnesic syndrome and withdrawal. Diagnostic guidelines for dependence syndrome suggest that at least three or more of the following have been present together at some time during the previous year: • a strong desire or sense of compulsion to take the substance; • difficulties in controlling substance-taking behaviour in terms of its onset, termination, or levels of use; • a physiological withdrawal state; • evidence of tolerance; • progressive neglect of alternative interests or pleasures; • persisting with substance abuse despite clear evidence of overtly harmful consequences.
Tolerance and neuroadaptation Continued administration of a psychoactive drug may lead to changes at three main levels: receptor (up- or downregulation through decreased expression or affinity); transmitter (increased or decreased release); and metabolism (e.g. enzyme induction or inhibition). The first two types of change may be regarded as neuroadaptation, their consequences leading to the development of tolerance. Pharmacodynamic tolerance is present when higher doses of the drug are needed to produce a given response. Metabolic tolerance is the increased capacity to metabolize a drug. Cross-
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tolerance occurs when tolerance to a drug is accompanied by tolerance to those of a different chemical group (e.g. alcohol and benzodiazepines). Dependence and withdrawal Some of the changes outlined above also mediate the processes of craving, relapse and dependence. Most commonly the reinforcing properties of drugs of addiction are mediated through the limbic (ventrotegmental) dopaminergic pathway, which projects to the ventral striatum, with the nucleus accumbens as pivotal. On stopping the drug the neuroadaptive response to chronic administration is then unopposed, and the syndrome of withdrawal ensues. Prevalence of substance abuse. The 1996 OPCS survey of psychiatric morbidity in the UK population showed the prevalence of substance abuse to be 4.7 per cent for alcohol dependence and 2.2 per cent for drug dependence. Slightly higher rates are suggested by American data with the 1991 EGA study giving lifetime prevalences as 6.1 per cent for substance abuse disorder, 13.5 per cent for alcohol abuse, 3.2 per cent for co-morbid substance abuse and other mental disorder, with male to female ratios of 2:1 for alcohol and 4:1 for substance use disorders. Unsurprisingly, rates tend to be higher in the inner cities, and in the young and unemployed, and are greatly affected by cultural and geographical variables. Aetiology
Drug factors The precise constellation of the perceived subjective effects of different drugs clearly shows wide interpersonal variation. Drug class, purity and especially route of administration have marked effect upon the reinforcing potential of the use of drugs. As the dose of a drug increases, the role of the environment in drug effect becomes less noticeable, while the pharmacologically mediated roles of arousal or sedation become more marked. Genetics Estimates of the contribution of genetics to drug dependence vary between 30 per cent and 70 per cent. It has been suggested that certain D2 polymorphisms coding for the dopamine receptor may underlie vulnerability to substance dependence. Other neurotransmitter systems have been implicated such as 5-HT, opiates and GAB A.
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Personality The concept of an addictive personality is not currently in vogue, though there are doubtless certain personality traits that may predispose to or otherwise associate with drug use. For example, both dissocial personality disorders and borderline personality disorders are associated with substance misuse, though the direction and nature of causality is unclear. Other personality traits such as low impulse control or adventurousness may increase one's substance abuse liability. For example, Cloniger suggests that those who are high in novelty-seeking and low in harm avoidance may be more prone to substance misuse. It is important to note that the effect of a drug on a given individual will depend upon the interplay of cognitive 'set' (mood state the person was in at the time of drug consumption) and environmental setting, as well as the dose and type and purity of drug. Hence expectations and past experience will also affect drug use and such an understanding helps explain the notion of self-medication. Psychological models Operant and classical conditioning as well as observational (modelling) learning have all been used to explain the patterns of drug use observed, especially withdrawal avoidance through repeated use. The reinforcing effects of drugs will vary both between users and drug type. Psychoanalytic models have also suggested route of administration as an important clue to aetiology (oral fixation), while the self-destructive behaviours associated with drug dependence may be seen as a parallel to the death instinct. Social Social deprivation, peer group influence, familial drug use, cultural attitudes and drug availability should all be considered in evaluating the aetiology of drug use in an individual. Dual diagnosis This is defined as having concurrent diagnoses of a severe mental illness and substance abuse or dependence. This group has higher relapse rates with more hospitalizations, poorer compliance with medication, relative neuroleptic unresponsiveness, as well as having higher rates of both forensic contact and homelessness. Unfortunately they are a difficult group to engage and maintain contact with; in the USA this has prompted the development of small case load, assertive outreach, and dual diagnosis teams, which, although limited in size and time frame, suggest a possible service response.
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Taking a drug history • Current drug usage. Types, amount, route of administration, effects sought and current social context and treatment status. • Typical day. Time after waking of first use. High-risk behaviours, crime, withdrawal, intoxication. Daily expenditure on drugs. • Other drugs used. Enquire specifically about all classes, especially alcohol, and methadone. • Drug usage history. Age first used, injecting behaviour (can inject most drugs, cocaine, amphetamine, benzodiazepines, 'Ecstasy', alcohol). • Past treatments. Types: inpatient or outpatient. Duration. Chemically assisted or not. Post-detoxification follow-up. • Duration of abstinent periods. Circumstances of relapse.
Physical examination Acute intoxication (see Table 17.1) Table 17.1 Drug Cannabis Opiate 'Ecstasy' Glue
Signs of acute intoxication
Pupil size
Light reflex
Mouth
Conjunctiva
Coordination
Dry
Injected
Small Big Big
Sluggish Reduced Sluggish Sluggish
Decreased Decreased Decreased Decreased
Dry Rash
Chronic intoxication Track marks or abscesses from intravenous use, liver signs, peripheral neuropathy, cerebellar syndrome and signs of HIV.
Investigations Urine screens Self-reported use needs confirmation by laboratory testing, most commonly urine. Supervised urines are sometimes appropriate, since false negatives can arise through dilution or contamination of samples. The time windows for detection after last use of commonly used illicit substances are given in Table 17.2. Table 17.2
Detection of drug use
Drug
Detection window after use
Cannabis Heroin Methadone Stimulants
3 days-6 weeks 2-3 days 7 days 1-3 days
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Viral tests Among injecting drug users the risk of HIV transmission is high and routine testing should be available, with counselling to those at risk. Rates among users show wide geographic variation reflecting differing injecting patterns, but in Europe at least, intravenous drug users will soon form the largest group of AIDS cases of any population group. Rates of hepatitis B and C are much higher among injecting populations than HIV, with studies showing rates of 70 per cent for hepatitis C and 20-40 per cent for hepatitis B infection. Drug classification
Opiates: (opium, heroin, methadone, buprenorphine) Opium is derived from the ripe seed capsule of the poppy, Papaver somniferum. The extract contains about 15 per cent morphine and 5 per cent codeine by weight. These are alkaloid opiate analgesics. Heroin (diamorphine), dihydrocodeine and pholcodine are semisynthetic congeners of morphine, while pethidine and methadone are non-opiate morphine-like analgesics. Street purity varies widely (usually 30-60 per cent) and cost about £60-80/g. Daily consumption is commonly in the region of 0.25-1 g.
Mode of action Opiates mimic the effect of endogenous opiates such as enkephalins by binding to a group of specific peptide receptors in both the central and peripheral nervous systems (GI tract). There are four main types of receptor (mu, kappa, delta and sigma), of which the mu and kappa receptors are important in mediating abuse and dependence.
Method of administration Most heroin users climb the ladder of routes, which yield increasing bioavailabilty and speed of onset of the effect as one progresses from snorting intranasally, smoking ('chasing the dragon'), subcutaneous 'skin popping' to intravenous use. Different types of heroin are preferentially used for different routes of administration, which themselves are markedly influenced by cultural bias.
Metabolism Diamorphine and morphine are both extensively metabolized in the liver, with only 25 per cent bioavailability after oral administration. Diamorphine (tl/2 (half-life) 2min) is rapidly metabolized to morphine (tl/2 3 h), which is then further metabolized before excretion in the urine.
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Epidemiology Until recently the Home Office Addicts Index was the main national data source on registered opiate misuse in the UK and was used as an indicator of the prevalence of heroin abuse in the UK. Regional drug misuse databases have now replaced this system, but it remains difficult to estimate the true prevalence of injecting drug use and estimates for the prevalence of heroin use suggest a figure of less than 1 per cent. Taking all surveys together it appears that males outnumber females 3:1, with most new addicts being aged in their 20s.
Effects There is a multiplicity of effects mediated at different CNS sites through different receptors. They include: analgesia; drowsiness and sleep; mood change - euphoria/intense pleasure; respiratory depression; cough reflex suppression; sensitization of the labyrinth with nausea and vomiting; decreased sympathetic outflow (bradycardia and hypotension); lowering of body temperature; pupillary constriction.
Withdrawal The syndrome appears within 4-12 h, peaks at 48 h, subsiding by the end of 7-10 days. Symptoms include dysphoria, aching muscles and joints, increased sweating with goose-fleshing of the skin (hence 'cold turkey' or 'clucking'), diarrhoea, tearing, dilated pupils, shivering, yawning and fatigue. Insomnia (with increase in REM sleep) and craving for the drug may persist for weeks. Though uncomfortable, opiate withdrawal is not life-threatening in the same way as alcohol withdrawal may be.
Physical complications • Infection. Hepatitis and HIV; septicaemia and bacterial endocarditis (tricuspid valve); pneumonia, TB; skin abscesses and osteomyelitis. • cardiorespiratory. Pulmonary oedema, aspiration, pneumothorax and cardiac arrhythmias. • Renal. Rhabdomyolysis and membranous nephropathy. • Neurological. Transverse myelitis, peripheral neuropathy, brain abscess and myopathy. The annual mortality for opiate dependent users is 1-2 per cent, most commonly from overdose.
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Psychiatric co-morbidity Seventy per cent of addicts meet diagnostic criteria for a current psychiatric disorder, the commonest being depression, antisocial personality and alcohol dependency. Such diagnoses may be primary or secondary to opiate abuse and a careful assessment of mental state and social functioning when opiate free should be performed.
Social consequences Criminal conviction rates are high (70-80 per cent) with yearly rates of imprisonment being about 2 per cent. About 60 per cent are for non-drug-related offences and 20 per cent are for crimes of violence. Stabilization on methadone or abstinence from opiates is associated with a reduction in associated crime.
Synthetic opiates Methadone A synthetic opiate first produced in Germany around the time of World War I. May be taken orally or intravenously. It has a longer half-life than heroin (24-36 h) and can thus be given once or twice daily, and is the mainstay of treatment for heroin dependency in the Western world. A steady-state plasma level is reached within 3-4 days and provides a reasonably stable level of opiate receptor blockade. It does not produce a 'high' and for this reason many of those on methadone maintenance scripts use additional illicit opiates. Buprenorphine (Temgesic) This is a partial opiate agonist. Used medically as an analgesic (usually sublingually), it has abuse potential and may be injected. Overdose is less likely and in some centres it is used in treatment.
Management of opiate dependence Pharmacological management Patients may withdraw on a methadone mixture (usually linctus) over 10-21 days or be maintained on it for a longer period. Forty milligrams of 1 mg/ml mixture is approximately equivalent to 0.5 g of street heroin. Consult the most recent Department of Health guidelines (Drug Misuse and Dependency - Guidelines on Clinical Management 1999) when prescribing methadone for stabilization or withdrawal. The breakdown products of methadone may be detected separately from those of heroin in the urine, allowing non-prescribed opiate use to be identified. Studies would suggest that a minimum effective dose of about 60 mg daily is required to optimize the benefit from maintenance treatment and in
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many users significantly higher doses will be used (usual range 40lOOmg/day). Other means of opiate detoxification include the use of clonidine or lofexidine to reduce the noradrenergic hyperactivity that underpins the withdrawal syndrome. It should be considered as the preferred nonopiate method of assisting opiate withdrawal and can be safely used on an outpatient basis. In some centres withdrawal is precipitated with the long-acting opiate antagonist naltrexone, while symptomatic relief is given with clonidine and benzodiazepines. In others, this precipitant withdrawal is speeded up and the whole process takes place with the addict under general anaesthetic for periods of 24 h, but there are considerable reservations as to the efficacy and risks of this approach. Psychological management There are numerous approaches from cognitive behaviour therapy (CBT) to relapse prevention to psychotherapy (individual, family and group). Recently, motivational interviewing has become increasingly widespread. Based upon psychological theories such as Festinger's 'cognitive dissonance', it aims to move the client along a 'cycle of change' from precontemplator (no interest in changing current using behaviour) to contemplator and then determination and action. Movement in the desired direction is brought about by focused interview which attempts to let the user become aware of some dissonance between their drugusing behaviours and their own aims or desires. Once ambivalence has been reached, then the ways that support change are introduced. Physical management Good primary health care, ensuring adequate nutrition, contraception, screening and check-up facilities, should be readily accessible. Social management Educating the drug user about safe practices and harm-reduction techniques is important, as is appropriate liaison with other involved agencies such as social services or voluntary sector supports. Therapeutic communities and 'concept houses', based on a religious or abstinent theme, offer longer term care.
Outcome Regarding treatment contact samples, it is clear that longer treatment contacts are associated with better outcomes. Pretreatment levels of psychopathology are also related to outcome, with high-severity patients doing poorly. Suicide and accidental overdose account for between onethird and a half of all deaths of opiate addicts, with annual mortality running between 1 per cent and 2 per cent, with an excess mortality
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ratio of about 12. Long-term follow-up studies suggest that eventual cessation of opiate use is a very slow process and becomes increasingly unlikely if use continues into their late 30s. Stimulants (amphetamines, cocaine, MDMA - 'Ecstasy')
Amphetamine sulphate ('Speed', 'Whizz') Structurally similar to dopamine, amphetamines are synthetic sympathomimetic drugs. Stimulant amphetamines such as D-amphetamine and methyl amphetamine release dopamine from most brain regions. Illicit amphetamine is often of very low purity (5 per cent) and costs approximately £10-15/g. It can be taken orally, intranasally route or by injection. Prescribable stimulants such as methylphenidate (Ritalin) and diethylpropion (Tenuate) are also open to abuse. Dexamphetamine's half-life is about lOh. Effects
Euphoria, a sense of being filled with energy and being alert, combined with anorexia and verbosity, produce the characteristic pattern of the desired effects after use of the drug. However, not uncommonly unpleasant symptoms supervene such as anxiety and irritability, panic, repetitive behaviours, paranoia and hallucinations. A picture indistinguishable from paranoid schizophrenia may also be seen. Physically the stimulant properties are dose dependent and are characterized by sympathetic overdrive: tachycardia and a raised BP, mydriasis, sweating, dry mouth, tremor and blurred vision. Such a picture could be confused with that of opiate withdrawal.
Tolerance Tolerance does develop and there is now a recognized withdrawal syndrome following cessation of chronic use, characterized by dysphoria, irritability, fatigue, anhedonia, anxiety, hyperphagia and rebound REM sleep disturbance and a desire to reinstate use (craving). Management There is only a limited role for the use of adjunctive pharmacotherapy for the treatment of the amphetamine-dependent user. In a very few centres amphetamines are prescribed, but generally this is not widespread.
Cocaine ('Charlie', 'Coke', 'Snow') Cocaine is among the most reinforcing of the drugs of abuse, with 10-15 per cent of those who ever try it, going on to be cocaine abusers. Cocaine is the major alkaloid constituent of the Andean bush Erythroxylon coca.
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It was chewed by the indigenous people of Peru who thought it was a gift from God. Even Freud was influenced by the subtle euphoria and multiple physiological effects of cocaine, recommending it as a panacea for all ills, from altitude sickness to syphilis. Mechanism of action Its mechanism of action is through the inhibition of presynaptic reuptake of dopamine (and serotonin) and like other drugs of dependence its reinforcing mechanism is thought to lie in the dopaminergic ventrotegmental and mesolimbic systems. Its half-life is about 50 min, though depending upon the route of administration the subjective effects can be as short-lived as a few minutes. Method of administration Intranasal use is probably still the major route of administration, rendering a bioavailability of about 30 per cent. Intravenous use either alone or in combination with heroin ('Speedball') has a high associated mortality, while smoking the freed alkaloid base ('Crack') is common in some inner cities in the UK. Toxicity Toxicity may occur, presenting with sympathetic overdrive (hyperthermia, tachycardia, hypertension and severe agitation). Severe cardiac problems have also been described, including multiple arrhythmias, congestive failure, ischaemia and myocarditis. Pulmonary problems, including haemoptysis, oedema, respiratory failure and so-called 'Crack lung' have also been reported in connection with cocaine smoking. Cocaine is also epileptogenic and may provoke a generalized seizure after a single dose. Dependence Cocaine use may be occasional or develop into compulsive uncontrolled binges that characterize the heavy user. As with other drugs, severity of dependence is accompanied by a shift to higher bioavailability routes, such as smoking 'crack' cocaine. Withdrawal Since the late 1980s a withdrawal syndrome following cessation of cocaine use has been well described. There are three phases: crash, withdrawal and return. The 'crash' is the acute withdrawal, characterized by the opposite of the stimulant high, with low mood, anxiety and hypersomnia and relatively little desire to take cocaine. After three or four days the intermediate phase with prolonged and fluctuating low mood, irritability, low energy and appetite begin and this stage is accompanied by more severe craving. After 2-3 weeks a return to
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baseline mood occurs, though episodic and occasionally intense craving remains. Management Unfortunately there is no appropriate pharmacological intervention that parallels the use of methadone in the treatment of cocaine dependence. Detoxification from cocaine only requires abstinence, though the dysphoria of early withdrawal may lead to early relapse. Initial pharmacological support of the withdrawal is symptomatic with low-dose thioridazine, with more recent studies suggesting use of low-dose bromocriptine, which may help with depression and sleep disturbance. Many other pharmacological approaches have been suggested, including haloperidol, phenytoin, carbamazepine and desipramine. Recent work has indicated there might be role for the selective serotoninergic reuptake inhibitors such as fluoxetine.
MDMA ('Ecstasy') MDMA (3,4-methylenedioxymethamphetamine is an hallucinogenic amphetamine. Often incorrectly termed a designer drug, it was patented by Merck Chemical Company in 1914 as an appetite suppressant. Now firmly associated with the 'rave' music scene, MDMA is now an accepted member of the psychoactive drug experimenter's formulary. Mechanism of action After neuronal uptake, MDMA promotes the calcium-dependent release of brain monoamines as well as inhibiting their uptake. Animal studies suggest that MDMA is selectively neurotoxic to fine serotinergic neurons, especially those arising from the dorsal raphe nucleus, though at higher doses it may also be toxic to dopaminergic terminals. Such chronic structural change may be associated with longer term sequelae in the areas of mood, cognition and memory. Method of administration Taken most commonly as a capsule or tablet and swallowed (may be injected or 'snorted') and costing about £10, the effects start after 3060 min and last 3-12 h. Effects Periodic intense 'rushes' have been described, in combination with a feeling of closeness to others, increased sensuality and being filled with energy. Adverse symptoms such as anxiety, panic and paranoia are not uncommon, and a range of psychiatric disorders from psychosis to neuroses and affective disorders have been described following its use. Often there is also nausea, reduced appetite and insomnia. Both auditory
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and visual hallucinations have been described, as have delusions and suicidal feelings while intoxicated. Less rarely, severe physical complications arise. There have been over 50 'Ecstasy'-related deaths in the last 10 years. Causes have included syndrome of inappropriate ADH secretion (SIADH), which in combination with excessive attempts for the user to rehydrate themselves, has led to cerebral oedema. Hepatocellular necrosis with jaundice, neuroleptic malignant syndrome, subarachnoid haemorrhage and renal failure with rhabdomyolosis have all been reported. Khat This stimulant shrub, indigenous to the Yemen and surrounding areas, is becoming increasingly recognized as a problem in Somali and other immigrant communities. The active component cathionine has effects similar to other psychoactive stimulants. The bitter leaves are chewed and an amphetamine-like psychosis may arise. Phencyclidine ('Angel dust', POP) and ketamine Originally designed as a dissociative anaesthetic in veterinary practice, in humans PCP causes delirium, nightmares and hallucinations. Both cause analgesia, amnesia and eventually anaesthesia, as well as their stimulant and hallucinogenic effects. Aggression has been reported, but is often not recalled due to the marked amnestic qualities of the drug. Rigidity, convulsions and coma may also arise. Effects last 3-6 h, with a half-life of up to 3 days. Tolerance does arise and a mild withdrawal syndrome has been described. Benzodiazepines For details on the pharmacology of benzodiazepines see Chapters 4 and 29. Problems related to benzodiazepine dependence and withdrawal (see Table 17.3) were first highlighted in 1981. Onset occurs 2-3 days Table 17.3
Symptoms of benzodiazepine withdrawal
Physical
Psychological
Perceptual
Nausea, anorexia, sweating Flu-like symptoms
Anxiety, dysphoria
Hyperacuity to sound, light and smell Abnormal sense of body sway Metallic taste in mouth
Muscle tension, twitching and fasciculation Tremor, palpitations Convulsions may occur (days 5-7)
Insomia with rebound REM (nightmares) Depersonalization and derealization Rarely psychosis and delirium Restless, irritable with poor concentration
Visual disturbance and hallucinations Other abnormal bodily sensations
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after stopping, being maximum on days 7-10, usually abating by the end of the second week. Figures suggest that after 6 months between 20 per cent and 45 per cent of regular users will become dependent. Withdrawal should be carried out in steps until symptoms abate over 4-6 weeks. Dependency on shorter half-life benzodiazepines, such as lorazepam, may be managed by stabilizing the patient on an equivalent dose of diazepam before attempting withdrawal. Barbiturates These synthetic sedatives have become less popular since the introduction of benzodiazepines, which have less abuse potential and overdose toxicity than their predecessors. Once popular drugs of abuse, their intravenous usage was noted for its high associated mortality, particularly through arrest and respiratory depression. Preparations include phenobarbitone, amylobarbitone and secobarbital. Tolerance arises through enzyme auto-induction and there is therefore cross-tolerance to alcohol with a withdrawal syndrome not dissimilar to alcohol. Withdrawal should involve a tapering off of the drug by 10 per cent daily decrements. This may be done as an inpatient or outpatient depending on risk of severe withdrawal and fits (risk related to daily dependent dose). Cannabis Of the several hundred substances within the Cannabis sativa plant extract, delta-9 tetrahydrocannabinol (THC) represents the major psychoactive constituent. Acting on recently identified endogenous receptors, some of its effects are mediated through the same dopaminergic reward pathways as cocaine. Preparations vary in form and potency. Cannabis resin has a THC content of about 3-6 per cent and is commonly smoked in a 'joint' with tobacco. Herbal preparations (marijuana) vary widely in THC content, with a new hybrid breed of high potency ''skunk grass''.
Method of administration It may be taken in a variety of ways, most commonly smoked, often with tobacco; it may also be taken orally with food or in a herbal effusion ('ganja tea'}.
Effects Effects occur rapidly after inhalation and last 1-6 h. Physically it results in conjunctival injection, tachycardia, a rise in blood pressure and bronchodilatation. Increased appetite and a relaxed, mellow and sedating tendency are common, along with enhanced perceptual awareness and mild sensory distortion.
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Psychological complications Panic attacks, paranoia, depersonalization, derealization, hallucinations and psychotic episodes have all been reported with acute intoxication, though the current view is that there is no distinct psychopathological entity known as 'cannabis psychosis'. Patients with schizophrenia who use cannabis tend to have more positive features with less blunting and withdrawal. However, their prognosis is worse, with non-compliance and frequent relapses and readmissions. Dependence on cannabis occurs in about 10 per cent of regular users. A study of Swedish male conscripts showed a marked and linear association with use and risk of later developing schizophrenia, though the study and conclusions have been weakened with scrutiny. Hallucinogens (lysergic acid diethylamide, and mescaline) Lysergic acid diethylchloride (LSD) was discovered in 1943 and has remained popular as a drug of abuse (but not dependence) since the 1960s. It has found a new audience with the rave drug scene. The drug is usually absorbed onto a tab of blotting paper and taken orally. Doses as low as 20-50 /ig cause marked perceptual distortion with visual illusions and hallucinations, without any associated lowering of consciousness. Effects start after 30-90 min and may last 3-12 h or more. The half-life is 3 h.
Mechanism of action The serotinergic system mediates most the effects of LSD. Hallucinogenic effects are mediated through activation of the 5-HT2 receptor, with effects selectively antagonized by ritanserin. Tolerance occurs rapidly due to receptor densensitization, which is evident after three or four days of consecutive use. This explains why LSD is one of the few psychoactive drugs for which a dependence syndrome is not described.
Effects Marked perceptual changes, with an alteration in state of awareness and euphoria, are common. Visual (and less commonly auditory and other modality) hallucinations and distortions are frequently reported, as is the phenomenon of''synaesthesia' with loss of the normal boundaries between sensory modalities (e.g sounds are heard, colours seen). Sympathetic overactivity may help explain adverse symptoms such as anxiety and panic that are reported often with paranoid ideas (the so-called 'bad trip'}. Approximately 15 per cent of users report 'flashbacks'', a recurrence of experiences previously associated with LSD use, while the individual is drug free.
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Volatile substances The inhalation of volatile substances is commonly known as 'glue sniffing'. Cheap, easily and widely available, volatile substance abuse (VSA) continues to be common among UK teenagers. The range of abused compounds and the variety of preparations is vast (Table 17.4). It is important, as it is common and is responsible for about 100 deaths each year, with the modal age of death being 15 years. Studies suggest a prevalence of between 1 per cent and 10 per cent among secondary school children, with higher prevalences being associated with poverty and deprivation.
Method of administration Most commonly the substance will be placed in a bag, where the fumes are allowed to gather, before inhalation. Other solvents (trichloroethane) may be absorbed onto material such as clothing and inhaled. Aerosols may be inhaled directly or through rebreathing with a bag.
Effects The inhalation of these substances causes a rapid onset of emotional, perceptual and cognitive change lasting about 30 min, with hallucinations, a euphoric mood and an altered state of awareness. At higher doses ataxia, nystagmus, frightening hallucinations and confusion may occur, with the associated risks of accidental injury.
Complications Death may result from the induction of arrhthymias, respiratory depression, inhalation of vomitus and laryngeal spasm, with cardiac arrest secondary to vagal stimulation. Chronic use has been associated with a cerebellar syndrome, while inhalation of lead-containing petrol has been linked with cognitive decline. Liver damage and peripheral neuropathies have also been reported.
Table 17.4
Abused volatile substances
Type of product
Volatile constituent
Adhesives Aerosols Cleaning solvent products Fuel gases Inhalational anaesthetics
Toluene Propellant 11 and 12 Tetrachloroethylene n-butane, isobutane and propane Halothane and nitrous oxide
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Drugs and the law Mental Health Act 1983 This excludes drug or alcohol dependence from the definition of mental disorder. Compulsory admission is therefore not possible unless warranted by an abnormal mental state related to drug use. Misuse of Drugs Act 1971 Classes of controlled drugs are specified to perceived dangerousness, as follows: Class A. Opiates, cocaine, injectable class B Class B. Cannabis, codeine, amphetamines and barbiturates Class C. Dextropropoxyphene, benzodiazepines Reading list Andreasson, S., Allebeck, P., Engstrom, A. et al. (1987) Cannabis and schizophrenia: a longitudinal study of Swedish conscipts. Lancet, ii, 1483-6. Department of Health (1999) Drug Misuse and Dependence - Guidelines on Clinical Management. Freud, S. (1974) Uber Coca. In Cocaine Papers (ed. R. Byck). New York: Stonehill Publishing. Gossop, M., Marsden, J., Stewart, D. et al. (1997) The NTORS in the UK. Six month follow up outcomes. Psychology of Addictive Behaviours, 11(4), 324-37. Hall, W. and Solowij, N. (1997) Long term cannabis use and mental health. British Journal of Psychiatry, 171, 107-8. Henry, J.A., Jeffreys, K.J. and Dawlings, S. (1992) Toxicity and deaths from 3,4 methylenedioxymethamphetamine ('ecstasy'). Lancet, 340(8816), 384-7. Joseph, H. and Stimmel, B. (eds) (1997) The Neurobiology of Cocaine Addiction. Haworth: Medical Press. Leister, M., Grob, C., Bravo, G. and Walsh, R. (1992) Phenomenology and sequelae of 3,4 MDMA. Journal of Nervous and Mental Diseases, 180, 345-52. Lowinson, J.H., Ruiz, P., Millman, R.B. and Langrod, J.G. (1992) Substance Abuse: A Comprehensive Textbook. Baltimore: Williams & Wilkins. Miller, W.R. (1996) Motivational interviewing: research, practice and puzzles. Addictive Behaviour, 21(6), 835-42. Petersson, H. and Lader, M. (1984) Dependence on Tranquillisers. Oxford: Oxford University Press. Simpson, D., Joe, G. and Brown, B. (1997) Treatment retention and follow up outcomes in the drug abuse treatment outcomes study (DATOS). Psychology of Addictive Behaviours, 11(4), 294-307. Steele, T.D., McCann, U.D. and Ricaurte, G.A. (1994) Review: 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy'): pharmacology and toxicology in animals and humans. Addiction, 89, 539-51. Thornicroft, G. (1990) Cannabis: is there epidemiological evidence for an association with psychosis? British Journal of Psychiatry, 157, 25-33.
DO Suicide and deliberate self-harm TIM AMOS and LOUIS APPLEBY
Suicide Definition Suicide is a deliberate act of self-harm leading to death. Epidemiology There are approximately 400 000 suicides annually in the world. There is a wide variation between countries, reflecting probably both true suicide rates and the local determination and recording of suicides. From official figures, rates tend to be higher in the developed world, especially in European countries or in countries where a significant proportion of the population is of European origin. In Europe, the highest recorded rates are in Eastern Europe and Scandinavia. UK rates In England and Wales it is the responsibility of the coroner to determine the cause of death when there has been an unnatural death. Many will record a death as suicide only if there is strong evidence, particularly of intent, e.g. a suicide note. In England and Wales, suicide figures probably underestimate the incident of suicide by about 30 per cent and therefore open verdicts (deaths from external cause undetermined) are often included in official figures and in research. In Scotland and Northern Ireland, whether a death is suicide or not is determined by the government statistical agencies, who receive guidance from those who have investigated the deaths.
Incidence There are about 5000 suicides per year in England and Wales, with a further 500 in Scotland and Northern Ireland, representing about 1 per
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cent of total mortality. The overall annual rate is about 10 per 100000 population, but varies according to age, sex and geographical area. In the twentieth century, there have been rises in the suicide rate in the 1930s and 1980s, which were times of high unemployment, and falls during World Wars I and II. A third decrease in the 1960s has been associated with changes in the domestic gas supply from the coal gas to the less toxic natural gas. Since the 1970s the suicide rate has risen gradually, although this trend has reversed over the last 10 years.
Age and sex The ratio of men to women committing suicide is about 3:1. In England and Wales during the 1990s, the number of men taking their own lives has dropped from over 4000 to approximately 3700. In the same time period, the number of women has also decreased from about 1500 to around 1300. Suicide rates tend to increase with age, but in the last three decades the rate in young men has almost doubled while the rate in the elderly has decreased markedly. Consequently the rates for both younger men and older men is now similar. In young adults, suicide is now the leading cause of death.
Ethnicity Suicide rates among ethnic minorities tend to reflect rates in their country of origin. In England, therefore, the rate is relatively low among black and Asian people. Young Asian women, however, appear to be at higher risk than UK-born women.
Religion Lower rates in Southern Europe are said to reflect the predominance of Catholicism which condemns suicide. Rates in Muslim countries are low. Overall, Protestant and more secular societies tend to have higher reported rates.
Class and employment Suicide is now most common in socioeconomic class V. There used to be high rates in socioeconomic class I but this is less marked now, although many of the high-risk occupations are in the professional classes, e.g. vets, doctors, pharmacists and dentists. Farmers are also at high risk. All these occupations have relatively easy access to lethal means. Other high-risk occupations are linked to alcohol, e.g. bar staff. University students also appear to be at high risk. There is much evidence to link suicide and unemployment, but the exact nature of the association is complex; the case for direct causality has not been proved, and the mediating role of depression is unclear.
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Marital status People who are single, separated, divorced or widowed are at greater risk. Children seem to be protective.
Geography Regional and district differences occur in the UK, with the highest rates being associated with indices of deprivation.
Season The suicide rate tends to increase in the spring when the monthly rate is elevated by around 10 per cent. This rate is also seen in the spring months in the southern hemisphere.
Location About one-quarter of suicides have been in contact with specialist mental health services in the year before death. Five per cent of all suicides are current inpatients, although many of these are on leave. The number of prison suicides has risen in the last 20 years, mirroring increases in young men in the general population. Method The three most common methods of committing suicide in the UK are hanging, self-poisoning and carbon monoxide poisoning (mainly from car exhausts). These methods account for three-quarters of all suicides. Among other methods, the most common are jumping, drowning, suffocation and using firearms. There is a difference between the genders. The most common methods for men are hanging and car exhaust asphyxiation; for women, it is drug overdose. Certain methods are associated with specific groups, e.g. self-immolation in Asian women, hanging in ward-based patients and prisoners. Theories/aetiology Suicide appears to have occurred in all societies and at all ages, but attitudes to it have varied. Some cultures have seen it as an honourable response to disgrace; others have condemned it as immoral.
Social factors Durkheim's Suicide, published in 1897, demonstrated links between suicide and social factors. He suggested four main categories: altruistic suicide, committed for the benefit of others (includes politically motivated suicides); anomic suicide, by individuals living in a society lacking 'collective order'; egoistic suicide, by people with little or no integration
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with their social group; and fatalistic suicide, by individuals who feel hopeless because of over-regulation by their society. In general, social factors such as unemployment are probably the most important in determining suicide rates. In individuals, however, there are also psychological and biological factors which increase risk and may be targeted in prevention.
Psychological factors Analytic theories Freud considered suicide to be a conflict between wanting to kill a loved and hated object and the guilt of this desire. A simpler theory is that suicide results from internalized aggression.
Other psychological factors Both hopelessness and low self-esteem have been shown to be linked to suicide.
Biological factors Genetic theories An individual's risk of suicide is increased where there is a family history of suicide, though whether this is genetically determined is unknown. Evidence for genetic causation comes from both twin studies, which show that monozygotic twins have an increased concordance in comparison with dizygotic twins, and adoption studies, which show that there is a high rate of suicide in the biological parents of adoptees who commit suicide but not in their adoptive parents. It is not clear whether what is inherited is a vulnerability to mental illness or something more specific.
Biochemical theories Reduced serotonin metabolism has been found in the post-mortem brains and cerebrospinal fluid of those who have committed suicide. This is most likely to reflect general impulsivity rather than suicidal risk per se.
Medical factors Physical illness High rates have been reported in epilepsy, HIV infection, multiple sclerosis, neoplasms (especially head and neck cancer), peptic ulceration and renal dialysis. By comparison, the rates of suicide are low during pregnancy and in the first year after giving birth.
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Mental illness One of the strongest risk factors for suicide is mental illness. Psychological autopsy research, in which interviews are conducted with close family members and health professionals who knew the individual, suggests that up to 90 per cent of people who commit suicide are suffering from a mental disorder. Nearly all psychiatric disorders increase the risk of suicide and in the case of severe depression, alcoholism, schizophrenia and eating disorders the increase is up to 10-fold. There is also a strong association with deliberate self-harm (DSH) - most studies report that at least 50 per cent of suicides have a history of DSH.
Suicide in psychiatric patients Schizophrenia Five to 10 per cent of patients with schizophrenia will commit suicide. The factors which appear to increase the risk are demographic, e.g. being young and male, and mental state features such as depressed mood, suicidal ideas, hallucinations with a suicidal content, impulsive trait and clear insight. Affective disorders One influential review found the long-term risk of suicide in affective disorders to be 10-15 per cent, although more recent studies have suggested a lower figure. Risk is particularly associated with hopelessness, suicidal thoughts, anhedonia and poor concentration. Comorbid alcohol abuse is also likely to increase risk. Substance misuse Alcohol misuse is a major risk factor for suicide. The long-term rates are probably about 5-10 per cent, with risk being increased when there is a history of depression and a recent loss of a relationship or interpersonal conflict. Suicide rates among drug-dependent individuals are difficult to establish because many self-inflicted deaths are recorded as accidental. Neurotic disorders All neurotic disorders carry an increase risk of suicide, including phobic disorders, general anxiety and panic disorder. Risk tends to be associated with co-morbid personality disorder. Timing Suicide appears to be more likely in the first few years of an illness, although alcohol misuse may be an exception because risk appears to be greater after many years of misuse and its consequences. During an episode of illness, high-risk times are the beginning of the episode and during recovery. The first few months after discharge from hospital is a
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time of greatly increased risk, particularly in the first week immediately after discharge.
Role of health services Many patients have had recent contact either with mental health services or primary care services prior to suicide. Risk may be increased by certain aspects of services; for example, poor relationships with staff, inadequate staff numbers, and inadequate ward design or location. Research evidence that psychiatric services prevent suicide is lacking, but most services operate on the assumption that prevention is more likely if high-risk individuals are closely and regularly observed and 'frontline' staff are able to assess risk by clinical interview. Recent developments in the NHS have ensured that most suicides in contact with mental health services are reviewed locally by the multidisciplinary team and nationally by the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness. Suicide prevention Suicide prevention is a high priority both for the World Health Organization and within the UK. Reductions in the population suicide rate have been specified in the UK government documents, Saving Lives: Our Healthier Nation (in which the target is a 20 per cent reduction by 2010) and its predecessor, The Health of the Nation (15 per cent reduction by 2000). Routes to suicide prevention include: • a reduction in key risk factors in the general population such as depression and alcohol consumption, and indices of social adversity such as unemployment rates; • a reduction in the availability or lethality of common methods of suicide such as car exhaust asphyxiation and paracetamol. • specific measures targeted at high-risk groups such as those who present with deliberate self-harm, those with psychiatric disorders and young men. Aftermath of suicide There should be support available for those who have been in contact with an individual who commits suicide. This ought to be provided for both the family and the health staff who have been involved.
Deliberate self-harm Definition The term 'non-fatal deliberate self-harm' refers to non-fatal acts of selfpoisoning and self-injury and is often abbreviated to DSH. It will be
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used in this chapter to include attempted suicide, parasuicide, deliberate self-poisoning and deliberate self-injury. Epidemiology International rates of DSH are at record levels and seem to be increasing. In the UK there are no official national figures for DSH, but it has been estimated that there are at least 100 000 admissions to hospital annually. It is the most common cause of referral to hospital for women and the second most common cause, after cardiovascular disease, for men. There are also large numbers of people who self-harm who do not present to any medical services and others who present to their GP but are not referred to hospital. Population estimates for the lifetime prevalence have varied around 5 per cent, although reliable data are not available. By comparison, up to 15 per cent of the population have experienced suicidal ideas on at least one occasion.
Age and sex Those who self-harm are predominantly young, with the peak incidence occurring between the late teens and the early 30s. Until recently, DSH was considerably more common in women. However, in the last five years, the rate in young men has risen and recent studies have reported approximately equal numbers of men and women. This increase in DSH among young men appears to mirror the large rise in young male suicides.
Other factors DSH, like suicide, is linked to unemployment and other aspects of social adversity. DSH is associated with being single or divorced, and difficulties in interpersonal relationships are particularly common before an episode. There is a high rate of life events prior to deliberate self-harm. Method Around 90 per cent of all DSH episodes are self-poisoning, particularly with analgesics such as paracetamol and prescribed psychotropic drugs. Self-injury usually takes a form of self-laceration, particularly of the arms; other methods include self-inflicted cigarette burns. Violent methods of self-harm (e.g. attempted hanging or jumping from a height or in front of a vehicle) are usually associated with serious suicidal intent, but less serious methods do not mean little or no suicidal intent, particularly as an individual's understanding of the lethality of a particular method might be poor.
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Aetiology Despite substantial overlap with the aetiology of suicide, there are some factors of particular importance to DSH. Childhood events such as early parental loss or a history of physical or sexual abuse are common. There is often a background of long-term emotional problems, relationship difficulties, unemployment and ill-health, both mental and physical. Adverse interpersonal life events such as quarrels often precipitate DSH. Links with psychiatric disorders The majority of those who present with DSH have symptoms of psychological disturbance, often affective in nature. However, many do not have a formal psychiatric disorder and most of those who do, tend to have less severe forms of mental disorder.
Severe mental illness In patients with severe mental illness, i.e. schizophrenia or severe depression, it appears that most cases of DSH tend to have serious suicidal intent and tend to be more violent in nature. There may be links with auditory hallucinations and/or delusions.
Other disorders The most common diagnoses are mild depression or dysthymia, substance abuse and personality disorder. Alcohol is linked to DSH in two ways: alcohol misuse is a risk factor and alcohol itself is commonly taken at the time of self-harm. Personality disorder is present in a third to a half of DSH patients. Certain personality traits are linked to DSH, e.g. impulsivity. Outcome The most important risks after an episode of DSH are a repetition of DSH and suicide.
Repetition Fifteen to 25 per cent of individuals will harm themselves again in the first year and 1-2 per cent will go on to do so repeatedly. Risk factors for repetition include demographic factors such as male sex, low social class, unemployment, criminality, living alone and being divorced or separated, and clinical factors such as previous psychiatric contact, previous self-harm, drug or alcohol abuse, and personality disorder.
Suicide Up to 10 per cent of those people who carry out DSH eventually commit suicide, 1 per cent in the first year. Similarly, there is a history of DSH in
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about half of completed suicides. The risk factors for suicide reflect those of the general population, i.e. male sex, older age, living alone, being single/divorced/separated, unemployed, psychiatric illness (especially depressive order), personality disorder (especially dissocial) and alcohol or substance misuse. In young people, suicide after DSH is associated with alcohol and substance misuse, and mental illness. Previous DSH and features of the act, e.g. use of violent or high-risk methods, may also predict suicide. Management It is convenient to divide clinical management into three phases: risk recognition, risk assessment and risk management.
Risk recognition All patients who carry out DSH, including those who do so repeatedly or who use medically non-serious methods, should be viewed as being at significant risk and require more detailed assessment.
Risk assessment Risk assessment is based on information gathered from the history and mental state examination. The main elements of risk assessment are listed below. 1. Demographic and clinical risk factors Demographic:
older age (both sexes); young and middle-aged (men); male; divorced, single, widowed; living alone, socially isolated; unemployed or retired; occupational groups, e.g. doctors, farmers. Clinical:
family history of suicide/depression; mental illness; alcohol/substance misuse; previous DSH; physical illness; forensic history.
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2. Circumstances of current DSH Antecedents: planning; avoidance of discovery; final acts, e.g. note or will; major life events; unresolved life events. Method: availability; violent, e.g. attempted hanging or jumping from a heightmedical lethality; patient's concept of lethality; patient's expectation whether it would be fatal or not. 3. Current mental state examination Depressed mood. Features of depression. Hopelessness. Low self-esteem. Delusions, especially with suicidal content. Hallucinations, especially with suicidal content. Suicidal thoughts, especially if persistent and/or intense. Suicide plans. What will prevent these thoughts being translated into action. Attitude to DSH, i.e. whether regretful or not. 4. • • • •
Protective factors Social supports/network. Social responsibilities, e.g. children. Access to help in crisis. Resolution of precipitating problems.
Risk management Short-term risk of suicide should be estimated. When there is a high risk of suicide, admission to hospital is likely to be required. For lesser degrees of risk, early follow-up may be sufficient. Specific treatments should be initiated if there are signs of acute mental disorder. Referral to alcohol or drug services may be required. General monitoring of risk may be carried out by community mental health teams or primary care teams. Plans should be agreed on (a) how to seek help if a crisis recurs, e.g. by contacting family, voluntary or statutory services; (b) how to limit access to self-harm methods; (c) how to avoid precipitants such as being alone or overusing alcohol.
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Provided that the patient agrees, it is advisable to talk to family members or friends to ensure that there is adequate immediate support if needed. Evidence to support the use of more specific interventions to prevent repetition or suicide is generally poor. The most promising approaches are those designed to improve problem-solving and related coping skills. Communication is an important part of risk management. Detailed entries should be made in case notes, noting risk assessment and management. Other professionals involved in the individual's care, in particular the general practitioner, should be notified.
Reading list Appleby, L. (1992) Suicide in psychiatric patients: risk and prevention. British Journal of Psychiatry, 161, 749-58. Appleby, L., Shaw, J., Amos, T. et al. (1999) Safer Services. The Report of the National Confidential Inquiry into Suicide and Homicide by People with Mental Illness. London: Department of Health. Department of Health (1994). The Prevention of Suicide. London: HMSO. Department of Health (1999). Saving Lives: Our Healthier Nation. London: HMSO. Diekstra, R. (1989) Suicide and attempted suicide: an international perspective. Acta Psychiatrica Scandinavica, 80 (Suppl. 354), 1-8. Durkheim, E. (1952) Suicide. A Study in Sociology (transl. J.A. Spalding and G. Simpson). London: Routledge. Gunnel, D. and Frankel, S. (1994) Prevention of suicide: aspirations and evidence. British Medical Journal, 308, 1227-33. Harris, E.G. and Barraclough, B. (1997) Suicide as an outcome for mental disorders. British Journal of Psychiatry, 170, 205-28. Hawton, K. (1996) Deliberate self-harm. Medicine, 24(3), 77-80. Low, A.A., Farmer, R.D.T, Jones, D.R. et al. (1981) Suicide in England and Wales: an analysis of 100 years, 1876-1975. Psychological Medicine, 11, 359-68. Morgan, H.G. (1979) Death Wishes: The Understanding and Management of Deliberate Self-Harm. Chichester: Wiley. Stengel, E. (1964) Suicide and Attempted Suicide. Harmonsworth: Penguin.
19
Eating disorders FRANCES CONNAN and JANET TREASURE
Anorexia nervosa Epidemiology The incidence of anorexia nervosa (AN) is estimated to be 7 per 100 000 population, equivalent to 4000 new cases per year in the UK. There is no evidence of increased incidence over recent years. The disorder is chronic with a mean duration of 6 years and is thus one of the commonest of three chronic conditions of adolescence. Prevalence is estimated at 0.1-1.0 per cent of young women, 90-96 per cent of cases are female and the median age of onset is 17, with a range of 8-60 years. Increased prevalence is not associated with socioeconomic class as previously thought, but rather with educational achievement and yet average IQ. Classification See Table 19.1 for DSM-IV and ICD-10 diagnostic criteria. Differential diagnosis includes bulimia nervosa, depression, obsessivecompulsive disorder and physical causes of severe weight loss.
Co-morbidity Axis I co-morbidity is common and in part arises secondary to starvation. Fifty per cent have major affective disorder, 33 per cent social phobia and 25 per cent obsessive-compulsive disorder. For the binge/purge subtype, the rate of depression rises to 80 per cent and there is a 10-20 per cent prevalence of alcohol and substance misuse in this group. Deliberate-self harm occurs in a third. In terms of axis II co-morbidity, 25 per cent of those with restricting AN subtype reach criteria for avoidant, dependent and obsessional personality disorder, while 40 per cent of those with the binge/purge AN subtype have emotionally unstable or histrionic personality disorders.
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Criteria for the classification of anorexia nervosa
DSM-IV
ICD-10F50
Refusal to maintain body weight over a minimal norm, leading to body weight 15 per cent below expected
Significant weight loss (BMI<17.5kg/m2) or failure of weight gain or growth Weight loss self-induced by avoiding fattening foods and one or more of the following: (a) vomiting (b) purging (c) excessive exercise (d) appetite suppressants (e) diuretics
Intense fear of gaining weight or becoming fat
A dread of fatness as an intrusive overvalued idea and the patient imposes a low weight threshold on him/herself
Disturbance in the way in which one's body weight, size or shape is experienced, e.g. 'feeling fat'. Denial of seriousness of underweight or undue influence of body weight and shape on self evaluation Absence of three consecutive menstrual cycles
Widespread endocrine disorder: (a) amenorrhoea (b) raised growth hormone (c) raised cortisol (d) reduced T3
Restricting type: no binge eating or purging Binge/purging type: binge eating or purging
Aetiology Aetiology is multifactorial, including genetic, physiological, psychological, family and sociocultural factors.
Genetic Twin studies suggest that there is a significant genetic component; however, given the rarity of AN, there are no adoption studies and it is therefore difficult to separate genetic from family environment factors. There is a 7 per cent incidence in first-degree relatives and a ten-fold increased risk in female relatives. It is associated with leanness in the family.
Physiological There is evidence for dysfunction in the system that controls appetite and body composition. Serotonergic function appears to be reduced in
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the acute state, although this may be a state phenomenon arising secondary to starvation because 5-HT parameters and function tend to normalize in weight-restored subjects. An association has been demonstrated between a promoter polymorphism in the 5-HT2A gene and AN. Abnormalities have also been demonstrated in the hypothalamicpituitary-adrenal (HPA) axis in acute AN. Cerebrospinal fluid (CSF) corticotrophin-releasing hormone (CRH) is raised, plasma adrenocorticotrophic hormone (ACTH) is low or normal and plasma cortisol levels are raised with adrenal hypertrophy and hyperplasia. At least 60 per cent show dexamethasone nonsuppression. Again, these abnormalities tend to normalize with weight restoration, but there is renewed interest in the possibility of a trait abnormality. Leptin is synthesized by fat cells and its primary role may be to provide a signal to the hypothalamus that fat stores are sufficient for reproduction. Plasma leptin is proportional to body mass index in normals and in AN and there is no evidence for an abnormality in leptin function in AN. Onset follows a severe life event or difficulty in 70 per cent of cases in adults and in a smaller proportion of adolescents. In addition to roles in the control of body composition, the HPA axis and serotonergic systems are key components of the neuroendocrine response to stress. In biologically predisposed individuals, certain stressors may activate an abnormal neuroendocrine stress response which results in activation of catabolic pathways.
Psychological Psychodynamic formulations Crisp has written of AN as a regression to childhood and asexuality, while Bruch has focused upon a disturbed mother-child relationship giving rise to disturbance in the development of personality with deficits in the sense of self, identity and autonomy. Cognitive behavioural formulations Women with AN tend to show avoidance and helplessness in response to developmental and later life stressors. Weight loss is associated with restricted cognitions, the focus on food facilitating further avoidance of difficult issues. Self-disgust and self-criticism with compensatory perfectionism and placation are common features. Many have obsessional personality traits. The concept of 'fat phobia' is culturally biased and some authors argue that the concept of 'control phobia' is more generalizable. A powerful subjective sense of control is achieved through self-starvation.
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Family There is little evidence for gross disturbance in family functioning. Minuchin described AN families as rigid, lacking conflict resolution, enmeshed and overinvolved, although this is now known not to be specific to AN. Reduced skill in family problem-solving is specific to AN.
Sociocultural There is no evidence for increasing incidence associated with increased prevalence of dieting. Rather, sociocultural factors shape the presentation, increasing the proportion of binge/purge subtype, and they have a role in maintenance of illness, with a trend toward increased readmission rates and mortality. Clinical features
Behaviour Weight loss is self-induced by avoidance of high-calorie food with or without self-induced vomiting, misuse of laxatives, stimulants, diuretics or thyroxine and excessive exercise. There is a preoccupation with food, often manifest as shopping and cooking for others and occasionally as shoplifting. Rituals related to eating and exercise are common.
Physical features There is emaciation with amenorrhoea (which may be masked by contraceptive pill use). Consequent to starvation are lanugo; thinning of hair; thin skin and easy bruising; layered clothing to compensate for sensitivity to cold; poor circulation with cold, blue extremities, chilblains and gangrene; bradycardia and hypotension and muscular wasting manifest as difficulty brushing hair and inability to stand from squatting without using arms. Parotid/submandibular gland enlargement, calluses on knuckles (Russell's sign) and dental damage are indicative of vomiting. Body mass index =
AN< 17.5; Critical < 13
Mental state Women with AN usually describe themselves as not ill and are not seeking help. However, on direct questioning they will commonly admit to anhedonia, lack of motivation, reduced concentration, low mood, irritability, disturbed sleep, social impairment and physical complications. Overvalued ideas about weight and shape are not expressed by all patients with AN. Body image distortion is no longer considered a necessary criteria for AN, rather, the emaciated state is overvalued.
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Obsessive compulsive disorder and post-traumatic stress disorder symptomatology may also be present.
Medical complications See Table 19.2. Management Patients with AN are notoriously ambivalent about treatment. The transtheoretical model of Prochaska and DiClemente describes five stages of change: precontemplation, contemplation, preparation, action and maintenance. Patients with AN are usually in the precontemplation/ contemplation stage at presentation for treatment. It is important to develop a good therapeutic alliance, engender motivation and match the therapeutic process to the stage of change.
Choice of treatment model The choice of treatment model depends on age, medical severity and duration of the disorder. If age is less than 17 years research suggests
Table 19.2
Medical complications of anorexia nervosa
System
Medical complication
Musculoskeletal
Proximal myopathy; impaired respiratory function; osteoporosis and pathological fractures Erosion and loosening of teeth secondary to vomiting, carbonated drinks and osteoporosis of the jaw j Brain substance; | ventricular and sulcal space; J, pituitary size Cardiac muscle size and contractility; peripheral cyanosis and oedema Valvular problems (most murmurs are flow murmurs); QT prolongation and sudden death from arrhythmias FSH and LH; oestrogen and progesterone . Fertility; . birth weight; perinatal mortality; ability to feed infants Irritable bowel syndrome; motility and gastric emptying gastric dilatation rare; peptic ulceration common; pancreatitis (rare); salivary gland hypertrophy (amylase ); fatty infiltration of the liver and liver enzymes Bone marrow dysfunction - white cells precede red cells and platelets; reduced immune function Urea, glucose, potassium and others; hypercholesterolaemia; metabolic alkalosis with purgative behaviour | Growth hormone; cortisol T3 and , response to thyroid stimulating hormone (TSH)
Dental Central nervous system Cardiovascular
Reproductive function Gastrointestinal
Blood Blood chemistry Endocrine
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that the family should be involved in treatment. Parental counselling has been shown to be as effective and more acceptable than traditional family therapy. Clients over the age of 17 do better with individual therapy.
Inpatient treatment Inpatient treatment is considered if there is severe weight loss, dehydration, high suicide risk or if home circumstances are counter-therapeutic. In extreme circumstances the use of the Mental Health Act 1983 may be necessary. In terms of the Act, both psychotherapy and refeeding are legitimate treatments. The use of isolation and strict behavioural regimens are consigned to history: coercive practices are traumatic and reinforce the core features of the illness which are self-disgust and ineffectiveness. Specialist units provide a judicious mix of psychotherapy and nutritional support. The latter relies upon peer pressure and support from within the inpatient group. Food is reintroduced gradually during the first week, aiming for a normal and varied diet with a daily intake of around 3000 cal. Hunger can be frightening for patients but can be prevented by spreading the daily food intake into six meals per day. Most units aim for 1-2 kg weight gain per week. Failure to gain weight may be an indication of the use of purging behaviours or exercise. Target weight should be within the healthy range (BMI 19-24) and should take account of premorbid weight. Psychological work is undertaken alongside refeeding, as for outpatient treatment (see below).
Outpatient treatment Outpatient psychotherapy or counselling can be effective if there has not been too much weight loss (i.e. <25 per cent). Specialist psychotherapy such as cognitive analytic therapy or modified dynamic therapy is more effective than supportive psychotherapy. New models of cognitive behavioural therapy are being developed and tested as techniques to prevent relapse. Frequently, the therapy has to be continued long term. It is important that psychological treatment is supplemented with regular medical monitoring. Weight monitoring during therapy provides an invaluable objective measure of the efficacy of treatment for an individual. There is only a limited role for medication in the treatment of AN. Selective serotonin reuptake inhibitors (SSRIs) can be useful for the treatment of obsessive-compulsive symptoms and to reduce the frequency of binges for those with the binge/purge subtype. Preliminary evidence suggests that SSRIs may prevent relapse. Small doses of chlorpromazine
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or thioridazine may be useful in reducing the anxiety associated with mealtimes. Prognosis Early onset and short duration of illness with good premorbid function predict a good outcome. Even patients with good outcome often have residual problems such as abnormal attitudes to food and eating. Onethird have a poor prognosis. Mortality is approximately 1 per cent per year - the highest mortality of any psychiatric illness. Of deaths, 50 per cent are due to medical complications and 50 per cent due to suicide. Mortality rates are higher in areas without specialist services. Low serum albumin and weight < 60 per cent average body weight predict a lethal course.
Bulimia nervosa (BN) Epidemiology Bulimia nervosa (BN) is three times more common than AN, having an incidence of 14/100000 and prevalence of approximately 2 per cent of young women. Incidence is increasing, owing to increased sociocultural pressure to be thin. Only one-third of sufferers present for treatment. Classification DSM-IV and ICD-10 definitions are outlined in Table 19.3. Binge eating disorder was proposed by Spitzer in 1992 but its inclusion was not supported by a community-based cluster analysis and inclusion in DSM has therefore been put on hold pending further clarification. Clinical features Median age of onset is 18 years, with a male:female ratio of 1:10. BN is found in all socioeconomic groups. It is associated with premorbid obesity and family history of obesity. Onset is usually preceded by a period of weight loss and there is a history of AN in a third of sufferers. Patients are usually of normal weight and engage in protracted periods of fasting interspersed with binges of an array of 'forbidden' foods and leftovers. Transgression of self-imposed dietary rules and feelings of depression, anxiety, loneliness and boredom are frequently the precipitants for binges. Weight control measures to counteract effects of bingeing are varied but are most commonly vomiting, followed by laxative and diuretic misuse.
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Criteria for the classification of bulimia nervosa
I CD-10 Bulimia Nervosa (F50.1)
DSM-IV Bulimia Nervosa
Episodes of overeating
Recurrent episodes of binge eating large amounts and lack of control
Methods to counteract weight gain: (a) vomiting (b) laxatives (c) fasting (d) appetite suppressants (e) metabolic stimulants (f) diuretics
Compensatory behaviour to prevent weight gain: (a) vomiting (b) misuse of laxatives, diuretics, enemas (c) tasting (d) excessive exercise Binge eating and compensatory behaviour both occur on average at least 2 days a week for 3 months
Morbid fear of fatness with a sharply defined weight threshold
Self evaluation is unduly influenced by body shape and weight
Often a history of anorexia nervosa
Disturbance not exclusively present with anorexia nervosa or bulimia nervosa
Co-morbidity The lifetime risk of major depression is 35-70 per cent and for posttraumatic stress disorder, 37 per cent. Thirty per cent engage in acts of deliberate self-harm. Alcohol and substance misuse are common among clinic-based samples, but not community samples. Personality disorders are common, with equal numbers of anxious avoidant and emotionally unstable types. Aetiology
Genetic Heritability of 30-35 per cent has been demonstrated, although part of the genetic liability is nonspecific.
Physiological Early menarche is a risk factor, perhaps by association with obesity. There is evidence for reduced central 5-HT activity which may be important for aetiology and maintenance of disorder. Leptin levels are normal.
