Depressive Disorders - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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DEPRESSIVE DISORDERS A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

DEPRESSIVE DISORDERS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS

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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1

Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Depressive Disorders: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-497-00347-3 1. Depressive Disorders-Popular works. I. Title.

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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International, Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on depressive disorders. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.

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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications.

Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.

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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health

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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON DEPRESSIVE DISORDERS ........................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Depressive Disorders .................................................................. 12 E-Journals: PubMed Central ....................................................................................................... 68 The National Library of Medicine: PubMed ................................................................................ 72 CHAPTER 2. NUTRITION AND DEPRESSIVE DISORDERS ................................................................ 117 Overview.................................................................................................................................... 117 Finding Nutrition Studies on Depressive Disorders ................................................................. 117 Federal Resources on Nutrition ................................................................................................. 119 Additional Web Resources ......................................................................................................... 119 CHAPTER 3. ALTERNATIVE MEDICINE AND DEPRESSIVE DISORDERS ......................................... 125 Overview.................................................................................................................................... 125 The Combined Health Information Database............................................................................. 125 National Center for Complementary and Alternative Medicine................................................ 126 Additional Web Resources ......................................................................................................... 133 General References ..................................................................................................................... 159 CHAPTER 4. DISSERTATIONS ON DEPRESSIVE DISORDERS ........................................................... 161 Overview.................................................................................................................................... 161 Dissertations on Depressive Disorders ...................................................................................... 161 Keeping Current ........................................................................................................................ 162 CHAPTER 5. PATENTS ON DEPRESSIVE DISORDERS ...................................................................... 163 Overview.................................................................................................................................... 163 Patents on Depressive Disorders ............................................................................................... 163 Patent Applications on Depressive Disorders............................................................................ 182 Keeping Current ........................................................................................................................ 204 CHAPTER 6. BOOKS ON DEPRESSIVE DISORDERS .......................................................................... 205 Overview.................................................................................................................................... 205 Book Summaries: Federal Agencies............................................................................................ 205 Book Summaries: Online Booksellers......................................................................................... 206 Chapters on Depressive Disorders ............................................................................................. 213 CHAPTER 7. PERIODICALS AND NEWS ON DEPRESSIVE DISORDERS ............................................ 215 Overview.................................................................................................................................... 215 News Services and Press Releases.............................................................................................. 215 Newsletter Articles .................................................................................................................... 219 Academic Periodicals covering Depressive Disorders................................................................ 220 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................. 221 Overview.................................................................................................................................... 221 U.S. Pharmacopeia..................................................................................................................... 221 Commercial Databases ............................................................................................................... 224 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 229 Overview.................................................................................................................................... 229 NIH Guidelines.......................................................................................................................... 229 NIH Databases........................................................................................................................... 231 Other Commercial Databases..................................................................................................... 233 APPENDIX B. PATIENT RESOURCES ............................................................................................... 235 Overview.................................................................................................................................... 235 Patient Guideline Sources.......................................................................................................... 235 Associations and Depressive Disorders ..................................................................................... 239 Finding Associations.................................................................................................................. 240

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APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 243 Overview.................................................................................................................................... 243 Preparation................................................................................................................................. 243 Finding a Local Medical Library................................................................................................ 243 Medical Libraries in the U.S. and Canada ................................................................................. 243 ONLINE GLOSSARIES................................................................................................................ 249 Online Dictionary Directories ................................................................................................... 251 DEPRESSIVE DISORDERS DICTIONARY............................................................................. 253 INDEX .............................................................................................................................................. 317

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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with depressive disorders is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about depressive disorders, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to depressive disorders, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on depressive disorders. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to depressive disorders, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on depressive disorders. The Editors

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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON DEPRESSIVE DISORDERS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on depressive disorders.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and depressive disorders, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “depressive disorders” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: x

Depression and Diabetes (editorial) Source: Diabetes Care. 16(12): 1621-1623. December 1993. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: In this article, the author addresses the issue of whether depression is more common among people with diabetes compared with individuals without diabetes. Topics include the debilitating nature of depressive disorders; the treatment of depression; the relationship between depression and worsened glycemic control; endocrinological abnormalities in diabetes that may contribute to depressive disorders; depression in people with other chronic medical conditions; and disease-specific versus

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generic mechanisms of causation of depressive disorders. The author stresses that an understanding of psychiatric diagnosis and the rudiments of treatment are important clinical skills for the practitioner who sees large numbers of diabetes patients. The article concludes with a brief vignette of one patient that illustrates the points presented by the author. 14 references. x

Major Depressive Disorder: Psychopathology, Medical Management and Dental Implications Source: JADA. Journal of the American Dental Association. 132(5): 629-638. May 2001. Contact: Available from American Dental Association. ADA Publishing Co, Inc., 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2867. Website: www.ada.org. Summary: Major depressive disorder (MDD) is a psychiatric illness in which mood, thoughts, and behavioral patterns are impaired for long periods. The illness distresses the person and impairs his or her social functioning and quality of life. MDD is characterized by marked sadness or a loss of interest or pleasure in daily activities, and is accompanied by weight change, sleep disturbance, fatigue, difficulty concentrating, physical impairment, and a high suicide rate. This article considers the psychopathology, medical management, and dental implications of MDD. MDD may be associated with extensive dental disease, and people may seek dental treatment before becoming aware of their psychiatric illness. MDD frequently is associated with a disinterest in performing appropriate oral hygiene techniques, a cariogenic (cavity causing) diet, diminished salivary flow, rampant dental caries (cavities), advanced periodontal disease, and oral dysesthesias (reduced feeling in the mouth). Many medications used to treat the disease magnify the xerostomia (dry mouth) and increase the incidence of dental disease. Appropriate dental management requires a vigorous dental education program, the use of saliva substitutes and special precautions when prescribing or administering analgesics and local anesthetics. In addition, dentists cognizant of the signs and symptoms of MDD have an opportunity to recognize patients with occult MDD. After confirmation of the diagnosis and institution of treatment by a mental health practitioner, dentists usually can provide a full range of services that may enhance patients' self-esteem and contribute to the psychotherapeutic aspect of management. 1 figure. 4 tables. 74 references.

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Coping Strategies in Patients with Interstitial Cystitis: Relationships with Quality of Life and Depression Source: Journal of Urology. 169(1): 233-236. January 2003. Contact: Available from Lippincott Williams and Wilkins. 12107 Insurance Way, Hagerstown, MD 21740. (800) 638-3030 or (301) 714-2334. Fax (301) 824-7290. Summary: Previous research has demonstrated that interstitial cystitis (IC) patients experience depressive symptoms and decrements to quality of life. However, the extent to which patients may be able to influence quality of life and depressive symptoms through coping strategies has not been investigated in this population. In a number of other chronic conditions, specific coping strategies have been associated with the degree of impairment beyond disease severity. This article reports on a study of the association of coping strategies with depressive symptoms, quality of life, and self-reports of pain in patients with interstitial cystitis (n = 64). Patients coping by greater catastrophizing reported greater impairments in various domains, including depressive symptoms, general mental health, social functioning, vitality, and pain. Greater venting was associated with greater depressive symptoms and poorer mental health. Seeking

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instrumental social support was associated with fewer depressive symptoms. These findings suggest that maladaptive coping strategies are associated with higher levels of depressive symptoms and quality of life decrements in patients with this condition. The authors conclude that psychosocial interventions aimed at increasing adaptive coping may positively impact the female experience with interstitial cystitis. 2 tables. 25 references. x

Depression in Alzheimer Patients: Discrepancies Between Patient and Caregiver Reports Source: Alzheimer Disease and Associated Disorders. 7(4): 187-201. 1993. Summary: Researchers describe analyses of depressive symptoms of patients with dementia reported by patients and their caregivers, addressing: (1) how well patients' and caregivers' reports of patients' depressive symptoms correlate; (2) whether certain variables measured in the study are related to patients' or caregivers' reports; and (3) which symptoms are best for measuring depression. Thirty-one outpatients with probable Alzheimer's disease and their caregivers responded separately to depressive symptom questionnaires during interviews. Caregivers reported more depressive symptoms in patients with dementia than patients reported for themselves. Correlations between caregivers' and patients' reports of individual symptoms ranged between -0.23 to 0.76, with lowest correlations found for intrapsychic distress, cognitive impairment, and hallucinations. Patients' responses were not affected by stereotyped responding or severity of impairment, but patients under-reported their symptomatology. Caregivers' responses were associated with the extent of contact with the patients, familial relationship, and information sources used to determine patients' moods. Caregivers' responses were not correlated with their depression or ratings of how they would feel if they were the patients. 2 tables, 1 appendix, 26 references.

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Assessment of Depression in Dementia (Commentary) Source: Alzheimer Disease and Associated Disorders: An International Journal. 8(Supplement 1): S227-S229. 1994. Summary: The authors discuss four problems in the assessment of depression in institutionalized people with dementia. These difficulties concern the similarity between the clinical appearances of dementia and depression, the inability of patients with moderate to severe dementia to provide reliable reports of their moods, the narrow range of depressive symptoms addressed by instruments assessing people with severe dementia, and the inadequacy of some assessment instruments to measure depression in patients with only moderate cognitive impairment. Other problems include the inability of assessment instruments to take into account the characteristic instability and transience of depressive signs and symptoms in patients with dementia. According to the authors, additional research is needed regarding the validity, reliability, and concordance among information sources for the various depression measures in nursing home populations. 21 references.

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How To Manage Depression and Psychosis in Alzheimer's Disease Source: Geriatrics. 50(1): 43-46, 49. January 1995. Summary: This article defines manifestations of the various disorders associated with Alzheimer's disease (AD) and outlines an updated primary care approach to their management. It reports that depression and psychosis each occur in about 30 to 50 percent of patients with AD. Depressive syndromes range from grieving and mild

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depressive symptoms to major depression. Depression can also mimic the signs and symptoms of AD; this condition is known as dementia syndrome of depression. Psychotic syndromes include paranoid delusions, misidentification syndrome, and hallucinations. The diagnosis of both depression and psychosis is based on a careful history and a mental status examination. Treatment includes psychosocial intervention and, when symptoms are severe, drug therapy. According to the author, the newer antidepressants are suggested for depressive syndromes, whereas psychosis is treated with high-potency neuroleptics. 2 tables, 12 references. (AA-M). x

Dental Management of the Child and Adolescent with Major Depression Source: Journal of Dentistry for Children. 60(2): 125-131. March-April 1993. Summary: This article discusses dental management of children and adolescents with major depression. Topics include characteristics of depression in preschoolers, schoolage children, and adolescents; suicide risk; the epidemiology of major depression among children and adolescents; etiology; the medical management of major depression; dental findings; factors that lead to the development of advanced dental disease in this population; the importance of preventive dental education; and the role of the dentist in providing quality, multidisciplinary care for children with depressive disorders. The authors stress that dentists must be familiar with disorder, because of its frequent association with extensive dental pathology and must also be familiar with the possible need to modify standard plans of care. 51 references. (AA-M).

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Differential Diagnosis of Dementia, Delirium and Depression: Implications for Drug Therapy Source: Drugs and Aging. 5(6): 431-445. December 1994. Summary: This article discusses the differential diagnosis, evaluation, and treatment options for dementia, delirium, and depression. It presents the clinical features and causes of each disorder and the neuropsychological and laboratory tests used in diagnosis. Comprehensive clinical evaluation is necessary because these disorders are not mutually exclusive. Furthermore, physical diagnoses, such as chronic obstructive lung disease, congestive heart failure, stroke, and endocrine disorders are frequently associated with depressive symptoms. Laboratory testing is required to exclude concurrent metabolic, endocrine and infectious disorders, and drug effects. Imaging studies should be obtained selectively in patients with signs and symptoms, such as focal neurological findings and gait disturbances, which are suggestive of structural lesions: stroke, subdural hematoma, normal pressure hydrocephalus, and brain tumors. Appropriate management involving pharmacological and nonpharmacological measures could result in significant improvement in most patients with these syndromes. In delirious patients the underlying illness may be treated concomitantly with the use of psychotropics, if necessary. Although no current medications have been shown to have a significant effect on the functional status of patients with the two most common causes of dementia, Alzheimer's disease (AD) and multi-infarct dementia, the management of concomitant illness in these patients may result in improved function for as long as a year. Tacrine (Cognex) improves cognitive function slightly in selected patients with AD over short periods. Finally, the treatment of depression with medications or electroconvulsive therapy may result in significant reductions in mortality and morbidity. 4 tables, 43 references. (AA-M).

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Provisional Diagnosis Criteria for Depression of Alzheimer Disease: Rationale and Background Source: American Journal of Geriatric Psychiatry. 10(2): 129-141. March-April 2002. Summary: This article provides the rationale and background for the development of diagnostic criteria for depression of Alzheimer's disease (AD). First, it reviews what is known about possible neurobiological correlates and risk factors, epidemiology, clinical characteristics, and course of depression in AD. Then, it explains how to distinguish depression of AD from other disorders and reviews methods of assessing depression in AD. Next, it discusses the treatment of dementia with depression, including the indications and contraindications for specific treatments and the economic consequences of treating and not treating this syndrome. It also describes the recently proposed criteria for the diagnosis of depression of AD, compares them with diagnostic criteria for major depressive episode, and explains how they were developed. Finally, it outlines some of the most promising questions for future research. (See AZJA09221 for related article.). 2 tables, 128 references.

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Depression in Male Geropsychiatric Inpatients With and Without Dementia: A Naturalistic Study Source: Journal of Affective Disorders. 46: 243-246. 1997. Summary: This journal article compares the presentation and course of depression in male geriatric inpatients with and without dementia. Researchers studied 326 consecutive admissions to the inpatient psychogeriatric unit of the Houston Veterans Affairs Medical Center, Texas. The sample included 201 patients with dementia and 125 without dementia. Thirty-five patients with dementia and 22 without dementia had major depression. The dementia diagnoses of those with depression were vascular dementia (n=16), mixed dementia (n=14), Alzheimer's disease (n=4), and alcohol dementia (n=1). The groups of depressed patients with and without dementia were similar in age, length of stay, living arrangements prior to admission, and racial composition. Both groups showed significant improvements on measures of depressive symptoms, agitation, psychiatric symptoms, and side effects. However, the group without dementia improved significantly more than those with dementia on the psychological measures, primarily due to a greater improvement in mental status. The authors conclude that male geropsychiatric patients with major depression may improve substantially with treatment, regardless of the presence of dementia. 21 references.

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Psychopathologic and Functional Outcome in the Treatment of Elderly Inpatients With Depressive Disorders, Dementia, Delirium, and Psychoses Source: International Psychogeriatrics. 10(1): 71-83. March 1998. Summary: This journal article describes a study of the psychopathologic and functional outcomes of 148 older patients with depressive disorders, dementia, delirium, and psychoses admitted for inpatient treatment at the psychogeriatric university clinic in Aarhus, Denmark. The sample consisted of 80 patients with major depression, 34 with dementia, 26 with delirium, and 8 with psychoses. The average ages were 79, 80, 83, and 76 years, and median lengths of stay were 53, 35, 24, and 24 days, respectively, in the four groups. The patients were assessed at admission and again at discharge for psychopathology, behavioral disorders, depression, cognitive function, activities of daily living, and gait. Treatment included physiotherapy, occupational therapy, and drug therapy. At the end of their stay, patients with depression and delirium improved

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significantly on all health measures, and patients with psychosis showed a trend toward improvement in psychopathology and gait. Patient with dementia improved in psychopathology, but the other measures remained unchanged. The authors conclude that some older patients with depression, delirium, and dementia may benefit from treatment in a psychogeriatric hospital setting. 9 tables, 19 references. x

Factor Structure of the Cornell Scale for Depression in Dementia Among Probable Alzheimer's Disease Patients Source: American Journal of Geriatric Psychiatry. 6(3):212-220. Summer 1998. Summary: This journal article describes the factor structure of the 19-item Cornell Scale for Depression in Dementia (CSDD) among 137 patients with probable Alzheimer's disease who were seen at an outpatient memory disorders clinic. The sample was 50.4 percent Hispanic and 49.6 percent white non-Hispanic; their mean age was 78.2 years, mean duration of illness was 4.1 years, and mean educational level was 10.4 years. Depressive symptoms were assessed with the CSDD as part of an extensive psychiatric clinical interview conducted by bilingual psychiatrists. A principal-factors analysis with varimax rotation resulted in a four-factor solution that accounted for 43.1 percent of the common variation. The four factors were general depression (lack of reactivity to pleasant events, poor self-esteem, pessimism, loss of interest, physical complaints, psychomotor retardation, sadness); rhythm disturbances (difficulty falling asleep, multiple night awakenings, early morning awakenings, weight loss, diurnal variation of mood); agitation/psychosis (agitation, mood-congruent delusions, suicide); and negative symptoms (appetite loss, weight loss, lack of energy, lack of reactivity to pleasant events). These factors showed moderate consistency with the five symptom clusters proposed in the original presentation of the CSDD. 4 tables, 43 references.

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Early-Onset and Late-Onset Depression Are Independent of the Genetic Polymorphism of Apolipoprotein E Source: Dementia and Geriatric Cognitive Disorders. 10: 258-261. 1999. Summary: This journal article examines the association between apolipoprotein E (apoE) genotype and depressive illness in a large sample of Alzheimer's disease (AD) patients (n=102, mean age 74.4 years), depressed patients (n=160, mean age 68.0 years) recruited from the outpatient memory disorders clinic of the Psychiatric Department of the University of Bonn in Germany, and healthy controls (n=191, mean age 70.6 years). The depressed patients were divided into those with early-onset depression (EOD, n=129), defined as onset before age 60 years, or late-onset depression (LOD, n=31). AD patients were significantly more likely than the other groups to have at least one apoE4 allele. However, there was no significant difference in apoE4 allele frequency between the EOD, LOD, and control groups. Survival analysis was used to examine the cumulative incidence of depression depending on age-of-onset. There was no significant difference between depressed patients with at least one apoE4 allele and those with no apoE4 allele. In the authors' opinion, the results do not exclude the possibility that depression shares some pathophysiologic features with AD, but it is unlikely that apoE genotype will elucidate the assumed common mechanisms. 1 figure, 1 table, 22 references.

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Association Between Premorbid History of Depression and Current Depression in Alzheimer's Disease Source: Journal of Geriatric Psychiatry and Neurology. 12: 72-75. Summer 1999.

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Summary: This journal article presents a study of the association between a premorbid history of depression and current depression in patients with Alzheimer's disease (AD). The sample consisted of 243 AD outpatients evaluated consecutively at a universityaffiliated memory disorders center. Information about each patient's psychiatric history was obtained through semistructured interviews with the patient and caregiver. Current depressive symptoms were assessed with the Cornell Scale for Depression in Dementia. A positive history of depression was significantly more common among patients with current depression (23%) than among those without current depression (11%). This relationship remained significant after controlling for the effects of age, education, gender, ethnicity, and level of cognitive impairment. Neither gender nor the interaction of gender and history of depression was associated with risk of depression. 2 tables, 25 references. x

Family Interaction and Caregivers of Alzheimer's Disease Patients: Correlates of Depression Source: Family Process. 31(1): 19-33. March 1992. Summary: This journal article reports on a study that explored the relationship between depression in the primary family caregivers of persons with Alzheimer's disease and the overall behavioral patterns of these families. The study specifically focused on the affective responses between the caregiver and other family members. Family affective responses have proven important in studies of major psychiatric disorders, and this study found that they were equally salient to depressive symptoms in family caregivers. In the study, 30 caregivers and extended family members participated in problem solving discussions that were videotaped, transcribed, and coded. Results showed that the angry and sad responses of extended family members to the caregiver accounted for over 44 percent of the variance in caregiver depressive symptoms. The article suggests that the angry, sad, and depressed feelings might develop because the caregiver is looking for emotional support, while other family members are focusing more on problem solving issues. The relevance of these findings for treatment approaches and future research efforts is discussed. 26 references.

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Clinical Features in Depression in Old Age: A Case for Minor Depression Source: Current Opinion in Psychiatry. 4(4): 596-599. August 1991. Summary: This journal article reviews research indicating that minor depression may be an important clinical entity for resolving many of the epidemiologic and diagnostic dilemmas confronting clinical investigators of depression in late life. The first part discusses the epidemiologic dilemma presented by discrepancies between the increased burden of depressive symptoms identified in elderly populations and the relatively low prevalence of depressive disorders found in community studies of the elderly. The second section presents phenomenologic data on minor depression that may account for these discrepancies. These data suggest that minor depression is not a single entity but may include many syndromes, including those described by various authors as persistent anhedonia, recurrent depressive disorders, and chronic minor depressive disorder associated with cognitive impairment and dementia. The third section reviews findings on the pharmacologic treatment of minor depression. 19 references.

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Treatment of Depressive Disorders of Spousal Caregivers of Persons With Alzheimer's Disease: A Review Source: American Journal of Alzheimer's Disease. 14(5): 289-293. September-October 1999. Summary: This journal article reviews studies on the methods and efficacy of interventions for depressive disorders in spousal caregivers of people with Alzheimer's disease (AD). Support groups are one of the most popular forms of caregiver interventions; and research suggests that these groups are helpful for information sharing and peer support, but they do not adequately meet the affective needs of the participants. Psychoeducational intervention groups are more focused on helping caregivers develop a specific set of coping skills to deal with their depression while managing the problematic behaviors of the person with AD. These groups appear to be the most effective treatment for depression in AD caregivers. Although research on psychotherapy and counseling for caregivers is limited, one study suggests the efficacy of cognitive therapy. The author recommends further research on psychoeducational intervention groups and cognitive therapies. 31 references.

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Interrelations Between Psychosis, Behavioral Disturbance, and Depression in Alzheimer Disease Source: Alzheimer Disease and Associated Disorders. 13(Supplement 2): S3-S8. 1999. Summary: This journal article reviews the literature on behavioral disturbances, psychosis, and depression in Alzheimer's disease (AD), using data from a recent study. Behavioral changes are common in AD, and heterogeneous in their presentation. Subtle personality changes such as apathy, irritability, and the inability to pay attention, tend to occur early. In later stages, agitation, aggression, and disinhibited behaviors may appear. In a recent study, the Columbia University Scale for Psychopathology in Alzheimer's Disease was used to monitor a number of behavioral symptoms in 235 patients with early probable AD. Markov analyses were conducted to predict the probability of developing or retaining a particular symptom at 6-month follow-up. Results show that the symptoms of psychopathology in AD fluctuate over time. Agitation was both the most frequent and persistent symptom, whereas paranoid delusions and hallucinations were less common and moderately persistent. Most behavioral disturbances, except paranoid delusions, were associated with greater cognitive impairment. There was no association between depressive features and either cognitive or functional impairment. 37 references.

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Alzheimer's Disease and Depression Source: Journal of Consulting and Clinical Psychology. 60(3): 379-391. June 1992. Summary: This journal article reviews the research literature on the prevalence, phenomenology, assessment, and treatment of depression in Alzheimer's disease. The review focuses on empirical studies in which depression and Alzheimer's disease have been objectively and clearly defined, but it also includes selected clinical and theoretical work and studies of mixed dementia and depression as relevant. The review is organized into the following topic areas: definition and scope of the problem; conceptual issues regarding the coexistence of dementia and depression; factors complicating the assessment of depression in patients with Alzheimer's disease; issues in research methodologies; prevalence of depression symptoms and depressive disorders in Alzheimer's disease and comparison with prevalence in other populations; correlation of coexisting disease with excess patient disability and caregiver disturbance;

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and treatment of depression in patients with Alzheimer's disease. A final section contains conclusions and recommendations for further research. 98 references. x

Factors Complicating the Diagnosis of Depression in Cerebrovascular Disease, Part II: Neurological Deficits and Various Assessment Methods Source: Canadian Journal of Psychiatry. 39(10): 601-607. December 1994. Summary: This review article discusses issues related to the diagnosis of depression in subjects with aphasia, aprosodia, anosognosia, and dementia and evaluates the usefulness of various diagnostic methods. It states that neurological deficits associated with cerebrovascular disease may impair the ability to express or experience depressive symptoms. Identification of depression in the absence of verbal reports on subjective mood state is a difficult task. The value of various diagnostic methods, including depressive rating scales, and standard psychiatric interviews, and biological variables in the diagnosis of depression in cerebrovascular disease is considered. The review concludes by focusing on the limitations of existing approaches in the diagnostic assessment of depression in patients with severe communication and comprehension deficits. It emphasizes the importance of devising a standard diagnostic method with less reliance on verbal responses. Biological markers, in conjunction with a structured clinical interview that relies on clinical history, vegetative symptoms, and observed behavior may provide a reliable alternative approach. 1 table, 53 references. (AA-M).

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Depression in Alzheimer's Disease Patients: Caregivers As Surrogate Reporters Source: Journal of the American Geriatrics Society. 43(2): 150-155. February 1995. Summary: This study evaluated the use of caregivers as surrogate reporters of depressive symptoms in patients with Alzheimer's disease (AD) on five depression measures. Researchers compared scale characteristics, including means, ranges, internal consistency, sensitivity, and item content of modified self-report questionnaires and depression interviews. Participants were 76 patients diagnosed with both depression and AD, and their family caregivers. All subjects were community-residing participants in an outcome investigation of behavioral treatment for depression. Researchers completed a Schedule for Affective Disorders and Schizophrenia (SADS) interview on all subjects to establish a diagnosis of depression. Caregivers then completed three additional questionnaires about their patients: the Beck Depression Inventory, the Geriatric Depression Scale, and the Center for Epidemiological Studies-Depression Scale, all modified to provide a surrogate report of their patient's depressive symptoms. In addition, two interview measures were completed based on interviews with the caregiver and patient: the Hamilton Depression Rating Scale (HDRS) and the Cornell Scale for Depression in Dementia (CSDD). Mean scores were above the recommended cutoff score for mild levels of depression on all measures. Coefficient alpha levels were comparable to levels reported for the traditional self-report formats. Sensitivity varied among the measures, with the CSDD most sensitive and the HDRS least sensitive. Based on these results, the study suggests that caregivers are able to act as surrogate reporters of depression in AD patients. The modification of self-report questionnaires did not decrease their internal consistency, and they remained highly correlated with each other, supporting their validity when used in this manner. The authors recommend a two-step process of evaluating patients with AD for depression: first, a surrogate report questionnaire completed by caregivers to screen patients, eliminating those who are unlikely to be depressed, and then a more extensive interview with those patients who appear likely to be depressed and their caregivers. 4 tables, 35 references. (AA-M).

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Federally Funded Research on Depressive Disorders The U.S. Government supports a variety of research studies relating to depressive disorders. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to depressive disorders. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore depressive disorders. The following is typical of the type of information found when searching the CRISP database for depressive disorders: x

Project Title: ADJUNCTIVE ACUPUNCTURE TO TREAT BIPOLAR DEPRESSION Principal Investigator & Institution: Suppes, Patricia; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2004 Summary: Complementary and alternative therapies for psychiatric disorders are increasingly popular despite the lack of rigorous scientific data addressing their safety, tolerability, or efficacy. The proposed study adds to a small but growing body of literature to evaluate acupuncture in the treatment of mood disorders. The primary aims are to evaluate the feasibility and efficacy of acupuncture treatment in conjunction with psychopharmacology alone. The study will replicate methods of acupuncture diagnosis and treatment designed in a previous NIMH- funded study. The role of subjects' expectancies for acupuncture treatment will be evaluated. Patients will be randomized to either acupuncture plus stable medications (ACUP N=15) on clinical outcome or nonspecific acupuncture plus stable medications (NS ACUP N=15). Clinical contact with an acupuncturist will be equivalent for both groups (12 sessions, 8 weeks). Patients, raters, and psychiatrists will be blind to group assignment. The criteria for inclusion now require moderate (vs. mild) depression for study entry to minimize study confounds such as spontaneous improvement. Safety measures and procedures to maintain study retention have been strengthened. Acupuncture patients will meet weekly with an RA and psychiatrist to complete ratings (IDS-C, CGI-BP, YMRS, GAF) and to assess side effects and symptom severity. We will include a comparison group (TAU) of patients who met entry criteria but refused the acupuncture intervention. Those subjects will continue to receive pharmacological treatment, and retrospective chart audit will allow us to determine the degree of change expected from medication treatment alone in this sample. While clinical trials have addressed the efficacy of acupuncture treatment for unipolar depression, a unique opportunity exists to bring similar rigor to the study of acupuncture for depressive symptoms in bipolar disorder. A strength of this proposal is its replication of methodology developed and used by other researchers in a study of acupuncture in MDD. Should acupuncture demonstrate efficacy in the treatment of

2

Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).