Family There are high levels of adversity within the family, with discord, neglect, increased childhood sexual and physical abuse and more later
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adverse sexual experiences. A family history of dieting or eating disorders is common.
Sociocultural The incidence of BN has increased in recent years, probably as a result of increased dieting among younger women. BN is especially common in groups where weight and shape are of importance, such as ballet dancers, models and actresses.
Medical complications Medical complications occur secondary to nutritional deficits or to the effects of vomiting and laxative misuse, as in AN. Management The Royal College of Psychiatrists Report of 1992 recommends a stepped approach to treatment: • Low-intensity treatment. Self-help manuals; groups or guided self-care. • Medium-intensity treatment. Medium-term cognitive behavioural therapy (CBT) or interpersonal therapy (IPT) - both are of proven benefit in BN but 50 per cent nevertheless remain symptomatic. • High-intensity treatment. Long-term psychotherapy or inpatient treatment - suitable for those with significant personality difficulties or physical complications. Education and development of skills for both nutritional and emotional balance are essential. Treatments can be provided individually or in groups.
Pharmacological treatments SSRIs are widely used, although the effect size is smaller than that of psychotherapy. Prognosis Median duration of BN is 3-6 years; 5-10 years after presentation 50 per cent have no disorder and 20 per cent meet full criteria for BN. The crude mortality rate is 0.3 per cent. Poor prognosis is associated with impulsivity.
Obesity Epidemiology Obesity is the commonest nutritional disorder and is associated with low socioeconomic class, being female and increasing age. In Western
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countries, prevalence is rapidly increasing, obesity occurring in 10 per cent of males and 15 per cent of females. Definition Obesity is defined as body mass index (BMI) > 30, with severe obesity if BMI > 40. Differential diagnosis includes endocrine disorders such as hypothyroidism and rare syndromes such as the Prader-Willi syndrome. Aetiology Obesity is familial. Environmental factors are possibly more important than genetic. The rapid increase in prevalence of obesity is thought to be due to changes in lifestyle, in particular, the decrease in physical activity. Food intake is decreasing but is unable to compensate for the reduced metabolic demand. Organic causes are rare. One family with a failure of leptin production has been reported. Medication such as prednisolone, phenothiazines and clozapine may cause obesity. The obese tend to control eating more in response to external than visceral stimuli and tend to underestimate meal size. Most sufferers eat no more than others. Binge eating occurs in some, one-third having binge eating disorder. The obese do not show greater psychological disturbance than the general population, but may have low self-esteem and social anxiety. Some studies have indicated that a proportion of women with obesity have had childhood trauma. Medical complications Obesity is associated with increased risk of cardiac disease, diabetes mellitus, arthritis and other disorders. Mortality is increased. Management Psychological treatments employ a cognitive behavioural approach with monitoring of food intake and its antecedents and consequences, and a cognitive approach to self-esteem. Long-term outcomes are very poor. Ideal weight is rarely appropriate as a target weight and a more appropriate and achievable goal should be selected. It is interesting to note that self-help treatment for binge eating disorder reduced frequency of bingeing but did not alter weight. Physical treatments include medication (e.g. phentermine. D-fenfluramine has been withdrawn because of the risk of damage to heart valves) and surgical interventions (e.g. jaw wiring or gastric restriction). They should be reserved for only very severe obesity as the risks are high and outcome poor, with frequent weight gain after cessation of treatment.
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Pica Pica is defined as the eating of nonnutrient items such as soil or paper. It is very common in childhood and is managed by simple commonsense interventions to ensure safety, the behaviour usually disappearing with age. However, pica can be indicative of deprivation and is associated with autism, learning difficulties and mental illness. In this context the disorder is managed by treatment of the underlying condition where possible and behaviour modification. Pica may sometimes reflect a specific trace element deficit.
Reading list Brewerton, T.D. (1995) Towards a unified theory of serotonin disturbances in eating and related disorders. Psychoneuroimmunology, 20, 561-90. Crisp, A.H., Callender, J.S., Halek, C. and Hsu, L.K.G. (1992) Long-term mortality in anorexia nervosa: a 20-year follow-up of the St. George's and Aberdeen cohorts. British Medical Journal, 161, 104-7. Fairburn, C.G., Welch, S.L., Doll, H.A., Davies, B.A. and O'Connor, M.E. (1997) Risk factors for bulimia nervosa: a community based case control study. Archives of General Psychiatry, 54, 509-17. Fairburn, C.G., Welch, S.L., Doll, H.A., Davies, B.A. and O'Connor, M.E. (1999) Risk factors for anorexia nervosa: three integrated case-control comparisons. Archive of General Psychiatry, 56, 468-76. Fairburn, C.G., Doll, H.A., Welch, S.L., Hay, P.J., Davies, B.A. and O'Connor, M.E. (1998) Risk factors for binge eating disorder: a community-based, casecontrol study. Archive of General Psychiatry, 55, 425-32. Fombonne, E. (1995) Anorexia nervosa. No evidence of an increase. British Journal of Psychiatry, 166, 462-71. Herzog, W., Deter, H.C., Fiehn, W. and Petzold, E. (1997a) Medical findings and predictors of long term physical outcome in anorexia nervosa - a prospective 12 year follow-up study. Psychological Medicine, 27, 269-79. Herzog, D.B., Keller, M.B., Lavori, P.W., Kenny, G.M. and Sacks, N.R. (1992) The prevalence of personality disorders in 210 women with eating disorders. Journal of Clinical Psychiatry, 53, 147-52. Keel, P.K. and Mitchell, J.E. (1997) Outcome in bulimia nervosa. American Journal of Psychiatry, 154, 313-21. Lee, S. (1995) Self starvation in context: towards a culturally sensitive understanding of anorexia nervosa. Social Science Medicine, 41, 25-36. Prochaska, J.O. and DiClemente, C.C. (1992) The transtheoretical model of change. In Handbook of Psychotherapy Integration (eds J.C. Norcross and M.R. Goldfried). New York: Basic Books. Russell, G.F.M. (1995) Anorexia nervosa through time. In Handbook of Eating Disorders: Theory, Treatment, Research (eds G. Szmukler, C. Dare and J. Treasure). Chichester: Wiley. Russell, G.F.M., Szmukler, G., Dare, C. and Eisler, I. (1987) An evaluation of family therapy in anorexia nervosa and bulimia nervosa. Archives of General Psychiatry, 44, 1047-56.
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Schmidt, U. (1998) Treatment of Bulimia nervosa. In The Integration of Neurobiology in the Treatment of Eating Disorders (eds H.W. Hoek, J.L. Treasure and M.A. Katzman). Chichester: Wiley. Spitzer, R.L., Devlin, M., Walsh, B.T. et al. (1992) Binge eating disorder. A multisite field trial of the diagnostic criteria. International Journal of Eating Disorders, 11, 191-203. Treasure, J.L. and Connan, F. (1998) The neurobiology of anorexia nervosa and bulimia nervosa. In The Integration of Neurobiology in the Treatment of Eating Disorders (eds H.W. Hoek, J.L. Treasure and M.A. Katzman). Chichester: Wiley. Treasure, J.L. and Holland, A.J. (1995) Genetic factors in eating disorders. In Handbook of Eating Disorders: Theory, Treatment and Research (eds G. Szmukler, C. Dare and J. Treasure). Chichester: Wiley. Treasure, J.L. and Szmukler, G. (1995) Medical Complications. Handbook of Eating Disorders: Theory, Treatment and Research (eds G. Szmukler, C. Dare and J. Treasure). Chichester: Wiley. Ward, A., Troop, N., Todd, G. and Treasure, J.L. (1996) To change or not to change. 'How' is the question. British Journal of Medical Psychology, 69, 139-46.
20
Postpartum and related disorders MARY ROWSELL and LOUIS APPLEBY
A number of psychological disorders are specific to women, and are associated with their childbearing capacity. For ease of description, such problems will be classified as: • psychiatric disorders of pregnancy; • postnatal psychiatric disorders; • attachment difficulties; • psychological disorders associated with gynaecological conditions including (a) the menstrual cycle; (b) the menopause; (c) hysterectomy, and (d) oral contraception.
Psychiatric disorders of pregnancy Mild disturbance of affect occurs in up to 50 per cent of pregnant women; low mood, worries, anxiety and irritability are particularly common, especially in the first and last trimesters. The peak incidence (about 10 per cent) of significant depression or anxiety during pregnancy occurs in the first trimester and is associated with: past history of psychiatric disorder; anxieties about the fetus; previous termination of pregnancy; current consideration of termination of pregnancy; marital conflict; anxious personality. Affective symptoms occurring during pregnancy often resolve later in pregnancy but some persist or recur postnatally, reflecting a vulnerability to depression. Reduced rates of contact with psychiatric services are found during pregnancy. Pregnant women are also less likely to commit suicide; these findings suggest a reduced prevalence of severe mental illness during pregnancy. Women with severe psychiatric disorder who become preg-
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nant require much support during pregnancy and post-delivery, to ensure the well-being of the mother and protection of the baby. Pharmacological treatments should be avoided where possible, especially in the first trimester (Table 20.1). When the severity of illness is such that discontinuation of treatment is not advisable, older antipsychotic and antidepressant drugs are usually prescribed in preference to newer compounds or drugs known to be teratogenic, such as lithium. There is increasing evidence for the safety of the main tricyclics and SSRIs but absolute assurance cannot be given. Excessive alcohol consumption and certain illicit drugs used during pregnancy may complicate the pregnancy and result in adverse effects on the fetus or baby (Table 20.1). Pregnancy in the opiate addict is also complicated by poor antenatal clinic attendance and the social, physical and psychological problems of addiction. Successful management of the opiate addict requires effective, coordinated care between the drug service and obstetrician. Assessment and social services support is advised. If done with caution, opiates may be withdrawn, although this may lead patients to default. Termination of pregnancy Psychiatric assessment is now rarely required before a termination. Possible psychiatric indications for termination of pregnancy include: chronic mental disorder, a previous postpartum psychotic disorder and inability to cope. Psychological distress is said to improve following a therapeutic termination, presumably because the distress is often related to an unwanted pregnancy or worries about abortion. However, increased distress may occur post-termination ( < 10 per cent) - risk factors being: a past psychiatric disorder; poor social support; young age; multiparity; a sociocultural setting which discourages abortion. The incidence of psychotic illnesses after abortion is approximately 0.03 per cent. Stillbirth Stillbirth may be associated with clinically significant psychological distress, with a risk of 'pathological' grieving. Guilt and feelings of failure as a woman may be prominent.
Postnatal psychiatric disorders The major postnatal psychiatric disorders are linked to illnesses arising at other times and are similar in clinical appearance and risk factors.
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Table 20.1
Effects of drugs in pregnancy and breastfeeding*
Effect(s) when taken in pregnancy
Effect(s) when taken while breastfeeding
Antidepressants Tricyclics
NEAE but can cause neonatal withdrawal syndrome (irritability, insomnia, restlessness) if used in third trimester
Use with care
MAO Is
NEAE
NEAE
SSRIs
NEAE
NEAE but caution needed
Neuroleptics
NEAE in general Use of clozapine not advised by pharmaceutical industry in pregnancy
NEAE in general Most neuroleptics enter milk in only small amounts (except clozapine and respiridone) Clozapine may also cause agranulocytosis and sedation in infant
Lithium
ROT: cardiac abnormalities, hypotonia, thyroid goitre, hypothyroidism
Contraindicated
Anxiolytics and hypnotics Beta-blockers
NET but use with caution
May cause bradycardia and hypoglycaemia in high doses
Drug
Buspirone
NET
Contraindicated
Zopiclone
Not contraindicated
Contraindicated (excreted in breast milk in appreciable amounts)
Benzodiazepines
ROT Long-acting benzodiazepines (e.g. diazepam) can cause 'floppy baby syndrome' with facial abnormalities and CNS effects May cause neonatal withdrawal effects, depressed respiration and feeding problems
Use with caution
Anticonvulsants
ROT
Use with caution
Opiates
NET But, abrupt cessation of opiates in pregnancy may cause dangerous withdrawal reactions and fetal damage NEAE with maintenance dose use NEAE when maternal doses May cause neonatal withdrawal of up to 20mg/day used syndrome in first 24 h
Methadone
Postpartum and related disorders Table 20.1
373 Continued
Effect(s) when taken in pregnancy
Effect(s) when taken while breastfeeding
Heroin
May affect growth (catch-up growth by 12 months), low birth weight, preterm delivery, fetal death, abnormal development with abnormal Moro test at 7-8 months May cause a neonatal withdrawal syndrome Complications of i.v. use including vertical transmission of HIV infection
NEAE
Alcohol
cause fetal malformations, including the fetal alcohol syndrome (facial dysmorphology, microcephaly, low IQ and behavioural disturbances), growth retardation, low birth weight and intrauterine death
Heavy drinking may cause insomnia, liver damage and pseudo-Cushing's syndrome in neonate
Cannabis
Controversial Some reports of preterm delivery, impaired maturation of visual system and unusual widespread eyes
Nicotine
Evidence of intrauterine growth retardation and small-for-dates baby
Drug
'Drugs should always be prescribed with caution during pregnancy and breast-feeding. NEAE, no evidence of adverse effects; ROT, risk of teratogenicity; NET, no evidence of teratogenicity; MAOIs, monoamine oxidase inhibitors; SSRIs, selective serotonin reuptake inhibitors.
Some people, however, become ill only postnatally, and presumably have a greater or specific postnatal vulnerability. In addition, the context of childbirth alters the risks, consequences and service needs associated with many mental disorders. For these reasons it is convenient to consider postnatal psychiatric disorders separately from other disorders. The following are widely used categories: • puerperal psychosis; • postnatal depression; • maternity blues. Puerperal psychosis
Clinical features The onset is usually within 2 weeks of delivery (some authorities include this in their definition).
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Classically the first symptoms are agitation, excitability and insomnia. These are followed by the acute development of psychotic features, especially mood disturbance (including lability), delusions, and confusion. In at least 70 per cent of cases the clinical picture is of an affective or schizoaffective disorder; 5-25 per cent are schizophrenic in nature, the remainder being nonspecific acute psychotic states. The course is often a fluctuating one.
Epidemiology Psychotic illnesses complicate 0.1-0.2 per cent of full-term pregnancies and are commoner in first pregnancies. Psychiatric hospital admissions are 18 times more common during the first postpartum month than in any month during pregnancy.
Aetiology Genetic The incidence of bipolar affective disorder is increased in patients' families. There is also an increased risk of developing puerperal psychosis in individuals who have relatives with bipolar affective disorder.
Biochemical Most theories are based on the observation that the onset of the disorder is at a time of great metabolic change, suggesting that a rapid fall in oestrogen and/or progesterone influences catecholamine (especially dopamine) activity in the CNS or reduces tryptophan availability for serotonin synthesis. Attention has also been focused on prolactin and other pituitary hormones, as well as endorphins. These theories reflect those proposed for affective disorders, but consistent supportive evidence has not been found.
Social/psychological The stress of delivery may act as a precipitant. Some research suggests an association with complicated deliveries, particularly Caesarean section, or with single marital status. Although psychosis is commoner after first pregnancy, this effect cannot be assumed to be mediated by stress, since pre-eclampsia is also commoner in primiparous women.
Management Hospital admission should be offered when: • there is a risk of suicide or serious assault to others; • there is a risk of harm to the baby by either neglect or assault; • the severity of disturbance makes outpatient or day-patient care impractical.
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The indications for compulsory admission are as for other mental illnesses. Admission with the baby allows observation of mothering skills and continuation of mother-baby bonding. The mother may receive support and assistance with mothering activities such as feeding or changing. Assessment of mothering skills is advised, because of the potential risk of harm to the infant including: • risk of direct harm; • risk of indirect harm (clumsiness, poor care); • risk of neglect, resulting from: (a) impaired emotional responsiveness; (b) a limitation in practical skills, and (c) a lack of persistence of parenting input. Medication is prescribed as for other psychotic illnesses (Table 20.1). As with prescribing in pregnancy, the potential risks and benefits have to be compared. Antipsychotic drugs may be taken by breastfeeding women, but many clinicians prefer to limit drug doses, e.g. 300 mg/day for chlorpromazine. Indications for ECT are as for other illnesses, although some clinicians regard it as the treatment of choice. Psychotherapeutic support should focus on feelings of self-confidence as a mother. Marital support may be indicated, including following discharge. Education should concentrate on mothering skills and the nature of the illness, particularly the risk of puerperal or non-puerperal relapse.
Prognosis Immediate Approximately 70 per cent recover fully from their illness. If admitted to hospital, the average length of stay is 2-3 months. If the clinical presentation is that of schizophrenia, the immediate prognosis is worse. Injury to the infant and infanticide are important but rare consequences. Long term Approximately 40 per cent have a further psychotic episode, while around 30 per cent have another puerperal psychotic episode. The risk of relapse in each subsequent pregnancy is approximately 20 per cent. Poor clinical and social prognosis is related to a schizophrenic presentation. Persistently impaired mother-infant interaction may occur, especially in schizophrenic cases. Later disturbed behaviour in the children of psychotic women is related to associated marital and social disruption, rather than to the presence of the illness alone. Postnatal depression
Clinical features The onset, usually within 6 weeks of delivery, is marked by low mood with prominent anxiety, especially over the baby's health and feeding.
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The patient feels unable to cope and consequently expresses self-criticism and guilt. A range of depressive symptoms may be pronounced: tiredness, irritability, initial insomnia, anorexia and loss of libido. Psychotic features, such as hallucinations and delusions, are absent.
Epidemiology Clinically significant depression is found following 10-15 per cent of full-term deliveries. Some studies suggest that a similar prevalence of depression occurs in nonpostnatal women; one study has found a higher incidence of depression in postnatal women (i.e. new cases) but a prevalence similar to that of other women. Many predisposing features have been suggested: Psychiatric factors • Past history of depression. • Family psychiatric history. • Psychiatric history in partner. Obstetric factors • Unplanned pregnancy. • Subfertility. • Premature delivery. • Maternal age over 30 years. Psychosocial factors • Antenatal anxiety. • Ambivalence about the pregnancy during the first trimester. • Poor relationship with partner. • Poor relationship with mother. • No job to return to. • Partner unemployment.
Aetiology Genetic There is evidence of a higher incidence of depression, including postnatal depression, in the families of sufferers from postnatal depression. Biochemical Postulated mechanisms are based on the numerous endocrine changes postpartum and include falling corticosteroid and/or progesterone levels influencing CNS neurotransmitters (especially serotonin). However, the evidence is weak and the onset of clinical depression often occurs long after the major hormonal changes. There is evidence of thyroid dysfunction in some cases.
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Social/psychological The predisposing features listed above suggest that the risk of postnatal depression increases when the pregnancy and/or the delivery is an emotionally traumatic event, falling below expectation and leading to a change in role in which the woman feels unsupported, or bringing difficulties in other relationships to the fore.
Management Three trials have shown simple psychological treatments (non-directive counselling and cognitive behavioural counselling) to be effective. One of these trials also showed the effectiveness of conventional antidepressants (fluoxetine), and one further trial (with more severe cases) showed oestrogen to be effective. Education in mothering skills is often helpful using simple behavioural techniques for coping with the baby and other infants, especially for difficulties with feeding and sleeping. Care must be taken, however, not to reinforce the mother's feelings of inadequacy. The partner should be included in discussions of practical and emotional support. In the majority of cases of postnatal depression, treatment may be effectively given in the community. A small minority of women, however, may require hospital admission, and in these cases admission with the baby is desirable.
Prognosis Approximately 70 per cent recover; about one-third run a chronic or relapsing course. Postnatal depression may have detrimental effects on the motherchild interaction, the security of the child's attachment to the mother, parenting abilities, the child's cognitive development (as demonstrated by later lowered scores on cognitive assessments) and behavioural development in the subsequent 18 months to 4 years. The impaired mother-child relationship is generally characterised by a lack of positive affect and mutual responsiveness. This impaired early relationship is thought to impair secure attachment and cognitive development. The mechanisms underlying the reported association between postnatal depression and child behavioural disturbance are not clear. Maternity blues
Clinical features The blues is a syndrome marked by low mood, emotional lability (often preceded by elation), weeping, anxiety, insomnia and irritability.
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Epidemiology Estimates of incidence vary with definition, but at least 50-70 per cent of births are followed by these symptoms. Their peak is on or around the fifth day postpartum. Onset is uninfluenced by the timing of discharge from hospital.
Aetiology The timing and transient nature of the blues suggest a link with the biological changes after delivery, especially altered sodium excretion, falling sex steroid levels and reduced plasma beta-endorphins. Many patients with premenstrual tension later suffer from the blues, suggesting a similar cause.
Management Reassurance and support are given; no other treatment is necessary.
Prognosis Symptoms resolve in a few days. Failure of attachment (bonding failure) Attachment refers to normal emotional ties between mother and newborn infant. It depends on several factors, including physical contact, the baby's behaviour and the mother's emotional responsiveness. Poor emotional attachment is claimed to lead to maternal rejection, nonaccidental injury, failure to thrive and, as previously described, to impaired child cognitive and behavioural development. Physical and psychiatric disorders in the mother can impair the developing mother-infant relationship. The exact mechanism underlying the association between postnatal psychiatric illness and 'bonding disorder' is as yet unclear. In women with postnatal psychiatric disorders requiring inpatient care, admission with the baby facilitates attachment by encouraging contact between mother and baby, and providing practical and emotional support. Psychological disorders associated with gynaecological conditions Premenstrual syndrome
Clinical features The main symptoms are low mood, irritability, insomnia and bloating, although major psychiatric disturbances have also been described.
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Some women report a worsening of premenstrual dysphoria after pregnancy, and occasional cases of psychotic symptoms have been reported.
Epidemiology The prevalence depends on the definition used. Up to 90 per cent of menstruating women have been described as suffering cyclical symptoms - physical, behavioural and psychological - which are usually worse premenstrually.
Aetiology The exact cause is unknown, although it is assumed to be related to falling sex steroids and consequent CNS neurotransmitter changes, and/ or changes in electrolyte and fluid balance.
Management Hormone preparations, diuretics and vitamin B6 are often used. Their effectiveness has been difficult to demonstrate, owing to a large placebo response. Menopausal disorders No clear association between mood disturbance and the menopause itself has been found. The midlife peak in affective disturbance precedes the timing of the clinical menopause. Many potentially distressing psychosocial changes may occur at this time and may be causal: children leaving home, retirement, husband's retirement, death of parents, loss of fertility; depressed menopausal women have a high rate of these preceding life events. Hysterectomy Psychiatric morbidity is high preoperatively and falls postoperatively but remains higher than in the general population. Poor psychiatric outcome is associated with preoperative mental symptoms, neuroticism, previous psychiatric illness and a family history of mental illness. Oral contraception Transient mild psychiatric symptoms may occur during the first month of use. There have been occasional reports of acute psychosis linked to the use of the Pill.
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Mental health services for childbearing women There are a number of psychiatric services available to childbearing women, both community and hospital based. However, most cases of postnatal depression are either untreated or treated in primary care. A comprehensive mental health service for childbearing women should include: • consultant with a special interest in perinatal disorders; • a full multidisciplinary mental health team, including staff with counselling skills; • liaison with the obstetrics and gynaecology department; • liaison with the primary health care team, including GP and health visitor - health visitors should be trained to screen for and counsel postnatal depression; • liaison with child psychiatrist, learning disabilities services and drug teams; • day hospital with nursery facilities; • outpatient facilities able to accept urgent referrals; • admission to specialist mother and baby units, allowing acute treatment and assessment of parenting.
Reading list Appleby, L. (1991) Suicide during pregnancy and in the first postnatal year. British Medical Journal, 302, 137-40. Appleby, L. and Dickens, C. (1993) Mothering skills of women with mental illness. British Medical Journal, 306, 348-9. Appleby, L., Warner, R., Whitton, A. and Faragher, B. (1997) A controlled study of fluoxetine and cognitive-behavioural counselling in the treatment of postnatal depression. British Medical Journal, 314, 932-6. Brockington, I.F. and Kumar, R. (1982) Motherhood and Mental Illness. London: Academic Press. Brockington, I.F., Cernik, K.F., Schofield, E.M., Douning, A.R., Francis, A.F. and Keelan, C. (1981) Puerperal psychosis: phenomena and diagnosis. Archives of General Psychiatry, 38, 829-33. Clare, A.W. (1979) The treatment of premenstrual symptoms. British Journal of Psychiatry, 135, 576-9. Cogill, S., Caplan, H.L., Alexandra, H., Robson, K.M. and Kumar, R. (1986) Impact of postnatal depression on cognitive development of young children. British Medical Journal, 292, 1165-7. Cox J.L., Murray, D. and Chapman, G. (1993) A controlled study of the onset, duration and prevalence of postnatal depression. British Journal of Psychiatry, 163, 27-31. Dean, C. and Kendell, R.E. (1981) The symptomatology of puerperal illnesses. British Journal of Psychiatry, 139, 128-33. Gath, D., Cooper, P. and Day, A. (1982) Hysterectomy and psychiatric disorder. I: Levels of psychiatric morbidity before and after hysterectomy. British Journal of Psychiatry, 140, 335-42.
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Gregoire, A.F.P., Kumar, R., Everitt, B., Henderson, A.F. and Studd, J.W.W. (1996) Transdermal oestrogen for treatment of severe postnatal depression. The Lancet, 347, 930-3. Harris, B. (1994) Hormonal aspects of postpartum depressed mood. British Journal of Psychiatry, 164, 288-92. Holden, J.M., Sagorsky, R. and Cox, J.L. (1989) Counselling in a general practice setting: controlled study of health visitor intervention in the treatment of postnatal depression. British Medical Journal, 298, 223-6. Kendell, R.E. et al. (1976) The influence of childbirth on psychiatric morbidity. Psychological Medicine, 6, 297-302. Kumar, R.C. (1997) 'Anybody's child': severe disorders of mother-to-infant bonding. British Journal of Psychiatry, 171, 175-81. Kumar, R. and Brockington, I.F. (1988) Motherhood and Mental Illness: Causes and Consequences. Bristol: Wright. Kumar, R. and Robson, K.M. (1984) A prospective study of emotional disorders in childbearing women. British Journal of Psychiatry, 144, 35-47. London, J.B. (1987) P.sychotropic drugs. British Medical Journal, 294, 167-9. Murray, L. (1992) The impact of postnatal depression on infant development. Journal of Child Psychology and Psychiatry, 33, 543-61. Gates, M. (1995) Risk and childbirth in psychiatry. Advances in Psychiatric Treatment, 1, 146-53. Osborn, M. (1984) Depression at the menopause. British Journal of Hospital Medicine, 32, 126,128-29. Pitt, B. (1968) Atypical depression following childbirth. British Journal of Psychiatry, 114, 1325-35. Pitt, B. (1973) Maternity blues. British Journal of Psychiatry, 122, 431-3. Protheroe, C. (1969) Puerperal psychosis: a long term study 1927-1961. British Journal of Psychiatry, 115, 9-30. Stein, A., Gath, D.H., Bucher, J., Bond, A., Day, A. and Cooper, P.J. (1991) The relationship between postnatal depression and mother-child interaction. British Journal of Psychiatry, 158, 46-52. Warner, R., Appleby, L, Whitton, A. and Faragher, B. (1996) Demographic and obstetric risk factors for postnatal psychiatric morbidity. British Journal of Psychiatry, 168, 607-11. Watson, J.P., Elliott, S.A., Rugg, A.J. and Brough, D.I. (1984) Psychiatric disorder in pregnancy and the first postnatal year. British Journal of Psychiatry, 144, 453-62. Weissman, M.M. and Slaby, A.E. (1973) Oral contraceptives and psychiatric disturbance: evidence from research. British Journal of Psychiatry, 123, 513-8. Whitton, A., Warner, R. and Appleby, L. (1996) The pathway to care in postnatal depression: women's attitudes to postnatal depression and its treatment. British Journal of General Practice, 46, 427-8. Wickberg, B. and Hwang, C.P. (1996) Counselling of postnatal depression: a controlled study on a population based Swedish sample. Journal of Affective Disorders, 39, 209-16. Wieck, A. (1989) Endocrine aspects of postnatal mental disorders. Baillieres Clinical Obstetrics and Gynaecology, 3, 857-77. Zolese, G. and Blacker, C.V.R. (1992) The psychological complications of therapeutic abortion. British Journal of Psychiatry, 160, 742-9.
21
Sexual disorders SUE SMITH and ALAIN GREGOIRE
Development from the early embryonic stage to the mature sexual adult is affected by a multitude of influences. The process can go wrong in a variety of ways, leading to problems with sexual functioning, with the stimulus needed for that functioning and with the development of gender.
Normal sexual functioning A host of psychological, physical and pathological factors can influence the physiological responses necessary for satisfactory sex at any point along the five phases described by Master and Johnson and Kaplan: • Desire. Influenced by social, personal, cultural and hormonal factors • Excitement. Physical and psychological stimulation leads to subjective sexual excitement and accompanying objective physiological changes, i.e. genital vasodilatation (parasympathetic) and erection in the male, vaginal swelling and lubrication in the female • Plateau. Increase in blood pressure, heart rate, respiratory rate and muscle tension as excitement continues. In the male, testes rise and enlarge and the bulbo-urethral glands produce pre-ejaculatory mucoid secretion. In the female, lower vaginal and vulval swelling continues, the cervix elevates and the upper vagina balloons (orgasmic platform). The skin is flushed and the breasts are swollen, with erect nipples and areolae. • Orgasm. Further increase in heart and respiratory rate and blood pressure as sympathetic activity increases. (a) In the male: emission - testes, vas deferens, seminal vesicles and prostate contract, feeling of ejaculatory inevitability; ejaculation 1-3 seconds later, semen ejected with rhythmic contraction of perineal muscle and prostate; orgasm - sensation accompanying ejaculation.
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(b) In the female: outer third of the vagina and perineal muscles contract. • Resolution. Reversal of above changes, with a refractory period in men which increases with age. Slower without orgasm. Females are capable of multiple orgasm.
Sexual dysfunction Classification Sexual dysfunction (Table 21.1) is characterized by absolute or relative deficit in sexual performance as defined by the individual's expectations. Other clinical categories to consider: primary - sexual function never normalsecondary - after a period of normal functioning; acute or insidious in onset; total or partialglobal or only occurring in specific situations.
Definitions Lack or loss of sexual desire There is impaired arousal to erotic stimulation. More common in women. Often reflects general relationship difficulties. It may be symptom of a depressive disorder. Sexual aversion There is persistent or severe dislike of sex, accompanied by avoidance of almost all genital sexual contact. Lack of sexual enjoyment Lack of expected pleasure despite normal sexual responses and orgasm occurring. More common in women. Table 21.1
ICD-10 Classification of sexual dysfunction
Sexual dysfunction, not caused by organic disorder or disease (F52) Lack or loss of sexual desire Sexual aversion and lack of sexual enjoyment Failure of genital response Orgasmic dysfunction Premature ejaculation Nonorganic dyspareunia Nonorganic vaginismus Excessive sexual drive
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Failure of genital response In women, it is principally a problem of reduced lubrication due to: • inadequate foreplay; • lack of sexual interest; • anxiety about intercourse. Organic causes include oestrogen deficiency and infection. In men, erectile dysfunction, or erectile impotence, is difficulty achieving or sustaining erection and is experienced transiently by most men at some time. It is more common with increasing age, and has a significant psychological component if erection occurs at some time, e.g. on waking or on masturbation. Orgasmic dysfunction Absent or markedly delayed orgasm. In women this may not be regarded as abnormal and could be secondary to inadequate stimulation. In men it is usually associated with general psychological inhibition or secondary to drug treatment. Premature ejaculation Ejaculation before, during or too soon (to satisfy partner in Masters and Johnson's definition) after penetration. More common in younger men and generally psychological in origin. Non-organic dyspareunia Most cases of pain during intercourse are due to a local pathological cause but it is occasionally related to emotional factors. Non-organic vaginismus Involuntary spasm of perineal muscles whenever penetration is attempted, leading to occlusion of the vaginal opening. Excessive sexual drive Occasionally complained of by both men and women as a problem in its own right, but more commonly associated with other psychiatric disorders. Other • Partial ejaculatory incompetence: emission of semen but no ejaculation. • Retrograde ejaculation: semen propelled backward into the bladder due to an incompetent internal sphincter. • Priapism: sustained and painful erection. • Female pelvic engorgement: discomfort following intercourse in the absence of orgasm.
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Epidemiology The prevalence of sexual dysfunction is still uncertain, with most studies subject to problems of sampling, definition and reporting. Kinsey reported impotence as the commonest male problem with rates of 7 per cent under 50 years old, 20 per cent under 60, 30 per cent by 70 and 75 per cent over 75 years. Premature ejaculation is commoner in young men. Kinsey reported 75 per cent of men as ejaculating within 2 minutes of penetration. One community survey of women reported impaired sexual interest in 17 per cent, infrequent orgasm in 16 per cent and dyspareunia in 8 per cent. In those presenting for treatment, 50 per cent complained of impaired sexual interest, 20 per cent of orgasmic dysfunction. In one-third of couples seeking treatment, both have a problem. Sexual dysfunction occurs in 10 per cent of psychiatric outpatients, with much higher rates in those on certain psychotropic drugs. Aetiology Bancroft proposes the psychosomatic circle in which input from tactile and cognitive stimuli triggers activity between the limbic system and spinal pathways. Interruption anywhere in this circle may produce sexual dysfunction.
Psychological factors • Poor general relationship. • Performance anxiety secondary to fear of failure or unrealistic expectations can be associated with spectatoring, in which a person observes rather than participates in his or her own love-making. • Ignorance about anatomy and sexual techniques. • Guilt and negative attitudes towards sex, perhaps deriving from home background. • Fear of consequences such as pregnancy, pain or loss of control. • Low self-esteem as trait or resulting from depression, following disfiguring surgery, etc. • Adverse circumstances, e.g. general stresses, overcrowded housing. • Previous traumatic sexual experiences. • Psychological factors associated with any physical causes of sexual dysfunction can exacerbate the problem, e.g. fear associated with cardiovascular disease in patient or partner.
Physical Genital • Congenital: hypospadias, imperforate hymen. • Infection: pelvic inflammatory disease, balanitis, herpes.
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Surgical: episiotomy, prostatectomy. Trauma. Endometriosis. Failure of vaginal lubrication Peyronie's disease. Vascular • Peripheral vascular disease. • Penile vascular disease. Neurological • • • •
Spinal cord lesions. Peripheral nerve damage. Neurosyphilis. Multiple sclerosis.
Other • Diabetes mellitus: small-vessel disease, autonomic neuropathy, metabolic disturbance and secondary performance anxiety all contribute. Hypopituitary dysfunction. Renal failure. Liver failure. Carcinomatosis. Musculoskeletal, e.g. arthritis. Alcoholic neuropathy.
Drugs affecting sexual function • Antidepressants. Tricyclics, MAOIs and SSRIs all associated with development of decreased sexual interest, erectile failure, impaired ejaculation and impaired orgasm. The exception appears to be nefazadone. Trazodone is associated with priapism. • Anxiolytics. Barbiturates are especially associated with erectile impotence. • Antipsychotics. Erectile impotence, delayed ejaculation, retrograde ejaculation; priapism with clozapine. • Antihypertensives. Erectile impotence. • Diuretics. Especially bendrofluazide, impotence. • Steroid contraceptives and hormones. Possibly associated with decreased drive and orgasm • Alcohol and drugs of dependence. Erectile impotence, decreased drive and orgasm. • Cimetidine. Erectile impotence, decreased drive. • Antiepileptics.
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Specific situations • Post-myocardial infarction: fear in patient or partner about effect sexual activity may have on health. • Pregnancy and postpartum loss of sexual interest in women: probably mixed psychological and physical causation; postpartum dryness helped by lubricants or artificial vaginal moisturizer. • Epilepsy: may be associated with reduced enjoyment and activity, occasionally hypersexuality. Assessment The couple should be interviewed separately and together to obtain the following information: • Nature of problem, origin and course. • Marital history. • Sexual history, including family attitudes, puberty, masturbation, early sexual experiences, subsequent relationships, contraception, premorbid sexual functioning, past history of sexual dysfunction, intercourse and technique, effects of menstruation, childbirth and menopause. • Level of communication, commitment and conflict in relationship. • Psychiatric, medical, drug and alcohol history. • Attitudes to problem and expectations of treatment. • Physical examination, especially if there is ill health, dyspareunia, unexplained recent loss of desire, absence of normal erection, men over 50, peri- or post-menopausal women, menstrual irregularity, infertility, abnormal puberty or endocrine history or the patient has particular concerns. • Mental state examinations of both partners, including observation of their interaction.
Basic investigations • glucose in secondary erectile problems or late-onset ejaculatory disorders; • hormone profiles; • intracaversonal prostaglandin E differentiates vasculogenic from other causes of impotence as it gives no response; • nocturnal penile tumescence gives unreliable results - little used now. Management Any underlying disorder should be treated. Explanation, reassurance, education, discussion and advice with self-help literature is essential and may be sufficient.
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Couple therapy Masters and Johnson suggest mainly behavioural therapy with practical suggestions and education. It is not now thought necessary for there to be a male and female therapist or for treatment to be daily as they advocated. The aims of therapy are to decrease performance anxiety and spectatoring and to learn how to give and receive sexual pleasure. This involves the therapist taking the couple through a series of stages, carried out as 'homework', discussed and reviewed in therapy sessions.
Sensate focus Stage 1. Sensate focus without genital contact - 'touching your partner for your own pleasure': • The couple take turns to initiate and touch each other, both unclothed, comfortable and private. They agree to no genital touching or intercourse. • The person touching is doing so for his/her own pleasure only (selfassertion) to remove performance anxiety. • The person being touched says if anything is unpleasant and if so it is changed (self-protecting). Stage 2. Sensate focus without genital contact - 'touching for your own and your partner's pleasure': • The person being touched communicates what gives pleasure as well as what is not comfortable Stage 3. Genital sensate focus • Genital touching is allowed. • Partners still take turns to perform and receive touch. • Touching is still done and received for the pleasure of it. Orgasm is not the aim but is allowed. Stage 4. Genital sensate focus with simultaneous caressing. Stage 5. Vaginal containment: • Penile entry into the vagina for a limited period without movement Stage 6. Vaginal containment with movement: • Either partner can say 'stop' at any time. An equivalent process can be applied to single clients but usually with less success.
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Management and prognosis of specific sexual dysfunctions Erectile impotence There may be need for liaison with a urologist if there is an organic cause. There is a choice of physical treatments available which can be used in both organic and psychogenic dysfunction. Intracavernosal injections of prostaglandin E or papaverine can produce erection but priapism can occur requiring aspiration of blood and injection of an alpha-1-antagonist. Oral treatments: sildenafil is effective for most causes of dysfunction. Vacuum devices are safe, without significant side effects, but are considered clumsy and unsexy by many patients. If there are proven vascular abnormalities, vascular surgery may be indicated. Semi-rigid or inflatable penile protheses are another alternative. In all cases, intrapersonal and relationship issues must be considered and sex therapy is sometimes indicated, alone or in combination with physical treatment. Premature ejaculation 'Squeeze technique' involves squeezing the base or the glans penis just before ejaculation. Used in stages 3 and onwards of sex therapy. Vaginismus Treatment involves relaxation exercises combined with vaginal dilatation, e.g. with gradually increasing size of dilators, until penetration by the partner can be achieved. Good results achieved. Anorgasmia Masturbation, with or without sex aids should eventually lead to orgasm unless there is an organic cause. Premature ejaculation in men and vaginismus in women have the best outcome. Low sexual desire in women is the least amenable to improvement. In general, good prognostic factors are: acute onset; presence of a precipitant; short duration; absence of severe relationship disturbance; absence of psychiatric problems; high motivation and enthusiasm for treatment; normal premorbid sexual function.
Disorders of sexual preference Disorders of sexual preference (Table 21.2) were historically considered as offences against the laws of religion. Behaviour does not conform to
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a socially accepted view of what is 'normal', harm may be done to the other person involved or suffering is experienced by the person themselves. Help may be asked for by the person themselves, via their partner or via the courts. It may present as sexual dysfunction. Abnormalities in preference of the sexual object
Fetishism An inanimate object is the most important or sole stimulus for sexual arousal and gratification. Articles of clothing, shoes, rubber or plastic are common examples. Texture and smell are as important as look. Almost exclusively it occurs in men, usually starting in adolescence. They may spend much time looking for the object, or buying or stealing it. It is probably uncommon, but no exact figures are available. The cause is unknown; learning theory suggests that the object and sexual excitement occur together by chance at first. The prognosis depends on the extent of social and sexual relationships. Psychoanalysis and behaviour therapy are tried as treatment, but there have been no controlled trials of effectiveness.
Fetishistic transvestism The wearing of clothes of the opposite sex as means of obtaining sexual excitement. It varies from occasional to complete cross-dressing. Prevalence is not known, but it is rare among women. It starts at puberty, and there are no doubts about gender. Most are heterosexual, and many are in stable relationships and hide the behaviour from partner. There is no firm evidence of abnormal chromosomal or hormonal make-up. It is not familial. It may be related to association learning in the same way as fetishism. Probably it continues for years, decreasing in frequency with declining sexual desire in later life. A few may begin to resemble transsexuals. There is no specific treatment.
Paedophilia Repeated sexual activity (or fantasy of it) with prepubertal children as the preferred or sole sexual activity. There are no reliable prevalence
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figures, but it is probably very uncommon in women. The pattern is established early. Abused girls are commonly 6-12 years old, boys 12-15. In two-thirds of cases the victim is abused by the same adult more than once, the child's involvement often being through fear. The aetiology is unknown. The men often have a marked incapacity for relationships with adults. Prognosis is uncertain. If the behaviour is frequent it is likely to persist despite treatment. There is no convincing evidence that group or behavioural therapy is effective. Abnormalities in the preference of the sexual act
Exhibitionism Repeated exposing of the genitals to unprepared strangers without a wish for further contact. It usually results in sexual excitement and masturbation, but some are inhibited men who feel guilt and expose a flaccid penis. Behaviour may be persistent or episodic and is usually preceded by a build-up of tension. Mostly it is heterosexual men who expose to women and excitement is often heightened by the shocked reaction of the witness. The prevalence is not known, but exhibitionists make up one-third of sexual offenders referred for treatment and one-quarter of those dealt with by the courts. Those seen by doctors are usually between 20 and 40 years old and two-thirds are married. The aetiology is unknown, but the men are often unassertive and passive in everyday relationships. There is no reliable information about prognosis; there is some repeat behaviour only at times of stress, while in others it persists despite treatment. The reconviction rate is low after the first offence, high after the second. Most do not go on to commit violent sexual acts or interfere with children. Various types of psychotherapeutic treatment have been tried. Any associated psychiatric disorder should be treated.
Voyeurism Usually men who spy on women undressing or couples engaging in sexual behaviour. It is usually accompanied or followed by masturbation. The voyeur's own sexual activities are often inadequate. They may take considerable risks and are often reported by passers-by. The behaviour is not uncommon in adolescents and may persist in those who are shy with girls or have another obstacle to normal sexual activity. Behavioural theories involve chance association learning. No information is available on prognosis or conclusions as to effectiveness of the various psychotherapeutic techniques attempted as treatment.
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Sadomasochism Preferred or sole means of achieving sexual gratification involves receiving (masochism) or giving (sadism) pain or humiliation. Sadism Involves beating, whipping and tying. It is probably uncommon as a predominant sexual practice. The act may be symbolic rather than leading to injury. 'Lust murders' are extreme examples. The aetiology is unknown and there is no reliable information about prognosis. Masochism Involves being beaten, tied or symbolically humiliated. Dangerous assault may be allowed. The prevalence is unknown, but it is probably uncommon. The aetiology is unknown but there is a suggestion of a relation to beatings delivered to prepubertal children. The prognosis is unknown, but the behaviour is likely to persist.
Assessment and management Mental illness needs to be excluded. A detailed sexual history is taken and the partner is interviewed if possible. It is important to determine the part the behaviour is playing in person's life. Removing it may leave more difficult problems. Others, especially courts, prompt a request for help, but strong motivation is needed for success. The goal may be to control the behaviour or adapt better to it, and counselling may help these processes. If the goal is to give up, there is a need to anticipate how to fill the gap. Oestrogens, antiandrogens and behavioural therapy have all been used.
Sexual development and development of identity and gender Sexual development involves both inborn determinants, including genetic and hormonal factors, and environmental influences. It involves interaction between social learning where behaviour is shaped by its consequences and cognitive learning where stimuli and the responses evoked are categorized cognitively. Bancroft has suggested an eclectic interactional model of sexual development in which there are three strands and six stages. Strands • sexual differentiation into male or female and the development of gender identity; • sexual responsiveness; • the capacity for close dyadic relationships.
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Stages prenatal; childhood; adolescence and early adulthood; marriage; early parenthood, late parenthood; mid-life. The three strands develop relatively independently until adolescence when they begin to interweave. Sexual behaviour has various different functions such as pleasure, tension reduction, exertion of power or influence and maintenance of self-esteem. Interaction of these functions can lead to development of different sexual preferences. It is still unclear whether sexual preference is permanently formed early in the developmental process or whether it continues to be influenced and changed later. Gender is manifested in at least seven ways: chromosomes; gonads; hormones; internal sex organs; external genitalia and secondary sexual characteristics; gender assigned at birth; gender identity. The belief about whether one is a boy or a girl becomes fixed between the ages of 2 and 4 years - 'core gender identity'. If incorrect assignment occurs, it is probably easier to reverse later if the identity has remained equivocal. Gender identity disorders
Transsexualism A conviction of being the opposite sex, with feelings of estrangement from their body and an overpowering wish to live as a member of the opposite sex. The prevalence is of the order of 1 in 3500 men and 1 in women. In men, it tends to start before puberty, though follow-up studies have shown that effeminate boys are more likely to grow up as homosexuals than transsexuals. They are usually cross-dressing by the time help is sought. They also seek changes in their social role. Their sexdrive is usually low. They are often very distressed by their situation and depression is common. About one-third are married, and half of these will divorce. They will present to doctors for help to change sex.
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The women are often really homosexual, but will describe a strong conviction of being a man since childhood and strive to behave as such. The aetiology is uncertain. Sex chromosomes are normal, and there are no definite endocrine abnormalities or evidence that transsexuals are brought up in the wrong gender role. The disorder is possibly related to hormonal abnormalities during intrauterine development. There is no reliable information about prognosis, but the disorder probably persists and the suicide rate is increased. Patients seek treatment to change sex, and this must be done carefully in planned stages, with at least a year of living in the role of the opposite sex before surgery is performed. Dual-role transvestism Wearing of clothes of the opposite sex without sexual excitement and without the desire for permanent membership of that sex.
Gender identity disorder of childhood Prepubertal desire to be the opposite sex with distress about assigned sex. A preoccupation with the dress and activities of the opposite sex. It is relatively uncommon. One- to two-thirds of boys will show homosexual orientation during and after adolescence. Very few exhibit transsexualism in adult life. There is no evidence for endocrine causation. Family influences may be important.
Intersexual disorders Errors occurring during the process of sexual differentiation in the embryo can lead to sexual ambiguity or discordance between the chromosomal sex and the appearance of the external genitalia. True hermaphroditism This is extremely rare. Testicular and ovarian tissue are both present, genitalia often ambiguous. May have an ovary on one side and a testis on the other, or a mixture of ovarian and testicular tissue on both in an ovotestes. Most have 46XX karyotype. Male pseudohermaphroditism Gonadal tissue of only one sex, ambiguous genitalia or genitalia of the opposite sex. There are several causes: • Testicular feminization (androgen insensitivity) is the most common. External genitalia are female, but the vagina ends blindly, and there is no uterus or fallopian tubes. Testes are in abdomen or inguinal canal. It is caused by absence of androgen receptors in target organs. Psychological development is typically female. Sexual interest and preference are no different from normal women.
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• Reifenstein syndrome: incomplete androgen insensitivity, look male but with small testes, hypospadias and gynaecomastia. • Enzyme defects in testosterone synthesis, e.g. 5-alpha reductase deficiency: ambiguous genitalia, usually raised as girls with virilization at puberty; Chromosome mosaicism. Female pseudohermaphroditism Female karyotype, external genitalia ambiguous or male in appearance. There are several causes: • Congenital adrenal hyperplasia. This is the most common. It can be caused by various autosomal recessive enzyme defects. Reduced cortisol reduction leads to increase in ACTH and hyperplasia of the adrenal glands. One study compared a group treated from birth and a group treated later and found that both showed tomboyish behaviour as children, but the later treated group was more likely to report homosexual or bisexual fantasies. • Androgen-secreting tumour. • Maternal androgen ingestion during pregnancy.
Reading list Bancroft, J. (1989) Human Sexuality and its Problems. London: Churchill Livingstone. Beck, J.G. (1995) Hypoactive sexual desire disorder: an overview. Journal of Consulting and Clinical Psychology, 63(6), 919-27. Connor, M. (1997) Essential Medical Genetics. Oxford: Blackwell. Gregoire, A. and Pryor, J.P. (1993) Impotence: An integrated Approach to Clinical Practice. Edinburgh: Churchill Livingstone. Hawton, K. (1985) Sex Therapy: A Practical Guide. Oxford: Oxford University Press. Kinsey, A.C., Pomeroy, W.B. and Martin, C.E. (1948) Sexual Behaviour in the Human Male. Philadelphia: W.B. Saunders. Kinsey, A.C., Pomeroy, W.B., Martin, C.E. and Gebhard, P.H. (1953) Sexual Behaviour in the Human Female. Philadelphia: W.B. Saunders Rachman, S. and Hodgson, R. (1968) Experimentally induced 'sexual fetishism': replication and development. Psychological Record, 18, 25. Reamy, K.J. and White, S.E. (1987) Sexuality in the Pueperium. Archives of Sexual Behaviour, 16(2), 165-86. Rooth, F.G. (1971) Indecent exposure and exhibitionism. British Journal of Hospital Medicine, April, 521. Schott, R.L. (1995) The childhood and family dynamics of transvestites. Archives of Sexual Behaviour, 24(3), 309-27. Spengler, A. (1977) Manifest sado-masochism of males: results of an empirical study. Archives of Sexual Behaviour, 6, 441. Sugar, M. (1995) A clinical approach to childhood gender identity disorder. American Journal of Psychotherapy, 49(2), 260-81. Tomlinson, J. (1999) ABC of Sexual Health. London: BMJ Books.
22 Disorders of childhood and adolescence JANE WHITTAKER and RICHARD HARRINGTON
Most children show isolated emotional or behavioural symptoms at one time or another, and these are not usually a cause for concern. However, some children have psychiatric disorders that interfere with normal development and which require treatment. Therefore, an issue when a child is referred to a psychiatrist is whether a disorder is present that warrants treatment. To assess the possibility of psychiatric disorder, several different criteria are employed. These include: age and sex appropriateness of the behaviour or symptom of concern; persistence; sociocultural setting; pervasiveness; persistence; severity and frequency of symptoms; change in behaviour; degree of impairment of social functioning. Cases in child psychiatry are described using a multi-axial formulation, following the International Classification of Diseases, 10th edition (ICD-10). This format allows the succinct description of a child's disorder in six axes as follows: Axis 1 -clinical psychiatric syndrome. Axis 2-disorders of psychological development (specific developmental delay). Axis 3 - intellectual level (global developmental delay). Axis 4-medical conditions (medical diagnosis). Axis 5-associated abnormal psychosocial situations. Axis 6 - global assessment of psychosocial disability.
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Epidemiology The pre-school child (0-5 years) About one-fifth of pre-school children have a psychological problem. The rate for moderate and severe behavioural and/or emotional problems is less, about 1 in 10 children, and there is a male preponderance. There is some stability of symptomatology over time; about two-thirds of these children have problems that persist into their school years. Middle childhood (5-11 years) The main source of data on this age group is still the Isle of Wight (IOW) and Inner London Borough (ILB) studies conducted by Michael Rutter and colleagues. Overall, the point prevalence rates were 7 per cent IOW (semi-rural), 13 per cent ILB (urban), with more boys affected than girls. Importantly, increased prevalence rates occurred in physical disorders: any physical disorder =12 per cent; brain disorders = 44 per cent; epilepsy = 29 per cent; brain lesion and epilepsy = 58 per cent. Adolescence (> 12 years) Estimates of the extent of psychiatric disorder in this age group are complicated because the boundaries of adolescence are not easy to define. Estimates of psychiatric problems in adolescence suggest an overall prevalence of about 20 per cent, and a handicapping psychiatric disorder in 8 per cent. This figure includes disorders persisting from childhood and those arising anew in adolescence. Aetiology Biomedical factors
Genetic A variety of psychiatric disorders of childhood have a genetic component in their aetiology. Heritability of autism is of the order of 90 per cent. Other disorders with a genetic component include depression, Gilles de la Tourette syndrome, attention deficit disorder and enuresis. Psychotic disorders have a genetic component in their aetiology. For many of the observed genetic effects in child and adolescent psychiatric disorders, however, their impact is thought to be interactive, in the sense that they predispose to psychiatric disorder in the presence of adversity. Genetic factors may play a part in determining the child's temperament, but it is the temperamental factors, in conjunction with environmental and family factors, that is likely to drive the disorder.
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Neurophysiology, neurochemistry and neuropsychology Little is known, relative to adults, about paediatric neurophysiology and neurochemistry. Substantial developmental changes occur in the brain from birth through to adolescence, so assumptions about neurobiological mechanisms in children based on adult studies are likely to be fairly weak. A clinical example of this is the apparent lack of efficacy of tricyclic antidepressants in early adolescent depression.
Prenatal and perinatal factors Single gene disorders and chromosome abnormalities may be associated with general or specific (behavioural phenotype) psychiatric symptomatology. All manner of intra-uterine insults can afflict the developing fetus, influencing the risk of future psychiatric disorder. These include maternal drug and alcohol misuse and maternal infection. Prenatal maternal rubella infection can cause learning disability, including an autistic-like syndrome, and a link has been postulated between maternal influenza infection and schizophrenia in adult life. Obstetric complications are associated with various psychiatric disorders of childhood (conduct disorder, attention deficit disorder, specific learning difficulties), although pathways of causality are not clear.
Temperament Thomas and Chess suggested that children were active participants in their own development, in contrast to more behavioural formulations of child development. A child's experiences had an influence on their development, but different children negotiated experiences differently and different children were predisposed to seek out different kinds of experience. Thomas and Chess proposed that this predisposition had a constitutional, biological basis, and used the term temperament to describe it. Different children had different behavioural styles, or types of temperament, and different temperaments might contribute to different types of disorder. The New York Longitudinal Study examined parental reports of behaviour of a large number of small children. Three categories of temperament, based on nine behaviour characteristics were defined. The three categories of temperament were (1) easy; (2) slow to warm up and (3) difficult. The features of each category and related disorders are shown in Table 22.1.
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Categories of temperament in children Easy
Slow to warm up
Difficult
Reactions: Mood state: Regularity of function: Reactions to novelty:
mild positive ++ positive
intense negative
Adaptability to new situations: Predisposed to:
good
mild intermediate +/initial withdrawal, then positive slow phobic disorders
withdrawal poor behaviour disorders
Neurological disorder All forms of brain disorder and brain injury, at any age, increase the risk of all types of psychiatric disorder. In childhood and adolescence, however, the effects on the developing brain may be diverse and far reaching. Disorders may affect brain systems not yet developed or subsidiary systems on which subsequent brain development depends. Brain disorders may be psychopathogenic via direct effects on the brain, e.g. epilepsy, or indirectly by virtue of obstacles placed in the way of development, such as chronic physical disorders causing decreased school attendance and reduced opportunities for peer group interaction.
Other medical disorders All forms of medical disorder, especially chronic disorder, can increase the likelihood of psychiatric problems in childhood. Indirect mechanisms are similar to those in neurological disorders, but direct mechanisms may be less clear. At adolescence, continuing dependence on parents or extra parental supervision of an adolescent by parents can lead to difficulties. Diabetic control may be disrupted in adolescence because of these types of difficulties. Delayed puberty in boys is associated with mood disorders. Psychological factors
Cognitive development, learning disability and cognitive impairment Learning disability and cognitive impairment, of any aetiology, increases the likelihood of all forms of psychological symptomatology and psychiatric disorder (see above). This may be a result of direct effects on the brain, or indirect effects such as increased vulnerability to life events or diminished ability to cognitively reflect on events. Moderate and severe levels of learning disability are associated with increased rates of attention deficit and autistic symptomatology. Milder degrees of learning
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disability and specific developmental delays (language and reading especially) are associated with attention deficit disorder and conduct disorder.
Attachment Bowlby and Ainsworth described the concept of attachment, which concerns the child's first significant relationships. The term attachment has come to mean many things and describe many aspects of early carer-child relationships. However, the core definition of attachment applies to an internal psychological process, with external observable behaviours, and has a developmental sequence. Babies below 6-8 months old are usually indiscriminately friendly, showing a profound curiosity in and about other people. In the later half of the first year of life babies begin to become cautious of people they do not know (stranger anxiety). They begin to show a preference for familiar people in their environment (selective attachments), such as parents, grandparents, sibs and other key caregivers (attachment figures). Particularly when upset, worried, in unfamiliar surroundings or ill, small children will try to stay close to their attachment figures (proximity seeking). When playing, children will frequently check back with their attachment figure, using him or her as a secure base. If subjected to long or surprise separations from attachment figures small children will sometimes demonstrate a series of behaviours. Initially, they will protest, manifested by crying out for the attachment figure (usually, but not invariably, the mother). If the separation is prolonged the child can become withdrawn, and avoidant (despair). On reunion, the child might be observed to be angry and upset with the parent for leaving them, and even act as though they wish to avoid the parent (detachment). Most children tolerate relatively brief situations without too much difficulty. Brief separations followed by reunion form the basis of the Strange Situation Paradigm, developed by Ainsworth. In this research scenario, children are briefly separated from their mother (usually). The effect of separation and then reunion is observed and recorded. On the basis of children's responses Ainsworth described a series of categories of attachment. These are avoidant (A), secure (B), resistant-ambivalent (C) and disorganised-disorientated (D). The paradox of attachment is that the more securely attached a child is, the better able they are to separate from the parent, and the more able to explore their environment. It is hypothesized that the observable behaviours reflect an internal, dynamic and cognitive process, wherein the child is incorporating key attachment figures into internal working models, forming templates for future relationships. Disruption of attachment has implications for later relationships, and perhaps other aspects of social and cognitive development.