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bipolar disorder, further studies will be proposed to evaluate its utility for maintenance and prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: ALCOHOLISM AND FAMILY INTERACTION Principal Investigator & Institution: Seilhamer, Ruth A.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-AUG-1978; Project End 31-DEC-2002 Summary: APPLICANT'S ABSTRACT: The broad objective of this research program has been to develop an empirically based understanding of alcoholics and their families, and in so doing, to contribute to the methodological, descriptive, and predictive goals of the field. To this end, the project's past 19 years have involved in-depth assessments of 287 families, including individual, marital, parental, and whole family measures. Initial assessments include psychiatric and family history assessments, videotaped laboratory interactions under drinking and nondrinking conditions, audiotaped home interactions, a variety of interview and questionnaire self reports, and neurological and academic assessments of children. Five and ten year follow-up assessments have been completed on the first samples (50 families of male alcoholics, 50 families of male depressives, 50 families of non-distressed social drinkers), and a five year follow-up has been completed on the second samples (37 families of female alcoholics, 50 families of female depressives, and another 50 families of male alcoholics). The proposed four-year renewal involves completion of a parallel ten year follow-up assessment of the psychiatric/personality, drinking, and psychosocial status of the second samples, as well as further assessment of offspring in the first samples who have now attained adult life roles. Comprehensive interview and questionnaire procedures will be gathered from parents, offspring, and spouses of married adult children, with a projected data base over 1600 individuals. Specific aims include examination of: 1) predictor domains that moderate and/or mediate the nature and severity of adult child outcomes; 2) effects related to gender of affected parent, gender of offspring, and subtype of alcoholism exhibited by the affected parent; 3) intergenerational relationships of adult offspring and family of origin, and the impact of these relationships on drinking and nondrinking outcomes; 4) risk factors and developmental pathways specific to depressive disorders; and 5) further, complex sequential analyses of naturalistic observational data given the recent completion of detailed coding of all observational data in the second samples. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: ANTIDEPRESSANT & CBT FOR INSOMNIA TO DEPRESSION OUTCOME Principal Investigator & Institution: Manber, Rachel; Acting Associate Professor; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2006 Summary: (provided by applicant): Context: The purpose of the proposed Exploratory/Developmental R21 Grant is to pilot test a combined treatment of an antidepressant medication and cognitive-behavioral therapy for insomnia (CBTi) in patients with depressive disorders who have concomitant difficulty initiating and/or maintaining sleep. The proposed combined approach targets the patients' insomnia, because this common depression symptom is often associated with less favorable outcome of standard treatment and with increased risk of relapse. Specific aims: 1) To test whether the proposed intervention improves response to acute treatment (12 weeks)

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for depression, as measured the percent of patients who remit and the time course to remission, relative to the control treatment; 2) To test whether the proposed citalopram + CBTI intervention enhances longer-term outcome by reducing the proportion of participants who relapse during a 6-months follow-up phase, relative to the control treatment. Research Design and Method: In this prospective, randomized, controlled study, participants will be randomized to receive 12 weeks of acute treatment with the SSRI citalopram plus either CBTI or a validated, placebo psychotherapy for insomnia. Participants will be followed-up for 6 months after the end of acute treatment phase. Participants will be transitioned to community care during the first follow-up month. Participants: Participants will be 58 men and women ages 18 to 65 who 1) meet DSM-IV criteria for Major Depressive Disorder; 2) have a score greater than or equal to14 on the first 17 items of the 24-item Hamilton Depression Rating Scale (HRSD); 3) have difficulty initiating sleep (sleep onset latency > 30 minutes) and/or maintaining sleep (wake after sleep onset > 30 minutes per night at least 3 nights per week), to be confirmed by one week of sleep diary recording. Participants will also have to meet all study exclusion criteria. The ethnic distribution of the sample will be representative of the ethnic distribution in the San Francisco Bay Area. Women-to-men ratio is expected to be 2:1 as it is the case for depression. Main Outcome Measure(s): The primary outcome measures are the HRSD and the depression portion of the SCIDIV, to be administered at baseline, at the end of weeks 1, 2, 4, 8, and 12 of the acute phase, and at the end of 1, 2, 3, and 6 months of the follow-up phase. Other important measures include the Beck Depression Inventory (weekly), measures of sleep (diaries and wrist activity monitors, weekly) and measures of provider and patient expectations, adherence, and compliance. Expected Outcomes: We hypothesize that the group of patients who receive the combination of citalopram and CBTI will have higher remission and partial response rates following acute treatment and lower relapse rates during follow-up as compared to the group that receive citalopram and placebo psychotherapy for insomnia. The study will assess the feasibility and acceptability of the combination of the two treatments and will provide estimates of effect sizes, and attrition rate. The findings from the proposed pilot study will inform the design of a subsequent full-scale randomized controlled trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DISORDERS

BDNF

MUTANTS:

GENETIC

MODELS

FOR

DEPRESSIVE

Principal Investigator & Institution: Rios, Maribel; Anatomy and Cellular Biology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Depressive disorders are debilitating conditions that affect millions of individuals and create an enormous burden on society. Close to 100 billion dollars per year are spent treating patients with severe and mild forms of depression in the United States alone. However, the underlying molecular mechanisms that trigger depression remain to be elucidated so that treatment alternatives for patients that are unresponsive to the current forms of therapy can be created. A potential target for the design of novel treatment strategies is brain derived neurotrophic factor (BDNF). Compelling evidence shows that BDNF modulates affective behavior but the specific role and the mechanism of action of this neurotrophin remain elusive. We recently generated conditional mutations of BDNF using the cre recombinase/IoxP system. These mice have a pre or postnatal depletion of BDNF in the central nervous system that does not compromise their viability as the global depletion

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of BDNF does. These mutants display dramatic changes in behavior including hyperaggression and hypersensitivity to stress, both of which are often symptoms of depression. We propose using these mutants, and others that we are currently generating, as genetic models of depressive disorders to dissect the role of BDNF in the regulation of behavior. Different lines of mutants that through genetic manipulation have depletion or over expression of BDNF in different regions of the brain associated with mood disorders will be tested using standard behavioral models for depression and aggression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: BIOLOGICAL RISK FACTORS IN RELATIVES OF ALCOHOLIC WOMEN Principal Investigator & Institution: Hill, Shirley Y.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-JAN-1990; Project End 31-JAN-2009 Summary: (provided by applicant): Breaking the cycle of intergenerational transmission of alcohol dependence from women alcoholics to their offspring through intervention requires identification of relevant mediating and moderating risk/protective factors. Because we need a better understanding of how to identify those children at highest risk, study of offspring of parents with the most severe form of the disorder is needed. A "double proband" methodology was first developed in our laboratory to select families with more severe cases of male alcoholism (early onset, high familial aggregation). Using a double proband methodology to identify a severe form of alcoholism in women, we have now completed recruitment of a sample of mothers and their offspring for longitudinal follow-up and successfully followed children with good retention (80% at the fourth annual visit). To date, offspring of these women alcoholics have shown significantly earlier onset to begin regular drinking, and have an earlier onset of depressive disorders, conduct disorders and "any psychiatric disorder." The first goal of the renewal effort is to model psychiatric outcome by age 18 through identification of important interactions between a quantified estimate of familial risk, neurobiological indicators (e.g., P300 developmental trajectories), prenatal use of alcohol/drugs in mothers, and a number of environmental factors including the mothers' continued use of alcohol/drugs. Establishing which predictors influence the age of onset to begin drinking, a variable that is highly correlated with alcohol dependence outcome in national surveys will be determined using a similar set of environmental and familial/genetic predictors. Finally, a young-adult follow-up involving participants for whom multiple waves of child/adolescent data has been collected will enable us to study the effect of these factors on outcome, including substance dependence by young adulthood. Young adulthood has been identified as a period of considerable importance in that many individuals "mature out" of abusive patterns of use while others may go on to severe problems. Studying these young adults will also allow us to capture changes in drinking and drug use during young adulthood and concomitant environmental changes (e.g., marriage, first career-related job) during this period as they relate to risk status and its interaction with other familial/genetic and other environmental factors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: BUPROPION AS AN ADJUNCT TO THE NICOTINE PATCH PLUS CBT Principal Investigator & Institution: Fava, Maurizio; Director, Depression Clinical & Res. Pro; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114

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Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: We are proposing a five-year, double-blind, placebo-controlled trial on the smoking cessation efficacy of bupropion as an adjunct to the standard combination of group cognitive-behavioral therapy (CBT) plus nicotine replacement. Our primary aims are 1) to examine the additional benefit of adding the antidepressant bupropion to a standard treatment for smoking cessation of CBT and nicotine replacement among smokers who have a history of either current or past unipolar depressive disorders (major depressive disorder, dysthymia, and minor depression), and 2) to determine, if bupropion indeed improves in this population a smoker's odds of quitting, whether its effect is achieved mainly through its impact on the negative mood states associated with depression. In order to provide a powerful test of both hypotheses, this study will enroll only smokers with a history of either current or past unipolar depressive disorders. In addition, allowing the inclusion of patients with a history of unipolar depressive disorders makes the proposed study more clinically relevant and its findings more generalizable, as several studies suggest that, as the prevalence of smoking continues to diminish in the general population, an increasing percentage of those who remain smokers are patients with psychiatric illnesses, especially depression. We expect that the efficacy of the standard combination of group CBT plus nicotine replacement will be greatly enhanced by the addition of bupropion in all smokers, but that the addition of bupropion will be especially helpful to those smokers who currently suffer from clinically significant depressive symptoms. The study involves the enrollment over 48 months of 300 individuals. We predict that 50 percent of the enrolled patients will meet criteria for current unipolar depressive disorders. After the 12-week acute treatment phase, patients will be followed for 12 months. The study design therefore involves the random assignment of current or past history of unipolar depressed patients to two treatment conditions: 1) group CBT plus nicotine patch plus bupropion (current depressive disorder bupropion group, estimated n=75; past depressive disorder bupropion group, estimated n=75); 2) group CBT plus nicotine patch plus placebo (current depressive disorder placebo group, estimated n=75; past depressive disorder placebo group, estimated n=75). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: BUPROPION IN ADOLESCENTS WITH COMORBID ADHD & DEPRESSION Principal Investigator & Institution: Daviss, William B.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 06-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Attention deficit hyperactivity disorders (ADHD) in youth occur comorbidly with other psychiatric conditions approximately two thirds of the time. Major depressive disorder and dysthymic depression are common, occurring in as many as 40% of youth with ADHD. The comorbid occurrence of ADHD and depression (ADHD + Dep) may cause substantial long-term morbidity. While psychopharmacology is widely used to treat juvenile ADHD and/or depression, no research has established an efficacious treatment for ADHD + Dep, or for most other comorbid ADHD disorders. This five year Mentored Patient-Oriented Research Career Development Award (RCDA) will provide the candidate, a board certified child and adolescent psychiatrist, training to undertake pharmacological trials of youth with ADHD and comorbid disorders. The candidate has had extensive previous clinical experience and some research experience in the pharmacological treatment of juvenile ADHD + Dep. The RCDA will provide the candidate formal training in pharmacology,

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clinical trial design, and statistical analyses as well as the empirical assessment of juvenile ADHD, depression, and other comorbid psychopathology. The candidate will also receive training in ethical issues germane to juvenile psychopharmacology studies. Training will occur through a combination of formal coursework, guided readings, and consultation with mentors having relevant expertise. This training will be applied in a pharmacologic study of adolescents with ADHD and depression (major depression, dysthymia). The protocol will consist of a 2-week washout/observational period, then an 8-week randomized, placebo-controlled trial (RCT) to determine the efficacy of bupropion SR. Then a 24-week open label continuation phase will be used to determine if treatment response and tolerability persist. Exploratory analyses will assess correlations of initial treatment response with both pharmacological variables (plasma levels of bupropion and its metabolites; noradrenergic and dopaminergic effects as estimated by reuptake blockade of rat synaptosomes) and psychosocial variables (baseline psychopathology and psychosocial impairment). The candidate' s training and research experiences during the RCDA will enable him to pursue larger, more scientifically rigorous pharmacologic trials of youth with ADHD and depressive or other comorbid psychopathology. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: CAMBODIAN REFUGEES: PROBLEM ALCOHOL USE AND COMORBIDITY Principal Investigator & Institution: Marshall, Grant N.; Rand Corporation 1700 Main St Santa Monica, Ca 90401 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2005 Summary: (provided by applicant): The proposed household survey of Cambodian refugees residing in the United States will constitute the first-ever community-based, epidemiologic study assessing the prevalence of alcohol use disorders in this population.The research would also assess the co morbidity between alcohol disorders and other psychological disorders and their relation to pre-migration torture/trauma. The proposed survey is to be conducted in conjunction with an ongoing NIMH-funded study of this population. The broad purpose of the ongoing study is to determine the mental health needs of this highly traumatized population, focusing on PTSD, anxiety disorders and depressive disorders. In addition to this assessment, the ongoing study aims to relate these disorders to the respondents' experience of trauma, as well as a number of economic, social, cultural, and physical health status measures. Using a twostage random sampling strategy, 500 adult male and female refugees, ages 35-70, will be recruited for participation from Cambodian residents in Long Beach, California. Study participants will complete a 120-minute, face-to- face interview in the Khmer language conducted by lay interviewers. As part of this interview, respondents will be given three measure to assess their alcohol use: a version of the Composite International Diagnostic Interview (CIDI, World Health Organization, 1997) will be used to measure alcohol disorders, the quantity-frequency-variability(QFV) scale (Cahatan, Cisin, & Crossley, 1969) will be used to assess consumption patterns, and a scale constructed from the Cambodian terms for alcohol use will be used assess respondents relative to their culturally defined typology of drinking. The bread aims of the proposed NIAAA research are: 1. to describe the alcohol consumption patterns and to estimate the prevalence of alcohol use disorders and problem drinking in a community-based sample of Cambodian refugees residing in the United States. 2. To identify the sociodemographic factors and environmental stressors associated with higher drinking. Factors of particular interest include those relatively unique to this Southeast Asian

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Depressive Disorders

group's life experience (refugee standing, exposure to trauma/torture), those common to many new immigrants (e.g., acculturation status, and changes in family structure), as well as factors known to predict alcohol use and abuse more broadly (e.g., gender, and SES). 3. To examine the co morbidity between alcohol abuse and the psychological disorders associated with severe trauma exposure. More specifically, the study will investigate if alcohol use partially mediates the relationship between traumatic experiences and PTSD, depression and anxiety disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: CENTER FOR MENTAL HEALTH SERVICES RESEARCH Principal Investigator & Institution: Smith, G Richard.; Marie Wilson Howells Professor and Chair; Psychiatry and Behavioral Scis; University of Arkansas Med Scis Ltl Rock Little Rock, Ar 72205 Timing: Fiscal Year 2002; Project Start 30-SEP-1990; Project End 31-AUG-2003 Summary: The NIMH Center for Mental Health Services Research at the University of Arkansas for Medical Sciences addresses major research and policy questions related to the provision of mental health care services with an emphasis on rural populations by providing a productive, cooperative, nationally recognized interdisciplinary research environment. The Center's goal is to improve mental health care in the US through policy relevant and clinically relevant health services research by enhancing research capacity for mental health services research, both within the Center and nationally, and performing high-quality funded mental health services research. For individuals with mental disorders living in rural and non- rural areas, we seek to accomplish 5 specific aims: (1) Characterize policy relevant predictors of mental health service use, (2) Explain variations in the utilization and costs of mental health care services for people with psychiatric disorders, (3) Improve methods for measuring the patient characteristics, processes of care, and the outcomes of mental health care received in clinical settings, (4) Contribute to the improvement of patient care by assessing the outcomes effectiveness, and efficiency of mental health treatment, and (5) Enhances the knowledge base for mental health care by identifying, developing, and testing interventions that seek to improve the appropriateness of treatment. The Center continues its 4-fold emphasis on mental health disorders: (1) depressive disorders, (2) dementia, (3) Schizophrenia, and (4) comorbid disorders and has working groups for each area of emphasis with a corresponding portfolio of research. With this research we seek to formally broaden the focus of the Center for address mental health services problems beyond those that afflict people in rural areas. This broader focus more accurately reflects the faculty's research portfolio and interests, the increasing maturity of our research organization, and substantial expansion of our faculty since the last renewal. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: CHILDREN AT HIGH AND AT LOW RISK FOR DEPRESSION Principal Investigator & Institution: Weissman, Myrna M.; Professor; Psychiatry; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JUL-1987; Project End 31-DEC-2002 Summary: The overall aim of this high risk longitudinal (a decade) study has been: 1) to understand the nature and familial patterns of psychiatric problems in offspring at high and low risk for major depression (MDD) from childhood, adolescence and through young adulthood; 2) to determine the psychiatric status of the next generation (the grandchildren). The first aim is completed. The grandchildren were young at the last

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interview but any who were at that time age 6 or over (N=90) were assessed. Preliminary findings show the same pattern of illness in the high risk grandchildren as seen in their parents and grandparents including a prepubertal onset MDD, often comorbid with anxiety disorders, with onset of anxiety as young as age 6. This pattern transmits across the generations. The aim of this renewal is to conduct a more comprehensive assessment of an expended sample of grandchildren. Sufficient time has passed for the sample to have aged into the period of risk and the additional grandchildren will increase power so that we will be able: 1) to determine if the grandchildren demonstrate the same depressive features, impairment, medical, and behavioral problems as their parents and; 2) to add psychophysiologic measures as potential biological markers of a familial diathesis for depressive and anxiety disorders. We will measure quantitative electroencephalographic (qEEG) measures at rest, and startle responses, as well as autonomic nervous system measures, during adverse stimulation, in both grandchildren and their parents. In the context of a multigenerational high risk study such measures may: 1) simplify phenotypes through the reduction of heterogeneity; and 2) identify markers for latent, potentially genetic risk. The strength of this proposal is the availability and careful assessment of three generations of persons at high risk for MDD. This will provide a database on the magnitude, risk and sequence of psychiatric disorders which can ultimately be used to develop preventive intervention strategies and more focused treatments. Moreover, the biological markers will offer another tool for refining the phenotype for genetic and other studies and for identifying high risk offspring. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: CLINICAL IMPLICATIONS OF DEPRESSION-BASED STIGMA Principal Investigator & Institution: Miranda, Martha J.; Research Professor; Psychiatry & Biobehav Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-AUG-2006 Summary: (provided by applicant): This grant examines stigma as it relates to depressive illness. Depressive disorders are among the most significant contributors to disability and reduced quality of life worldwide, but most patients don't receive appropriate care. This is particularly true of ethnic minorities and the poor. In this grant, we examine the extent to which stigma related concerns explain failure to receive appropriate care for depression. Specifically, we examine the extent to which concerns about depression-related stigma, such as fears about losing a job, insurance, or friends due to other people's awareness of illness or treatment, explain unmet need for depression care. We will also investigate if efforts to provide treatments or improve rates of treatment predict outcomes for both persons with and without stigma concerns. We use two existing data sets: (1) Partners in Care, a randomized, controlled trial of improving quality care for depression in primary health care settings and (2) We Care, a randomized controlled trial of providing access to guideline care (either CBT or paroxetine) for disadvantaged, young minority women. These studies allow us to examine the impact of stigma related concerns on acceptance and outcomes of depression care and include large samples of poor and ethnic minorities. Finally, we include stigma items in a nationally representative community study, Healthcare for Communities, funded by the Robert Wood Johnson Foundation that will allow us to estimate rates of depression-related stigma in a nationally representative sample. The specific aims of this grant are: 1) to assess rates of concerns about depression-related stigma in a nationally representative community sample; 2) to determine the impact of

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Depressive Disorders

concerns about depression-related stigma on use of mental health services, controlling for need, predisposing, and enabling factors known to affect access to care; 3) to examine whether interventions to increase the use of guideline-concordant primary care treatments for depression are effective at improving the quality of care for both persons with high and low levels of concern about depression-related stigma; 4) to examine whether use of guideline-concordant treatments for depression (as opposed to quality improvement programs that promote access to those treatments) improve outcomes for both persons with high and low concerns about depression related stigma. Within each of the aims, we will explore the extent to which the findings vary by ethnicity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: COGNITIVE SEQUELAE OF EARLY AND MID-LIFE DEPRESSION Principal Investigator & Institution: Lee, Hochang B.; Mental Hygiene; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): This K23 application will prepare the candidate for an independent research career in the clinical epidemiology of late-life mental disorders. The focus of the research project is to determine the degree to which early and mid-life depressive spectrum disorder increases risk of developing cognitive deficits in later life. Late-life depression has been associated with subsequent development of cognitive deficits in late life,but no previous study has examined the association between early and mid-life depression and later life cognitive deficits. The proposed study provides an unusual, time-sensitive opportunity to test this hypothesis by taking advantage of the recently funded fourth wave of the Baltimore Epidemiologic Catchment Area (ECA) study. Using a retrospective cohort design, the investigator proposes to sample people with depression before age 50 as assessed in previous waves of the Baltimore ECA studies, and examine their neuropsychological outcomes 10 to 23 years later. The specific aims of the proposal are: 1) to determine whether early and mid-life depressive spectrum disorder (before age 50) increases risk of developing Mild Cognitive Impairment or dementia in later life (after age 60), 2) to investigate the longitudinal association between early and mid-life depressive spectrum disorder and late life cognitive deficits in specific neuropsychological domains (i.e. executive function and memory), and 3) to estimate what extent duration, number of episodes, and severity of early and mid-life depressive spectrum disorder predict cognitive impairment in late life. This study will serve as a vehicle for the candidate to obtain invaluable experience in the design and fieldwork of an epidemiologic study of the aging population. To complement his practical research training, the candidate will concurrently enroll in formal courses in Epidemiology and Biostatistics of Aging and fulfill the requirements for a Master's degree. He will participate in seminars in the post-doctoral program in neuropsychology to develop advanced knowledge in use and interpretation of neuropsychological instruments. A panel of mentors and consultants (Drs. Constantine Lyketsos, William Eaton, Jason Brandt, George Rebok, Kung-Yee Liang, George Alexopoulos, and Anand Kumar) will guide his research and training. This award will provide groundwork for his long term goal of becoming an expert in clinical epidemiology of late life mental disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: COLLABORATIVE DEPRESSION STUDY Principal Investigator & Institution: Coryell, William H.; Professor; Psychiatry; University of Iowa Iowa City, Ia 52242

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Timing: Fiscal Year 2004; Project Start 01-JUL-1977; Project End 31-JAN-2009 Summary: (provided by applicant): The Collaborative Depression Study (CDS) has advanced the long-term prospective study of mood disorders. This revised application seeks to extend the prospective annual follow-up of the CDS probands to at least 27 years for all subjects. Renewed funding will permit us to better address the general aim of describing the long-term course of moderate to severe major mood disorders in ways not previously possible and to further investigate the general hypothesis that many individuals with moderate to severe mood disorders will develop a lifelong illness. Since no similar data set exists to collect information of this nature, the next 5 years of continued data collection are essential to gaining a complete perspective of the lifetime course of mood disorders, particularly as many more of our subjects pass the age of 65 when the effects of aging on the course of mood disorders can be better assessed. The specific aims are to provide long-term, prospective, data that will help investigators to study: (1) the patterns and predictors of course of illness and psychosocial outcome in mood disorders; (2) morbidity, mortality and suicide associated with mood disorders; (3) somatic treatment as a mediating variable of outcome in mood disorders; (4) the longitudinal course of syndromal and sub-syndromal affective symptoms in subjects with unipolar and bipolar depressive disorders; and (5) mood disorders and aging. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: COMORBID ANXIETY DISORDERS IN ADOLESCENTS WITH ASTHMA Principal Investigator & Institution: Katon, Wayne J.; Professor; Psychiatry and Behavioral Scis; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2007 Summary: (provided by investigator): Asthma is the most common chronic illness of childhood and adolescence, and the prevalence rate is increasing. Results from prior studies have suggested an increased prevalence of panic disorder and other anxiety disorders in populations of children and adults with asthma. However, these studies have been limited by having been carried out in tertiary-care settings with small numbers of patients and by a lack of information on the effect of comorbid anxiety and depressive disorders on asthma outcomes. In this epidemiologic study, we propose to (1) compare adolescents with panic disorder and asthma to those with asthma alone in order to measure the impact of panic comorbidity on the personal, familial and societal impacts of asthma such as symptom burden, functional status, quality of life, medical costs and on the quality of asthma self-management; (2) compare adolescents with asthma with one or more anxiety and depressive disorders to adolescents with asthma alone in order to measure the impact of anxiety/depression on the same outcomes as Aim #1. By self-management, we refer to both patients' and providers' roles in ongoing care of a recurrent or chronic illness. These analyses will control for severity of asthma, medical comorbidity and, in Aim #1, psychiatric comorbidity. In addition, two secondary aims include (3) estimating the prevalence of panic disorder and other anxiety and affective disorders in a population-based sample of 1,300 12- to 17-year-olds with asthma enrolled in an HMO and the accuracy of mental health diagnoses and quality of the mental health care provided for these anxiety and depressive disorders; and (4) demonstrating that adolescents with asthma and DSM IV anxiety and/or depressive disorders will have higher parental- and self-ratings of anxiety and depressive symptoms. We anticipate that the results of this study will increase epidemiologic knowledge regarding the effects of comorbid panic disorder and other important anxiety and depressive disorders in adolescents with asthma, and will

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increase awareness of the impact of these psychiatric disorders on asthma management and outcomes in adolescents. Our research team has over a decade of experience designing population-based intervention studies to improve outcomes for both patients with anxiety and depressive disorders as well as asthma within primary care settings. The results of this grant will be used to develop future treatment programs for adolescent patients with comorbid asthma and anxiety. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: CORONARY RELATIONSHIP

HEART

DISEASE

ANXIETY:

PREVALENCE,

Principal Investigator & Institution: Carmin, Cheryl N.; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): The goals of this career development award are designed enable the candidate to develop a program of independent research examining the relationship between anxiety disorders and coronary heart disease (CHD). This study would contribute to the investigator's long-term career goal of examining the relationship between anxiety disorders and medical illness, such as CHD. There is a relatively well-established link between emotional and behavioral variables and the risk for CHD. Despite the comorbidity of anxiety and depressive disorders, the lines of research investigating these conditions and CHD have remained largely independent of one another. Further, despite it being more prevalent than and often pre-dating the onset of depression, less attention has been paid to the relationship between anxiety and CHD. The existing research focusing on anxiety disorders in those at risk for or who have CHD is limited by the use of descriptive, rather than state-of-the-art diagnostic measures of psychopathology. It remains unclear to what extent clinically significant anxiety disorders serve as independent risk factors and may be influential in the development of CHD. In order to address the risk that anxiety disorders pose in CHD prone individuals, the initial phase of this award will allow the investigator to develop background in areas related to the interface between cardiology and psychology including psychosocial epidemiology, biostatistics, psychophysiological assessment, and scanning technology related to CHD. Existing epidemiological databases that assess CHD will be utilized to determine whether anxiety disorders are independently related to the development of CHD. The 2 nd phase of the award will be used to apply the skills acquired in coursework and in analyzing existing data to execute a study comparing a sample of anxiety disordered subjects to a matched control group based on anxiety symptoms (severity, frequency, duration), cardiac calcium as assessed by electron beam tomography, lipid levels, and heart rate variability. The investigator is in the unique position of having access to individuals who are being screened for CHD using EBT as well as having access mentors and collaborators involved in multicenter cardiovascular research (Drs. Lynda Powell, Peter Buttrick, Kiang Liu, George Kondos), psychophysiological research (Dr. Stephen Porges) and who are experienced in the psychopathology and treatment of anxiety disorders (Dr. Richard Heimberg). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: CORPUS CALLOSUM IN MALTREATED CHILDREN WITH PTSD Principal Investigator & Institution: Kaufman, Joan R.; Associate Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2003; Project Start 04-DEC-2002; Project End 30-NOV-2007

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Summary: (provided by applicant): Child abuse occurs at epidemic rates, with victims of abuse comprising a significant proportion of all child psychiatric admissions. Posttraumatic Stress Disorder (PTSD) is a common and often debilitating consequence of early child maltreatment, and currently little is known about the mechanisms that initiate and maintain the symptoms associated with this disorder. Emerging evidence in human and non-human primates suggest that the neurobiological changes associated with early stress may vary at different developmental periods. While much of the preclinical and clinical work on the effects of early stress point to the importance of the hippocampus as a key structure involved in the pathophysiology of PTSD in adults, recent findings suggest that alterations in the corpus callosum may be more prominent in juvenile samples. Consequently, in this study, assessments of the corpus callosum will be obtained using structural and diffusion tensor imaging in three groups of children: 50 maltreated children with PTSD, 50 trauma (e.g., maltreated) controls without psychopathology, and 50 normal controls with no lifetime history of intrafamilial or extrafamilial trauma and no lifetime history of psychopathology. Measures of inter-hemispheric transfer and memory function will also be obtained, together with comprehensive assessments of early trauma, social supports, current life stressors, and family loading for psychopathology. Neuroanatomical assessments will be obtained at baseline, and clinical and psychosocial assessments will be obtained at six-month intervals for two years after study intake. It is hypothesized that when compared to trauma and normal controls, maltreated children with PTSD will have reduced cross sectional area of the medial and caudal portions of the corpus callosum, and reduced fractional anisotropy in these regions (e.g., poorer integrity of white matter tracts). No changes in hippocampal volume are expected. A greater loading for anxiety and depressive disorders among first-degree relatives, an absence of positive stable supports, and exposure to ongoing stressors is expected to be associated with more severe PTSD symptomatology at intake, greater persistence of symptoms at follow-up, and more marked neuroimaging abnormalities. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: CORTICOSTEROID NEUROMODULATION OF SEROTONIN SYSTEM AGING Principal Investigator & Institution: Lakoski, Joan M.; Professor; Pharmacology; Pennsylvania State Univ Hershey Med Ctr 500 University Drive Hershey, Pa 170332390 Timing: Fiscal Year 2002; Project Start 01-FEB-2000; Project End 31-JUL-2002 Summary: Depressive disorders are linked to impairments in the regulation of glucocorticoid and serotonin (5-HT) systems. Examination of depression in the elderly patient has revealed a role for the interaction of the adrenal hormone corticosterone and 5-HT receptors and may also underlie deficits in memory, learning and losses in ability to adapt to stress with aging. Our long term goal is to understand corticosterone and 5HT receptor interaction in the aging hippocampus and provide new clinical approaches for improving the treatment of depression and memory loss in geriatric patients. Using a corticosterone treatment paradigm, we will test the hypothesis that the cellular pharmacological characteristics of the 5-HT1A receptor subtype, as modulated by corticosteroids in the hippocampus, change with aging and loose responsiveness to this hormone, including losses in signal transduction. Electrophysiological, neurochemical and molecular biological approaches will be utilized in the female Fischer 344 rat (3, 12 and 18 mo) under several conditions of corticosterone hormone exposure (adrenalectomy plus low, moderate and high concentrations of hormone replacement) sham adrenalectomy or intact treatment. Aim 1 will utilize in vivo extracellular

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Depressive Disorders

recording techniques in the chloral hydrate anesthetized rat chronically treated with corticosterone and evaluate neuronal responses to selective 5-HT1A receptor agonists with aging. Aim 2 will establish the effect of chronic corticosterone exposure on binding and gene expression characteristics of the 5-HT1A receptor in the aging hippocampus using radioligand binding, quantitative autoradiography and in situ hybridization techniques. Aim 3 will address signal transduction in the aging hippocampus mediating corticosterone and 5-HT receptor interactions. Chronic corticosterone administration effects on G protein levels will be examined by Western blot techniques and compared with assessment of age- associated declines in 5-HT1A receptor-mediated G proteincoupling. The results of these studies may lead to an indication that specific glucocorticoid antagonists may facilitate the onset of therapeutic efficacy for antidepressants in the elderly via actions at the serotonergic system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION

CULTURALLY

RELEVANT

PSYCHOTHERAPY--PERINATAL

Principal Investigator & Institution: Grote, Nancy K.; None; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-JAN-2008 Summary: (provided by applicant): Depression during the perinatal period has adverse effects on the mother, on the development of her newborn infant, and on her family relationships. The purpose of this proposed mentored Patient-Oriented Research Career Development (K23) Award is to promote the Candidate's long-term goal of conducting clinical trials of culturally relevant, psychosocial interventions for perinatal depression in low-income, African American and White Ob/Gyn patients to ameliorate their depression during pregnancy and prevent postpartum depression. The training and research activities described in this application will take place in the cross-disciplinary environment of the School of Social Work and the Department of Psychiatry, University of Pittsburgh. Training will enable the Candidate to assess perinatal mood disorders, develop culturally relevant strategies to effectively engage and retain Ob/Gyn patients in multi-session psychosocial interventions, conduct randomized clinical trials of psychosocial treatments, and collaborate with health services researchers to enhance the public health value of the intervention. Interpersonal psychotherapy (IPT) addresses both depressive symptoms and problematic interpersonal relationships and is an efficacious treatment for depression in general (Weissman, Markowitz, & Klerman, 2000), as well as for depressed African American and White primary care patients (Brown et al, 1999). The first phase of this research plan consists of employing an 8session form of IPT 0PT-B; Swartz, Frank, & Shear, 2002) and modifying it to be more culturally relevant to poor, African American and White Ob/Gyn patients by incorporating a number of engagement strategies to minimize practical and psychological practical barriers to care. The second phase of the research plan consists of a small, randomized pilot trial comparing treatment as usual to culturally relevant IPT-B (followed by monthly maintenance IPT up to 6 months postpartum) in a sample of depressed, pregnant, low-income African American and White patients in a public care Ob/Gyn clinic. Participants will be assessed at baseline, posttreatment, and 2 months and 6 months postpartum. The skills, training, and pilot data obtained from this award will support the development of an RO1 application in Years 03-05 of the award period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEPRESSION AND ALTERED PAIN PERCEPTION Principal Investigator & Institution: Symonds, Laura L.; Assistant Professor; Psychiatry; Michigan State University 301 Administration Bldg East Lansing, Mi 48824 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2005 Summary: (provided by applicant): The broad, long-term objective of this proposal is to understand the pathophysiology underlying altered pain perception in depressed individuals as a way of understanding the neural dysfunction in depression. The specific aims are to (1) test the effectiveness of our recently developed mood induction paradigm that will effectively induce depressed mood in both pain and fMRI experiments, (2) use phasic and tonic pain stimuli to rest the hypothesis that depressed mood potentiates the perception of pain, and (3) use fMRI to test the hypothesis that mood-altered pain perception is accompanied by activity changes in limbic and prefrontal regions. The health relatedness of the project is that an understanding of the underlying pathophysiology of altered pain in depression could lead to the development of new treatment strategies for both depressive disorders and chronic pain. The research designs are (1) test the effectiveness of a mood induction paradigm to induce depressed moods, (2) measure the ability of depressed mood to alter perceived intensity of both phasic and tonic pain stimuli and to reduce tolerance to tonic pain, and (3) use fMRI in phasic pain experiments to compare activity in limbic and prefrontal brain regions during depressed and non-depressed moods. The methods to be used are psychological mood scales, delivery of phasic electric shock and tonic cold pressor pain, and functional magnetic resonance imaging during delivery of pain stimuli in different mood states. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEPRESSION AND BRAIN STRUCTURE IN TYPE 1 DIABETES Principal Investigator & Institution: Jacobson, Alan M.; Senior Vice President; Joslin Diabetes Center Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2006 Summary: (provided by applicant): There is growing evidence that type 1 diabetes leads to an increased prevalence of depressive disorders and preliminary data suggesting that the metabolic disturbances associated with diabetes, both severe hypoglycemia and persistent hyperglycemia, lead to changes in brain structure and cognition. These findings, together with research on structural changes in the brain among depressed patients without diabetes, suggest that diabetes could cause structural changes in the brain that lead to depression. No studies have evaluated mechanisms underlying the etiology of depression among patients with type 1 diabetes. Using a cross sectional research design, we propose to study six groups of subjects: All subjects (N = 180) will be ages 30-40, right-handed and matched according to age, gender and SES. Diabetic patients will have between a 15-25 year history of types of diabetes. There will be three groups of diabetic subjects without psychiatric history: 1. Well controlled (0-1 episodes of severe hypoglycemia; mean HbA1c over history of diabetes equal to or 3 episodes of severe hypoglycemia; mean HbA1c over time equal to or 9.0%; 0-1 hypoglycemic episodes). A fourth group of diabetic subjects with a history of unipolar major depression and who equally represent the glycemic control characteristics of the other three diabetic groups will also be studied. In addition, two non-diabetic control groups (history of depression; no psychiatric history) will also be studied. We will assess these patients as to brain structure, using Magnetic Resonance Imaging (MRI); depression, using the Structured Clinical Interview for DMS IV (SCID); and cognition using the

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Depressive Disorders

Wechsler Adult Intelligence Scale III (WAIS III) and other neuropsychological tests of memory, psychomotor speed and mental efficiency. We will also evaluate medical factors (e.g., glycemic control-HbA1c; and history of severe hypoglycemia). We will examine whether: 1) structural abnormalities are more common in diabetic subjects compared to the matched community controls; 2) there is a relationship between diabetes specific medical variables, such as long-term glycemic control, and brain structure abnormalities; 3) structural abnormalities are more common in diabetic patients with a history of unipolar major depression than diabetic patients without a history of depression; and 4) the frequency of structural abnormalities in the brain among diabetic patients with a lifetime history of unipolar depression differs from the depression control group. The proposed research will, for the first time, provide evidence regarding the linkage between structural changes in the brain and depressive disorder in diabetes, and evidence about the relationship of type I diabetes and its attendant metabolic disturbances to structural changes in the brain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION AND END OF LIFE CARE IN ALS Principal Investigator & Institution: Albert, Steven M.; Gertrude H Sergievsky Center; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 20-AUG-2000; Project End 31-JUL-2004 Summary: (Adapted from investigator's abstract) Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that results in death, usually from respiratory insufficiency or aspiration, within 3 to 5 years of diagnosis. The disease affects all voluntary motor function except eye movement and sphincter control. In the final 6-9 months of life, patients must choose (either explicitly or by default) palliation or tracheostomy and long-term mechanical ventilation (LTMV). In this 4 year project, we will follow 140 patients diagnosed with definite or probable ALS who face a high likelihood of death within 6-9 months, as defined by poor pulmonary function, dysphagia and weight loss, or hospice certification or eligibility. These patients will be followed with bimonthly in-home assessments, and with an additional assessment in the last weeks of life. We will also interview the primary family caregiver on the same schedule and once after the patient's death, as well as conduct a survey of medical providers' influence on end-of-life decisions. In this observational cohort study, we propose (1) to assess the prevalence and course of depressive disorders and symptoms in ALS patients in the final months of life and its relevance for decision-making at the end of life; (2) to identify predictors of tracheostomy/LTMV use; (3) to examine the degree to which patients and families take steps to control the timing of death by adopting a strict palliative care regime; and (4) to examine associations between patient and caregiver distress in the final months of life. Key questions include the following: Do levels of distress and depressive symptoms increase as patients approach death, and does this relationship differ according to choice of palliative care or LTMV? What maintains hope in these patients, who are, in a medical sense, hopelessly ill? Of patients who receive LTMV, in what proportion is LTMV consciously planning for, as opposed to an unplanned emergency procedure? Is patient mental health or caregiver burden associated with decisions to forego or undergo LTMV? To what degree does use of noninvasive, temporary nasal ventilation (Bi-Pap) prevent use of LTMV? These questions have not been investigated in a prospective study. We will be able to address them through repeated, detailed assessments of patients and caregivers. This information will be critical for understanding the experience of patients with terminal disease as they and their families face end-of-life care decisions.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION IN BLACK AND WHITE ADOLESCENT GIRLS Principal Investigator & Institution: Franko, Debra L.; Psychology; Wesleyan University Middletown, Ct 064590241 Timing: Fiscal Year 2002; Project Start 01-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The broad, long-term goal of this research is the development of effective preventive interventions to reduce the prevalence of common mental disorders among adolescent and young adult women. Specifically, the aims of this project are to clarify the risk factors for and consequences of depression and related psychopathology in female Black and White adolescents and young adults. By increasing our understanding of the vulnerabilities for and outcomes of depression, more specific and effective prevention strategies can be developed. The three major aims of this project are: 1) To determine ethnicity-specific prevalence rates of depressive symptoms and syndromes of depression in Black and White females during adolescence and early adulthood; 2) To test a bio-psycho-social model of risk for depression in Black and White girls, by exploring the relationship between risk factors (e.g., coping style, body image, pubertal timing, and stressful life events) and the emergence of depressive symptoms during adolescence; 3) To examine the outcomes of adolescent depression for Black and White women. The following outcome variables will be investigated: obesity and health services utilization, psychosocial factors, and psychiatric comorbidity. Capitalizing upon the availability of extensive data collected prospectively among an exceptionally well-maintained cohort of 2,3 79 Black and White females over a 12-year period (from ages 9-10 to ages 2 1-23), we propose to apply innovative analytic procedures to further the scientific understanding of risk factors, course, and outcomes of depressive symptoms in adolescence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEPRESSION INTERVENTIONS

IN

OBGYN:

EPIDEMIOLOGY/SERVICES

Principal Investigator & Institution: Melville, Jennifer; Obstetrics and Gynecology; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2004; Project Start 05-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Depressive disorders are twice as prevalent in women as in men and frequently comorbid with gynecologic disorders such as urinary incontinence (UI). OB-GYNs have exceptional access to women during the reproductive years, which is the time of peak incidence of depression. OB-GYNs therefore have a unique but unrealized opportunity to detect and initiate treatment or referral for depression in reproductive age and postmenopausal women. The increased prevalence of current major depression in women with UI indicates that this disorder may provide a useful avenue for improving detection of depression in the OB-GYN clinical setting. The goal of this 5-year Mentored Patient-Oriented Research Career Development Award is to enable the applicant to obtain the necessary skills and training to become an independent women's mental health investigator working at the interface of Psychiatry and OB-GYN, with specific focus on elucidating interactions between depression and UI and on developing health services interventions to improve treatment outcomes of depression in women with UI in the OB-GYN clinical setting. This career development award will consist of coursework, mentorship, and supervised investigations focusing on: 1) determining the prevalence and impact of major depression in women with UI, 2)

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Depressive Disorders

examining reciprocal relationships between major depression and UI, and 3) developing health services interventions in the OB-GYN clinical setting to improve treatment outcomes of depression in women with UI. Career development activities will be applied to three mentored research studies. In Study 1, analyses of two existing population data sets will be used to develop a conceptual framework for the relationship between major depression and UI in women. In Study 2, in-depth qualitative assessments of women with major depression and UI will assess how incontinent women with depression view their depression and how comorbid disease influences illness perceptions and care seeking behaviors. In Study 3, findings from Studies l and 2 will be integrated with award training activities to design and implement a pilot intervention to improve treatment outcomes of depression in women with UI in the OB-GYN clinical setting. Results from this study will be used to prepare an R01 clinical effectiveness trial. This K23 award will enable the applicant to bridge the gap between OB-GYN and mental health services research, an alignment that is necessary to integrate these fields and improve women's mental health. The award will provide crucial support for the applicant's ongoing development as an investigator in the area of depression in women. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION IN TEMPORAL LOBE EPILEPSY Principal Investigator & Institution: Jones, Jana E.; Neurology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2006 Summary: (provided by applicant): The proposed study would be the first controlled prospective investigation of the incidence and predictors of depressive disorders in individuals with chronic temporal lobe epilepsy (TLE). Beginning four years ago, a large cohort of individuals with TLE and healthy controls underwent a baseline psychiatric interview, MRI, cognitive testing, and assessment of quality of life. For this project, a consecutive series of individuals with TLE and controls (n = 118) will be seen four years later in order to: 1) determine the prospective incidence and relative risk of DSM-IV major depression and other depressive disorders in chronic TLE compared to controls; 2) identify the psychiatric, stressful life events, MRI, and clinical epilepsy variables predictive of prospective episodes of major depression and other depressive disorders over the interval; 3) identify the incidence of depressive episodes which meet the DSMIV-TR criteria for minor depressive disorder and recurrent brief depressive disorder. The methodology will include: l) a comprehensive standardized psychiatric re-interview of DSM-IV Axis I disorders (SCID); 2) identification of stressful life events that occurred over the interval; and 3) review of medical records with participant interview to determine change in interval regarding seizure frequency and treatment. This study will make a significant contribution to understanding a major psychiatric complication in epilepsy and will integrate psychosocial, neurobiological, and clinical factors to provide a more comprehensive understanding of depressive episodes in epilepsy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEPRESSIVE DISORDERS IN PRIMARY CARE AND WORK SETTINGS Principal Investigator & Institution: Druss, Benjamin G.; Assssociate Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2002

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29

Summary: The proposed K08 Mentored Clinical Scientist Development Award outlines a program of training and health services research studying the impact of depressive disorders outside of the specialty mental health sector. The candidate is an Assistant Professor of Psychiatry and Public Health at Yale University with a clinical background in psychiatry and primary care internal medicine, as well as postdoctoral health services research training. The career award will allow the candidate to successfully conduct the proposed studies and develop a career as an independent researcher through classes in research design, statistics, economics, and organizational theory at Yale, and via off-site training with experts in the field. Yale University offers a rich source of resources and faculty and a growing breadth of experience in health services research. The career award mentor, Robert A. Rosenheck MD, is a nationally known health services researcher and director of the Health Services Research and Treatment Outcomes Division for the Yale Department of Psychiatry; the candidate and Dr. Rosenheck have developed a close collaborative relationship. The growing importance of purchasers and primary care providers in determining benefits and delivering care for depression has made it an increasing priority to understand the costs of depression in the workplace and general medical settings. The research program seeks to fill gaps in the previous literature studying the impact of depression in these two areas. The first project will seek to provide a better understanding of the causal mechanisms underlying the association between depression and increased use of general medical services. It will examine the role of health beliefs--a person's perception of his or her medical condition, and of the benefits and barriers to treatment--in mediating the relationship between depression and medical utilization. The second project will use a longitudinal database combining work and health claims data for employees of a major US corporation. This project will compare the impact of depression and three chronic medical illnesses on health costs, absenteeism and job performance ratings both cross-sectionally and over time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DETECTING DEPRESSIVE SYMPTOMS IN OLDER ADULTS Principal Investigator & Institution: Duberstein, Paul R.; Associate Professor; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): One consistent and disturbing finding in the suicide literature compels this investigation. Most older adults who take their own lives have an affective disorder, but the potential risk for suicide was unrecognized by family members and health professionals. The central thrust of our symptom detection model is that specific factors deter the detection, diagnosis, and treatment of depression in older adults. ROl funding is sought to test aspects of this model in a demographically and clinically heterogeneous sample of 1000 primary care patients 65 years of age and older. Beginning in August 2001, these patients were recruited into a naturalistic study, "Depression Outcome in Primary Care Elderly" (DPC) (NIMH ROl MH61429-O1A1, J. Lyness, M.D., P.I.). For this proposed ROl, we will collect data from informants who are members of the social networks of participants in the DPC study in order to examine informant detection of depressive disorders and symptoms of depression and anxiety. We will strive to recruit one informant for each subject in that study, and plan to collect data from more than 628 informants. We will ask the informants questions about themselves and the DPC participants' psychiatric symptoms. Specifically, we will examine informant detection of depression as a function of: the severity and history of patients' psychiatric disorders (Aim 1), patients' psychosocial (personality and social

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Depressive Disorders

support) characteristics and physical health parameters (Aim 2), patients' demographic characteristics (Aim 3), and informants' psychiatric history and self-reported health (Aim 4). We will explore the role of informants' personality traits and attitudes toward mental illness, and differences between African-Americans and Whites will be explored. We hypothesize the detection will be poorer for: disorders that are less severe and first episode (Aim1); patients with certain personality traits (e.g., low extraversion; low openness to experience) or poor physical health (Aim 2); and men and unmarried participants (Aim 3). Detection will also be poorer when informants have no prior history of depression or are in poor physical health (Aim 4). For Aim 2, the mediating effect of social support will be examined. Confirmation of these hypotheses will indicate needed revisions in current approaches to late-life depression and suicide. Findings will help guide the development of screening instruments, educational and clinical interventions, and surveillance strategies to lessen the public health impact of unrecognized and untreated depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DETECTION AND TREATMENT OF POSTPARTUM DEPRESSION Principal Investigator & Institution: Yonkers, Kimberly A.; Associate Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 01-SEP-1999; Project End 31-AUG-2004 Summary: This Mentored Clinical Scientist Development Award (MRSCA) application defines a training program which will facilitate the development of the Principal Investigator (PI) as an independent investigator in effectiveness research. The educational activities outlined will enable the PI to change her focus from pharmacotherapy-based clinical trials in controlled environments to an investigator who examines the effectiveness, applicability, and costs of clinical interventions in actual clinical care settings. The training entails mastering a new treatment technique (Interpersonal Psychotherapy) and applying methods to measure a variety of health outcomes (symptomatic, quality of life, economic) in a diverse patient population. In order to achieve these training goals, the PI has developed a program that includes unique preceptorships, didactic courses, tutorials and several pilot projects. The proposed pilot projects will afford a hands-on experience, reinforcing the information and technqiues learned in the mentored and classroom settings. Specifically, the research will focus on the screening, recruitment, engagement and treatment of underserved women suffering from postpartum depression. Depression, which is a serious medical condition, has a lifetime prevalence in women of 21 percent. The postpartum period constitutes a time of increased risk for depressive disorders, and encompasses an especially critical time in the life cycle of both mother and infant. Despite the magnitude of this problem, postpartum depressive illnesses are frequently unrecognized. Under diagnosis and under detection are especially germane to socioeconomically disadvantaged women since they have a greater likelihood of suffering from depressive disorders, yet have more limited access to health care. The screening and treatment techniques investigated in this proposal will be piloted in this population through the UTSWMC Maternal Health and Family Planning Clinics (MHFPCs). It is anticipated that the programs instituted through this grant will ultimately be employed in an ongoing and cost-effective manner. This MRSCA is crucial in launching the PI into the arena of effectiveness research. Through this award, she will be able to extend her previous research commitment by adding new skills and knowledge which will enable her to contribute more meaningfully to our understanding of psychiatric interventions in real world settings.

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Project Title: DEVELOPMENT OF A GROUP CBT PROGRAM FOR PTSD AFTER A MVA Principal Investigator & Institution: Beck, J. Gayle.; Professor; Psychology; State University of New York at Buffalo Suite 211 Ub Commons Buffalo, Ny 14228 Timing: Fiscal Year 2002; Project Start 19-AUG-2002; Project End 31-JUL-2005 Summary: (provided by applicant): The goal of this application is to refine and pilot test a brief Group Cognitive Behavioral Treatment (CBT) to address the symptoms of Posttraumatic Stress Disorder (PTSD) following a motor vehicle accident. The application has 2 phases that encompass 3 specific aims. Phase 1 will Consist of completion of the treatment manual for Group CBT for PTSD in MVA survivors (Aim 1). Also included during Phase 1 will be efforts to finalize and empirically test procedures to ensure therapists' adherence and competence in using the treatment manual (including measures to assess adherence and competence - Aim 2). 15 individuals with MVA-reiated PTSD will participate in Phase 1. to be treated in 3 groups of 5 each. Participants will be diagnosed with the Clinician Administered PTSD Scale and will complete a battery of additional clinician and self-report measures before and after treatment. Phase 1 will be an iterative process across the 3 waves of 5 cases each. After each wave, the treatment manual and measures of adherence and competence will be refined. Phase 2 will involve a randomized pilot study, consisting of 2 treatment conditions: Group CBT and a Minimal Contact Control (MCC) condition. The aim of Phase 2 is to determine if Group CBT produces significant reductions in PTSD symptoms, anxiety, depression, health care use, and pain-related distress and impairment (Aim 3). 48 individuals with MVA-related PTSD will be randomly assigned to one of the 2 conditions. Outcome will be assessed using clinician measures of PTSD symptoms, anxiety disorders, and depressive disorders. As well, participants will complete questionnaires evaluating PTSD, anxiety, depression, health care utilization, and pain. It is hypothesized that patients with PTSD who receive Group CBT will show greater reductions in PTSD symptoms, anxiety, depression, health care use, and pain, relative to patients who receive MCC, at post-treatment assessment. Additionally, it is hypothesized that patients who receive Group CBT will maintain these gains at 3-month follow-up. Following participation, individuals in the MCC condition will be offered Group CBT, permitting uncontrolled replication. Examination of intent-to-treat participants will permit initial evaluation of the acceptability of Group CBT. Because MVAs are the single leading cause of PTSD in the general population, this application has the potential to provide a cost-efficient treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: INITIATIVES

DRUG

ABUSE

PHARMACOTHERAPY:

METHODOLOGIC

Principal Investigator & Institution: Nunes, Edward V.; Associate Professor of Clinical Psychiat; Psychiatry; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-APR-1996; Project End 31-JUL-2006 Summary: (Provided by Applicant) The overall aim of this proposal is to support the continuing development of the applicant as a scientist in the field of drug abuse treatment. The applicant's program of research is driven by two main themes: 1) That pharmacotherapies may be developed by considering the heterogeneity of drug

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Depressive Disorders

addicted samples and targeting interventions to specific subgroups; and 2) That the efficacy of medications may be enhanced by developing combined behavioral and pharmacologic interventions and by examining the implications of initial abstinence during a placebo lead-in upon medication effects. During the proposed K02, the applicant will serve as principle investigator on four main projects: I.) A placebocontrolled trial of venlafaxine for cocaine abusers with depressive disorders (P50 DA09236, Project 3); II.) A Stage I project to develop a behavioral therapy for depression in opiate dependent patients based on operant theory (R01 DA13118); III.) Cocaine medication development trials examining the efficacy of the NMDA antagonist memantine and the GABA enhancer gabapentin, and also examining the impact of abstinence during an initial placebo lead-in upon demonstration of medication effects (P50 DA12761, Project 1); and IV.) A controlled trial testing the efficacy of a behavioral therapy designed to improve the success of oral naltrexone maintenance for opiate dependence, and simultaneously testing the efficacy of an initial injection of a longacting depot naltrexone formulation in improving retention in naltrexone maintenance treatment (R01 DA10746). The applicant will continue to assume a leadership role in the Department in mentoring young investigators, including junior colleagues on the above projects and research fellows. These mentorships extend the applicant's main research themes, for example addressing the treatment implications of comorbid disorders other than depression (e.g. attention deficit disorder, impulsive aggression, pathological gambling) and seeking opportunities for early intervention in children and adolescents at high risk for drug abuse. The applicant will continue to pursue a training plan focused on methodology and statistics of clinical trials, behavioral interventions, and the responsible conduct of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION

ELUCIDATING

THE

NEUROBIOLOGY

OF

POSTPARTUM

Principal Investigator & Institution: Moses-Kolko, Eydie L.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 05-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This revised Mentored Patient-Oriented Research Career Development Award Application (K23 describes a program of training and research using positron emission tomography (PET) to identify neurobiological processes mediating women's depressive syndromes that occur at reproductive transitions. Career development activities will focus on PET advanced analysis and modeling techniques reproductive endocrinology, cellular and molecular neuroscience, Psychiatric assessment, and clinical research design and statistical methods. These skills will be applied to the study of serotonin-IA (5HT1A receptor binding potential (BP) and resting cerebral blood flow (CBF) in DSM-lV-defined major depressive disorder (MDD) with postpartum onset. The association of female gonadal steroids (FGS with MDD and its treatment suggests FGS are important mediators of depressive disorders in women Because postpartum major depression (PPD) occurs in the setting of massive endocrine shifts, this provides a unique opportunity to explore the neurobiology of depressive syndromes that occur a reproductive transitions. Based upon existing characterization in the literature and in our PET Facility of depressive populations using probes for 5HT1A receptor BP ([11C] WAY-100635) and CBF ([15O] water) methods for measuring these targets will be applied in women with PPD, non-postpartum MDD postpartum healthy controls, and non-postpartum healthy controls. Hypothalamic-pituitary-ovarian (HPO and hypothalamic-pituitary-adrenal (HPA) axis function will be assessed in relation to

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PET measures Multidisciplinary didactic training, research experience, and preliminary data garnered from the proposed application will enable the candidate to become an independent investigator of the neurobiology of depressive syndromes associated with reproductive transitions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: EMERGENCE:CO-OCCURRING DEPRESSION/EXTERNALIZING PROBLEMS Principal Investigator & Institution: Vander Stoep, Ann; Psychiatry and Behavioral Scis; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 16-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): This application entitled: "Emergence of Cooccurring Depressive and Externalizing Problems: Phenomenology, Course, and Outcome" was written as a response to RFA: MH-01-002. The Principal Investigator is a new investigator, who has convened a team of experienced developmental psychologists and research methodologists. Mental illness is a significant public health problem that is common in children and adversely affects their development. According to the recently published Surgeon General's Report, "mental illnesses exact a staggering toll on millions of individuals, as well as on their families and communities, and our Nation as a whole." Critical to the Healthy People 2010 objective of reducing the prevalence of mental disorders among children and adolescents is a clearer understanding of the developmental processes underlying childhood psychopathology. For children who have mental disorders, co-occurrence of multiple disorders is more the rule than the exception. Yet very little is known about the differences in phenomenology, course, and outcome when disorders co-occur and when they do not. The proposed study is designed to identify developmental precursors, describe phenomenology, document developmental sequences, identify moderators and mediators of longitudinal course, and document functional outcomes in four groups of children. Study subjects will include children in three "vulnerable" groups: depressive, only; externalizing, only; and co-occurring depressive and externalizing; and a comparison group of children without these vulnerabilities. The study will be conducted in King County, Washington. Study subjects will be selected on the basis of school problem status and parent-reported internalizing and externalizing problems from among 6th grade students in the Seattle Public Schools. In-person structured interviews focusing on key study constructs will be conducted with children and their caregivers and teachers at Baseline and at 12 and 24-month follow-up, with telephone/mail interviews conducted at intervening points. To address study aims, longitudinal data will be analyzed using logistic regression, Cox proportional hazards, growth mixture models, and classification and regression tree (CART) methods. Understanding the nature of co-occurring psychopathology will have important implications for nosology, as well as for the development of effective prevention and treatment approaches. The availability of a diverse population of children, the collaborative relationship between the University of Washington and the Seattle Public School District, and the experienced team of researchers create excellent conditions to conduct a study that can specifically address the questions posed in this RFA. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Depressive Disorders

Project Title: EMOTIONAL DYSREGULATION: DEPRESSION AND FAMILY STRESS Principal Investigator & Institution: Sheeber, Lisa B.; Oregon Research Institute Eugene, or 97403 Timing: Fiscal Year 2004; Project Start 18-DEC-2003; Project End 30-NOV-2008 Summary: (provided by investigator): Within the developmental psychopathology literature there is an increasing awareness that childhood and adolescent disorders, like their adult counterparts, are characterized to a large degree by disturbances in emotional processes. Despite this awareness and the substantial research base on normative emotional development and socialization, however, there has been very little research examining emotional processes in clinical samples of children and adolescents. This gap is perhaps most notable in the case of unipolar depressive disorder where the prominence of affective symptomatology has led numerous researchers and theorists to define it as a disorder of emotion. A key task awaiting attention is the delineation of the emotional processes characteristic of unipolar depressive disorder, as well as the identification of both continuities and discontinuities with normative developmental functioning (NIH, PA-00-105, 2000). The current application is aimed at addressing these limitations by proposing the following aims: 1) To delineate the aspects of emotional functioning that are disrupted in unipolar affective disorder by conducting a betweengroup analysis comparing dimensions of emotion functioning (e.g., frequency, intensity, duration; using a multi-method assessment of the key domains of emotional output (behavior, experience, & physiology;), and focusing on dysregulation of negative and positive emotional states; 2) To examine and identify family processes that serve to influence the level of adolescent emotion dysregulation displayed; and 3) To test a hypothesized mediational model whereby emotional dysregulation mediates the relation between family processes and adolescent depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: DEPRESSION

GLUCOCORTICOID

RESISTANCE

IN

IMMUNE-BASED

Principal Investigator & Institution: Raison, Charles L.; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-JAN-2002; Project End 31-DEC-2006 Summary: (provided by applicant): The training and research components of this Research Career Development Award application are designed to prepare the applicant for a career as an independent investigator in the area of mind-body interactions. The long-term objectives are to examine bi-directional relationships between the hypothalamic-pituitary-adrenal (HPA) axis and the immune system and determine the effect of these interactions on the regulation of mood and related neurovegetative functions in medically ill patients. The applicant will devote the 5-year K23 project period to combining his expertise in clinical diagnosis and treatment with rigorous training in neuroimmunology and neuroendocrinology, as well as in research methodology, data organization, biostatistics, and the ethical conduct of research. The training program will consist of an integrated curriculum of formal didactic course work and tutorials with the sponsor and other consultants. The applicant's immediate research goal during the award period will be to examine the relationship between immune system activation and glucocorticoid resistance in patients who develop depressive symptoms during treatment with interferon (IFN)-alpha for chronic hepatitis C virus (HCV) infection. The hypotheses to be tested are as follows: 1) Chronic

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treatment with IFN-alpha will induce resistance to the inhibitory effects of endogenous glucocorticoids leading to unrestrained release of corticotropin-releasing hormone (CR1I) and proinflammatory cytokines in the CNS, which in turn will lead to depressive symptoms and 2) Impaired glucocorticoid feedback inhibition at baseline (prior to IFNalpha treatment) will predict depressive symptoms as a result of relatively unrestrained immune system activation and release of CRH during IFN-alpha therapy. To test these hypotheses, the following specific aims are proposed: 1) To measure concentrations of the proinflammatory cytokines interleukin (IL)-l, IL-6 and tumor necrosis factor-alpha (TNF-alpha), and CRH in cerebrospinal fluid (CSF) of 100 patients with HCV, randomized to receive IFN-alpha treatment or to post-pone treatment until study completion, 2) To determine the correlation among CSF concentrations of proinflammatory cytokines and CRH and behavioral endpoints in these patients, and 3) To explore the effect of chronic IFN-alpha treatment on sensitivity to glucocorticoidmediated inhibition and to determine the relationship between glucocorticoid-mediated negative feedback and concentrations of IL-1, IL-6, TMF-alpha and CRH in CSF of IFNalpha-treated patients. All subjects will undergo in vivo and in vitro assessment of sensitivity to glucocorticoid inhibition of the HPA axis and immune system at baseline (prior to beginning IFN-alpha for subjects randomized to active treatment) and again one month later. At study week 12, subjects will receive a lumbar puncture to measure CSF concentrations of CRH, arginine vasopressin and proinflammatory cytokines. Results from this study will enable further understanding of the pathways by which mood disorders arise out of conditions of immune activation and will provide the foundation for the development of novel strategies to treat depression in the medically ill. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: INCREASING TREATMENT ADHERENCE IN CO-OCCURRING DISORDERS Principal Investigator & Institution: Pantalon, Michael V.; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 25-SEP-2002; Project End 31-AUG-2007 Summary: (Provided by Applicant): This application is for a "Mentored Patient-Oriented Research Career Development Award" (K23) to study treatment adherence in cooccurring psychiatric and drug use disorders (COD), under the mentorship of Bruce J. Rounsaville, M.D. and Richard S. Schottenfeld, M.D. Nonadherence is a critical issue in COD, especially among those with depressive disorders, as it occurs frequently and limits the maximal benefit achieved by efficacious treatments, particularly those with the potential to improve both conditions (e.g., antidepressants). Therefore, adherenceenhancing interventions for COD can optimize the efficacy of treatments. They are also adaptable to new treatments that are being developed. While preliminary studies indicate that adherence-enhancing interventions are efficacious for patients with nonCOD, little systematic evaluation has occurred in COD. Compared to developing new contents for treatment, studying brief strategies to improve adherence to existing treatments is a highly cost-efficient approach that can have a large and rapid payoff. The research plan for this K23 application entails: 1) the evaluation of adherence issues in 9 ongoing studies and 2) completion of a new clinical trial evaluating innovative adherence-enhancing methods for COD in a dual-diagnosis outpatient clinic. This new clinical trial will employ a dismantling design, within which 75 outpatients with cooccurring depressive disorders and drug abuse/dependence (CODDA) will be randomly assigned to: 1) Treatment-as-Usual (TAU), a control condition offering