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Family adversity, life events and adverse experiences Adverse life events may affect children directly (loss of a parent by divorce or death) or indirectly, via their impact on a child's parents or psychosocial circumstances. Events may be acute or have a chronic component or chronic sequelae. However, chronicity of adversity, or chronicity of sequelae of acute life events, are more important and toxic aetiological factors for childhood psychiatric disorder. The form of life event particularly relevant to children that has exercised much public attention is abuse. Physical, sexual and emotional abuse and neglect can all have significant short- and long-term sequelae, as discussed in the later section on child protection. Psychosocial factors Families are especially important in child and adolescent psychiatry because children are brought to health services by their parents, who are important in achieving a successful therapeutic outcome for the child. Parents are vital in implementing a behavioural modification programme and in family therapy. They will set the context and determine attitudes towards psychodynamic psychotherapy and medication. There are a number of family factors that are important in the aetiology of childhood psychiatric disorder: discordant family relationships, lack of emotional warmth in family relationships, psychiatric disorder in a parent, criminality in a parent, and large family size.
Parenting Parenting practices have a large impact on children. Recent work has used a classification with three main parenting styles: authoritarian (autocratic, unaffectionate), permissive (laissez-faire, indulgent and affectionate) and authoritative (rules with explanations, boundaries set, child listened to, but parents remain final arbiter). Some parenting styles are associated with some types of psychological difficulties; authoritarian parenting is said to be associated with over-compliance, dependency and withdrawal in the child, and permissive parenting with immaturity, lack of purpose and lack of self-control.
Parental mental illness The relationship between parental mental illness and psychiatric disorder in children is one of the strongest in child psychiatry. The risks are partly due to genetic effects. However, there are also nonspecific effects of parental mental illness on children, mediated by environmental factors. The impact of parental psychiatric disorder seems to be related to severity and chronicity of disorder in a parent, and the disorder's capacity to induce intra-familial discord, increase psychosocial deprivation and
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cause inconsistencies in parenting. Occasionally, parental mental illness may place the child at particular risk, particularly when a youngster is incorporated into a parent's delusional beliefs. Postnatal depression is a special case, which if untreated has potentially damaging, long-term effects on the developing relationship between mother and child.
Depressive disorders Depressive disorders occur at all ages; symptoms will vary depending on the child's age and development. Symptoms of depression in childhood As in adults, symptoms seen in children include depressed mood, sleep disturbance, irritability and suicidal ideation. More common in prepubertal children are somatic complaints, psychomotor agitation, separation anxiety, weepiness and clinging and phobias. More common in adolescents are hopelessness/helplessness, anhedonia and hypersomnia. Depression in this age group has high associated co-morbidity. Misuse of alcohol and drugs is seen and somatic complaints may be reported. About 35 per cent of children who are depressed also have an anxiety disorder and a similar number a co-morbid conduct disorder. Epidemiology Prevalence of depression in prepubertal children is between 0.5-2.5 per cent. Prevalence in adolescents is higher, 2-8 per cent. In younger children the prevalence is approximately equal between males and females; in adolescence, girls outnumber boys. Aetiology This is multifactorial, as in adults. Parental depressive disorder is important, because of genetic factors, and because of the impact of depression on parenting. Evidence for a role for biological factors is still unclearwork in adults suggests an abnormality in brain neurotransmitter systems involving catecholamines and serotonin. Less support for this exists in children. Early adverse experiences, e.g. early separation, loss of a parent, lack of care, physical illness, have all been found to be important in predisposing to depression, both within childhood and into adult life. Life events act as precipitant to the onset of a depressive episode, e.g. bereavement, parental separation and disasters. Adversities, e.g. poor friendships, chronic illness in the family and poor housing, can increase the impact of life events. Treatment Psychological treatments are the first-choice therapy in children and adolescents with moderate and severe depressive disorders. Cognitive
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behaviour therapy is of proven effectiveness. Additional work with parents may be needed too. Antidepressants are generally second-line therapy, only used in more severe cases, especially those with a more 'adult' pattern of symptomatology. SSRIs are the medication of choice, in view of their relatively more acceptable side effect profile, and they are less toxic than tricyclics if taken in overdose. Sudden deaths have been reported in children and adolescents receiving tricyclics. ECT is only very rarely prescribed for children and adolescents. Prognosis For a single episode, prognosis is usually good but risk of relapse is high. Untreated or recurring depressions are associated with poor psychosocial outcome, school failure, an increased risk of later depressions, increased substance misuse and increased rates of suicide (especially in boys).
Obsessive-compulsive disorder Symptoms of obsessive-compulsive disorder (OCD) in childhood Symptoms seen in childhood are much as those found in adults. In adults, acknowledgement of the ridiculousness of the thought or ritual and the recognition the thought as an unwanted product of one's own mind is important to distinguish OCD from other disorders. This quality of insight may not be present in child and adolescent patients. OCD can occur as part of/along with depression, Gilles de la Tourette syndrome and occasionally as a herald to schizophrenia. Mild obsessional symptoms are seen in normal development. Key distinguishing features are age of child, nature of ritual, severity of symptom, its persistence beyond normal developmental stage and degree of interference with activity. Healthy young children often want activities, e.g. bedtime routines, to conform to a set pattern, but will show some degree of flexibility. Epidemiology OCD in children and adolescents is probably under-reported. Approximately 1 in 200 youngsters are reported to have significant OCD symptomatology. Aetiology Various psychological and psychodynamic theories have been proposed. These include having perfectionistic parents, issues of ambivalence, control and sexuality. The evidence for these is relatively weak. Biological factors are thought to be more important. OCD is related to basal
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ganglia dysfunction. Serotonin (5-HT) has been implicated, supported by the good response to SSRIs. Treatment The mainstays of therapy are cognitive behavioural therapy, including a graded programme of activity, response prevention and in vivo exposure. Medication, especially SSRIs, is of proven benefit in OCD. SSRIs are much safer than clomipramine. Family work is crucial, particularly supporting parents and helping them resist being drawn into a child's symptoms. Prognosis Approximately half of the adults who have OCD report an onset in childhood or adolescence. For these patients OCD seems to be a lifelong disorder that waxes and wanes throughout life.
Anxiety disorders with onset specific to childhood Symptoms ICD-10 defines several anxiety disorders of childhood. These disorders include anxiety disorders which are specific to childhood, but also very early onset, but essentially adult-type anxiety disorders. ICD-10 defines separation anxiety disorder, phobic anxiety disorder, social anxiety disorder, overanxious disorder of childhood and sibling rivalry disorder as childhood anxiety disorders. Sibling rivalry disorder is somewhat contentious. Other anxiety disorders seen in adults, but seen in children and adolescents too, include panic disorder, dissociative disorders and generalized anxiety disorder.
Specific symptoms • Separation anxiety - unrealistic worries about parents or getting lost, school refusal, nightmares, fear of being alone, distress before separation. • Phobic anxiety disorder - abnormal intense fear with avoidance of specific objects or situations which would not normally have that effect. • Social anxiety disorder - persistent recurrent fear of strangers beyond that expected for the child's age and associated with impaired social functioning. Epidemiology Community samples estimate the prevalence of anxiety disorders at between 5.4 per cent and 15.4 per cent. Females equal males in early and mid-childhood, but females outnumber males from adolescence.
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Aetiology Predisposing factors include genetic influences, slow to warm up temperament, adverse early separation experiences and overprotective, anxious parents. Anxiety disorders can be precipitated by life events and physical illness, and be maintained by ongoing family factors, such as maternal anxiety and depression. Treatment Psychological treatments are usually used and include individual psychological therapies, including cognitive behaviour therapy and behaviour therapy. Supporting parents is crucial, and may include formal family therapy. Prognosis This is generally favourable. The continuity of childhood anxiety disorders with adult anxiety disorders is not well researched, and as yet little is known.
School non-attendance Failure to attend school is a symptom, rather than a syndrome, requiring investigation. Treatment, however, is of both the underlying syndrome and the school non-attendance; in other words, getting the child back to school as quickly and as smoothly as possible. Common underlying disorders are depressive and anxiety disorders and conduct disorder. School refusal generally implies a more emotional or depressive disorder underlying school non-attendance. School non-attendance due to truancy generally implies a conduct problem. Distinguishing features are shown in the Table 22.2. Some children are actively withdrawn from school by their parents. In these circumstances the child may well have been withdrawn from school because of the parents' need. An agoraphobic mother, who cannot function without the presence of the child, may withhold the child from school, using him or her as a talisman.
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Parents know that child is not attending school Associated conduct problems Associated emotional problems Family relationships Day spent? Gender distribution School performance Family history Possible precipitating factors Time of onset
Classifying school refusal
School refusal
Truancy
Yes
No
No
Yes
Yes
No
Over-involved, anxious mother, absent father At home Girls > boys Usually good, relative to ability Anxiety and depressive disorders Illness, interpersonal distress May coincide with change of school, e.g. primary to secondary school
Large, chaotic, inconsistent and/or punitive parenting Out, with or without peers Boys > girls Usually poor, relative to ability Conduct disorders, +/— personality disorder Possibly disciplinary dispute, otherwise none Not usually related to school change, mid to later secondary school years
Suicide and deliberate self-harm Adolescent suicide Psychological post-mortems have shown that in half of cases a family member has sought psychiatric help. Most subjects were living at home with one or both parents at the time of their death and had evidence of antisocial behaviour, affective disturbance or both. IQ was usually average, but the youngster was not usually achieving full potential. A disciplinary crisis was often reported immediately prior to death. Social isolation may also be important. Many of those who go on to complete suicide discuss killing themselves in the preceding 24 hours. Adolescent overdose Family histories show increased rates of psychiatric disorder and overdose and family circumstances are often disrupted. A diagnosis of depression is made in around | of cases. Many more adolescents report significant distress, significant numbers have a conduct disorder and psychosis is rare. This group also have increased rates of contact with helping agencies. Social isolation is a feature. Treatment Medical management of overdose or deliberate self-injury comes first, followed by a detailed psychiatric assessment of the child, interview with the family and, perhaps, teachers and GP. Additional questions to
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an adolescent include enquiries about bullying, abuse and, in girls, the possibility or fear of pregnancy. Management of any underlying psychiatric disorder is needed, but problem-solving work with the adolescent can impact on the likelihood of further acts of self-harm.
Conduct disorder (CD) and oppositional defiant disorder (ODD) Symptoms Conduct disorder is typified by a repetitive and persistent pattern of antisocial, aggressive or defiant conduct, more serious than childish mischief or adolescent rebelliousness. CD is subclassified into socialized and unsocialized types. In the former, disturbed behaviour is often a group activity and the child is able to make relationships within the group. In the latter, the child finds it much harder to make relationships and will tend to act alone. The essential feature of ODD is a pattern of persistently negativistic, hostile, defiant, provocative and disruptive behaviour outside the normal range of a child of the same age in the same sociocultural context. Distinguishing ODD and CD from naughtiness, mischievousness and adolescent disobedience should not be problematic, but can be conceptually difficult, and is not just a function of age, severity or pervasiveness. ODD is not simply a mild form of CD. A key feature is that ODD does not include children whose behaviour violates the law (whether or not they are caught) or the basic rights of others. Such children would be described as having a CD. However, some would see ODD as a precursor to CD. Co-morbidity is high. Children often have accompanying mood disorders and/or attention deficit disorder and/or speech and language delay and/or specific reading retardation. Epidemiology The Ontario Study reported a prevalence for children and teenagers between 4 and 16 years of 5.5 per cent. Boy to girl ratio was 4:1. Rates in urban areas tend to be slightly higher than in rural areas, especially for younger children. Aetiology Biological factors play a role (epilepsy, mental handicap) and there is a relationship between conduct disorder and clumsiness, impaired language development and specific reading retardation. Affected children are often described as impulsive, assertive and active - consistent with a 'difficult' temperament. However, the strongest aetiological factors are family dysfunction, parental mental illness, alcoholism and criminality in parents and significant psychosocial deprivation and poverty.
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Treatment Treatment is difficult, and has to be applied bearing in mind the child's age, developmental level and motivation. Family motivation to effect change and support the youngster is crucial, but families are often difficult to engage in a consistent therapeutic programme. Individual work may be appropriate if the child has an accompanying mood disorder, or if they are motivated to work on an aspect of their behaviour, e.g. controlling temper outbursts. Parent management training is especially suitable for younger children. This and 'parent-child game' are two treatment programmes of proven efficacy. Community interventions have been tried, on the principle that intervening early with high-risk groups reduces the extent of later CD. Community programmes focus on learning skills and nonviolent alternative responses to problems.
Prognosis One-third of children with CD go on to develop antisocial personality disorder in adulthood. A number of prognostic indicators have been identified, as shown in Table 22.3. Table 22.3
Prognostic Factors for CD and ODD
Good prognosis
Bad prognosis
Young child Motivated parents Stable/intact family Precipitating factor Accompanying emotional disorder No learning difficulties No physical/brain dysfunction No family history
Older age Aggression Pervasive problems Unsocialized type Learning difficulties Family history psychiatric disorder Unstable family Inconsistent discipline Social disadvantage Lack of precipitant
Attention deficit hyperactivity disorder (ADHD) Symptoms Key features of ADHD are distractibility, and difficulty sustaining attention and focusing on a task. These symptoms are associated with impulsiveness, regardless of consequences. Children with ADHD are often intrusive, unable to complete tasks and easily distractible. They have problems conforming to classroom expectations, and children are often referred in the first years of school (6-8 years old), often with a history of overactivity and restlessness since infancy. Symptoms should be persistent, pervasive and present in more than one situation, e.g. school and home.
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Co-morbidity is high. Patients can also have concurrent anxiety or depression. Overactivity is common in children with learning difficulties, but may be a reflection of developmental level, not disorder. Overactivity can be a symptom as well as a syndrome. Children who are depressed, distressed and anxious can be active, distractible and have poor concentration. However, management of these children will be quite different from treatment of the child with ADHD. Epidemiology Definitions of the disorder vary widely, particularly between the USA (high prevalence) and the UK (relatively low prevalence). Estimates vary from 0.1 per cent to 10 per cent. A good UK estimate would be 4 per cent. In the USA some children who are diagnosed as having ADHD would have received a diagnosis of conduct disorder in the UK. Boy to girl ratio is 4:1. Aetiology A genetic link has been established, based on evidence from family studies, twin studies (MZ vs. DZ) and adoption studies. Neuropsychological studies of children with ADHD have demonstrated impairments on tasks implicating frontal lobe systems. These findings support neuroimaging studies demonstrating hypoperfusion of the frontal areas of the brain. EEC studies show higher incidence of nonspecific, non-epileptic abnormalities, although the significance of these is unclear. There is some evidence for abnormalities in serotonin, noradrenaline and dopamine pathways, but results to date are not specific. Lead and food additives have both been proposed as possible aetiological agents, but the evidence for these is weak. The evidence for psychosocial deprivation suggests a nonspecific effect, but the disorder is associated with poor family coping and hostility towards the child. Whether this hostility is causal or a result of ADHD is uncertain - probably both (akin to high EE). Treatment Treatment comprises two components: • Medication, using stimulants (methylphenidate and dexamphetamine), which have been shown to reduce levels of hyperactivity. Side effects of stimulants include abdominal pain, headaches, depression, insomnia, anorexia, growth retardation, and unmasking of and/or exacerbation of tic disorders. The last is particularly important - tics may not disappear on withdrawal of stimulant medication. Treatment with medication is long term. • Psychological therapies include psycho-educational work with parents to help them deal with their child's behaviour. Behavioural approaches
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reward desired behaviour and (if possible) ignore unwanted behaviour. When possible, environmental manipulations, e.g. in school, reduce opportunities for disruption, distraction and loss of concentration. Prognosis Prognosis depends more on intelligence, socioeconomic group and extent of family hostility and degree and severity of co-morbid disorders (especially conduct disorder), than degree of hyperactivity. The worst outcome is seen in late-presenting adolescents, when patients are often aggressive, show antisocial behaviour and are involved in antisocial activities. They are otherwise inattentive, impulsive and remain isolated and unpopular with their peers. They do not achieve academically. A good prognosis disorder (early diagnosis and treatment, supportive nonpunitive parenting, absence of co-morbid conduct disorder) may settle in adult life and some subjects have a relatively good outcome.
Tic disorders Once considered rare, improved diagnostic skills have demonstrated that this group of disorders is relatively common. G/7/es de la Tourette syndrome (GTS)
Symptoms This disorder includes complex motor (including vocal) tics, but these features alone are not considered sufficient for diagnosis. Multiple complex motor tics should be present, usually occurring in the context of other motor abnormalities (e.g. echopraxia) and language abnormalities (echolalia, pallilalia). Coprolalia (and copropraxia) are seen, but are not required criteria for diagnosis. Some patients describe somatosensory triggers for tics. Tics reduce, but do not altogether disappear, during sleep. Stress and distress can worsen tics. Some patients can exert a degree of transient, voluntary control over tics, but usually this cannot be sustained. Equally, tics may be associated with an irresistible inner urge to allow the movement (or vocalization) to occur. Complex motor tics need to be distinguished from dystonic and choreiform movements. Peak age of onset is 7 years, with a range of 2-15 years. Co-morbidity is very high. Depending on diagnostic criteria, 30-60 per cent of sufferers also have OCD, and 40-50 per cent have ADHD.
Epidemiology This varies, depending on study and criteria. About 5 children per 10 000 have GTS.
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Aetiology GTS, like autism and to a lesser extent ADHD, is a neuropsychiatric disorder. Genetic factors are important; family pedigrees demonstrate a high incidence of GTS, tic disorders and OCD among relatives. Neuropathology and neuroimaging studies implicate the basal ganglia and, especially, corticostriatal circuitry, in the pathogenesis of the disorder. Abnormal levels or functions of various neurotransmitters and their respective systems have been described - these include dopamine, GABA, neuropeptides and serotonin.
Treatment A crucial first step is to educate families and teachers about the disorder. Children with GTS rapidly become isolated and stigmatized at home and at school. High levels of punitive or hostile responses to tics stress the child and are likely to make tics worse. A vicious cycle can rapidly become established. The main role of psychological treatments, both individually and family based, is reduction of levels of hostility, treatment of intercurrent behaviour disorders and cognitive behaviour therapy for concurrent OCD symptomatology. The mainstay of therapy for more severe cases is medication. Haloperidol or sulphide, in small doses, reduces tics, but adverse effects on cognition, and therefore school, have to be borne in mind. The risks of short- and long-term (tardive dyskinesia) side effects have to be carefully balanced against benefits, especially in a disorder whose natural history is one of relapse and remission. Clonidine may be beneficial, but effects on blood pressure, and problems associated with sudden discontinuation have to be borne in mind. Treating GTS and concurrent ADHD poses a particular problem. Psychostimulants (methylphenidate and dexamphetamine) make GTS worse. Concurrent OCD responds to SSRIs.
Prognosis GTS is a disorder that waxes and wanes. About a third of cases will remit during adolescence, a third will show good improvement by adolescence and a third of cases will continue to remain symptomatic into adulthood. GTS is a devastating disorder. Patients are stigmatized and often isolated. Co-morbidity is high (see above), and all forms of psychiatric disorder are elevated.
Developmental disorders Developmental disorders have the following features in common: • an onset that is invariably during infancy or childhood;
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• an impairment or delay in functions that is strongly related to biological maturation of the central nervous system; • a steady course that does not involve the remissions and relapses that tend to be characteristic of psychiatric disorders. Developmental disorders are divided into three types: (1) specific developmental disorders; (2) mixed developmental disorders, and (3) pervasive developmental disorders. Specific developmental disorders These disorders describe delay of the equivalent of two standard errors of prediction or two standard deviations in one academic or functional domain. These domains are speech and language, motor function or scholastic ability (specific reading retardation, specific spelling disorder, specific disorder of arithmetical skills). Criteria are based on extent of delay, relative to other functions. In addition, the delay observed has to be present in the absence of other factors which might account for it: low global ability, brain damage, diminished opportunity to attend school or inadequate schooling or visual impairments. In children with specific reading disorder, concomitant emotional and behavioural problems are seen. Mixed developmental disorders Mixed disorders involve several functions, and may include subtle impairments of social function too. However, the overriding features are not in the social communicative domain - such disorders would be classed as pervasive developmental disorders. These disorders are still poorly defined, but represent a useful diagnostic category to account for children who do not have a mental handicap, but do have complex developmental delays in several scholastic and/or motor and/or speech and language domains. Pervasive developmental disorders (PDD) These tend to involve most or all aspects of development. The exemplar disorder is autism. It is usual, but not invariable, for there to be some degree of general cognitive impairment. However, pervasive developmental disorders are defined in terms of behaviour that is deviant in relation to mental age. In other words, if a child's language and social development are delayed, but this delay is no greater than would be expected on the basis of the general cognitive level, then the child would be regarded as having general mental retardation, not a pervasive developmental disorder. Several subtypes of pervasive developmental disorder are recognized: infantile autism (Kanner's syndrome), Asperger's syndrome, disintegra-
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tive disorders and Rett's syndrome. A fifth subtype, semantic-pragmatic disorder is being considered, but its validity as a separate category is not yet conclusively established. Autism The diagnostic criteria for autism are: • • • •
an onset before 30 months; delayed and deviant social development; delayed and deviant language development; stereotyped behaviours and routines.
Typically, children with autism have impaired social relationships, do not engage in reciprocal play with other children, and do not show normal attachment behaviours. They rarely initiate social interchanges and tend to ignore others. About 50 per cent of children with autism never develop useful speech. Of those that do, speech and language is delayed. Non-verbal social communication (e.g. pointing, eye contact, gesture) is impaired. Individuals with autism fail to use language in social settings, and show a lack of social reciprocity. Autistic children who develop some speech show characteristic abnormalities: delayed echolalia, you/I (pronominal) reversal and neologisms. The play of autistic children tends to be stereotyped, nonfunctional and lacking in imagination. Often there are attachments to inanimate objects, which they have to carry around with them. Ritualistic and compulsive phenomena are common. Typically, there is intense resistance to change.
Epidemiology Four to six per 10000 children have autism, more have atypical forms, prevalence varying with how strictly the disorder is defined. Boys are affected more than girls (boy:girl ratio 3:1). There is no association with socioeconomic status.
Aetiology Evidence points to an organic basis; there is a strong association with mental retardation (about 75 per cent have IQ < 70), about 25 per cent later develop epilepsy, and autism has been described in association with a number of medical conditions (e.g. fragile X, tuberose sclerosis, rubella embryopathy). Twin studies of cases of autism without diagnosable medical conditions (the majority of cases) suggest there is a strong genetic component. Heritability of the disorder is of the order of 90 per cent. Autism is rare in families of autistic children, the risk of having another child with
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autism is around 3 per cent, but this represents an increased frequency of 50-100 times compared to the rest of the population. Developmental disorders (e.g. mental handicap, language disorders and social communication impairments) appear to be quite common in the families of autistic children, suggesting that what is transmitted is a genetic vulnerability rather than the disorder as such. Just how a neurobiologically-based developmental disorder causes the psychological deficits that characterize autism is not known. However, current theories emphasize: • The specific nature of the deficits (cf. idiots savants who are often autistic, who show islands of superior functioning (e.g. musical ability, mathematics) against a background of general retardation). • Cognitive deficits in mentalizing (so-called 'theory of mind').
Treatment There is no cure for autism. The goals of treatment are: fostering normal development where possible, promoting the child's learning more generally, reduction of rigidity and stereotypy, elimination of maladaptive behaviours and support for and alleviation of family distress. An overall treatment programme should include: • appropriate medical care (e.g. of medical conditions, genetic counselling, discuss prognosis, facilitating dental care); • special educational provision (e.g. suitable class or unit, extra services); • family support (behavioural methods, practical help, respite, support, books); • direct treatment (drugs, social skills groups, speech therapy). Pharmacotherapy is of no proven benefit.
Prognosis Most children with autism will be unable to live independently as adults. About 10 per cent are able to work, and 50 per cent show improved interpersonal relationships as they grow older, but they are still obviously abnormal. The best predictors of a positive outcome are IQ (IQ > 75 better prognosis) and language level at age 5 years. Good verbal abilities at 5 years indicate a better prognosis. About 25 per cent develop seizures (all types of seizure), and about 10 per cent show a deterioration in abilities in adolescence, the cause of which is unknown. Asperger's syndrome
Symptoms Severe impairments in reciprocal social interaction, all-absorbing, often unusual, circumscribed interests, desire for routine. Speech (vocabulary)
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is superficially good, but use of language (pragmatics and prosody) and comprehension of language (what people mean as opposed to what they say) is poor. Receptive and expressive non-verbal communication is usually impaired and odd. Motor clumsiness is a common feature. Asperger's syndrome is distinguished from high-functioning autism by the absence of language delay. Whether this syndrome is a variant of autism is still debated. Asperger's syndrome is not 'mild autism'.
Epidemiology About 3 per 1000 have Asperger's syndrome, boys more than girls.
Treatment As for autism. A significant proportion go on to develop mood disorders, which may present atypically because of the Asperger's syndrome.
Prognosis Hard to define, because follow-up studies have used widely varying diagnostic criteria. The less carefully defined the disorder, the better the prognosis; however, most adults with Asperger's syndrome struggle to live alone, nor do they often marry or form long-term adult relationships. They may succeed academically, sometimes finding a niche within which they are able to function relatively independently.
Disorders of elimination Enuresis Symptoms Enuresis is the involuntary voiding of urine, in the absence of adequate, explanatory physical disorder, in a child under 5 years. Primary enuresis implies that the child has never achieved continence, secondary enuresis means that the child has resumed wetting after a period of continence. Most cases of uncomplicated enuresis are managed by community paediatric services, and rarely reach child and adolescent psychiatrists, unless there is other significant psychopathology.
Epidemiology By age 5 years, 3 per cent of children are still wetting during the day and f 0 per cent at night. Pre-school girls are as likely to be wet as preschool boys. By middle childhood, boys outnumber girls. By 14 years, 1 per cent of youngsters are still regularly wetting at night.
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Aetiology Children are more likely to achieve continence late if there is a positive family history, especially in fathers. Developmentally delayed children will achieve continence later than nondelayed. Delayed or chaotic toilet training may delay acquisition of continence. Secondary enuresis can occur in association with a period of upset.
Treatment A kind, sensitive approach on the part of parents is crucial; parent education about toilet training, normal development and a nonpunitive stance is vital. Night waking to go to the toilet and encouraging the child to report bed-wetting are simple first steps. Behavioural methods include star charts and pad and bell. Occasionally, especially if the child is staying away from home, synthetic intranasal antidiuretic vasopeptides can be used. Tricyclic drugs have been shown to reduce nocturnal enuresis, but sudden deaths have been reported in children being given these drugs.
Prognosis This is good. Encopresis
Symptoms True' encopresis is the voluntary passage of formed faeces in inappropriate places. It is not the same as soiling due to accident, developmental delay or faulty toilet training. Encopresis has to be distinguished from constipation with overflow, a result of physical problems such as anal fissure or Hirschsprung's disease (and other congenital causes of severe constipation), or poor diet.
Epidemiology Bowel control is normally fully established by a child's 4th birthday. By 8 years, approximately 1.5 per cent of children are soiling. Boys outnumber girls.
Aetiology Aetiology of true encopresis is hard to define. Soiling is associated with various physical precipitants. Clinically, high levels of intra-familial hostility are seen, but whether this is a cause or effect of the soiling is difficult to judge. There is an association between soiling, encopresis and enuresis, suggesting a role for developmental delay.
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Treatment Behavioural methods, especially a toileting programme, with star charts and rewards, if necessary supplemented by laxatives. Reducing parental hostility towards the child is vital, but often difficult, especially if the child is being scapegoated. Family therapy may be needed in addition to a behavioural programme.
Prognosis Little known. There are case reports of patients who continued to soil into adult life. The clinical assumption is that most cases of encopresis resolve spontaneously by adolescence.
Psychosomatic disorders Symptoms Many children present to health services with physical complaints that are not easily explained by physical pathology or disorder. Common ones are: headaches, abdominal pains, fatigue. Rare ones are: paralysis, blindness, paraesthesia, seizures, aphasia, aphonia. Epidemiology Great variation is found, depending upon symptom considered and type of population being studied. These disorders make up 1 per cent of referrals to psychiatric clinics. Non-organic abdominal pain is seen in 10 per cent of patients attending paediatric clinics. Aetiology Onset of a psychosomatic disorder may be related to a stressful situation or event, or during or following a minor physical illness. The affected child's temperament is often described as conformist, conscientious, sensitive, insecure, anxious or 'difficult'. Often, there is a family history of similar problems. A hostility to psychological explanations, concern about illness or preoccupation with loss or death is sometimes found. Family functioning is often abnormal, causal and a consequence of the child's psychosomatic disorder. There may be communication difficulties within the family, plus poor conflict resolution with overprotection and close (enmeshed) relationships. Children with a somatizing disorder are more likely to come from a disrupted family. Treatment It is vital to reach a consensus between GP, paediatrician and psychiatrist as to diagnosis, but retain continuing involvement of these professionals.
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Being drawn into the 'it must be either psychological or physical debate' leads to sterile and non-therapeutic disputes. Programmes of physical rehabilitation, if appropriate, e.g. psychosomatic paralysis, chronic fatigue or chronic invalidism due to pain, can be very useful, and detract from fruitless discussions about aetiology which often alienate families early on in therapy ('it's not all in her head you know...'). Confrontation or accusations of malingering are counter-therapeutic. The child needs the opportunity to 'retreat with honour' from their predicament. Individual and family therapy may be indicated and useful, but often families wish to disengage from therapy on symptomatic improvement. Treatment of any psychiatric disorder diagnosed during assessment is mandatory. Prognosis Generally good, but a minority of patients have somatic symptoms unaccounted for by physical disease throughout life.
Psychiatric disorders of adolescence A wide range of psychiatric disorders are seen in adolescence. Some patients present with problems that may be seen in younger patients. Others present with disorders more typically seen in adults. Adolescent psychiatry marks this period of transition.
Psychoses The teenage years are the start of a rise in frequency of these disorders, peaking in early and middle adulthood. Some differences are seen in early, as opposed, to later onset psychosis.
Schizophrenia Symptomatology seen in adolescent onset schizophrenia is often more ephemeral, and may be harder to distinguish from other types of psychosis. Adolescent onset schizophrenia may have an affective component, but is often associated with a more 'biological' aetiology, and usually with poorer prognosis than seen in later onset disorders. Caution has to be exercised with antipsychotic agents. Adolescents may need antipsychotic doses similar to those needed by adults, but the developing brain is more vulnerable to both short- and long-term side effects. The major disruption to family life and education caused by relapse has to be balanced against the risks of long-term antipsychotic maintenance therapy.
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Bipolar disorders This is associated with a poorer prognosis, the earlier it starts. In recurrent illnesses there are special considerations about lithium, if it is prescribed, one of which is its adverse effect on growth. Anorexia nervosa This is the only disorder in which onset is linked to adolescence. More detail is available in Chapter 19. This section focuses on those aspects of particular relevance to the younger patient. Definition of the disorder in children and adolescents is the same as for adults. However, prepubertal girls with anorexia will have delayed menarche and loss of or delay in acquisition of secondary sexual characteristics. Boys with anorexia nervosa will have pubertal delay or diminution of male secondary sexual characteristics.
Epidemiology Prevalence varies with age: younger teenagers (under 15) approximately 0.1 per cent, older teenagers (16-18 years) approximately 1 per cent.
Aetiology Aetiology is similar to adults, but important additional considerations are the role of individual psychological factors and family dynamics. Intra-personal factors include a fear of maturation, inability to recognize and/or fear of own feelings and desires. Families of anorexic children have been characterized as being enmeshed, rigid, conflict avoiding and overprotective. The effect of media and cultural ideals and ambitions may be important as trigger factor, but their role as a significant maintaining factor is probably overestimated.
Treatment When treating younger patients, engaging the patient and their family is absolutely crucial. Individual psychotherapy, of all types, creative therapies and support during weight gain are important aspects of therapy. Family therapy is of proven usefulness in treating younger patients with anorexia nervosa. The prognosis in younger patients is usually better than later onset patients.
Child abuse Abusive acts towards children can be understood as acts of commission (doing something to a child, physical harm, sexual harm and/or emotional harm) and acts of omission (failing to do something necessary for
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a child's well-being, essentially neglect, or failing to protect a child from avoidable harm). From the psychiatric point of view, it is crucial to keep in mind that all forms of abuse are events, not disorders. Abuse, the event, does not require psychiatric treatment per se. However, its sequelae might, a distinction often lost on professionals and patients alike. Also, living in an environment in which it is possible for abuse of any kind to occur may be just as damaging for a child as the act of abuse alone. All professionals have a responsibility to the child if they become aware that or suspect that a child is being abused. The first consideration for any professional is to the safety of the child. Procedures and protocols exist to guide doctors about how to proceed. In cases of doubt, it is considered good practice to discuss concerns with peers and other professionals, including the local child protection team. The duty of care to the child overrides the duty of patient confidentiality.
Risk factors Some risk factors, identifying children more likely to be abused, particularly in relation to physical and emotional abuse, have been described. These include: young child rather than adolescent, young (especially teenage) parents, large family size,.adverse parental experience of being parented, difficult temperament in the child, parental mental illness (depends on nature of disorder and context) and psychosocial deprivation. Less is known about risk factors for sexual abuse.
Sequelae There is no specific syndrome associated with abuse. Elevated incidence of abusive experiences in childhood have been described in various adult psychiatric disorders (antisocial personality disorder, substance abuse, suicidal and self-harming behaviour, somatization disorders, anxiety and depressive disorders, dissociative states and eating disorders). In terms of psychiatric disorder, childhood disorders described include post-traumatic stress disorder, depressive disorder, conduct disorder and anxiety disorders. A history of maltreatment is a requirement for a diagnosis of attachment disorder. A growing body of literature is documenting nonspecific sequelae of abuse. Physical abuse and neglect have been linked to impairments in affect regulation, impairments of development of self-concept and selfesteem, abnormalities of play, abnormal peer group relationships and school failure. Children who have been sexually abused may well have better peer group relationships than their physically abused peers, but are sometimes observed to be prematurely sexualized in their behaviour.
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The responsibilities of the child psychiatrist Few psychiatrists are actively involved in child abuse investigations. However, a child may disclose that they are being abused in the course of contact with child psychiatrists. An adult psychiatry patient may pose a risk to their children, which becomes evident to the adult psychiatrist caring for them. The doctor's responsibility, regardless of specialism, is to act in the best interests of the child and in accordance with guidelines (see above), and, if indicated, discuss the child's case with social services. The Children Act 1989 The Children Act embodies the legal means of protecting children who are at significant risk of harm or who are being harmed. Several implicit and explicit assumptions are included in the working of the Act. These are: acting in the best interests of the child, preventing significant harm, working with families when possible, least draconian measures first, and, upholding whenever possible, parental rights and responsibilities. Removing a child from a family should never be undertaken lightly; it will of itself be distressing and disruptive to all concerned. If legal action, including removing parental responsibility from parents, is judged to be the safest way forward for a child a series of orders are available. An emergency protection order (EPO) can be instituted in urgent circumstances, lasts for 8 days, and can be renewed for a further 7 days. The implication is that the child will be immediately removed from the parents' care. Interim care orders last longer, usually 28 days, and have to be regularly reviewed by social services and the courts. They represent time during which assessment and planning can be undertaken. Sometimes a child may then go on to be subject to a full care order. The implication is that local authorities have assumed parental responsibility for a child, although not in a manner which totally removes the parents' rights and responsibilities. Parents have the right of appeal at all stages of the process.
References Bailey, A., Phillips, W. and Rutter, M. (1996) Autism: towards an integration of clinical, genetic, neuropsychological and neurobiological perspectives. Journal of Child Psychology and Psychiatry, 37, 89-126. Berg, I. (1985) Management of school refusal. Archives of Disease in Childhood, 60, 486-8. Bernstein, G.A., Borchardt, C.M. and Perwien, A.R. (1996) Anxiety disorders in children and adolescents: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1110-19. Birmaher, B., Ryan, N.D., Williamson, D.E. et al (1996) Childhood and adolescent depression: a review of the past 10 years. Part I. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1427-39.
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Birmaher, B., Ryan, N.D., Williamson, D.E. et al. (1996) Childhood and adolescent depression: a review of the past 10 years. Part II. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1575-83. Bretherton, I. (1992) The origins of attachment theory: John Bowlby and Mary Ainsworth. Developmental Psychology, 28, 759-75. Cantwell, D.P. (1996) Attention deficit disorder: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 978-87. Cicchetti, D. and Toth, S.L. (1995) A developmental psychopathology perspective on child abuse and neglect. Journal of the American Academy of Child and Adolescent Psychiatry, 34, 541-65. Department of Health, British Medical Association, and the Conference of Royal Colleges (1992) Child Protection: Medical Responsibilities, Guidance for Doctors Working with Child Protection Agencies. London: HMSO. Eminson, D.M. and Postlethwaite, R. (1992) Factitious illness: recognition and management. Archives of Disease in Childhood, 67, 1510-16. Goodman, R. and Scott, S. (1997) Child Psychiatry. Oxford: Blackwell Science Ltd. Hay, D.F., Castle, J. and Jewett, J. (1994) Character development. In Development Through Life: A Handbook For Clinicians (eds M. Rutter and D.F. Hay). Oxford: Blackwell. Hazell, P., O'Connell, D., Heathcote, D. et al (1995) Efficacy of tricyclic drugs in treating child and adolescent depression: a meta-analysis. British Medical Journal, 310, 897-901. Kazdin, A.E. (1997) Practitioner review: psychosocial treatments for conduct disorder in children. Journal of Child Psychology and Psychiatry, 38, 1161-78. Leckman, J.F., Peterson, B.S., Anderson, G.M. et al. (1996) Pathogenesis of Tourette's syndrome. Journal of Child Psychology and Psychiatry, 38, 119-42. Lombroso, P.J., Pauls, D.L. and Leckman, J.F. (1994) Genetic mechanisms in childhood psychiatric disorder. Journal of the American Academy of Child and Adolescent Psychiatry, 33, 921-38. March, J.S. and Leonard, H.L. (1996) Obsessive-compulsive disorder in children and adolescents: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 1265-73. Offord, D.R., Boyle, M.H., Szatmari, P. et al. (1987) Ontario Child Health Study: I Six month prevalence of disorder and service utilization. Archives of General Psychiatry, 44, 832-6. Robertson, M.M. (1994) Gilles de la Tourette syndrome - an update. Journal of Child Psychology and Psychiatry, 35, 597-611. Rutter, M. (1995) Clinical implications of attachment concepts: retrospect and prospect. Journal of Child Psychology and Psychiatry, 36, 549-71. Rutter, M., Taylor, E. and Hersov, L. (eds) (1994) Child and Adolescent Psychiatry: Modern Approaches, 3rd edn. Oxford: Blackwell. Rutter, M., Tizard, J., Yule, W. et al. (1976) Isle of Wight Studies, 1964-1974. Psychological Medicine, 6, 313-32. Shaffer, D. (1974) Suicide in childhood and early adolescence. Journal of Child Psychology and Psychiatry, 15, 275-91. Tantam, D. (1991) Asperger syndrome in childhood. In Autism and Asperger Syndrome (ed. U. Frith). Cambridge: Cambridge University Press. Thomas, A., Chess, S. and Birch, H.G. (1968) Temperament and Behaviour Disorders in Children. London: University of London Press.
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Volkmar, F. (1996) Childhood and adolescent psychosis: a review of the past 10 years. Journal of the American Academy of Child and Adolescent Psychiatry, 35, 843-51. Webster-Stratton, C. (1991) Annotation: strategies for helping families with conduct disordered children. Journal of Child Psychology and Psychiatry, 32, 1047-62. Wood, A.J., Harrington, R.C. and Moore, A. (1996) A controlled trial of a brief cognitive behavioural intervention in adolescents with depressive disorders. Journal of Child Psychology and Psychiatry, 37, 737-46.
23 Learning disability ROBERT GOODMAN and THERESE VAN AMELSVOORT
In this chapter, following current British usage, the term learning disability (LD) is used to refer to what used to be called mental retardation. Unfortunately, the term is not understood in the same sense throughout the English-speaking world. Thus in North America, LD refers to specific learning difficulties such as dyslexia, whereas developmental disability refers to what used to be called mental retardation. Sadly, widespread prejudice leads to any new term for mental retardation becoming pejorative and stigmatizing within a short time; this is likely to persist until society comes to value people with learning disabilities.
Definitions For some purposes LD is defined solely in terms of an intellectual disability; for other purposes, social impairment is also essential. Associated educational difficulties are not central to the definition. Intellectual disability At its simplest, LD is defined by IQ level alone: an IQ of 50-69 is mild LD; an IQ under 50 is severe LD. Social impairment Legal and administrative definitions of LD generally stipulate that, in addition to intellectual disability, the individual's level of social functioning is such that they are in need of special care or protection. In English law, this insistence on social as well as intellectual impairment is found in the definitions of mental impairment and severe mental impairment of the Mental Health Act 1983.
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Prevalence • Mild LD, as defined by IQ criteria, affects about 2 per cent of the general population, as would be expected if IQ is normally distributed. (An IQ of 70 is 2 standard deviations below the mean and 2.3 per cent of any normally-distributed population falls more than 2 s.d. deviations below the mean.) Many of these individuals are never identified by medical, educational or social services - sometimes this is because their social functioning is adequate and they are coping well enough in mainstream schools, but in other instances they are drowning quietly without the extra input that might have helped them had their LD been recognized. • Severe LD, as defined by an IQ under 50, affects about 0.4 per cent of the population, which is some 10 times higher than would have been expected if IQ were normally distributed, i.e. there is a small extra 'hump' at the bottom of the normal IQ distribution. Individuals with severe LD are nearly always known to health, education or social services, either because of the severity of their educational difficulties or because of coexisting physical features such as cerebral palsy or epilepsy.
Aetiology Mild LD Most mild LD is assumed to be due to the same sorts of polygenic and environmental factors that determine IQ within the normal range. Just as the polygenic component is assumed to be due to many genes, each of which has a small but additive effect on IQ, so the psychosocial component seems to involve many factors - such as parental attitudes, positive interactions with the child or stressful life events - each of which has a small additive effect on IQ. Adverse factors in the physical environment - such as exposure to low-level lead - may also add to the effects of genetic and psychosocial factors. Severe LD The organic causes that account for the majority of severe LD (and a minority of mild LD) are conventionally subdivided according to their time of onset.
Prenatal For example, chromosome abnormalities, single gene defects, congenital infections, fetal alcohol syndrome.
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Perinatal For example, intraventricular haemorrhage in premature neonates, severe neonatal jaundice. Though much used to be made of obstetric complications, it now seems unlikely that these are a common cause of LD. If a child has a difficult delivery and subsequently turns out to have severe LD, was the delivery to blame? Not usually. More often, the obstetric complications were either irrelevant or a consequence of pre-existing abnormalities in the unborn child. Thus children with chromosomal problems or prenatal brain damage are at greater risk of an abnormal delivery.
Postnatal For example, encephalitis and meningitis, trauma due to child abuse and accidents, severe lead poisoning. Some specific causes
Down's syndrome Down's syndrome affects up to 1 in 600 births, with older mothers at much greater risk. This is the commonest single causes of severe LD, accounting for up to a third of all cases. Ninety-five per cent are due to an extra chromosome 21 resulting from nondisjunction, which is commoner in older mothers; 4 per cent are from translocations, which are familial; and 1 per cent are mosaics. Physical features include: small head; round face; upslanting eyes; epicanthic folds; large fissured tongue; low-set simple ears; short stature; single palmar crease; incurved little fingers; and hypotonia. Cardiac and gut malformations are common.
Fragile X syndrome This is probably the commonest cause of inherited LD. Though once said to affect about 1 in 1000 births, more recent estimates based on DNA analyses suggest that the rate may be closer to 1 in 5000. It affects both males and females, though the degree of intellectual impairment tends to be greater in males. Physical characteristics are highly variable, but may include a long face, prominent ears, wide jaw, hyperextensible joints and large testes after puberty. It is due to an excess of trinucleotide repeats at a specific site on the long arm of the X chromosome and may be detected by direct DNA analysis.
Fetal alcohol syndrome (FAS) FAS may cause up to 10 per cent of mild LD, with up to 1 in 300 births having a full or partial FAS. Maternal alcohol intake above 80g/day carries a high risk, but 20-80 g/day may also be harmful. Physical
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features can include: low height, weight and head circumference from birth onwards; maxillary hypoplasia; short palpebral fissures, short nose and smooth philtrum.
Single gene disorders There are many rare genetic disorders that sometimes or always cause LD. Most are autosomal recessive but there are exceptions: the LeschNyhan and Hunter (but not Hurler) syndromes are sex linked; and tuberous sclerosis and neurofibromatosis are autosomal dominant.
Sex chromosomal anomalies Individuals with the common anomalies - XO (Turner's syndrome), XXY (Kleinfelter's syndrome), XXX and XYY - are usually of normal or low-normal intelligence, though there is some excess of mild and severe LD.
Diagnostic assessment Children with severe LD are usually referred to a paediatrician because of associated physical abnormalities, or because of slow development noted by parents or picked up on developmental screening. Mild LD may not be noticed until learning difficulties become apparent in school. Parents and teachers are usually fairly accurate judges of a child's ability level - if asked, they are often able to give a good estimate of the child's mental age. Nevertheless, even experienced parents and teachers sometimes grossly misjudge a child's intelligence. Thus a child with autism and normal intelligence (as judged by non-verbal tests) may be thought to have a severe LD on the basis of their poor performance on verbal tests and their lack of 'common sense' - a misjudgement that may lead to an inappropriate placement in a school for severe learning difficulties. Even more commonly, children with mild LD are believed by their teachers to be of near average ability, with poor academic performance being attributed to lack of effort, emotional problems or social disadvantage. Once again, the misjudgement leads to inappropriate academic provision and pressure. Given this, it is sensible to supplement parent and teacher reports with formal psychometric testing. Besides measuring IQ reliably, a detailed psychometric assessment generates a useful profile of the child's cognitive strengths and weaknesses. For children of school age, the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III) or the British Ability Scale, 2nd edition (BAS-2) provide a suitably wide-ranging battery of verbal and visuospatial tests. Diagnosis of the underlying cause of LD is based on: • A thorough history, with particular attention to family history, prenatal infections and prenatal alcohol exposure.
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• A careful physical examination, particularly for neurological signs, dysmorphic features and the skin signs of the neurocutaneous syndromes, e.g. tuberous sclerosis. • Selected special investigations, particularly for the fragile X syndrome, chromosomal abnormalities and metabolic diseases. Although very few treatable causes will be found, the search for a cause is valuable for genetic counselling and because many parents are relieved by a diagnostic label (partly because this opens the way to joining the relevant parent self-help group). In Britain, diagnosis and counselling usually involve paediatricians rather than psychiatrists.
Prevention Reducing biological hazards Many approaches can reduce the prevalence of the organic syndromes that sometimes or always result in LD. Thus widespread rubella vaccination can prevent congenital rubella, folic acid supplementation around conception and in early pregnancy can prevent neural tube defects, and advice on alcohol consumption in pregnancy can prevent the fetal alcohol syndrome. Prenatal diagnosis of organic syndromes is increasingly possible on the basis of blood tests, ultrasound scans, chorionic villous sampling and amniocentesis; specific treatments are rarely available but parents may opt for termination of pregnancy. Continuing advances in obstetric and neonatal care may further reduce the rate of early brain damage, e.g. by reducing the rate and complications of premature birth. Neonatal screening for phenylketonuria, galactosaemia and hypothyroidism permits early treatment before irreversible brain damage has occurred. Immunization can protect children against diseases that cause meningitis (e.g. Haemophilus influenzae type b) and encephalitis (e.g. pertussis). Measures to reduce the rate of domestic accidents, road traffic accidents and physical abuse can reduce liability to brain damage secondary to head injury. Social interventions Less progress has been made in reducing the rate of normal-variant LD. Some interventions have targeted the infants of mothers with LD in socially deprived neighbourhoods. These can result in significant increases in scholastic achievement and measured IQ, at least in the short term. Continuing input in the school years may help maintain these gains in the long term. Just as there is no one critical period after which environmental damage is irreversible, so there is no one therapeutic window after which environmental enrichment is no longer necessary. It is important, though, not to overestimate the likely effect of environ-
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mental interventions; one adoption study that compared the effect of being raised by parents from the highest and lowest socioeconomic groups found that it resulted in an IQ difference of around 12 points. A lasting effect of this size is well beyond anything that intervention projects have yet achieved.
Children's services Service provision is generally governed by a philosophy of 'normalization', i.e. the promotion of as ordinary a life as possible in the community. Social provision Children develop best if they grow up as part of a family. Nowadays, most children with LD live with their biological family. This can be a very positive experience for parents and siblings, but there is often a substantial burden of care too, particularly with severe LD - though this can often be greatly eased by extra assistance and support, e.g. mobility allowances, respite care (usually arranged by social services). If the family's capacity to cope is overwhelmed even with maximum respite care, placement in an alternative family setting is highly desirable, either by adoption or long-term fostering. Rarely, a child will require a specialist residential placement. Educational provision No matter how severe their LD, all children are entitled by law to an appropriate education. No child can be denied all schooling on the grounds that they are 'ineducable'. It is increasingly possible for children with mild LD to receive the extra help they need within mainstream schools. Children with severe LD generally attend special schools. Reports from doctors and other health professionals can help education authorities identify special needs and provide for them accordingly. Medical provision Appropriate medical care generally involves the family practitioner and the paediatric team based at a Child Development Centre. Involvement of child mental health services is not routinely necessary, but may be helpful for the high proportion of learning disabled children who have coexistent psychiatric problems (see below).
Psychiatric disorders in children with learning disabilities Learning disorder is a powerful risk factor for psychiatric disorders. Roughly a third of all children with mild LD have psychiatric diagnoses,
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as do roughly half of all children with severe LD, as compared with some 10-15 per cent of nondisabled children judged by the same criteria. The combination of LD and psychiatric disorder is particularly stressful for families, many of whom find it harder to live with the psychiatric problems than with the problems intrinsic to LD. Psychiatric problems are the commonest reason for family placements breaking down. Type of disorder
Mild LD Among children with mild LD, the mixture of psychiatric disorders is generally similar to that seen in children without learning disability, being dominated by emotional, conduct and hyperactivity disorders.
Severe LD In severe LD, the mixture of psychiatric disorder is somewhat more distinctive, although emotional, conduct and hyperactivity disorders are still common. Autistic disorders are also common, with partial variants of autism being commoner than the full syndrome. Thus a substantial minority of children with severe LD are socially aloof or relate to others in a bizarre way; imaginative play is characteristically impoverished; and stereotypies can be prominent, and may be exaggerated by boredom, isolation, blindness or deafness. Severe hyperactivity sometimes occurs in association with autistic features or simple stereotypies, and sometimes occurs alone. Self-injurious behaviour (SIB) is particularly common in severe LD; it includes eye-poking, head-banging and hand-biting. These behaviours have a functional component that can be shown to vary from individual to individual. Thus in different individuals, self-injury may serve to reduce boredom, to attract attention or to avoid unwanted attention. Difficulties with the acquisition of self-help skills (including feeding, toileting and dressing) are also common in severe LD, as are sleep problems. Specific links Some organic causes of LD are particularly associated with specific psychiatric problems. The Lesch-Nyhan syndrome, for example, is much more likely to lead to severe self-injury than other organic disorders resulting in equally low IQs. When the organic syndrome is genetic or chromosomal, the common behavioural characteristics are referred to as the behavioural phenotype of the disorder. Other examples include the social anxiety, gaze avoidance and litany-like speech associated with the fragile
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X syndrome; and the insatiable overeating associated with the PraderWilli syndrome. Non-genetic syndromes can also have associated behavioural features, and these too are sometimes referred to as behavioural phenotypes. Thus congenital rubella is associated with autistic features, while the fetal alcohol syndrome is associated with hyperactivity. Management Treating the psychiatric disorders of children with LD differs in emphasis but not in principle from treating similar disorders in other children. Behavioural treatment is particularly valuable in building up self-help skills and in reducing undesirable behaviours such as self-injury, stereotypies and frequent night wakenings. To be effective, behavioural therapy must be carefully tailored to the individual child. For self-injurious behaviour, for example, advice to ignore the child during episodes of self-injury may be appropriate for a child who uses the behaviour primarily to attract extra attention, but would only succeed in reinforcing the self-injurious behaviour if applied to a child who primarily uses the behaviour to avoid unwanted attention. In addition to behavioural therapy, a wide range of other therapies can be deployed, including family therapy, cognitive therapy and supportive psychotherapy (depending on the nature of the problem and the age and cognitive level of the child). The role of medication in the treatment of psychiatric problems associated with LD remains controversial. In the short term, neuroleptics do reduce serious aggression and may therefore be useful in an emergency. The benefits soon wear off, however. It is then tempting to increase the dose to gain another temporary respite. Unless this temptation is resisted, the dose is likely to escalate progressively, leaving the child on high-dose long-term neuroleptic medication with all its attendant hazards. The pointlessness of this long-term medication is often only evident when the medication is finally withdrawn: aggression typically worsens for a while and then returns to its previous level. Challenging behaviour requires social and psychological management, not pharmacological treatment. With this reservation, medication can be useful at times. Moderate doses of neuroleptics can sometimes reduce stereotypies, hyperactivity, self-injury and agitation, perhaps particularly in adolescents with LD and autistic features. Stimulants may sometimes improve the hyperactivity of children with IQs of around 40 or more, but rarely work for children with lower IQs; at any IQ, stimulants may exacerbate coexistent ritualistic and repetitive behaviours.
Psychiatric disorders in adults with learning disabilities The diagnosis and classification of mental illness in people with LD can be a complicated issue, because the clinical assessment can be
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confounded by the person's intellectual impairment, particularly if they have poor verbal skills. Hence, the true prevalence of mental illness in people with LD is difficult to establish; and the reported prevalence rates vary significantly. Nevertheless, most studies find increased rates of mental illness in people with LD as compared to the general population. Factors which increase the vulnerability of people with LD to mental illness may be biological (e.g. brain damage or genetic), psychological (e.g. low self-esteem), or social (e.g. isolation, lack of social skills or discrimination). The clinical assessment of people with LD should focus on establishing patterns of symptomatology and changes in behaviour using objective measures wherever possible (e.g., sleep and weight charts). Information may be obtained from the patient or, if this is impossible, from a close relative or carer. It is important to take into consideration the impact that a patient's intellectual handicap has on the expression of symptoms. For example, people with LD may not be able to describe their feelings or thought content easily, and so a history from a carer or relative becomes vital. In addition, for routine clinical assessments, instruments have been developed to examine and quantify the type and severity of psychiatric symptoms in people with LD, for example the Psychopathology Instrument for Learning Disabled Adults (PILDA) or the Psychiatric Assessment Schedule for Adults with Developmental Difficulties (PASADD). Finally, clinicians should admit openly to limitations of knowledge in cases where there is diagnostic ambiguity. Type of disorder
Schizophrenia Point prevalence of 3 per cent compared with 1 per cent in non-LD population. Age of onset tends to be earlier in people with LD. Clinical presentation includes hallucinations, delusions, catatonia, withdrawal, tearfulness and sleep disturbances. Hallucinations and delusions usually take a very simple form and people may present with childish and stereotypical behaviour. It is sometimes difficult to distinguish symptoms of learning disability from negative symptoms associated with schizophrenia.
Affective disorder Depressed mood is the commonest symptom of affective disorder in adults with LD. Suicidal behaviour is a relatively rare event; other features of depression include decreased motor activity, somatic complaints, decreased appetite, sleeplessness or hypersomnolence. Mania is usually not characterized by infectious gaiety, but rather by irritability, increased motor activity, aggression and sleeplessness.
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Neurotic disorder Acute anxiety in response to stress is common. The occurrence of bereavement and adjustment reactions in the LD population are underestimated and commonly ignored. It is a misconception that because people with LD have difficulty in expressing feelings they do not have them. The prevalence of obsessive-compulsive disorder (OCD) has been estimated at 3.5 per cent versus 1 per cent in the general population. Ordering (insistence on symmetry) is more common in people with LD and OCD, whereas other ritualistic behaviours such as hand-washing and checking are the most common compulsions in the general population.
Personality disorder Difficult to diagnose and manage in this population. It is unclear whether the diagnosis of personality disorder in a severely LD person is appropriate. The term 'behavioural phenotype' is increasingly used to describe the set of behaviours that a person exhibits. In some disorders these behaviours may be characteristic of a specific developmental syndrome. For example, in Prader-Willi syndrome, people may be hyperphagic, hypersomnolent and have aggressive outbursts.
Challenging behaviour This term is used to describe behaviours 'of such intensity, frequency or duration that the'physical safety of the person or others is likely to be placed in serious jeopardy, or behaviour which is likely to seriously limit or delay access to and use of ordinary community facilities.' It includes aggressive behaviour to the environment, to other people and to the self. Challenging behaviour may be associated with pain, discomfort, medication, communication problems and levels of arousal. In the adult LD population approximately 15 per cent exhibit severe behavioural disorder. Such behaviour disorders are more common in men, in people with verbal abnormalities, in restrictive residential placements, in people with epilepsy, and in people with a coexisting psychiatric disorder.
Criminal behaviour People with LD show higher rates of criminal behaviour than the general population. Rates are increased further by a positive family history and negative environmental factors (e.g. poverty). In addition, people with LD are more likely to get caught, may be easily exploited, and might not always understand that what they are doing is wrong. Also, when people with LD become involved with the criminal justice system, particular care must be taken because they tend to be more suggestible. For example, they may make inappropriate confessions. Arson and
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sexual offences (most often exhibitionism in males) are the criminal offences said to be particular common in LD people. Treatment Whenever psychiatric disorders are diagnosed, they should be treated in the same way as the nonintellectually impaired. Unfortunately, antipsychotic medication is often inappropriately prescribed for people with LD to control disruptive behaviour (as a 'chemical restraint'). However, unless clear psychotic symptoms are present, antipsychotic drugs should not be used as a first-line treatment for behavioural disorders - antipsychotics give rise to reversible (e.g. drowsiness) and irreversible (e.g. tardive dyskinesia) side effects. Lithium, carbamazepine, beta-blockers and serotonin reuptake inhibitors have all been used as an attempt to control disruptive behaviours. Our understanding of human brain function remains limited, and the neuropsychopharmacological treatment of behavioural disorders in LD people remains an art rather than science. However, there may be circumstances where pharmacological strategies may be used, in the absence of coexisting psychiatric disorder, for management of a life threatening behavioural disturbance. A behavioural treatment approach is usually the preferred strategy in dealing with disruptive behaviours in people with LD. Such an approach involves analysing antecedents, the behaviour itself, and the consequences of disruptive behaviours. Once these have been identified, changes in behaviour may be obtained by systematic modification of the antecedent (e.g. explaining something to the patient calmly and patiently rather than demandingly) or by changing the consequences of the behaviour (not rewarding unacceptable behaviour by disattending rather than arguing). If possible, a patient with LD should be assessed and treated in his/ her home environment. If not, inpatient treatment is generally best provided in an environment with facilities for rehabilitation and where there is an emphasis on behaviour modification. Wards which emphasize a psychodynamic approach are probably less appropriate. Treatment of adults with LD who have a coexisting psychiatric disorder in the community requires a multidisciplinary approach, and is similar to the community treatment of psychiatric patients in the general population. Developing self-help skills, language and communication skills, social skills and community living skills are particularly important in the community care of people with LD.