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Depressive Disorders

medication management, standard education regarding diagnosis and the importance of adherence, and group counseling, 2) TAU+Adherence Feedback (TAU+AF), in which patients receive TAU plus computerized feedback on medication and counseling adherence, based on Medication Event Monitoring System (MEMS; Aprex Corporation, Fremont, CA) data and attendance records, or 3) TAU+Motivationally Enhanced Feedback (TAU+MEF), in which TAU plus Motivational Enhancement Therapy and Contingency Management will be added to AF. Primary outcome measures are: 1) rates of adherence to antidepressant medication, as measured by MEMS caps and self-report, 2) rates of counseling attendance, and 3) reductions in illicit drug use, including achievement of abstinence, as assessed by twice-weekly urine toxicology tests and selfreport. Secondary outcomes include reductions in depressive symptomatology and rates of re-hospitalization. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: INFORMATION PROCESSING BIASES IN DEPRESSION Principal Investigator & Institution: Gotlib, Ian H.; Professor; Psychology; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-MAR-2004 Summary: Depression is among the most prevalent of all psychiatric disorders, accounting for over 20 percent of economic costs for all mental illness. A great deal of theoretical attention has focused on the possibility that negative thinking might represent not only a feature of depression, but a vulnerability factor for this disorder as well. A recent influential research paradigm has operationalized depressotypic cognitions in terms of selective attention to, and memory for, negative emotional stimuli. The overall goal of the proposed investigations is to utilize this paradigm to investigate the role of cognitive biases in onset and course of depression, and to examine neurobiological foundations of cognitive biases in depression. Specific aims include (1) examining the utility of cognitive biases to predict the course of depressive symptoms and diagnostic status over a two-year period; (2) localizing the neurobiological underpinnings of these biases; and (3) examining the breadth of these biases and their specificity to depression. To achieve these aims, standardized cognitive information- processing tasks will be used to identify 30 "high-bias" and 30 "low- bias" depressed patients in psychiatric outpatient clinics. The nature and breadth of these biases in the depressed patients will be compared to cognitive biases among 30 patients diagnoses with generalized anxiety disorder, 30 patients diagnosed with social phobia, and 30 non-patient controls. Each depressed patient will be followed for one year, and the degree of cognitive biases will be reassessed when the patient achieves clinical remission. Hypotheses concerning the neurobiological underpinnings of depressotypic cognitive biases will be tested by conducting functional magnetic resonance imaging (MRI) of depressed (and later, remitted) patients while they are performing informationprocessing tasks. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: IS EEG SLEEP ABNORMAL IN THOSE AT RISK FOR DEPRESSION Principal Investigator & Institution: Giles, Donna E.; Professor; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-FEB-1987; Project End 31-MAY-2004 Summary: (adapted from applicant's abstract): The proposed project is the second revision of the competitive renewal of R01 MH39531-13. This project has two major aims

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and one exploratory aim. The first major aim is to elucidate the role of cholinergic sensitivity in modulation of affective morbidity and REM sleep dysregulation within families. A cholinergic probe will test the hypothesis that cholinergic effects mediate the familial occurrence of affective morbidity and that REM sleep dysregulation is a risk factor. The second major aim is to estimate the influence of EEG sleep measures, family of origin and cognitive and psychosocial measures on the risk of new onset depression, adjusting for age and sex, among at-risk relatives with evidence of sleep dysregulation, compared to at-risk relatives with normal sleep. The finding that different domains predict the first episode of depression in at-risk relatives, based on premorbid sleep dysregulation will also be tested in a more complex model. Sleep dysregulation in unaffected at-risk relatives doubles risk for onset of depression. When at-risk relatives with normal sleep have their first episode, however, they are susceptible based on premorbid negative cognitions. Our exploratory aim is to evaluate the power spectral profile of EEG sleep to determine whether a profile can be identified that is specific to risk for depression among families. Although genetic studies are not part of the proposed project, results of the project can identify pedigrees that will be informative in future work. The cohort of 348 individuals from 69 families is a unique resource for mechanistic studies directed at the role of cholinergic mediation of both mood disorders and sleep dysregulation. Families are identified by 1) depressed probands with short REM latency, 2) depressed probands with normal sleep and 3) probands with no psychiatric history and where sleep was free to vary. After careful study of sleep physiology and psychiatric and medical history, families have been followed clinically over the 13 year course of this study. PSG abnormalities aggregate in families and increase risk for depression. Prospective study of the course of unaffected individuals has identified premorbid factors that predict the first mood disorder. Among affected relatives, divergence in morbidity is based on familial sleep profiles. Our well-studied cohort can address mediation of depressive morbidity by neurophysiological mechanisms separate from psychological mechanisms. These procedures will identify informative families for genetic studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: IV COCAINE ABUSE TREATMENT: A LABORATORY MODEL Principal Investigator & Institution: Foltin, Richard W.; Professor of Neuroscience; Anatomy and Cell Biology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-JAN-1990; Project End 31-MAY-2007 Summary: (provided by applicant): This protocol continues implementation of a laboratory model to evaluate medications potentially useful in the treatment of cocaine abuse, investigating problems relevant to understanding and reducing uncontrolled cocaine use. Psychiatric comorbidities are pervasive in the cocaine-dependent population, and are significant in the population seen in community treatment centers. However, these comorbidities are rarely addressed in either clinical trials or laboratory settings. While it has been hypothesized that treatment for cocaine dependence could be improved by targeting cocaine users with specific psychiatric comorbidities, this has not been systematically evaluated. We will examine the relationship between psychiatric comorbidity and potential medications for cocaine dependence using two approaches. First, we will compare the subjective and reinforcing effects of cocaine under controlled laboratory conditions, in groups of abstinent cocaine abusers with Major Depressive Disorders (MDD), Attention Deficit/Hyperactivity Disorder (ADHD) or no psychiatric comorbidity. If cocaine use in individuals with comorbid disorders is related to their

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Depressive Disorders

comorbid. disorder, then the behavioral effects of cocaine should vary across the groups being studied. Second, we will compare responses to cocaine under three separate conditions: maintenance on 1) gabapentin, 2) venlafaxine, and 3) the combination of the two medications. The laboratory, setting of the current proposal offers a unique opportunity to test the hypothesis that individuals with comorbid MDD or ADHD respond differently to cocaine than those without a comorbid psychiatric disorder, and that treating the MDD or ADHD alone will not sufficiently reduce the response to cocaine. Treating the comorbid disorder or decreasing the behavioral effects of cocaine will be necessary but not sufficient pharmacotherapy for individuals with comorbid disorders. A combination of the gabapentin for cocaine and venlafaxine for depressive symptoms will have a synergistic effect in these individuals. The laboratory is an ideal setting in which to carry out this research, allowing us to carefully monitor participants and collect maximal data with the fewest number of participants. The proposed research offers a unique opportunity to evaluate medications in cocaine-dependent individuals with MDD, ADHD or no comorbid disorder, and will provide important information about differential responses of these groups to cocaine and to gabapentin and venlafaxine, alone and in combination. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION

LONG-TERM

ANTIDEPRESSANT

OUTCOME

IN

BIPOLAR

Principal Investigator & Institution: Ghaemi, S Nassir.; Cambridge Health Alliance 1493 Cambridge St Cambridge, Ma 02139 Timing: Fiscal Year 2002; Project Start 10-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from the Applicant's Abstract):Summary: This is an application for an NIMH Mentored Patient-Oriented Research Career Development Award (K-23) to develop expertise in evaluating, designing and applying research methods for assessing pharmacological treatments for bipolar depression, based on a balanced program of didactic, tutorial, and practical research experiences. The applicant will study the impact of continuing vs. discontinuing antidepressants in a naturalistic, but controlled and randomized, long-term (up to 3 year) clinical study of patients with bipolar disorder who are clinically maintained on mood-stabilizing treatment. The proposal will be completed as part of the national NIMH-sponsored Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) project. Rationale: In contrast to unipolar major depression, bipolar depression is among the least studied depressive illnesses, with very little research on the long-term efficacy or safety of antidepressants used in conjunction with mood-stabilizing agents, or their effect on the course of bipolar disorders, including induction of mania, mixed states, psychosis, or rapid-cycling. Despite these potential risks, the depressive phase of bipolar disorder is sufficiently compelling clinically that antidepressants rather than mood-stabilizing agents are the most commonly used treatments in bipolar disorder, supporting the timelines of the present proposal. It is unknown if these antidepressant treatments are effective or even safe in these circumstances. Environment: The project is based at the Massachusetts General Hospital project site of the NIMH national STEP-BD study of long-term treatment of bipolar disorder, with the collaboration of two other STEP-BD sites. Included are a program of practical training and supervised research under primary mentorship of Ross J. Bladessarni MD, co-sponsorship by Gary S. Sachs MD, and consultation by bipolar disorder expert Frederick K. Goodwin MD and biostatistician John Hennen PhD. Career development plan: Training is designed to assume that the applicant achieves competence in the critical evaluation and design of long-term

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pharmacological studies in adults with major affective disorders, as well as in applying these skills to the design, conduct, and analysis of a supervised clinical trial. Training includes completion of MPH coursework at the Harvard School of Public Health and tutorials on the theory and analysis of research designs and statistical methods for longitudinal studies supervised by the biostatistical consultant in collaboration with the mentor, co-sponsor, and consultants. In this process, the applicant will develop competence to lead independent studies of the long-term treatment of bipolar disorder as a principal investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: MARIJUANA DEPENDENCE & DEPRESSION: VENLAFAXINE TREATMENT Principal Investigator & Institution: Levin, Frances R.; Q. J. Kennedy Associate Professor of Cli; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-MAY-2007 Summary: (provided by applicant): To our knowledge there are no effective pharmacologic treatments for marijuana dependence. One subgroup that might benefit from a targeted pharmacologic intervention is marijuana-dependent individuals who have depressive disorders. The prevalence of current depression in marijuanadependent individuals in clinical samples ranges from 20-24%. This rate is substantially higher than what is found in the general population (2-10%). Given the comorbidity of depression and marijuana dependence, pharmacotherapies aimed at treating these dually-disordered patients may be particularly effective. Venlafaxine-extended release, a once-a-day medication that is commonly used to treat depression, is a promising option. Recent work completed by our group has found that a reduction in psychiatric symptoms is correlated with a reduction in substance use. However, abstinence has been more elusive. It is becoming increasingly clear that no one intervention, whether it be pharmacologic or nonpharmacologic, will be successful in treating substancedependent individuals with comorbid depression. Instead, an integrated treatment is needed. We therefore propose a placebo-controlled trial of the venlafaxine extended release, Ven-XR, an antidepressant, which is both a selective serotonin reuptake inhibitor and a noradrenergic reuptake inhibitor, in a sample of marijuana-dependent patients with current major depression. All patients in the trial will receive weekly motivational enhancement and cognitive behavior therapy. The following specific aims will be addressed: 1. To determine whether Ven-XR, along with motivational enhancement/relapse prevention therapy, reduces symptoms of depression compared to placebo. 2. To determine whether Ven-XR, along with motivational enhancement/relapse prevention therapy, increases the achievement of sustained abstinence. 3. To examine the relationship between medication treatment, mood improvement, cognitive functioning and improvement in marijuana abuse using mediational analyses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MARITAL ADJUSTMENT, DEPRESSION AND MYOCARDIAL INFARCTION Principal Investigator & Institution: Gallo, Linda C.; Psychology; San Diego State University 5250 Campanile Dr San Diego, Ca 92182 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2004

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Summary: (provided by applicant): Depression and Coronary Heart Disease (CHD) are each prevalent disorders, which frequently co-occur. Approximately 15-23% of individuals recovering from a heart attack (e.g., myocardial infarction; MI) will meet criteria for major depression and up to 65% will experience elevations in depressive symptoms. Yet, history of depression and disease severity are only moderately predictive of this co-morbidity. Importantly, depression is embedded within social context and, in particular, depression is strongly associated with marital adjustment. The primary goal of the current research is to examine if individuals with worse marital adjustment experience higher levels and a more persistent course of depressive symptoms following MI, in a 6-mo, 3-wave, prospective study of 150 men and women. Some research suggests that marital distress and depressive symptoms are more closely linked in women than in men. Therefore, the current research will examine if gender moderates the associations between marital adjustment and level and course of depression, with the hypothesis that associations will be stronger for women than for men. Previous research suggests that depression and possibly marital adjustment represent risk factors for negative physical health outcomes following MI. Further, when psychosocial risk factors occur in combination, the probability of negative outcomes is likely to increase substantially due to additive or synergistic effects. A secondary goal of the study will therefore be to examine the joint and independent effects of depression and marital adjustment on quality of life, functional status, and the probability of recurrent events following Ml. Women may experience worse outcomes following MI, and psychosocial factors could contribute to this trend. The proposed research will therefore examine if gender moderates the relationships between depression, marital adjustment, and health outcomes following CHD, with the hypothesis that effects will be stronger for women than for men. The broader goal of the proposed research is to identify aspects of social functioning that could represent potent, modifiable risk factors for CHD and depression co-morbidity, in the hopes of informing more effective prevention and intervention efforts. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: MOOD FLUCTUATIONS IN PARKINSON'S DISEASE Principal Investigator & Institution: Richard, Irene H.; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 27-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted From The Applicant's Abstract): The candidate has a clinical background in neurology with an expertise in movement disorders and has completed a two year NIH-funded fellowship through the Department of Neurology in Experimental Therapeutics. This fellowship provided the candidate with both theoretical knowledge and practical experience pertaining to the design and conduct of clinical trials. She has focussed most of her efforts thus far on the understanding and treatment of the behavioral aspects of Parkinson's disease (PD) The candidate's short term goals include the following: 1) to increase her knowledge of basic pharmacology and gain experience using techniques relevant to pharmacologic mechanism oriented research, 2) to gain a better understanding of molecular medicine, 3) to obtain training in psychiatric assessment techniques, 4) to expand her knowledge of areas fundamental to clinical investigation including biostatistics, epidemiology and outcomes research. The focus of her research plan during this career development award will be understanding mood fluctuations in PD. Mood fluctuations have been reported in up to 2/3 of advanced PD patients who experience motor fluctuations. These can be frequent, dramatic and distressing. Research involving the phenomenology and underlying mechanisms of

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mood fluctuations in PD has been limited. The specific aims of this study are to: 1) better understand the phenomenology of mood fluctuations in PD (frequency, quality, magnitude), 2) better understand the relationship between mood fluctuations and more pervasive depressive disorders in PD, 3) clarify the temporal relationship between changes in mood and motor states in PD, 4) elucidate the neurobiological mechanisms of changing mood states in PD and to determine, in particular, whether mood fluctuations in PD are the result of dopamine dysregulation, and 5) gather preliminary information regarding the optimal treatment of mood disorders in PD. These findings may lead to the development of therapeutic interventions for patients with PD who suffer from these disabling fluctuations on a daily basis. It may also provide a better understanding of the mechanisms responsible for more pervasive forms of depression in PD, and perhaps even in primary psychiatric mood disturbances. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: NEGATIVE COGNITION DEPRESSION: ETIOLOGY AND COURSE Principal Investigator & Institution: Alloy, Lauren B.; Professor; Psychology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 31-DEC-2003 Summary: This competing continuation is part of a 2-site collaborative research grant with an identical application submitted concurrently by Dr. Lyn Y. Abramson at the University of Wisconsin. Prior research did not provide an adequate test of the hopelessness theory (HT) and Beck's theory (BT) of depression and may have been misleading about those cognitive theories' validity. Thus, the overarching goal of this project is to provide a more powerful test of HT's and BT's predictions about the etiology of depression and a validation of the Hopelessness Depression subtype. To this end, a large scale, 5.5-year prospective study was conducted at both sites. Initially nondepressed, non-psychopathological Ss (n=349) who were at either high or low cognitive risk for depression were followed prospectively with independent and blind self-report and interview assessments of stressful life events, cognitions, social support, coping, and psychiatric status/symptoms in order to predict onsets and subsequent recurrences of depression. Familial and developmental origins of cognitive vulnerability to depression were also examined, including assessment of the parents(n=335) of highrisk and low-risk Ss. In this renewal, differential predictors of first onsets vs. recurrences of depression, factors that increase resilience among high-risk Ss and promote depression among low-risk Ss, factors that mediate and moderate change in cognitive vulnerability, and different models of cognitive vulnerability-stress relations are also investigated. This project contributes to: 1) the scientific understanding of the etiology and course of a subset of the mood disorders; 2) a more valid nosology of the depressive disorders; 3) an understanding of the origins and continuity/change of cognitive vulnerability to depression; 4) an understanding of factors that promote resilience to depression; and 5) the development of interventions for treating and preventing depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEGATIVE COGNITION DEPRESSION: ETIOLOGY AND COURSE Principal Investigator & Institution: Abramson, Lyn Y.; Professor; Psychology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-DEC-2003

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Summary: (provided by applicant): This competing continuation is part of a 2-site collaborative research grant with an identical application submitted concurrently by Dr. Lauren B. Alloy at Temple University. Prior research did not provide an adequate test of the hopelessness theory (HT) and Beck's theory (BT) of depression and may have been misleading about those cognitive theories' validity. Thus, the overarching goal of this project is to provide a more powerful test of HT's and BT's predictions about the etiology of depression and a validation of the Hopelessness Depression subtype. To this end, a large scale, 5.5-year prospective study was conducted at both sites. Initially nondepressed, non-psychopathological Ss (n=349) who were at either high or low cognitive risk for depression were followed prospectively with independent and blind self-report and interview assessments of stressful life events, cognitions, social support, coping, and psychiatric status/symptoms in order to predict onsets and subsequent recurrences of depression. Familial and developmental origins of cognitive vulnerability to depression also were examined, including assessment of the parents (n=335) of highrisk and low-risk Ss. In this renewal, differential predictors of first onsets vs. recurrences of depression, factors that increase resilience among high-risk Ss and promote depression among low-risk Ss, factors that contribute to and moderate change in cognitive vulnerability, and different models of cognitive vulnerability-stress relations also were investigated. This project contributes to: 1) the scientific understanding of the etiology and course of a subset of the mood disorders; 2) a more valid nosologv of the depressive disorders; 3) an understanding of the origins and continuity/change of cognitive vulnerability to depression; 4) an understanding of factors that promote resilience to depression; and 5) the development of interventions for treating and preventing depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: NET - SELECTIVE LIGANDS FOR THE TREATMENT OF DEPRESSION Principal Investigator & Institution: Johnson, Kenneth M.; Professor; Acenta Discovery, Inc. Suite 300 Tucson, Az 85747 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): World-wide public health surveys point to an increased global health burden for serious psychiatric disorders, particularly depression. Indeed, by 2020 it is expected that depression may be the second most serious medical condition with respect to global disease burden. It is clear that more effective pharmacotherapies are needed in treating depressive illness. Selective ligands for the norepinephrine transporter (NET) such as desipramine are quite effective in some patient populations, but their use is often limited by side effects, particularly those thought to be mediated by their anticholinergic properties. More selective NET ligands may have considerable application in the treatment of depression. However, currently there are very few NET-selective ligands available. The studies described in this research proposal involve the synthesis and pharmacological evaluation of novel conformationally constrained tricyclic tropane analogues that are designed to be potent NET-selective inhibitors. For the best NET inhibitors identified, we will then screen them in animal models of depression. Additionally, it is reasonable that such ligands could be utilized with positron emission tomography (PET) imaging to assess changes in noradrenergic terminal fields in a variety of human conditions including depression. Thus, these ligands could be a significant addition to the clinical armamentarium available to treat and diagnose psychiatric disease. Within the context of this grant, it is our intention to follow up on our exciting preliminary findings of potent NET-selective

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compounds by conducting the following studies: 1. Further elaborate the biaryl and thienyl series of conformationally constrained tricyclic tropane analogues based on the SAR information already in hand; 2. Investigate certain phenylacetylene analogues that are derived from our biaryl analogues by the replacement of Ar1 with a triple bond as an aromatic ring bioisostere.; 3. Assay the inhibitory activity of all new ligands at the NET, SERT, DAT and the muscarinic receptor; 4. Scale up the synthesis of the most drug-like NET-inhibitors and study these in animal models of depression. Key words: depression, norepinephrine transporter (NET) inhibitors, conformationally constrained tricyclic tropanes, pharmacotherapy, PET imaging, chemical synthesis, behavioral testing. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: NEUROBIOLOGY OF DEPRESSION AND ANTIDEPRESSANTS Principal Investigator & Institution: Mann, Joseph J.; Professor; Psychiatry; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 01-MAR-1990; Project End 31-JAN-2008 Summary: (provided by applicant): This competing continuation application proposes a set of patient studies of the serotonergic system in major depression and the effects of somatic antidepressants on the serotonergic system that builds on recent findings from patient studies of the biology of depression and from animal studies of the action of antidepressants. Recently, PET and SPECT studies have begun to provide more direct evidence in both bipolar and unipolar disorders that major depressive episodes are associated with serotonergic system abnormalities. In the current two plus years of funding, we have developed a method for quantifying 5- HT1A binding in human subjects in vivo using positron emission tomography (PET) and the ligand [11C]WAY100635. We have acquired pilot data indicating lower regional brain 5-HT1A binding in depressed patients. We now propose to systematically investigate the neurobiology of a major depressive episode in both unipolar and bipolar disorders. To determine whether the biological changes associated with depression are reversible, we propose to study the short-term effects of antidepressant treatment, and also to examine a cohort of longterm, remitted and medication-free unipolar patients. In studying the action of antidepressants, we will compare depressed, unipolar patients from the baseline study above, after a six week course of an SSRI, paroxetine. The study of long-term recovered, drug-free patients will help distinguish the effects of recovery from the effects of treatment. The delayed therapeutic benefit of antidepressant medications such as SSRIs has been linked to delayed enhancement of intra-synaptic serotonin levels resulting from 5-HT1A autoreceptor downregulation found in animal studies. SSRIs (or serotonin transporter gene knockout) do not change post-synaptic terminal field 5-HT1A receptors, but downregulate the raphe autoreceptor. These observations have not been adequately tested in man because antidepressant actions on the 5-HT1A receptors may, at least partly, involve the same receptor population that is implicated in the pathogenesis of major depression, such effects need to be evaluated in patients. We propose to test these hypotheses directly in vivo using PET and the ligand [11C]WAY100635, and to quantify the 5- HT1A receptor in healthy volunteers and patients with a major depressive episode. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: NEUROGENETICS OF STRESS VULNERABILITY Principal Investigator & Institution: Gershenfeld, Howard K.; Associate Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105

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Depressive Disorders

Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): Depression and anxiety are common psychiatric illnesses in the U.S. with about 23 million and 28 million people suffering annually. In the1990's, the annual economic burden to society of depressive disorders and anxiety disorders were each estimated at $43 billion dollars. We aim to understand the neurobiology of "stress vulnerability," which leads to anxiety and depressive disorders. Stress is a well known "common factor" contributing to many disorders. While the causal association with stress is more direct for depressive and anxiety disorders, evidence has accumulated for stress aggravating cardiovascular and inflammatory diseases. Stress responses vary greatly among individuals. This project proposes to explore the mechanism of vulnerability to acute stress. The mouse tail suspension test (TST) reflects these individual differences in behavior to an uncontrollable stressor. This acute stress model has become a facile model of individual differences in stress reactivity (including psychogenic fever/hyperthermia) and antidepressant responses. This project focuses on the genetic factors predisposing to differences in stress responses induced by TST. The specific aims include: 1) positionally cloning a confirmed locus (Tsti1) on chromosome 5,2) performing secondary and tertiary screens of ENU mutagenized, mutant mice with altered TST behavior, and 3) dissecting the role of gender and cytokines in TST behaviors via selected transgenic mice. The ENU mutant screens will include TST-induced hyperthermia, antidepressant response, and neural activity mapping. Despite the effectiveness of antidepressants, we know little about how these treatments work. The goal is to define robust factors influencing the fundamental biology of individual differences in "stress reactivity," favoring assumption free genetic strategies. We hypothesize that the TST paradigm in mice may probe a genetic shared liability for "general distress," which is a risk factor for psychiatric disorders. An understanding of the molecular pathophysiology of the mammalian stress response will contribute to integration of established genes and pathways, attach functions to unknown genes, and define new pathways for improved therapy. Ultimately, this work may contribute to our etiological understanding of stress vulnerability, identifying individuals at high risk for stress-induced disorders, and provide rational drug design to sever the link between acute stress and pathological consequences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: NICOTINE, BIOGENIC AMINES AND DEPRESSION Principal Investigator & Institution: Tizabi, Yousef; Howard University Washington, Dc 20059 Timing: Fiscal Year 2002; Project Start 01-JUN-1977; Project End 31-JUL-2006 Summary: Because of high incidence of cigarette smoking among depressed individuals, it has been postulated that smoking may reflect an attempt at self-medication with nicotine by these individuals. We have observed anti-depressant effects of nicotine in an animal model of depression. Moreover, the effects of nicotine can be blocked by preadministration of the nicotine antagonist, mecamylamine. There is also a differential expression of nicotinic receptors in depressed rat lines compared to their controls. These findings suggest a role for nicotinic receptors in depressed rat lines compared to their controls. These findings suggest a role for nicotinic receptors in depressive characteristics of animals. Nicotinic receptors are potent modulators of a variety of neurotransmitters including biogenic amines which have been directly implicated in human depression. Although nicotinic manipulation may constitute a novel intervention in depressive disorders, a clearer understanding of the role of specific nicotinic receptors in depression is critical in developing pharmacotherapies for this

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devastating mental disorder. Here, we hypothesize that depression is associated with inherent changes in specific nicotinic and/or biogenic amine pathways. Furthermore, we postulate that nicotine would tend to normalize these neurotransmitter systems. These hypotheses will be tested in two rat models of depression by examining the role of nicotinic receptor subtypes as well as the contribution of selective dopaminergic noradrenergic and serotonergic pathways to depressive characteristics in these animals. Specifically, we will: 1) determine the effects of selective noradrenergic and serotonergic neurons in selective pathways implicated in mood regulation; 3) determine the basal function of biogenic amines in selective pathways; 4) determine the effects of nicotine functionality of these pathways; 5) determine central and peripheral bioavailability of nicotine. Behavioral analysis will include measurements of several parameters in the forced swim test as well as locomotor activity. Neuronal densities will be assessed by stereological technique. In-vivo microdialysis will be used to determine the functionality of the neurotransmitter systems. Plasma and brain nicotine and cotinine levels will be measured by gas chromatograph-mass spectrometry. The information provided by these studies will significantly advanced our understanding of biological substrates of depression and can lead to novel pharmacotherapies for this disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: NORADRENERGIC SYSTEM IN DEPRESSION Principal Investigator & Institution: Ordway, Gregory A.; Associate Professor; Psychiatry and Human Behavior; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 30-SEP-1991; Project End 31-AUG-2006 Summary: (provided by applicant): Our research has led us to postulate that major depression is associated, at least in part, with noradrenergic overdrive and a deficiency of synaptic norepinephrine. This postulate is based on the fact that biochemical alterations identified by us in the postmortem locus coeruleus (LC; brain norepinephrine neurons) of major depressive subjects can be produced experimentally in rats by treatments (e.g chronic stress) that elevate noradrenergic activity and deplete central norepinephrine. Also, repeated treatment of rats with antidepressant drugs reduces LC activity and downregulates specific proteins that we have found elevated in the LC of major depressive subjects. Together, these findings suggest that abnormalities in the LC are strongly associated with major depression. The central hypothesis of this proposal is that the noradrenergic pathobiology of depression is associated with elevated excitatory and reduced inhibitory inputs to the LC. A critical component of neuronal circuitry driving emotion-laden activation of the LC is corticotropin releasing factor (CRF) input from the amygdala. This circuit and other major "stress-sensitive" excitatory and inhibitory inputs to the LC, including substance P, glutamate, serotonin, and GABA, will be studied in the LC in postmortem brains from psychiatrically characterized subjects. Preliminary evidence of elevations of CRF and substance P input to the human LC in major depression is provided. Molecular pathways responsible for certain activation-induced biochemical changes in the LC include receptor-second messenger systems linked to gene expression through trans-activating factors. Potential disruption of these pathways in depression will be studied, emphasizing factors regulating longterm changes in LC gene expression. The overall goals of this application are to study neurotransmitter inputs that likely contribute to noradrenergic overdrive in major depression, and to investigate the molecular underpinnings of noradrenergic pathobiology. To achieve these goals, postmortem brain tissues from major depressive subjects (suicide and non-suicide), suicide victims lacking major depression, and