Reading list Bouras, N. (1994) Mental Health in Mental Retardation: Recent Advances and Practices. Cambridge: Cambridge University Press.
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Flint, J. (1996) Behavioural phenotypes: a window onto the biology of behaviour. Journal of Child Psychology and Psychiatry, 37, 355-67. Kiernan, C. (1985) Behaviour modification. In Mental Deficiency: The Changing Outlook, 4th edn (eds A.M. Clarke, A.D.B. Clarke and J.M. Berg). London: Methuen. Scott, S. (1994) Mental retardation. In Child and Adolescent Psychiatry, 3rd edn (eds M. Rutter, E. Taylor and L. Hersov). Oxford: Blackwell.
24
General hospital (liaison) psychiatry CHRIS DICKENS and FRANCIS CREED
In recent years increasing attention has focused on the co-morbidity of psychiatric and physical illnesses, the possible mechanisms of interaction between these disorders and the possible impact of psychiatric illness on the outcome of physical illness. This new awareness of the importance of psychiatric illness in the physically ill has resulted in a number of landmark meetings between the Royal College of Psychiatrists and the Royal Colleges of Physicians and Surgeons. Joint reports have been produced highlighting the scale of the problem and how this might best be addressed, with recommendations for changes in education and service provision. The provision of psychiatric services for patients with physical problems has been termed liaison psychiatry, referring to the liaison of psychiatrists with physicians, surgeons and other nonpsychiatric healthcare professionals, or consultation-liaison psychiatry highlighting different models of such a service (see below). We consider that the term general hospital psychiatry more accurately describes this practice and removes implications on the nature of the service referred to.
Rationale for a general hospital psychiatry service General hospital psychiatry is required for the following reasons. Psychiatric morbidity in the general hospital • Between 14 per cent and 25 per cent of general medical and surgical inpatients suffer from psychiatric disorder. The figure is similar for outpatients who have organic disease. • Up to 40 per cent of new medical outpatients do not have organic disease and in this population between 35 per cent and 60 per cent have psychiatric disorder. • Medical admissions following deliberate self-harm still number more
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than 100000 per annum in the UK. In additon, a large number are seen in accident and emergency and are discharged without admission. • Up to 20 per cent of male inpatients have alcohol-related problems. Drug-related disorders and sexual or eating disorders are also common. Psychiatric disorders and utilization of medical services Patients with psychiatric disorders have different patterns of utilization of healthcare services. Mayou and colleagues found that patients admitted to medical wards had an increased rate of contact with psychiatric services (compared with the expected rate) during the 2 years before and after the medical admission. This was not confined to selected diagnostic groups - it reflects the positive association of physical and psychiatric disorders, which has also been demonstrated in community studies. Fink noted that patients with a history of psychiatric treatment had significantly longer general hospital admissions. Katon and colleagues found that half of the patients who were high utilizers of general medical health services had psychiatric disorders; 3 per cent had depressive disorders, 22 per cent anxiety disorders and 20 per cent somatization. The Pathways to Care study indicated that approximately one-quarter of all new patients reaching a district psychiatric service did so via general hospital, either through the accident and emergency department or through other inpatient or outpatient departments.
Models of a liaison service There are two main service models by which psychiatry is practised in the general hospital setting - the consultation model and the liaison model. Consultation model A reactive model wherein the psychiatrist provides a consultancy service on demand, the request for assessment often coming from a senior clinician on the medical team. Liaison model An active model in which the psychiatrist is a member of the medical firm, attending ward rounds, accepting referrals from any member of the firm as well as dealing with staff anxieties. As such, he/she has a central role as a mediator between staff and patients. Consultation-liaison model Though the liaison model offers a higher degree of psychiatric support and multidisciplinary care for the physically ill patient compared with
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the consultation model, the former is inefficient in terms of the time and effort of the psychiatrist. It is now recognized that using elements of these two former models together, the so-called consultation-liaison model offers the most efficient use of limited resources. In such a model, a liaison-type service could be offered in high-risk areas, such as oncology units or casualty, though a consultation service may be adequately used in less high-risk areas.
Psychiatric disorders in general hospital The disorders seen in the general hospital are listed in Table 24.1. Psychiatric disorders associated with organic diseases The development of organic illness can result in a number of psychological stresses which, if not addressed, may result in considerable distress and possible psychological disorders. The issues associated with organic illnesses may relate to the illness itself or to the effects of treatment. Illness-related factors which may result in stress include uncertainty about the future, searching for meaning in the illness, loss of control of one's life, a sense of failure that their bodies have let them down, the stigma of disease and a feeling of isolation. The effects of Table 24.1
Classification of psychiatric and psychological problems that may be encountered in general medical units
Category
Sub-category
A. Organic disease with associated psychiatric disorder
1. 2. 3. 1. 2. 3.
B. Cerebral complications of organic disease C. Physical symptoms not due to organic disease (medically unexplained symptoms)
1. 2.
D. Patients who abuse alcohol and drugs E. Deliberate self-harm (DSH) F. Patients with sexual or relationship problems or eating disorders
1. 2. 1. 2. 1. 2.
Adjustment disorder Anxiety disorder Depressive disorder Delirium Dementia Focal defects: personality or perceptual changes Stress reactions/fears of illness and somatic presentation of anxiety and depressive disorders (somatization) Chronic multiple unexplained symptoms (chronic somatization): (a) somatoform disorders; (b) simulated disorders As a cause of admission Detected during inpatient stay Inpatients following DSH Outpatients seen in A. & E. Direct presentation Complicating other disease (e.g. diabetes)
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treatment may cause stress if the treatment itself results in disfiguration, e.g. loss of a body part or impairment of body function. With some treatments, e.g. chemotherapy, the treatment itself may result in unpleasant physical effects which make the person feel worse in the short term. Adjustment disorders occur in approximately one-quarter of general medical patients, and are related to severity of physical illness, premorbid personality and experience of illness and social support. Anxiety and depressive disorders occur in approximately 12-15 per cent of patients with physical illness. The prevalence of anxiety and depressive disorders is higher (20-35 per cent) in the following groups: • those illnesses affecting the brain, e.g. stroke; • acute painful and/or life-threatening illness, e.g. malignancy; • chronic, painful, disabling or disfiguring illness which impedes selfcare, e.g. rheumatoid arthritis; • major and unpleasant treatments, e.g. chemotherapy; • elderly people. Anxiety and/or depressive disorders in association with physical illness may lead to: • impairment of the patient's quality of life through increased pain, worsened disability and, occasionally, serious depression with suicidal ideas; • delayed recovery (e.g. depressive disorder after a stroke and anxiety following a heart attack); • increased chance of problematic illness behaviour (e.g. increased frequency of clinic attendance, increased consumption of analgesics, worry about illness and resistance to the doctor's reassurance). Improved recognition and management of psychiatric disorders in the physically ill therefore carry the potential to improve a patient's quality of life, to reduce disability and distress, to reduce healthcare utilization and detect suicidal risk. Cerebral complications of organic diseases
Dementia and delirium Delirium is detected in at least 10 per cent of those admitted to hospital with acute illness. It is most likely in those who also have dementia, defective hearing and vision, Parkinson's disease and advanced age. Precipitating factors for delirium include pneumonia, cardiac failure, urinary infection, carcinomatosis, hypocalcaemia and prescribed medications. It is not surprising, therefore, that high death rates for delirious patients have been reported.
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Between a quarter and a third of elderly medical inpatients have dementia. The practical importance, apart from achieving appropriate care, is the fact that cognitively-impaired patients stay significantly longer in hospital than the unimpaired. This may be partly attributable to lack of suitable accommodation following discharge, but also reflects the fact that cognitive impairment limits compliance with medication, making management more complex. Improved services for patients with cognitive impairment leads to decreased length of stay. Physical symptoms not due to organic disease
Unexplained symptoms in patients attending medical clinics Between a quarter and a half of new medical outpatients experience physical symptoms that cannot be explained on the basis of organic disease; they are given the diagnosis of a recognizable syndrome (such as irritable bowel syndrome or chronic fatigue syndrome) or as 'illdefined symptoms and signs'. The commonest symptoms are fatigue, chest pain, dizziness, headache, back pain and abdominal pain. Reasons for attendance at the medical clinic which are unrelated to an underlying organic disorder may be related to psychiatric disorders (anxiety, depression, adjustment disorders, hypochondriasis, etc.), other psychological factors (abnormal illness attitudes, impaired coping), social factors (social isolation/stress) or a combination of these factors. The process by which psychiatric or psychological factors present as physical symptoms is referred to as somatization. A narrower, though more commonly used, definition of somatization is the somatic symptoms associated with diagnosable psychiatric disorders. This definition excludes subjects who fail to reach accepted diagnostic criteria for a psychiatric disorder but in whom psychological processes may play an important part in the presentation of physical symptoms, such as patients with abnormal illness attitudes. The process of somatization should not be confused with the somatoform disorders (which includes somatization disorder); these disorders are psychiatric syndromes and will be discussed later in this chapter. Psychiatric disorders associated with the process of somatization are often categorized into acute and chronic groups according to the duration of the somatic symptoms (Table 24.2). This categorization is problematic, however, since there are no broadly accepted criteria distinguishing acute from chronic in this context. The usefulness of categorizing these disorders thus lies in the fact that disorders associated with chronic somatization are much more likely to be associated with significant other problems (e.g. abnormalities of personality) and thus be more resistant to treatments, requiring specialist input, compared with disorders associated with acute somatization.
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Psychiatric diagnoses in somatizing patients (ICD-10 diagnoses)
Acute
Chronic
Adjustment disorder Depressive disorder Anxiety disorder Phobic disorder Panic disorder Dissociative disorder
Somatization disorder Undifferentiated somatoform disorder Hypochondriacal disorder Persistent somatoform pain disorder Factitious disorder
Subjects who somatize may also be divided into 'true somatizers', who have no insight into the link between their physical symptoms and the underlying psychopathology, and 'facultative somatizers'. Facultative somatizers readily recognize the link of physical symptoms with underlying psychological problems but who choose to present with physical problems as they believe they will be better received by the attending doctor.
Epidemiology of somatization Epidemiological studies on somatization have provided widely discrepant findings, owing to the differences in the criteria for identifying somatization and the variability of the groups studied. Among community samples in the USA 4 per cent of subjects have been shown to experience at least four medically unexplained in their lifetime. In primary care in the UK, up to 26 per cent of patients attending their GP were identified as true somatizers. Hospital studies have given even greater range of prevalences for somatization, with rates as high as 50 per cent in some pain clinics. Not only does the prevalence of somatization vary with the site of the study, but so does the nature of the associated psychiatric disorder. Whereas affective and somatoform disorders predominate among hospital subjects, adjustment disorders are the most common psychiatric diagnoses in primary care somatizers.
Aetiology of somatization Studies have shown familial associations between somatization, alcohol misuse and antisocial personality disorder. Others studies have shown complex associations between the characteristics of biological and adoptive parents and somatization in their offspring. It is not clear what role genetic factors play in somatization. Childhood experiences of illness in themselves or in significant others have been shown to be important risk factors in the later development of somatization. Cognitive factors, such as abnormal illness beliefs, often based on previous illness experience,
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are thought to predispose certain individuals to present with physical symptoms due to inappropriate interpretation of normal physical sensations. Financial or social gain may act as potent maintaining factors for somatization. The role of alexithymia remains an issue of contention.
Specific disorders associated with chronic somatization A much smaller number of subjects presenting to general hospital clinics have chronic physical symptoms in numerous bodily systems for which no organic cause can be found. Such patients use a disproportionate amount of healthcare resources. These chronic, multiple unexplained symptoms occur in a number of overlapping disorders which are grouped together in the ICD-10 under the categories of Somatoform disorders, Dissociative disorders and a number of simulated disorders (see Table 24.3). Diagnoses of disorders from these groups may only be considered once a medical cause for the symptoms has been ruled out.
Somatoform disorders Repeated reports of physical symptoms, often associated with requests for medical investigations in the absence of any recognizable physical cause for the complaints, characterize these disorders. Reassurance from the examining doctor is ineffective. Somatization disorder This diagnosis requires the presence of: (1) multiple physical symptoms without adequate physical explanation, occurring over a period of at least 2 years; (2) persistent refusal to accept reassurance from a number of doctors that no physical cause can be found, and (3) some degree of impairment of family or other social functioning must be present. Table 24.3
Principal disorders characterized by multiple unexplained physical symptoms.
Somatoform disorders
Dissociative disorders
Somatization disorder Undifferentiated somatoform disorder Hypochondriacal disorder Persistent somatoform pain disorder Other somatoform disorders
Dissociative amnesia Dissociative fugue Dissociative stupor Dissociative disorders of movement and sensation
Other disorders of adult personality and behaviour Elaboration of physical symptoms for psychological reasons, e.g. compensation neurosis Intentional production or feigning of symptoms or disabilities e.g. Munchausen's syndrome Malingering
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Undifferentiated somatoform disorder This diagnosis is justified when multiple, persistent and varying physical symptoms, with inadequate physical explanation, occur in an individual who fails to meet the diagnostic criteria for somatization disorder. Hypochondriacal disorder In this disorder there is a persistent preoccupation with the possibility of having at least one serious physical illness, or a preoccupation with presumed deformity, despite negative findings from medical investigations and reassurance from several doctors that there is no underlying physical abnormality. Somatoform autonomic dysfunction Attribution of subjective symptoms of autonomic arousal to a body system which is primarily under autonomic control (e.g. the gastrointestinal tract), in association with the preoccupation that there may be a serious underlying physical abnormality in that system, characterize this disorder. This group of disorders is subdivided into individual disorders depending on the system in which the symptoms are perceived. Persistent somatoform pain disorder In this disorder there is persistent, severe and distressing pain which is not fully explained by any recognized physiological process or physical disorder. On assessment it may be possible to identify emotional conflicts or psychosocial problems which may have aetiological relevance. Management Full physical investigation to exclude medical cause for the physical symptoms is mandatory. Clear, unequivocal statements of negative findings should be made to the patient. A full psychiatric assessment (including evaluation of health beliefs, the presence of psychosocial factors and the role of the family in the illness) should enable the examining psychiatrist to reformulate the problem in terms of detected psychopathological processes. These should be discussed tactfully with the patient, ideally allowing the patient themselves to make links between psychological processes and physical symptoms. Family members, general practitioners and other healthcare professionals involved in the patient care should be involved as appropriate. Bland reassurances and challenges to the validity of symptoms are often counter-productive. Agreement should be reached on a plan of treatment which should be directed at improving physical symptoms, reducing distress and abnormal illness behaviour, reducing disability and/or improving quality of life. A complete resolution of symptoms may be unrealistic. Primary psychiatric disorders such as anxiety or depression should be treated
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aggressively. Abnormal health beliefs, inadequate coping or abnormal illness behaviour are best treated by cognitive behavioural methods. Some individuals are resistant to engagement in treatment, in which case further management should be directed at minimizing the demands made on health care services.
Dissociative disorders ICD-10 has replaced hysteria with dissociative disorder. The fundamental feature is complete or partial loss of the ability consciously to integrate and control aspects of mental functioning such as memory and awareness of personal identity. This notion of a dissociation of the different parts of consciousness was advanced at the turn of the century by Janet. No physical disorder exists to explain the symptoms which may have a symbolic meaning and are presumed to originate in the unconscious mind from unresolved psychosocial conflicts. Additional features may include primary gain (reduction of anxiety by excluding a problem from consciousness) and secondary gain (usually the care and attention of others). Belle indifference (markedly less than expected amount of distress and concern) is a classical sign. Denial of problems and any distress resulting from any disability may be striking. Symptoms may resemble those previously experienced by the patient or others known to him/her. Different subtypes of dissociative disorder are listed in Table 24.3 and depend on the function most affected. A full description of these subtypes is beyond the scope of this chapter. Epidemiology, aetiology, management and prognosis Presentation of dissociative disorders is most common in women under 40, though dissociative symptoms may accompany other disorders (e.g. depression, organic disorders) at any age and in either sex. There is no evidence of a genetic contribution from twin studies. Prevalence of dissociative disorders is greater in first-degree relatives, suggesting that behavioural modelling may be important. Psychoanalytic theories suggest that unresolved, unconscious conflicts result in anxiety which manifest themselves as symbolic symptoms. Histrionic personality traits are common but their significance is unclear. The link between personality types and dissociative disorders is tenuous. Management should include adequate physical investigation and treatment of coexisting disorder. Attention should be directed at factors which provoke and reinforce the patient's symptoms and are amenable to change. Positive aspects of personality and coping strategies should be reinforced. Psychotherapy may be tried but over dependence and acting-out are common. Physiotherapy and rehabilitation may provide symptomatic relief. Abreaction may be useful, especially in acute cases, though this is more diagnostic than therapeutic.
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Acute and recent onsets of symptoms predict better outcome. In Slater's 9-year follow-up of 85 patients diagnosed with hysteria, 33 per cent developed a definite organic illness, a further 15 per cent developed depression or schizophrenia and 12 patients died.
Other disorders of adult personality and behaviour Compensation neurosis Following injury, complaints of more extensive and persistent symptoms are commoner in those claiming compensation. In compensation neurosis, this accentuation is said to be unconsciously motivated. Typically, patients are said to be semi-skilled or unskilled middle-aged employees of large corporations. It was formerly believed that symptoms recovered after compensation was awarded, but it is now recognized that they persist in a high proportion of cases. Munchausen 's syndrome There are repeated presentations to hospitals, usually casualty departments, with dramatic symptoms suggesting acute physical or, less frequently, psychological illnesses. Frequent admissions are followed by urgent surgical treatment or administration of powerful analgesics demanded by patients. Any presentation is possible but abdominal symptoms, haematemesis, precordial pain and renal colic are common. Munchausen by proxy is a variant in which parents systematically provide fictitious information about their children, leading to a series of unnecessary investigations. Epidemiology and aetiology. It is uncommon, more often seen in males, with a mean age of onset in the late 30s. Asher postulated anger against doctors, satisfied by frustrating and deceiving them, as the root cause. Management and prognosis. Usually ineffective as patients discharge themselves soon after admission. Course appears to be chronic with multiple admissions. Malingering The simulation of physical or psychological illness is conscious and deliberate, and usually serves to avoid unpleasant consequences or to gain compensation. Such reasons are strongly denied. Symptoms are rarely sustained continuously for long. Misuse of alcohol and drugs, deliberate self-harm, sexual problems and eating disorders These topics are covered in detail in Chapters 16-19 and 21. It should be recognized that these disorders are common in general hospital wards
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and clinics. These disorders should be considered in cases of medically unexplained symptoms. The complex association of psychiatric, physical and social factors means that a multidisciplinary treatment is the preferred approach.
Abnormal illness behaviour Abnormal illness behaviour is not a psychiatric diagnosis but refers to abnormal cognitions and behaviours in response to physical illness or perceived physical illness. It frequently complicates the diagnostic process and management in the general hospital setting and will thus be dealt with here. Abnormal illness behaviour is defined as the persistence of an inappropriate mode of perceiving, evaluating and acting in relation to one's own state of health. These cognitive and behavioural components are deemed inappropriate in that they are ill-suited to maximize health or deviate markedly from the usual range of responses. This may occur despite appropriate explanation or reassurance. It is characterized by persistent claims or denials of illness, arising from the subject's view of the state of his/her health, which is at variance with that of the physician. The concept of abnormal illness behavioural arose from the work of Parsons on the sick role and Mechanic on illness behaviour. Sick role Parsons suggests that sick people are expected to act in accordance with certain patterns of socially prescribed and acceptable behaviour - the sick role. The various forms of this role are conditioned from childhood. Legitimate adoption of the role requires sanction from relatives, medical practitioners, employers and others in authority. It is contingent upon seeking advice and help, cooperating with assessment, accepting diagnosis and complying with prescribed treatment. In return, exemption from some obligations is allowed and the role places a duty of care on the relatives, health professionals and others. The sick person is not held responsible for the 'sickness' nor expected to recover by an act of will. Illness behaviour Illness behaviour is the way in which individuals react to aspects of their own functioning which they evaluate as 'illness' rather than 'health'. Mechanic stressed the dynamic interaction between symptomatology, cultural norms, and personal values and expectations, in the pattern of illness behaviour. Though the term abnormal illness behaviour does not refer to a single psychiatric diagnostic category, its existence characterizes the disorders listed in Table 24.3.
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General hospital psychiatry in special settings The liaison psychiatrist usually provides a service to an entire general hospital, but sometimes in practice develops a close working relationship with certain specialities who use his expertise to extend their capacity to assess and treat patients. There is then a greater chance of a successful therapeutic alliance. Examples of such integrated services include casualty departments, pain clinics, obstetric and dermatology services, cardiology services for the assessment of atypical chest pain and neuropsychiatric assessment of blackouts or hysterical paralysis. Casualty department Here, decisions have to be arrived at quickly, often with inadequate evidence as the patient may be disturbed and uncooperative. The priority therefore is to assess whether admission is required because of suicidal risk, occult medical illness, or the presence of psychosis. Violent and aggressive behaviour must be brought quickly under control with adequate numbers of staff and, if clinically indicated, the use of parenteral tranquillizers. Only then can an adequate medical and psychiatric evaluation take place. The intoxicated patient is a common problem. Such a patient cannot be assessed satisfactorily. Intoxication may mask serious medical, surgical or psychiatric conditions, therefore assessment must concentrate on these (e.g. suicide risk, psychosis, head injury, diabetes, etc.). Pain clinic The liaison psychiatrist's role can be summarized as: • to look for a primary psychiatric disorder, e.g. depression; • to assess the psychological contribution to the patient's request for medical help, e.g. anxiety; • to support the patient in his/her response to chronic pain, e.g. help to cope with the fear of undiagnosed illness and to adjust daily activities; • to look for secondary psychiatric disorder, e.g. depression; • to assess the family and social consequences of the chronic disorder, e.g. symptom-maintaining responses such as concern and attention, disturbances of family dynamics through chronic invalidism, and financial disadvantage through job loss; • to carry out or supervise psychological or pharmacological management of any of the above; • to advise on prescriptions of psychotropic drugs for possible medical reasons, e.g. tricyclic antidepressants for chronic pain, benzodiazepines for painful muscle spasm; • to help staff responses to difficult problems, e.g. unresponsive or resentful patients.
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Human immunodeficiency virus (HIV) infection The current epidemic of HIV infection highlights some of the issues facing liaison psychiatrists.
Psychiatric complications of the infection The prevalence of these is directly related to the extent of the disease. The commonest presentations are adjustment reactions (50 per cent), depression (16 per cent), and anxiety (15 per cent). Organic brain syndromes, including presenile dementia, are common (25 per cent) and up to 40 per cent of individuals with an asymptomatic infection may show a degree of cognitive impairment. There may be considerable anger concerning the manner of the diagnosis, guilt about past or present relationships and terror of a premature death.
Relatives and staff ambivalence The ambivalent responses of relatives, health care staff and significant others to those with AIDS may need to be dealt with if the patient is not to be ostracized and prevented from having adequate support and care. This also applies to those with asymptomatic HIV infection or in high-risk groups, e.g. homosexuals and opiate abusers.
Psychological distress presenting as AIDS Some anxious and obsessional individuals may misinterpret somatic complaints as AIDS. They present to their doctor seeking frequent reassurance and tests to exclude the diagnosis. Occasionally, patients with a severe psychiatric illness, such as depression or schizophrenia, may present complaining that they have contacted AIDS. Chronic fatigue syndrome/neurasthenia/myalgic encephalomyelitis There has been considerable confusion surrounding the terminology used in conditions in which the primary complaint is chronic fatigue without identifiable physical cause. Much controversy has centred on the argument over whether the aetiology for the condition is physical or psychological. Neurasthenia was first described in the early part of the nineteenth century and became one of the most commonly-made diagnoses by the latter part of that century. It later fell into disfavour and was rarely used by British psychiatrists despite its inclusion in the ICD-9 as a type of neurosis. Neurasthenia has been retained in ICD-10. Myalgic encephalomyelitis (ME) describes the syndrome of chronic, persistent and disabling fatigue in association with a constellation of
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other minor physical symptoms. More recently this latter label has fallen into disfavour as it implies that a definite pathophysiological process is causing the fatigue. Despite numerous reports of various physical abnormalities in patients complaining of otherwise apparently idiopathic fatigue, no consistent physical abnormality has yet been detected in this group. Chronic fatigue syndrome is now widely regarded as the preferred label for patients presenting with persistent fatigue unexplained by physical or psychiatric disorder. Diagnostic criteria have been developed enabling consistency in diagnosis, comparison of research findings and development of therapeutic algorithms. Once an organic cause has been excluded, treatment should aim to detect any associated psychological disorders, social stresses or abnormal illness beliefs which may be perpetuating the fatigue. Intervention in these areas should be offered where possible. Fatigue is most likely to respond to graded physical activity as part of a cognitive-behavioural approach or exercise programme. The physical activity should avoid severe overexertion which is likely to result in gross worsening of fatigue and muscle pains. Improvement is often only partial.
Reading list Barsky, A.J., Wyshak, G. and Klerman, G.L. (1986) Medical and psychiatric determinants of out-patients' medical utilization. Medical Care, 24(6), 548-60. Bass, C. (ed.) (1990) Somatization: Physical Symptoms and Psychological Disorder. Oxford: Blackwell. Benjamin, S., Barnes, D., Berer, S. et al. (1988) The relationship of chronic pain, mental illness and organic disorders. Pain, 32, 185-95. Bridges, K. and Goldberg, D. (1985) Somatic presentations of DSMIII psychiatric disorders in primary care. Journal of Psychosomatic Research, 29, 563-9. Craig, T, Boardman, A.P., Mills, K. et al. (1993) The south London somatization study: I. Longitudinal course and the influence of early life experiences. British Journal of Psychiatry, 163, 579-88. Feldman, E., Mayou, R., Hawton, K., Ardern, M. and Smith, E. (1987) Psychiatric disorder in medical inpatients. Quarterly Journal of Medicine, 63, 405-12. Fink, P. (1992) The use of hospitalizations by persistent somatizing patients. Psychological Medicine, 22, 173-80. Gater, R. and Goldberg, D. (1991) Pathways to psychiatric care in south Manchester. British Journal of Psychiatry, 159, 90-6. Hawton, K.E. (1990) Self cutting: can it be prevented? In Dilemmas and Difficulties in the Management of Psychiatric Patients (eds K.E. Hawton and P.J. Cowan). Oxford: Oxford University Press. Katon, W., Von Korff, M., Lin, E., Bush, T, Russo, J., Lipscomb, P. and Wagner, E. (1992) A randomised trial of psychiatric consultation with distressed high utilisers. General Hospital Psychiatry, 14, 86-98. Kroenke, K. and Mangelsdorff, A.D. (1989) Common symptoms in ambulatory
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care: incidence, evaluation, therapy and outcome. American Journal of Medicine, 86, 262-6. Lloyd, G., Chick, J., Crombie, E. and Anderson, S. (1986) Problem drinkers in medical wards: consumption patterns and disabilities in newly identified male cases. British Journal of Addiction, 81, 789-95. Maguire, P. and Haddad, P. (1996) Psychological reactions to physical illness. In Seminars in Liaison Psychiatry (eds E. Guthrie and F. Creed). London: Gaskell. Mayou, R.A. and Hawton, K.E. (1986) Psychiatric disorder in the general hospital. British Journal of Psychiatry, 149, 172-90. Mayou, R., Seagroatt, V. and Goldacre, M. (1991) Use of psychiatric services by patients in a general hospital. British Medical Journal, 303, 1029-32. Mechanic, D. (1961) The concept of illness behaviour. Journal of Chronic Disorders, 15, 184-94. Morriss, R. and Mayou, R. (1996) International overview of consultation-liaison psychiatry. In Seminars in Liaison Psychiatry (eds E. Guthrie and R Creed). London: Gaskell. Parsons, T. (1951) Illness and the role of the physician. American Journal of Orthopsychiatry, 21, 452-60. Pilowski, I., Murrell, T.G.C. and Gordon, A. (1979) The development of a screening method for abnormal illness behaviour. Journal of Psychosomatic Research, 23, 203-7. Royal College of Physicians and the Royal College of Psychiatrists (1995) Psychological Care of Medical Patients: Recognition of Need and Service Provision. London: Royal College of Physicians Publications. Sensky, T., Cundy, T., Greer, S. and Pettingale, K.W. (1985) Referrals to psychiatrists in a general hospital: a comparison between two methods of liaison psychiatry. Journal of the Royal Society of Medicine, 78, 463-8. Simon, G.E. and Von Korff, M. (1991) Somatization and psychiatric disorder in the NIMH epidemiological catchment area study. American Journal of Psychiatry, 148(11), 1494-500. Van Hemert, A.M., Hengeveld, M.W., Bolk, J.H., Rooijmans, H.G. and Vandenbroucke, J.P. (1993) Psychiatric disorders in relation to medical illness among patients of a general medical outpatient clinic. Psychological Medicine, 23(1), 167-73. Wessley, S. and Sharpe, M. (1995) Chronic fatigue, chronic fatigue syndrome and fibromyalgia. In Treatment of Functional Somatic Symptoms (eds R. Mayou, C. Bass, and M. Sharpe). Oxford: Oxford University Press.
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Social and community psychiatry SHAILESH KUMAR and GRAHAM THORNICROFT
Social psychiatry Social psychiatry is concerned with the effects of the social environment on the mental health of the individual, and with the effects of the mentally ill person on his/her social environment. It has also been defined as the study of the interaction between mental illness and the social milieu. Social factors in the causation of mental disorder
Sex There is a female excess in parasuicides and treated depressive and anxiety neuroses; a male excess in treated schizophrenia, alcohol dependence and suicide. One study has found that the prevalence rates for all disorders were: women 150 per 1000 population, men 60 per 1000 population.
Ethnic group Most studies of Afro-Caribbeans (AC) in Britain have shown a high rate of psychiatric morbidity, particularly schizophrenia. Psychiatric admissions with a diagnosis of schizophrenia are particularly high in this group compared with the indigenous population. The reasons postulated for this excess have included the stress hypothesis (the stress of migration and resettlement causes mental illness), the selection hypothesis (people who are vulnerable to mental illness are more likely to migrate) and cultural explanations. One prospective epidemiological survey of severe mental disorder in AC patients found that the rates for schizophrenia among AC were 12-13 times higher than for the general population and that, for the British-born AC, in the age group 16-29 years, the mean annual incidence rates were 18 times those in the general
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population. These high rates, particularly in the second-generation AC, cannot be accounted for purely by the selection hypothesis or the stress of migration. Social factors such as poverty, high unemployment, poor housing and racial discrimination, and biological factors such as heredity, perinatal trauma and, viral infections, have to be taken into account. Attempted suicide in AC has been reported to occur more frequently than in Jamaica but not as frequently as in the native UK population, although for those under 25 years of age there may not be significant difference between AC and the indigenous population. Inconsistent rates for neuroses and personality disorders have been reported in various studies. Similarly, most studies have reported compulsory admissions of AC patients occurring at least twice as frequently as other groups, with most of the extra detentions accounted for by the excess of admissions with schizophrenia. Rates of psychosis may be lower in Irish people. Epidemiological studies on psychiatric morbidity in people of Indian and Pakistani origin in Britain have produced conflicting results. There is no clear evidence that overall morbidity is either increased or decreased. The most common hospital diagnosis is schizophrenia, which does occur more frequently than in the general population. No significant differences in the rates for affective disorders have been found. As with AC, rates for attempted suicide in this group are higher than in the countries of origin but lower than the British rates. Rates for neuroses and personality disorders vary widely.
Life events Life events have been studied as causal factors, mainly in relation to schizophrenia, depression, mania, anxiety and deliberate self-harm. Problems with research exploring relationship between life events and mental illnesses include: most studies are retrospective, people are known to find meaning after an incident has occurred which is likely to distort recall, mental illnesses often have an uncertain date of onset (which makes it difficult to ascertain the temporal relationship between the onset of illness and life events); life events may occur independently of the illness (by coincidence) and the dose-response relationship between the life events and the mental illnesses can be difficult to ascertain. Reporting of life events may also be confounded by personality factors. Scales have been developed to overcome these problems. For example, the Social Adjustment Rating Scale ranks the amount of social readjustment involved in more than 40 life experiences. Research using this scale has established that the more severe life events are related to a higher risk of mental disorder. Other scales include the Life Events and Difficulties Schedule (LEDS). Using this scale, one study of schizophrenia
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found a threefold increase in life events in the 3 months before relapse compared with normal controls. Adverse life events clustered in the three weeks before relapse. Brown and Harris (1978) studied depression in women in Camberwell (London) and described: • provoking agents - severe life events or long-term difficulties, e.g. poor housing, especially carrying long-term threat or loss; • vulnerability factors - lack of a confiding relationship, three or more children under 14 years at home, the loss of mother before the age of 11 years, and no employment outside the home. Working-class women had higher rates of depression and more vulnerability factors. Provoking agents were found in 83 per cent of recent cases of depressive onset. Life events in the previous 6 months give a relative risk of 3 for schizophrenic onset, 5 for depression and 6 for suicide attempts.
Expressed emotion The concept of expressed emotion (EE) was developed to denote a measure of emotion expressed (determined by content and the form of speech) within a family towards a patient in family interview. Vaughn and Leff (1976) have demonstrated that schizophrenic relapse is related to high EE, 35 h or more contact with relatives each week and the use of maintenance medication. Where all are adverse, 92 per cent of patients relapse within 9 months. The same authors have also reported that schizophrenic patients from low EE families were more likely than those from high EE families to have experienced a life event before the index relapse and that for unmedicated schizophrenic patient either the chronic stress of living with high EE relatives or the acute stress of a recent life event was sufficient to provoke relapse.
Unemployment and work Employment offers protection to a person's mental health through nine environmental features in a nonlinear manner; • opportunity for control; • opportunity for skill use; • attainment of externally-generated goal (e.g. routines and cycles of behaviour); • variety in experience; • environmental clarity; • availability of money; • physical security; • opportunity for interpersonal contact; • a sense of valued social position.
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Most prospective studies note an association between loss of work, job instability or unemployment and suicide or attempted suicide, but the mechanisms are not clear. Higher rates of anxiety and depression are related to duration of unemployment and improve with re-employment. A correlation has been reported between economic recession and higher aggregate mental hospital admission rates 1 year later. Job loss has been associated with depression, psychosomatic complaints, increased cigarette abuse and worse children's health. Qualitative studies suggest that certain types of work may be associated with stress - as many as 10 per cent of workers are reported to experience occupational strain on any one day. Assembly-line workers, teachers and police personnel are reported to have a higher prevalence of job-related strain. Several occupations are associated with increased rates of mental disorder, e.g. alcohol abuse among employees in the licensing trade. Employment also has a supportive function: outpatients who have jobs during their treatment or recovery phase are more likely to improve than those who are out of work. A general sense of well-being is more prevalent at higher occupational levels, with movement up the occupational hierarchy being associated with improved mental health.
Socioeconomic class In England, the Registrar General's Office recognizes five social classes (determined by classifying the head of the household's occupation) (Table 25.1). Highly significant associations have been found between social class and prevalence rates of treated psychiatric disorders; the forms of disorder presenting to psychiatrists, with disproportionately more psychoses in lower classes; the kinds of treatment received, with lower class patients receiving more physical treatments and less psychotherapy. Lower social class of origins has been found to predict the prevalence of treated and untreated affective disorder. There are a number of proposed explanations of this correlation between lower social class and psychiatric illness. The social selection theory or drift hypothesis suggests that low socioeconomic status is more likely to be a consequence than a cause of mental illness, particularly schizophrenia. The alternative Table 25.1 I. II. III. IV. V.
Registrar General's socioeconomic classes
Professional and higher managerial, e.g. doctor, dentist, lawyer Intermediate occupations, e.g. schoolteachers Skilled occupations, e.g. motor mechanic Semiskilled occupations, e.g. clerk Unskilled occupations, e.g. labourer
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view is that social stress itself precipitates psychiatric disorder (social causation theory, generation hypothesis).
Area of residence Admission rates for psychosis are strongly associated with neighbourhood levels of deprivation. One study in Chicago showed that rates of admission for schizophrenia in the central slum district were three times those of the suburbs. The explanations offered for this finding include: higher levels of psychosis in deprived areas (excess precipitant factors), poorer prognosis of illness in deprived areas (excess perpetuating factors) and patients with poor prognosis drifting into deprived areas. Other studies have found increased psychiatric morbidity in those areas with poorer housing, but no consistent patterns between mental disorder and high-rise flats, new housing estates or new towns have been shown.
Homelessness Homelessness is a major problem in many cities, and studies have shown rates of psychiatric morbidity of 40-90 per cent in those using night shelters. Over half of these have alcohol dependence and chronic physical and mental problems. British studies report higher estimates of the prevalence of schizophrenia (15-30 per cent as opposed to the US findings of 10-15 per cent) and lower estimates of affective disorders (5-10 per cent, US findings 10-15 per cent). Certain characteristics of the homeless mentally ill require special consideration for service provision: distrust in existing services, lack of social support, poverty and predominance of men (homeless women are less likely to be socially isolated and more likely to be successful in obtaining financial entitlements). These factors warrant innovative approaches in service planning, including setting up special clinics in easily accessible locations, shelter-based interventions, street outreach programmes, mobile assertive treatment programmes and case management programmes that can bring together various skills such as income maintenance, housing, treatment and rehabilitation.
Social support The origins of social support hypotheses lie in theories of social network, social disorganization and basic human needs. The central idea is that social networks provide protection against stress-related morbidity (buffer hypothesis). The alternative view is that lack of social support increases the risk of disorder irrespective of the presence of other life stresses (main effect hypothesis). A recent prospective study of service use by patients with non-organic psychosis from South London has suggested that a larger social network may be associated with a lower
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likelihood of hospitalization and a wider use of non-hospital services (day-care, CPN, contact with key worker, etc.). Research into the effects of social support on mental health is fraught with difficulties: life events may change social support (e.g. bereavement resulting in loss of a supportive relationship); changes in social support can alter the likelihood of life events; social support is not a datable event and therefore its causal relationship with mental disorder may be difficult to establish. Longitudinal data incorporating measurements at two points of time is considered vital in research in this field. Because deficiencies in social networks are probably the result of combination of environmental and intrapersonal causes operating over a long period of time, any intervention is more likely to succeed when the person and his/her environment are targets of intervention. Social consequences of mental disorders
Disability Three key concepts are described in the International Classification of Impairments, Disability and Handicap. Impairment is loss of normal function at the organ level. Disability describes the disturbance in performing normal actions or functions as a result of impairments and operates at the person's level. Handicap reflects interaction with, and adaptation to, the environment and describes the disadvantages suffered by an individual due to impairments and disabilities. Along similar lines, Wing and Morris identified three levels of psychiatric disability: • primary clinical symptoms; • secondary handicaps from the experience of illness, e.g., avoidance and withdrawal; • tertiary or social disablement, such as a restricted social network, stigma, poverty, unemployment and isolation, which persist over time.
Stigma The word stigma was first used to describe the brand received by slaves in ancient Greece to mark them off from the rest of the population. It still retains similar connotations in psychiatry, i.e. having a mental illness is seen as being lesser as an individual in the society. Studies have shown that public attitudes to the mentally ill are marked by fear, distrust and dislike. Stigma may be associated with different aspects of psychiatry: public attitudes about the mentally ill makes them to be perceived as permanently disabled; the patients are seen as different from others; and labelling or attribution of a diagnosis pressurizes the mentally ill to be treated in a hospital setting as opposed to in the community. Individuals may respond to such labelling or stigmatization by withdrawing socially, feigning competence and attempting to pass 'as
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normal'. Means of reducing stigma include offering treatment in a nonhospital setting as well as educating family members and society in general about mental illness.
Effects on the family Various studies have shown a relationship between mental illness and an increased divorce rate for both sexes, even by the age of 35 years. Living with mentally ill relatives can be stressful. It has been suggested that the profound sense of loss experienced by many family members when a relative becomes mentally ill and the adjustment to the loss is similar to grief following death. The extent of this grief depends on personal characteristics of family members, the severity of the illness, and the extent of social support available. Having a relative with mental illness who resides with the family, and needs caring for, is a significant stressor. Nine themes have been identified which relate to the origin of stress: emotionally painful and disturbing feelings; fears about the safety of the patient as well as of other family members; unpredictability of the episodic characteristics of mental illness; prejudice or unfairness toward patient and family; acceptance of the illness; cognitive, emotional and behavioural coping strategies; hope as an element to come to terms with the mental illness; emotional support; the need for informational and instrumental support. Subsequently these nine themes were categorized into three main groups: emotional impact, adapting to the illness, and support needs. Mental health professionals need to develop an understanding of these themes, their origins and their impact on families. Social forms of treatment and management Lehman etal. (1995), from the Schizophrenia Patient Outcomes Research Team (PORT), have provided an up-to-date review of literature on different treatment outcome measures for schizophrenia, with an initial report drawing the following conclusions.
Vocational rehabilitation Six types of vocational rehabilitation were reviewed: • hospital-based programmes; • sheltered work; • assertive case management;
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• .psychosocial rehabilitation (prevocational training, transitional employment, and volunteer placements); • supported employment; • counselling and education. It was noted that most vocational rehabilitation programmes have a positive influence on work-related activities, but evidence to support substantial and enduring impacts on independent, competitive employment was lacking.
Psychosocial skills training There is some evidence that, in schizophrenia, operant techniques improve speech abnormalities, reducing talk about abnormal experiences and delusions, and modify hallucinations. Social skills training includes modelling, practice and feedback, but its effectiveness is related to motivation. Because of the recent trend of including cognitive skills and/or cognitive remediation techniques in traditional social skills training, the term psychosocial skills training was preferred by the PORT team. They commented that the impact of psychosocial skills training on measures of social functioning was modest and may be time limited when it occurred. Social skills training appeared to be effective in improving patients self competence.
Family interventions The PORT review summarized the main elements of family interventions most frequently used in differing combinations as: psychoeducation, behavioural problem-solving, family support and crisis management. The construct of expressed emotion (EE) was thought to have played a significant role. Intervention studies have suggested that reduction of EE or structured problem-solving with families can reduce schizophrenic relapse rates, positive and negative symptoms and hospital admissions in the 9 months after discharge. These methods are especially effective when combined with antipsychotic medication.
Community psychiatry Definition The network of services which offer continuing treatment, accommodation, occupation and social support and which together help people with mental health problems to regain their normal social roles. Development of the community psychiatry movement In the USA, the Community Mental Health Centres Act 1963 began the formal policy of community care. In 1983, only 116 000 of an estimated
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2 million chronic psychiatric patients were in hospital. In the UK, there has been a large decrease in the numbers of psychiatric hospital beds over the last 30 years. Policies of deinstitutionalization have produced alternatives to hospital admission, modifications of conventional admission, and alternatives to continued long-term hospitalization. Most research evidence suggests that the alternatives to hospital care produce outcomes better than, or no different from, conventional admission. The clinical outcomes for psychiatric patients after discharge from hospital can be described in terms of six types of outcome criteria: hospital readmission rates, community tenure, social role performance, social readjustment, symptom levels and combined global ratings. The deinstitutionalization movement owes its origins partially to the recognition of harmful effects of institutionalization.
Institutionalization Goffman described the main features of total institutions: • • • • •
all social functions are performed in one environment; highly regulated daily routine; patients are dispossessed of usual social roles; rigid rules of social distance between staff and patients; nurses are both gatekeepers of access to psychiatrists and 'culture carriers' of the hospital; • patients suffer a progressive loss of autonomy. Wing and Brown (1970) compared the outcome of schizophrenia in three hospitals. They found a high degree of association between environmental poverty (few personal possessions, less interesting activities, few visitors, more time doing nothing) and a clinical poverty syndrome (social withdrawal, flattening of affect, poverty of speech). Both increased with length of stay, and were termed institutionalism. The most socially stimulating hospitals contained patients with fewest negative symptoms. Deterioration was associated with restrictive staff attitudes. Institutionalized patients were indifferent about leaving hospital. Use of industrial therapy and therapeutic community methods improved social function. Community psychiatry in Britain Contemporary British policy for mental health services can be considered to have begun in the 1975 White Paper Better Services for the Mentally III and modified by the 1984 Short Report of the House of Commons Social Services Committee on Community Care. The services for the mentally ill proposed in 1975, per 100000 of population, are given in Table 25.2. In the Short Report, community care is seen as the deployment of health and social services in settings and in ways which meet patients'
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Services for the mentally ill proposed in 1975 per 100 000 of population
Unit service
Size
District general hospital psychiatric unit Day activity unit Long-stay elderly, severely mentally ill Day-care elderly, severely mentally ill New long-stay (length of stay 1-5 years)
50 beds 65 places 38-45 places 40-45 places Not specified
Social Service Short-stay hostels Long-stay residential care Day care
4-6 beds 15-24 beds 60 places
needs, as far as possible, in their normal physical and personal environments. Key characteristics are: • network of services - a combination of statutory, voluntary and selfhelp agencies; • coordinated services - through joint planning and care groups in multi-disciplinary teams liaising with primary care; • accessible services - locally based with clear and rapid referral; • user-responsive services - offering choice, flexibility and accountability. Progress towards the targets set can then be summarized by noting the changes in services in the period 1974-94 (see Table 25.3).
The NHS and Community Care Act, 1990 The main features of this Act are: • • • •
a clear distinction between purchasing and providing functions; the requirement for local community care plans; the creation of provider trusts and fund-holding general practices; care management - this term was introduced in 1991 to describe the role of qualified social workers who assess the needs of clients and then purchase direct care services from other providers; • a clear indication of the source of funds for residential care. Table 25.3
Progress towards the White Paper* targets summarized by the changes in services in the two decades 1 974-94
Service provision
1974
1984
1994
Target
Daily occupied psychiatric beds Day-hospital places Local authority residential places Local authority day-centre places
89900 11233 3548 5404
67000 16996 6804 8957
45000 17-22600 5200 9000
None set 45800 11500 28200
'Better Services for the Mentally III (1975).
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Care programme approach 1991 The CPA was launched in 1991 as guidelines from the government to mental health services and social services in order to promote good clinical practice and prevent patients from 'slipping through the net'. It consists of four components: • • • •
assessment of health and social care needs; a written care plan which should preferably be agreed by the patient; allocation of a key worker; regular review meetings. It became clear that applying the CPA to every patient used a significant amount of resources - both financial and staff time. The government therefore issued a document called 'Building Bridges' which outlined a revised tiered approach for appropriate implementation of the CPA (Table 25.4).
The Health of the Nation, 1992 Mental health was included as one of five 'key areas' for a national health strategy outlined in the 1992 government White Paper The Health of the Nation. The first target (to improve the clinical and social functioning of people with severe mental illness) has led to the creation of the Health of the Nation Outcomes Scale (HoNOS). The specific targets for mental health are: • to reduce the overall suicide rate by at least 15 per cent by the year 2000 (from 11.1 per 100000 population to no more than 9.4); • to reduce the suicide rate of severely mentally ill people by at least 33 per cent by the year 2000 (from the estimate of 15 per cent in 1990 to no more than 10 per cent).
The Supervision Register, 1994 The Supervision Register is a list of names, which is held locally by each provider trust, of patients with a severe mental illness who are 'known Table 25.4 Three tiers of the Care Programme Approach Minimal CPA:
More complex CPA:
Full multidisciplinary CPA:
Limited health care needs Low support needs Stable illness Usually one practitioner involved Medium level of support needed Often more than one service involved Needs less likely to remain stable Require multidisciplinary assessments Allocate a key worker Severe mental illness and severe social dysfunction or who present significant risk Allocate a key worker Consider inclusion in the supervision register
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to be at significant risk or potentially at significant risk of committing serious violence, or suicide or of serious self neglect as the result of severe and enduring mental illness'. The register should include the names of the patient, the Responsible Medical Officer (RMO), and key worker as well as the nature of the risk, and basic details of the CPA (date of registration, components of the care plan and review date), and is considered as the most intensive tier of the CPA. It requires allocation of a key worker and a risk assessment on all appropriate patients.
The Mental Health (Patients in the Community) Act 19957 Supervised Discharge Orders This Act complements the supervision register and allows the RMO to apply for powers of post-discharge formal supervision of patients under sections 3, 37 or 48 of the Mental Health Act. Under the Act, a supervisor, typically a CPN acting as key worker, has the power to take and convey the patient, to home or to a place of treatment, with ambulance or police if necessary. The Spectrum of Care, 1996 This is a booklet issued by the Department of Health to summarize the components of care that should be offered to people with mental illness on a local level. The key components are outlined in Table 25.5.
Table 25.5
The Spectrum of Care (Department of Health, 1996) Acute/emergency care
Home based
Sector teams Sustainable out of hours cover Intensive home support
Day care
Day hospitals
Residential support
Crisis accommodation Acute units Local secure units
Rehabilitation/ continuing care Domiciliary services Key workers Care management and care programme approach Drop-in centres Support groups Employment groups Day care Ordinary housing Unstaffed group homes Adult placement schemes Residential care schemes Mental nursing homes 24-hour nursed NHS accommodation Medium secure units High secure units
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National Service Framework 1999 The National Service Framework spells out national standards for mental health, what they aim to achieve, how they should be developed and delivered and how to measure performance in every part of the country. There are seven standards: 1. mental health promotion and combat of discrimination of individuals with mental health problems, 2. mental health needs should be identified and assessed and appropriate effective treatment given, 3. access to local services as necessary, 4. clear written management (case) plan; 24 hour access to services, 5. access to hospital bed and subsequent discharge plan, 6. assessment of carers' needs, 7. prevention of suicide.
Guiding principles for community psychiatric services MIND have proposed 10 principles which should underpin any community psychiatric service. So services should: be local and accessible, be comprehensive, be flexible, be consumer oriented, empower clients, be racially and culturally appropriate, focus on strengths, be normalized and incorporate natural supports, meet special needs, be accountable to the consumers and carers and evaluated. Components of a comprehensive local psychiatric service The above principles form the guidelines for developing a comprehensive mental health service. Strathdee and Thornicroft have suggested though that the community service once formed should have the following 10 components: a case register, a crisis response service, hospital and community places, assertive outreach and care management services, day care, assessment and consultation services, carer and community education and support, primary care liaison, physical and dental care, user advocacy and community alliances.
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Primary care psychiatry Pathways to care Goldberg and Huxley (1980) have described the selection process by which people with psychological disorders seek care; which of them have their disturbances detected; and finally which of them will be treated in the primary or secondary sector. An outline is given below of their model (Table 25.6). Table 25.6 Pathways to care (Goldberg and Huxley, 1980) Level 1
The community
Level 2
Total mental morbidity attenders in primary care
Level 3
Conspicuous psychiatric morbidity (mental disorders identified by doctors) Total morbidity - mental illness services
Level 4 Level 5
Psychiatric inpatients
260-315/1000 per year 230/1000 per year 101.5/1000 per year 23.5/1000 per year
First filter (Illness behaviour) Second filter (Ability to detect disorder) Third filter (Referral to mental health services) Fourth filter (Admission to psychiatric beds)
5.71/100 per year.
From Goldberg and Huxley (1980), by courtesy of Tavistock Publishers, London.
Psychiatric morbidity in primary care The amount of psychiatric morbidity seen in primary care settings is shown in Table 25.7. Table 25.7 The amount of psychiatric morbidity seen in primary care settings Level of morbidity Conspicuous psychiatric morbidity in primary care All psychiatric patients (from case registers) Psychiatric inpatients
Annual period prevalence/ 1000 population at risk 102-104 (UK) 90-93 (USA) 15-20 (UK) 27-29 (USA) 6.3-6.8 (UK) 7.0-7.5 (USA)
Models of primary and secondary interface in psychiatry Community mental health team Such teams aim to make multidisciplinary mental health treatment more widely available in the community and some prioritise their services for the seriously mentally ill. They can provide a single point of
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referral for multidisciplinary care with pooling and discussion of referrals and varying patterns of integration and responsiveness to the needs of primary care. They should be distinguished from community mental health centres (CMHCs), which had origins in the USA and blurred the distinction between primary and secondary care by drawing the focus of care from primary to secondary care.
Shifted outpatient clinic In this model, visiting psychiatrists operate clinics within health centres and see both new and follow-up patients. Members of primary and secondary care teams do not have timed meetings and may have little or irregular contact and therefore often have independent treatment approaches.
Attached mental health professionals Many professionals other than psychiatrists (e.g. CPNs, clinical psychologists, social workers, counsellors) establish links with the primary care to provide mental health care in this model.
Consultation-liaison This model is based on developing close links within a primary care team and psychiatric staff with the following goals: reducing referrals of milder disorders; selectively encouraging referral of serious mental disorders; and enhancing GPs' skills in the detection and management of mental illness. CPNs or psychologists may take the lead in developing liaison with the primary team. Other forms of psychiatric practice may take place in primary health: seeing patients directly referred by GPs or conjointly with the GP; consulting with the primary health care team on specific patients; acting as facilitator to the primary care team at staff meetings; and joint home visits by the GP and psychiatrist.
Current themes in community psychiatry Rehabilitation Rehabilitation is helping psychiatrically disabled persons make the best use of residual abilities in order to function in normal social context as best as possible. The components are assessment, treatment and management. Outcome reports suggest that rehabilitation programmes decrease readmission rates.
Clinical case management A term with broader origins in the USA and is used interchangeably in the UK with 'assertive community treatment'. It is characterized by
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small case loads, broader clinical remit, individualized treatments, programmatic flexibility, outreach, care of the most severely mentally ill, inter-agency cooperation and continuity of care.
Care management This term is adopted by the British Social Services and preferred to 'case management' to describe their approach to case management and based on 'extended brokerage case management' (i.e. assessing needs and then purchasing appropriate care packages). It was introduced in April 1993 and is centrally denned by a central brokerage function with a varying degree of budgetary control.
Needs assessment In order to plan an effective treatment package it is important to know the needs of the target population, because offering inappropriate services is a waste of resources. This, however, is a challenging task, because the mentally ill population have multiple and complex needs. Several tools have been developed for assessing needs, including for example the Camberwell Assessment of Need. An ideal tool for assessing needs should be brief, take little time to administer, be usable within a multidisciplinary team without extra personnel help, and can be used as an integral part of routine clinical work.
Sectorization This term is generally used to denote a delineated geographic area with a denned catchment population. The size of the catchment population differs between different countries; for instance, in West Germany it is 250000, the Netherlands 300000 and much smaller for the Scandinavian countries. It is regarded as an essential prerequisite for service development in the UK; around 80 per cent of the districts nationally had divided their catchment area into sectors by 1993. Various factors may influence sectorization of services: rural/urban nature of the area, presence of a river or natural structure that may impair access, the need to share with social services or general practice sector boundaries etc.
Crisis response teams Crisis response teams should be available 24 hours a day, on a 7-day basis, manned by experienced professionals and known to providers, families, clients and the community for rapid evaluation, diagnosis and medications needed. Properly run crisis intervention teams can be instrumental in avoiding admissions and provide accessible and acceptable services to its clients.
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Assertive community treatment Treatment offered at the place, wherever in the community, where the patient lives. The most commonly offered home treatment these days is assertive community treatment (ACT), in which the staff-patient ratio is about 1:10. It aims to help clients manage their illnesses, facilitate an optimal supportive environment and training them in activities of daily living and social relations and work.
Partial hospitalization This is the most thoroughly investigated alternative to hospitalization in which multidisciplinary acute care is given during the day, with the patients returning home each day. It is also known as day hospitalization. There may be fewer differences in clinical outcome between the inpatient treatment and partial hospitalization.
Crisis houses These are short-term residential alternatives to hospitalization and are found to be appropriate for a range of situations: young adults experiencing an initial acute episode of major mental illness, long-stay users of day hospitals, adolescents with psychiatric difficulties, situation crises and, for the homeless, mentally ill crises.
24-hour nursed care The 1996 NHS Executive report on 24-hour nursed care stressed the need for providing 24 hours of nursed care for the 'new long stay' group of patients which, according to various estimates, may be needed for approximately 5000 patients in England and Wales. These include people who respond only partially to acute treatment, remain substantially disabled, and require transfer to longer term high-intensity treatment and support (without which they risk occupying acute psychiatric beds for too long). The care aims to monitor their mental state daily, monitor their risk frequently, supervise medication, assist with self-care and daily living, manage challenging behaviour and provide ongoing evening and weekend support. Finally the report clarifies that providing the full range of care for this group of patients is entirely the responsibility of the NHS.
References and Reading list Bebbington, P., Hurry, J. and Tennant, C. (1981) Psychiatric disorders in selected immigrant groups in Camberwell. Social Psychiatry, 16, 43-51. Becker, T., Thornicroft, G,. Leese, M. et al. (1997) Social networks and service use among representative cases of psychosis in South London. British Journal of Psychiatry, 171, 15-19.
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Brown, G.W. and Harris, T.O. (1978) Social Origins of Depression: A Study of Psychiatric Disorder in Women. London: Tavistock. Burns, T. (1997) Case management, care management and care programming. British Journal of Psychiatry, 170, 393-5. Cask, L., Sibbald, B. and Creed, F. (1997) Evaluating models of working at the interface between mental health services and primary care. British Journal of Psychiatry. 170, 6-11. Goffman, E. (1961) Asylums. New York: Doubleday. Goldberg D. and Huxley P. (1980) Mental Illness in the Community. London: Tavistock. Harrison, G., Owens, D., Holton, A. et al. (1988) A prospective study of severe mental disorder in Afro-Caribbean patients. Psychological Medicine, 18, 643-57. Hollingshead, A. and Redlich, F. (1938) Social Class And Mental Illness. New York: Wiley. Kluiter, H. (1997) Inpatient treatment and care arrangements to replace or avoid it - searching for an evidence base. Current Opinions in Psychiatry. 10, 160-7. Lehman, A.F., Thompson, J.W., Dixon, L.B. and Scott, J.E. (1995) Schizophrenia: treatment outcomes research - Editors introduction. Schizophrenia Bulletin. 21, 561-6. Paykel, E. (1978) Contribution of life events to causation of psychiatric illness. Psychological Medicine, 8, 245-53. Solomon, P. and Draine, J. (1995) Subjective burden among family members of mentally ill adults: relation to stress, coping, and adaptation. American Journal of Orthopsychiatry, 65, 419-27. Strathdee, G. and Thornicroft, G. (1997) Community psychiatry and service evaluation. In Essential Postgraduate Psychiatry. Cambridge: Cambridge University Press. Stein, L.I. and Test, M.A. (1980) Alternative to mental hospital treatment. Archives of General Psychiatry, 37, 392-7. Tyrer, P. and Malone, S. (1992) Psychiatry without hospital beds: a review of treatment strategies. In Recent Advances in Clinical Psychiatry (ed. K. GrossmanGranville). Edinburgh: Churchill Livingstone, van Os, J., McKenzie, K. and Jones, P. (1997) Cultural differences in pathways to care service use and treatment outcomes. Current Opinions in Psychiatry, 10, 178-82. Vaughn, C. and Leff, J.P. (1976) The influence of family and social factors on the course of psychiatric illness: a comparison of schizophrenic and depressed neurotic patients. British Journal of Psychiatry, 129, 125-37. Warner, R. (1985) Recovery from Schizophrenia. London: Routledge Kegan Paul. Warr, P. (1989) Work, Unemployment and Mental Health. Oxford: Clarendon Press. WHO (1980) International Classification of Impairments, Disability and Handicap. Geneva: World Health Organization. Wing, J. and Brown, G. (1970) Institutionalism and Schizophrenia. Cambridge: Cambridge University Press.