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carefully matched control subjects lacking major psychiatric disorders will be utilized. Diagnoses are made via a rigorous psychiatric/neurologic autopsy program under the direction of Dr. Craig Stockmeier. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: OMEGA-3 FATTY ACIDS IN THE TREATMENT OF DEPRESSION Principal Investigator & Institution: Mischoulon, David; American Psychiatric Association 1400 K St Nw Washington, Dc 20005 Timing: Fiscal Year 2002; Project Start 27-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): This is a resubmission of an application for a mentored patient-oriented K-23 award, designed to enhance clinical training and research expertise in the area of major depression and the role of nutrition in the development and treatment of depressive disorders. This proposal differs from the original in that it uses an omega-3 mix as opposed to pure DHA; consists of a double blind omega-3 versus placebo acute treatment phase, followed by a continuation phase of open treatment for non-responders, and continued treatment for responders with the double blind medication from the acute phase; and includes more modern biostatistical techniques. Omega-3 long chain fatty acids are found in eggs, red meats, and cold-water fish. There is one recently published small clinical trial with bipolar patients and a few case reports/series with psychotic patients, suggesting that omega-3 fatty acid mixes may have a role in symptom alleviation in depression, bipolar disorder, and psychotic disorders. Research on omega-3s as well as other natural treatments represents an underdeveloped area in psychopharmacology, and rigorous studies in this field are needed. The goals of the project will be to assess the role of omega-3 fatty acid mix compared to placebo in the treatment of major depression. Additional studies will examine the nutritional status of depressed patients vis-a-vis intake of fish and other omega-3-rich foods. The proposed study will be based at the Massachusetts General Hospital in the Depression Clinical and Research Program, under the mentorship of Maurizio Fava, MD, and will include consultation from experts. There will also be a didactic component to the project, including coursework in biostatistics and research design, nutrition science, and ethics. The development of a larger scale RO1 project comparing omega-3 fatty acids to a selective serotonin reuptake inhibitor (SSRI) for treatment of depression will be started during the last two years of the project period. It is hoped that this project will provide the critical fund of basic knowledge and practical experience necessary to aid the candidate in becoming an independent investigator. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PANIC OUTCOMES IN PRIMARY CARE--RACIAL DIFFERENCES Principal Investigator & Institution: Johnson, Michael R.; Assistant Professor; Psychiatry; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2002; Project Start 01-JAN-1999; Project End 31-DEC-2003 Summary: This application is designed to provide the candidate with the skills necessary to improve the care of patients with anxiety disorders presenting to providers in primary care (PC) settings. While there is a growing body of work examining the need for care, processes of care, and outcomes of care for patients with depressive disorders in PC settings, there are few published studies providing similar information about patients with anxiety disorders. The focus of the proposed research is panic disorder(PD), a severely disabling condition which is highly prevalent in PC settings. PD is common among high utilizers of PC services and among PC patients who are

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perceived as "difficult-to- treat" by their clinicians. Yet the limited available data suggests that PD is frequently not recognized and that the rate of recovery from this illness in PC populations is low. We know little about the factors which contribute to these poor recognition and recovery rates. There is evidence to suggest that African American patients with PD experience unique barriers to care and are even more likely than other racial groups to present with panic symptoms to PC providers. Yet there is no available empirical work that sheds light on the process of care or illness outcomes for this group. Another barrier to research in this area is the absence of validated psychometric tools for assessing PD in PC settings. Finally, there is an absence of a practical approach to identification of the targeted population. Therefore, the major goals of this proposal are to (1) explore fundamental issues regarding the processes and outcomes of services provided to patients with PD served in PC settings; (2) validate instruments for clinical and research use in this population; and (3) to develop a practical approach to case identification. New knowledge gained from this research will subsequently inform the development of PC interventions that will improve the quality of care provided for patients with PD in PC settings. In order to develop the skills necessary for carrying out this research the candidate will implement a program which will provide an opportunity for mentoring from experts in PCservices research and anxiety disorders in African Americans, as well as supervision with research methods and statistics and the use of computer technologies for applying psychometric instruments. The candidate's short-term career goal is to become an independent investigator studying the processes, cultural appropriateness, and outcomes of care for patients with PD in PC settings. His long-term goal is to develop effective and efficient interventions to improve the quality of PC services for individuals of different racial groups with panic and other anxiety disorders. The proposed research will be carried out in a set of three PC clinics which together serve large patient populations of both African Americans and Caucasians from all socioeconomic groups. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: PERSONALITY, ANXIETY, AND DEPRESSION IN COMMUNITY ADULTS Principal Investigator & Institution: Bienvenu, Oscar J.; Psychiatry and Behavioral Scis; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 12-SEP-2003; Project End 31-AUG-2008 Summary: This is a revised K23 application, the purpose of which is to prepare the candidate for an independent career in the genetic epidemiology of personality and anxiety and depressive disorders. The overall focus of the research project is to determine how personality traits and anxiety and depressive disorders relate. There is currently little empirical data regarding such relationships in the general population, especially with a longitudinal perspective, multiple methods of assessment, and genetic informativeness. The proposed study provides a unique opportunity to investigate these issues, using data from the Baltimore Epidemiologic Catchment (ECA) Study, The Virginia Twin Study (VTS), and The Virginia Twin-Family Study of Adolescent Behavioral Development (v-rSABD). The specific aims of this proposal are: 1) To determine longitudinal relationships between normal personality traits and anxiety and depressive disorders, using data from the Baltimore ECA, V'I'S, and VTSABD cohorts; 2) To determine longitudinal relationships between personality disorder traits and anxiety and depressive disorders in adults, using data from the Baltimore ECA cohort; 3) To determine associations between personality traits and treatment seeking, using data from the Baltimore ECA cohort; and 4) To determine to what extent associations

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between neuroticism and extraversion and anxiety and depressive disorders reflect common genetic or environmental determinants, using data from the V'I'S and VTSABD cohorts. The products will include an enhanced understanding of the influence of personality traits on risk for and persistence of anxiety and depressive disorders, new information on the risk of development of personality disorder traits in adulthood as a complication of anxiety and depressive disorders, new knowledge regarding the influence of personality traits on treatment seeking, and a more detailed understanding of etiologic relationships between normal personality traits and anxiety and depressive disorders. The results will have implications for prevention and other public health efforts. The Principal Investigator's research career development will be enhanced substantially through protected time for mentored analyses of longitudinal and twin data, and for relevant coursework. He will be guided by exceptionally talented mentors, including Drs. Gerald Nestadt, Kenneth Kendler, William Eaton, Kung-Yee Liang, Paul Costa, Murray Stein, Patrick Sullivan, and Lindon Eaves. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: PET IMAGING--COMORBID COCAINE DEPENDENCE AND DEPRESSION Principal Investigator & Institution: Rubin, Eric; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Applicant's Abstract) Comorbidity of cocaine dependence and major depressive disorder (MDD) poses an important clinical challenge. The relatively high incidence of such comorbidity and a variety of previous investigations raise intriguing questions about neurobiological connections between these disorders. We will use positron emission tomography (PET) of human brain metabolism, before and after treatment of the comorbid disorders, as a window into such neurobiological relationships. Our team combines expertise in advanced functional brain imaging with experience in the diagnosis and treatment of comorbid MDD and cocaine dependence. Subjects for this study will be carefully screened volunteers in four samples: cocainedependent (CD) only, MDD alone, CD comorbid with MDD, and normal controls. Equal numbers of males and females will be recruited to assess gender differences. The MDD and CD+MDD groups will be treated for 12 weeks with venlafaxine, an antidepressant which our pilot data indicates is effective in the comorbid population. Specific hypotheses about the profile of cerebral metabolism in these groups will be examined as follows: 1) at baseline in all groups, 2) following treatment, when baseline and posttreatment scans will be compared to identify brain sites potentially involved in treatment effects, and 3) following treatment, when baseline scans for responders and non-responders in each treatment group will be correlated with treatment outcome to identify pre-treatment metabolic features which predict responsiveness. We will apply advanced quantitative procedures for examining global, regional, and "network" brain metabolism, and will correlate these measures with standardized measures of treatment success. This methodologic rigor will contribute to understanding the pathophysiology and treatment of patients with comorbid depression and cocaine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PHYSIOLOGY OF ESTROGEN'S MOOD EFFECT IN MENOPAUSAL WOMEN Principal Investigator & Institution: Joffe, Hadine; Instructor Massachusetts General Hospital 55 Fruit St Boston, Ma 02114

in

Psychiatry;

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Timing: Fiscal Year 2003; Project Start 07-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): This Mentored Patient-Oriented Career Development Award focuses on developing expertise in the interdisciplinary field of perimenopausal depression. Menopause is universal in women, and depressive disorders occur in 10% of perimenopausal women. This project will dissect the mechanisms by which estrogen replacement therapy (ERT) treats depression in menopausal women. We hypothesize that ERT improves mood by a direct CNS effect, rather than by simply treating hot flushes and sleep disruption. A physiologic intervention study will compare the mood effect of ERT with that of a hypnotic agent in depressed perimenopausal women. The direct neuromodulatory effect of ERT on mood will be unmasked by controlling for ERT's effect on sleep. Polysomnographic (PSG) studies will be used to explore changes in sleep architecture that occur with ERT and the hypnotic agent zolpidem. This study will: (1) identify the elements critical to estrogen's antidepressant benefit; (2) characterize subpopulations of perimenopausal women whose depression can be treated with non-hormonal therapies and those who require treatment with ERT; and (3) define optimal management of depression in perimenopausal women. Understanding the components of ERT's effect on mood will also advance the field of hot-flush research by examining the impact of hot flushes on sleep, mood, and quality-of-life. This is critical for the development of novel estrogen alternatives and putative hot-flush therapies increasingly used in women with breast cancer and others unable or unwilling to take ERT. ENVIRONMENT: The proposed study will be based at Massachusetts General Hospital (MGH), with outstanding interdisciplinary sponsorship and consultant input. PSG studies will be performed at McLean Hospital. I will receive mentorship from Lee Cohen, M.D., in the Department of Psychiatry, and Janet Hall, M.D., in the Reproductive Endocrinology Unit of the Department of Medicine at MGH. Both sponsors are internationally recognized in their respective fields and have exceptional track records as effective research mentors. Their combined expertise will shape my career development in this interdisciplinary field. CAREER DEVELOPMENT PLAN: Physiologic investigation of mood disturbance in menopausal women requires that I acquire knowledge of (1) sleep medicine; and (2) research methods for healthoutcomes assessment and clinical intervention studies using physiologic measures. I will receive formal training in each of these specific research areas under the supervision of expert consultants. Such training will lay the foundation for a career of clinical investigation into the physiology of perimenopausal depression and the impact of hot flushes on sleep, mood, and quality-of-life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION

PILOT--PREVENTIVE

INTERVENTION

FOR

MATERNAL

Principal Investigator & Institution: Lagomasino, Isabel; Charles R. Drew University of Med & Sci 1731 East 120Th Street Los Angeles, Ca 900593025 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2007 Summary: Elevated rates of depressive symptoms have been well-documented among low-income mothers, including Latinas who are at high risk for living in poverty. However, Latinos have consistently been found to underutilize mental health services when these services are needed for such disorders as depression. Despite maternal depression in this group representing a disparity in health and functioning for both Latino mothers and their children, there is a lack of effective intervention strategies to decrease this health disparity. One way to address this disparity is by delivering services through Promotoras, lay health workers who are familiar with the

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neighborhood, culture, language and social status of immigrant Latinas. This proposal will examine the effectiveness of a preventive intervention for postpartum Latina women in decreasing symptoms of minor depression and will explore how treatment of these mothers may affect their parenting of and attachment to their infants. Teh Promotoras who regularly conduct home visits for postpartum Latinas will be trained in administering a screening instrument for detection of minor depression, the PrimeMD. Four Promotoras will then be trained and supervised in delivering a standardized 12session cognitive behavioral therapy intervention developed to prevent depression in pregnant women and new mothers. 100 postpartum Mexican American immigrant women recently discharged from the hospital following childbirth, will be identified as having minor depression and will be consented to participate in the study. The participants will be randomized to either the intervention group or a control condition. The main outcome variable will be maternal depression symptoms as measured by a structured interview for the Hamilton Rating Scale. Data will also be collected on appropriateness of parenting, attachment, and developmental outcome measures to estimate effect sizes and sample size needed (through power calculations) for a full-scale trial of the preventive intervention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: PREADOLESCENT PRECURSORS TO DEPRESSION IN GIRLS Principal Investigator & Institution: Keenan, Kathryn E.; Assitant Professor; Psychiatry; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2004; Project Start 18-DEC-2003; Project End 30-NOV-2008 Summary: (provided by applicant): By the time girls reach late adolescence there is a 1 in 5 chance of their experiencing a major depressive episode. This is twice the rate of depression in males, and represents the most common and disabling disorder for women. There has been very little effort at identifying precursors to depression, however, and as a result, there are few existing programs aimed at preventing this major public health problem. In current models the emergence of depression at adolescence is conceptualized as resulting from a combination of psychological challenges, biological changes (i.e., puberty) and social demands that are specific to adolescence. In contrast, the proposed study is based on the premise that the roots of adolescent depression lie at least partly in the preadolescent period. We have a unique opportunity to address issues in the development of depression in girls by taking advantage of an ongoing community-based study of young girls, the Pittsburgh Girls Study (PGS). In the proposed study, we will test the hypothesis that there are measurable, meaningful differences in a number of psychological correlates during preadolescence that serve as precursors to later depression. These include excessive levels of empathy and compliance, and difficulty with emotion regulation. Such correlates have not been incorporated into traditional models of psychopathology, but indirect evidence exists to support their role in the development of depression in girls. In addition, we will test hypotheses about types of caregiving environments and school experiences that interact with preadolescent characteristics of girls to increase the likelihood of later depression. These hypotheses will be tested in a longitudinal study of 240 girls identified from the PGS, half of whom already demonstrate elevated, but sub-clinical depression scores. The girls and their mothers will be observed in laboratory assessments at ages 8, 10, and 12, and will be administered semi-structured interviews covering depressive and anxiety disorders annually from ages 8 to 12. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREDISPOSITION MODEL OF INSOMNIA Principal Investigator & Institution: Drake, Christopher L.; Internal Medicine; Case Western Reserve Univ-Henry Ford Hsc Research Administraion Cfp-046 Detroit, Mi 48202 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Candidate's Plans/Training: The candidate's goal is for a career in patient-oriented clinical research in the field of sleep medicine with a focus on insomnia and concomitant psychiatric disease. The training plan will include 11 courses at two local Universities and formal didactic and laboratory training from experts on insomnia pathophysiology and treatment, magnetoencephalography, endocrinology, and post-traumatic stress disorder. Training will be organized in modules each providing specific instruction and consultation regarding topics related to the proposed research plan and the candidate's long-term career goal of becoming an independent investigator. Environment: Henry Ford Sleep Center is a well-established research facility and would be an ideal training site for this award. Proven mentorship, strong within and across departmental collaboration, and an institution with a dedicated research commitment combine to provide a setting well suited for the career development of a young scientist. Research: The prevalence of chronic insomnia has been estimated to be between 10-15 percent of the general population. Insomnia is associated with a two to five-fold greater incidence of depressive disorders across the lifespan, and a significant negative impact on quality of life. Models of primary insomnia generally conceptualize the pathophysiology of this disorder in the context of a precipitating event superimposed upon predisposing and subsequent maintaining factors. However, to date, factors that predispose individuals to acute sleep disturbance and the significance of that predisposition for the development of chronic insomnia has not been investigated. Our model of primary insomnia proposes that hyperarousability (markers: emotional reactivity, beta frequency EEG, and HPA axis activation in response to a "challenge") is associated with vulnerability to acute sleep disruption. It is our view that hyperarousability and its associated vulnerability to acute sleep disruption represents a predisposition to the subsequent development of chronic primary insomnia by sustaining sleep disruption following the removal of a precipitant. Within the framework of this model we propose two experiments to identify and characterize a predisposition to insomnia in which 1) a subset of individuals without insomnia but who have elevated arousal as marked by emotional reactivity (NER) similar to that seen in patients with primary insomnia, have a general vulnerability to sleep disturbance induced by a first night in the laboratory and nocturnal caffeine administration; 2) however, unlike individuals with chronic insomnia, on non-challenge nights, these high NER individuals show normal sleep; 3) high NER individuals have increased physiological arousal similar to chronic insomniacs; 4) finally, predisposed individuals have protracted sleep disturbance following the removal of a sustained sleep disrupting precipitant when the possibility of sleep disruption remains. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PREVENTION OF DEPRESSION (POD) Principal Investigator & Institution: Clarke, Gregory N.; Senior Investigator; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2003; Project Start 01-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): This application is one of four interlocking R01's to assess the impact of a group cognitive behavioral program (CBP) on the prevention of

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Depressive Disorders

depression in adolescents at risk for depression. Eligible teens must have a parent with active depression; teens themselves must have either a past depressive episode or current subsyndromal depressive symptoms. In this 5-year study, 320 at-risk adolescents (80 at each site) drawn from managed care organizations will be randomized to either CBP or usual care (UC) and followed for 32 months post intake to determine the impact of CBP vs. UC on onset of depressive disorders and symptoms, level of functioning, and medical and mental health care utilization. We hypothesize that participants in the CBP intervention will have a significantly lower prospective incidence of first and repeated episodes of depressive disorders and symptoms compared to adolescents in the usual care group. In addition, we will explore whether participants in CBP have a reduced prospective incidence of non-affective symptoms and disorders, and will show improved global functioning relative to the comparison group. Analyses also will focus on the incremental cost-effectiveness of providing the CBP over usual care from the health care perspective. This study builds on previous work by the Portland site (Clarke et al., 2001) showing a nearly six-fold reduction in the incidence of depression in CBP vs. UC, and extends this work in two ways - first, by testing whether the program can be replicated at several different sites, thereby greatly increasing the generalizability of the original findings; and second, by changing the timing and spacing of the intervention to provide continuation sessions to prolong the duration of the effect of CBP. This program of research is significant for several reasons: (1) depression is a chronic, prevalent, and impairing condition in adolescence that is often undetected, and which is more difficult to treat as chronicity increases; (2) there have been no large-scale studies of the prevention of depression in adolescence; and (3) by basing this study in managed care organizations, it will be possible to ascertain the costs and benefits of incorporating this intervention into "best practice" in real world settings. This application is based in Nashville (Judy Garber, PI), and interlocks with applications from Boston (William Beardslee, PI), Pittsburgh (David Brent, PI), and Portland (Greg Clarke, PI). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: PREVENTION OF DEPRESSION IN AT-RISK ADOLESCENTS Principal Investigator & Institution: Brent, David A.; Professor, of Psychiatry; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 03-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): This application is one of four interlocking R01's to assess the impact of a group cognitive behavioral program (CBP) on the prevention of depression in adolescents at risk for depression. Eligible teens must have a parent with active depression; teens themselves must have either a past depressive episode or current subsyndromal depressive symptoms. In this 5-year study, 320 at-risk adolescents (80 at each site) drawn from managed care organizations will be randomized to either CBP or usual care (UC) and followed for 32 months post intake to determine the impact of CBP vs. UC on onset of depressive disorders and symptoms, level of functioning, and medical and mental health care utilization. We hypothesize that participants in the CBP intervention will have a significantly lower prospective incidence of first and repeated episodes of depressive disorders and symptoms compared to adolescents in the usual care group. In addition, we will explore whether participants in CBP have a reduced prospective incidence of non-affective symptoms and disorders, and will show improved global functioning relative to the comparison group. Analyses also will focus on the incremental cost-effectiveness of providing the

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CBP over usual care from the health care perspective. This study builds on previous work by the Portland site (Clarke et al., 2001) showing a nearly six-fold reduction in the incidence of depression in CBP vs. UC, and extends this work in two ways - first, by testing whether the program can be replicated at several different sites, thereby greatly increasing the generalizability of the original findings; and second, by changing the timing and spacing of the intervention to provide continuation sessions to prolong the duration of the effect of CBP. This program of research is significant for several reasons: (1) depression is a chronic, prevalent, and impairing condition in adolescence that is often undetected, and which is more difficult to treat as chronicity increases; (2) there have been no large-scale studies of the prevention of depression in adolescence; and (3) by basing this study in managed care organizations, it will be possible to ascertain the costs and benefits of incorporating this intervention into "best practice" in real world settings. This application is based in Nashville (Judy Garber, PI), and interlocks with applications from Boston (William Beardslee, PI), Pittsburgh (David Brent, PI), and Portland (Greg Clarke, PI). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: PRIMARY CARE DIAGNOSIS & TREATMENT OF DEPRESSED CHILDREN Principal Investigator & Institution: Rushton, Jerry L.; Pediatrics & Communicable Dis; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 31-MAY-2003 Summary: (provided by applicant): Dr. Rushton proposes a career award to study and improve the diagnosis and treatment of children and adolescents with depressive disorders by primary care physicians. Recent changes in health care have important implications for management of depression including primary care gatekeeping, limited access to mental health providers and counseling, and new antidepressants. Yet, little information exists on the current role of primary care physicians, or how these physicians can improve coordination of care and services to improve patient outcomes. Dr. Rushton plans two phases of research to address his aims using complementary methods: (1) analysis of health system administrative data, (2) survey of primary care physicians. The proposed studies will describe depressed children and adolescents and their health care utilization; define the scope of primary care and relationships to mental health providers; analyze variations in prescriptions, referrals, and management of depressed youth; and examine influences on physician triage and treatment decisions. This research will be accomplished over five years and incorporate coursework and training in survey techniques (quantitative and qualitative), statistical analysis, pharmacology, child and adolescent psychiatry, and health services research. In the final years of the grant period, Dr. Rushton will develop a grant proposal based on his findings to design interventions to improve the quality of mental health services and integrate primary care with specialty and community providers. The University of Michigan provides the clinical and research environment to accomplish the proposed aims and career goals with support from many disciplines led by co-mentors, Dr. Gary Freed (Pediatric Health Services Research) and Dr. John Greden (Psychiatry). The candidate will acquire skills and connections that will allow him to become an independent researcher working at the important interface of delivery systems. The proposed research will set the stage for additional mental health services for children, quality improvement interventions on prescriber practices, and health system efforts to coordinate mental health services with primary care.

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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: DEPRESSION

PROBLEM-SOLVING

TREATMENT

FOR

PRIMARY

CARE

Principal Investigator & Institution: Oxman, Thomas E.; Professor; Psychiatry; Dartmouth College 11 Rope Ferry Rd. #6210 Hanover, Nh 03755 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: Minor depression is one of the most common types of depressive disorders in primary care. It is not clear that antidepressants are indicated for minor depression, and even if they are, a substantial proportion of patients cannot or will not take them. Alternative treatment approaches are indicated. The purpose of this project is to use a four-week watchful waiting period to identify patients with persistent minor depression, potentially most in need of depression specific treatment, and then test the therapeutic effect of Problem- Solving Treatment for Primary Care (PST-PC), a manual driven, six-session, behavioral treatment for depression in primary care. In this project, 300 primary care, minor depression patients will be identified and followed. The relationship of patient predictors to remission will be examined. After four weeks, patients who do not demonstrate symptomatic remission (approximately 50 percent or 150 patients) will be entered into a randomized nine-week clinical trial comparing PSTPC with Usual Care. Subjects will be followed for six months after completing the trial. The primary aim of this project is to test the therapeutic effect of PST-PC versus Usual Care for persistent minor depression in primary care. As a subsidiary aim the project will examine the relationship of characteristics of the patient (social support, adverse life events, personality traits, comorbidity) to early remission of minor depression. Patient and therapy characteristics will also be examined as predictors of recovery six months after the trial. The broader, long-term goal of this line of investigation is to disseminate practical, non-pharmacologic mental health treatments for use by non-physician practitioners (e.g. psychologists, nurses, social workers, counselors) who will increasingly be working in primary care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: RISK AND PREDICTORS OF POSTPARTUM DEPRESSION Principal Investigator & Institution: Altshuler, Lori L.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 11-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The postpartum period is a time of heightened risk for the emergence of psychiatric illness, particularly in women who already have a history of mood disorder. Given the prevalence of depressive disorders during the childbearing years, it is crucial to identify women who are at highest risk for new onset or recurrence of depression during the postpartum period. Identification of those women at greatest risk for postpartum depression may allow for interventions that would limit maternal morbidity associated with untreated postpartum depression. This proposal outlines a multi-institutional collaborative research project (R01) in response to PA-00-074, in which risk for postpartum depression will be evaluated in women with histories of major depressive disorder. Subjects who have had at least one episode of DSM-IV major depression will be followed prospectively from late pregnancy (32-36 weeks gestation) up to six months after delivery using a series of standardized instruments. The primary aims of this investigation are (1) to identify clinical and psychosocial predictors of postpartum depression and functional impairment and (2) to

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determine the extent to which treatment (pharmacologic, nonpharmacologic or a combination) proximate to delivery modulates risk for postpartum relapse. How clinical and psychosocial variables including history of postpartum depression, severity of past depression, number of previous episodes, age at illness onset, depression during pregnancy, and social support affect risk for postpartum depression, as well as psychosocial functioning, will be investigated. The current submission is a natural extension of an ongoing academically productive collaboration in which risk for depressive relapse is evaluated in pregnant women with histories of major depression who either discontinue or maintain antidepressant treatment. This proposal provides an opportunity to study a rigorously followed population into a period of risk -- the postpartum period -- and to investigate the factors that confer or modulate risk for depression at this time. The three participating sites for this investigation include the Perinatal and Reproductive Psychiatry Clinical Research Program at the Massachusetts General Hospital, Harvard Medical School (Drs. Cohen, Nonacs and Otto), the Women's Life Center and Mood Disorders Research Program at UCLA (Dr. AItshuler, Dr. Hendrick), and the Emory Women's Mental Health Program at Emory University School of Medicine (Dr. Stowe). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: RISK AND PREVENTION OF DEPRESSION IN YOUTH Principal Investigator & Institution: Garber, Judy; Professor; Psychology & Human Development; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This is a request for an NIH Independent Scientist Award (K02) to enhance the Pl's ability to contribute to the understanding of the processes underlying the development of depressive disorders in children and adolescents and to develop and test interventions aimed at preventing depression in youth. The Pl's research program has evolved from studying psychosocial risk factors that predict depression in children and adolescents, to examining the role of these risk factors as mediators of the link between parent and child psychopathology, to testing a prevention program that targets several of the risk factors identified in the earlier studies. This proposal describes three research programs involving five different but related studies. The first program includes two separate longitudinal studies that examine the contribution of varbus psychosocial factors (e.g., family dysfunction, social feedback, stress) to the development of negative cognitions and depressive disorders in children and adolescents. The second program is comprised of two different investigations of whether decreases in parents' depression as a result of treatment (cognitive-behavioral and/or pharmacotherapy) are associated with changes in their children's psychopathology and functioning, and whether these changes are mediated by improvements in parent-child relationships, negative cognitions, and/or decreases in stressful life events. The last project uses knowledge about risk factors learned from the first two research programs to test a cognitive-behavioral intervention for preventing depression in adolescents at risk for mood disorders due to their having a parent in treatment for depression, and themselves having either a past depressive ecandidatesode or current subsyndromal depressive symptoms. The goal of the career development plan is to expand the candidate's skills in two areas: quantitative methods and prevention science. Because most of the candidate's research is longitudinal, learning state-of-the-art statistical methods (e.g. latent growth curve, linear and nonlinear mixed effects models, survival analysis, structural equations modeling) will broaden the kinds of research questions that can be addressed with both existing and

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Depressive Disorders

new data. In addition, she will update and expand her knowledge of preventive interventions, particularly cognitive-behavioral approaches, with the aim of further developing and testing the efficacy of programs for preventing depression in high-risk adolescents. This K award will allow the candidate to bridge emcandidaterical research with practice by using basic knowledge about etiology to address the practical problem of preventing the onset and recurrence of the serious public health condition of depression, particularly among those at greatest risk for the disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: RISK FOR PSYCHOPATHOLOGY AMONG LESBIANS AND GAY MEN Principal Investigator & Institution: Cochran, Susan D.; Professor; Ctr for AfroAmerican Studies; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 29-SEP-2000; Project End 31-AUG-2004 Summary: (Applicant's abstract): Within the last 2 decades, research examining psychopathology among lesbians and gay men has moved away from viewing homosexuality as causal to investigating the role of social stress arising from this population's common experiences with discrimination and victimization. Consistent with a psychosocial stress model predicting that higher rates of distress and perhaps mental disorders will result, evidence suggests that lesbians and gay men may be more likely than others to experience depressive disorders, dysfunctional drug/alcohol use, and suicide attempts, though findings are mixed. In addition, research hints that lesbians and gay men may have different mental health care needs and utilization patterns. These issues, though, are largely understudied and, unfortunately, the majority of work has been hampered by critical methodological limitations, primarily a near total reliance on convenience-based sampling designs without similarly sampled heterosexual controls. A recent Institute of Medicine report on lesbian health issued in response to NIH and CDC requests for guidance on research with this population concluded that population-based studies and development of methodological improvements were needed to provide essential information about morbidity risk and protective factors. In response to the IOM recommendations and NIMH RFA PA-99-121, the current application proposes to capitalize on the existence of several populationbased datasets that offer a means of examining mental health and related services use by lesbians and gay men as a population. Specifically, we will identify in 6 national surveys individuals likely to be lesbians or gay men using sexual behavior and relationship status indicators. We will then compare these samples to similarly identified heterosexual women and men in order to estimate prevalence of mental health morbidity, quality of life indicators, and treatment utilization. Findings will clarify the nature of excess psychiatric risk, as well as factors that may promote resiliency, among lesbians and gay men. A further goal of the study is to facilitate developments in research methodology with this population. To that end, we will conduct comparisons using data from population-based and previously collected convenience-based surveys (including approximately 1 0,000 lesbians) in order to identify possible demographic and mental health morbidity differences between women in the two source populations sampled. Findings will greatly assist developing more efficient sampling frames in future studies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: S-ADENOSYL METHIONINE(SAME)AUGMENTATION OF SSRIS IN MDD Principal Investigator & Institution: Papakostas, George I.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 27-JAN-2004; Project End 30-NOV-2008 Summary: (provided by candidate): This is a submission of an application for a mentored patient-oriented K-23 award, designed to enhance clinical training and research expertise in the area of major depressive disorder on (MDD) and the role of natural remedies in the development and treatment of depressive disorders. Natural remedies, although used for centuries throughout the world, have become increasingly popular in the US over the past few years. S-adenosyl methionine (SAMe) is one such compound. Although results obtained from double-blind preliminary studies support the hypothesis that this compound may have antidepressant effects, oral SAMe has not yet been studied as a potential augmenting agent for contemporary, first-line antidepressants, such as the Selective Serotonin Reuptake Inhibitors (SSRIs). As many as 29% to 46% of depressed patients show only partial or non-response to an adequate course of an antidepressant, with most patients taking an SSRI as an initial treatment. The goal of this project will be to assess the efficacy of oral SAMe compared to placebo as an augmentor of SSRIs in the treatment of major depression refractory to treatment with SSRIs. This application involves enrolling outpatients with MDD, with partial or no response to an SSRI trial of adequate dose and duration. Patients will be treated for 6 weeks in a double-blind fashion with either oral SAMe tosylate, up to 1600mg/day, or placebo for 6 weeks. We hypothesize that there will be a statistically significant difference in the response rates between the two treatment groups at endpoint, with a greater response rate in the group that received SAMe augmentation. The proposed study will be based at the Massachusetts General Hospital in the Depression Clinical and Research Program, under the mentorship of Maurizio Fava, MD, and will include consultation from experts in the area of MDD, alternative medicine, and biostatistics. There will also be a didactic component to the application project, including coursework research design, neuronal biology, biostatistics, and ethics. It is hoped that this project award will provide the critical fund of basic knowledge and practical experience necessary to aid the candidate in becoming an independent investigator in this area. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY AND EFFICACY OF SERTRALINE FOR DEPRESSION CHF Principal Investigator & Institution: Krishnan, Ranga R.; Chairman and Professor; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 20-FEB-2003; Project End 31-JAN-2008 Summary: (provided by applicant): The significance of co-morbid depression upon the medically ill has recently been recognized in the medical literature. Higher prevalence rates of mood disorders above that of the normal population has been found in patients who suffer from chronic medical illnesses, including vascular disease (cerebrovascular and coronary artery disease). Additional work has shown increased in-patient hospitalizations, cost of care, morbidity and mortality in these patients. More than 2 million United States citizens suffer from congestive heart failure (CHF), accounting for the highest category for hospitalization in the Medicare population, with annual expenses exceeding $10 billion. One leading source of heart failure is ischemic heart disease. Despite knowledge that depressive disorders lead to increased morbidity, mortality and poorer outcomes in ischemic heart disease, little is currently known about