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Transcultural psychiatry CATHY SHAW and STEPHEN REID
Transcultural psychiatry is the comparative study of mental disorders in ethnic groups, and the practice of psychiatry when the ethnicity of patient and psychiatrist may not be the same. Cultural considerations should inform all psychiatric practice, if the aim is to understand patients' distress, illness and predicament in their own terms.
Culture and Ethnicity Ethnic group or ethnicity refer to socially defined groups, based on shared cultural characteristics, including beliefs, attitudes, behaviour patterns, language and history. For research purposes, if this social definition is accepted, subjects should be asked to classify themselves according to their own perceived ethnicity. The 1991 census was the first in the UK to include self-assigned ethnicity and birth place as separate variables. Three million people (5.5 per cent of the national population) identified themselves as belonging to a minority ethnic group (not white): these included 840000 Indian, 500000 African Caribbean, 477000 Pakistani, 212000 African, 163000 Bangladeshi, 290000 other non-Asian, 198000 other Asian, 178000 other, and 157000 Chinese. Problems of undercounting mean these figures may be underestimates. Race, as a biological construct (in which people are differentiated on the basis of physical characteristics with a presumed underlying genetic difference), has largely been rejected as having no scientific foundation - the amount of genetic variation within any 'racial' group is larger than that between groups. Ethnicity as a variable used in research, has also been criticized. Culture itself is not fixed, but changes over time; ethnic groups are heterogeneous and membership is fluid; ethnicity is therefore difficult to measure, and findings of research may not be generalizable. Ethnicity is not the same as either skin colour, birth place,
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nationality, migrant status, religion, language - all of which have been used to classify individuals. Medical anthropologists (e.g. Kleinman) have described how culture affects or determines illness experience. Explanatory models include beliefs about the nature, meaning and causation of illness, pathways to appropriate treatment, the sick role, and responses of the family or wider society to illness. In response to mental distress, it may be seen as more appropriate to treat oneself with herbal remedies, or consult a lay healer or religious leader, than a doctor, by members of some ethnic groups in Britain. Cultures also vary in their tolerance or promotion of behaviour which may be protective or harmful to health (e.g. at a population level, alcohol consumption is less in the African Caribbean, Indian, Pakistani and Bangladeshi communities than among white Europeans). Concepts of mental illness can be classified as either etic - in which disorders are seen as universal, described by psychiatric nosology, assessed using standardized instruments - or emic - generated from within a particular culture, using that culture's health beliefs and illness models. Social and cultural factors are particularly important in the understanding of the manifestations of mental disorders, in the absence of pathophysiological tests and explanations (in many instances). Furthermore, mental disorder and psychiatry have also been linked to society's fluctuating notions of normality and deviance. Psychiatry itself is a cultural system, developed within late nineteenth and twentieth century Western European medicine. Psychiatry has been criticized for being eurocentric and racist; blaming different cultures for illness; failing to understand non-Western cultures and labelling deviant behaviour mental illness; emphasizing negative aspects of health in minority ethnic groups; and causing harm to members of ethnic minority groups as a result of inappropriate treatment. Critics argue that greater emphasis should be placed on the psychological and social effects of racism within society in causing mental illness. Institutional racism is likely to promote low self-esteem and the cognitive patterns associated with depression. Increased social and economic adversity, such as higher rates of poverty, unemployment and physical ill health, are experienced by minority ethnic populations in inner cities, and may be expected to have an adverse effect on mental health.
Epidemiology Epidemiological studies identifying differences in rates of mental disorders between groups are useful in order to elucidate aetiology, and to inform the provision of appropriate services. In the absence of pathological tests, internationally agreed diagnostic systems have been
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developed to enable comparisons between countries and cultures, often translated and back-translated into appropriate languages. Such instruments assume that mental disorders are fundamentally similar in all humans, with culture only having a pathoplastic effect. Kleinman has suggested that Western psychiatric concepts such as depression lack meaning in other cultures, and cannot be universally applied ('category fallacy') and pointed out how standardized instruments fail to detect indigenous expressions of distress. International comparisons The World Health Organization has carried out a series of studies to establish the recognition of diagnostic categories across cultures, and compare their frequency, course and outcome, including the International Pilot Study of Schizophrenia and the Collaborative Study of Determinants of Outcome of Severe Mental Disorders. These studies were linked to the development of standardized instruments (the International Classification of Diseases (ICD), and the Present State Examination (PSE)). Although the incidence of broadly defined schizophrenia varied between countries (1.5 to 4.2 per 100000), the incidence rates of narrowly defined schizophrenia were similar, ranging from 0.7 to 1.4 per 100000 (in the age group 15-54 years). Furthermore, the similarity of the patterns of onset associated with age and gender led the researchers to conclude that this was the same disorder, present in people throughout the world. Diagnostic practices of local psychiatrists were also broadly in agreement with diagnoses established by the PSE, with the exception of psychiatrists in the USA and the USSR. An unexpected finding of the research into the 2-year follow-up of first-contact psychotic subjects was that, in developing countries, schizophrenia appeared to have a more favourable outcome, with greater likelihood of a remitting course, full remission between episodes, longer time in remission, and less impairment of social function. Epidemiological surveys using standardized methodology in individual countries have shown that prevalence rates of common mental disorder (depression and anxiety) are at least as high in developing countries as in the UK (rates ranging from 10 per cent to 25 per cent), although beliefs about illness, forms of presentation patterns of help-seeking behaviour, and the provision of services vary widely. Similarly, prevalence rates of childhood mental disorders have also found to be similar in developing countries, with similar patterns of risk factors. Comparisons between ethnic groups in Britain epidemiological data and clinical issues Earlier research was beset by methodological problems, including lack of consistency in definition of ethnicity, and the use of proxy variable
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such as birth place. Rates of hospital admission in relation to population data based on censuses were compared, using routinely collected data, often of poor quality, and biased by the exclusive emphasis on those patients requiring admission, and the under-enumeration of minority ethnic groups in censuses. Population-based surveys often involved small, unrepresentative samples, and failed to use standardized assessment instruments. Differences between ethnic groups were confounded by social and economic differences. More recently, epidemiological methods have been applied more rigorously, in several national and local studies identifying rates of mental disorder in different ethnic groups, the results of which are summarized below. Recent national surveys include: • the Office of Population Censuses and Surveys (OPCS) Survey of Psychiatric Morbidity in Great Britain; although it covered a national sample of over 12000, only 4 per cent of the 10000 respondents were from minority ethnic groups; • the Policy Studies Institute study, including 1205 African Caribbean, 2001 Indian/African Asian, 1776 Pakistani/Bangladeshis and 2867 white respondents.
The African Caribbean community Recent surveys employing sound methodology, albeit still reliant on identifying all those in contact with services, have consistently found annual treated incidence rates of psychotic illness in African Caribbean people in Britain to be 3-12 times as high as rates in Whites, and higher than equivalent rates in Caribbean countries. African Caribbean people born in Britain ('second generation') were found to have even higher rates than among the population who had migrated. Possible hypotheses to explain this, many of which have been tested in recent studies include: • genetic predisposition among African Caribbean people (but the incidence of schizophrenia is not elevated in Caribbean countries); • migration stress or selection (but rates are highest among African Caribbeans born in Britain, not those who migrated); • greater susceptibility to intra-uterine viral infection (this might explain higher rates in the children of migrants, but not in migrants themselves); • increased rates of obstetric complications (white patients with schizophrenia have been found more likely to have history of obstetric complications than African Caribbean patients); • misdiagnosis (an experiment in which Caribbean and British psychiatrists compared their diagnoses of patients in London failed to demonstrate overdiagnosis of schizophrenia by the British psychiatrists);
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• other environmental factors, e.g. social deprivation or racism (two studies have found that the morbid risk of schizophrenia for firstdegree relatives of patients with schizophrenia is similar for white relatives, and African Caribbean relatives born in the Caribbean, but greatly increased for African Caribbean siblings born in Britain: genetic factors could not explain this). Differences in clinical management have been highlighted by other studies: compared to their white counterparts, African Caribbean people with psychosis are more likely to be admitted compulsorily under the Mental Health Act; admitted using a section 136 (i.e. involving the police); treated in a secure setting; and receive larger quantities of antipsychotic medication. Although most research has focussed on the issue of psychotic disorders in African Caribbeans, recent general population surveys have found a higher prevalence of depression, but lower rates of anxiety, in African Caribbeans compared to Whites, taking social and economic factors into account. Overall, the prevalence of common mental disorder was similar in both ethnic groups in an inner city setting.
The South Asian community There have been no epidemiologically rigorous studies to establish clearly whether or not there are differences in incidence rates of psychotic disorders in people of Indian, Pakistani or Bangladeshi origin in Britain. Concerning common mental disorder (depression and anxiety), findings of surveys have been conflicting. Studies in primary care have shown a high prevalence of depression among Pakistani and Indian General Practice attenders. However, general population surveys have found lower rates of anxiety in Indians, Pakistanis and Bangladeshis, compared to Whites, and lower rates of depression in Bangladeshis. Increased rates of deliberate self-harm have been identified in Indian women aged 16-24 years. Clinically, problems have been identified in the areas of lack of recognition or detection of mental disorders, and communication problems between doctor and patient. Mental health services have recognized that Indian, Pakistani or Bangladeshi patients are underrepresented in mental health services. As with African Caribbean patients, concerns have been expressed about the lack of access to psychological treatments.
The Chinese community Very little information is available concerning the epidemiology of mental disorders within this group: the PSI study mentioned above included a sample of only 214 Chinese people, insufficient to provide robust data.
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Other Clinical Issues Migrants and refugees Migration has long been recognized as a potentially stressful life event and source of ongoing difficulties which can increase vulnerability to mental disorder. Refugees often have even more problems, due to the extremity of difficulties necessitating their departure (including torture, persecution and bereavement), and on arrival in Britain (fear, uncertainty, involvement with authorities). Post-traumatic stress disorder is especially likely. A number of organizations exist to help resettle refugees. Somatization Traditionally there has been a stereotype within psychiatry that people of minority ethnic groups were more likely than white Europeans to present psychological distress in the form of somatic symptoms. However, research in primary care has shown that the majority of white Europeans with mental disorder present to their GP with somatic symptoms. It is a widely-held belief that doctors expect to hear about physical complaints in a consultation, rather than psychological distress. Somatization is therefore an extremely common phenomenon in all ethnic groups. Improving services Access to existing services, and issues of appropriate mental health services for minority ethnic groups in Britain, have been the subject of government policy (e.g. in the Health of the Nation documents) and criticism by representative groups (highlighting issues of discrimination). Some issues have been highlighted above. A further criticism has been that patients from minority ethnic groups are less likely to receive psychological treatments, compared to Whites, and more likely to get physical treatments. However, other research has shown that African Caribbean people with depression, for example, were less likely to be receiving antidepressant medication than their white counterparts. Areas for improvement of access to appropriate services and treatments for mental disorder for members of minority ethnic groups in Britain include: • an emphasis on improving mainstream services (rather than marginalizing minority ethnic groups); • improving training to minimize discrimination, mis-, under-, or overdiagnosis of mental disorder in members of minority ethnic groups; • recruiting staff from minority ethnic groups to be trained in the mental health professions (employment policy); • identifying needs of service users from minority ethnic groups; • seeking and responding to community representation; • providing staff and interpreters with appropriate languages; • setting up outreach and health promotion programmes;
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• promoting and working together with independent or non-statutory providers of mental health services. Culture-bound syndromes This term was introduced by Yap in 1967 to describe disorders that are restricted to a particular culture or geographical area. Within the ICD-10 these syndromes are described under the categorization 'other specified neurotic disorders', and are described as 'mixed disorders of behaviour, beliefs and emotions which are of uncertain etiology and nosological status and which occur with particular frequency in certain cultures'. These syndromes involve a manifestation of distress, which has symbolic meaning for the individual and social group within a particular culture, and a specific response or treatment is linked to it. Twelve culture-specific disorders are listed in ICD-10 (Diagnostic criteria for research, Annex 2): • amok (Indonesia, Malaysia, Philippines) - outburst of homicidal or destructive behaviour, usually following an imagined insult, and in turn followed by amnesia or suicide; • dhat (India)Ishen-kui - (China) premature ejaculation, impotence, anxiety and somatic symptoms, particularly weakness, palpitations and poor sleep; • koro/suk-yeong (south-east Asia, south China, India) - intense anxiety, fear of genital retraction into abdomen, belief this will be fatal; can occur in epidemics; • latah (Indonesia, Malaysia, Philippines) - exaggerated response to trauma, echolalia, echopraxia, occasionally coprolalia, trance - may be a dissociative state, mainly in women; • nerves (Europe, central/south America) - chronic anxiety, somatic symptoms; • pa-leng, frigophobia (Taiwan, southeast Asia) - fear of cold; • piblotoq, Arctic hysteria (Inuits, Arctic) - fatigue, depression followed by outburst of disturbed behaviour (including tearing off clothes and running wildly about), then amnesia, maybe a short-lived dissociative state; • susto (central/south America) - chronic complaints, 'soul loss' (linked to an acute anxiety state); • taijin kyofusho, anthropophobia (Japan) - somatic symptoms, fear of social contact, fear of disease, and self-consciousness; • ufufuyane, saka (southern Africa) - anxiety, trance, dissociative symptoms attributed to spirit possession or poisoning; • uqamairineq (Inuits, Arctic) - sudden paralysis, borderline sleep states; • windigo (native Americans) - depression, nausea and a distaste for food, then ideas of cannibalism, homicidal/suicidal thoughts. The standardized diagnostic system has struggled to accommodate such syndromes, and recognizes their 'controversial' status, with some
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psychiatrists asserting that they are not separate conditions, but can be understood as cultural variants of other disorders such as phobic anxiety, depression, neurasthenia, somatoform disorders, dissociative (conversion) disorders, or reactions to stress. The emphasis on the exotic within this list has been criticized: non-European psychiatrists have commented that eating disorders and deliberate self-harm could be seen as culturebound syndromes.
Reading list Bhugra, D., Leff, J., Mallet, R. et al. (1997) Incidence and outcome of schizophrenia in whites, African Caribbeans and Asians in London. Psychological Medicine, 26, 791-8. Cox, J. (ed.) (1986) Transcultural Psychiatry. London: Groom Helm. Fernando, S. (1991) Mental Health, Race and Culture. London: Macmillan/MIND Publications. Gater, R., De Almeida, E., Sousa, B. et al. (1991) The pathways to psychiatric care: a cross-cultural study. Psychological Medicine, 21, 761-74. Harrison, G., Glazebrook, C., Brewin, J. et al. (1997) Increased incidence of psychotic disorders in migrants from the Caribbean to the UK. Psychological Medicine, 26, 799-806. Jablensky, A., Sartorius, N., Ernberg, E. et al. (1992) Schizophrenia: manifestations, incidence and course in different cultures. A WHO 10-country study. Psychological Medicine (Monograph Suppl. 20). Kleinman, A. (1980) Patients and Healers in the Context of Culture. Berkeley: University of California Press. Kleinman, A. (1987) Anthropology and psychiatry. British Journal of Psychiatry, 151, 447-54. Krause, I-B. (1989) Sinking heart: a Punjabi communication of distress. Social Science and Medicine, 29, 563-75. McKenzie, K. and Cowcroft, N.S. (1996) Describing race, ethnicity and culture in medical research. British Medical Journal, 312, 1054. Modood, T, Berthoud, R., Lakey, J. et al. (1997) Ethnic Minorities in Britain. London: Policy Studies Institute. Nazroo, J.Y. (1997) Ethnicity and Mental Health. Findings from a National Community Survey. London: Policy Studies Institute. Patel, V., Gwanzura, P., Simunyu, E. et al. (1995) The phenomenology and explanatory models of common mental disorder: a study in primary care in Harare, Zimbabwe. Psychological Medicine, 25, 1191-9. Senior, P.A. and Bhopal, R. (1994) Ethnicity as a variable in epidemiological research. British Medial Journal, 309, 286-7. Shaw, C.M., Creed, R, Tomenson, B., et al. (1999) Prevalence of anxiety and depressive illness and help seeking behaviour in African Caribbeans and White Europeans: two phase general population survey. British Medical Journal, 318, 302-5. Wilson, M. (1993) Mental Health and Britain's Black Communities. London: King's Fund. World Health Organization (1973) International Pilot Study of Schizophrenia. Geneva: WHO.
27 Forensic psychiatry TRACEY HEADS and DAVID FORSHAW
Criminology Statistical aspects An estimate of the amount of crime in a community may be obtained by house-to-house surveys which ask residents about crime that they have experienced. The 1991 British Crime Survey found a significant discrepancy between crime reported by the community and that reported to the police. Many crimes were not reported to the police because the victims considered them too trivial or believed there was little chance of solving them, or they were too embarrassed or afraid of retaliation. The Criminal Statistics for England and Wales record an increase in known indictable offences from 0.5 million per annum in the 1950s to over 5 million per annum in the 1990s, with a proportionately greater increase in offending by women. Offending reaches a peak at 14-16 years and then declines with increasing age, though in females there is a small increase again around 40-50 years. West and Farrington followed up 400 boys from 8 years of age in inner-city London (The Camberwell Study). Eighty per cent had committed a crime by 17 years but only 20 per cent had been caught and half of these went on to further convictions. By 25 years, 33 per cent had convictions. The overall ratio of male to female offenders convicted or cautioned for indictable offences is around 5:1, although the proportions vary for different types of crime. Females commit less serious offences and there are 30 times as many males in prisons as females. Explanations for gender differences in offending include biological theories, e.g. biological factors underlying greater aggression in males, and social influences on behaviour, e.g. girls being conditioned to be better behaved.
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Factors associated with delinquency
Social factors Predictive factors associated with the family environment were identified by the Camberwell study, including: • low income family; • large size family, i.e. 5 or more children; • unsatisfactory parenting, including rejection or neglect, inconsistent or harsh discipline and marital conflict (separation from parents because of death or illness was not significant, but separation arising out of marital breakdown was highly so); • parental criminality. Broader social influences include: • urban environment. Delinquency rates are lower in rural areas and moving to a rural environment has been found to be associated with a decrease in delinquency in urban offenders; • schools and peer groups; • exposure to violence. The effect of exposure to offending and violence in the media on offending is controversial. Exposure to violence in the home environment is associated with offending behaviour; • labelling. Juveniles caught offending go on to offend more than matched undetected juvenile offenders. Rutter and Giller noted several social factors which seem to protect against delinquency, including: good peer group; successful employment; good marriage; improvement in life circumstances; one good relationship; good life experience outside the home. Racial differences in reported offending may be due to many factors, such as differences in reporting rates and policing methods, different cultural attitudes to offending and greater levels of social disadvantage in certain groups.
Inherited and constitutional factors Genetic Criminality has greater concordance in monozygotic (35 per cent) than in dizygotic (14 per cent) twins. Adoption studies have shown the importance of both rearing and genetic factors, with some researchers concluding that the latter is more important.
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Neurophysiological Abnormal EEGs and CNVs (contingent negative variations) have been reported in violent criminals. Skin conductance in psychopaths is lower with less spontaneous fluctuation than normals and conditioning to painful stimuli is slower. These observations have led to the proposal that delinquency arises from an inability to condition normally due to an abnormality within the autonomic nervous system or to defects in cortical arousal. Other organic factors Low intelligence has been found to be associated with delinquency, and particular patterns of cognitive deficits may be important, including low nonverbal IQ and deficits in executive functions. Attention deficit disorder, although overlapping to a degree with conduct disorder, appears to be independently linked with delinquency and later offending behaviour. Temperament West and Farrington showed that the best predictor of delinquency is troublesomeness at primary school (i.e. poor concentration, disobedience and problems with relations with other children). Impulsivity, which may be linked with attention deficit disorder, is also associated with delinquency. Other temperamental traits, such as greater social competence, may protect against delinquency. Causes of violence The main hypotheses include: • instinct hypothesis (Lorenz); • frustrated-drive hypothesis (Bollard and colleagues); • learned-response hypothesis (Bandura). Factors modifying violent responses include: • personality. Blackburn noted four main types: undercontrolled and low social anxiety; undercontrolled and high social anxiety; overcontrolled and low social anxiety; overcontrolled and high social anxiety; • immediate social group; • behaviour of the victim, e.g. up to a quarter of homicide victims have been reported as provoking the aggressor; • presence of disinhibiting factors, e.g. alcohol or drugs; • environmental factors, e.g. availability of weapons; • physiological factors may alter irritability, e.g. fatigue and lack of sleep; • presence of mental abnormality.
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Crimes against the person Ninety per cent of violent offenders are male and over half are aged between 17 and 24 years. Male victims are more frequent than female. Violent offending is frequently associated with alcohol intoxication. The homicide rate in England and Wales is about 12 per million of population per annum (approximately 650-700 confirmed cases per annum). Children under 1 year are the group most at risk of homicide. The homicide victim knows their killer in 75 per cent of cases; in half, the killer is a family member or lover. One-third of murderers have previous convictions, most for crimes against property. Legal definitions of homicides Murder is the unlawful killing of a human being with malice aforethought, i.e. the intention to kill or to cause grievous bodily harm. Manslaughter is homicide not meeting the full criteria for murder or where there are mitigating circumstances, and is divided into Voluntary' and 'involuntary'. In voluntary manslaughter, malice aforethought is present but there are mitigating circumstances which include: • provocation; • diminished responsibility; • killing as part of a suicide pact. Involuntary manslaughter includes all cases of unlawful killing where no malice aforethought exists, e.g. causing death by gross negligence. 'Abnormal' homicide refers to offenders with psychiatric disorder and covers those found insane or unfit to plead, diminished responsibility verdicts, infanticide or killing as part of a suicide pact. One-third of homicides in England and Wales are abnormal. Killing of children and infants Of women who kill, most kill their own children, whereas of men who kill, only 15 per cent kill their own children. Of children under 1 year who are killed, 60 per cent are killed by their mothers. Infanticides and child murders by mothers can be divided into those where the killing occurs in the first 24 hours following birth, termed neonaticide, and those occurring later. The majority of neonaticides are committed because the child is unwanted, with a minority committed by acutely psychotic mothers. In killing of children over 24 hours old, approximately half are associated with child abuse and the other half occur in the context of depressive or psychotic illness.
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Spouse abuse ('wife battering') Spouse abuse refers to deliberate, severe and repeated physical assaults from a marital partner, although psychological abuse and intimidation may also be present. The incidence is unknown. Factors such as possessiveness, the need to oppress and control and alcohol intoxication are thought to be important. Symptoms of depression and anxiety are common in victims and many make suicide attempts.
Sexual offences Sexual offences account for less than 1 per cent of all indictable offences. Rape In about 30 per cent of cases the offenders are strangers to the victim, in another 30 per cent brief acquaintances and in the rest either longterm acquaintances or relatives. In about 30 per cent of rapes there is more than one attacker. Rapists are often under 25 years old. Around half of rape victims are threatened either verbally or with weapons, and around one-third of rapes involve additional physical violence. Alcohol is a significant factor in many rapes. The victim may be killed in order to silence them, either during the assault or to stop them later giving evidence; or in sadistic sexual killing, when the killing itself is sexually arousing. The majority of rapists receive prison sentences. Most therapeutic approaches used with rapists aim at treating any underlying mental disorder and improving social functioning using individual and group approaches. Anti-libidinal treatment may also help in some cases. In a 22-year follow-up study of males charged with rape, 90 per cent did not rape on a subsequent occasion, but 15 per cent were reconvicted of a sexual assault and 17 per cent of a violent offence. Victims often respond to the trauma of rape with shock, disbelief, anxiety, guilt and shame. Most symptoms resolve over the course of some weeks; however 20 per cent of victims experience chronic symptoms of anxiety and depression. Psychosexual and relationship difficulties may also result. Factors which predispose to prolonged reactions involve the nature of the assault and psychological characteristics of the victim. The trauma of the legal investigation of rape may be alleviated by the use of women police officers and doctors to interview and examine victims. Rape victims often benefit from referral to rape crisis centres which provide support and counselling. Indecent assault Indecent assault covers a wide range behaviour, from touching to more serious sexual assaults. The majority of victims are female. Factors
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contributing to rape, and treatment approaches to rapists, may also be relevant for this group of offenders. Indecent exposure Two broad types of exhibitionist have been described: Type 1. Offender feels impelled to expose themselves. They tend to expose a flaccid penis and not to masturbate at the time. Type 2. Offender derives considerable pleasure from exposing an erect penis and masturbating. Eighty per cent of exposers are only convicted once; however those who are convicted a second time have a high risk of further recidivism. Most exposers do not progress to other sexual or nonsexual crimes. Approximately 10 per cent of those convicted of rape, arson or robbery with murder, however, have previous convictions for indecent exposure. Child sexual abuse True incidence is difficult to establish; however, some studies have found that 10-15 per cent of women, and a smaller percentage of men, report sexual abuse during childhood.
Extra-familial Paedophilia is much more common in men than in women. In most instances sexual activity consists of fondling, petting and genital manipulation. Attempts at vaginal or anal intercourse are uncommon. Homosexual paedophiles have the highest rate of recidivism. Alcohol use is frequently a significant factor. Sexual offences against children may be committed by men of all ages, social classes and educational and intellectual backgrounds.
Incest It is an offence for a man to have sexual intercourse with a woman whom he knows to be his granddaughter, daughter, sister, half-sister or mother. Incest is similarly defined for a woman. The most common incest is between brother and sister, but the vast majority of reported cases are of father-daughter incest. Mother-son incest is rare. Half of reported cases go to trial. Social Services Departments have a statutory duty to inform the police of suspected cases of incest under the Children's and Young Persons Act 1969.
Property offences In England and Wales approximately 95 per cent of recorded crimes are property offences, including acquisitive offences such as theft and hand-
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ling stolen goods, burglary, fraud and forgery; and destructive offences such as criminal damage and arson. Shoplifting Shoplifting is extremely common and has been reported in up to 1 in 12 shoppers. Normal people may shoplift in association with absentmindedness or forgetfulness and stress related to major life events. Other shoplifters are professional or shoplift in the context of other delinquent activities. In 5 per cent there is an association with mental disorder, including: depression and anxiety, particularly in middle-aged women; chronic schizophrenia, in the context of general deterioration or rarely in association with psychotic symptoms; organic states; and substance abuse, to finance use or in association with impaired concentration. Kleptomania, or compulsive stealing, is defined in ICD-10 as a repeated failure to resist impulses to steal objects that are not required for personal use or monetary gain. There is reported to be an increasing sense of tension before, and a sense of gratification immediately after, the act. Feelings of guilt and anxiety may occur between episodes. Assessment involves a full psychiatric history and examination, establishing the circumstances of the offence, and an exploration of the links between any mental abnormality and the offending. Underlying serious mental disorders, such as depression, should be treated. Several behavioural techniques have been reported to be successful for compulsive shoplifting. Arson One-third of those cautioned or arrested for arson are under 13 years, over two-thirds are under 21. Around 90 per cent of arsonists are male. Faulk classified arson as: • fires as a means to an end (e.g. insurance fraud, earn money, covering up a crime, political; gang activity for excitement, revenge, anger, a cry for help, desire to feel powerful or be seen as hero); • fires as things of interest in themselves (e.g. irresistible impulse, sexual excitement, tension or depression reduction). Psychiatric abnormality may be associated with any of these categories and occurs in approximately 10 per cent of arsonists. Arson may result from variety of psychiatric conditions including schizophrenia, mental impairment, personality disorder, organic brain damage and alcohol dependence or harmful use. English criminal law Police refer suitable cases to the Crown Prosecution Service which then decides whether to prosecute. Criminal offences are defined by statute
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or common law and are divided into minor (summary) offences tried by magistrates (e.g. drunkenness and simple criminal damage) and serious offences where the defendant has to be indicted (accused) before judge and jury (e.g. murder). Indictable offences are those which may be punished by 3 or more months of imprisonment. Magistrates Court Ninety-eight per cent of crimes are tried by magistrates who are unpaid laymen appointed by the Lord Chancellor. The Clerk of the Court advises on points of law. Magistrates Courts serve two main functions in criminal proceedings, either as the court of trial or as a court of preliminary investigation where the magistrates determine if the prosecution has established a case. The defendant is discharged if not, but bound over to trial at the Crown Court if there is a case to answer. Juvenile Court Three magistrates, one of whom must be female, try the cases of those under 17 years. However, homicide cases are tried in the Crown Court. Crown Court In indictable cases, the defendant may opt, or be required, to stand trial before judge and jury. The judge may be a High Court Judge, Circuit Judge or Recorder, depending upon the severity of the offence. Children and criminal responsibility Children under 10 years are not considered to be criminally responsible. If a child under 10 commits a serious criminal act the remedy at law is often a care proceeding. Children over 10 but under 14 are also free from criminal responsibility unless it is proved that they committed the crime knowing it to be wrong either morally or legally. Children over 14 are considered responsible. Actus rea and mens rea In many criminal proceedings the prosecution are required to prove, beyond reasonable doubt, that an event or action (actus rea) forbidden by the criminal law occurred because of the defendant's conduct and that this was accompanied by a 'guilty mind' (mens rea). Mens rea refers to the mental attitude of the defendant at the time of the offence. The following are definitions relevant to mental attitude: • Intention. A person foresees the consequences of their actions and desires them.
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• Recklessness. A person, while not desiring the consequences, behaves in a way which involves taking a deliberate and unjustifiable risk that they will arise. • Negligence. A person brings about a consequence by behaving in a way which a 'reasonable and prudent man' would have foreseen and avoided. Offences of strict liability require no mens rea, e.g. most motoring offences, such as speeding.
Mental disorder, violence and offending Recent evidence suggests that, as a group, patients with mental disorder have a significantly increased risk of violent behaviour compared with the general population, although for the most part this is minor. The American Epidemiologic Catchment Area Surveys found that in the year prior to assessment patients with substance misuse reported 10 times, and patients with schizophrenia 4 times, the rate of violent behaviour of the nondisordered group. Overall, however, the mentally ill account for only a very small proportion of total violence or offending in a community. Violence and mental abnormality may be related as follows: • Direct relationship. Violence is directly associated with symptoms such as delusions, hallucinations or thought disorder. • Indirect relationship. Illness induces a change in social circumstances and this in turn leads to offending. • Coincidental relationship. A violent person develops a mental disorder but continues to be violent. Schizophrenia Much offending by patients with schizophrenia is trivial and relates to social deterioration and the difficulties these patients face in coping with everyday life. In a study of remand prisoners charged with violent offences, it was noted that there was an excess of men with schizophrenia, particularly among those who were subsequently convicted of a homicide. The Epidemiologic Catchment Area Survey also found increased rates of reported violence among those with schizophrenia. Serious violence usually occurs several years after illness onset. Violence may be associated with various symptoms, including: • high level of arousal, distress, fear, irritability and anger, which may be associated with other symptoms such as delusions; • positive psychotic symptoms, particularly delusions, which appear to
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be the commonest direct cause of violent behaviour, e.g. where a patient acts violently on the basis of a perceived threat; • thought disorder; • deterioration in personality and social functioning. The combination of schizophrenia and substance misuse is associated with increased rates of violence. Affective disorders Depression may be rarely associated with violence, including homicide. In the context of thoughts of failure, guilt, self-blame and mood congruent delusions others may be included in suicide attempts ('extended suicide') or altruistic killing may occur. The victims of such attacks are usually family members, for example infanticide in the context of puerperal depression. Depression may be associated with irritability, tension and frustration which may also predispose to violence. Shoplifting is occasionally linked with depression in the context of impaired concentration. Mania or hypomania are rarely associated with serious violence, but may lead to public order offences and minor violence. Personality disorder Personality disorders are characterized by maladaptive inflexible responses to a range of personal and social situations. This inflexibility, associated with a lack of alternative coping strategies, can contribute to antisocial and violent behaviour. Offending or violent behaviour is most characteristic of patients with dissocial/antisocial personality disorder, where disregard of social norms and a low threshold for aggression and violence are included in the diagnostic criteria. Many offenders, however, will show features of more than one personality disorder, with a range of interconnected personality difficulties evident. Personality disorder may well be associated with other psychiatric conditions, particularly substance misuse, which may exacerbate antisocial behaviour. The legal term 'psychopathic disorder', defined in the Mental Health Act 1983 (see below), may cover patients with a variety of personality disorders. Substance misuse Alcohol and drug use are commonly associated with antisocial behaviour. Drinking prior to offending has been reported in between half and two-thirds of those committing homicides and assaults, 50 per cent of rapists and around 40 per cent of those committing property offences. Victims of violent crime have also frequently been drinking prior to being assaulted. Around 80 per cent of opiate users have at least one conviction. In some studies in the USA, around 50-60 per cent of those
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committing violent offences or property offences are reported to have used opiates. Substance misuse is often associated with other mental disorders, particularly personality disorders and affective illness. In a number of forensic patients, substance misuse is co-morbid with antisocial personality disorder. The nature of the relationship between substance misuse, mental disorder and antisocial behaviour is often complex in individual cases. Learning disabilities Low IQ is a factor associated with the development of delinquency and offending. Allowing for the possibility that the mentally impaired may be more likely to be caught, or that low IQ may be associated with other risk factors for offending, such as large families or poverty, the evidence suggests that low IQ is an independent risk factor for antisocial behaviour. Low or borderline IQ may be associated with low self-esteem, emotional disturbance, impulsivity, social difficulties, frustration over limitations and difficulties and lack of ability to develop alternative coping strategies. Antisocial behaviour may arise in the context of these difficulties. It has been suggested that mental impairment is particularly associated with sexual offending and arson. Organic conditions Symptoms of dementia may include personality change, disinhibited behaviour and impaired judgement which may lead to crimes such as theft and sexual offending and aggressive or violent behaviour. Brain damage, particularly frontal lobe damage, from any cause, may lead to personality change with disinhibition, and aggressive and violent behaviour. The prevalence of epilepsy among prisoners is greater than that of the general population. This finding is probably due to social and biological disadvantages which predispose to both epilepsy and imprisonment and there is in general no evidence of a direct causal link between epilepsy and violence. Very rarely chaotic, nongoal directed violence may occur as an ictal phenomenon or during a post-ictal confusional state. Pathological (morbid) jealousy The boundary between normal jealousy and pathologically intense jealousy is often unclear. Classically morbid jealousy refers to delusions of infidelity associated with persistent seeking of evidence to confirm this belief. Morbid jealousy may be associated with schizophrenia, depressive illness, personality disorder, alcohol dependence and organic disorders. Jealousy may result in partners being intimidated, controlled,
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repeatedly threatened and pressed for confessions. It is a common cause of violence between partners.
Mentally disordered offenders and criminal proceedings Not fit to stand trial The patient is unfit to attend court because of serious illness such as severe psychotic illness or mania. Fitness to Plead A defendant is considered unfit to plead if he cannot: understand the nature of the charge; understand the difference between guilty and not guilty pleas; instruct legal advisers; challenge jurors; follow the proceedings and understand the evidence presented to the court. This is decided by a jury before a judge. The law relating to fitness to plead was amended by the Criminal Procedure (Insanity and Unfitness to Plead) Act 1991. If the defendant is found unfit to plead, a trial of the facts of the case is heard before a jury. If the evidence is weak, the defendant is acquitted; if it appears that the defendant committed the act, a range of possible disposals is available, including discharge, guardianship, supervision and treatment orders or a hospital order with or without restrictions. Not guilty by reason of insanity (McNaughton Rules) In 1843 a Scottish wood-turner, Daniel McNaughton, shot Edward Drummond, the Private Secretary to Sir Robert Peel. At his trial he was found 'not guilty on the grounds of insanity'. Although he was detained and in due course admitted to hospital, McNaughton's apparent 'acquittal' resulted in much public concern and the issue was debated in the House of Lords. The Judges were asked to answer several specific questions. The answers are called the 'McNaughton Rules': • every person is considered to be sane until the contrary is proved; • it is for the defence to prove (to the jury) that at the time of committing the offence, the accused was suffering from disease of the mind so as not to know the nature and the quality of his act, or (if he did know this) that what he was doing was wrong; • when a criminal act is committed by a man suffering from delusion, then his responsibility is the same as if the facts with respect to which the delusion exists were real; e.g. if he believed that a man was
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attempting to kill him, and he killed that man, as he thought, in selfdefence, he would be exempt from punishment. However, if he merely believed that his victims had been responsible for his loss of wealth then he would be liable to punishment. If the accused is found insane a range of disposals are available under the Criminal Procedure (Insanity and Unfitness to Plead) Act 1991. Prior to this Act, the use of a 'not guilty by reason of insanity' plea was rare, with the defence of diminished responsibility tending to be used instead. This pattern may change with the introduction of the new act. Infanticide Infanticide is the killing of a child under 12 months by the mother when 'the balance of her mind was disturbed by reason of her not having fully recovered from the effect of giving birth to the child or by reason of the effect of lactation...'. Ninety per cent of women convicted of infanticide are either committed to hospital or put on probation. Diminished responsibility The Homicide Act 1957 (Section 2) permits a defence of diminished responsibility to a charge of murder. This defence does not apply to other charges. In order to satisfy the requirements of this defence the accused must show that: (a) he was suffering from an abnormality of mind; and (b) that such abnormality of mind (i) arose from a condition of arrested or retarded development of mind or any inherent causes or was induced by disease or injury; and (ii) was such as substantially impaired his mental responsibility for his acts in doing or being a party to the killing. If successful, the conviction is of manslaughter which permits a wider choice of disposal. The issue of diminished responsibility is decided by the jury. Automatism Automatism refers to a state where the individual is not conscious of what they are doing. The individual concerned cannot therefore be held responsible for their actions. Legally there are two types: automatism resulting from a disease of the mind and having an internal cause, termed insane automatism, or automatism resulting from some other condition having an external cause, termed noninsane automatism. This division is legal not clinical. Examples of insane automatism include behaviour resulting from epileptic fits, brain tumours or other diseases
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of the brain and sleepwalking. Examples of noninsane automatism include hypoglycaemia and concussion. In insane automatism, the patient is sentenced under the provisions of the Criminal Procedure (Insanity and Unfitness to Plead) act 1991, whereas in noninsane automatism the individual is acquitted. Amnesia Amnesia for the offence, or the period around the offence, is common. The Appeal Court in the case of R. v. Podola ruled that amnesia (genuine or feigned) of the offence is not sufficient grounds in itself for unfitness to plead. Alcohol and drugs The effects of intoxication with alcohol or drugs can only be used as a defence against criminal liability in very limited circumstances. Intoxication may be a defence in offences requiring specific intent, such as murder. If there is a mental disorder consequent on alcohol or drug use, such as delirium tremens, drug-induced psychosis or alcoholic dementia, a defence of insanity or diminished responsibility may be possible. Psychiatric disposals following conviction A psychiatric report may be requested after conviction to assist in appropriate disposal. Psychiatric disposals include: • • • •
hospital order with or without restrictions (Sections 37 and 41); interim hospital order (Section 38); guardianship order; probation with a condition of treatment.
In making a recommendation, consideration should be given to nature of the disorder and need for treatment, likely compliance, need for compulsory treatment, and the most appropriate location for treatment, taking into account the severity of the offence and ongoing risk to others.
Court reports Requests for psychiatric reports may be made by the court or by defence solicitors at different stages of criminal proceedings, either pre-trial or post-conviction pending sentencing. In preparing a report it is important that the patient understands that the normal rules of confidentiality do not apply. Reports should be written using clear language, avoiding technical terms and professional jargon. Relevant background information, such as details of the charges, witness statements, the police
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summary of the case, previous psychiatric records, other available reports and history from informants, should be obtained where appropriate in addition to a full assessment interview(s) of the patient. The author may occasionally have to attend court and be cross-examined on the report. The report should include the following: 1. Introduction: stating on whose behalf the report has been prepared, details of the charges, where and when the patient was assessed, sources of information, whether the patient understands the nature of the charges. 2. Psychiatric history: family history, personal history, past psychiatric history (including alcohol and drug use or dependence), past medical history, past forensic history, including history of violence for which charges may not have been brought. 3. The alleged offence(s): patient's description of events, other information, e.g. from depositions; antecedents, including alcohol or drug use at the time. 4. Description of mental state at the time of offence(s): mental state abnormalities such as psychotic symptoms, mood disorder, effects of alcohol or drug use/dependence. The relationship between any such symptoms and the offence should be described, including the affect on ability to form intent and criminal responsibility. 5. Mental state at assessment and results of investigations if relevant. 6. Opinion and recommendations: (a) fitness to plead and fitness to stand trial; (b) presence of mental disorder in terms of the Mental Health Act 1983; (c) relationship between any mental disorder or abnormality and offending, including in relation to intent, McNaughton Rules and diminished responsibility if appropriate; (d) contribution of any mental abnormality to risk of reoffending; (e) prognosis if relevant; (f) recommendations regarding need for treatment; 7. Name and qualifications of author (including whether approved under Section 12(2) of the Mental health Act 1983) and date.
Dangerousness and risk assessment The Butler Committee defined dangerousness as 'a propensity to cause serious physical injury or lasting psychological harm'. Dangerousness is a dynamic issue rather than a one-off prediction, varying over time in association with changes both within the individual and the environment. Prediction is more accurate when limited to a short time period.
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Psychiatrists may need to assess dangerousness in a variety of circumstances, such as when considering compulsory admission, advising courts, considering discharge or transfer of patients with a history of offending or in general psychiatric practice when there is evidence of deterioration or a significant change in social circumstances. In general, psychiatrists over-predict dangerous behaviour, although they may under-predict in female patients. There is evidence that forensic patients released against medical advice have higher rates of reoffending. The components of risk assessment include: 1. The outcome criteria. What is the risk of, how serious is it, is it general or specific, is it likely to be frequent or rare? 2. Variables related to risk (after the MacArthur Risk Assessment Study): (a) dispositional factors: personality features such as impulsivity, difficulty coping with frustration and poor anger management, interpersonal difficulties, lack of empathy with others; cognitive abilities; (b) historical factors: deprivation, abuse, poor parenting and exposure to criminality and violence; evidence of long-term behavioural, social and psychosexual difficulties; past psychiatric history, including response to treatment, treatment resistance, poor compliance, low insight, and history of substance misuse; past history of violence or offending and context in which it occurred; nature of any links between mental disorder and previous violence/offending; (c) contextual factors: perceived stress, accommodation and financial difficulties, social support, potential victims, availability of weapons; (d) clinical factors: diagnosis, including substance misuse or dependence; symptom profile, features such as aggressive or threatening behaviour, agitation, anger, irritability, psychotic symptoms, jealousy, lack of insight. It is useful to consider which risk factors are amenable to change. 3. The likelihood of the outcome variable. Assessment is aided by an understanding of the pattern and severity of identified risk factors and the coping strategies and strengths of the patient in relation to these. Assessment of previous violence or offending may indicate a pattern of circumstances likely to give rise to such behaviour again in the future. 4. The time frame. Prediction should be located within a particular time frame as circumstances may change rapidly. The process of risk assessment involves a detailed history, including information obtained from informants and other sources, mental state examination and further investigations if indicated. Once assessment is
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completed the information must be formulated and a plan to manage risk developed.
Forensic psychiatry services in England and Wales Special Hospitals There are three maximum security hospitals in England and Wales owned and managed by the NHS: Broadmoor in Berkshire, Ashworth in Merseyside and Rampton in Nottinghamshire, with a total of approximately 1500 beds. Patients may be referred by the courts, prisons or other psychiatric facilities and occasionally referrals involve conditionally discharged restricted patients residing in the community. Those referred are not only offenders but patients with aggressive or violent behaviour which cannot be contained elsewhere. Assessment is undertaken by a psychiatrist from the Special Hospital concerned and admission is then considered by the hospital admission panel. To be admitted the patient must be mentally disordered within the meaning of the Mental Health Act 1983, and considered to be a 'grave and immediate danger to the public' and require treatment within conditions of maximum security. Approximately 85 per cent of patients in Special Hospital are male. Seventy per cent have a diagnosis of schizophrenia, 25 per cent are classified as psychopathic disorder and a minority have mental impairment or other disorders. Three-quarters are on court orders: of these approximately 20 per cent are for homicide, 40 per cent for other violent offences (including arson) and 5 per cent for sex offences. The average length of stay is about 8 years and in many cases there is considerable delay associated with the transfer process. Outcome studies of patients discharged from Special Hospital were reviewed, in 1981, by Bowden: 50 per cent reoffend and although most are trivial offences, 10 per cent are serious violent offences including 1 per cent homicide. Sixty per cent remained in the community and 20 per cent were recalled to special hospital. Regional Secure Units These units were developed following recommendations from the Interim Butler and Clancy Committee reports in 1974. They range in size from 25 to 100 or more beds and provide medium security for patients who need to be treated in secure surroundings but do not need the high security of a Special Hospital. Patients are referred from the courts, prisons and from other psychiatric services, including Special Hospitals. Referrals are usually considered by multidisciplinary teams. Admission is limited to those who are not likely to require inpatient care for more than 2 years. The majority
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of patients are male and approximately two-thirds have a diagnosis of schizophrenia, 15 percent personality disorder and a further 15 per cent affective disorders. Local adult psychiatric services Some general psychiatrists have a special interest in forensic psychiatry and are involved in assessment and treatment of patients with offending or violent behaviour who do not require management by forensic services. Many general psychiatrists will have patients who at some stage of their career will be involved with the legal system. Special care wards Some catchment area hospitals have opened special care wards or secure wards which are used to treat acutely disturbed patients who require brief admission to a locked unit because of disruptive or dangerous behaviour. Prison services Recent studies have found up to 40 per cent of prisoners have a psychiatric diagnosis: the most common diagnosis was alcohol or drug misuse, occurring in nearly 20 per cent, approximately 10 per cent had personality disorder and 2 per cent had a psychotic illness. The suicide rate in prisoners is approximately eight times that of the general population. Prisons have their own medical centres, but these are not recognized under the Mental Health Act 1983 and hence compulsory treatment is not permitted unless in an emergency. Some specialized facilities exist for mentally disordered prisoners within the penal system, including sex offender treatment programmes. A therapeutic community programme is established at HMP Grendon. Community forensic psychiatric services These services provide links with local psychiatric services, probation, police, prisons, courts and follow-up of patients discharged from inpatient forensic services. Court diversion schemes These schemes aim to facilitate the rapid diversion of mentally disordered offenders from the legal system to mental health services. Psychiatrists or community psychiatric nurses may be on-call or have regular clinics at the court and in some schemes other professionals are also involved. Mentally disordered offenders are able to be rapidly identified and
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assessed, and suitable arrangements made for appropriate treatment, including transfer to hospital if necessary. In some cases the Crown Prosecution Service may discontinue proceedings once such arrangements for treatment have been made. Many of those transferred to hospital by such services have serious chronic mental illness, are recidivist offenders and have been charged with relatively minor offences. Mental Health Act 1983 Definitions in the Act include: • Mental disorder - mental illness, arrested or incomplete development of mind, psychopathic disorder and any other disorder or disability of mind. • Mental impairment - a state of arrested or incomplete development of mind (not amounting to severe mental impairment) which includes significant impairment of intelligence and social functioning and is associated with abnormally aggressive or seriously irresponsible conduct on the part of the person concerned. • Severe mental impairment - a state of arrested or incomplete development of mind which includes severe impairment of intelligence and social functioning and is associated with abnormally aggressive or seriously irresponsible conduct on the part of the person concerned. • Psychopathic disorder - a persistent disorder or disability of mind (whether or not including significant impairment of intelligence) which results in abnormally aggressive or seriously irresponsible conduct on the part of the person concerned. The Act specifically notes that immoral conduct, sexual deviancy or dependence on alcohol or drugs are not regarded as 'mental disorder'. The Act does not define mental illness. Part II of the Act relates to compulsory admission to hospital under 'civil sections' (see Table 27.1). Part III deals with those charged or convicted of criminal offences (see Table 27.2).
Section 17. Leave of absence from hospital This section permits the Responsible Medical Officer to grant leave of absence from the hospital. The section also deals with the return and readmission of patients who are absent without leave. Patients may not be returned under this provision after a continual absence of 28 days or if an original 3- or 28-day section has expired.
Section 117. Aftercare This section requires health authorities and social services, in cooperation with other agencies, to provide aftercare for patients who have been detained in hospital for treatment.
Table 27.1
Provision for compulsory detention of patients in England and Wales under Part II of the Mental Health Act 1983
Nature of Section provision
Applicant
Medical recommendations
2
Admission for assessment
Nearest relative or approved social worker
Two doctors, one approved under S. 12
3
Admission for treatment
As for S.2
As for S.2
4
Emergency admission for assessment
As for S.2
One doctor, preferably with previous knowledge of the patient
Appeal procedures
Necessary conditions
Duration
1 . That the patient suffers from a mental disorder (not further classified) of a nature or degree which warrants detention in hospital for assessment 2. That he/she ought to be so detained in the interests of his/her own health or safety or with a view to the protection of others 1. Mental illness, mental impairment, severe mental impairment or psychopathic disorder 2. Psychopathic disorder or mental impairment only if treatment is likely to alleviate condition or prevent deterioration 3. It is necessary for the health or safety of the patient or protection of others that he/she receive such treatment and it cannot be provided unless he/she is detained under this Section Mental disorder and urgent necessity for the patient to be admitted
Up to 28 days
Patient can apply to a Mental Health Review Tribunal during the first 1 4 days of detention
Up to 6 months, renewable for a further 6 months and then yearly
Mental Health Review Tribunal once in every period of detention
Up to 72 hours
None
Table 27.1 Nature of Section provision 5(2)
5(4)
7
Applicant
Detention of an Doctor in informal inpatient charge of the case or his/ her nominated deputy Nurses' holding First-level power (allows registered detention until a nurse doctor is found)
Guardianship As for S.2 The Guardian can require the patient to: reside at a specified place, to attend for treatment, and allow access by doctor, ASW or other specified person
Medical recommendations
Continued
Necessary conditions
Doctor in charge Appears to doctor that application of the case or should.be made his/her nominated deputy Not applicable Appears to nurse that patient suffers from a mental disorder to a degree that makes it necessary for his/her own health or safety or for the protection of others, for him/her to be immediately restrained from leaving hospital and a doctor is not immediately available As for S.2 Suffering from a specified mental disorder and necessary for the welfare of patient or protection of others
Duration
Appeal procedures
Up to 72 hours
None
Up to 6 hours
None
6 months, renewable for a further 6 months and then yearly
Mental Health Review Tribunal during each period of guardianship
Table 27.2
Provision for compulsory detention of mentally disordered offenders under Part III of the Mental Health Act 1983
Section Nature of Provision
Authority Required
Recommendations
35
Remand to hospital for report
Magistrates or Written or oral Crown Court evidence from one doctor approved under S.12
36
Remand to hospital for treatment
Crown Court
Crown or Magistrates Court
37
Hospital and Guardianship orders
38
Interim Hospital Crown or order Magistrates Court
47
Transfer to hospital of sentenced prisoner
Secretary of State
Written or oral evidence from two doctors, one approved under S.12 Written or oral evidence from two doctors, one the doctor who will take charge of the treatment. One must be approved under S.12 Written or oral evidence from two doctors, one approved under S.12, one on the staff of the hospital specified As for S.2
Necessary Conditions
Duration
1. Suspicion of mental disorder 2. Impractical to obtain report if prisoner remanded on bail 3. Bed available within 7 days
28 days, renewable for further periods of 28 days up to a maximum of 12 weeks 28 days, renewable for further periods of 12 days up to a maximum of 12 weeks 6 months, renewable for a further 6 months then at yearly intervals
1. Mental illness or severe mental impairment 2. Bail impractical 3. Bed available within 7 days 1. Convicted of an imprisonable offence but not yet sentenced 2. As for S.3 3. Bed available within 28 days
1. Convicted of an imprisonable offence 2. Evidence of mental disorder 3. Possibility that hospital order would be appropriate 4. Bed available within 28 days 1. Convicted of an imprisonable offence 2. As for S.3 3. Bed available within 14 days
12 weeks renewable every 28 days, limit 6 months [extended to 12 months by the Crime (Sentences) Act 1997] Detention in hospital as under S.37. May be returned to prison when treatment no longer necessary
Table 27.2 Section Nature of Provision
Authority Required
Recommendations
Necessary Conditions
Duration
Secretary of State
As for S.2
1. In prison on remand 2. Mental illness or severe mental impairment 3. Urgent need of treatment 4. Bed available within 14 days 1 . Subject to S.37 2. Necessary for protection of the public
May be terminated by RMO report or trial
Subject to S.47
As under S.47
48*
Transfer to hospital of remanded prisoner
41
Restrictions on Crown Court discharge Leave outside hospital and discharge may be granted only by Secretary of State Secretary of Restriction on State discharge
49
Continued
One of the doctors giving evidence for S.37 gives oral evidence in court
Not applicable
*Restriction order under S.49 normally applies. Also civil prisoners and detainees under the Immigration Act 1971.
Duration specified by court, often without limit of time
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Section 135. Warrant to search for and remove mentally disordered persons An approved social worker, on presenting appropriate evidence, can request a magistrate to issue a warrant to permit a police officer, accompanied by a doctor and the approved social worker, to enter a patient's premises and remove him/her.
Section 136. Mentally disordered persons found in public places A police officer is empowered to remove to a place of safety, such as a hospital or a police station, for assessment, a person who is apparently suffering from a mental disorder and found in a public place - valid for 72 hours. Consent to treatment In general, treatment requires the real consent of the patient. Some patients, however, may refuse treatment because of lack of insight related to their illness, or may lack the capacity to give real consent. Part IV of the Mental Health Act is the statutory law relating to psychiatric treatment. Patients on Sections 4, 5(2), 35, 135, 136 and 41 (conditionally discharged and not recalled) are not included in the consent to treatment provisions, and can only be treated under Common Law. Consent to treatment provisions refer only to treatment for mental illness. Treatment for physical illness is excluded and comes under Common Law provisions. Patients on long-term sections can be treated for 3 months with or without their consent.
Mental Health Act (Patients in the community) 1995 This Act was implemented in 1996 and amends the Mental Health Act 1983. It includes: (a) Provisions for aftercare under supervision, referred to as supervised discharge (Section 25A-I). This allows for the patient to be subject to formal supervision after discharge. It aims to ensure effective aftercare and incorporates the principles of the Care Programme Approach. Patients under supervised discharge should normally be included on a supervision register. Supervised discharge applies initially for 6 months and can then be renewed if appropriate. An application for supervised discharge is made by the patient's responsible medical officer and can only be made at a time when the patient is liable to be detained under the Mental Health Act 1983. Three conditions must be met:
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(i) the patient is suffering from one of the four categories of mental disorder denned in the Act; and (ii) that there would be substantial risk of serious harm to the health or safety of the patient or the safety of other people, or of the patient being seriously exploited, if the patient did not receive aftercare services under Section 117 of the Act; and (iii) that supervision is likely to help ensure that the patient receives those services. The arrangements for aftercare under supervision form part of the normal discharge planning process. Requirements which may be imposed on the patient with supervised discharge include: (i) that the patient should live in a particular place; (ii) that the patient should attend a particular place at set times for medical treatment, occupation, education or training; (iii) that the supervisor, or a person authorised by the supervisor, should be allowed access to the patient at their place of residence. The supervisor has the power to take and convey a patient to a place where they are required to reside or to attend for treatment. There is however no authority to impose medication or other treatment against the patient's wishes. (b) The removal of the previous 6 month time limit on leave of absence under Section 17. The patient may thus be given leave of absence for as long as they remain liable to detention, i.e. for up to 6 months or 1 year. (c) The extension of the period during which a patient who is absent without leave may be returned.
Special measures for treatment in the community These include: (a) (b) (c) (d) (e) (f) (g)
Conditional discharge of restricted patients. Guardianship orders. Supervised discharge. Leave of absence under Section 17. Section 117 aftercare arrangements. The Care Programme Approach. Supervision registers: these were introduced in 1994 with the proposed aim to ensure appropriate care and follow-up for those most at risk and need of support, including those who pose a significant risk of suicide, severe self-neglect or serious violence to others. The content includes: identification data, the nature of the risk, key worker and relevant professionals and details of the care programme.
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Mental Health Review Tribunals There are 15 regional mental health review tribunals in England and Wales. The function of the tribunals is to decide whether patients should continue to be detained in hospital. Each tribunal panel has three members, a lawyer (chairman), psychiatrist and a layman. In the case of restricted patients, the president will be either a judge or a Queen's Counsel. Patients detained under the provisions of the Mental Health Act 1983 can appeal against their detention to a tribunal (see above). For those who do not apply, automatic referral is made by hospital managers or, in the case of restricted patients, by the Home Secretary. The tribunals are kept relatively informal and usually sit in the hospital where the patient is detained. Tribunals are attended by the patient, patient's legal representative (application for legal aid may be submitted), the responsible medical officer, social worker, and other relevant people such as relatives or nurses. The tribunal must direct discharge if a patient does not have a mental disorder, or if hospital treatment is not appropriate or necessary. The tribunal may also recommend leave of absence or transfer to another hospital. For restricted patients the grounds for absolute discharge are similar. In restricted cases tribunals may also order a conditional discharge, where the patient remains liable to recall to hospital and must comply with various conditions such as psychiatric and social work supervision. Tribunal decisions may be deferred to allow for suitable aftercare arrangements to be made.
Mental Health Act Commission The commission was established to protect the rights of detained patients. Commissioners are appointed by the Secretary of State and come from various backgrounds including law, psychiatry, nursing, social work and the laity. Faulk (1994) has summarized the functions of the commissioners as follows: • to appoint medical practitioners and other professionals to supervise the consent to treatment procedures; • to receive reports about treatments given under the consent to treatment procedures; • to keep under review the way in which the powers and duties of the Mental Health Act are carried out, to visit patients and to investigate complaints; • to draw up proposals for a Code of Practice relating to detained patients.
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Court of protection The Court of Protection is part of the Supreme Court and is for the protection and management of the property and affairs of persons under disability by reason of mental disorder.
References and reading list Faulk, M. (1994) Basic Forensic Psychiatry, 2nd edn. Oxford: Blackwell. Forshaw, D.M. and Strang, J. (1993) Drugs, aggression and violence. In Violence in Society (ed. P.J. Taylor). London: Royal College of Physicians. Gunn, J., Maden, A. and Swinton, M. (1991) Treatment needs of prisoners with psychiatric disorders. British Medical Journal, 363, 338-41. Mednick, S.A. and Finello, K.M. (1983) Biological factors and crime. Implications for forensic psychiatry. International Journal of Law and Psychiatry, 6, 1-15. Monahan, J. and Steadman, H.J. (1994) Violence and Mental Disorder. Developments in Risk Assessment. Chicago: University of Chicago Press. Rutter, M. and Ciller, H. (1983) Juvenile Delinquency. Trends and Perspectives. Harmondsworth: Penguin. Swanson, J.W., Holzer, C.E., Ganju, V.K. and Jono, R.T. (1990) Violence and psychiatric disorder in the community: evidence from the Epidemiologic Catchment Area Surveys. Hospital and Community Psychiatry, 41, 761-70. Taylor, P.J. and Gunn, J. (1984) Violence and psychosis I - risk of violence amongst psychotic men. British Medical Journal, 288, 1945-9. Taylor, P.J. and Gunn, J. (1984) Violence and psychosis II - effect of psychiatric diagnosis on conviction and sentencing of offenders. British Medical Journal, 289, 9-12. Trick, K.L.K. and Tennent, T.G. (1981) Forensic Psychiatry: An Introductory Text. London: Pitman. Walker, N. (1968) Crime and Insanity in England, Vol. 1. The Historical Perspective. Edinburgh: University Press. West, D.J. (1982) Delinquency: Its Roots, Careers and Prospects. London: Heinemann Educational Books.
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PART THREE
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28
Psychological methods of treatment NIGEL PEARSON and ULRIKE SCHMIDT
There are many different types of psychotherapy but there are similarities between all therapies, with different language being used to describe analogous phenomena and techniques. All therapies share the common factor of the availability of someone who listens carefully and tries to understand. In clinical practice, therapists are often eclectic and may incorporate a wide variety of approaches.
Definition Meltzof and Kornreich's definition of psychotherapy remains useful: The informed and planful application of techniques derived from established psychological principles, by persons qualified through training and experience to understand these principles and to apply these techniques with the intention of assisting individuals to modify such personal characteristics as feeling, values, attitudes and behaviours which are judged by the therapist to be maladaptive.
History of psychotherapy provision in United Kingdom Before World War II, psychological treatments were largely psychoanalytic and available to only a few. After 1948 the Tavistock clinic started to offer treatment through the NHS. The British Object Relations school begun by Klein was followed through by Winnicott, Balint, Fairbairn and Guntrip. The experiments at Northfield military hospital bore fruit, with the development of therapeutic communities (notably the Henderson and the Cassel Hospitals) and group therapies. Theories of learning derived from animal experimentation were applied to humans in the 1950s (Skinner and Wolpe) and by the 1960s behavioural treatments were available in many mental health services
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throughout Britain. At the same time, clinical psychology changed from a discipline of measurement ancillary to psychiatry to a therapeutic profession in its own right and, following the 1960s 'cognitive revolution' in academic psychology, emphasis was placed on cognitive processes in therapy (Beck and Meichenbaum). This new technique of cognitive behavioural therapy was initially applied to depression and subsequently extended to other neurotic disorders, personality disorders and, more recently, to psychosis. The 1970s saw an explosion of new therapies - existential, gestalt, client-centred counselling, psychodrama. Of these, client-centred counselling continues to be practised in primary care, while art therapy and drama therapy are conducted on hospital wards by occupational therapists. Partly in response to these developments the 1970s and 1980s saw the development of briefer focal psychodynamic treatments. These decades also witnessed the development of systemic family therapy. By the 1980s clinicians were using a wide range of techniques pragmatically. This has led to approaches which combine several theoretical schools, an example being cognitive analytic therapy. Psychotherapy research has run in parallel. Research has changed from largely uncontrolled studies in the 1950s and 1960s to placebo controlled, and trials comparing several therapies in the 1970s and meta-analyses in the 1980s. Studies have moved from the question of 'Is psychotherapy effective?' to 'which form of psychotherapy is effective for which disorder?'. Cost analyses are also becoming increasingly important. Parry and Richardson's review of the state of provision of therapies within the NHS in the mid-1990s was divided as follows: A. Those integral to mental health care services. These are provided alongside medical and nursing care and include a wide range of psychological interventions, e.g. a behavioural programme devised by a psychiatrist in combination with medical treatment, family interventions provided by nurses in schizophrenia, social skills training by occupational therapists. B. Eclectic psychological therapies and counselling. The patient is offered a set of sessions informed by more than one theoretical framework where nonspecific factors result in improvement; e.g. GP counselling. C. Formal psychotherapies. These are informed by a specific model which is supported by a well-developed theoretical background with protocols for practice and undertaken by, or under the supervision of, a specialist practitioner; e.g. psychodynamic psychotherapy, cognitivebehavioural and systemic family therapy. There is overlap between the groups, e.g. supportive psychotherapy could fit into either group A or B.
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Cognitive and behavioural therapies General principles Behavioural therapy is loosely based on learning theory, whereas cognitive therapy has been influenced by experimental psychology, behavioural therapy and psychodynamic theory. Both are brief time-limited treatments aiming to help patients change distressing thoughts, feelings and behaviours. The emphasis is on current difficulties rather than the origins of a problem. The frequency, severity, triggers, maintaining factors and other aspects of the main problems are carefully identified, as is their impact on the patient's life and that of the family. Specific treatment goals are defined at the outset of treatment and strategies are planned to achieve these. Often rating scales (self- or therapistadministered) are used to monitor progress. The duration of treatment depends on the complexity and severity of problems. The therapist is active and directive, but over the course of treatment shifts responsibility to the patient with the aim of increasing their ability to help themselves. Behavioural therapy
Treatment of phobias Graded exposure is the treatment of choice for agoraphobia and simple phobias. The patient is required to enter previously avoided situations in a planned fashion and for a prolonged period of time until habituation occurs, i.e. anxiety lessens. Other techniques now less frequently used are as follows: • In systematic desensitization, patients are asked to face anxietyprovoking situations (either in imagination or in vivo) and hierarchically progress from situations that cause them little anxiety to those that cause more and more. At each stage, anxiety is neutralized through relaxation. • Inflooding,patients enter situations that give them maximum anxiety and remain there until anxiety lessens. This is an effective but potentially aversive treatment. • Implosion is flooding in fantasy. Research on agoraphobia has shown that prolonged exposure is superior to exposure in fantasy and to brief exposure. Group exposure is about equally as effective as individually-conducted exposure programmes. Frequent practice is more effective than spaced practice. Treatment can be conducted as a self-help programme (manual or computer based). Effects of exposure are long-lasting. In patients with social phobia, systematic desensitization is more difficult to conduct. Treatment
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programmes combining exposure, social skills training and cognitive therapy lead to improvement.
Treatment of obsessive-compulsive disorder Obsessive-compulsive disorder with rituals responds well to exposure and response prevention. Both are essential components of treatment. Exposure tackles avoided stimuli which trigger the urge to ritualize. In response prevention, the patient is asked to refrain from performing rituals. This may initially need to be done under supervision. Obsessional thoughts without rituals are much more difficult to treat. Cognitive therapy, prolonged exposure to thoughts and thought stopping are possible options. Cognitive therapy A precursor of cognitive therapy was rational emotive therapy developed by Albert Ellis in the 1950s. Aaron Beck is the founder of cognitive therapy. He wrote extensively about the 'cognitive triad' which includes people's beliefs about themselves, the world around them and their future. Many individuals, in particular those with depression, tend to have negatively biased thinking patterns. The aim of cognitive therapy is to identify, reality test and modify distorted cognitions. Different levels of cognitive structures have been postulated: • Automatic thoughts. The most accessible and easily modified, these are frequent, credible to the individual and alter mood and behaviour. They can be categorised into different types including arbitrary inference, selective abstraction, over-generalization, magnification, minimization, personalization, absolutistic and dichotomous thinking. These categories are overlapping. • Basic assumptions describe the general psychological rules that govern the individual's thoughts and behaviour. They are conditional, e.g. 'Unless I behave perfectly nobody will like me'. They can be modified by circumstances. • Early maladaptive schemata are absolute and unconditional, e.g. 'I am worthless', or 'I can't trust anybody'. They are essential to the individual sense of self-identity and may be difficult to change.
Principles and techniques The patient is taught to: • • • •
recognize links between cognition, affect and behaviour; monitor negative automatic thoughts by keeping a daily record; examine the evidence for and against distorted automatic thoughts; substitute more reality-based interpretations for these biased cognitions.
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Often these methods of cognitive restructuring are backed up by behavioural techniques designed to modify cognitions. Hence cognitive therapy is often referred to as cognitive-behavioural therapy (CBT). Fifteen to twenty sessions at weekly intervals with regular homework assignments are usually offered. In CBT of personality disorders, attempts are made to change basic assumptions and underlying schemata (schema-focused cognitive therapy). In contrast to cognitive therapy of axis one disorders, in personality disorders more emphasis is put on the therapeutic relationship as one arena where dysfunctional beliefs about others and interpersonal behaviours can be explicitly assessed. Treatment of personality disorders usually takes longer than that of other disorders.
Research Cognitive therapy was initially used and evaluated in the treatment of depression where it was found to be as effective as antidepressants in treating moderately depressed individuals. In recent years there has been an explosion in the applications of CBT. They have been shown to be of value in the treatment of a wide range of psychological disorders including panic disorder, generalized anxiety disorder, bulimia nervosa and substance misuse disorders. An area of further development is the use of CBTs in psychosis and psychosomatic disorders including, for example, chronic fatigue. Dialectical behavioural therapy developed by Linehan is a variant of cognitive behavioural treatment developed for the treatment of chronically suicidal, borderline patients. It has been found to lead to a reduction in suicidal behaviour compared to standard treatment. Other treatments based on a cognitive or behavioural model
Assertiveness training Practical training is given, often in groups, to individuals with low selfesteem. Skills taught include making clear and specific requests, learning how to say no, handling criticism, learning about appropriate use of body language, managing the expression of feelings, especially anger, receiving compliments and taking initiatives. This is achieved through instruction, modelling and role play.
Social skills training Patients are those with social anxieties or deficits in social skills. Instruction, modelling and role play are used to teach people how to behave appropriately in a variety of social situations.
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Contingency management The basic principle is that positive reinforcement strengthens and makes more frequent desired behaviours, while withholding reinforcement weakens or lessens undesired behaviours. Reinforcers are usually individually tailored.
Covert sensitization This is an aversion technique in which mental images of unwanted behaviour are associated with mental images the individual finds unpleasant or disgusting. This has been used for the treatment of sexual deviance. The results are unclear.
Relapse prevention This was developed by Marlatt and Gordon as a technique for preventing relapse in substance abuse disorders. In stages the individual is helped: • • • •
to identify high-risk situations for relapse; to develop strategies for coping with these situations; to practise these strategies in vivo; to learn cognitive strategies to master the negative feelings that often accompany lapses in self-control; • to conceptualize lapses as learning experiences.
Individual psychodynamic psychotherapy Psychoanalysis Main proponents Sigmund Freud Freud's initial interest in psychological treatment stemmed from the treatment of hysteria through hypnosis and the idea that symptoms were meaningful communications about inner conflicts. He found that encouraging patients to talk about whatever came to their minds (free associations) brought to light repressed unconscious material and alleviated symptoms. Dreams and parapraxes (slips of the tongue) were also seen as important pointers towards unconscious conflicts. Later he replaced the simple distinction between unconscious and conscious mental processes by the structural theory of mental functioning (ego, id, super-ego). His theory of psychosexual development postulated oral, anal, phallicoedipal, latency, puberty and genital phases of development. Alfred Adler Adler, although initially a discipline of Freud, broke with him and founded his own movement (individual analysis). He emphasized the
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influence of social factors in people's development. He saw neurosis as originating from feelings of inferiority, sometimes based on physical handicaps, giving rise to compensatory striving for power (inferiority complex). He coined the term masculine protest for reactive behaviour in women who saw themselves as members of the inferior sex. Carl Gustav Jung Jung, another of Freud's disciples, also founded his own school (analytical psychology). He was particularly interested in the expression of the inner world through dreams and artistic productions, and also in unconscious phenomena common to all mankind (collective unconscious) as expressed in symbols, myths and culture. He saw that the aim of treatment was to allow the individual to discover hidden or undeveloped aspects of his/her personality. Melanie Klein Klein was initially a child analyst and many of her ideas are based on her work with children. She emphasized the role of the mother in an infant's development, and the importance of the earliest stages of development. She postulated a paranoid-schizoid followed by a depressive position of development. In the former, infants use primitive defence mechanisms like introjection, projection and splitting to master their own persecutory fears. Disturbances in this phase are seen as responsible for psychosis and obsessive-compulsive disorder. In the depressive position the infant learns to tolerate ambivalence. Failure to work through this position results in neurotic disorder. Winnicot, Guntrip These post-Freudians emphasized the importance of relationships with significant others in emotional life (object relations theory).
Aims These are relief of symptoms, personality change, to increase insight into and understanding of the self and to help patients understand their current problems in the light of difficulties in their early relationships.
Assessment In assessing the suitability of a patient for dynamic psychotherapy, the patient is seen for a period of 1-2 h, during which a psychodynamic formulation is reached. This is a hypothesis of the patient's inner world and how they relate to the external world. It is based on how they talk about their current life situation, their description of their childhood and how they relate to the assessor. The assessor tests his hypothesis by seeing how the patient responds to a trial interpretation.
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Procedures In classical psychoanalysis the patient attends five times a week for 50 min for several (3-5) years. Lying on a couch, with the analyst sitting behind them, the patient freely associates, while the analyst comments when appropriate without directing the patient. Therapy is open-ended, with the ending being negotiated by therapist and patient. Dynamic psychotherapy is based on the same principles as analysis, but less strict. Patients come to therapy fewer than five times a week, may be sitting or lying, and therapy is open-ended. In the NHS the therapy is usually once weekly for a period of 6 months to 1 year.
Key terms Treatment alliance The reality-based aspects of the patient-therapist relationship, the patient's recognition that he or she needs help and that the therapist is there to assist with this task. Transference The patient re-experiences thoughts and feelings originally directed towards key figures of their past in relation to the therapist; understanding and analysing these phenomena is regarded by psychoanalysts to be at the very centre of their therapeutic technique. Countertransference The transfer of feelings and thoughts belonging to the therapist's past onto their relationship with the patient or, more broadly, any feelings engendered by the patient in the therapist. Freud thought countertransference was an obstacle to treatment, but it is seen now as a useful pointer towards the patient's problems. Interpretation Sometimes all of the therapist's verbal utterances are called interpretations but, more strictly, the term refers to the therapist's interventions that have the aim of making patients aware of some aspect of their psychological functioning of which they were not previously conscious. This insight is supposed to bring about therapeutic change. Working through In order to help patients change accustomed and deeply ingrained patterns of thinking and feeling, it is often not enough to interpret them once. The process required to demonstrate to the patient the same pattern repeatedly at different times or in various connections is called working through.
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Resistance The patient's reluctance to enter into a transference relationship with the therapist, to abandon old patterns and to be confronted with unconscious meanings.
Indications and contraindications There are no clear-cut indications, but the following selection criteria have been mentioned: • • • •
psychological mindedness; flexibility; desire to change; YAVIS (young, attractive, verbal, intelligent, successful).
Contraindications include psychotic illness, active alcohol or drug dependence and organic states. Short-term dynamic psychotherapy This term is applied to brief interpretative psychotherapies. The main proponents are Malan, Sifneos, Davanloo and Mann. In the initial consultation a dynamic formulation is proposed in which a core internal conflict is identified as the focus for treatment and the duration of therapy agreed (usually 12-20 sessions at weekly intervals). The therapist uses the concepts of transference, countertransference and resistance and the technique of interpretation but the style is more active and confrontational than in classical analysis.
Other forms of individual psychotherapy Interpersonal therapy This was developed by Klerman and colleagues for the treatment of depression. In interpersonal therapy (IPT) depression is seen as a response to interpersonal disturbances. The focus is on current rather than past problems. Treatment goals evolve from four main interpersonal problem areas: grief, interpersonal disputes, role transitions and interpersonal deficits. In the early phase of treatment a diagnostic evaluation is conducted whereby the therapist reviews symptoms, gives the patient the sick role and links the depressive syndrome to the patient's interpersonal situation. Together they decide which of the four interpersonal areas should be the main focus. In the middle phase the therapist pursues strategies specific to the chosen interpersonal problem area. For grief the therapist aids mourning and helps the patient to find new activities and relationships to compensate for the loss. For role disputes, i.e.
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conflicts with a significant other, the therapist helps the patient explore the relationship and the nature of the dispute. They consider options to resolve it. For role transitions the patient is helped to deal with the change by identifying positive and negative aspects of the new role and the old role. Interpersonal deficits address the lack of social skills that may have led to difficulties in initiating or sustaining relationships. In the final phase of treatment therapeutic gains are consolidated. There is evidence from controlled trials to suggest that IPT is a reasonable alternative or addition to antidepressant medication and can be used as acute, continuation or maintenance treatment for patients with major depression. IPT has also shown promise in patients with bulimia nervosa, dysthymia, HIV-positive depressed patients and depressed patients in primary care. Cognitive analytical treatment This is a brief structured form of psychotherapy which was developed by Ryle. Cognitive, behavioural and psychodynamic principles are combined. Maladaptive patterns of thinking and behaving are understood in the context of the patient's life story and early relationships. In therapy, so-called neurotic procedures (traps, snags and dilemmas) and underlying emotional states are identified. An example for a neurotic procedure is the so-called placation trap, in which an individual constantly has to please or placate another individual so as to not lose their affection or make them angry. After three or four sessions of therapy, patients are offered a reformulation letter which summarizes their current problems, life story, typical procedures and affective states. Additionally, a 'map' of typical emotional states and procedures and the links between them is drawn up (sequential diagrammatic reformulation). Cognitive and behavioural strategies are used to help patients modify their neurotic procedures and the transference relationship is addressed. This treatment has shown promise in depression, psychosomatic disorders, eating disorders and personality disorders. Motivational interviewing, motivational enhancement therapy and compliance therapy Motivational interviewing is a counselling style developed by Miller and Rollnick for the treatment of addiction behaviour. Its aim is to increase the patient's motivation to change. The therapeutic style is empathic and actively avoids confrontation. Through the use of open-ended questions, affirmation, reflective listening and other strategies the patients' concerns about their problem but also about potential difficulties with change are elicited, getting the patient not the therapist to express reasons for change.
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Motivational enhancement therapy (MET) uses the style of motivational interviewing. Its underlying assumption is that different individuals presenting for treatment will be at different stages of change. Those in the 'pre-contemplation phase' will not believe that there is anything wrong with them. Those in the 'contemplation phase' will be ambivalent about the advantages and disadvantages of change. Those in the 'preparation phase' are beginning to make a commitment to change. Those in the 'action phase' have started to work on change. Those in the 'maintenance phase' have succeeded in overcoming their problem but may be grappling with how to stay well. Lastly there is 'relapse', from which any of the previous phases can be re-entered. Therapeutic interventions need to match the stage of change of the patient. MET does not guide patients step by step to recovery, instead it attempts to get patients to define their own problem-solving strategies. MET (four sessions) has been evaluated in the treatment of alcohol problems against 12 sessions of CBT and 12 sessions of the 12-step approach. The overall outcome with MET was equally good as with the other treatments. Compliance therapy is a hybrid of the techniques of motivational interviewing, educational and cognitive-behavioural strategies and has been used in the treatment of psychotic patients to improve compliance with medication. Client-centred therapy This was developed by Carl Rogers in the 1940s. People are seen as having a capacity to move towards maturity (self-actualization, growth tendency). A therapist who shows genuineness, unconditional positive regard and empathic understanding provides 'the client' with the emotional climate in which such personal growth can occur. Gestalt therapy Developed by Frederick Perls. This is a noninterpretative approach which encourages the client to focus on immediate feelings rather than past experience. Existential psychotherapy Victor Frankl noted the inherent need in humans to find meaning (logos) in life and his approach centres on helping individuals to find it. Transactional analysis Developed by Eric Berne in the 1950s. Each person is considered to have three dynamic ego states: parent (exteropsyche), adult (neopsyche) and child (archaeopsyche). When two people communicate, each of
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their ego states may communicate (transaction). A game is a series of transactions. Clinically, transactionalists may focus on analysing a person's ego states, transactions and games with the aim of modifying behaviour. Supportive psychotherapy Introduction Supportive psychotherapy is the most commonly practised form of psychotherapy. However, because it deals with maintenance rather than cure it has tended to be neglected by researchers and clinicians alike. It is eclectic psychological treatment for patients with chronic and disabling problems which overcome personal resources and strengths. Patients are seen for extended periods of time (sometimes years), in order to help them manage their lives.
Aims These are: • to promote the best possible psychological and social functioning in the face of disability; • to minimize or prevent deterioration, relapse and hospitalization; • to give the minimum support necessary so as to avoid excessive dependency.
Procedure Treatment should foster an atmosphere that allows the patient to talk about practical and emotional problems. The patient is helped to cope with problems on a practical common-sense level. Deep insights are not encouraged. The therapist has to be aware that achievements are going to be limited and must help the patient to recognize this. Several techniques are used, sometimes combined with medication, including: ventilation of emotions; reassurance; encouragement; explanation; advice; environmental manipulation (i.e referral to a day centre) others, such as cognitive and behavioural techniques. In order to avoid making therapy unfocused and haphazard the therapist tries to decide at the onset of therapy how often, for how long and for what period of time he/she is going to see the patient. Regular reviews are useful.
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Indications and contraindications Patients with chronic psychosis, neurosis and personality difficulties may be tried with supportive therapy. There are no absolute contraindications.
Psychological treatments in primary care Counselling is commonly practised in primary care, usually on a shortterm basis. Counsellors often come from a wide range of professional backgrounds and may have different theoretical orientations (psychodynamic, client-centred or humanistic) in their approach. Counselling is often used for situational crises, adjustment reactions and relationship problems. The usefulness of counselling has been poorly evaluated. Brief problem-solving and cognitive-behavioural treatment have been evaluated in depressed and anxious patients in primary care and have been found to be of use.
Family and couple therapy Introduction Family therapy has evolved over the last 4 decades, during which time there have been many changes in theory and technique. The essential idea is that some of a patient's symptomatology is caused and maintained by their family and thus any cure which does not also address the family will either fail or be only partly successful. While there are separate literatures on couple therapy and family therapy, they share similar concepts and techniques. Specific problems in couple work include the apparent pressure for the therapist either to take sides or be the arbiter in a dispute, and the issue of the couple's sexual relationship (or lack of one). For the purposes of this section the term 'family' will be used to apply to any grouping from a couple to an extended family, including any individual who plays an important role in the patients life (i.e. close friend). Family therapy is practised in many settings, from specialized psychiatric family therapy clinics with a one-way screen and an observing team to child-guidance clinics and schools. It may be either systemic, behavioural, cognitive or psychodynamic. Systemic family therapy The three main schools of systemic therapy are described below.
Structural family therapy Of all the models of family therapy, structural therapy is perhaps the best known and most easily understood. Minuchin developed it while
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working with disorganized slum families. He saw families as a set of subsytems (i.e the parental couple, the children, the grandparents, etc.). In his model of a 'normal' family there are clear but semi-permeable boundaries between subsystems. Dysfunction is produced and maintained when the boundaries are either too rigid (disengaged) or too weak (enmeshed). In the initial sessions, in order to see how a family functions the therapist deliberately gets them to interact around problematic issues (enactment). In subsequent sessions, interventions are made to attempt to perturb the dysfunctional equilibrium. These include intensification - the therapist encourages the family to go further than it normally would in a problematic pattern of behaviour to try to precipitate a crisis; and unbalancing - by temporarily joining with one member of the family against the others the therapist disturbs the balance of power. The hope is that once perturbed the family can develop ways of behaving that are more functional for them. This model has attracted criticism for being a form of social engineering and culturally insensitive and as a result its practitioners have made considerable changes to their methods in recent years.
Strategic and brief therapies Strategic therapies are any therapy where the therapist actively designs an intervention or strategy to fit the problem. The therapy focuses on the details of the presenting symptom rather than the family as a whole. They are often short in duration and limited to helping the family with the problem they bring to the therapy. The central assumption is that the symptom is being maintained by the apparent solution. For example, a husband who nags his wife to spend more time with him may only drive her further away. The therapist often 'reframes' the problem to help the family to think in a new way about it, e.g. temper tantrums can be reframed as 'good at getting angry' and the family asked who is the best at getting angry, who is the next best and so on. A related stategy is the paradoxical intervention whereby the family is told to continue or expand the problem behaviour. Both techniques can be used to expose the ways in which a symptom is maintained by the family.
The Milan group The original Milan group has evolved into several quite different schools, but perhaps their most significant contribution is that of circular questioning. The therapeutic team develop a hypothesis about how a problem started and how it is maintained. The therapist then persistently questions the family members to try to prove or refute the hypothesis but also to refine it and allow the family to question their own belief systems.
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Behavioural family therapy Adapted from the principles of social learning theory. Initially a behavioural analysis is carried out to identify specific family problems and goals are set. Intervention strategies are devised which include communication training, limit setting, operant-conditioning strategies and homework tasks.
Psychoeducational approach in schizophrenia This approach was developed after it was observed that schizophrenics in families with high expressed emotion had a high rate of relapse following discharge from hospital. Its aim is to reduce the level of expressed emotion. It combines ideas from behavioural and structural family therapy. The family sessions are combined with educational sessions for family members and a relatives' group. Cognitive family therapy This method adapts techniques developed from individual cognitivebehavioural therapy for use with families. Psychodynamic family therapy Adapted from individual psychodynamic psychotherapy, this form is based on the assumption that each family member's early experiences, unconscious wishes, fantasies and expectations are the cause of problems in the present. For example, a woman who experienced her own father as distant and critical may project this image onto her partner. The therapist is less directive than in other forms and tries to help the family understand these links through interpretation. The transference between the family members is explored, but less so the transference between therapist and the family. Research Family therapy has been shown to be effective for a number of conditions. Examples include schizophrenia, where the psychoeducational approach reduces relapse rates, and anorexia nervosa. Couple therapy has been shown to be effective in treating depression.
Group treatments Introduction Group therapy is a means of treating a larger number of patients economically, but there are also factors which may make group therapy
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more powerful than individual therapy, including the confrontation by other patients, the ability to help others and gain self-respect. Psychodynamic group therapy The most significant school in Britain today is Foulkes' group analysis.
Aims Treatment aims are symptom relief, personality and attitude change, development of new ways of relating to others.
Procedure Psychodynamic outpatient groups tend to have seven or eight patients and one or two therapists. They meet once or twice a week for 90 minutes for one to several years. Groups may be open (members stay according to their needs, new members enter at various points) or closed (everybody starts and finishes at the same time).
Therapeutic factors (Yalorn) In a group, individual patients who have often felt isolated and separate from society develop a sense of solidarity that binds them together (cohesiveness). They have hope for improvement. This encourages selfdisclosure and catharsis which leads to a recognition of shared fears and preoccupations (universality}. Through a process of exploration of their relationship with each other and the therapist (interpersonal learning] they gain insight into to how they interact with others and how others experience them and can learn new ways of behaving (imitative behaviour}. By supporting others and helping them gain similar insight they develop self-respect (altruism).
Tasks Tasks of the group members are to share difficulties openly and honestly; to attend regularly and on time; not to meet others outside; and to keep the group informed of important changes in their life. Tasks of the therapist are to help the group concentrate on current conflicts; to help members recognize the various levels of functioning of the group, i.e. current adult relationships, individual transference relationships, shared feelings and fantasies; and, most importantly, to help the individual to gain insight into themselves as they relate to the events in the group. The therapist remains minimally active so as to not disrupt free flow of communications between members, but monitors, fosters, clarifies and points out unrecognized latent contents.
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Development stages of groups 1. At the beginning of the group, members look for guidance and direction and expect the leader to provide the answers to their problems. They may idealize the leader and compete for his/her attention. 2. The group discovers that the leader does not have all the answers, so becomes disillusioned and ambivalent; some may drop out. 3. A cohesive working group with a unique group culture develops. There are multiple, real and transferential relationships. The group is a safe and containing environment in which problems can be expressed, explored and new behaviours can be tried. 4. In the termination phase the group once again looks towards the leader to help them to separate from each other and the group as a whole and to mourn this loss.
Indications and contraindications Psychodynamic groups are useful for problems such as lack of identity, low self-esteem, lack of direction and difficulties with interpersonal relationships. Contraindications include acute psychosis and active substance abuse. Other therapy groups These include cognitive-behavioural, psychodrama, gestalt and encounter groups. Support and self-help groups People with particular problems have formed self-help groups for sufferers and relatives, in which sharing of burden, mutual support and information giving are factors. Examples are Alcoholics Anonymous, Overeaters Anonymous, etc.
How to assess an individual for psychotherapy The problem facing the clinician is which individuals are suitable for psychotherapy, when to treat and which therapy should be used for which disorder. For some conditions the evidence clearly supports one modality over another but for many conditions the case is less clear-cut. In essence, the decision is whether a cognitive, behavioural or dynamic therapy should be used and then whether treatment should be as an individual, as a couple or family or in a group setting with other patients. The choice is also likely to be affected by the patient's preference and local availability of the service. A further dimension is whether the patient's problems are rated as
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severe and treatment is more likely to be maintenance, or whether a 'cure' is hoped for. For example, some conditions respond well to shortterm structured treatments following which the rate of relapse is low (phobias, panic disorder, PTSD, OCD), whereas in chronic or severe disorders with co-morbidity brief treatments are often ineffective and longer term treatments more appropriate (e.g. recurrent depression and substance abuse). Psychological treatments may improve medication compliance and conversely pharmacological treatments may make patients accessible to psychological interventions. There is a general trend to try to achieve evidence-based practice, but clinicians are often ill-informed about findings from psychotherapy research and the available literature has so far had limited impact on services. Fonagy and Roth's review of the literature presented a summary of conclusions regarding evidence-based practice. They accepted treatments where there was replicated evidence of benefit from well-controlled clinical trials in which there was a clear description of therapeutic method and a good description of the patient group. The results are summarized below, where good = clearly effective; moderate = promising/ having limited support for their efficacy.
Schizophrenia • Family intervention programmes - good. • Cognitive therapy for delusions - moderate.
Mood disorders Depression • Cognitive-behaviour therapy - good. • Interpersonal psychotherapy - good. • Psychodynamic psychotherapy - moderate.
Bipolar affective disorder There is limited research with this disorder. There is some evidence for possible increased compliance and reduced hospitalization with either group therapy or individual cognitive-behavioural therapy. Anxiety • Exposure therapy is the treatment of choice for specific phobias and agoraphobia. • Cognitive-behavioural therapy is the most effective in generalized anxiety disorder and panic disorders. Both of the above are effective in social phobia.
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Obsessive-compulsive disorder • Exposure and response prevention - good. • Cognitive behavioural therapy - moderate. Post-traumatic stress disorder • Stress inoculation therapy in combination with cognitive techniques good. • Short-term dynamic psychotherapy - moderate.
Eating disorders Anorexia nervosa • Behavioural, cognitive and eclectic psychotherapy including dietary management - good. • Family therapy with younger patients - moderate. Bulimia nervosa • Cognitive-behavioural therapy - good. • Interpersonal psychotherapy - good.
Alcohol abuse • Behavioural treatments to enhance social adaptation (social skills training, marital therapy) - good. • Brief educational interventions, including motivational interviewing good.
Sexual dysfunctions • Cognitive-behavioural treatment for erectile dysfunction - good. • Exposure based behavioural techniques for vaginismus - good. • Behavioural techniques for premature ejaculation - moderate.
Personality disorders • Social skills training for avoidant personality disorder - good. • Dialectical behaviour therapy - good. • Psychodynamic psychotherapy - moderate.
Interventions with older people • Behavioural, cognitive-behavioural and structured psychodynamic psychotherapy for depression - good. • Psychosocial intervention for carers - good. • Reality orientation for people with dementia - moderate.
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Reading list Asen, E. (1996) Advances in families and couples therapy. In Psychotherapy, Psychological Treatments and the Addictions (eds G. Edwards and C. Dare). Cambridge: Cambridge Unversity Press. Bloch, S. (1996) An Introduction to the Psychotherapies, 3rd edn. Oxford: Oxford University Press. Brown, D. and Pedder, J. (1979) Introduction to Psychotherapy. London: Tavistock. Fonagy, P. and Roth, A. (1966) What Works for Whom?New York: Guilford Press. Kemp, R., Hayward, P., Applewhaitte, E. et al. (1966) Compliance therapy in psychotic patients. A randomised controlled trial. British Medical Journal, 312, 345-9. Miller, W. and Rollnick, S. (1991) Motivational Interviewing. Preparing People to Change Addiction Behaviours. New York: Guildford Press. Parry, G. and Richardson, A. (1996) NHS Psychotherapy Services in England. London: UK Department of Health. Project Match Research Group (1997) Matching alcohol treatments to client heterogeneity: project match post treatment drinking outcomes. Journal of the Study of Alcohol, 58, 7-29. Ryle, A. (1990) Cognitive Analytic Therapy: Active Participation in Change. Chichester: Wiley. Weissman, M.W. and Markowitz, J.C. (1994) Interpersonal psychotherapy: current status. Archives of General Psychiatry, 51, 599-606.
29
Pharmacological treatments in psychiatry RICHARD DRAKE and SHON LEWIS
The clinical use of drugs is considered in this chapter, as basic pharmacology is covered in Chapter 4. Each major category of drugs is divided into sections on indications, contraindications, actions, unwanted (side) effects, interactions and specific preparations.
Antipsychotic drugs Also known as neuroleptics or major tranquillizers, they are divided into 'classical' or 'conventional' and 'atypical' on the basis of their extrapyramidal side effects. Classical antipsychotics
Indications The main indications are as follows: 1. Treatment of psychotic symptoms and/or disturbed behaviour in the functional psychoses, such as schizophrenia, mania and delusional depression. 2. Treatment of acute agitation in organic states, agitated depression and severe anxiety. 3. Long-term treatment and prophylaxis in functional psychoses, particularly schizophrenia. 4. Other indications include: drug-induced psychoses; Gilles de la Tourette syndrome; and occasionally anorexia nervosa. In delusional depression (or sometimes refractory depression in the elderly), antipsychotics and antidepressants can be combined.
Contraindications Caution is needed in the presence of the following: myasthenia gravis, Addison's disease, glaucoma, Parkinson's disease, epilepsy, liver disease
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(particularly chlorpromazine, least with sulphide) and cases with evidence of previous sensitivity.
Actions These drugs are reversible dopamine receptor antagonists {see Chapter 4 for details). Although nonspecific sedation and unwanted effects occur rapidly, the specific antipsychotic action is usually delayed for 1-3 weeks. Classical antipsychotics may also have anti-alpha adrenergic, anticholinergic, antiserotonergic and antihistaminic activity.
Unwanted effects Motor ('extmpymmidal') A. Early
effects
1. Acute dystonia. Distressing, painful and involuntary contraction of the neck (torticollis), facial, orbital, lingual or spinal muscles, or less commonly the limbs, often associated with upturning of the eyes (oculogyric crisis). It is due to dopamine blockade, and affects about 5 per cent of those taking antipsychotics, typically younger patients during the first 2 days of treatment. Prompt treatment with an anticholinergic is warranted, such as procyclidine 5-10mg intramuscularly or slowly intravenously. 2. Akathisia. Defined as subjective and objective motor restlessness, particularly in the legs. The mechanism is uncertain, though it is commoner with more potent neuroleptics (which block receptors relatively completely at lower doses, such as haloperidol) and rapid increases in dose. Treatment is reduction of the drug dose if possible, or adding an anticholinergic or beta-blocker. 3. Parkinsonian symptoms. Muscular rigidity, bradykinesia and (rarely) tremor. The earliest signs are loss of arm swinging when walking and loss of facial expression, often accompanied by salivation (sialorrhoea) and greasy skin secretion (seborrhoea). It affects 25-40 per cent, especially the elderly, and is due to blockade of striatal dopamine receptors. Treatment is by reducing the dose of antipsychotic, adding an anticholinergic or changing to an atypical antipsychotic. Tolerance to Parkinsonian effects usually develops, so if anticholinergics are started early they should be reviewed after about 3 months. B. Late 1. Tardive dyskinesia. Abnormal, involuntary repetitive movements. The most common presentation is orobuccolingual dyskinesia, characterized by chewing and pouting, often with mild choreiform movements of the extremities. Severe cases show shoulder shrugging and rocking of the trunk. An early sign is inability to keep the tongue extruded.
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It seldom appears before at least 6 months of drug use and occurs in about 2 per cent of patients having treatment per year (rates vary depending on definition). It may be irreversible in a third to a half of these. Risk increases with: • • • •
increasing duration and dose of antipsychotic drug treatment; increasing age (elderly women are said to be the most affected); underlying brain disease; and anticholinergic drug treatment exacerbates existing and reveals latent tardive dyskinesia.
Tardive dyskinesia may be related to the late development of hyperactivity in the basal ganglia's dopamine systems, which adapt to prolonged dopamine blockade by supersensitivity of the postsynaptic dopamine receptors. Hence tardive dyskinesia is made worse by Ldopa and amphetamine, and transiently worsens when antipsychotics are stopped. Conversely, cholinergic agents such as physostigimine can rarely improve tardive dyskinesia, and if the dose of antipsychotic is increased there can be transient improvement. However, modern models of tardive dyskinesia have other features. These include other systems (e.g. neurons producing the inhibitory transmitter gamma aminobutyric acid, which interact with the basal ganglia dopaminergic systems) or prolonged blockade of autoreceptors. Prevention of tardive dyskinesia is by judicious use of antipsychotics with low doses wherever possible. Atypical antipsychotics are less likely to produce tardive dyskinesia. Treatment is to stop the antipsychotic drug, though improvement, if it occurs, may take months. Alternatively transfer to an atypical antipsychotic. Clozapine may be particularly effective. Tetrabenazine, oxypertine and highdose vitamin E are said to be effective in some severe cases. 2. Tardive dystonia and tardive Tourette's syndrome have been described; anticholinergics may have a role in the treatment of tardive dystonia.
Other unwanted effects 1. Sedation. Marked with chlorpromazine and thioridazine (antihistaminic effect); less with haloperidol and trifluoperazine. Tolerance develops over 5 or 6 days. 2. Antimuscarinic effects. Dry mouth, blurred vision, stuffy nose (antiadrenergic also), constipation, urinary retention and reflex tachycardia. Especially with thioridazine. 3. Anti-adrenergic effects. Postural hypotension (particularly with chlorpromazine and droperidol) and inhibition of ejaculation but not erection. 4. Endocrine effects. Dopamine inhibits prolactin release. Antipsychotics are dopamine antagonists and may produce hyperprolactinaemia
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5.
6.
7. 8. 9.
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with associated gynaecomastia in men, and galactorrhoea and amenorrhoea in women. Glucose tolerance is impaired. Increased skin pigmentation and photosensitivity. Skin reactions include increased pigmentation of exposed skin, photosensitivity (particularly chlorpromazine), hypersensitivity and contact dermatitis. Corneal and lenticular opacities (e.g. chlorpromazine) can also occur. Cardiovascular toxicity. Prolonged QT interval with flattened T waves are EGG changes particularly associated with pimozide and to a lesser extent chlorpromazine and thioridazine. Pimozide requires an EGG before treatment and regular EGG monitoring at higher doses; but arrhythmias occur rarely with other drugs. Lowered seizure threshold. Risk of seizures is less with haloperidol and trifluoperazine, greater with chlorpromazine. Weight gain (particularly with less potent antipsychotics). Hypothermia (a hypothalamic effect commoner in the elderly) and decreased libido. Rare idiosyncratic reactions. Blood dyscrasias, including agranulocytosis. Cholestatic jaundice, especially with chlorpromazine in the past. Retinitis pigmentosa, particularly with prolonged high doses of thioridazine. Neuroleptic malignant syndrome. Sudden hyperthermia, autonomic changes, akinesia and rigidity, reduced level of consciousness and confusion mark the full syndrome. There is also neutrophilia and raised serum creatine kinase. This develops 24-72 h after the drug is started or increased, especially with fluphenazine or haloperidol. Death occurs in 10 per cent due to respiratory failure. The cause is probably excess dopamine blockade in the hypothalamus and basal ganglia. Emergency treatment is needed, including supportive measures such as parenteral fluids and ventilation if necessary; bromocriptine and/or dantrolene are recommended. The antipsychotics are stopped at once. The frequency is disputed and there is controversy about whether there are partial forms of the disorder, or these cases are due to the combined side effects of anticholinergics and antipsychotics. Similar syndromes occurred before the introduction of neuroleptics; antidepressants can occasionally produce it.
Interactions Antidepressant plasma levels can double, especially when tricyclics and phenothiazines are combined. Anticholinergics can decrease plasma levels. Drugs which increase QT interval (e.g. some anti-arrhythmics, erythromycin, tricyclics) can interact. Antihypertensives: chlorpromazine particularly can increase the effect, and propranolol increases chlorpromazine levels. Lithium slightly increases risk of extrapyramidal effects, and possibly neurotoxicity with haloperidol if both are at high
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doses. Cimetidine competes for metabolism in the liver, and antacids can reduce absorption from the gut. Also with the antiviral drug ritonavir. Table 29.1 lists classical antipsychotic drugs.
Depot preparations Decanoates of flupenthixol and fluphenazine, zuclopenthixol and haloperidol and pipothiazine palmitate are given weekly to 4-weekly in maintenance treatment of chronic schizophrenia. Zuclophenthixol and haloperidol may need to be given at shorter intervals and (rarely used) fluspirilene weekly. Depot antipsychotics may help overcome poor compliance, and some evidence suggests greater efficacy than oral antipsychotics. However, there is a higher risk of Parkinsonian side effects and tardive dyskinesia. A small test dose should be given first to test sensitivity.
High doses Patients are treated with high doses of antipsychotics either because they are severely agitated and unwell, or because they do not respond to conventional doses. Large doses, particularly when several antipsychotics are combined or given parenterally to physically agitated patients, have been linked to arrhythmias and sudden death. Doses specified in the British National Formulary should not be exceeded, except in special circumstances, on the instructions of senior staff. It is good practice to avoid combining antipsychotics as far as possible. In patients who do not improve with conventional doses of classical
Table 29.1. Classical antipsychotic drugs
Drug
Group
Extrapyramidal Sedation effects
Chlorpromazine* Thioridazine Trifluoperazine Haloperidol
P P P Bu
++ + ++ + +
++ + +++ +++
300-1000 300-800 10 upwards 5-120
Pimozide Sulpiride Promazine
D Be P
+ + + ++
++ + ++
4-20 800-2400 25-50
Typical doses (mg)
Comments
Also used for Tourette's EGG monitoring 'Pure' D2 blocker Not antipsychotic Used for sedation in elderly
'Equivalent doses to 100mg chlopromazine are: 100mg thioridizine, 5mg trifluoperazine, 2mg pimozide and 2mg haloperidol. Doses much lower in elderly. P = phenothiazine; Bu = butyrophenone; D = diphenylbutylpiperadine; Be = benzamide.
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neuropleptics there is no evidence from systematic studies that doses above this level are more effective in treating the underlying illness, and if persistent high doses are ineffective, then reducing the dose can improve agitation due to motor side effects, for instance. Atypical antipsychotics may be effective in some patients who are refractory to conventional antipsychotics. If further sedation is needed for acutely disturbed patients, then benzodiazepines for short periods are relatively safe, in combination with antipsychotics to avoid the paradoxical disinhibition that they can cause. Respiratory arrest is the main hazard of these drugs. Intramuscular doses often need only be half oral, since the drug bypasses the liver and enters the circulation directly. Intravenous drugs are more dangerous still. The Royal College of Psychiatrists has published guidelines on this area. Atypical antipsychotics
Indications 1. As for conventional antipsychotics, but particularly patients unable to tolerate the motor side effects of conventional antipsychotics or refractory to conventional antipsychotics. 2. Clozapine has a special role in patients refractory to both conventional and other atypical antipsychotics. It is effective in 30-50% of patients who do not respond to other antipsychotics. It is also the antipsychotic of choice in sufferers from tardive dyskinesia. The atypical have fewer Parkinsonian side effects than the conventional antipsychotics, and they therefore reduce the 'secondary' negative symptoms of schizophrenia. Evidence about their effects on primary negative symptoms is still lacking. They have been suggested to produce tardive dyskinesia less often, and in schizophrenia produce better cognitive function and have greater effect on depressive symptoms. The truth of these claims is also still uncertain. Only clozapine has been shown to be clearly more effective for positive symptoms. Clozapine also produces even fewer motor side effects than other atypicals.
Contraindications Atypical antipsychotics are relatively contraindicated in Parkinson's disease (clozapine least) and Addison's disease. Particularly for clozapine, epilepsy, glaucoma, myasthenia gravis, liver disease and previous sensitivity are reasons for caution.
Actions Clozapine blocks 5-HT2 receptors and partially (50-60%) dopamine D2 receptors. Other atypical antipsychotics, to varying degrees, bind to 5HT2 receptors and have reduced dopamine receptor occupancy.
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Unwanted effects Clozapine 1. Blood dyscrasias. Agranulocytosis occurs in 0.5 per cent of unmonitored patients on clozapine, though it is much less common now the dose is gradually increased at the start of treatment, and that blood monitoring is mandatory. Use of other myelosuppressant drugs at the same time, such as benzodiazepines, anti-epileptics, other antipsychotics or antidepressants, is discouraged. Blood monitoring is mandatory weekly for the first 18 weeks and less commonly thereafter. It effectively protects against dyscrasias. 2. Lowered seizure threshold. About 2 per cent of patients using clozapine have fits, particularly at doses above 600mg/day, and some centres cover this with sodium valproate. EEG can be used to predict problems before an increase to higher doses. 3. Other effects. Clozapine often causes sialorrhoea, possibly by an antialpha2 adrenergic effect, which may be treated by conventional anticholinergics or amitriptyline. Sedation, largely an antihistaminergic effect, and weight gain can also be prominent. Nocturnal enuresis can also occur. Other atypical antipsychotics 1. Motor (extrapyramidal) effects. In risperidone at above 8mg/day, less in other atypicals. 2. Sedation. 3. Cardiovascular toxicity. 4. Weight gain.
Anticholinergics
Indications The main indications in psychiatry are acute dystonic and Parkinsonian side effects of antipsychotic drugs (L-dopa cannot be used because the Table 29.2. Atypical antipsychotic drugs Drug
Sedation
Risperidone Olanzapine Clozapine
+ ++ +++
Quetiapine Ziprasodone Amisulpiride
++ ++ +
AntiExtramuscarinic pyramidal ++ +++
Typical daily doses (mg)
++ + -
4-8 5-20 200-900
(+ ) + +
200-800 80-160
Comments
Needs FBC monitoring
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dopamine receptors are already blocked). Akathisia responds relatively poorly. They may increase compliance with antipsychotics by reducing side effects.
Contraindications Tardive dyskinesia, glaucoma and prostatism.
Unwanted effects These include: • • • •
dry mouth, blurred vision, urinary retention, constipation; uncovering or exacerbating tardive dyskinesia; delirium (atropine psychosis), especially in the elderly; abuse for mild euphoriant effects; perhaps less with benztropine and orphenadrine.
These side effects mean that anticholinergics should not be prescribed routinely with antipsychotics.
Interactions Enzyme induction can lower the serum levels of antipsychotics.
Tricyclic and related antidepressant drugs Indications 1. Major depressive episode, particularly with vegetative features. They are less successful in deluded depressive patients, who may also need antipsychotics or ECT. 2. Severe panic attacks, and generalized anxiety disorder, with or without clinical depression. 3. Obsessive-compulsive disorder (especially clomipramine). 4. Nocturnal enuresis in children (in much reduced doses). 5. Chronic and neuropathic pain.
Contraindications Relative contraindications include glaucoma, prostatism, epilepsy, recent myocardial infarction, heart block and cardiac arrhythmia.
Actions Sixty to 80 per cent of patients with moderate or severe depression improve with an adequate trial of antidepressants, compared to 30 per cent with placebo. Tricyclics increase the synaptic activity of monoamines, principally noradrenaline and 5-HT by blocking their presyn-
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aptic reuptake and through other post-synaptic effects (see Chapter 4 for details). The antidepressant effect is usually delayed for 1-3 weeks, but adverse effects, if present, occur early. With no therapeutic effect, the maximum tolerated dose should be tried for 6 weeks before giving up. One-third of non-responders would improve if larger doses were given, although a therapeutic window effect may occur with nortriptyline (i.e. higher doses having less clinical efficacy).
Unwanted effects 1. Anticholinergic effects (dry mouth, blurred vision, constipation, impotence, slowed reaction times). 2. Sedation, and confusion in the elderly. 3. Cardiovascular effects (less common with lofepramine): • postural hypotension; • tachycardia, arrhythmias including lengthened PR interval or heart block; • T-wave inversion on ECG. 4. Fine resting tremor. 5. Lowered seizure threshold (especially with maprotiline, less with viloxazine or trazodone). 6. Weight gain with tricylics, oedema with tetracyclics. 7. Mania in susceptible patients. 8. Nausea, particularly with the more serotonergic drugs. 9. Sexual side effects, including anorgasmia; priapism with trazodone. 10. Hyponatraemia and the secretion of inappropriate antidiureic hormone (SIADH), particularly in the elderly. 11. Rare idiosyncratic reactions: these include hepatoxicity (particularly lofepramine) and blood dyscrasias. 12. Withdrawal effects (unusual): tremor, nausea, loose stools, sweats, insomnia. Prevented by withdrawing over 2-6 weeks.
Interactions 1. Increased risk of arrhythmias with drugs prolonging QT interval. Increasing plasma levels with antipsychotics. 2. Hypotensive effects of most antihypertensives increased (including diuretics), but antagonism of adrenergic neuron blockers and clonidine (increased risk of hypertension on clonidine withdrawal). Hypertension and arrythmias with systemic adrenaline, hypertension with noradrenaline. 3. Increased plasma levels with enzyme inhibitors like cimetidine, oral contraceptives (which antagonize antidepressant effect also) and disulfiram. Levels decreased by enzyme inductors like carbamazepine. Possibly interactions with ritanovir and other related antiviral drugs.
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Specific preparations The early tricyclic drugs (e.g. amitriptyline, imipramine) have the most side effects. They are very cardiotoxic in overdose. Lofepramine is relatively safe in overdose, because lofepramine counteracts the proarrhythmic effects of the main metabolite, desipramine. Other related non-tricyclic drugs also have fewer autonomic side effects, such as trazodone and viloxazine (which can, however, cause priapism and migraine, respectively). Reboxitine is a new, particularly selective, noradrenaline reuptake inhibitor with cholinergic side effects. It is as yet unclear how much advantage it has over tricyclics like lofepramine. There is no clear evidence of differences in efficacy between different drugs in this group. The older tricyclics affect a wider spectrum of monoamine receptors than the newer drugs and they are sometimes suggested to be more efficacious (as well as less expensive). All have a similar delay for their antidepressant or anti-anxiety effects. In depression they should be prescribed for at least 4-6 months after remission to avoid relapse, and tailed off gradually. Table 29.3 gives a list of antidepressants.
Selective serotonin reuptake inhibitors Indications As for tricyclic antidepressants. They have also been claimed to exert their antidepressant effect more quickly, but the evidence is not conclusive. SSRIs have fewer side effects and are much less toxic in overdose than the early tricyclics. The newer drugs are therefore safer for those patients in whom tricyclics are contraindicated by physical illness or risk of overdose. However, the SSRIs are also more expensive than the tricyclics. Compared to the tricyclics, patients may comply better with SSRIs.
C ontraindications Safety in pregnancy is uncertain. Fluoxetine may accumulate in liver disease.
Actions SSRIs selectively inhibit 5-HT reuptake with minimal binding to other receptors (see Chapter 4 for details).
Unwanted effects 1. Agitation with some (particularly with fluoxetine), more rarely sedation with others, such as fluvoxamine. Agitation and increased anxiety tend to occur early and reduce after about 5 days, and sedation tends to increase more gradually.
537
Pharmacological treatments in psychiatry Table 29.3. Antidepressants
Drug
Unwanted effects Arti ardiocholinergic vascular
Sedating TCA: Amitriptyline + ++ Trimipramine ++ Dothiepin + Doxepin ++ Non-sedating TCA: Imipramine ++ Nortriptyline ++ Desipramine + Lofepramine + Others: Viloxazine + Maprotiline ++
++ ++ ++ +
++ ++ ++ ( +)
Monoamine action 5-HT NA
++
+ ++
+
+ + +
++ ++ +
+
++ ++
( +)
( +)
++
( +) ( +)
( +) ( +)
+ ++ + ++ + ++ + ++ + ++
++
+
+ ++
++
Isocarboxazid ++ MAOI nonhydrazines: Tranylcypromine + +
+
+ ++
++
+ ++
++
( +)
+ ++
++
+
++
4- +
Reversible MAO Inhibitor Moclobemide SNRI Venlafaxine
+
+
(dosulepin)
++ + ++ ++
++
Trazodone SSRIs: Fluvoxamine Fluoxetine Paroxetine Sertraline Citalopram MAOI hydrazines: Phenelzine
Comments
Bicyclic oxazine Tetracyclic related Triazolopyridine sedative
First-choice MAOI
Mild amphetaminelike action
Can cause hypertension
2. Nausea and diarrhoea, particularly early on. 3. Anorgasmia is relatively common. 4. Far fewer anticholinergic effects (but dry mouth with sertraline particularly). 5. Mania in susceptible patients. 6. Serotonin syndrome occasionally if the dose is too high: restlessness, myoclonus, hyperreflexia, shivering, tremor and reduced conscious level, potentially leading to arrhythmias and fits.
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7. Withdrawal effects, such as insomnia, tremor and agitation, are reported, particularly with the shorter acting drugs paroxetine and (less so) sertraline. Nefazodone is a primarily serotonergic drug, but because it also has post-synaptic receptor antagonist effects it has fewer unwanted effects on sleep and sexual function.
Interactions The SSRIs cause varying degrees of inhibition of liver cytochrome P450 oxidases, of which there are several. The most marked effects are with fluoxetine and isoenzyme CyPIID, the least with sertraline and citalopram. Warfarin levels may possibly be increased. So are some antipsychotics, especially sertindole; carbamazepine and phenytoin; theophylline; antiviral drugs like ritanovir, and some antifungals. Serotenergic drugs may interact to produce the serotonin syndrome (see Unwanted effects, above). This is particularly true for MAOIs and moclobemide, and sometimes occurs with tricyclic antidepressants, and with sumatriptan for migraines.
Serotonin and noradrenaline reuptake inhibitors and related drugs The serotonin and noradrenaline transmitter systems interact: there are receptors for the other neurotransmitter on the neurons of each type. Combined serotonin and noradrenaline reuptake inhibitors (SNRIs) have been developed, e.g. venlafaxine. Another new drug, mirtazapine, is primarily an alpha2 antagonist, and causes an increase in noradrenergic activity, and also an increase in serotonergic neurons' activity via noradrenaline receptors on these cells. (Trazodone and nefazodone may have similar actions.) It is also a 5-HT2/3 agonist. Mirtazepine and venlafaxine therefore activate both 5-HT and noradrenergic systems. Because of this dual action they may be more effective in severe depression than purely serotonergic drugs.
Monoamine oxidase inhibitors Indications Monoamine oxidase inhibitors (MAOIs) are as effective as tricyclics in major depression and anxiety disorders, but may be especially effective in atypical depression with symptoms of anergia, hypersomnia and weight gain, rather than endogenous features. They have also been
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particularly used for phobic anxiety and panic attacks. Because of their potential interactions with foods and other drugs, they are now less commonly prescribed.
Contraindications Liver disease and cardiac failure. MAOIs should be withdrawn 2 weeks before general anaesthesia.
Actions These drugs inhibit intracellular breakdown of monoamines noradrenaline, 5-HT and dopamine (see Chapter 4 for details). Although MAO is blocked straight away, the antidepressant effect is delayed for 1-3 weeks.
Unwanted effects 1. CNS stimulation. Fine tremor, excessive sweating, sleeplessness, hypomanic behaviour and convulsions. Tranylcypromine has amphetamine-like actions, which has led to some abuse. 2. Autonomic effects. Postural hypotension and anticholinergic effects. 3. Sodium and fluid retention. 4. Peripheral paraesthesiae. 5. Hypertensive crisis. This is rare. MAOIs prevent the metabolism of catecholamines and sympathomimetic compounds in the gut, liver and CNS. Therefore, ingestion of sympathomimetics like tyramine with MAOIs can cause CNS stimulation and hypertensive crisis. Foods rich in such compounds include: cheese (especially mature, soft; not cottage); yeast and related products like marmite and Twiglets; bovril; pickled herring; and broad bean pods. Patients should avoid them. Also implicated are beer, wine (particularly Chianti), pilchards, sardines, well-hung pheasant, liver, canned figs, banana skins (in some stews), large quantities of coffee and citrus fruits. The emergency treatment of such reactions is usually with the alpha-adrenergic blocker phentolamine, but chlorpromazine can be used if none is available. 6. Uncommonly, hepatocellular jaundice and exacerbation of migraine.
Interactions 1. Serotonergic drugs: tricyclics, SSRIs, SNRIs, sumatriptan, tryptophan. Can cause serotonin syndrome. Two weeks should be left between stopping an MAOI and other antidepressant prescription, and variable delay between other antidepressants (e.g. 5 weeks for fluoxetine, 2 weeks for most others) and MAOIs.
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2. Sympathomimetic and dopaminergic drugs: e.g. in cold remedies, local anaestheics, drugs of abuse, guanethidine, bethanidine, L-dopa, methyldopa, tetrabenazine. 3. Opioids have their hypotensive effect increased. Pethidine has some serotonergic effects and can cause hypertension as well. Low doses of morphine are best if opioid analgesia is needed. 4. Others: carbamazepine (and other liver-metabolized drugs) can interact, and antihistamines can enhance muscarinic and histaminic side effects. The effect of sulphonylureas and insulin is enhanced. Clozapine may enhance central effects, and oxypertine can interact. General precautions Patients should be issued with warning cards about drug and food interactions.
Specific preparations See Table 29.3. Moclobemide, a reversible MAO-A inhibitor (MAO has two forms, A and B, with different neurotransmitter substrates at physiological concentrations) has been developed. It causes the hypertensive response only at concentrations of sympathomimetics which are not usually reached in a normal diet, though caution with the same range of foods and drugs should be advised. It also has a much shorter half-life, and can be discontinued later before surgery, for instance. However, it has not yet been clearly demonstrated to have full efficacy in the range of conditions that better established antidepressants have.