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Depressive Disorders

the association of CHF and depression. There is evidence that the rate of depression may be high in the CHF population, but no studies have addressed the impact on morbidity and mortality in CHF patients when depression is adequately treated. Funding is requested for a two site, prospective placebo treatment of patients with congestive heart failure and clinically diagnosed major depression. Patients will be enrolled in this study with clinically diagnosed heart failure of NYHA functional > II. Patients will be interviewed and evaluated for major depression by use of the protocol developed by the NIMH-supported Duke Center for the Study of Depression in the Elderly. This includes sections that assess depressive symptoms, psychiatric comorbidity, cognitive status, functional status and disability, daily and chronic stress, and social support, the longitudinal component of this study will include collecting data on all enrolled subjects. Information collected in these follow-up contacts will include deaths, re-hospitalizations, cardiac events, functional status/quality of life measures, and level of depressive symptoms. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: SLEEP AND PREFRONTAL CORTEX ASYMMETRY IN DEPRESSION Principal Investigator & Institution: Rattenborg, Niels C.; Psychiatry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 31-MAR-2002 Summary: (Verbatim from the Applicant's Abstract) Major depressive disorders are associated with distinct changes in sleeping and waking brain activity. Sleep in depressives is characterized by increased rapid-eye-movement (REM) sleep, shortened REM latency, as well as decreased slow-wave sleep and sleep efficiency. During wakefulness depressives show decreased activation of the left prefrontal cortex (PFC) when compared to the right. Changes in sleep architeckture and asymmetries in waking PFC activity may be related since PFC asymmetries also persist during sleep. Indeed recent positron emission tomography (PET) studies suggest that under normal cirecumstances actrivationh of the left PFC inhibits activity in the amygdala, a structure actively involved in processing negative emotions and anatomically positioned to modulate both REM sleep and arousal. Thus in expression, decreased left PFC activation mazy release the amygdala from left PFC inhibition, resulting in increased REM sleep expression. Increased amygdala actiovation may also decrease slow-wave sleep and sleep efficiency by raising arousal levels. These hypotheses will be tested using two complementary approaches. In the firsz, sleep measures will be correlated with patterns of PFC activation asymmetry and amygdala activation using a combination of EEG and PET imaging techniques in depressives. In the second, the effect of lesioning either the left or right PFC on sleep will be investigated in rhesus monkeys. Ultimately, a greater understanding of the mechanisms involved in abnormal sleep in depression promises to provide insight into the etiology and treatment of depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SLEEP DISTURBANCES AND RISK FOR ALCOHOL DISORDERS Principal Investigator & Institution: Crum, Rosa M.; Associate Professor; Epidemiology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2002; Project Start 29-SEP-2001; Project End 31-AUG-2004 Summary: (Provided by applicant): The overall aim of this application is to extend and strengthen prior work which has examined the relationship of insomnia and other sleep disturbances with the development of alcohol use disorders and problem drinking. The

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focus of the proposed analyses is the assessment of these association using data from two existing longitudinal surveys: 1) the Johns Hopkins Precursors study, and 2) the Baltimore ECA Follow-up Study. The primary goal of the current application is to assess the following specific aims: 1) to test whether insomnia and other sleep disturbances are associated with an increased risk for problematic alcohol use, and alcohol abuse and dependence; and whether this relationship differs by sex; 2) to test whether psychiatric comorbidity (such as depressive symptoms , depressive disorders, anxiety, and psychiatric distress) are mediators of this relationship; 3) to assess whether those with remitted alcohol abuse or dependence have higher rates of sleep disturbance compared to those who never abused alcohol; and 4) to assess the natural history of individuals with alcohol abuse and dependence who self-report insomnia and other sleep disturbances, specifically to test whether the prognosis for remission, drinking patterns presence of comorbid psychopathology, and subsequent sleep patterns differ for individuals with an alcohol use disorder, or problem drinking, if they have insomnia at baseline relative to those with alcohol abuse and dependence, or problem drinking who have no sleep disturbance. Prospective analyses of the relationship of insomnia with alcohol use disorders or problematic drinking have been few and of these prior studies, the follow-up intervals have been relatively short. We propose to complete secondary analyses of two well-studied prospective data sets, that have long follow-up intervals (mean of 13 years for the Baltimore ECA Follow- up study, and 36 to 50 years for the Johns Hopkins Precursors Study), and relatively low study attrition, which if successfully completed can improve our understanding of insomnia and other sleep difficulties as potential long term risk factors for problematic drinking behavior and alcohol abuse or dependence. Information from these unique data sets allow the ability to assess important mediating, as well as potential confounding and effect modifying characteristics such as the occurrence of depressive symptoms as well as other psychopathology and substance use. The data analyses should provide, in a costeffective manner, information on the relationship of insomnia and alcohol condition, which will help guide future experimental and observational studies. The results may highlight a potential focus for future investigations of prevention and early intervention efforts for reducing the incidence and prevalence of alcohol abuse and dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: LIFECOURSE

SOCIAL

INEQUALITIES

IN

DEPRESSION

ACROSS

THE

Principal Investigator & Institution: Buka, Stephen L.; Associate Professor; Maternal and Child Health; Harvard University (Sch of Public Hlth) Public Health Campus Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: This application addresses two major current themes in the epidemiology and prevention of adult mental disorders: a) social and economic disparities in health status: and b) early origins of adult health status. Where most of the current work in these areas has focused on physical health conditions (e.g., cardiovascular illness. diabetes) there is mounting evidence of the relevance of these lines of inquiry to psychiatric disorders. Furthermore, while socioeconomic disparities in depression in adulthood have been documented consistently, the mechanisms generating these disparities have yet to be fully elucidated. Accordingly, we seek to conduct new data analyses examining socioeconomic disparities in major depressive disorder in relation to adult and childhood socioeconomic status, and to examine the role of other childhood environmental factors in the development of depression. These investigations will be

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based on the Providence follow-up National Collaborative Perinatal Project, a thirtyyear, longitudinal study of 1,263 individuals who were enrolled at birth and systematically followed for an average of 27.8 years. Comprehensive prospective assessment of childhood environmental conditions have been obtained at multiple points in time and adult psychiatric diagnoses obtained using structured diagnostic interviews. We will employ a range of analytic strategies including discrete-time survival analyses. The specific aims of this study are to examine the effects of childhood socioeconomic status on the occurrence and severity of major depressive disorder in adulthood. Furthermore, we will assess the direct role of childhood environmental factors in the occurrence of depression as well as their potential to mediate the association between early-life socioeconomic conditions and subsequent depression. Finally, we will study the risk that substance abuse disorders pose on the incidence of depression and examine whether this risk is modified by childhood conditions. The prospective nature of this study, the comprehensive assessment of parental and childhood variables, and the rigorous measurement of psychiatric disorders in adulthood make this sample uniquely suited to addressing these aims. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: STUDY OF YOUNG CHILDREN AT RISK FOR DEPRESSION AND ADHD Principal Investigator & Institution: Hirshfeld-Becker, Dina R.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2002; Project Start 25-SEP-2001; Project End 31-AUG-2006 Summary: (provided by applicant): Clinical and epidemiological studies document a substantial overlap of at least 30 percent between attention deficit hyperactivity disorder (ADHD) and major depressive disorder (MD). Moreover, children comorbid for ADHD and MD are at heightened risk for morbidity and dysfunction. Clearly the ability to identify early the children most at risk for this comorbid presentation would be of the highest clinical and public health importance. To study early risk factors, it is necessary to choose a population known to be at especially high risk. Since parental MD has been shown to increase a child's risk for both MD and ADHD, and familial ADHD has been shown to increase risk for both MD and ADHD, a useful approach to studying early risk factors for these disorders in non-clinical samples is to focus on children at risk for MD and/or ADHD. Our work and that of others indicate that the temperamental trait "Behavioral Disinhibition" (BD) may be a powerful predictor of ADHD and externalizing symptoms and specifically of comorbid ADHD+MD. BD, which can be measured via laboratory observations in children ages 2 to 5 yrs, reflects the extreme tendency to seek out novelty, approach unfamiliar stimuli, and display disinhibition of speech and action. These responses may indicate a predisposition to develop ADHD+MD that can be measured before the disorders can be assessed accurately with standard psychiatric instruments. We therefore propose a 5-year longitudinal study of laboratory-observed BD in 2-5-year-old children and its psychiatric and functional outcomes (at age 6) in 100 offspring of parents with MD and 100 offspring of parents with ADHD, compared with 100 children of parents with neither disorder. We propose to examine BD as a predictor of (a) ADHD and (b) comorbid ADHD+MD. To examine the specificity of BD for these conditions, we will also examine rates of the broader categories of persistent disruptive behavior disorders, including oppositional-defiant disorder and conduct disorder, and of comorbid behavior disorders+MD. This study will form the foundation of a long-term follow-up study aimed at testing the usefulness

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of BD as a predictor of ADHD, comorbid ADHD+MD and of persistent disruptive behavior disorders in children at risk growing-up into later childhood and adolescence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: SUBMISSIVE BEHAVIOR AS A MODEL OF DEPRESSION Principal Investigator & Institution: Tunnicliff, Godfrey; Pharmacology and Toxicology; Indiana Univ-Purdue Univ at Indianapolis 620 Union Drive, Room 618 Indianapolis, in 462025167 Timing: Fiscal Year 2002; Project Start 01-JUL-2001; Project End 31-OCT-2003 Summary: (provided by applicant): Depression is one of the most prevalent mental disorders in the United States and is associated with high levels of morbidity and mortality. It is estimated that costs associated with depression (from absenteeism, lost productivity, lost earnings, treatment and rehabilitation) exceed $40 billion in the United States alone. Our work is focused on the investigation of the mechanism of depression and antidepressant drug action. We developed a new animal model of depression, reduction of submissive behavior (RSBM) that differs from existing behavioral tests by not subjecting animals to pain or artificially stressful conditions. Instead, pairs of rats compete during a daily 5-minute trial period for a limited amount of food. Half of the rats tested under this condition develop a dominant/submissive relationship that is a characteristic feature of normal animal social behavior. The submissive behavior observed can be objectively measured as the amount of time spent on the feeder relative to that by the paired dominant animal. We have shown that this submissive behavior has qualities of human depression and can be greatly reduced or eliminated by treatment with a wide variety of antidepressant drugs. We want to adopt the RSBM to mice for testing mouse mutants for candidate gene related to depression. The extension of the dominance-submissive model to mice is of particular importance because of the development of many genetically distinct mouse strains and the availability of mice with specific genetic modifications (i.e. knockout strains). The studies in this proposal are designed to test the hypothesis that mice, like rats, will form dominant-submissive behavior and to demonstrate the activity of antidepressant drugs in mice using the model as described above. We will also determine whether selected mouse strains are more prone to submissiveness than others. Furthermore we will study whether specific knockout mice showing depressive-like behaviors in other models of depression will be submissive as compared with the wild type animals. Human depression shows an inheritance pattern consistent with a genetic component. The identification of genetic elements in mice associated with depression-like behavior can be tested for homology in human patients that could ultimately lead to an understanding of genetic defects underlying depression in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SUBSTANCE DEPENDENT TEENS--IMPACT OF TREATING DEPRESSION Principal Investigator & Institution: Riggs, Paula D.; Associate Professor of Psychiatry; Psychiatry; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: (Applicant's Abstract) Adolescents with substance use disorders (SUD) and conduct disorder (CD) have high rates of comorbid depression. Despite the high prevalence of depression in such youth, little is known about effective treatment of such

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depressions. Moreover, the effects of treating depression on substance use and other problem behaviors in such youth are not known. Only serotonergic agents, fluoxetine (FLX) and paroxetine, with most support for FLX, have empirical support in the treatment of depression in adolescents without serious comorbidity. It is not known whether FLX (or paroxetine) are effective in treating the depressions of adolescents with SUD and CD. The proposed study is a randomized, placebo-controlled trial comparing placebo to fluoxetine for major depressive disorder (MDD) in 120 adolescents with SUD and CD. Adolescents with DSM-1V SUD, CD, and MDD assessed both clinically and with structured assessment instruments, will be randomized to one of these two treatment cells for 16 weeks. All subjects will also receive standardized, manual-driven cognitive behavior treatment for adolescent SUD for the duration of the trial as the background "treatment as usual" Medication compliance will be electronically monitored. Adverse side effects will be monitored weekly. The specific aims of this study are to test the following hypotheses: 1. Fidoxeline + CBT will be more effective in treating unipolar depression in adolescents with SUD and CD than placebo + CBT. 2. The treatment of depression with RX + CBT, in depressed adolescents with SUD and CD will be more effective than placebo + CBT in reducing substance use and improving conduct symptoms. 3. The treatment of depression with RX will result in greater retention in, and compliance with substance treatment (CBT) and reduction in both substance use and conduct problems than treatment with placebo. This research will contribute important knowledge regarding effective treatment of depression in conduct-disordered adolescents with SUD and provide information about the effects of treating depression on substance and other behavioral outcomes as well. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: THE ROLE OF NITRIC OXIDE IN ANTIDEPRESSANT ACTIVITY Principal Investigator & Institution: Paul, Ian A.; University of Mississippi Medical Center 2500 N State St Jackson, Ms 39216 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-AUG-2007 Summary: GRANT=6673590;P20RR Numerous laboratories have published evidence for a significant role of intracellular calcium homeostasis in major depressive disorders. Recent data implicates excitatory amino acid (EAA) neurotransmission in major depression and antidepressant activity. Synaptic activation at EAA receptive neurons is often mediated by the calcium-calmodulin-nitric oxide synthase-guanylyl cyclase cascade. We have recently demonstrated that antagonists of the several isoforms of nitric oxide synthase are as efficacious as imipramine in preclinical behavioral and biochemical screening procedures sensitive to antidepressants. We hypothesize that neuronal NOS inhibitors will produce antidepressant-like effects on behaviors and neurobiological sites know to be affected by antidepressants. Conversely, we hypothesize that the effects of clinically active SRI antidepressants on these behaviors and neurobiological sites is dependent upon their ability to inhibit neocortical NO production by NOS. Our SPECIFIC AIM 1 is to determine whether selective inhibition of nNOS will have antidepressant-like effects in mice. By extension of the central hypothesis, we predict that inhibition of neuronal NOS is absolutely required to produce the selective effects of antidepressants on behavior and neurobiological sites. Our SPECIFIC AIM 2 is to determine whether cotreatment with the nNOS substrate Larginine will disrupt the effects of known antidepressants on behavior and neurobiological adaptation. SPECIFIC AIM 3 will determine whether the effects of known antidepressants can proceed in mice lacking the nNOS isoform. Conversely, we hypothesize that lesion of monoaminergic neurons which modulate EAA signaling in

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forebrain will disrupt the ability of classical antidepressant but not neuronal NOS inhibitors to produce antidepressant-like effects in mice. Our SPECIFIC AIM 4 is to determine whether functional monoaminergic neurotransmitter systems are required for the antidepressant-like effects of NOS inhibitors. Finally, we hypothesize that antidepressant treatments will produce an adaptive response in EAA-receptive neurons utilizing nNOS as a subcellular messenger. Our SPECIFIC AIM 5 is to determine whether desensitization of neuronal NOS is produced by antidepressant treatments. We will test these hypotheses by examining the antidepressant-like effects of these treatments: (1) in acute behavioral tests and; (2) on neuronal substrates after chronic treatment. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: TREATMENT OF DEPRESSED ADOLESCENTS WITH PHYSICAL ILLNESS Principal Investigator & Institution: Szigethy, Eva M.; Children's Hospital (Boston) Boston, Ma 021155737 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The identification and treatment of depressive disorders in adolescents with chronic physical illness is an understudied area. The purpose of this Mentored Patient-Oriented Research Development Award (K23) is to enable the candidate to become an independent clinical researcher in the area of innovative approaches to evaluation and treatment of depression in adolescents facing physical illnesses. The proposal will focus on patients with inflammatory bowel disease (IBD). The project will be conducted at Children's Hospital Boston (CHB), where a large population of adolescents with IBD is available. William R. Beardslee, MD, with expertise in depressive disorders and prevention, will serve as the primary mentor. John March, MD, MPH and John Weisz, PhD, experts in clinical psychiatric outcome research and psychotherapy interventions, will serve as co-sponsors. Research plan: The aims are: 1) Conduct randomized comparison trial of cognitive behavioral therapy (CBT) enhanced with physical illness narrative, family education, and social skills components (n=24) to standard of community care treatment (n=24) in depressed adolescents with IBD, and 2) Investigate underlying neurobehavioral changes in adolescents with depression and IBD. Career development plan: The training will emphasize skills necessary for conducting comparative clinical trials in the treatment of depression in adolescents with chronic physical illness and begin to explore underlying neurological mechanisms of the disease process. Didactic work in intervention research design and statistics, developmental psychopathology, and assessment of methodologies for biological and neurobehavioral correlates of treatment response will complement supervision by the program consultants. With a sound understanding of pathobiology and change mechanisms, the long-term goals of the candidate are to develop and evaluate cognitive-behavioral and pharmacological treatments for physically ill children and adolescents with depression and to investigate neurobiological correlates of treatment effect. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TREATMENT OF DEPRESSION IN PARENTS--IMPACT ON CHILDREN Principal Investigator & Institution: Diamond, Guy S.; Assistant Professor; Children's Hospital of Philadelphia 34Th St and Civic Ctr Blvd Philadelphia, Pa 191044399

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Timing: Fiscal Year 2002; Project Start 15-SEP-1998; Project End 31-MAY-2005 Summary: (Adapted from applicant's abstract): The proposed project will study the impact of treating parental depression on children's socio-emotional adjustment. This project will interface with two newly funded NIMH treatment studies of adults diagnosed with major depressive disorder. The first is a two-site study being conducted at Vanderbilt University (PI, Steve Hollon, Ph.D.) and at the University of Pennsylvania (PI, Rob DeRubeis, Ph.D.). The second study will be at the University of Washington (PI, Neil Jacobson, Ph.D.). Across the three sites, 640 adults will receive cognitive therapy, pharmacotherapy, or placebo (plus a behavioral cell at UW). Based on preliminary data collected in the last four months, we estimate that about 25% of the patients will have children between 8 and 16 years old and will agree to participate. These preliminary data provide evidence of the feasibility and acceptability of the project, and showed that the targeted children of currently depressed parents were experiencing significant levels of symptoms and dysfunction. The proposed project will involve a comprehensive assessment of an index child with regard to psychopathology and functioning at the time the parent enters the treatment study and again at 2,4,8,12,18, and 24 months. A comparison group of children whose parents are lifetime-free of psychiatric and medical disorders also will be included. The primary aims of the study are: (a) to examine the relation between decreases in parent's depression and changes in children's functioning;(b) to explore possible mediators of these changes including the parent-child relationship, marital functioning, stressors, and cognitions; and (c) to test whether changes in child adaptation, the hypothesized mediators, and the relation between parent and child symptoms differ as a function of the type of treatment the parent received. Data analysis will involve traditional methods of repeated measures multivariate analyses of variance and a more general and innovative approach of individual growth curve modeling using covariance structure analysis. This study represents a truly unique opportunity to further our theoretical understanding of the link between parent and child psychopathology that can serve as a guide for the development of preventive interventions for high risk populations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: TREATMENT OF WOMEN WITH DEPRESSION AND SEXUAL ABUSE Principal Investigator & Institution: Zlotnick, Caron; Associate Professor; Butler Hospital (Providence, Ri) 345 Blackstone Blvd Providence, Ri 02906 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2004 Summary: Major depression is one of the most common psychiatric disorders among patients seeking treatment. Over the years, there has been the development and refinement of an array of treatment modalities for depression. Although research has demonstrated the effectiveness of pharmacological and psychosocial treatments for depression, a substantial number of depressed patients do not respond fully to available treatments. Recent theory and research suggest that depressed individuals with histories of childhood sexual abuse constitute, in part, those who respond poorly to available treatments and/or suffer from chronic depression. Despite the high prevalence of childhood sexual abuse in depressed populations, and the poor prognostic outcome of this subgroup of depressed patients, no treatments for depression that address the specific clinical needs of depressed patients with histories of sexual abuse have been developed or systematically evaluated. Based on an integration of the literature on the treatment of depression and childhood sexual abuse, it is proposed to develop a 24week treatment, Schema-Focused Therapy, for this subgroup of depressed patients,

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which may improve treatment retention and efficacy for this challenging population of patients. The aims of this treatment development proposal are to: 1) modify and expand a schema-focused treatment manual for depressed patients with histories of childhood sexual abuse; 2) develop and implement a therapist training program for the proposed treatment; 3) develop and test competence and adherence rating scales for the proposed treatment; 4) expand the clinical management component of the control condition, pharmacotherapy plus clinical management; 5) conduct a pilot study of the treatment program, which will evaluate the initial efficacy, feasibility, and acceptability of the proposed treatment in conjunction with expanded pharmacotherapy-plus-clinicalmanagement compared to a control condition (expanded pharmacotherapy-plus-clinical management) in a sample of 24 female patients with major depression and histories of childhood sexual abuse. Primary treatment outcomes will be: a) treatment retention; and b) depressive symptoms; 6) test the feasibility and acceptability of the control condition for depressed patients with histories of childhood sexual abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: TREATMENTS FOR COMPLEX PATIENTS IN NEW SETTINGS Principal Investigator & Institution: Hall, Sharon M.; Professor & Vice Chair; Langley Porter Psychiatric Institute; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 941222747 Timing: Fiscal Year 2002; Project Start 29-SEP-1994; Project End 31-AUG-2004 Summary: (Applicant's Abstract) This is the competing continuation application of the San Francisco Treatment Research Center (TRC). In the last 3-1/2 years, TRC investigators have collaborated productively in science, training, and dissemination. The specific aims of the four currently funded components will be met, and expanded upon. The current application is unified around a theme of behavioral treatments of complex drug abusing patients in new settings. Four scientific components are proposed, supported by two cores. The primary project in each component is a controlled clinical trial of an innovative intervention in a "real-life" setting, with cross-component collaboration in descriptive, pilot, and integrative studies. Each component targets a group of drug abusers with a serious co-occurring disorder. The four components are: (1) a trial of a behavioral skills training intervention to promote reduction in drug use of drug dependent seriously mentally ill patients in clinical case management programs; (2) a trial evaluating the effects of a voucher-based contingency system on drug use and health maintenance behaviors of HIV-positive opioid users in methadone treatment; (3) a trial to evaluate intervention strategies provided in a hospital-based medical emergency department to link opioid users with acute medical problems to methadone treatment; and (4) a trial to evaluate a behavioral intervention for nicotine dependence for smokers with depressive disorders who are patients of a psychiatric outpatient clinic. The scientific and administrative core provides support for training, dissemination, measurement, health economics, and administration, as well as providing an integrating intellectual focus. The biostatistical core provides advanced statistical support, and uses data from the planned components to complete relevant research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: TRYPTOPHAN DEPLETION: A PHENOTYPIC MARKER FOR DEPRESSION Principal Investigator & Institution: Moreno, Francisco A.; Psychiatry; University of Arizona P O Box 3308 Tucson, Az 857223308

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Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The research objectives of this study are to improve our understanding of major depression and its pathophysiology, improve our ability to predict future episodes, and identify susceptibility genes predisposing to major mood disorders. We expect to accomplish these by utilizing a candidate gene approach to study the association of several monoamine related genotypic markers and the depressive response to tryptophan (TRP) depletion as a newly defined phenotype. The TRP depletion paradigm is a broadly utilized research methodology that safely and effectively has contributed to our improved understanding of the physiological effects of serotonin neurotransmission in a variety of research models and subject populations. Specifically, the neurotransmitter depletion paradigms have been proposed as phenotypes for major affective disorders based on their ability to induce brief and reversible depressive responses in subjects considered at risk for depression - such as remitted depressives, and subjects with multigenerational family history of affective disorders - but not in healthy controls. We propose to study a new phenotypic definition because "depression" is a highly heterogeneous condition. This, along with the lack of objective biological measurements of the disease, has limited progress in the field. The present study will conduct TRP depletion testing in 100 subjects with history of major depression but who are currently in remission and medication-free for at least three months. TRP depletion involves two 3-day sessions (active depletion and control) in a double blind, controlled, crossover design. Day one involves the ingestion of a TRP-free 15 amino acid drink or a TRP-supplemented 16 amino acid drink. Clinician and selfrated behavioral measurements of depression, anxiety, and somatic symptoms, as well as blood samples for measurement of plasma TRP and large neutral amino acids will be obtained prior to, during, and after testing. Subjects will be monitored prospectively for major depressive recurrences during the follow-up year. TRP depletion testing will take place at two sites: The University of Arizona, and University Hospitals of Cleveland / Case Western Reserve University Departments of Psychiatry. Polymerase Chain Reaction based Genotyping will be performed in order to study several candidate gene polymorphisms relevant to monoamine function. Genotyping will take place at the University of Arizona. A thoughtfully implemented procedure for protection of human subjects is in place to safeguard participant's safety. Compelling pilot data are presented to support the study feasibility and validity of the proposed hypotheses. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: TSH HYPERSECRETION IN WKY: POSITIONAL CANDIDATE ANALYSIS Principal Investigator & Institution: Baum, Amber E.; Psychiatry and Behavioral Scis; Northwestern University Office of Sponsored Research Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2004 Summary: (provided by applicant): The high comorbidity between hypo- and hyperthyroidism and depressive disorders illustrates the influence of hypothalamicpituitary-thyroid (HPT) axis function on behavior. The inbred Wistar-Kyoto (WKY) rat strain has persistently elevated TSH despite elevated thyroid hormone levels and normal negative feedback to the pituitary. Also, WKY are hypoactive in a variety of behavioral tests, including the open-field test. The strain is thus an excellent model for dissecting the relationships between multigenic behavioral traits and complex hormonal control systems using forward genetics. Genetic architectures of these traits will be investigated with quantitative trait locus (QTL) analysis. An F2 intercross population has been created from reciprocal crosses between WKY and the genetically, hormonally

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and behaviorally polymorphic Fischer-344 strain. The WKYxF344 F2 generation is sufficient to segregate phenotypic traits and create a linkage map to perform a QTL analysis. By demonstrating an association between an extreme expression of these phenotypes and marker alleles whose genetic map position is known, loci will be mapped to specific regions of individual chromosomes, and commonalities between the behavioral and hormonal traits? genetic architectures will be revealed. Significant loci of interest will be introgressed into congenic strains using marker-and phenotype-assisted selection, which will confirm the locus? role in the phenotype and permit its further analysis in isolation from other segregating loci that may modify its expression. The loci will also be analyzed using a positional candidate approach utilizing homology maps linking rat, mouse and human genomes. These experiments will contribute to the understanding of HPT regulation, and also illuminate any genetic links that may exist between these phenotypes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: TWIN COMORBIDITY

STUDY

OF

SEPARATION

ANXIETY

DISORDER

Principal Investigator & Institution: Cronk, Nikole J.; Psychological Sciences; University of Missouri Columbia 310 Jesse Hall Columbia, Mo 65211 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Comorbidity among anxiety and depressive disorders has been well documented, yet the etiological pathways contributing to this comorbidity are not clearly understood. Most of the research regarding the genetic and environmental sources of comorbidity among these disorders has been conducted using adult samples and suggests that genetic and nonshared environmental sources of covariation are important. Relatively little is known about the behavioral genetic aspects of comorbidity among anxiety and depressive disorders in children and adolescents. In an effort to extend the current knowledge regarding the comorbidity of internalizing disorders to younger populations, the proposed research will employ data from a large population-based sample of female twins to explore the comorbidity among Separation Anxiety Disorder (SAD), Depression (DEP) and Generalized Anxiety Disorder (GAD) and parse the sources of comorbidity into latent genetic and environmental factors using multivariate genetic analyses. In addition, the proposed research seeks to further clarify the nature of comorbidity of SAD with DEP and GAD by including measured personality (introversion and neuroticism) and environmental characteristics (socioeconomic disadvantage and paternal absence) in multivariate genetic analyses. Advances have been made in the study of comorbidity as well as personality and environmental characteristics as risk factors for internalizing disorders among youth; yet, these areas of study remain largely independent of one another. The proposed project seeks to integrate these areas of investigation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen x

Project Title: UNDERSTANDING CHILDHOOD CONDUCT PROBLEMS AND DEPRESSION Principal Investigator & Institution: Shaw, Daniel S.; Professor; Psychology; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 20-SEP-1999; Project End 31-AUG-2004 Summary: The aim of this RSA application is to expand the candidate's ability to understand the development, prevention, and treatment of two types of childhood

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disorders: conduct problems and depression. The candidate proposes two programs of research and a plan for professional development. The goal of the first program (NIMH R01-50907) is to identify developmental pathways leading to antisocial behavior from infancy to middle childhood. The first hypothesis is that parent-infant interaction in the first year, characterized by infant demandingness and maternal unresponsiveness, leads to coercive cycles of interaction at preschool-age, which in turn spread to relationships the child has with siblings, peers, and teachers at school-age. It is further hypothesized that the young child who as established a pattern of conduct problems, has been rejected by caregivers, and has shown coercive patterns of interaction with adults and siblings will more likely demonstrate a persistent pattern of conduct problems from ages 6-12. This model will be tested with a sample of 310, ethnically diverse boys from low-income families followed from infancy through school-age. The goal of the second program (NIMH PO1-56193) is to investigate selected attributes and mechanisms of emotionregulatory kills in the offspring of mothers with childhood-onset depression (COD) that may contribute to the children's own risk for depressive disorders. The offspring in the COD group will be compared with two others: (1) the offspring of probands with childhood-onset anxiety disorder (AD), and (2) the offspring of probands with no childhood-onset disorder (NCOD). It is hypothesized that in COD families, there will be greater impairment in (1) the child's regulatory strategies, (2) maternal attributes, and (3) maternal parenting, in comparison to AD and NCOD families. An accelerated longitudinal design will be utilized so that group differences can be evaluated crosssectionally and longitudinally from ages 1 to 9 during the five-year span of the project. Participants will include 132 offspring of COD, AD, and NCOD probands. The purpose of the RSA is to permit the candidate to conduct these two programs of research, to enhance his ability to train students, and to increase his professional development by broadening his knowledge of research design and methods, psychophysiology, cultural context, and intervention research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “depressive disorders” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for depressive disorders in the PubMed Central database: x

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Admission for depression among men in Scotland, 1980-95: retrospective study. by Shajahan PM, Cavanagh JT.; 1998 May 16; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28549

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.