L-tryptophan This amino acid is a monoamine precursor. It has weak antidepressant properties and few side effects except nausea. It is sometimes used with MAOIs and tricyclics in resistant depression. It is used on a namedpatient basis after impurities in preparations formerly used were found to rarely cause the serious eosinophilia-myalgia syndrome.
Lithium Indications 1. Prophylaxis of bipolar affective disorder, severe unipolar affective disorders and schizoaffective psychoses. 2. Treatment of acute mania. When sedation is needed it is used with an antipsychotic. The antimanic effect takes at least 1 week.
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3. Treatment of resistant depression. 4. Treatment of refractory schizophrenic symptoms, together with an antipsychotic. 5. Some efficacy in persistant aggressive behaviour, or affective instability of borderline personality disorder.
Contraindications Cardiac failure, chronic renal disease, thryoid disease, Addison's disease, pregnancy (particularly the first trimester), and breast feeding. Also caution in epilepsy and myasthenia gravis.
Action Mechanism of action unknown (see Chapter 4 for further details).
Unwanted effects Early Usually transient: 1. Nausea and diarrhoea. 2. Fine tremor (can be treated with propranolol) and muscular fatigue. 3. Mild natriuresis causing transient polyuria and thirst. Late 1. Nephrogenic diabetes insipidus. This happens in 1-5 per cent and is due to inhibition of adenylate cyclase synthesis. When renal tubules become insensitive to ADH, as a result, persistent but reversible polyuria results. Reports of irreversible histological changes in longterm users' kidneys have not been confirmed and there is no evidence of increased mortality from renal disease. 2. Euthyroid goitres and hypothyroidism. These thyroid changes occur in 5 per cent of cases, usually women. This is due to inhibited release of thyroid hormones with resultant rise in TSH. Thyroid antibodies may be present. Replacement therapy may be needed. 3. Other late effects. These include T-wave inversion on ECG, rarely arrhythmias; water retention; weight gain; benign leucocytosis; precipitation of seizures; extrapyramidal syndromes; osteoporosis; and allergic reactions. 4. Teratogenic effects. Particularly cardiac abnormalities. 5. Toxicity. Normal levels are less than 1.2 to 1.4mmol/l. Toxicity may occur at normal levels in the elderly. Toxicity almost always occurs at levels over 2 mmol/1 and is heralded by vomiting and diarrhoea. It is marked by arrhythmias, coarse tremor, twitching, ataxia, dysarthria and nystagmus. Severe toxicity may cause confusion, convulsions, coma and death. Blood lithium is increased by dehydration, low-salt
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diets and thiazide diuretics. Mild toxicity is treated by increased fluid intake and oral sodium chloride, or saline infusion if necessary. In severe cases intravenous mannitol is used, and if serum levels exceed 3 mmol/1, forced alkaline diuresis or dialysis is indicated. Starting and monitoring lithium treatment 1. Before starting lithium, check blood pressure and note any history of heart, kidney or thyroid disease. 2. Check FBC, electrolytes, thyroid function tests, serum creatinine and possibly clearance. 3. Measure blood lithium 4-7 days after starting and adjust dose accordingly: aim for 0.9-1.4 mmol/1 in acute treatment of mania or depression and 0.5-1.0 in long-term prophylaxis. Record the serum level and electrolytes weekly until stable for 4 weeks and then every 612 weeks. Serum levels should be measured at least 12 h after the last dose. 4. In long-term therapy, FBC, electrolytes, creatinine and thyroid function should be checked every 6 months.
Interactions Lithium excretion is reduced by thiazide, potassium-sparing and loop diuretics (though loop diuretics safer than thiazides), ACE inhibitors, and NSAID analgesics; and increased by sodium bicarbonate and theophyline. CNS toxicity can occur with SSRIs and sumatriptan, methyldopa, rarely calcium channel blockers, carbamazepine and antipsychotics. There have been suggestions that haloperidol and lithium can produce an encephalopathy when haloperidol doses are above 40 mg and at the same time lithium levels above 1.0 mmol/1, but this has been disputed. Muscle relaxants' action is increased and lithium should be stopped at least 2 days before elective surgery.
Withdrawal Lithium should be withdrawn gradually over several weeks, and there is limited evidence that it may precipitate mania if withdrawn within 30 months of initial prescription for prophylaxis.
Carbamazepine Indications 1. Epilepsy, particularly partial seizures. 2. Trigeminal neuralgia and neuropathic pain. 3. Prophylaxis and treatment of recurrent affective disorders (particu-
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larly mania). May be best in patients resistant to lithium, especially young patients with 'rapid cycling' disease. Also for patients intolerant of lithium. 4. Possibly in recurrent paroxysmal aggression with abnormal EEG findings (episodic dyscontrol syndrome).
Contraindications Cardiac AV node conduction abnormalities, history of bone marrow depression or porphyria. Caution in pregnancy (can cause neural tube defects if folate low) and glaucoma.
Unwanted effects Nausea, vomiting, diarrhoea; skin rashes (may be transient, can progress to Stevens-Johnson syndrome and be fatal); renal failure or hepatitis; commonly mild leucopenia but other blood dyscrasias; cardiac arrhythmias; mild antimuscarinic effects; hyponatraemia, galactorrhoea and gynaecomastia; and cerebellar ataxia symptoms.
Interactions Reduces serum levels of: tricyclics, some antipsychotics, thyroxine and steroids, including contraceptives, and anticoagulants. Fluoxetine, fluvoxamine, cimetidine and viloxazine decrease its levels. Neurotoxicity may rarely occur with lithium.
Valproate and other anticonvulsants Sodium valproate has also been shown to have an antimanic effect like carbamazepine, and is used in people with refractory disease. Phenytoin is an effective treatment for chronic pain.
Treatment of refractory depression Electroconvulsive therapy may be used: particular indications are discussed elsewhere. Psychological treatments, alteration of social circumstances and admission to day hospital or an inpatient bed are important and may be considered at different stages. 1. Reconsider diagnosis. Check compliance, possibly measuring serum levels. 2. Increase to maximum tolerable dose within BNF limits, and consider further increase with expert advice. 3. Change to a different class of antidepressant, e.g. SSRI to tricyclic or venlataxine. 4. Add lithium (or other mood stabilizer) unless contraindicated.
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5. Brief courses of triiodothyronine or thyroxine in low doses have been advocated as adjuncts to antidepressants (as has pindolol, particularly with SSRIs). 6. Sometimes tryptophan may be added to lithium and an antidepressant. 7. In highly refractory depression, combinations of tricyclics, MAOIs and possibly tryptophan have been used. For instance, amitriptyline and phenelzine monitored in hospital, increased cautiously after a drug-free period. It is important to avoid adding a tricyclic to a fulldose MAOI, or combining clomipramine and tranylcypromine. Phototherapy, using a relatively bright, daylight-spectrum light source to reset the internal circadian rhythm, has been shown to treat depression which recurs only in winter (seasonal affective disorder).
Benzodiazepines Indications 1. Short-term (e.g. up to 2 weeks) treatment of acute anxiety states. 2. Short-term treatment of acute insomnia (short-acting hypnotics). 3. Withdrawal from alcohol and other sedative drugs. 4. Acute behavioural disturbance, e.g. psychotic emergencies. 5. Premedication or minor medical procedures. 6. Acute treatment of fits, or status epilepticus. 7. Muscle spasm in CNS disorders. 8. Rarely, intravenously in abreaction.
C ontraindications History of drug or alcohol abuse, chronic severe lung disease.
Actions Their actions are mediated by benzodiazepine receptors in the CNS which increase GABA activity. Their safety and efficacy ensured their popularity in the treatment of anxiety disorders, but studies have shown that physical dependence is not uncommon even after courses at moderate dosage. Counselling is as effective for moderate anxiety seen in general practice at 6 months' follow-up, and antidepressants are also effective and widely used for this. Effective hypnotic properties decline after 2-3 weeks. Thus the use of these drugs should be short term only. Unwanted effects 1. Addictive potential. Physical and psychological dependence occurs, especially with potent short-acting drugs like lorazepam. Withdrawal
Pharmacological treatments in psychiatry
2.
3. 4. 5. 6.
545
symptoms include anxiety, agitation, restlessness, insomnia, myalgia and convulsions. Psychotic episodes have been reported. CNS depression. An extension of the pharmacological effects (manifested by drowsiness and ataxia). In the elderly, confusion can occur. These drugs have a high margin of safety unless taken with other CNS depressants. Alcohol is potentiated. Increased aggressiveness. Paradoxical increase in hostility, irritability and anxiety may be noted (paradoxical disinhibition). Early development of tolerance to therapeutic effect. Teratogenic effects. Particularly cleft lip and cleft palate. Other side effects. Weight gain, menstrual irregularities, anovulatory cycles and skin rashes.
Table 29.4 gives a list of benzodiazepines.
Interactions Benzodiazepines enhance the sedative effects of other drugs, and this can potentially lead to respiratory arrest. Patients who abuse one sedative drug (e.g. opioids, alcohol, chlormethiazole) often use others, and these can interact with benzodiazepines. Rifampicin and cimetidine increase, and disulfiram can decrease, metabolism of these drugs.
Drugs used to treat dependence Benzodiazepines They reduce agitation, insomnia and the risk of fits or delirium during withdrawal of hypnotics or alcohol. For alcohol withdrawal, long-acting drugs are prescribed in reducing doses over about 10 days. Withdrawal of benzodiazepines in those dependent on prescribed drugs is usually by transferring from a short to an equivalent dose of a long-acting preparaTable 29.4. Benzodiazepines* Drug Long-acting: Diazepam Chlordiazepoxide Flurazepam Short acting: Lorazepam Loprazolam Temazepam Lormetazepam
Active half-life (h)
Active metabolites
10-200 8-2
+ +
8-20 6-12 2-18
'Several other benzodiazepines are on the NHS 'limited list'.
Main use Anxiety
Insomnia
+ + + + + + +
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tion (e.g. diazepam) and then negotiating a steady reduction. This is often over 4-6 weeks but can take several months or more. This strategy is more controversial for people solely dependent on illicit benzodiazepines and inpatient detoxification may be better. Carbamazepine has been used as an alternative to benzodiazepines during alcohol detoxification, and is used as an adjunct to benzodiazepines when risk of fits is high. Benzodiazepines also provide relief from nonspecific symptoms of opioid withdrawal, but care needs to be taken to avoid subsequent benzodiazepine dependence. Naltrexone This is a long-acting oral opioid antagonist. Once taken in the morning it will block the effects of opioids, so it can be used to deter impulsive return to opioid use in those abstaining. It produces a severe withdrawal syndrome in actively-using dependent patients and should not be started until patients have abstained for 7-10 days, unless it is used as part of accelerated detoxification. In that case, alpha-2 noradrenergic agonists (clonidine or lofexidine) and possibly benzodiazepines are used to ameliorate symptoms. Naloxone is also used for rapid detoxification. Default rates from continuous use are high and supervised consumption has been described. Liver function needs monitoring during treatment. There is growing evidence that it may reduce craving for alcohol in the abstainant. Methadone This long-acting opioid agonist is used to replace illicit opioids. It may be used for detoxification by gradually reducing the dose over months at home. An alternative is to reduce the dose more rapidly, usually as an inpatient and with drugs to ameliorate withdrawal symptoms. Maintenance treatment can reduce the amount of illicit drug use and crime that opioid users indulge in. Programmes are effective, provided that the doses are adequate and they have the right conditions for treatment, support for users and monitoring of illicit drug use. Methadone can be abused itself and patients may exaggerate their illicit opioid use to get more. In that case there is a risk of fatal overdose, or if they use illicit opioids or hypnotics as well as methadone. Partial opioid agonists Buprenorphine is such an agent. The effects of partial agonists by definition have a lower ceiling than full agonists, so they have theoretical advantages over full agonists as replacement therapy. However, buprenorphine is still abused, and is not widely prescribed as replacement therapy.
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Disulfiram The first product in the oxidative metabolism of alcohol is acetaldehyde. Disulfiram blocks its oxidation, and causes it to accumulate to toxic levels. This produces nausea, headache and flushing, and in patients with ischaemic heart disease may cause arrhythmias. Taken daily, sometimes supervised, this can deter abstaining alcohol-dependent patients from impulsive use. Because it is an irreversible enzyme inhibitor it is ineffective below a threshold dose, but if effective continues to act until a significant proportion of the enzyme has 'turned over' after about 2 weeks. Other side effects are metallic taste, impotence and confusion (even without alcohol). Citrated calcium carbimide is similar but less toxic. Acamprosate This acts on the GABA (gamma-aminobutyric acid) and glutamatergic systems, and there is evidence that it reduces craving and return to drinking in alcohol-dependent patients. It is effective even after lapses into drinking, and is usually prescribed for at least a year after detoxification. Antidepressants SSRIs such as citalopram may reduce craving and return to use of alcohol in dependent patients for a few weeks after detoxification, but there is some evidence against a long-term effect. SSRIs, and more commonly noradrenergic drugs like desipramine, have been used in the withdrawal of sympathomimetic drugs of abuse. Evidence of benefit to patients without depression is still lacking.
Other drugs Beta-blockers Propranolol blocks autonomic symptoms of anxiety where these predominate. It is of little use in anxiety without these features. It is effective in akathisia. It is contraindicated in cardiac failure and asthma. Hypnotics Chloral hydrate, dichlophenezone and chlormethiazole can be useful in the elderly. Barbiturates were once widely used for their anxiolytic and sedative effects. They are now rarely used, for short-term sedation of seriously disturbed behaviour. All these drugs can produce tolerance and dependence, particularly chlormethiazole and the barbiturates. The
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barbiturates are particularly toxic in overdose, and produce a dangerous withdrawal syndrome. Zopiclone and zolpidem are short-acting non-benzodiazepine hypnotics which act on the GABA (gamma-aminobutyric acid) receptor. They should only be prescribed for short periods: their abuse and dependence potential is unclear. Stimulants
Main indications 1. Hyperkinetic syndrome of childhood: methylphenidate is paradoxically effective in severe cases, improving attention, cognition and behaviour. 2. Narcolepsy: modafinil and dexamphetamine. Appetite suppression is no longer an indication.
Adverse effects Stimulants should be prescribed with great caution, because they cause tolerance and dependency and are popular drugs of abuse. Arrhythmias and paranoid psychosis can also occur. Cyproterone and other anti-libido agents Used to control severe deviant male hypersexuality, cyproterone blocks androgen receptors and inhibits testosterone production. Unwanted effects include weight gain, gynaecomastia, reversible reduction in spermatogenesis, infertility, depressed mood and hepatocellular jaundice (usually at higher doses used in prostatic cancer). Also used for the same purpose are progestogens, oestrogens (which have similar antiandrogenic side effects) and benperidol, which has a weaker effect. Drugs for dementia Enhancement of the cholinergic system can temporarily counter the degradation caused by Alzheimer's disease. Donepezil is a largely irreversible acetylcholinesterase inhibitor. It can temporarily increase cognitive function in 50 per cent of patients and can delay progression of cognitive decline in mild to moderate Alzheimer's disease when taken over 6 months to 2 years. Longer term outcome, effect on the activities of daily life and social function is uncertain. In trials it has few side effects at lower doses and mainly causes constipation and nausea, though it also has potential cardiac and urological side effects.
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Reading list Bazire, S. (2000) Psychotropic Drug Directory. Dinton, Wilts: Mark Allen Publishing. BMA (2000) British National Formulary, No. 40 (September). London: British Medical Association/Royal Pharmaceutical Society of Great Britain. Royal College of Psychiatrists (1993) Consensus Statement: The Use of High Dose Antipsychotic Medication. Council Report CR26. London: Royal College of Psychiatrists. Cochrane collaboration reviews are available on many of the drug treatments reviewed. They are regularly updated.
30
Physical methods of treatment PAUL COTTER and MICHAEL PHILPOT
Electroconvulsive therapy History Several physicians, including Auenbrugger who was famed for introducing percussion into the physical examination, prescribed large doses of camphor, producing convulsions, as a specific treatment for insanity in the eighteenth century. During the 1930s Meduna used metrazol to produce convulsions. In 1938, Cerletti and Bini devised the first electroshock box and used it to treat schizophrenia. The rationale for its use was based on the erroneous belief that schizophrenia and epilepsy were biologically antagonistic. Since the late 1940s convulsions have been modified by the use of general anaesthetics and muscle relaxants. Originally used for a broad range of psychiatric disorders (up to 30 per cent of patients entering hospital), the number of patients receiving ECT has fallen dramatically over the last 30 years. Its use is virtually outlawed in certain parts of the world and it is of varying popularity among psychiatrists. Indications and efficacy
Depressive illness The main indication is for patients with severe depression who have not responded to treatment with antidepressant drugs or who are sensitive to adverse effects of medication. ECT is used as a first-line treatment in severely depressed patients at serious risk from suicide, dehydration or malnourishment, as it appears to act more rapidly than pharmacotherapy. Double blind trials of real vs. sham treatment (in combination with antidepressive medication) carried out in the UK in the 1970s and 1980s
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demonstrated the superiority of real ECT in depression. However, the outcome at follow-up was similar to patients treated with medication alone. Direct comparisons between the effectiveness of ECT and medication have rarely been carried out. ECT may act more rapidly than tricyclic antidepressants and response rates are higher. Several attempts have been made to predict successful response to ECT using quantitative methods. These include the Newcastle scale and the CORE system. These scales and other studies indicate that patients with psychomotor retardation and those experiencing delusions or hallucinations respond better. ECT may be more effective in elderly depressed patients. Although a good initial outcome (70-85 per cent) is reported in most studies, the relapse rate is high (up to 50 per cent over 3 years) despite the use of continuation or maintenance antidepressive medication.
Schizophrenia ECT may be of use in catatonic or stuporose states, or patients with affective symptoms. It is less effective than antipsychotics but may have some value as an adjunct to medication. In any case, the benefits are short-lived.
Mania Since the introduction of effective antimanic drugs, ECT is rarely used but has a possible role in resistant mania. High success rates are reported but no randomized controlled trials have been carried out.
Depression and dementia The combination of these disorders is a frequent clinical presentation in the elderly. It is often difficult to determine whether cognitively impaired depressed patients have a 'true' underlying dementia or 'pseudodementia' and it is often more appropriate to treat rather than withhold a potentially valuable treatment. Depressive symptoms in demented patients are reduced in about fifty per cent of cases. Post-ictal confusion is likely to be a problem and the cognitive state should be carefully monitored in between treatments. The course should be terminated if cognitive impairment worsens.
Neuropsychiatric disorders ECT has recently been used in a range of neurological disorders including Parkinson's disease (with or without depressive symptoms), tardive dyskinesia, neuroleptic malignant syndrome and chronic pain. Randomized controlled trials in these conditions have not yet been published.
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Special considerations
ECT in pregnancy and the puerperium ECT is safe in pregnancy, although little is known about its effects on the fetus in the first trimester. Joint management with the obstetrician is recommended. Most postpartum psychoses are affective in nature and ECT can therefore be therapeutic in those who have failed to respond to conventional pharmacotherapy.
ECT and the elderly depressed Indications are as for younger patients. ECT may be safer than tricyclic antidepressants in patients with cardiac abnormalities and life-saving in those with severe illness complicated by dehydration and cachexia. The recovery phase is prolonged after bilateral administration. Memory loss and other cognitive difficulties are minimized with the use of unilateral electrode placement. Contraindications to use There are no absolute contraindications to ECT, although extreme caution must be used in patients with raised intracranial pressure. The risks of ECT must be balanced against the risks of the psychiatric illness. Caution should be exercised in patients with a history of: recent myocardial infarct, or arrhythmias; cerebral infarction or aneurysm; brain tumour; acute or chronic respiratory disease; acute closed-angle glaucoma. Administration The Royal College of Psychiatrists has produced guidelines on good practice in the administration of ECT. Ideally, a suite of at least three rooms should be available for waiting, treatment (with resuscitation equipment) and recovery. The waiting patient should not see the treated patient. Staff should consist of an anaesthetist, a psychiatrist and 1-3 nurses (at least one with experience of ECT). Patients should be accompanied to the treatment room, preferably by a nurse familiar to them. In addition to equipment required to deliver a general anaesthetic and assist recovery and, if necessary, resuscitation, treatment rooms should be equipped with a functioning ECT machine and back-up, and devices for monitoring BP and pulse, ECG and peripheral oxygen saturation. Modern ECT machines incorporate EEG and EMG monitoring.
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Preparation • Written informed consent (see later section on legal requirements). • Medical history and physical examination to assess cardiovascular, respiratory and dental status, allergy and previous anaesthetic response. • Full blood count; sickle cell test, urea and electrolytes, glucose, chest X-ray and EGG if clinically indicated. • Assessment of handedness, if unilateral ECT is to be given. • Concurrent medication should be checked. The patient should be withdrawn from drugs which affect seizure threshold and duration, e.g. long-acting benzodiazepines, anticonvulsants and lithium carbonate. • Nil by mouth for at least 6 h before treatment. • Mild tranquillization may be given 1-2 h before treatment to highly anxious patients.
Anaesthetic Induction is with a short-acting intravenous anaesthetic (e.g. methohexitone or thiopentone). A muscle relaxant (suxamethonium) is also administered. The patient is ventilated with oxygen. This prevents hypoxia during treatment, but also lowers the seizure threshold and may prolong the seizure. A mouth gag is inserted.
Application Electrode placement For bilateral ECT the bifrontotemporal position is now standard. Bitemporal and anterior bifrontal positions have also been evaluated. Electrodes are placed 3-4 cm above the midpoint of an imaginary line joining the external auditory meatus and the outer angle of the eye. For uniateral ECT the d'Elia position has become standard: the first electrode is placed in the same position as for bilateral ECT on the nondominant side, and the second is placed near the vertex on the same side of the head, 1-2 cm from the midline.
Application Electrical stimulus ECT machines delivering constant-current brief-pulse stimulus with the capacity to give a wide 'dose' range are now favoured. The 'dose' of electrical charge delivered depends on a number of electrical features of the stimulus waveform and the ECT machine used. Modern machines determine the impedance of the electrode-patient circuit prior to the delivery of the charge and alter the voltage output accordingly.
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Application Stimulus dosing The electrical charge required to induce a generalized seizure can vary greatly (between about 25 and 800 mC). Seizure threshold is greater in men, those with large or bald heads, increases with age and depends on concomitant medication as mentioned above. However, ECT given at or just above the seizure threshold is known to be therapeutically ineffective. The optimum effects are obtained if the applied dose is 2.5 times the threshold for bilateral electrode placement or 5 times the threshold for unilateral placement. The degree of post-ictal cognitive impairment is related to the 'excess' dose of electrical charge used. It is therefore appropriate to determine the patient's seizure threshold on an individual basis. There are a number of protocols in use for determining this which depend on the ECT machine used, but the essential principle involves beginning treatment with the lowest possible dose setting and gradually increasing this at each successive attempt to induce a seizure. Once the threshold is determined, the course may proceed using the dose adjusted accordingly. Other methods of stimulus dosing depend on algorithms based on the patient's age (which correlates positively with seizure threshold). As seizure threshold rises during a course of ECT, the stimulus dose may also need increasing.
Seizure monitoring It is essential to ensure that a bilateral convulsion of at least 25s has occurred. It is important to avoid brief, partial or missed seizures as they are not only untherapeutic but may be physically deleterious. Stimulation should be repeated after 90s if seizures are less than 15s. Re-stimulation policies will vary locally. The Hamilton cuff method may be used to determine whether a convulsion has occurred. A BP cuff is inflated on an arm (ipsilateral in unilateral ECT) to well above systolic pressure after anaesthetic but before muscle relaxant.
Recovery The patient is reoxygenated and the mouth gag removed. After spontaneous respiration is re-established, the patient is nursed in the recovery position. Close observation of pulse, BP and respiration rate should be made until stable. It is important to give reassurance while the patient regains consciousness.
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Number and frequency of treatments There is no set 'course' of ECT. Most patients will respond to between 6 and 10 treatments. Twice-weekly administration should be given, with regular assessments of the patient's response. If response to unilateral ECT is poor, bilateral ECT should be used. If there is no improvement after 12 ECTs, alternative therapies should be considered. Continuation and maintenance ECT Some patients prone to early relapse of depression after ECT benefit from continuation and/or maintenance therapy. It may also be indicated in those who are intolerant or resistant to maintenance medication. Regimens of treatment vary from weekly to monthly administration. In some studies, relapse rates a year after initial recovery have been halved in those receiving maintenance ECT. Physiological concomitants of ECT
Cardiovascular Transient asystole occurs during the passage of the electrical current. This is followed, during the tonic phase, by bradycardia and a brief fall in blood pressure due to vagal stimulation. During the clonic phase, there is a tachycardia and a rapid rise in blood pressure due to the release of catecholamines. Transient cardiac arrhythmias occasionally occur. There is no correlation between the degree of memory impairment and the magnitude of the rise in blood pressure.
Neurophysiological A typical EEC shows initial low-amplitude fast activity. This is followed by high-frequency polyspike activity, concurrent with the tonic and early clonic phase, then slower spike and wave complexes. Termination of the seizure is characterized by a relative flattening of the trace, due to post-ictal cortical EEG suppression. The normal pattern gradually returns to within 30 min. There is a transient 2-3-fold increase in cerebral blood flow and blood-brain barrier permeability, increase in glucose and oxygen metabolism, and a decreased amount of REM sleep. Over a course of ECT, the inter-ictal EEG shows a short-term increase in slow-wave activity, particularly in the frontal regions.
Neurochemical There is a decrease in cerebrospinal fluid and plasma calcium, suggesting intracellular calcium transfer, and an increase in dopamine and 5-HT turnover.
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In animal studies, there is increased 5-HT, dopamine and noradrenaline receptor sensitivity, and reduced beta-adrenergic receptor sensitivity. Although animal studies have shown increased S-HT2 receptors and decreased S-HTj receptors after ECT, the net effect on 5-HT neurotransmission is probably negligible in humans. Animal and human studies have shown downregulation of the hypothalamic a2-adrenergic receptor sensitivity. There are increased acetylcholine levels in the brain and cerebrospinal fluid, and increased cholinesterase activity in CSF and blood. Neuroendocrinological Numerous neuroendocrine changes have been described following ECT, possibly due to central and peripheral neurotransmitter systems stimulating or inhabiting the activity of the hypothalamic-pituitary axis:
• ACTH and prolactin levels are immediately and greatly increased and remain so for several hours. • Increased vasopressin, oxytocin, /?-endorphin, TRH and cortisol. • No real change in growth hormone, TSH or sex hormones. • Transient increase in blood glucose, sodium, potassium, calcium, chloride, neutrophils and lymphocytes. Morbidity and mortality
Early Headache and confusion are common but short-lived. Retrograde amnesia and difficulty in learning new material are of brief duration. These problems are associated with bilateral ECT and increasing number and frequency of treatments, but not with the magnitude or waveform of the electrical stimulus. Rare complications include precipitation of mania in bipolar patients, prolonged seizures or spontaneous grand mal fits, fractures, dislocations and fat embolism. Patients may become increasingly anxious about receiving the treatment; many dislike the sensation of general anaesthesia. This can be minimized by counselling prior to treatment and support and reassurance during and after treatment.
Late Most studies have been unable to demonstrate any degree of objective memory impairment even though subjective complaints are common. These complaints may be related to persistent depression or the use of psychotropic drugs.
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There is no clear evidence that ECT causes alterations to brain structure. The mortality from ECT is approximately 2 deaths per 100000 treatments, mainly from anaesthetic complications. Legal requirements for administration In England and Wales, ECT is specified under section 58 of the Mental Health Act 1983 as a treatment requiring valid (real) informed consent or a second opinion from the Mental Health Act Commission (MHAC). It can also be given as an emergency treatment under common law (section 62). Different laws and regulations govern the administration of ECT in other countries. For valid consent, the patient must be able to give voluntary and continuing permission for treatment with an adequate understanding of the purpose, nature, likely effects and risks of the treatment, including the likelihood of its success and any alternatives to it, as well as the likely consequences of not receiving it. If these conditions are satisfied, the patient should sign a consent form, co-signed by the patient's doctor. Patients should be informed that consent to treatment may be withdrawn at any time. If a detained patient consents to ECT, the responsible medical officer (RMO) or the second opinion appointed doctor should complete Form 38, which records the proposed maximum number of treatments. If the patient does not consent or cannot give valid consent, a second opinion doctor is required to consult with the RMO, a qualified nurse involved in managing the patient, and one other professional concerned with the patient's care. They then certify in writing (using Form 39) that the patient does not give consent, or is unable to give it, and that the treatment should be given in the patient's best interests, again stating the proposed maximum number of treatments. In some circumstances, the need for ECT treatment may be so urgent as to be considered life-threatening should there be any delay. Under common law (section 62), ECT can then be administered as an emergency procedure. This decision is the responsibility of the RMO, who should discuss this decision with others involved with the care. The MHAC should be informed of this so that arrangements can be made for a second opinion as soon as possible.
Psychosurgery There are no standard clinical protocols to follow before psychosurgery is considered, nor are there universally accepted assessment schedules or surgical procedures. Furthermore, no randomized controlled trials or good case-controlled series with patients matched for severity, chronicity
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or prior treatment have been carried out. Evidence of the efficacy comes from strong clinical opinion, case reports and open series. History 1891 Burckhardt obtained disappointing results after cutting frontal connections in severely disturbed schizophrenics. Control of impulsivity and excitement had been noted in monkeys after this procedure. 1936 Moniz first suggested the use of localized frontal lesions in patients with chronic psychiatric disorders. Together with Lima, about 100 leucotomies were subsequently carried out, at first by injection of alcohol, then by the use of a leucotome which cut the white matter of the frontal lobe. Patients with schizophrenia were little improved, while the best results were in those with affective disorders. 1942 Freeman and Watts developed the standard prefrental leucotomy which became extensively used. Small coronal incisions in the frontal lobe were made by a double-edged blade inserted into the brain via the orbit. Serious side effects were common, including epilepsy, incontinence, obesity, aggression, apathy, disinhibition and intellectual impairment. 1942-54 Over 10 000 operations were performed in the UK during this period, 75 per cent of which were standard leucotomies. Twothirds of the patients had schizophrenia and about a quarter had affective disorder. Improvements were claimed in 63 per cent of those with affective disorder and in 30 per cent of schizophrenics. Epilepsy developed in 1.3 per cent, and the illness was made worse in 2 per cent. Mortality from the procedure was 4 per cent. 1949 Scoville introduced the technique of orbital undercutting. 1965 Knight further modified this technique and described the first use of stereotactic subcaudate tractotomy. This procedure has been refined over the years and now uses yttrium rods implanted into the orbitomedial quadrants of the frontal lobes. 1973 Kelly developed stereotactic limbic leucotomy which involves cryogenic (freezing) or electrocoagulation induction of lesions in the cingulum and ventromedial quadrant. Other stereotactic procedures used in psychosurgery include cingulotomy and capsulotomy which involve radiofrequency heating (thermolesions) of target areas in, respectively, the cingulate bundle on both sides and the anterior capsular radiation. Current use Psychosurgery is currently carried out in 7 centres in the UK. In the years 1980-96, a total of 438 operations were performed in England
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and Wales. Most of these (about 320) were performed at the Geoffrey Knight Unit for Affective Disorders (formerly at the Brook Hospital). In the UK, most psychosurgery is carried out for severe treatment-resistant depression, while a minority are for severe obsessive-compulsive disorder (OCD). The most common procedure now in use is the stereotactic subcaudate tractotomy. In this procedure, an incision is made in the frontal bone above the air sinuses, and yttrium rods are inserted via burr-holes under the caudate nucleus. These rods emit beta-radiation and induce a lesion in an area 2 mm around the rod. Outside the UK, where cingulotomy or capsulotomy are preferred procedures, severe anxiety disorders and OCD are the main indications for psychosurgery. Indications for psychosurgery
Depression Severe, recurrent or intractable illness which has failed to have a sustained response to other treatments. Good prognostic factors are onset after age 40 years, a past history of good response to ECT and the presence of an undisturbed personality between episode of depression.
Obsessional neurosis and chronic anxiety Severe intractable illness, with or without depression, after failure of other treatments due to lack of efficacy or intolerable side effects. Contraindications to psychosurgery Patients with diffuse brain damage (including dementia), pronounced hysterical or antisocial personalities, or those prone to addictions, respond unfavourably to psychosurgery. Advanced age and concurrent medical disorders are not contraindications in themselves, but physical status must be optimized. Adverse effects Early complications include cognitive impairments such as confusion and memory disturbance which may last for up to 1 month. This is probably due to local postoperative oedema. Major complications include epilepsy in about 2 per cent and disinhibition or apathy in about 6 per cent. Mortality is now effectively zero with stereotactic procedures. Legal requirements for psychosurgery Psychosurgery is specified under section 57 of the Mental Health Act 1983 as a treatment requiring both informed consent and a second opinion. Three Mental Health Commissioners (one of whom is a doctor)
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have to certify that the patient is able to give consent. Should consent be withdrawn, treatment must not be given.
Other physical treatments Transcranial magnetic stimulation (IMS) was originally used as a method of stimulating motor or sensory areas of the brain for investigative purposes. Since the early 1990s rapid IMS - i.e. the application of an intense, pulsating magnetic field to areas of the prefrontal cortex - has been employed as an experimental treatment for medication-resistant depression. The mode of action is not known, but short periods of stimulation each day for 5 days has been shown to bring about substantial but transient elevation of mood. Research continues to determine the optimum treatment protocol. The surgical implantation of hormones to control male sexuality is also subject to controls under section 57 of the Mental Health Act 1983. This provision is rarely used. The implantation of cerebellar stimulators has been employed in small numbers of schizophrenics but has been poorly studied. The implantation of fetal neural cells into the substantia nigra or the nucleus basalis to replace dopamine or cholinergic deficits has been successful in experimentally lesioned animals and may eventually lead to surgical treatment for Parkinson's or Alzheimer's' disease, respectively. Early reports of Parkinson's disease treated in this way have proved encouraging.
Reading list Abrams, R. (1997) Electroconvulsive Therapy, 3rd edn. New York: Oxford University Press. Bridges, P.K. et al. (1994) Psychosurgery: stereotactic subcaudate tractotomy, an indispensable treatment. British Journal of Psychiatry, 165, 599-611. Department of Health and Welsh Office (1999) Code of Practice. London: The Stationary Office. Devanand, D.P. et al. (1994) Does ECT alter brain structure? American Journal of Psychiatry, 151, 957-70. Freeman, C. (1997) Neurosurgery for mental disorder in the UK. Psychiatric Bulletin, 21, 67-9. Hickie, I. et al. (1996) Prediction of ECT response: validation of a refined signbased (CORE) system for defining melancholia. British Journal of Psychiatry, 169, 68-74. Klein, E. et al. (1999) Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression. Archives of General Psychiatry, 56, 315-20. Philpot, M. (1999) Advances in electroconvulsive therapy in the elderly. In:
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Everything You Need to Know About Old Age Psychiatry (ed. R. Howard). Petersfield: Wrightson Biomedical Publishing Ltd. Royal College of Psychiatrists (1995) The ECT Handbook. London: Royal College of Psychiatrists. Sackeim, H.A. et al. (1993) Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. New England Journal of Medicine, 328, 839-46. Tharyan, P. and Seifas, R. (1997) Electroconvulsive therapy for schizophrenia. In Schizophrenia Module of the Cochrane Database of Systematic Reviews (eds C. Adams et al.). Oxford: The Cochrane Collaboration.
Appendix
The MRCPsych examination TIM AMOS and HELEN BARKER
The form of the examination Part 1 The Part 1 examination consists of one multiple-choice question (MCQ) paper and a clinical examination for candidates who pass the MCQ. The MCQ is currently made up of 50 five-part questions to be answered in11/2hours. Each begins with a stem statement or question followed by five subsidiary statements or answers. The style of the MCQ is changing to single item questions. You must indicate whether each of these is true or false by filling in the appropriate space on a separate computer sheet. You will be sent instructions and samples showing how to complete the sheet, which you should read carefully in preparation. In the clinical examination you will interview a patient in 60 minutes before presenting your assessment to two examiners. This lasts 30 minutes, divided evenly into case presentation, patient interview and further questions. The clinical examination is due to be replaced by an Observed Standardised Clinical Examination (OSCE). Part 2 The Part 2 examination consists of two MCQ papers (sciences basic to psychiatry and clinical topics); one essay; one critical review paper; a clinical examination consisting of an Individual Patient Assessment (IPA) and Patient Management Problems (PMPs). As in Part 1, each MCQ paper contains 50 five-part questions, to be answered in 1^ hours. In the essay paper, also lasting11/2hours, you will choose two questions, one each from a pair of questions. You will therefore have to answer one general adult psychiatry question out of two and one 'subspeciality' question out of two questions from different
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subspecialities. The critical review paper consists of an article, or extract thereof, followed by several questions relating to the article. The Individual Patient Assessment allows 1 hour with the patient and 30 minutes with the examiners for case presentation, patient interview and further questions. The usual sequence is: • case presentation including questions (10 minutes); • patient interview (5 minutes); • management, prognosis, further questions (15 minutes). In the 30-minute oral examination, emphasis is on patient management problems (PMPs), i.e. fictitious cases. There are usually four PMPs, although currently individual examiners do vary from this format. In the future the PMPs will become more structured and standardised.
The content of the examinations Parti The examinable subjects are: • psychopathology (descriptive and psychoanalytic); • clinical assessment; • psychopharmacology (including pharmacokinetics and pharmacodynamics); • psychology and human development (including basic psychology, social psychology, neuropsychology). The clinical examination tests basic clinical skills and knowledge. The clinical case is an adult not requiring an informant and may come from the areas of general adult psychiatry, old-age psychiatry, liaison psychiatry or alcohol/drug misuse psychiatry. You are marked on your history and mental state assessment, your patient interview and your ability to relate to the patient, integrate your information into an overall assessment and answer questions. No plan of management is needed, although you should know previous and current treatment and how to investigate the case. Part 2 The examinable subjects are: everything in Part 1; neuroanatomy; neurophysiology; neurochemistry; neuropathology; genetics;
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• social sciences - including social and transcultural psychiatry; • epidemiology; • statistics and research (called principles of evaluation and psychometrics in the curriculum); • medical ethics, principles of law and history of psychiatry. The clinical examination tests clinical skills, knowledge and attitude. All clinical psychiatry is examinable, including old-age psychiatry, substance misuse, liaison psychiatry, psychotherapy, child and adolescent psychiatry, mental handicap and forensic psychiatry. The clinical case will be aged over 17 years and an informant may be present. Marks are given for your case assessment, management plan, comments on prognosis, patient interview and your ability to integrate information and answer questions.
Marking The MCQ papers are marked with + 1 for a correct answer and zero (0) for a wrong answer or for any question left blank. Negative marking, i.e. — 1 for an incorrect answer, has been discontinued for both Part 1 and Part 2 MCQ papers. For written papers, examiners are given guidelines on required answers but ultimately use their own judgement. For the clinical examination in both parts, the examiners agree a mark on a closed marking scale (0-10) on the individual sections and then an overall mark. If examiners disagree they explain their disagreement to the College whose examination subcommittee makes a final judgement. In Part 2 you must pass the clinical, but failure in other papers can be balanced by a good performance elsewhere. The clinical examination in Part 2 refers to the clinical case (IPA) and oral examination (PMPs) combined, so it is possible to fail one of these parts and pass overall. The marks from the written papers and clinical examination are combined to give an overall grade. Comparison is made with other candidates (peer reference) before the final grade is awarded. There is no fixed percentage pass rate and pass rates do vary, but in general the pass rate for both examinations is approximately 50 per cent.
Preparation You will need to decide when you are going to sit the examination, whether Part 1 or 2, at least 6 months in advance and preferably further ahead than that. Both parts are held each spring and autumn. The first task is to write to the College and ask for an examinations timetable and general information about the examination including the curricula. You will be informed about the practicalities of the examina-
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tion and also importantly what experience and qualifications you require to sit Part 1 or Part 2. Many candidates ask for various postgraduate experiences to be taken into account and the College examinations department may take some time to confirm a candidate's eligibility. The examinations timetable not only gives you the dates of the papers and clinicals but also the times when you can request an application form and return date. These dates are rarely more than 6 weeks apart, so you need to be well organised. Once you have decided on the date of your sitting of the examination, you need to plan your revision. Initially you need to decide for how long you are intending to revise. College tutors recommend a continual learning process during all posts. Most candidates tend to revise more intensively towards the time of the examination. Planning is very important and timetables are useful aids but should not become the focus of despair and multiple time-consuming rewriting. Some people like to revise alone, others in a small study group. The latter offers the benefits of moral support, some yardstick of the level of other people's knowledge and a way of reinforcing any learning you have done by yourself. The process of revision for most people includes reading major text book(s), looking at recent journals/review articles, being guided by past example questions from the College and other sources, and practising MCQs and essays. Textbooks generally either cover the whole of psychiatry in a single volume or cover specific areas, e.g. basic sciences, clinical specialities. The College publish a series of books entitled 'Seminars in ' covering most of the major areas. These are generally written by leading experts but are of variable standard and not always as examination orientated as candidates might like. There are many MCQ books which may help, but beware of assuming that all answers are correct. The British Journal of Psychiatry is recommended by many candidates as it appears that some examiners, especially those setting the essays, use it at times to guide their questions. The Psychiatric Bulletin is generally worth glancing at, not least because it informs candidates of general policy issues as well as changes to the examination. Other journals to consider are Advances in Psychiatric Treatment, Psychological Medicine, British Medical Journal, Lancet, Current Opinion in Psychiatry, Medicine and the British Journal of Hospital Medicine. Quoting 'classic' articles can look impressive but should be seen as icing rather than substance. Other useful written material includes the two curricula (basic sciences and clinical) from the College, College guidelines (e.g. on high-dose antipsychotics, benzodiazepines), a copy of ICD-10 (DSM-IV) as appropriate, College sample MCQ/past essay/critical appraisal papers, and unofficial banks of MCQs, e.g. remembered by candidates. Further sources of information are your local MRCPsych course,
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though not all courses are examination orientated, and revision courses which are worth considering. There are several to choose from - they can vary from a day or weekend to a week's residential course. Talk to recent candidates (both successful and unsuccessful) and find out about their experiences. On top of learning all the material you have collected, preparation for the individual papers is important. For the MCQ paper, practise as many as you can from sources such as books, banks of questions, and computerized questions (available from some drug companies). Prepare 10-20 outlines for the essay paper covering a range of topics, mainly to check your knowledge and technique. Write a couple of essays, in full, under examination conditions as you will probably not have written essays for several years. You could also try to spot possible topics. It is important that, while doing all the above which is mainly for the written papers, your preparation for the clinical must continue at the same time. The most important element is ongoing practice. Continually presenting cases makes it routine, as in driving a car, and can take place during ward rounds, to seniors or peers and at times to consultants whom you do not know, especially if they are College examiners. This process will help both with the long case/individual patient assessment and the patient management problems (PMPs). It is worth practising the PMPs with peers or consultants as they do require a different technique. You can increase your readiness for the individual patient assessment because in general you know what you are going to be asked. Many candidates therefore prepare answers to the standard questions for all the main diagnoses. These include, for both parts, possible differential diagnoses, aetiology and investigations. Aetiology can be considered under three main headings - biological (physical), psychological and social - with factors in the areas of predisposing, precipitation and maintaining. A three-by-three grid (three headings by three areas) on all diagnostic categories is a useful aide-memoire. Categories of investigations are similar for most cases, e.g. further information, nursing observations and physical investigations. The last in particular should be justified in helping to confirm the diagnosis. For those taking Part 2, overall management plans can be arranged into immediate, mediumand long-term plans and also be devised in advance for the major diagnostic groups. Similarly the prognosis for all diagnoses can be considered during preparation. As the time of the examinations draws near, do not panic and try to keep working steadily. Even prizewinners cannot be certain they will pass. Mental preparation is very important. Think about practicalities, e.g. logistics of where to stay/how to travel; what to wear (answer: dark suit for both sexes!). On the day of the examinations, focus on the examination you are
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doing. On the day of the written examinations, disregard other candidates' comments on the papers, as people are often poor at assessing their own performance. At the clinicals, ignore other candidates, try to relax, get used to waiting, and be in a suitable frame of mind.
Examination technique The way you present yourself and your knowledge in an examination can be as important as the knowledge itself. MCQ paper Read the questions carefully and deliberately. There is enough time to answer every question. Begin by going through the paper answering all the questions where you feel certain. This will give you an encouraging start. You then need to go through the paper once or twice more, answering all the questions. You score + 1 for a correct answer and zero (0) for a wrong answer or for any question left blank. There is therefore no reason not to answer all the questions even where you have no idea of the answer as, by chance, you will make some correct guesses and increase your mark overall. As negative marking, i.e. — 1 for an incorrect answer, has been discontinued, you will not lose marks for those answers you get wrong. Some candidates choose to answer every question in order and you should have discovered during your revision the method you prefer. If you write your answers on the examination sheet before transcribing them onto the computer card, do this with great care. Check your paper for errors but try to resist the temptation to make last-minute changes. Make sure that you leave sufficient time at the end of the examination to fill in the answer paper. Ignore candidates who leave early. MCQ wording The answer may depend on the precise wording used in the question. You may know the factual information required to answer a question correctly but still get it wrong if you fail to spot certain key words. Table A.I gives definitions for some of the important key words found in MCQ stems. Beware the double negative and be cautious when the question includes words which are easily mistaken for other, similar words, e.g. tryptophan and tyramine, XYY and XXY. Written papers Remember that the examiner wants to find your main points quickly. Write neatly in paragraphs, underlining key words and headings. Use lists and large, neat, labelled diagrams. Use a precise academic style and
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MCQ key words
Word
Definition
can/may occur
These terms do not include an assumption of how frequently an event occurs. They imply a possibility of occurrence, however remote A characteristic feature is one which is expected to occur before the diagnosis can be made A term which implies that an event occurs frequently, i.e. more than 50 per cent of the time An essential feature is one that must be present for the diagnosis to be made A pathognomonic feature is one that occurs in a particular disorder and no other (and is diagnostic) A recognized feature is one that has been reported to occur in a disorder but it is not neccesary for this to be a common or typical feature A synonym for characteristic
characteristic commonly essential pathognomonic recognized typical
try to avoid repetition or subjective opinion. Allow time to plan your answer before writing, particularly in the essay paper. This will ensure that the answer is balanced and it prevents later panic. When planning, make sure that you have read the question carefully and that you are covering the different aspects appropriately and comprehensively. When a question has two parts to it, judge the importance of each, e.g. Define dementia (brief answer). What are the chief causes of dementia under 65 years? (main bulk of answer). Quote key research references if you are able and if this is appropriate. It is not essential to quote references to pass the written papers. Clinical examination In the opening moments of the individual patient assessment (IPA), remind the patient that you have limited time and you may need to interrupt. Help the patient to relax by adopting a friendly but professional manner and ensure that you are both comfortable. Spend a few minutes recording the information which will provide the basis of your assessment: name, age, job, social circumstances, inpatient or outpatient, time of first admission, number of admissions, doctor's diagnosis, current treatment. If there are any signs of cognitive disturbance, assess this fully before proceeding further. Allow 35-40 minutes for the interview, dividing the time between history and mental state examination. Examiners know that you cannot ask everything, so concentrate on the most important facts. A brief, relevant physical examination is essential in all cases but may need to be longer in cases of alcoholism, anorexia or dementia. Use the remaining time to prepare your presentation, keeping the
The MRCPsych Examination
569
patient present to allow you to clarify uncertainties. Try and think what aspects of the case the examiners will want to focus on and make sure that you have the details required to do this. Before meeting the examiners try to memorize and rehearse your opening statement. This will enable you to appear organized and in control of the situation. The examiners will be influenced by the 'right attitude', one of respectful confidence. Be enthusiastic and interested but avoid arrogance or arguments. Try to pick up the cues they might be giving you. Present the case to the examiners under the headings assessment, management and prognosis. You should have a detailed and structured presentation prepared but don't be put off if the examiners interrupt, ask questions or want you to skip parts of the presentation. They are feeling the same time pressure that you did with your patient. There is no College rule on the order of the history, so present it in your normal way, emphasizing important details and omitting most negative findings to make it clear where your assessment is leading. A full presenting complaint, including the precise reason for referral or admission, is vital. Withhold some of the less important details for use in later answers. A complete mental state examination should be given, including relevant negative findings. A good differential diagnosis will contain all the reasonable possibilities with pros and cons. Mention which is your preferred diagnosis if possible but if there is good reason for uncertainty, say so. Comment on the aetiology under the three main headings: biological, psychological and social. Identify the likely predisposing, precipitating and maintaining factors. An extensive management plan is necessary for Part 2 and can be divided into: 1. Investigations, including further information, physical investigations, nursing observations. 2. Biological interventions, usually treatment with drugs. 3. Psychological interventions, including supportive psychotherapy, marital and family work. 4. Social interventions, including housing, rehabilitation, occupational therapy. If appropriate, divide the management into immediate, short term and long term. Quote prognosis figures where possible and relate prognostic factors to your patient. Comment on the prognosis both for this episode and in the longer term. When interviewing patients in front of the examiners, be polite and sensitive. Do not lead the patient but keep control of the interview and do not let the patient ramble. Reassure the upset patient. If the patient brings up some new or contradictory information, don't panic and clarify the point. Examiners know that patients may alter their stories. For the Patient Management Problems (PMPs), the technique is
570
Postgraduate Psychiatry
essentially the same as in the IPA. Try to think broadly and safely. If you don't know something, say so. If you go blank or say something which you then realize is wrong, admit it. In both examinations, look for signs of good progress: nodding relaxed examiners, examiner's anecdotes, abrupt changes of subject when you are talking fluently.
Reading list Brown, T. and Wilkinson, G. (1998) Critical Reviews in Psychiatry. London: Royal College of Psychiatrists (Gaskell). Buckley, P., Bird, J. and Harrison, G. (1995) Examination Notes in Psychiatry, A Postgraduate Text. Oxford: Butterworth-Heinemann. Bhugra, D. and Potts, S. (1993) Case Presentations in Psychiatry. Oxford: Butterworth-Heinemannn. Cohen, R.I. and O'Halloran, A. (1989) MCQ Tutor: Psychiatry Today. Oxford: Butterworth-Heinemann. Cormac, I. and Marston, G. (1999) How to pass the MRCPsych examination. Psychiatric Bulletin, 23, 172-6. Green, B. (1993) The MRCPsych Study Manual. Lancaster: Kluwer Academic Publishers. Hawton, K. and Cowen, P. (1990) Dilemmas and Difficulties in the Management of Psychiatric Patients. Oxford: Oxford University Press. Holden, N.L. (1990) MRCPsych Parts One and Two: the clinical examinations. British Journal of Hospital Medicine, 43, 466-8. Howells, R. (1995) Multiple Choice Questions for the MRCPsych Part II Clinical Topics Examination. Oxford: Butterworth-Heinemann. The Institute of Psychiatry (1993) Psychiatric Examination: Notes on Eliciting and Recording Clinical Information on Psychiatric Patients. Oxford: Oxford University Press. Johnson, B.A. (1991) Solving Conundrums in Clinical Psychiatry. Lancaster: Kluwer Academic Publishers. Mindham, R. (1996) Preparing a trainee for the MRCPsych examinations. Advances in Psychiatric Treatment, 2, 265-70. Patel, A.G. (1994) The Complete MRCPsych Part II. London: W.B. Saunders. Williams, C, Trigwell, P. and Yeomans, D. (1995) Pass the MRCPsych Parts I and II. London: W.B. Saunders. Yatham, L.N. and Dinan, T.G. (1992) Basic and Clinical Multiple Choice Questions in Psychiatry. Oxford: CNS (Clinical Neuroscience) Publishers.
Index
Abnormal grief reactions, 189-90 Abnormal illness behaviour, 446 Absorption of drugs, 62 Acamprosate, 71, 328 in treatment of dependence, 546 Acceleration of thought, 11 Accessory nucleus, 94 Acetyl cholinesterase, 120 Acetylcholine, 67, 127-8 cholinergic drugs, 260 Acquired immunodeficiency syndrome, 117-18 Acquisition, 41 Actus rea, 484-5 Acute dystonia, 528 Acute organic psychosis, EEC in, 277 Acute stress reaction, 226 Acute toxic confusional state, 174 Addison's disease, 255 Adjustment disorders, 228-9 Adler, Alfred, 19, 512-13 Adolescence, psychiatric disorders of, 418-20 anorexia nervosa, 419 epidemiology, 397 psychoses, 418-19 self-harm, 406 suicide, 405-6 see also Children, psychiatric disorders of Adoption studies, 141-2 affective disorders, 197 Adrenocortical leucodystrophy, 239 Adrenocorticotrophic hormone, 360 Adverse effects, 65, 67-8, 69-70 see also Pharmacological treatment and individual drugs Affective disorders, 186-208 aetiology, 196-202
and alcohol misuse, 324-5 assessment for psychotherapy, 524 classification, 190-3 clinical features, 186-90 differential diagnosis, 193-6 EEC in, 279 epidemiology, 196 learning disability in, 432 management, 203-7 outcome and prognosis, 207 suicide risk, 351 and violent behaviour, 486 Affective psychosis, 272 Affinity of drugs, 66 African Caribbean community, psychiatric problems of, 472-3 Age and alcohol misuse, 314 and neurotic disorders, 212 and risk of self-harm, 353 and suicide risk, 348 see also Old age psychiatry Aggregate studies, 160 Aggression, 107-8 Agnosia, 35-6, 288 Agonists, 65 Agoraphobia, 219, 509 Agraphia, 106 AIDS, 117-18 AIDS dementia complex, 252-3 Akathisia, 528 Alcohol and criminal liability, 490 intoxication, 319-20 metabolic effects, 320 metabolism, 314 misuse see Alcoholism pregnancy and breastfeeding, 373 and sexual function, 386
572 Alcohol (continued) withdrawal, 4, 326-8 Alcohol dehydrogenase, 314 Alcoholic hallucinosis, 15, 324 Alcoholics Anonymous, 329, 523 Alcoholism, 313-30, 445-6 aetiology, 316-19 assessment for psychotherapy, 525 Cloniger subtypes, 317 definition, 313 EEC in, 281 epidemiology, 314-15 identification of cases, 315-16 neurobiology, 319 in old age, 298 pharmacotherapy, 328-9 physical problems, 319-24 post-detoxification, 328 prognosis, 330 psychological disorders, 324-6 psychological interventions, 329 service provision, 330 social damage, 326 see also Alcohol Alexia, 106 Alexithymia, 5, 6, 442 Alleles, 136 segregation, 137-8 Allocortex, 84 Alpha antichymotrypsin, 114 Aluminium hypothesis of Alzheimer's disease, 290 Alzheimer's disease, 113-14, 288-90 aetiology, 289-90 aluminium hypothesis, 290 aphasia in, 288 cholinergic hypothesis, 131-2 EEC in, 277 inheritance, 139 pathology, 289 see also Dementia Amantadine, 196 Ambitendency, 5 Amblyopia, 323 Amitriptyline, 74, 536, 537 Amnesia, 287-8, 490 Amnesic syndrome, 241-2 Amok, 475 Amphetamine, 196, 339 Amygdala, 84, 86, 108 Amyloid precursor protein, 113 Anankastic personality, 304 Angel dust, 342 Angiotensin-converting enzyme inhibitors, 64 Angular gyms syndrome, 234 Anhedonia, 5, 186
Index Animal studies genetics, 144 neurotransmitters, 119-23 Anorexia nervosa, 358-64 in adolescence, 419 aetiology, 359-61 assessment for psychotherapy, 525 classification, 358-9 clinical features, 361-2 epidemiology, 358 management, 362-4 medical complications, 362 prognosis, 364 see also Bulimia nervosa Anorgasmia, 389 Antabuse, 71, 328 Antagonists, 65 Anthropophobia, 475 Anti-epileptics see Anticonvulsants Anti-libido agents, 548 Antibiotics, 260-1 Anticholinergics, 534 Anticonvulsants, 78-80, 260, 274-5, 543 pregnancy and breastfeeding, 372 and sexual function, 386 see also individual drugs Antidepressants, 73, 77, 205, 534-6, 537 actions, 535 contraindications, 534 indications, 534 interactions, 535-6 monoamine oxidase inhibitors see Monoamine oxidase inhibitors pregnancy and breastfeeding, 372 and sexual function, 386 in treatment of dependence, 546 tricyclic see Tricyclic antidepressants unwanted effects, 535 see also individual drugs Antihypertensives, and sexual function, 386 Antineoplastic drugs, 260 Antipsychotics, 71-3, 527-33 actions, 528, 532-3 atypical, 532-3 classification of, 72-3 contraindications, 527-8, 532 depot preparations, 531-2 indications, 527 interactions, 530-1, 532 and sexual function, 386 unwanted effects, 528-30, 533 see also individual drugs Antisocial personality, 304 Anxiety, 6, 133, 210-11 and alcohol misuse, 325 assessment for psychotherapy, 524
Index in children, 404-5 differential diagnosis, 211 psychosurgery in, 559 treatment see Anxiolytics Anxiety neurosis, 193 Anxiolytics, 76 pregnancy and breastfeeding, 372 and sexual function, 386 see also individual drugs Anxious personality, 304 Apathy, 6 Aphasia, 288 expressive, 106 jargon, 107 motor, 106 nominal, 107 Appearance, 32-3 Apraxia, 97, 105, 288 constructional, 99 Arachnoid mater, 90 Arctic hysteria, 475 Area of residence, and mental health, 455 Argyll-Robertson pupil, 100, 251 Arousal, 181 Arson, 483 Asperger's syndrome, 414-15 Assertiveness training, 511 Association cortex, 84, 85 Association, measures of, 154-6 Association nuclei, 87 Astrocytes, 83-4 Asyndesis, 9 Athetosis, 4 Attachment, 399-400 failure of, 378 Attachment figures, 400 Attachment theory, 201 Attention, 34, 181 Attention deficit hyperactivity disorder, 397, 408-10 Attitudes, 51-2 Attributable risk, 154 AUDIT questionnaire, 315 Auditory evoked potential, 282 Auditory system, 100-2 Autism, 413-14 heritability of, 397 Autochthonous delusions, 7 Automatism, 489-90 Autonomic nervous system, 109-10 Autonomic responses, 49 Autopagnosia, 288 Autoradiography, 121 Autosomes, 136 Avoidance, 42 Avoidant personality, 304
573 Axon, 83 Azapirones, 217 Babinski's sign, 104 Balloon cells, 114 Barbiturates, 76, 79, 278 abuse, 343 Barr body, 136 Basal ganglia, 86, 104 Beck, Aaron, 510 Behaviour, 32-3 Behavioural family therapy, 521 Behavioural therapy, 309, 509-12 Belle indifference, 444 Bell's palsy, 94 Benign essential tremor, 265 Benzodiazepines, 76-7, 278, 544-5 abuse, 342-3 actions, 544 contraindications, 544 indications, 544 interactions, 545 neurotic disorders, 216 pregnancy and breastfeeding, 372 receptors, 133 in treatment of dependence, 545-6 unwanted effects, 544-5 see also individual drugs Bereavement, 193 Berne, Eric, 517 Beta-amyloid, 113 Beta-blockers, 260, 546 pregnancy and breastfeeding, 372 Bias, 156-7 Binomial distribution, 148 Binswanger's disease, 117, 234 see also Dementia Bioavailability of drugs, 62 Bipolar cells, 98 Blepharospasm, 264 Bleuler, Eugene, 9 Blood-brain barrier, 63, 83 Blunted affect, 6 Body mass index, 361 Bonding failure, 378 Borderline personality, 304 Bouffee delirante, 173 Boxing, and head injury, 246 Brain stem, 89 Breastfeeding, prescribing in, 69, 372-3 Brief focused psychodynamic therapy, 206 Brief therapies, 520 British Ability Scale, 427 British National Formulary, 69 Broca's area, 35, 105, 106 Brought-forward time, 202
574
Bulimia nervosa, 364-6 aetiology, 365-6 assessment for psychotherapy, 525 classification, 364, 365 clinical features, 364 co-morbidity, 365 epidemiology, 364 management, 366 prognosis, 366 see also Anorexia nervosa Buprenorphine, 337 in treatment of dependence, 546 Buspirone, 77 pregnancy and breastfeeding, 372 Butyrophenones, 73 CAGE questionnaire, 315 Cannabis, 343-4 pregnancy and breastfeeding, 373 urine screens, 334 Cannabis psychosis, 344 Cannon-Bard theory, 49 Capgras syndrome, 8, 12 Carbamazepine, 64, 78, 79, 204, 274, 542-3 Carbon monoxide poisoning, 117 Carcinoid syndrome, 258 Carcinoma, 258 Cardiac glycosides, 260 Cardiovascular system, alcohol effects on, 320 Care management, 465 Carotid arteries, 91 Case-control studies, 160-1 Casualty department, 447 Catalepsy, 5 Catatonia, 4-5, 169 in schizophrenia, 171 schnauzkrampf in, 4 Catecho-orthomethyl transferase, 120 Catharsis, 522 Cattell's theory, 47 Causal inference, 156-9 Causation, 157 Central limit theorem, 150 Central nervous system blood supply, 91-2 control of emotions, 107 infections, 117-18 EEC in, 278 venous drainage, 92 Central pontine myelinosis, 324 Centrum semiovale, 84 Cerebellar degeneration, 323 Cerebellum, 90, 104-5 Cerebral cortex, 84 Cerebral dominance, 105-6
Index Cerebral gumma, 251 Cerebral peduncles, 89 Cerebral trauma, 242-6 EEC in, 278-9 head injury, 242-5 Cerebral tumours, 253-4 Cerebrospinal fluid, 91, 122-3 Cerebrovascular disease, 116-17 Cerebrovascular disorder, 247-9 Chaining, 42 Challenging behaviour, 433 Chance, 156 Charles de Bonnet syndrome, 12 Charlie, 339-41 Chi square test, 152 Child abuse, 420-1 Children and criminal responsibility, 484 gender identity disorder, 394 killing of, 480 learning difficulties see Learning disability prescribing in, 69 psychiatric disorders of, 396-418 aetiology, 397-401 anxiety disorders, 404-5 attention deficity hyperactivity disorder, 408-10 conduct disorder, 407-8 depressive disorders, 402-3 developmental disorders, 411-15 disorders of elimination, 415-17 epidemiology, 397 and learning disabilities, 429-31 obsessive-compulsive disorder, 403-4 psychosomatic disorders, 417-18 school non-attendance, 405 suicide and deliberate self-harm, 405-6 tic disorders, 410-11 sexual abuse of, 390-1, 482 Children Act 1989, 421 Children's services, 429 Chinese community, psychiatric problems of, 473 Chlordiazepoxide, 327, 545 Chlorpromazine, 182, 531 Cholecystokinin, 129 Choline, 132 Choline acetyl transf erase, 120 Cholinergic drugs, 260 Chomsky, Naom, 59 Chorea, 4 Choroid plexuses, 91 Chromosomes, 136-7 abnormalities, 137
Index deletions, 137 translocation, 137 Chronic fatigue syndrome, 448-9 Chronic subdural haematoma, 249 Ciliary ganglion, 93 Cimetidine, and sexual function, 386 Cingulate cortex, 108 Circle of Willis, 92 Citalopram, 74 Clanging, 33 Classical conditioning, 40 Client-centred therapy, 517 Clinical assessment, 29-39 collateral history, 37 interviewing technique, 29 mental state examination, 32-6 physical examination and investigations, 36 psychiatric history, 30-2 risk evaluation, 37-9 Clinical case management, 465 Clinical trials, 135 Clonidine, 71 Clozapine, 73, 182, 533 adverse effects, 533 Cocaine, 339-41 Cochlea, 101 Coenestopathy, 13 Cognitive analytic therapy, 28, 516 Cognitive assessment, 285 Cognitive deficits, 244, 247, 273 children, 398 Cognitive development, 398 Cognitive dissonance, 51, 338 Cognitive family therapy, 521 Cognitive learning, 42 Cognitive psychotherapy, 309 Cognitive revolution, 508 Cognitive state, 34-5 Cognitive therapy, 509-12 affective disorders, 205-6 obsessive-compulsive disorder, 510-11 Cohesiveness, 522 Cohort/longitudinal studies, 161-2 Coke, 339-41 Coma, 34 Community Care Act 1990, 460-1 Community mental health team, 464 Community psychiatry, 458-63, 494 assertive community treatment, 466 care management, 465 clinical case management, 465 crisis houses, 467 crisis response teams, 466 definition, 458 development of, 458-9 guiding principles, 463
575 institutionalization, 459 needs assessment, 466 nursed care, 467 partial hospitalization, 466-7 rehabilitation, 465 sectorization, 466 UK policy, 459-63 care programme approach, 461 Community Care Act 1990, 460-1 Health of the Nation 1992, 461 Mental Health (Patients in the Community) Act 1995, 462 Supervised Discharge Orders, 462 Supervision Register 1994, 461-2 Compensation neurosis, 445 Compliance, 68 Compliance therapy, 517 Computed tomography, 36 Concentration, 34 Concrete thinking, 9 Conditioning, 59 Conduct disorder, 407-8 Conduction deafness, 101 Cones, 97 Confidence intervals, 150 Conformity, 53 Confounding, 158 adjustment for, 158-9 Consciousness, 34 delirium, 15 reduced, 14 restricted, 14-15 Consent to treatment, 500 Constructional apraxia, 99 Constructional dyspraxia, 36 Consultation model for hospital psychiatry, 437 Consultation-liaison, 437-8, 465 Contingency management, 512 Contingent negative variation, 281 Continuous positive airways pressure, 280 Conversational model, 27-8 Coping, 50-1 Coprolalia, 410 Copropraxia, 410 Core Conflictual Relationship Theme (CCRT) method, 25 Corpus callosum, 84 Corpus striatum, 86 Correlation, 155-6 Cortex, 84-5 Cortical relay nuclei, 87 Corticobulbar tracts, 89 Corticospinal tract, 89, 103 Corticotrophin-releasing hormone, 111 anorexia nervosa, 360
576 Cotard's syndrome, 187 Counselling, 508 Countertransference, 24, 514 Couple therapy, 387-8, 519-21 Court diversion schemes, 494-5 Court of Protection, 300, 503 Court reports, 490-1 Covert sensitization, 512 Crack cocaine, 340 Cranial nerve nuclei, 89 Cranial nerves, 92-5 abducens, 93 accessory, 94 facial, 93-4 glossopharyngeal, 94 hypoglossal, 94-5 oculomotor, 92-3 trigeminal, 93 trochlear, 93 vagus, 94 Creutzfeldt-Jakob disease, 4, 115, 237, 292 EEC in, 278 new variant, 115 Crimes against the person, 480-1 Criminal behaviour, 433-4 Criminal proceedings, and mental disorder, 488-90 alcohol and drugs, 490 amnesia, 490 automatism, 489-90 diminished responsibility, 489 fitness to plead, 488 infanticide, 489 not fit to stand trial, 488 not guilty by reason of insanity, 488-9 psychiatric disposals following conviction, 490 Criminology, 477-9 causes of violence, 479 factors associated with deliquency, 478-9 statistics, 477 Crisis houses, 467 Crisis response teams, 466 Critical appraisal, 164-5 Cross-sectional surveys, 160 Crown Court, 484 Cullen, William, 209 Culture see Ethnicity Cuneate tract, 96 Cushing's syndrome, 255 Cycle of change, 338 Cycloid psychosis, 173 Cyclothymia, 7, 192, 194, 195 Cyproterone, 548 Cytochrome P450, 63
Index De Clerambault's syndrome, 174 Deafness, 101 Defence mechanisms, 24-5, 26 Deliberate self-harm see Self-harm Deliquency, factors associated with, 478-9 Delirium, 15, 231-66, 294 amnesic syndrome, 241-2 cerebral trauma, 242-6 cerebrovascular disorder, 247-9 dementia see Dementia dysexecutive syndrome, 246-7 endocrine disorders, 254-6 general hospital psychiatry, 439-40 intracranial infection, 249-53 metabolic disorders, 256-8 neurological disorders, 261-5 prion diseases see Prion diseases space-occupying lesions, 253-4 stupor, 232-3 vitamin deficiency syndromes, 259-61 Delirium tremens, 12, 326 Delta-9 tetrahydrocannabinol, 343 Delusions, 7, 33 classification of, 8 grandiose, 8, 33 nihilistic, 33 paranoid, 8 of reference, 8 in schizophrenia, 170 types of, 7-8 Demence precoce, 169 Dementia, 194-5, 233-6, 287-93 catatonia in, 5 causes of, 288-92 clinical features, 287-8 diagnosis, 287 driving and, 300 drug treatment, 548 EEC in, 277-8 electroconvulsive therapy in, 551 frontal lobe, 115, 234-5, 291-2 general hospital psychiatry, 439-40 investigation of, 293 management, 293 multi-infarct, 116-17, 234 reversible, 292 strategic single infarct, 234 subcortical, 237-8, 292 vascular, 233-4, 290-1 see also Alzheimer's disease; Huntington's chorea; Lewy body disease; Pick's disease Dementia praecox, 4-5, 169 Dentrites, 83 Deoxyribonucleic acid see DNA
577
Index Dependence, drugs used to treat, 545-7 Dependent personality, 304 Depersonalization, 14 Depressed mood, 5-6 Depression, 6, 27, 186-7 appearance and behaviour, 186 assessment for psychotherapy, 524 atypical, 187 biological features, 187 in children, 402-3 cognitive changes, 187 differential diagnosis, 193-5 drug-induced, 70 EEC in, 281 electroconvulsive therapy, 550-1 emotional features, 186 masked/atypical, 189 monoaminergic theories of, 132-3 in old age, 294-57 postnatal, 375-7 psychosurgery in, 559 treatment, 203, 543-4 see also Antidepressants Depressive position, 20 Depressive pseudodementia, 187 Depressive ruminations, 187 Depth psychology, 16-17 Derailment, 10 Desipramine, 537 Desire, 382 loss of, 383 Detachment, 400 Developmental disorders, 411-15 Dexamethasone suppression test, 111, 198 Dexamphetamine, 409 Dhat, 475 Diabetes insipidus, 257 Diagnostic and Statistical Manual of Mental Disorders, 48, 146 affective disorders, 191-2 neurotic disorders, 210 schizophrenia, 172 Diazepam, 545 Dibenzodiazepines, 73 Diencephalon, 86-8 Differential misclassification, 157 Differential reinforcement of other, 42 5,7-Dihydroxytryptamine, 120 Diminished responsibility, 489 DiphenylbutyIpiperadines, 73 Discrimination, 42 Disease frequency measures, 152-4 Dissocial personality, 304 Dissociative disorders, 444-5 Distribution, 63
Disulfiram, 71, 328 in treatment of dependence, 546 Diuretics, and sexual function, 386 DNA, 136 sequencing, 142 Donald Duck speech, 95 Donepezil, 71 L-Dopa, 63, 196 Dopamine, 64, 68, 124-5 in schizophrenia, 130-1, 176 Dorsal columns, 89, 90, 96 Dose-response curve, 65, 66 Dothiepin, 537 Down's syndrome, 137, 426 and Alzheimer's disease, 289 Doxepin, 537 Drive theory, 16-20 depth psychology, 16-17 object relations and interpersonal theories, 19-20 psychosexual development, 17, 18 structural model of mind, 17-19 Drivelling, 10 Driving and alcohol misuse, 326 and dementia, 300 Droperidol, 73 Drug abuse see Substance misuse Drug development, 134-5 Dura mater, 90 Dynamic mutation, 140 Dysarthrias, 11, 35 Dysexecutive syndrome, 246-7 Dyslexia, 424 Dyspareunia, 384 Dysphasias, 35 Dyspraxias, 36 Dyssomnias, 279 Dysthymia, 5, 192, 194 Dystonia, 528 Eating disorders, 325, 358-69, 445-6 anorexia nervosa, 358-64 assessment for psychotherapy, 525 bulimia nervosa, 364-6 obesity, 367-8 pica, 368 Echo de la pansee, 12 Echolalia, 5, 410 Echopraxia, 5, 410 Ecological studies, 160 Ecstasy, 6, 341-2 Edinger-Westphal nucleus, 93, 100 Edward's syndrome, 137 Efficacy, 66 Ekbom's syndrome, 173 Elation, 6
578 Elderly see Old age psychiatry Electroconvulsive therapy, 550-7 administration, 552-4 affective disorders, 205 continuation and maintenance, 555 contraindications, 552 dementia, 551 depression, 550-1 in elderly depressed, 552 history, 550 legal requirements for administration, 557 mania, 551 morbidity and mortality, 556-7 neuropsychiatric disorders, 551 number and frequency of treatments, 555 physiological symptoms, 555-6 pregnancy and puerperium, 552 schizophrenia, 184, 551 Electroencephalogram, 36, 108-9, 275-82 abnormal, 276-7 arousal and sleep, 108-9 history, 275-6 normal, 276 specific conditions, 277-82 Electrolyte disturbance, 257 Elimination, disorders of, 415-17 Elimination of drugs, 63-4 Ellis, Albert, 510 Emic concepts of mental illness, 470 Emotion-focused coping, 50 Emotional incontinence, 7 Emotional lability, 7 Emotions, 49-50, 107 abnormal emotional states, 5-7 CNS control of, 107 disorders of, 5 physiological correlates, 107 Enactment, 520 Encephalins, 129 Encephalitis, 249-50 tics in, 4 Encephalitis lethargica, 250 Encopresis, 416-17 Endocrine disorders, 254-6 Endocrine system, alcohol effects on, 321 Endorphins, 97, 129 English criminal law, 484-5 Enkephalins, 97 Enuresis, 397, 415-16 Ependyma, 91 Epidemiology, 145-7 analytical, 145 definition/classification of cases, 146
Index descriptive, 145 predictive value, 147 sampling, 145 study designs, 159-63 validity/reliability of data, 147 see also individual conditions Epilepsy, 267-83 aetiology, 269 and alcohol misuse, 324 classification, 267-8 definition, 267 differential diagnosis, 269 EEC in, 277 epidemiology, 269 head injury inducing, 245 legal aspects, 274 management, 274-5 see also Anticonvulsants myoclonic, 4 psychiatric aspects, 269-75 interictal, 271-3 affective psychosis, 272 disorders of cognitive function, 273 neurotic conditions, 272 personality problems, 273 schizophreniform psychosis, 271-2 peri-ictal, 270-1 auras, 270 ictal, 270-1 postictal, 271 precipitation of seizures, 270 prodrome, 270 sexual disorders, 273-4 Epileptic personality, 11 Erectile impotence, 388-9 Erikson's stages of psychosocial development, 58 Erotomania, 174 Ethnicity African Caribbean community, 472-3 and alcohol misuse, 314 Chinese community, 473 culture-bound syndromes, 475-6 and eating disorders, 361, 366 improving services, 474-5 and mental disorder, 451-2 migrants and refugees, 474 and neurotic disorders, 213 somatization, 474 South Asian community, 473 and suicide risk, 348 transcultural psychiatry, 469-76 Ethosuximide, 79 Etic concepts of mental illness, 470 Event-following potentials, 282
Index Event-related potentials, 281-2 Evidence-based medicine, 163-5 Excitement, 382 Executive function, 105 Exhibitionism, 391 Existential psychotherapy, 517 Exit events, 202 Expressed emotion, 453 Extinction, 41 Extrapyramidal side effects, 72 Extrapyramidal system, 104 Eysenck Personality Inventory, 47 Eysenck Personality Questionnaire, 47 Eysenck's theory, 47 Facial motor nucleus, 93 Fairburn, 20-1 Family, effects of mental disorder on, 457 Family interventions, 458 Family studies, 140 affective disorders, 197 schizophrenia, 175-6 Family therapy, 308, 519-21 behavioural, 521 cognitive, 521 Milan group, 520 psychodynamic, 521 strategic and brief, 520 structural, 519-20 Fatal familial insomnia, 237 Female pseudohermaphroditism, 395 Ferenczi, 19 Fetal alcohol syndrome, 425, 426-7 Fetishism, 390 Fetishistic transvestism, 390 First-order kinetics, 62 First-pass effect, 62 Flattened affect, 6 Flexibilitas cerea, 5 Flight of ideas, 11 Flumazenil, 75 Fluoroscein key, 121 Fluoxetine, 74, 377, 537 Flupenthixol, 195, 531 Fluphenazine, 531 Flurazepam, 545 Fluvoxamine, 74, 537 Folk acid deficiency, 259 Folie a deux, 8 Forensic history, 32 Forensic psychiatry, 477-503 community forensic psychiatric services, 494 court diversion schemes, 494-5 Court of Protection, 503 court reports, 490-1
579 crimes against the person, 480-1 criminology, 477-9 dangerousness and risk assessment, 491-3 English criminal law, 484-5 local adult psychiatric services, 494 mental disorder, violence and offending, 485-8 Mental Health Act 1983, 495-500 Mental Health Act Commission, 502 Mental Health Act (Patients in the Community) 1995, 500-1 Mental Health Review Tribunals, 502 mentally disordered offenders and criminal proceedings, 488-90 prison services, 494 property offences, 482-3 Regional Secure Units, 493-4 sexual offences, 481-2 special care wards, 494 Special Hospitals, 493 treatment in the community, 501 Forgetting, 45 Formal thought disorder, 9,171 Formication, 13 Foulkes' group analysis, 522 Fovea, 98 Fragile X syndrome, 426, 430-1 Frankl, Victor, 517 Free-floating anxiety, 6 Fregoli syndrome, 8 Freidreich's ataxia, 265 Freud, Anna, 24-5 Freud, Sigmund, 16, 512 dream terminology, 17 stages of psychosexual development, 18 Frigophobia, 475 Frontal lobe, 84 dementia, 115, 234-5, 291-2 disorders, elation in, 6 syndrome, 246-7 Fugue states, 14, 271 Fusion, 10 GABA, 76-7, 79, 128-9 in neurotic disorders, 215 in schizophrenia, 177 GABA-transaminase, 120 Gabapentin, 80, 275 Gallon, Francis, 53 Gamma-aminobutyric acid see GABA Ganglion cells, 98 Ganja tea, 343 Ganser's syndrome, 11 Gastrointestinal tract, alcohol effects on, 320
-580 Gate theory of pain, 97 Gaucher's disease, 240-1 Gedankenlautwerden, 12 Gegenhalten, 5 Gender and alcohol misuse, 314 development, 392-5 and mental disorder, 451 and neurotic disorders, 212 and risk of self-harm, 353 and suicide risk, 348 Gender identity disorder, 393-5 of childhood, 394 Gene expression, 122 General hospital psychiatry, 436-50 abnormal illness behaviour, 446 models of, 437-8 psychiatric disorders, 438-46 rationale for, 436-7 special settings, 447-9 General paralysis of the insane, 6, 118, 252 Generalization, 42 Generalized anxiety disorder, 27, 225-6 Genes, 138-9 Genetic markers, 143 Genetics, 136-44 adoption studies, 141-2 affective disorders, 196-7 alcoholism, 316-17 Alzheimer's disease, 289 anorexia nervosa, 359 bulimia nervosa, 365 childhood psychiatric disorders, 397 chromosomal abnormalities, 137 and deliquency, 478-9 family studies, 140 genes and chromosomes, 136-7 Mendelian inheritance, 137-9 molecular genetics, 142-4 neurotic disorders, 214 non-Mendelian inheritance, 139-40 personality disorder, 306 schizophrenia, 175-6 substance misuse, 332 twin studies, 140-1 Geniculate nucleus, 94 Genital response, failure of, 384 Genomic imprinting, 140 Gerstmann-Straussler disease, 236 Gestalt therapy, 517 Gilles de la Tourette syndrome, 4, 397, 403, 410-11 Glasgow Coma Scale, 243-4 Glue sniffing, 261, 345 see also Substance misuse Glutamate, 131, 177
Index Glutamate decarboxylase, 120 Glycine, 129 Golgi tendon organ, 96 Good breast/bad breast concept, 19 Gracile tract, 96 Grey matter, 84 Grief, abnormal reactions, 189-90 Group decision-making, 53 Group polarization, 53 Group therapy, 308, 521-3 psychodynamic, 522-3 support and self-help groups, 523 Growth hormone, 112 Growth hormone-inhibiting hormone, 111 Growth hormone-releasing hormone, 111 Gustatory system, 102 Hachinski Ischaemia Score, 290 Haematological system, alcohol effects on, 321 Haemophilus influenzae, 428 Hakim's triad, 238 Half-life, 63 Hallucinations, 12-13, 34 auditory, 12 autoscopic, 13 dissociative, 13 functional, 13 gustatory/olfactory, 13 haptic, 13 hypnogogic/hypnopompic, 13 Lilliputian, 12 reflex, 13 in schizophrenia, 170-1 tactile, 13 visual, 12 Hallucinogens, 344 Haloperidol, 64, 73, 531 Hamilton Rating Scale for Depression, 146 Head injury, 242-5 boxing and, 246 chronic sequelae, 244-5 closed, 243 management, 245-6 open, 243 severity of, 243-4 Health of the Nation 1992, 461 Heavy metal toxicity, 261 Hebephrenia, 169 Heider's attribution theory, 51 Hepatic disease, 256-7 alcohol-induced, 320 Hermaphroditism, 394 Heroin, 335-7
581
Index pregnancy and breastfeeding, 373 urine screens, 334 Herpes simplex encephalitis, 118, 241-2, 249-50 Herpes zoster, 94 Heschl's gyrus, 101 Hill plot, 121 Hippocampal formation, 85 Histamine, 68 Histrionic personality, 304 HIV hospital psychiatry, 448 neuropsychiatric aspects, 252 Homelessness, and mental health, 455 Homicide, 480 Hope, 522 Human development, 55-9 heredity versus environment, 55 sensitive periods, 55 theories of, 56-8 Human immunodeficiency virus see HIV Hunter syndrome, 427 Huntington's chorea, 116, 235-6 EEC in, 277 tics in, 4 see also Dementia Hurler syndrome, 427 Husserl, Edmund, 3 Hydrocephalus, 238-9 normal pressure, 292 6-Hydroxydopamine, 120 5-Hydroxytryptamine see Serotonin Hyperalertness, 34 Hypercortisolism, 255 Hyperparathyroidism, 255 Hyperprolactinaemia, 72 Hyperthyroidism, 254 tremor in, 4 Hypnotics, 76, 546-7 pregnancy and breastfeeding, 372 Hypochondriacal disorder, 443 Hypofrontality, 179 Hypoglossal nucleus, 94 Hypoglycaemia, 256 Hypokalaemia, 257 Hyponatraemia, 257 Hypoparathyroidism, 255-6 Hypopituitarism, 256 Hypothalamo-pituitary-adrenal axis, 111-12, 197-8 anorexia nervosa, 360 Hypothalamo-pituitary-thyroid axis, 112, 198 Hypothalamohypophyseal tract, 88 Hypothalamus, 87-8 relations to pituitary, 88, 110-11 Hypothyroidism, 255
Hysterectomy, 379 Hysteria, 27 Id, 17-18 Ideational dyspraxia, 36 Idiopathic torsion dystonia, 264 Illness behaviour, 446 Illusions, 12 Imipramine, 74, 536, 537 Imitation, 59 Imitative behaviour, 522 Immunohistochemistry, 121 Impulsive personality, 304 Inattention, 45 Incest, 482 Incidence, 153 Incoherence, 33 Incongruous affect, 6 Incus, 101 Indecent assault, 481 Indecent exposure, 482 Infanticide, 489 Inferior salivatory nucleus, 94 Inferior temporal cortex, 99 Information bias, 156 Informed consent, 68 Insight, 36 disorders of, 15 Insight learning, 43 Institutionalization, 459 Intellectual disability, 424 Intelligence, 53-5 genetics of, 55 Intelligence Quotient see IQ Intention, 485 Intermetamorphosis, 8 Internal objects, 20 International Classification of Diseases, 48 affective disorders, 192 neurotic disorders, 209 schizophrenia, 172 Interpenetration of thoughts, 9-10 Interpersonal attraction, 53 Interpersonal learning, 522 Interpersonal theories, 25-7 Interpersonal therapy, 206, 515-16 Interpretation, 514 Intersexual disorders, 394-5 Intervention studies, 145 Interviews, 29 Intracranial infection, 249-53 Intramuscular injection, 62 Intravenous injection, 62 Introjection, 20 Inverse agonists, 76 Involuntary manslaughter, 480
582
Ion channel antagonists, 79-80 IQ, 54-5 Irreversible antagonists, 66 Isocarboxazid, 537 Isoniazid, 196 James-Lang theory, 49 Jargon aphasia, 107 Jaspers, Karl, 3, 7 Joint, 343 Jung, Carl Gustav, 22-3, 513 Juvenile Court, 484 Kappa statistic, 147 Karyotype, 136 Kelly's personal construct theory, 46 Kernberg, 22 Ketamine, 342 Khat, 342 Klein, Melanie, 19, 513 Klein-Levin syndrome, 280 Kleinfelter's syndrome, 137, 427 Kleptomania, 483 Knight's move thinking, 10 Kohlberg's theory of moral development, 57-8 Kohut, Heinz, 23-4 Koro, 475 Korsakoff's syndrome, 15, 45 Kuf's disease, 240 Kuru, 236 Lacrimal nucleus, 94 Lacune state, 117 Lamotrigine, 80, 275 Language, 106-7 development of, 58-9 Latah, 475 Late paraphrenia, 297-8 Lateral columns, 90 Lateral geniculate nucleus, 98 Law of mass action, 62, 65 Lead toxicity, 261 Leadership, 52 Learned helplessness, 50-1, 201 Learning, 40-3 associative, 40-2 cognitive, 42 ethology and, 43 insight, 43 observational, 42-3 social, 43 state-dependent, 45 Learning disability, 398, 424-35 aetiology, 425-6 catatonia in, 5 children's services, 429
Index definitions, 424 diagnostic assessment, 427-8 prevalence, 425 prevention, 428-9 and psychiatric disorders in adults, 431-4 in children, 429-31 stereotypies in, 4 and violent behaviour, 487 Learning theory of neurotic disorders, 215 Legal aspects electroconvulsive therapy, 557 epilepsy, 274 old age psychiatry, 299-300 psychosurgery, 559-60 substance misuse, 346 see also Mental Health Act 1983; Mental Health (Patients in the Community) Act 1995 Lentiform nucleus, 86 Leonhard's cycloid psychosis, 173 Leptin, 360 Lesch-Nyhan syndrome, 427, 430 Leucotomy effect, 248 Lewy bodies, 114 Lewy body disease, 114, 291 EEC in, 278 see also Dementia Liaison model for hospital psychiatry, 437 Liaison service see General hospital psychiatry Life events and childhood psychiatric disorders, 400-1 and mental disorder, 452-3 and neurotic disorders, 216 Life Events and Difficulties Schedule, 452 Likert scale, 51 Lilliputian hallucinations, 12 Limbic lobe, 85 Limbic system, 85-6 Linear regression, 155 Linkage disequilibrium, 144 Linkage studies, 143-4 Lithium, 64, 77-8, 173, 182, 204, 278, 540-2 action, 541 contraindications, 541 indications, 540-1 interactions, 542 pregnancy and breastfeeding, 372 toxicity, 4 unwanted effects, 541-2 withdrawal, 542
Index Loading dose, 64 Locked-in syndrome, 247 Lofepramine, 74, 536, 537 Lofexidine, 71 Logoclonia, 5 Logos, 517 Loprazolam, 545 Lorazepam, 545 Lormetazepam, 545 Low self-esteem, 202 LSD see Lysergic acid diethylamide Lumbar puncture, 36 Luschka, foramen of, 91 Luteinizing hormone-releasing hormone, 111 Lysergic acid diethylamide (LSD), 14, 344 McNaughton Rules, 488-9 Macula, 98 Magendie, foramen of, 91 Magistrates Court, 484 Magnetic resonance imaging, 36, 123-4 schizophrenia, 178-9 Mahler, Margaret, 22 Main sensory nucleus, 93 Male pseudohermaphroditism, 394-5 Malingering, 445 Malleus, 101 Mamillothalamic tract, 88 Manganese toxicity, 261 Mania, 187-8 appearance and behaviour, 188 biological features, 188 cognitive changes, 188 differential diagnosis, 195-6 electroconvulsive therapy in, 551 emotional features, 188 secondary, 196 treatment, 204 Manic-depressive psychosis, 173 Manie sans delire, 302 Mann-Whitney test, 152 Mannerisms, 3-4 Manslaughter, 480 Mantel-Haenszel odds ratio, 159 Maprotiline, 74, 537 Marchiofava-Bignami syndrome, 323 Marital status, and suicide risk, 349 Masculine protest, 19 Masochism, 392 MAST questionnaire, 315 Maternal preoccupation, 21 Maternity blues, 377-8 Maudsley Personality Inventory, 47 MDMA, 6, 341-2 Mean, 149
583 Medial geniculate nucleus, 101 Medial lemniscus, 96 Median, 149 Medulla, 89 Meiosis, 136 Meisner's corpuscle, 95 Melatonin, 112-13 Memory, 35, 44-5 declarative, 45 disorders of, 15 long-term, 44-5 short-term, 44 Mendelian inheritance, 137-9 Meniere's disease, 102 Meninges, 90-1 Meningitis, 250-1 aseptic, 251 pyogenic, 251 tuberculous, 251 Meningovascular neurosyphilis, 251 Menopause, 379 Mens rea, 484-5 Mental handicap, EEC in, 278 Mental Health Act 1983, 299, 346, 495-500 Mental Health Act Commission, 502 Mental Health (Patients in the Community) Act 1995, 462, 500-1 Mental health review tribunals, 502 Mental health services, childbearing women, 380 Mental state examination, 32-6 abnormalities of thought, 33-4 agnosias, 35-6 appearance and behaviour, 32-3 cognitive state, 34-5 dysphasias, 35 dyspraxias, 36 hallucinations, 34 insight, 36 mood, 33 orientation, 34 speech, 33 Mercury toxicity, 261 Merkel's disc, 95 Mescaline, 344 Mesencephalic nucleus, 93 Meta-analyses, 163 Metabolic disorders, 256-8 Metabolic effects of alcohol, 320 Metachromatic leucodystrophy, 239 Methadone, 71, 337 pregnancy and breastfeeding, 372 in treatment of dependence, 546 urine screens, 334 Methanol poisoning, 320 Methylphenidate, 409
Index
584
Metonyms, 9 Meynert, basal nucleus of, 131 Microglia, 84 Midbrain, 89 Migrants, psychiatric problems of, 474 Milan group, 520 Minnesota Multiphasic Personality Inventory, 48 Misuse of Drugs Act 1971, 346 Mitgehen, 5 Mitochondrial mutation, 140 Mixed affective disorder, 189 Moclobemide, 537, 540 Mode, 149 Molecular cloning, 142 Monoamine oxidase inhibitors, 75, 217, 534-6, 537, 538^0 actions, 535, 539 contraindications, 534, 539 indications, 534, 538-9 interactions, 535-6, 539-40 pregnancy and breastfeeding, 372 unwanted effects, 535, 537 see also individual drugs Monoamine reuptake inhibitors, 73-5 Monosymptomatic hypochondrical psychosis, 173 Mood, 33 Mood congruency, 187 Mood stabilizers, 77-9 Moral derangement, 302 Moral insanity, 302 Morbid jealousy, 173-4 and alcohol misuse, 325 and violent behaviour, 487-8 Morbidity electroconvulsive therapy, 556-7 general hospital, 436-7 primary care settings, 464 Mother-infant relationship, 20 Motivation, 48-9 Motivational enhancement therapy, 517 Motivational interviewing, 338, 516 Motor dysphasia, 35 Motor homunculus, 104 Motor nucleus, 93 Motor systems, 102-5 cerebellum, 104-5 .extrapyramidal system, 104 lower motor neurons, 102-3 motor association cortex, 105 upper motor neurons, 103-4 Movement disorders, 3-5 MRCPsych examination, 562-70 content, 563-4 examination technique, 567-9 form of, 562-3
marking, 564 preparation, 564-6 Multi-infarct dementia, 116-17, 234 Multifactorial liability-threshold models, 139 Multiple sclerosis, 118, 263 Multivariate analysis, 159 Munchausen's syndrome, 445 Murder, 480 Musculoskeletal system, alcohol effects on, 321 Mutism, 11-12 Myalgic encephalomyelitis, 448-9 Myasthenia gravis, 263-4 Myoclonus, 4 Myxoedema, 36 Naltrexone, 71, 328 in treatment of dependence, 546 Narcissistic personality, 304 Narcolepsy, 280 Need for achievement, 48 Needs assessment, 466 Nefazodone, 75, 538 Negative reinforcement, 41-2 Negativism, 5, 187 Negligence, 485 Neocortex, 84, 85 Neologisms, 10, 33 Neostriatum, 86 Nerve deafness, 101 Nerve growth factors, 132 'Nerves', 475 Neurasthenia, 448-9 Neuroadaptation, 331-2 Neuroanatomy, 83-95 blood supply to CNS, 91-2 brain stem, 89 central nervous system, 84-8 cerebellum, 90 cranial nerves, 92-5 meninges, 90-1 neurons and neuroglia, 83-4 peripheral nervous system, 92 spinal cord, 90 spinal nerves, 95 Neurochemistry, 119-35 drug development, 134-5 neurotic disorders, 214-15 neurotransmitters, 124-9 psychiatric disorders, 129-3 research methods, 119-24 Neuroendocrinology, 110-11 Neuroglia, 83-4 Neuroleptics, 278-9 pregnancy and breastfeeding, 372 Neuromuscular spindle, 96
Index Neurons, 83-4 Neuropathology, 113-18 Neurophysiology, 95-110 aggression, 107-8 autonomic nervous system, 109-10 cerebral dominance, 105-6 EEG, 108-9 emotional behaviour, 107 executive function, 105 language, 106-7 motor systems, 102-5 somatosensory systems, 95-102 Neuroscience, 83-118 Neuroses, 244, 299 Neurosyphilis, 251-2 Neurotic disorders aetiology, 214-16 agoraphobia, 219 anxiety, 210-11 classification, 209-10 course and prognosis, 218 epidemiology, 211-14 generalized anxiety disorder, 225-6 learning disability in, 433 mixed anxiety and depressive disorder, 226 obsessive-compulsive disorder see Obsessive-compulsive disorder panic disorder, 221-3 social phobia, 219-21 stress-related disorders, 226-9 suicide risk, 351 treatment, 216-18 Neurotransmitters, 124-9, 199 animal studies, 119-23 biochemical methods, 120 blood estimations, 123 cerebrospinal fluid examination, 122-3 early immediate gene activity, 122 electrical stimulation, 123 empirical behavioural models, 119 focal intracerebral injections, 123 gene expression studies, 122 immunohistochemistry, 121 lesion studies, 119-20 receptor binding techniques, 120-1 release and uptake studies, 121-2 specific behavioural models, 119 human studies, 123-4 see also individual neurotransmitters Nicotine, pregnancy and breastfeeding, 373 Nicotinic acid deficiency, 259 Nodes of Ranvier, 84 Nominal aphasia, 107 Nominal dysphasia, 35 Non-Mendelian inheritance, 139-40
585 Non-steroidal anti-inflammatory drugs, 64 Nonspecific nuclei, 87, 96 Noradrenaline, 64, 67, 125-6, 199 Noradrenaline uptake inhibitors, 538 Normal distribution, 148 Northern blot analysis, 122 Nortriptyline, 537 Nucleus ambiguus, 94 Nucleus gigantocellularis, 131 Null hypothesis, 150 Number needed to treat, 155 Nystagmus, 102 Obedience, 52-3 Obesity, 367-8 Object relations theories, 20-1 Observational learning, 42-3 Obsessional thoughts, 9 Obsessive-compulsive disorder, 27, 194, 223-5 aetiology, 224-5 assessment for psychotherapy, 525 in children, 403-4 clinical features, 223-4 course and prognosis, 225 differential diagnosis, 224 epidemiology, 224 management, 225 psychosurgery in, 559 treatment, 510 Occipital lobe, 84 Occupation, and alcohol misuse, 315 Oculomotor nucleus, 92 Odds and probability, 153-4 Olanzapine, 533 Olanzepine, 73, 182 Old age psychiatry, 284-301 alcohol and drug misuse, 298 assessment for psychotherapy, 525 delirium, 294 dementia see Dementia depression, 294-7 electroconvulsive therapy, 552 history and examination, 284-7 late paraphrenia, 297-8 legal aspects, 299-300 Court of Protection, 300 driving and dementia, 300 guardianship, 299 Power of Attorney and Enduring Power of Attorney, 300 testamentary capacity, 299 neuroses, 299 personality disorder, 298 prescribing in, 69 pseudodementia, 293-4 suicide, 297
586 Olfactory system, 102 Oligodendroglia, 84 Oligogenic inheritance, 139 Omission, 10 Operant conditioning, 40-1 Opiates, 335-7 dependence, 71, 337-8 pregnancy and breastfeeding, 372 Opium, 335-7 Oppositional defiant disorder, 407-8 Optic chiasma, 98 Oral administration, 62 Oral contraceptives, 379 and sexual function, 386 Orgasm, 382 Orgasmic dysfunction, 384 Orientation, 34 Oromandibular dystonia, 264 Othello syndrome, 173-4 and alcohol misuse, 325 and violent behaviour, 487-8 Overeaters Anonymous, 523 Overinclusivity, 9 Overmatching, 158 Overvalued idea, 7 Oxytocin, 110, 129 Pa-leng, 475 Paccinian corpuscle, 95 Paedophilia, 390-1, 482 Pain, 96-7 Pain clinics, 447 Pallilalia, 5, 410 Panic disorder, 221-3 Papaver somniferum, 335 Papez circuit, 86, 87 Paranoid personality, 304 Paranoid psychosis, 173-4, 194 Parapraxes, 17 Paraventricular nucleus, 110 Pareidolia, 12 Parenting, 401 Parents, mental illness in, 401 Parietal cortex, 99-100 Parietal lobe, 84 Parkinsonian symptoms, 528 Parkinsonian tremor, 87 Parkinson's disease, 89, 116, 261-2 Paroxetine, 74, 537 Paroxysmal choreoathetosis, 264 Partial agonists, 66 Partition coefficient, 62 Passivity phenomena, 8, 9, 33-4 in schizophrenia, 170 Patau syndrome, 137 Pathological jealousy see Othello syndrome
Index Pavlov, Ivan, 40 PGP, 342 Pearson correlation coefficient, 155 Perception, 43-4 disorders of, 12-14 Peripheral nervous system, 92 Perls, Frederick, 517 Perplexity, 6 Perseveration, 11, 33 Persistent somatoform pain disorder, 443 Personal history, 31-2 Personality, 32, 45-8 and alcoholism, 318-19 change in, 244, 248, 273 idiographic theories of, 46-8 and neurotic disorders, 215 nomothetic theories of, 47 and substance misuse, 333 Personality disorder, 174, 194, 279, 302-12 aetiology, 305-6 assessment for psychotherapy, 525 clinical management, 306-11 definition of, 303-5 history, 302-3 learning disability in, 433 in old age, 298 prevalence, 305 prognosis, 311 and violent behaviour, 486 Personality testing, 45-8 Phaeochromocytoma, 256 Pharmacodynamics, 64-8 Pharmacokinetics, 61-4 absorption, 62 distribution, 63 elimination, 63-4 Pharmacological treatment, 527-49 adverse effects, 65, 67-8, 69-70 see also individual drug types Phencyclidine, 342 Phenelzine, 537 Phenobarbitone, 274 Phenothiazines, 72 Phenytoin, 64, 79, 274 Phobias, 6, 27, 193 treatment, 509-10 Phobic anxiety disorders, 218-26 Physical examination, 36 Physical illness, prescribing in, 69 Physostigmine, 132 Pia mater, 91 Piaget's theory of intellectual development, 57 Piblotoq, 475 Pica, 368 Pick bodies, 114
Index Pick's disease, 114-15, 235 EEC in, 278 see also Dementia Pimozide, 73, 531 Pineal gland, 112 Piperazine, 72 Piperidine, 72 Pipothiazine palmitate, 531 Piracetam, 80 Pituitary gland, 110 hypothalamic control of, 110-11 Pituitary portal system, 88 Plasma protein binding, 63 Poisson distribution, 148 Polydypsia, 258 Polygenes, 139 Polymerase chain reaction, 122, 143 Polysomnography, 279 Pons, 89 Porphyria, 258 Positive reinforcement, 41 Positron emission tomography, 123 schizophrenia, 179-80 Post-concussional syndrome, 244 Post-traumatic stress disorder, 27, 226-8 assessment for psychotherapy, 525 Postnatal depression, 375-7 Postnatal psychiatric disorders, 371-8 bonding failure, 378 maternity blues, 377-8 postnatal depression, 375-7 puerperal psychosis, 373-5 Potency, 66 Power of Attorney, 300 Prader-Willi syndrome, 431, 433 Pralidoxime, 132 Praxia, 97 Praxis, 99 Pregnancy electroconvulsive therapy in, 552 prescribing in, 68-9, 372-3 psychiatric disorders of, 370-1 still-birth, 371 termination, 371 Premack principle, 41 Premature ejaculation, 384, 389 Premenstrual syndrome, 378-9 Preoccupations, 9 Prevalence, 153 Primary care psychiatry, 463-5 psychological treatments in, 519 Primary motor cortex, 85, 103 Primary sensory cortex, 85 Prion diseases, 115, 236-8 fatal familial insomnia, 237 Gerstmann-Straussler disease, 236
587 kuru, 236 see also Creutzfeldt-Jakob disease Prison services, 494 Problem-focused coping, 50 Procedural sequence model, 28 Progressive multifocal leucoencephalopathy, 250 Progressive supranuclear palsy, 116 Prolactin-inhibiting hormone, 111 Prolactin-releasing hormone, 111 Promazine, 531 Prompting, 42 Property offences, 482-3 Proposagnosia, 36 Propranolol, 77 Prosopagnosia, 99, 288 Proximity seeking, 400 Pseudodementia, 293-4 Pseudohallucinations, 13 Pseudohermaphroditism, 394-5 Psychiatric Assessment Schedule for Adults with Developmental Difficulties (PAS-ADD), 432 Psychiatric disability, 456 Psychiatric history, 30-2 Psychoactive substances, 32 Psychoanalysis, 308, 512-15 aims, 513 assessment, 513 indications and contraindications, 515 key terms, 514-15 procedures, 514 Psychodynamic family therapy, 521 Psychodynamic group therapy, 522-3 Psychological treatments, 507-26 assessment, 523-5 cognitive and behavioural therapies, 509-12 definition, 507 family and couple therapy, 519-21 group treatments, 521-3 history, 507-8 individual psychodynamic psychotherapy, 512-15 psychological treatments in primary care, 519 supportive psychotherapy, 518-19 see also individual treatment modalities Psychology, 40-59 human development, 55-9 social, 51-5 Psychoneuroendocrinology, 111-13 Psychopathic infirmity, 302 Psychopathic personality, 302, 303 Psychopathology, 3-28 descriptive, 3-15 dynamic, 15-28
588 Psychopathology Instrument for Mentally Retarded Adults (PILDA), 432 Psychopharmacology, 60-80 drug development 60-1 pharmacodynamics, 64-8 pharmacokinetics, 61-4 prescribing, 68-9 psychotropic drugs, 70-80 steady-state concentration and therapeutic index, 64 Psychosis in adolescence, 418-19 drug-induced, 70 head injury inducing, 245 Psychosocial skills training, 458 Psychosomatic disorders, 417-18 Psychosurgery, 557-60 adverse effects, 559 contraindications, 559 current use, 558-9 history, 558 indications, 559 legal aspects, 559-60 Psychotherapy, 151-18, 206 assessment for, 523-5 history, 507-9 short-term dynamic, 515 supportive, 518-19 see also Psychological treatments; and individual treatment modalities Psychotropic drugs, 70-80 Puerperal psychosis, 373-5 electroconvulsive therapy in, 552 Punishment, 42 Pupillary reflexes, 100 Pyramidal system, 103 Pyridoxine deficiency, 259 Quantitative trait locus, 139 Quetiapine, 73, 533 Rabies encephalitis, 250 Ramsay Hunt syndrome, 94 Random clustered sampling, 145 Random misclassification, 156-7 Random stratified sampling, 145 Randomized controlled trials, 162-3 pragmatic, 164 Range, 149 Rape, 481 Reactive psychoses, 173 Reboxitine, 74, 536 Recall bias, 157 Receptors, 65-8 Recklessness, 485 Refugees, psychiatric problems of, 474 Regional Secure Units, 493-4
Index Regression, 155-6 Rehabilitation, 465 Religion and alcohol misuse, 314 and suicide risk, 348 Respiratory tract, alcohol effects on, 321 Restriction enzymes, 142 Retardation of thought, 11 Reticular activating system, 275 Reticular formation, 89 Reticulospinal tract, 103 Retinogeniculostriate pathway, 98 Reverse causality, 157 Rhinencephalon, 85 Rinne's test, 101 Risk assessment, 37-9, 491-3 Risky shift effect, 53 Risperidone, 73, 182, 533 Rods, 97 Rogers, Carl, 517 self theory, 47 Rotter's concept of locus of control, 51 Rubrospinal tract, 103 Ruffini's endings, 95 Rule learning, 59 Russell's sign, 361 Ryle, Anthony, 28 Saccule, 101 Sadism, 392 Sadness, 193 Sadomasochism, 391-2 SADQ questionnaire, 316 Saka, 475 Sampling, 145 Scatchard plot, 120 Schedules for Clinical Assessment in Neuropsychiatry (SCAN), 3 Schema, 201 Schizoaffective psychosis, 172-3, 189, 195 Schizodepression, 189 Schizoid personality, 304 Schizomania, 189 Schizophrenia, 169-85, 194, 195 in adolescence, 418-19 aetiology, 175-81 anatomical, 177-80 biochemical, 130-1, 176-7 biological, 175-6 psychological, 180-1 assessment for psychotherapy, 524 in children, 403 classification and diagnosis, 172-4 Diagnostic and Statistical Manual of Mental Disorders, 172 differential diagnosis, 172-4
Index International Classification of Diseases, 172 clinical features, 170-2 abnormal mood states, 5, 6, 171 delusions, 170 formal thought disorder, 9, 171 hallucinations, 170-1 motor disorder, 171 negative syndrome, 171 passivity, 170 schizophrenic deterioration, 172 Schneider's first-rank symptoms, 171 stereotypies, 4 thought alienation, 171 EEC in, 279 electroconvulsive therapy, 184, 551 epidemiology, 174-5 family therapy, 521 history, 169 learning disability in, 432 management, 182-4 pharmacotherapy, 182 psychological therapies, 183 social interventions, 183-4 prognosis, 184 suicide risk, 351 and violent behaviour, 485-6 Schizophrenia Patient Outcomes Research Team (PORT), 457 Schnauzkrampf, 4 Schneider, Carl, 10 Schneider's first-rank symptoms of schizophrenia, 171 School non-attendance, 405 Seasonal affective disorder, 112-13 Sectorization, 466 Selection bias, 156 Selective attachments, 400 Selective serotonin reuptake inhibitors, 74, 536-8 actions, 537 contraindications, 536 indications, 536 interactions, 538 unwanted effects, 537-8 Self-administered questionnaires, 146 Self-blame, 187 Self-disclosure, 522 Self-harm, 352-7, 445-6 aetiology, 354 in children, 405-6 definition, 352-3 epidemiology, 353 management, 355-7 method, 353 outcome, 354-5
589 see also Suicide Self-image, 52 Self-injurious behaviour, 430 Self-psychology, 23-4 Semantic differential, 51 Semi-structured interviews, 146 Semicircular canals, 101 Sensate focus, 388 Sensitiver Beziehungswahn, 8, 173 Sensory distortions, 14 Sensory dysphasia, 35 Sensory homunculus, 97 Serotonin, 64, 67, 126-7, 199 in schizophrenia, 131, 176-7 Serotonin syndrome, 75 Serotonin uptake inhibitors, 538 Sertindole, 182, 533 Sertraline, 74, 537 Sex chromosomes, 136 abnormalities, 137, 427 Sexual aversion, 383 Sexual development, 392-5 Sexual disorders, 382-95, 445-6 aetiology, 385-7 assessment, 387-9 assessment for psychotherapy, 525 classification, 383 definitions, 383-4 epidemiology, 385 in epilepsy, 273-4 normal sexual functioning, 382-3 of sexual preference, 389-92 Sexual drive, excessive, 384 Sexual function drugs affecting, 386 normal, 382-3 Sexual offences, 481-2 Sexual preference, disorders of, 389-92 Shaping, 42 Shen-kui, 475 Shifted outpatient clinic, 464 Shoplifting, 483 Shy-Drager syndrome, 261 Sick role, 446 Silderafil, 389 Simultanagnosia, 99 Single photon emission tomography, 123 schizophrenia, 179-80 Skin, alcohol effects on, 321 Skin popping, 335 Skunk grass, 343 Sleep apnoea, 280 deprivation, 205 EEG, 279-81 Snow, 339-41 Social Adjustment Rating Scale, 452
590
Social factors, 451-6 area of residence, 455 culture see Culture and deliquency, 478 expressed emotion, 453 gender see Gender homelessness, 455 life events see Life events in schizophrenia, 181 social support, 455-6 socioeconomic class, 454-5 and suicide risk, 348, 349-50 unemployment and work, 453—4 Social impairment, 424 Social influence, 52 Social isolation, 202 Social learning theory, 43 Social networks, 202 Social phobia, 219-21 Social power, 52 Social psychiatry, 451-8 social factors see Social factors Social skills training, 458, 511 Social support, 455-6 Socioeconomic class and alcohol misuse, 315 and mental health, 454-5 Sodium valproate, 78-9, 204, 275, 543 Somatization aetiology, 441-2 chronic, 440 epidemiology, 441 ethnic minority groups, 474 psychiatric disorders in, 441, 442 Somatoform disorders, 442-4 hypochondriacal disorder, 443 management, 443—4 persistent pain disorder, 443 somatization disorder, 442 undifferentiated, 443 Somatosensory evoked potentials, 282 Somatosensory systems, 95-102 South Asian community, psychiatric problems of, 473 Southern blotting, 142 Space-occupying lesions, 253-4 Spasmodic torticollis, 4, 264 Special care wards, 494 Special Hospitals, 493 Speech, 33, 35 disorders production of speech, 11-12 stream of speech, 10-11 Speedball, 340 Spinal cord, 90 blood supply, 92 Spinal nerves, 95
Index Spinothalamic tracts, 89, 90, 96 Spongiform encephalopathies, 115, 292 Spouse abuse, 480-1 Standard deviation, 149 Standard error, 150 Stanford-Binet test, 54 Stapes, 101 State-dependent learning, 45 Statistical analyses, 147-52 descriptive statistics, 148-50 inferential statistics, 150-2 parametric/non-parametric statistics, 151-2 variables, 147-8 Steady-state concentration, 64 Steele-Richardson syndrome, 116 Stereotactic subcaudate tractotomy, 559 Stereotypies, 4 Steroids, 196, 260 Stigma, 456-7 Still-birth, 371 Stimulants, 339^2 urine screens, 334 Strange Situation Paradigm, 400 Stranger anxiety, 400 Strategic therapies, 520 Stratification, 159 Stress, 50-1 Stress-related disorders, 226-9 Structured interview, 146, 305 Student's Mest, 152 Stupor, 232-3 Subacute sclerosing panencephalitis, 250 Subarachnoid haemorrhage, 242, 248 Subcortical arteriosclerotic encephalopathy, 117 Substance misuse, 331-46, 445-6 aetiology, 332-3 barbiturates, 343 benzodiazepines, 342-3 cannabis, 343-4 and criminal liability, 490 definitions, 331 dependence and withdrawal, 332 drug history, 334 dual diagnosis, 333 hallucinogens, 344-5 investigations, 334-5 khat, 342 legal aspects, 346 in old age, 298 opiates, 335-7 phencyclidine, 342 physical examination, 334 prevalence, 332 stimulants, 339-42 suicide risk, 351
Index synthetic opiates, 337-8 tolerance and neuroadaptation, 331-2 and violent behaviour, 486-7 volatile substances, 261, 345 Substance P, 97, 123, 129 Substantia gelatinosa, 97 Substitution, 10 Suicide, 245, 347-52, 445-6 aetiology, 349-51 and alcohol misuse, 325 in children, 405-6 definition, 347 epidemiology, 347-9 incidence, 347-8 in old age, 297 prevention of, 352 in psychiatric patients, 352 risk of, 37-8 UK rates, 347 see also Self-harm Suk-yeong, 475 Sullivan, Harry Stack, 21 Sulpiride, 73, 531 Superego, 18-19 Superior salivatory nucleus, 94 Supervised Discharge Orders, 462 Supervision Register 1994, 461-2 Supraoptic nucleus, 110 Susto, 475 Sydenham's chorea, 264-5 Sylvian fissure, 84, 85, 106 Sympathetic ganglia, 95 Synapse, 83 Systematic reviews, 145 Systemic lupus erythematosus, 249 Tabes dorsalis, 251 Taijin kyofusho, 475 Talking past the point, 11 Tardive dyskinesia, 528-9 Tardive Tourette's syndrome, 529*" Tectum, 89 Telencephalon, 84 Temazepam, 545 Temperament in children, 398, 399 and deliquency, 479 Temporal lobe, 84 Tetrahydroamino acridine, 132 Thalamic syndrome, 87 Thalamus, 87 Thematic apperception test, 45 Theory of mind, 181 Therapeutic index, 64 Therapeutic window, 74, 535 Thioridazine, 195, 531 Thioxanthines, 72
591 Thought alienation, 171 Thought block, 10, 171 Thought broadcasting, 10, 171 Thought disorders, 7-11, 33-4 alienation, 10 content, 7-9 form, 9-10 stream of thought, 10-11 Thought echo, 12 Thought insertion, 10, 171 Thought withdrawal, 10, 171 Thryotrophin-releasing hormone, 111 Thurstone scale, 51 Tics, 4 in children, 410-11 Tolerance, 64, 331-2 Topiramate, 80 Topographical agnosia, 36 Tourette syndrome see Gilles de la Tourette syndrome Tractus solitarius, nucleus of, 94 Transactional analysis, 517-18 Transcranial magnetic stimulation, 560 Transcultural psychiatry see Ethnicity Transference, 24, 514 Transient global amnesia, 242 Transitional object, 21 Transsexualism, 393-4 Transtheoretical model of anorexia nervosa, 362 Transvestism dual-role, 394 fetishistic, 390 Tranylcypromine, 537 Trazodone, 75, 537 Treatment alliance, 514 Tremor, 4 benign essential, 265 Parkinsonian, 87 Treponema pallidum, 118, 251 Treponeme specific antigen, 252 Tricyclic antidepressants, 64, 74, 278, 534-6 actions, 535 contraindications, 534 indications, 534 interactions, 535-6 pregnancy and breastfeeding, 372 unwanted effects, 535 see also individual drugs Trifluoperazine, 531 Trimipramine, 74, 537 Trisomy 13, 137 Trisomy 18, 137 Trisomy 21 see Down's syndrome L-Tryptophan, 63, 75, 540 depletion, 205
Index
592 Turner's syndrome, 137, 427 Twin studies, 140-1 affective disorders, 196-7 alcoholism, 316-17 schizophrenia, 176 Twinship needs, 24 Tympanic membrane, 100 Type A personality, 50 Tyrosine hydroxylase, 120
Visual evoked potential, 282 Visual neglect, 99 Visual object agnosia, 35 Vitamin B12 deficiency, 117, 259 Vitamin deficiency syndromes, 259 Vocational rehabilitation, 457-8 Volatile substance abuse, 261, 345 Vorbeireden, 11 Voyeurism, 391
Ubiquitin, 114 Ufufuyane, 475 Undesirable events, 202 Unemployment, and mental health, 453-4 Universality, 522 Uqamairineq, 475 Uraemia, 257 Urine screens, 334 Utricle, 101
Wassermann reaction antigen, 252 Weber's test, 101 Wechsler Adult Intelligence Scale (WAIS), 54 Wechsler Intelligence Scale for Children, 427 Wernicke-Korsakoff syndrome, 15, 117, 241, 321-3 causes, 323 clinical features, 322-3 pathology, 322 prognosis, 323 Wernicke's area, 35, 101, 106, 178 Wernicke's encephalopathy see Wernicke-Korsakoff syndrome White matter, 84 Wife battering, 480-1 Wilson's disease, 263 Windigo, 476 Winnicot, Guntrip, 21, 513 Wisconsin Card Sorting test, 180 Word salad, 10, 171 Work, and mental health, 453-4 World Health Organization International Classification of Diseases, 146 Writer's cramp, 264
Vaginismus, 384, 389 Variance, 150 Vascular dementia, 233-4, 290-1 Vasoactive intestinal polypeptide, 129 Vasopressin, 110, 129 Venlafaxine, 75, 537 Ventroposterior nucleus, 96 Verbigeration, 10 Vertebral arteries, 91 Vestibular system, 101-2 Vestibulospinal tract, 103 Viagra, 389 Vigabatrin, 275 Viloxazine, 74, 537 Violence causes of, 479 and mental disorder, 485-8 Viral screens, 335 Vision, 97-100 eye movements, 100 inferior temporal cortex, 99 parietal cortex, 99-100 pupillary reflexes, 100 retinogeniculostriate pathway, 98 visual association cortex, 99 visual field defects, 98 visual perception, 98-9 Visual disorientation, 99
X-ray, 36 Yalom, 522 Yerkes-Dodson curve, 210-11 Yerkes-Dodson law, 50 Zero-order kinetics, 62 Ziprasodone, 533 Zolpidem, 77, 547 Zopiclone, 77, 547 pregnancy and breastfeeding, 372 Zuclopenthixol, 72, 531