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Antidepressant drugs and generic counselling for treatment of major depression in primary care: randomised trial with patient preference arms. by Chilvers C, Dewey M, Fielding K, Gretton V, Miller P, Palmer B, Weller D, Churchill R, Williams I, Bedi N, Duggan C, Lee A, Harrison G.; 2001 Mar 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=30555

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Comparison of 3 Depression Screening Methods and Provider Referral in a Veterans Affairs Primary Care Clinic. by Kanter JW, Epler AJ, Chaney EF, Liu CF, Heagerty P, Lin P, Felker B, Hedrick SC.; 2003 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=419394

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Cross-sectional survey of users of Internet depression communities. by Powell J, McCarthy N, Eysenbach G.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=317315

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Delivering interventions for depression by using the internet: randomised controlled trial. by Christensen H, Griffiths KM, Jorm AF.; 2004 Jan 31; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=324455

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Detection of depression and anxiety in primary care: follow up study. by Kessler D, Bennewith O, Lewis G, Sharp D.; 2002 Nov 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=131021

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Diagnosis and management of depression in primary care: a clinical update and review. by Remick RA.; 2002 Nov 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=134138

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Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. by Nemeroff CB, Heim CM, Thase ME, Klein DN, Rush AJ, Schatzberg AF, Ninan PT, McCullough JP Jr, Weiss PM, Dunner DL, Rothbaum BO, Kornstein S, Keitner G, Keller MB.; 2003 Nov 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=283585

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DSM depression and anxiety criteria and severity of symptoms in primary care: cross sectional study. by Nease DE Jr, Aikens JE.; 2003 Nov 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=261661

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Efficacy and tolerability of selective serotonin reuptake inhibitors compared with tricyclic antidepressants in depression treated in primary care: systematic review and meta-analysis. by MacGillivray S, Arroll B, Hatcher S, Ogston S, Reid I, Sullivan F, Williams B, Crombie I.; 2003 May 10; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=154760

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Escitalopram: A New SSRI for the Treatment of Depression in Primary Care. by Culpepper L.; 2002 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=315490

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Follow up study of longstanding depression as predictor of mortality in elderly people living in the community. by Pulska T, Pahkala K, Laippala P, Kivela SL.; 1999 Feb 13; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27733

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From the Bench to the Trench: A Comparison of Sertraline Treatment of Major Depression in Clinical and Research Patient Samples. by Lydiard RB, Perera P, Batzar E, Clary CM.; 1999 Oct; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181082

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Identifying depression in primary care: a comparison of different methods in a prospective cohort study. by Henkel V, Mergl R, Kohnen R, Maier W, Moller HJ, Hegerl U.; 2003 Jan 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=140277

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Incidence of major depression in Canada. by Patten SB.; 2000 Sep 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80167

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Increase in the cerebrospinal fluid content of neurosteroids in patients with unipolar major depression who are receiving fluoxetine or fluvoxamine. by Uzunova V, Sheline Y, Davis JM, Rasmusson A, Uzunov DP, Costa E, Guidotti A.; 1998 Mar 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=19726

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Influence of symptoms of anxiety on treatment of depression in later life in primary care: questionnaire survey. by Kirby M, Denihan A, Bruce I, Radic A, Coakley D, Lawlor BA.; 1999 Feb 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27763

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Managing depression as a chronic disease: a randomised trial of ongoing treatment in primary care. by Rost K, Nutting P, Smith JL, Elliott CE, Dickinson M.; 2002 Oct 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=130058

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Multifaceted shared care intervention for late life depression in residential care: randomised controlled trial. by Llewellyn-Jones RH, Baikie KA, Smithers H, Cohen J, Snowdon J, Tennant CC.; 1999 Sep 11; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=28220

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Multiple deletions of mitochondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthalmoplegia. by Suomalainen A, Majander A, Haltia M, Somer H, Lonnqvist J, Savontaus ML, Peltonen L.; 1992 Jul; http://www.pubmedcentral.gov/picrender.fcgi?tool=pmcentrez&action=stream&blobt ype=pdf&artid=443063

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National Patterns of Depression Treatment in Primary Care. by Stafford RS, Ausiello JC, Misra B, Saglam D.; 2000 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181143

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Phagocytosis and killing of Staphylococcus aureus: effects of stress and depression in children. by Bartlett JA, Demetrikopoulos MK, Schleifer SJ, Keller SE.; 1997 May; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&rendertype=abstr act&artid=170533

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Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: Relation to hypercortisolism and corticotropin-releasing hormone. by Wong ML, Kling MA, Munson PJ, Listwak S, Licinio J, Prolo P, Karp B, McCutcheon IE, Geracioti TD Jr, DeBellis MD, Rice KC, Goldstein DS, Veldhuis JD, Chrousos GP, Oldfield EH, McCann SM, Gold PW.; 2000 Jan 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26662

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Randomised controlled trial of midwife led debriefing to reduce maternal depression after operative childbirth. by Small R, Lumley J, Donohue L, Potter A, Waldenstrom U.; 2000 Oct 28; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27510

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Randomised controlled trial of problem solving treatment, antidepressant medication, and combined treatment for major depression in primary care. by Mynors-Wallis LM, Gath DH, Day A, Baker F.; 2000 Jan 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27250

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Randomised trial of monitoring, feedback, and management of care by telephone to improve treatment of depression in primary care. by Simon GE, VonKorff M, Rutter C, Wagner E.; 2000 Feb 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27299

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Reliability, validity and psychometric properties of the Greek translation of the Major Depression Inventory. by Fountoulakis KN, Iacovides A, Kleanthous S, Samolis S, Gougoulias K, Tsiptsios I, Kaprinis GS, Bech P.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=149454

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Reliability, validity and psychometric properties of the Greek translation of the zung depression rating scale. by Fountoulakis KN, lacovides A, Samolis S, Kleanthous S, Kaprinis SG, Kaprinis GS, Bech P.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=64635

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Risk factors, prevalence, and treatment of anxiety and depressive disorders in Pakistan: systematic review. by Mirza I, Jenkins R.; 2004 Apr 3; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=383372

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Routinely administered questionnaires for depression and anxiety: systematic review. by Gilbody SM, House AO, Sheldon TA.; 2001 Feb 17; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=26571

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Screening for depression in primary care with two verbally asked questions: cross sectional study. by Arroll B, Khin N, Kerse N.; 2003 Nov 15; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=261815

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Stillbirth as risk factor for depression and anxiety in the subsequent pregnancy: cohort study. by Hughes PM, Turton P, Evans CD.; 1999 Jun 26; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=31099

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The Comorbidity of Major Depression and Anxiety Disorders: Recognition and Management in Primary Care. by Hirschfeld RM.; 2001 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181193

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The greek translation of the symptoms rating scale for depression and anxiety: preliminary results of the validation study. by Fountoulakis KN, Iacovides A, Kleanthous S, Samolis S, Gougoulias K, St Kaprinis G, Bech P.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=317317

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The Norwegian naturalistic treatment study of depression in general practice (NORDEP) ---I: randomised double blind study. by Malt UF, Robak OH, Madsbu HP, Bakke O, Loeb M.; 1999 May 1; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=34546

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The Renin-Angiotensin-Aldosterone system in patients with depression compared to controls -- a sleep endocrine study. by Murck H, Held K, Ziegenbein M, Kunzel H, Koch K, Steiger A.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=280657

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Use of an Electronic Medical Record to Facilitate Screening for Depression in Primary Care. by Gill JM, Dansky BS.; 2003 Jun; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=406379

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Why treat depression differently from other medical problems? by Blier P.; 2002 Jul; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161655

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with depressive disorders, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “depressive disorders” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for depressive disorders (hyperlinks lead to article summaries): x

A case-control study of corticosteroid exposure as a risk factor for clinicallydiagnosed depressive disorders in a hospitalized population. Author(s): Patten SB, Williams JV, Love EJ. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1995 September; 40(7): 396-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8548719

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A comparison of descriptive variables for clinical patients and symptomatic volunteers with depressive disorders. Author(s): Rapaport MH, Zisook S, Frevert T, Seymour S, Kelsoe JR, Judd LL. Source: Journal of Clinical Psychopharmacology. 1996 June; 16(3): 242-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8784657

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A double blind trial of moclobemide versus amitriptyline in the treatment of depressive disorders. Author(s): Newburn GM, Fraser AR, Menkes DB, Mullen PE. Source: The Australian and New Zealand Journal of Psychiatry. 1990 December; 24(4): 475-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2073222

6

PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A double-blind comparison of moclobemide and fluoxetine in the treatment of depressive disorders. Author(s): Williams R, Edwards RA, Newburn GM, Mullen R, Menkes DB, Segkar C. Source: International Clinical Psychopharmacology. 1993 January; 7(3-4): 155-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8468437

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A factor analytical study of the Comprehensive Psychopathological Rating Scale among patients with anxiety and depressive disorders. Author(s): Martinsen EW, Friis S, Hoffart A. Source: Acta Psychiatrica Scandinavica. 1989 November; 80(5): 492-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2596349

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A model to evaluate the cost-effectiveness of oral therapies in the management of patients with major depressive disorders. Author(s): Einarson TR, Arikian S, Sweeney S, Doyle J. Source: Clinical Therapeutics. 1995 January-February; 17(1): 136-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7758056

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A risk-benefit assessment of moclobemide in the treatment of depressive disorders. Author(s): Norman TR, Burrows GD. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1995 January; 12(1): 46-54. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7741983

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Adrenal steroids and the physiopathology of a subset of depressive disorders. Author(s): Dubrovsky B. Source: Medical Hypotheses. 1991 November; 36(3): 300-5. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1787828

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Advances in treatment of anxiety and depressive disorders. Author(s): Lyles WB, Simpson B. Source: J Fla Med Assoc. 1990 August; 77(8): 731-4. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1979345

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Advocating for mental health services for children with depressive disorders. Author(s): De Santis JP. Source: Journal for Specialists in Pediatric Nursing : Jspn. 2003 January-March; 8(1): 3840. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12715406

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Aetiology of anxiety and depressive disorders in an inner-city population. 1. Early adversity. Author(s): Brown GW, Harris TO. Source: Psychological Medicine. 1993 February; 23(1): 143-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8475202

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Aetiology of anxiety and depressive disorders in an inner-city population. 2. Comorbidity and adversity. Author(s): Brown GW, Harris TO, Eales MJ. Source: Psychological Medicine. 1993 February; 23(1): 155-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8475203

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Al Ain community survey of psychiatric morbidity II. Sex differences in the prevalence of depressive disorders. Author(s): Daradkeh TK, Ghubash R, Abou-Saleh MT. Source: Journal of Affective Disorders. 2002 November; 72(2): 167-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12200207

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Alcoholism and depressive disorders in opioid addicts and their family members. Author(s): Kosten TR, Kosten TA, Rounsaville BJ. Source: Comprehensive Psychiatry. 1991 November-December; 32(6): 521-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1778079

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Alexithymia in somatoform and depressive disorders. Author(s): Duddu V, Isaac MK, Chaturvedi SK. Source: Journal of Psychosomatic Research. 2003 May; 54(5): 435-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12726899

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Alterations of drive in differential diagnosis of mild depressive disorders--evidence for the spectrum concept of endogenomorphic affective psychosis. Author(s): Ebert D. Source: Psychopathology. 1992; 25(1): 23-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1603907

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Amplification and attribution styles in somatoform and depressive disorders--a study from Bangalore, India. Author(s): Duddu V, Chaturvedi SK, Isaac MK. Source: Psychopathology. 2003 March-April; 36(2): 98-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12766320

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An interactionistic integrating view of depressive disorders and their treatment. Author(s): Perris C. Source: Acta Psychiatrica Scandinavica. 1991 November; 84(5): 413-23. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1776493

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Animal models of depression reflect changing views on the essence and etiology of depressive disorders in humans. Author(s): Richardson JS. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 1991; 15(2): 199-204. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1871322

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Anti-depressant prescribing patterns for prison inmates with depressive disorders. Author(s): Baillargeon J, Black SA, Contreras S, Grady J, Pulvino J. Source: Journal of Affective Disorders. 2001 March; 63(1-3): 225-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11246100

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Anxiety and depressive disorders in adult children caring for demented parents. Author(s): Dura JR, Stukenberg KW, Kiecolt-Glaser JK. Source: Psychology and Aging. 1991 September; 6(3): 467-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1930763

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Anxiety and depressive disorders in attention deficit disorder with hyperactivity: new findings. Author(s): Jensen PS, Shervette RE 3rd, Xenakis SN, Richters J. Source: The American Journal of Psychiatry. 1993 August; 150(8): 1203-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8328565

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Anxiety in depressive disorders. Author(s): Kuhs H. Source: Comprehensive Psychiatry. 1991 May-June; 32(3): 217-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1884601

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Assessment and treatment strategies for depressive disorders commonly encountered in primary care settings. Author(s): Perry MV, Anderson GL. Source: The Nurse Practitioner. 1992 June; 17(6): 25, 29-30, 33-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1608568

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Assessment of state and trait anxiety in subjects with anxiety and depressive disorders. Author(s): Kennedy BL, Schwab JJ, Morris RL, Beldia G. Source: The Psychiatric Quarterly. 2001 Fall; 72(3): 263-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11467160

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Association study of a brain-derived neurotrophic-factor genetic polymorphism and major depressive disorders, symptomatology, and antidepressant response. Author(s): Tsai SJ, Cheng CY, Yu YW, Chen TJ, Hong CJ. Source: American Journal of Medical Genetics. 2003 November 15; 123B(1): 19-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582140

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Association study of angiotensin I-converting enzyme polymorphism and symptomatology and antidepressant response in major depressive disorders. Author(s): Hong CJ, Wang YC, Tsai SJ. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 September; 109(9): 1209-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12203048

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Association study of the 5-HT(6) receptor polymorphism (C267T) and symptomatology and antidepressant response in major depressive disorders. Author(s): Wu WH, Huo SJ, Cheng CY, Hong CJ, Tsai SJ. Source: Neuropsychobiology. 2001; 44(4): 172-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11702016

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Association study of the serotonin transporter promoter polymorphism and symptomatology and antidepressant response in major depressive disorders. Author(s): Yu YW, Tsai SJ, Chen TJ, Lin CH, Hong CJ. Source: Molecular Psychiatry. 2002; 7(10): 1115-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12476327

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Associations of the severity of depressive disorders in women with psychogenic low weight. Author(s): Dowson J. Source: Journal of Affective Disorders. 2004 March; 78(3): 279-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013255

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Benzodiazepines in depressive disorders. Author(s): Schatzberg AF, Cole JO. Source: Archives of General Psychiatry. 1978 November; 35(11): 1359-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=30428

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Benzodiazepines in depressive disorders: a clinical guide. Author(s): Schatzberg AF. Source: Southern Medical Journal. 1978 August; 71 Suppl 2: 18-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=28570

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Beta-adrenoceptor density of intact mononuclear leukocytes in subgroups of depressive disorders. Author(s): Jeanningros R, Mazzola P, Azorin JM, Samuelian-Massa C, Tissot R. Source: Biological Psychiatry. 1991 April 15; 29(8): 789-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1675894

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Better outcomes for depressive disorders? Author(s): Lee AS. Source: Psychological Medicine. 2003 July; 33(5): 769-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877391

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Bias in computerized neuropsychological assessment of depressive disorders caused by computer attitude. Author(s): Weber B, Fritze J, Schneider B, Kuhner T, Maurer K. Source: Acta Psychiatrica Scandinavica. 2002 February; 105(2): 126-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11939962

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Biochemical criteria for classifying depressive disorders and predicting responses to pharmacotherapy: preliminary findings from studies of norepinephrine metabolism. Contributions to biochemistry. Author(s): Schildkraut JJ. Source: Pharmakopsychiatr Neuropsychopharmakol. 1974 March; 7(2): 98-107. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4438430

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Biological markers of melancholia and reclassification of depressive disorders. Author(s): Greden JF. Source: L'encephale. 1982; 8(2): 193-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6809444

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Birth-cohort changes in manic and depressive disorders in relatives of bipolar and schizoaffective patients. Author(s): Gershon ES, Hamovit JH, Guroff JJ, Nurnberger JI. Source: Archives of General Psychiatry. 1987 April; 44(4): 314-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3566454

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Blood markers and depressive disorders: an association study. Author(s): Tanna VL, Winokur G, Elston RC, Go RC. Source: Comprehensive Psychiatry. 1977 May-June; 18(3): 263-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=858243

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Brain phosphorous metabolism in depressive disorders detected by phosphorus-31 magnetic resonance spectroscopy. Author(s): Kato T, Takahashi S, Shioiri T, Inubushi T. Source: Journal of Affective Disorders. 1992 December; 26(4): 223-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1479134

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Brain purinergic activity linked with depressive symptomatology: hypoxanthine and xanthine in CSF of patients with major depressive disorders. Author(s): Agren H, Niklasson F, Hallgren R. Source: Psychiatry Research. 1983 July; 9(3): 179-89. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6578531

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Bromocriptine treatment of depressive disorders. Clinical and biochemical effects. Author(s): Nordin C, Siwers B, Bertilsson L. Source: Acta Psychiatrica Scandinavica. 1981 July; 64(1): 25-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6172006

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Childhood brain tumors and depressive disorders. Author(s): Connemann BJ, Kassubek J. Source: The New England Journal of Medicine. 2003 November 6; 349(19): 1868-9; Author Reply 1868-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14602887

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Childhood depressive disorders. Author(s): Lyon DE, Morgan-Judge T. Source: J Sch Nurs. 2000 August; 16(3): 26-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11885086

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Chronic neurotic and depressive disorders as posttraumatic reactions in the Polish Siberians. Author(s): Monieta A, Midro H. Source: Rocz Akad Med Bialymst. 2002; 47: 139-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12533956

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Chronic stress and depressive disorders in older adults. Author(s): Dura JR, Stukenberg KW, Kiecolt-Glaser JK. Source: Journal of Abnormal Psychology. 1990 August; 99(3): 284-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2212279

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Chronoendocrine assessment of the risk of developing depressive disorders. Author(s): Hermida RC, Ayala DE, Halberg F. Source: Prog Clin Biol Res. 1990; 341B: 113-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2217304

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Circadian rhythm abnormalities of deep body temperature in depressive disorders. Author(s): Daimon K, Yamada N, Tsujimoto T, Takahashi S. Source: Journal of Affective Disorders. 1992 November; 26(3): 191-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1460169

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Clinical and biochemical aspects of depressive disorders: I. Introduction, classification, and research techniques. Author(s): Caldecott-Hazard S, Guze BH, Kling MA, Kling A, Baxter LR. Source: Synapse (New York, N.Y.). 1991 July; 8(3): 185-211. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1948669

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Clinical and biochemical aspects of depressive disorders: II. Transmitter/receptor theories. Author(s): Caldecott-Hazard S, Morgan DG, DeLeon-Jones F, Overstreet DH, Janowsky D. Source: Synapse (New York, N.Y.). 1991 December; 9(4): 251-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1685032

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Clinical and biochemical aspects of depressive disorders: III. Treatment and controversies. Author(s): Caldecott-Hazard S, Schneider LS. Source: Synapse (New York, N.Y.). 1992 February; 10(2): 141-68. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1585257

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Clinical guidelines for depressive disorders in childhood and adolescence. Author(s): Park RJ, Goodyer IM. Source: European Child & Adolescent Psychiatry. 2000 September; 9(3): 147-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11095037

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Clinical guidelines for depressive disorders. Summary of recommendations relevant to family physicians. Author(s): Kennedy SH, Lam RW, Morris B; CANMAT Depression Work Group. Source: Can Fam Physician. 2003 April; 49: 489-91. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12729245

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Clinical guidelines for the treatment of depressive disorders, I. Definitions, prevalence, and health burden. Author(s): Parikh SV, Lam RW; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 13S-20S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441768

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Clinical guidelines for the treatment of depressive disorders. Author(s): Canadian Psychiatric Association; Canadian Network for Mood and Anxiety Treatments (CANMAT). Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 5S-90S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12371438

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Clinical guidelines for the treatment of depressive disorders. II. Principles of management. Author(s): Reesal RT, Lam RW; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 21S-28S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441769

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Clinical guidelines for the treatment of depressive disorders. III. Psychotherapy. Author(s): Segal ZV, Whitney DK, Lam RW; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 29S-37S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441770

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Clinical guidelines for the treatment of depressive disorders. IV. Medications and other biological treatments. Author(s): Kennedy SH, Lam RW, Cohen NL, Ravindran AV; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 38S-58S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441771

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Clinical guidelines for the treatment of depressive disorders. V. Combining psychotherapy and pharmacotherapy. Author(s): Segal ZV, Kennedy SH, Cohen NL; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 59S-62S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441772

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Clinical guidelines for the treatment of depressive disorders. VI. Special populations. Author(s): Thorpe L, Whitney DK, Kutcher SP, Kennedy SH; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 63S-76S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441773

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Clinical guidelines for the treatment of depressive disorders. VII. Comorbidity. Author(s): Enns MW, Swenson JR, McIntyre RS, Swinson RP, Kennedy SH; CANMAT Depression Work Group. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46 Suppl 1: 77S-90S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441774

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Cognitive distortions and irrational beliefs in post-traumatic stress, anxiety, and depressive disorders. Author(s): Muran EM, Motta RW. Source: Journal of Clinical Psychology. 1993 March; 49(2): 166-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8486798

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Cognitive functions in depressive disorders: evidence from a population-based study. Author(s): Airaksinen E, Larsson M, Lundberg I, Forsell Y. Source: Psychological Medicine. 2004 January; 34(1): 83-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14971629

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Comparative study of the treatment with tetracyclic and tricyclic antidepressants in patients with minor depressive disorders. Author(s): Tudor S, Zaharia M. Source: Rom J Neurol Psychiatry. 1994 July-September; 32(3): 185-98. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7710969

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Comparative validity of three screening questionnaires for DSM-IV depressive disorders and physicians' diagnoses. Author(s): Lowe B, Spitzer RL, Grafe K, Kroenke K, Quenter A, Zipfel S, Buchholz C, Witte S, Herzog W. Source: Journal of Affective Disorders. 2004 February; 78(2): 131-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706723

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Depressive disorders after a spontaneous abortion. Author(s): Garel M, Blondel B, Lelong N, Kaminski M. Source: American Journal of Obstetrics and Gynecology. 1993 March; 168(3 Pt 1): 1005-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8456871

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Depressive disorders among elderly people in long-term institutional care. Author(s): Ames D. Source: The Australian and New Zealand Journal of Psychiatry. 1993 September; 27(3): 379-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8250780

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Depressive disorders and unprotected casual anal sex among Australian homosexually active men in primary care. Author(s): Rogers G, Curry M, Oddy J, Pratt N, Beilby J, Wilkinson D. Source: Hiv Medicine. 2003 July; 4(3): 271-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12859327

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Depressive disorders are related to nicotine dependence in the population but do not necessarily hamper smoking cessation. Author(s): John U, Meyer C, Rumpf HJ, Hapke U. Source: The Journal of Clinical Psychiatry. 2004 February; 65(2): 169-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003069

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Depressive disorders in Japanese primary care patients. Author(s): Mino Y, Aoyama H, Froom J. Source: Family Practice. 1994 December; 11(4): 363-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7895962

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Depressive disorders in long-term survivors of stroke. Associations with demographic and social factors, functional status, and brain lesion volume. Author(s): Sharpe M, Hawton K, Seagroatt V, Bamford J, House A, Molyneux A, Sandercock P, Warlow C. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1994 March; 164(3): 380-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8199792

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Depressive disorders in maltreated children. Author(s): Kaufman J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1991 March; 30(2): 257-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2016230

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Depressive disorders in older medical inpatients. Author(s): Koenig HG. Source: American Family Physician. 1991 October; 44(4): 1243-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1927839

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Depressive disorders: treatment patterns and costs of treatment in the private sector of the United States. Author(s): Hu TW, Rush AJ. Source: Social Psychiatry and Psychiatric Epidemiology. 1995 August; 30(5): 224-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7482008

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Efficacy and safety of tianeptine in the treatment of depressive disorders in comparison with fluoxetine. Author(s): Loo H, Saiz-Ruiz J, Costa e Silva JACE, Ansseau M, Herrington R, Vaz-Serra A, Dilling H, de Risio S. Source: Journal of Affective Disorders. 1999 December; 56(2-3): 109-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10701468

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Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Author(s): Soares CN, Almeida OP, Joffe H, Cohen LS. Source: Archives of General Psychiatry. 2001 June; 58(6): 529-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11386980

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Electrolytes in erythrocytes of patients with depressive disorders. Author(s): Kamei K, Tabata O, Muneoka K, Muraoka SI, Tomiyoshi R, Takigawa M. Source: Psychiatry and Clinical Neurosciences. 1998 October; 52(5): 529-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10215016

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Elevated platelet MAO activity in schizophrenia-related depressive disorders. Author(s): Schildkraut JJ, Orsulak PJ, Schatzberg AF, Cole JO, Gudeman JE, Rohde WA. Source: The American Journal of Psychiatry. 1978 January; 135(1): 110-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=618506

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Endocrine responses to thyrotropin-releasing hormone in major depressive disorders. Author(s): Asnis GM, Sachar EJ, Halbreich U, Nathan RS, Ostrow L, Soloman M, Halpern FS. Source: Psychiatry Research. 1981 October; 5(2): 205-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6117098

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Exercise as a treatment option for anxiety and depressive disorders. Author(s): Hales RE, Travis TW. Source: Military Medicine. 1987 June; 152(6): 299-302. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3112618

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Fengabine, a new GABAmimetic agent in the treatment of depressive disorders: an overview of six double-blind studies versus tricyclics. Author(s): Magni G, Garreau M, Orofiamma B, Palminteri R. Source: Neuropsychobiology. 1989; 20(3): 126-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2668780

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Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts. Author(s): Petrakis I, Carroll KM, Nich C, Gordon L, Kosten T, Rounsaville B. Source: Drug and Alcohol Dependence. 1998 May 1; 50(3): 221-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9649975

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Hypothalamic-pituitary-gonadal axis in major depressive disorders. Author(s): Unden F, Ljunggren JG, Beck-Friis J, Kjellman BF, Wetterberg L. Source: Acta Psychiatrica Scandinavica. 1988 August; 78(2): 138-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3146888

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Hypothalamo-pituitary-adrenal function in patients with depressive disorders is correlated with baseline cytokine levels, but not with cytokine responses to hydrocortisone. Author(s): Schuld A, Schmid DA, Haack M, Holsboer F, Friess E, Pollmacher T. Source: Journal of Psychiatric Research. 2003 November-December; 37(6): 463-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14563377

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Immune parameters in a population of institutionalized elderly subjects: influence of depressive disorders and endocrinological correlations. Author(s): Bartoloni C, Guidi L, Frasca D, Antico L, Pili R, Cursi F, Di Giovanni A, Rumi C, Menini E, Carbonin P, et al. Source: Mechanisms of Ageing and Development. 1991 September; 60(1): 1-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1745060

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Impaired mitogen-induced lymphocyte responses and the hypothalamic-pituitaryadrenal axis in depressive disorders. Author(s): Cosyns P, Maes M, Vandewoude M, Stevens WJ, De Clerck LS, Schotte C. Source: Journal of Affective Disorders. 1989 January-February; 16(1): 41-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2521650

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Increased incidence of anxiety and depressive disorders in persons with organic solvent exposure. Author(s): Morrow LA, Gibson C, Bagovich GR, Stein L, Condray R, Scott A. Source: Psychosomatic Medicine. 2000 November-December; 62(6): 746-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11138992

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Individualized medicine - implementation of pharmacogenetic diagnostics in antidepressant drug treatment of major depressive disorders. Author(s): Kirchheiner J, Bertilsson L, Bruus H, Wolff A, Roots I, Bauer M. Source: Pharmacopsychiatry. 2003 November; 36 Suppl 3: S235-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14677085

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Interrater reliability in clinical trials of depressive disorders. Author(s): Mulsant BH, Kastango KB, Rosen J, Stone RA, Mazumdar S, Pollock BG. Source: The American Journal of Psychiatry. 2002 September; 159(9): 1598-600. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12202285

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Involvement of the limbic system in multiple sclerosis patients with depressive disorders. Author(s): Sabatini U, Pozzilli C, Pantano P, Koudriavtseva T, Padovani A, Millefiorini E, Di Biasi C, Gualdi GF, Salvetti M, Lenzi GL. Source: Biological Psychiatry. 1996 June 1; 39(11): 970-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9162210

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Is there immune dysfunction in depressive disorders? Author(s): Hickie I, Silove D, Hickie C, Wakefield D, Lloyd A. Source: Psychological Medicine. 1990 November; 20(4): 755-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2284382

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Low-dose risperidone augmentation of antidepressants in nonpsychotic depressive disorders with suicidal ideation. Author(s): Viner MW, Chen Y, Bakshi I, Kamper P. Source: Journal of Clinical Psychopharmacology. 2003 February; 23(1): 104-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12544386

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Management of blood-drawing fears in adolescents with comorbid anxiety and depressive disorders. Author(s): Bernstein GA, Peterson SE, Perwien AR, Borchardt CM, Kushner MG. Source: Journal of Child and Adolescent Psychopharmacology. 1996 Spring; 6(1): 53-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9231299

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Measuring the outcomes of care for mental health problems. The case of depressive disorders. Author(s): Rost K, Smith GR, Burnam MA, Burns BJ. Source: Medical Care. 1992 May; 30(5 Suppl): Ms266-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1583938

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Mechanism of action of ECT in major depressive disorders: a neuroendocrine interpretation. Author(s): Nerozzi D, Graziosi S, Melia E, Aceti F, Magnani A, Fiume S, Fraioli F, Frajese G. Source: Psychiatry Research. 1987 March; 20(3): 207-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3108918

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Meta-analysis of the relationship between HIV infection and risk for depressive disorders. Author(s): Ciesla JA, Roberts JE. Source: The American Journal of Psychiatry. 2001 May; 158(5): 725-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11329393

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Methylphenidate for depressive disorders in cancer patients. An alternative to standard antidepressants. Author(s): Fernandez F, Adams F, Holmes VF, Levy JK, Neidhart M. Source: Psychosomatics. 1987 September; 28(9): 455-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3432548

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MHPG excretion in depressive disorders: relation to clinical subtypes and desynchronized sleep. Author(s): Schildkraut JJ, Keeler BA, Papousek M, Hartmann E. Source: Science. 1973 August 24; 181(101): 762-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4353428

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Minaprine and imipramine in the treatment of major depressive disorders. A comparative double-blind study. Author(s): Bohacek N, Ravic M, Biziere K. Source: Drugs Exp Clin Res. 1987; 13(7): 435-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3308390

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Mind and mood in modern art, II: Depressive disorders, spirituality, and early deaths in the abstract expressionist artists of the New York School. Author(s): Schildkraut JJ, Hirshfeld AJ, Murphy JM. Source: The American Journal of Psychiatry. 1994 April; 151(4): 482-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8147444

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Moclobemide and sertraline in the treatment of depressive disorders: a comparative study. Author(s): Orsel Donbak S, Turkcapar MH, Ozturk Kilic EZ, Demirergi N, Akdemir A, Sirin A, Ozbay MH. Source: Acta Psychiatr Belg. 1995 May-June; 95(3): 139-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8525856

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Multicenter double-blind comparison of sertraline and desipramine for concurrent obsessive-compulsive and major depressive disorders. Author(s): Hoehn-Saric R, Ninan P, Black DW, Stahl S, Greist JH, Lydiard B, McElroy S, Zajecka J, Chapman D, Clary C, Harrison W. Source: Archives of General Psychiatry. 2000 January; 57(1): 76-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10632236

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Naturalistic change after 2 years in neurotic depressive disorders (RDC categories). Author(s): Barrett JE. Source: Comprehensive Psychiatry. 1984 July-August; 25(4): 404-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6467920

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Nefazodone in the treatment of elderly patients with depressive disorders: a prospective, observational study. Author(s): Saiz-Ruiz J, Ibanez A, Diaz-Marsa M, Arias F, Carrasco JL, Huertas D, Martin-Carrasco M, Moreno I, Rico-Villademoros F. Source: Cns Drugs. 2002; 16(9): 635-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12153334

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Neurasthenia in the 1980s: chronic mononucleosis, chronic fatigue syndrome, and anxiety and depressive disorders. Author(s): Greenberg DB. Source: Psychosomatics. 1990 Spring; 31(2): 129-37. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2184452

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Neuroendocrine challenges in the diagnosis of depressive disorders. Author(s): Lopez-Ibor JJ Jr, Saiz-Ruiz J, Moral Iglesias L. Source: The British Journal of Psychiatry. Supplement. 1989 May; (4): 73-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2605013

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Neuroendocrinological and neurophysiological studies in major depressive disorders: are there biological markers for the endogenous subtype? Author(s): Berger M, Doerr P, Lund R, Bronisch T, von Zerssen D. Source: Biological Psychiatry. 1982 November; 17(11): 1217-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6758870

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New antidepressants and trends in the pharmacotherapy of depressive disorders. Author(s): Zarifian E, Rigal F. Source: The Psychiatric Clinics of North America. 1983 March; 6(1): 129-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6889169

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Non-psychotic depressive disorders: a ten year follow-up. Author(s): d'Elia G, von Knorring L, Perris C. Source: Acta Psychiatrica Scandinavica. Supplementum. 1974; 255: 173-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4533709

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Norepinephrine metabolites as biochemical criteria for classifying depressive disorders and predicting responses to treatment: preliminary findings. Author(s): Schildkraut JJ. Source: The American Journal of Psychiatry. 1973 June; 130(6): 695-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4701961

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Normal personality traits and comorbidity among phobic, panic and major depressive disorders. Author(s): Bienvenu OJ, Brown C, Samuels JF, Liang KY, Costa PT, Eaton WW, Nestadt G. Source: Psychiatry Research. 2001 May 10; 102(1): 73-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11368842

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Nutrient imbalances in depressive disorders. Possible brain mechanisms. Author(s): Wurtman RJ, O'Rourke D, Wurtman JJ. Source: Annals of the New York Academy of Sciences. 1989; 575: 75-82; Discussion 82-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2699207

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Occupational factors of anxiety and depressive disorders in the French National Electricity and Gas Company. The Anxiety-Depression Group. Author(s): Chevalier A, Bonenfant S, Picot MC, Chastang JF, Luce D. Source: Journal of Occupational and Environmental Medicine / American College of Occupational and Environmental Medicine. 1996 November; 38(11): 1098-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8941899

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One-year outcomes of depressive disorders in child psychiatric in-patients: evaluation of the prognostic power of a brief measure of expressed emotion. Author(s): Asarnow JR, Goldstein MJ, Tompson M, Guthrie D. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1993 February; 34(2): 129-37. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8444988

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Outcome of anxiety and depressive disorders in primary care. Author(s): Ronalds C, Creed F, Stone K, Webb S, Tomenson B. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1997 November; 171: 427-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9463600

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P300 changes in major depressive disorders with and without psychotic features. Author(s): Karaaslan F, Gonul AS, Oguz A, Erdinc E, Esel E. Source: Journal of Affective Disorders. 2003 February; 73(3): 283-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12547298

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Parallels to early onset alcohol use in the relationship of early onset smoking with drug use and DSM-IV drug and depressive disorders: findings from the National Longitudinal Epidemiologic Survey. Author(s): Hanna EZ, Grant BF. Source: Alcoholism, Clinical and Experimental Research. 1999 March; 23(3): 513-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10195827

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Parental bonding and depressive disorders in adolescents. Author(s): Burbach DJ, Kashani JH, Rosenberg TK. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 1989 May; 30(3): 417-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2745592

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Patients' versus informants' reports of personality disorders in predicting 7 1/2-year outcome in outpatients with depressive disorders. Author(s): Klein DN. Source: Psychological Assessment. 2003 June; 15(2): 216-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12847782

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Pemoline. An alternative psychostimulant for the management of depressive disorders in cancer patients. Author(s): Breitbart W, Mermelstein H. Source: Psychosomatics. 1992 Summer; 33(3): 352-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1410212

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Personality disorders in bipolar and depressive disorders. Author(s): Rossi A, Marinangeli MG, Butti G, Scinto A, Di Cicco L, Kalyvoka A, Petruzzi C. Source: Journal of Affective Disorders. 2001 June; 65(1): 3-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11426507

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Personality traits in the first degree relatives of outpatients with depressive disorders. Author(s): Ouimette PC, Klein DN, Pepper CM. Source: Journal of Affective Disorders. 1996 June 20; 39(1): 43-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8835653

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Pharmacokinetics of reboxetine in elderly patients with depressive disorders. Author(s): Poggesi I, Pellizzoni C, Fleishaker JC. Source: Int J Clin Pharmacol Ther. 2000 May; 38(5): 254-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10839469

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Pharmacotherapy of dysthymic and chronic depressive disorders: overview with focus on moclobemide. Author(s): Versiani M. Source: Journal of Affective Disorders. 1998 December; 51(3): 323-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10333986

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PHA-stimulated cellular immune function and T-lymphocyte subsets in major depressive disorders. Author(s): Anesi A, Franciotta D, Di Paolo E, Zardini E, Melzi d'Eril GV, Zerbi F. Source: Funct Neurol. 1994 January-February; 9(1): 17-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8082849

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Phenomenology of anxiety and depressive disorders in children and adolescents. Author(s): Kotsopoulos S. Source: The Psychiatric Clinics of North America. 1989 December; 12(4): 803-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2690026

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Phobic, panic, and major depressive disorders and the five-factor model of personality. Author(s): Bienvenu OJ, Nestadt G, Samuels JF, Costa PT, Howard WT, Eaton WW. Source: The Journal of Nervous and Mental Disease. 2001 March; 189(3): 154-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277351

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Plasma-free and sulfoconjugated MHPG in major depressive disorders: differences between responders to treatment and nonresponders. Author(s): Mine K, Okada M, Mishima N, Fujiwara M, Nakagawa T. Source: Biological Psychiatry. 1993 November 1; 34(9): 654-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8292695

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Polymorphonuclear (PMN) elastase levels in depressive disorders. Author(s): Deger O, Bekaroglu M, Orem A, Orem S, Uluutku N, Soylu C. Source: Biological Psychiatry. 1996 March 1; 39(5): 357-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8704067

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Postpartum depressive disorders: changing trends. Author(s): Unterman RR, Posner NA, Williams KN. Source: Birth (Berkeley, Calif.). 1990 September; 17(3): 131-7; Discussion 138. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2222638

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Predominance of anger in depressive disorders compared with anxiety disorders and somatoform disorders. Author(s): Koh KB, Kim CH, Park JK. Source: The Journal of Clinical Psychiatry. 2002 June; 63(6): 486-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12088159

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Preliminary experience with moclobemide for the treatment of depressive disorders in Malaysia. Author(s): Indran SK. Source: Singapore Med J. 1995 April; 36(2): 189-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7676265

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Preliminary findings of simultaneous 18F-FDG and 99mTc-HMPAO SPECT in patients with depressive disorders at rest: differential correlates with ratings of anxiety. Author(s): Conca A, Fritzsche H, Peschina W, Konig P, Swoboda E, Wiederin H, Haas C. Source: Psychiatry Research. 2000 February 28; 98(1): 43-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10708925

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Present use of the Hamilton Depression Rating Scale: observation on method of assessment in research of depressive disorders. Author(s): Snaith RP. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1996 May; 168(5): 594-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8733798

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Prevalence and course of depressive disorders in hospitalized stroke patients. Author(s): Morris PL, Robinson RG, Raphael B. Source: International Journal of Psychiatry in Medicine. 1990; 20(4): 349-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2086522

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Prevalence, 20-month incidence and outcome of unipolar depressive disorders in a community sample of adolescents. Author(s): Oldehinkel AJ, Wittchen HU, Schuster P. Source: Psychological Medicine. 1999 May; 29(3): 655-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10405087

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Prevalence, nature, and comorbidity of depressive disorders in primary care. Author(s): Coyne JC, Fechner-Bates S, Schwenk TL. Source: General Hospital Psychiatry. 1994 July; 16(4): 267-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7926703

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Primary care physicians' approach to depressive disorders. Effects of physician specialty and practice structure. Author(s): Williams JW Jr, Rost K, Dietrich AJ, Ciotti MC, Zyzanski SJ, Cornell J. Source: Archives of Family Medicine. 1999 January-February; 8(1): 58-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9932074

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Profile of the inflammatory bowel disease patient with depressive disorders. Author(s): Acosta-Ramirez D, Pagan-Ocasio V, Torres EA, Rodriguez M, Caro O. Source: P R Health Sci J. 2001 September; 20(3): 215-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11776721

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Prospective follow-up study lasting 2 years in patients with panic disorder with and without depressive disorders. Author(s): Scheibe G, Albus M. Source: European Archives of Psychiatry and Clinical Neuroscience. 1994; 244(1): 39-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7918700

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Psychomotor change as a feature of depressive disorders: an historical overview. Author(s): Parker G, Brotchie H. Source: The Australian and New Zealand Journal of Psychiatry. 1992 June; 26(2): 146-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1642604

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Psychopathology in families of children with major depressive disorders. Author(s): Weller RA, Kapadia P, Weller EB, Fristad M, Lazaroff LB, Preskorn SH. Source: Journal of Affective Disorders. 1994 August; 31(4): 247-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7989639

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Psychosocial risk factors for depressive disorders in late life. Author(s): Bruce ML. Source: Biological Psychiatry. 2002 August 1; 52(3): 175-84. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182924

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Psychostimulant treatment of geriatric depressive disorders secondary to medical illness. Author(s): Pickett P, Masand P, Murray GB. Source: Journal of Geriatric Psychiatry and Neurology. 1990 July-September; 3(3): 14651. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2282130

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Public health aspects of anxiety and depressive disorders. Author(s): Ustun TB, Sartorius N. Source: International Clinical Psychopharmacology. 1993 September; 8 Suppl 1: 15-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8254148

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Re: Clinical guidelines for the treatment of depressive disorders. Author(s): Ney PG. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 December; 46(10): 987. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12398074

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Reboxetine versus imipramine in the treatment of elderly patients with depressive disorders: a double-blind randomised trial. Author(s): Katona C, Bercoff E, Chiu E, Tack P, Versiani M, Woelk H. Source: Journal of Affective Disorders. 1999 October; 55(2-3): 203-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10628889

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Recognition and treatment of depressive disorders by internal medicine attendings and housestaff. Author(s): Penn JV, Boland R, McCartney JR, Kohn R, Mulvey T. Source: General Hospital Psychiatry. 1997 May; 19(3): 179-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9218986

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Recognition of depressive disorders by primary care providers in a military medical setting. Author(s): Hunter CL, Hunter CM, West ET, Kinder MH, Carroll DW. Source: Military Medicine. 2002 April; 167(4): 308-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11977882

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Regional cerebral blood flow in the patients with depressive disorders. Author(s): Murata T, Suzuki R, Higuchi T, Oshima A. Source: The Keio Journal of Medicine. 2000 February; 49 Suppl 1: A112-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10750356

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Relapse prevention with antidepressant drug treatment in depressive disorders: a systematic review. Author(s): Geddes JR, Carney SM, Davies C, Furukawa TA, Kupfer DJ, Frank E, Goodwin GM. Source: Lancet. 2003 February 22; 361(9358): 653-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12606176

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Relation between anxiety and depressive disorders in childhood and adolescence. Author(s): Axelson DA, Birmaher B. Source: Depression and Anxiety. 2001; 14(2): 67-78. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11668659

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Relation between lymphocyte beta-adrenergic responsivity and the severity of depressive disorders. Author(s): Mazzola-Pomietto P, Azorin JM, Tramoni V, Jeanningros R. Source: Biological Psychiatry. 1994 June 15; 35(12): 920-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8080891

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Relation of intelligence and religiosity to depressive disorders in offspring of depressed and nondepressed mothers. Author(s): Horowitz JL, Garber J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 May; 42(5): 578-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12707562

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Relationship between anxiety disorders and depressive disorders in patients with cerebrovascular injury. Author(s): Starkstein SE, Cohen BS, Fedoroff P, Parikh RM, Price TR, Robinson RG. Source: Archives of General Psychiatry. 1990 March; 47(3): 246-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2306166

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Relationship between reactive psychosis and the depressive disorders. Author(s): Goplerud E, Depue RA. Source: Comprehensive Psychiatry. 1978 May-June; 19(3): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=648127

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Relationship of dysphoric premenstrual changes to depressive disorders. Author(s): Halbreich U, Endicott J. Source: Acta Psychiatrica Scandinavica. 1985 April; 71(4): 331-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4039877

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Relationship of tobacco use to depressive disorders and suicidality among patients treated for alcohol dependence. Author(s): Patten CA, Hurt RD, Offord KP, Croghan IT, Gomez-Dahl LC, Kottke TE, Morse RM, Joseph Melton L. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 2003 January-February; 12(1): 71-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12623742

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Research selection bias and the prevalence of depressive disorders in psychiatric facilities. Author(s): Frank RG, Schulberg HC, Welch WP, Sherick H, Costello AJ. Source: Journal of Consulting and Clinical Psychology. 1985 June; 53(3): 370-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3874218

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Risk factors, prevalence, and treatment of anxiety and depressive disorders in Pakistan: systematic review. Author(s): Mirza I, Jenkins R. Source: Bmj (Clinical Research Ed.). 2004 April 3; 328(7443): 794. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15070634

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Role of diagnosis in resolving issues concerning the treatment of chronic depressive disorders. Author(s): Katz MM. Source: Adv Biochem Psychopharmacol. 1985; 40: 165-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4025036

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Rural-urban differences in stigma and the use of care for depressive disorders. Author(s): Rost K, Smith GR, Taylor JL. Source: The Journal of Rural Health : Official Journal of the American Rural Health Association and the National Rural Health Care Association. 1993 Winter; 9(1): 57-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10124199

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Scientific advances and risk benefit issues in the treatment of depressive disorders. Author(s): Montgomery SA. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 336A-337A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1498861

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Screening for adjustment disorders and major depressive disorders in cancer inpatients. Author(s): Razavi D, Delvaux N, Farvacques C, Robaye E. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1990 January; 156: 79-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2297623

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Screening for major depressive disorders in adolescent psychiatric inpatients with the mood modules from the Primary Care Evaluation of Mental Disorders and the Patient Health Questionnaire. Author(s): Kumar G, Kim AH, Krefetz D, Steer RA. Source: Psychological Reports. 2001 October; 89(2): 274-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11783547

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Separation of anxiety and depressive disorders: blind alley in psychopharmacology and classification of disease. Author(s): Shorter E, Tyrer P. Source: Bmj (Clinical Research Ed.). 2003 July 19; 327(7407): 158-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12869462

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Separation of anxiety and depressive disorders: maybe pharmaceutical failure has created culture of niche diagnosis. Author(s): Joffe M. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 870; Author Reply 870. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551118

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Separation of anxiety and depressive disorders: New tools will lead to more valid classification system. Author(s): First MB, Regier DA. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 869-70; Author Reply 870. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551116

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Separation of anxiety and depressive disorders: normal rules of critical evaluation were presumably suspended. Author(s): Weeks RL. Source: Bmj (Clinical Research Ed.). 2003 October 11; 327(7419): 869; Author Reply 870. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14551115

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Sequence variations in CREB1 cosegregate with depressive disorders in women. Author(s): Zubenko GS, Hughes HB 3rd, Stiffler JS, Brechbiel A, Zubenko WN, Maher BS, Marazita ML. Source: Molecular Psychiatry. 2003 June; 8(6): 611-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851637

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Serotonin-specific drugs for anxiety and depressive disorders. Author(s): Charney DS, Krystal JH, Delgado PL, Heninger GR. Source: Annual Review of Medicine. 1990; 41: 437-46. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2139556

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Service utilization and outcomes in medically ill veterans with posttraumatic stress and depressive disorders. Author(s): Kramer TL, Booth BM, Han X, Williams DK. Source: Journal of Traumatic Stress. 2003 June; 16(3): 211-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816332

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Sexual dysfunction secondary to depressive disorders. Author(s): Bartlik B, Kocsis JH, Legere R, Villaluz J, Kossoy A, Gelenberg AJ. Source: J Gend Specif Med. 1999 March-April; 2(2): 52-60. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11252862

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Short-term psychotherapy of depressive disorders: current status and future directions. Author(s): Jarrett RB, Rush AJ. Source: Psychiatry. 1994 May; 57(2): 115-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7938331

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Social factors and recovery from anxiety and depressive disorders. A test of specificity. Author(s): Brown GW, Lemyre L, Bifulco A. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1992 July; 161: 44-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1638328

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Social influences on the course of anxious and depressive disorders in school-age children. Author(s): Goodyer I, Germany E, Gowrusankur J, Altham P. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1991 May; 158: 676-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1860021

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Spouse concordance for depressive disorders in a community sample. Author(s): McLeod JD. Source: Journal of Affective Disorders. 1993 January; 27(1): 43-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8432960

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Standardized Assessment of Depressive Disorders: a replicated study from northern India. Author(s): Gupta R, Singh P, Verma S, Garg D. Source: Acta Psychiatrica Scandinavica. 1991 October; 84(4): 310-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746278

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Study of the unidimensionality of the Bech-Rafaelsen Melancholia Scale using Rasch analysis in a French sample of major depressive disorders. Author(s): Chambon O, Cialdella P, Kiss L, Poncet F, Chevance M, Milani-Bachman D. Source: Pharmacopsychiatry. 1990 September; 23(5): 243-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2251301

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Suicidal behaviors and childhood-onset depressive disorders: a longitudinal investigation. Author(s): Kovacs M, Goldston D, Gatsonis C. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1993 January; 32(1): 8-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8428888

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Suicidal ideation and quality of life among adult Brazilian outpatients with depressive disorders. Author(s): Berlim MT, Mattevi BS, Pavanello DP, Caldieraro MA, Fleck MP. Source: The Journal of Nervous and Mental Disease. 2003 March; 191(3): 193-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12637847

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Suicide risk factors in depressive disorders and in panic disorder. Author(s): Fawcett J. Source: The Journal of Clinical Psychiatry. 1992 March; 53 Suppl: 9-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1548256

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Symptom comorbidity in anxiety and depressive disorders. Author(s): Copp JE, Schwiderski UE, Robinson DS. Source: Journal of Clinical Psychopharmacology. 1990 June; 10(3 Suppl): 52S-60S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1973940

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Taste and odor: reactivity in depressive disorders, a multidisciplinary approach. Author(s): Steiner JE, Lidar-Lifschitz D, Perl E. Source: Percept Mot Skills. 1993 December; 77(3 Pt 2): 1331-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8170789

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Temperament in adolescents with anxiety and depressive disorders and in their families. Author(s): Masi G, Mucci M, Favilla L, Brovedani P, Millepiedi S, Perugi G. Source: Child Psychiatry and Human Development. 2003 Spring; 33(3): 245-59. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12564625

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The Bech-Rafaelsen Melancholia Scale (MES) in clinical trials of therapies in depressive disorders: a 20-year review of its use as outcome measure. Author(s): Clin Evid. 2002 Dec;(8):951-73 Source: Acta Psychiatrica Scandinavica. 2002 October; 106(4): 252-64. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12603922

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The core of loneliness: lack of pleasurable engagement--more so than painful disconnection--predicts social impairment, depression onset, and recovery from depressive disorders among adolescents. Author(s): Joiner TE Jr, Lewinsohn PM, Seeley JR. Source: Journal of Personality Assessment. 2002 December; 79(3): 472-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12511016

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The course and outcome of depression in different cultures: 10-year follow-up of the WHO Collaborative Study on the Assessment of Depressive Disorders. Author(s): Thornicroft G, Sartorius N. Source: Psychological Medicine. 1993 November; 23(4): 1023-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8134505

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The effect of Axis II disorders on the outcome of treatment of anxiety and unipolar depressive disorders: a review. Author(s): Reich J. Source: Journal of Personality Disorders. 2003 October; 17(5): 387-405. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632374

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The epidemiology of depressive disorders. Author(s): Angst J. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 1995; 5 Suppl: 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8775766

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The epidemiology of psychiatrist-ascertained depression and DSM-III depressive disorders. Results from the Eastern Baltimore Mental Health Survey Clinical Reappraisal. Author(s): Romanoski AJ, Folstein MF, Nestadt G, Chahal R, Merchant A, Brown CH, Gruenberg EM, McHugh PR. Source: Psychological Medicine. 1992 August; 22(3): 629-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1410089

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The MCMI-II depression scales: do they assist in the differential prediction of depressive disorders? Author(s): Piersma HL. Source: Journal of Personality Assessment. 1991 June; 56(3): 478-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1865306

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The natural history and heterogeneity of depressive disorders: implications for rational antidepressant therapy. Author(s): Keller MB, Hanks DL. Source: The Journal of Clinical Psychiatry. 1994 September; 55 Suppl A: 25-31; Discussion 32-3, 98-100. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7961539

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The naturalistic course of anxiety and depressive disorders. Author(s): Keller MB. Source: Clinical Neuropharmacology. 1992; 15 Suppl 1 Pt A: 171A-173A. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1498798

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The nonrecognition of depressive disorders: a continuing public health concern! Author(s): Joyce P. Source: N Z Med J. 1991 January 23; 104(904): 7-8. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2008262

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The outcome of depressive disorders in neurology patients: a prospective cohort study. Author(s): Carson AJ, Postma K, Stone J, Warlow C, Sharpe M. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 893-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810774

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The outcome of depressive disorders in the setting of neurological illness. Author(s): Rickards H. Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2003 July; 74(7): 842-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12810763

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The prevalence of depressive disorders and the distribution of depressive symptoms in later life: a survey using Draft ICD-10 and DSM-III-R. Author(s): Henderson AS, Jorm AF, MacKinnon A, Christensen H, Scott LR, Korten AE, Doyle C. Source: Psychological Medicine. 1993 August; 23(3): 719-29. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8234578

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The relationship of self-reported distress to depressive disorders and other psychopathology. Author(s): Fechner-Bates S, Coyne JC, Schwenk TL. Source: Journal of Consulting and Clinical Psychology. 1994 June; 62(3): 550-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8063981

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The role for stimulants in the treatment of depressive disorders. Author(s): Moldawsky RJ. Source: The Journal of Clinical Psychiatry. 1995 August; 56(8): 376-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7635858

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The role of stress in the onset of depressive disorders. A controlled study in a Spanish clinical sample. Author(s): Rojo-Moreno L, Livianos-Aldana L, Cervera-Martinez G, DominguezCarabantes JA, Reig-Cebrian MJ. Source: Social Psychiatry and Psychiatric Epidemiology. 2002 December; 37(12): 592-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12545237

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Treatment of anxiety and depressive disorders in patients with cardiovascular disease. Author(s): Davies SJ, Jackson PR, Potokar J, Nutt DJ. Source: Bmj (Clinical Research Ed.). 2004 April 17; 328(7445): 939-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15087342

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Treatment of depressive disorders with and without medication - a naturalistic study. Author(s): Hasler G, Schnyder U, Klaghofer R, Angst J. Source: Pharmacopsychiatry. 2002 November; 35(6): 235-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518272

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Urban-rural comparisons of depressive disorders in French Canada. Author(s): Kovess V, Murphy HB, Tousignant M. Source: The Journal of Nervous and Mental Disease. 1987 August; 175(8): 457-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3498009

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x

Use of the dexamethasone suppression test to detect depressive disorders of mentally retarded individuals. Author(s): Pirodsky DM, Gibbs JW, Hesse RA, Hsieh MC, Krause RB, Rodriguez WH. Source: Am J Ment Defic. 1985 November; 90(3): 245-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4083305

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Use of the Hamilton Rating Scale for classification of depressive disorders. Author(s): Overall JE, Rhoades HM. Source: Comprehensive Psychiatry. 1982 July-August; 23(4): 370-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7116832

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Venlafaxine treatment of cocaine abusers with depressive disorders. Author(s): McDowell DM, Levin FR, Seracini AM, Nunes EV. Source: The American Journal of Drug and Alcohol Abuse. 2000 February; 26(1): 25-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718161

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WHO collaborative study: assessment of depressive disorders. Author(s): Sartorius N, Jablensky A, Gulbinat W, Ernberg G. Source: Psychological Medicine. 1980 November; 10(4): 743-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7208732

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Work-related stress and depressive disorders. Author(s): Tennant C. Source: Journal of Psychosomatic Research. 2001 November; 51(5): 697-704. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11728512

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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Acute and continuation treatment of major depressive disorder. Author(s): Bauer M, Whybrow PC, Angst J, Versiani M, Moller HJ; World Federation of Societies Biological Psychiatry Task Force on Treatment Guidelines for Unipolar Depressive Disorders. Source: World J Biol Psychiatry. 2002 January; 3(1): 5-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479086

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World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance treatment of major depressive disorder and treatment of chronic depressive disorders and subthreshold depressions. Author(s): Bauer M, Whybrow PC, Angst J, Versiani M, Moller HJ; World Federation of Societies of Biological Psychiatry (WFSBF) Task Force on Treatment Guidelines for Unipolar Depressive Disorders. Source: World J Biol Psychiatry. 2002 April; 3(2): 69-86. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479080

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World Health Organization Schedule for Standardized Assessment of Depressive Disorders (WHO/SADD-5). Item combinations and interobserver reliability. Author(s): Bech P, Gjerris A, Andersen J, Rafaelsen OJ. Source: Psychopathology. 1984; 17(5-6): 244-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6537540

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CHAPTER 2. NUTRITION AND DEPRESSIVE DISORDERS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and depressive disorders.

Finding Nutrition Studies on Depressive Disorders The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “depressive disorders” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7

Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

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The following information is typical of that found when using the “Full IBIDS Database” to search for “depressive disorders” (or a synonym): x

L-5-hydroxytryptophan in depression and anxiety. Source: van Praag, H M Kahn, R S Schweiz-Rundsch-Med-Prax. 1988 August 23; 77(34A): 40-6 1013-2058

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Lithium augmentation for treatment-resistant depression in the elderly. Author(s): Department of Psychiatry, Lockraven VA Medical Center, Baltimore, MD 21218. Source: Lafferman, J Solomon, K Ruskin, P J-Geriatr-Psychiatry-Neurol. 1988 January; 1(1): 49-52 0891-9887

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Management of depression in the elderly. Author(s): Department of Family Practice, College of Medicine, University of Iowa, Iowa City. Source: Williams, G O Prim-Care. 1989 June; 16(2): 451-74 0095-4543

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Panic attack in a context of comorbid anxiety and depression in a Tibetan refugee. Author(s): Department of Social Medicine, Harvard Medical School, Boston, MA 02115, USA. Source: Jacobson, E Cult-Med-Psychiatry. 2002 June; 26(2): 259-79 0165-005X

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Role of selenium depletion in the etiopathogenesis of depression in patient with alcoholism. Source: Sher, L Med-Hypotheses. 2002 September; 59(3): 330-3 0306-9877

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Symptoms of depression in elderly Korean immigrants: narration and the healing process. Author(s): College of Nursing, Howard University, Washington, DC 20059, USA. Source: Pang, K Y Cult-Med-Psychiatry. 1998 March; 22(1): 93-122 0165-005X

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The male menopause and mood: testosterone decline and depression in the aging male--is there a link? Author(s): Department of Psychiatry, McGill University, Montreal, Quebec. Source: Margolese, H C J-Geriatr-Psychiatry-Neurol. 2000 Summer; 13(2): 93-101 08919887

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The treatment of psychotic depression in later life: a comparison of pharmacotherapy and ECT. Author(s): Department of Psychiatry, University of Toronto, Canada. [email protected] Source: Flint, A J Rifat, S L Int-J-Geriatr-Psychiatry. 1998 January; 13(1): 23-8 0885-6230

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Treatment of depression with fluoxetine in corticosteroid-dependent central nervous system Sjogren's syndrome. Author(s): Department of Psychiatry, Bellevue Hospital, New York. Source: Wyszynski, A A Wyszynski, B Psychosomatics. 1993 Mar-April; 34(2): 173-7 0033-3182

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Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: x

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: x

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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The following is a specific Web list relating to depressive disorders; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: x

Vitamins Folic Acid Source: Healthnotes, Inc.; www.healthnotes.com Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Folic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,887,00.html Niacin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,892,00.html Pantothenic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,882,00.html Pyridoxine Alternative names: Vitamin B6 (Pyridoxine) Source: Integrative Medicine Communications; www.drkoop.com Riboflavin Source: Integrative Medicine Communications; www.drkoop.com Thiamine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10067,00.html Vitamin B Complex Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,962,00.html Vitamin B1 (Thiamine) Source: Integrative Medicine Communications; www.drkoop.com

Nutrition

Vitamin B12 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B12 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B2 (Riboflavin) Source: Integrative Medicine Communications; www.drkoop.com Vitamin B6 Source: Healthnotes, Inc.; www.healthnotes.com Vitamin B6 Source: Prima Communications, Inc.www.personalhealthzone.com Vitamin B6 (Pyridoxine) Alternative names: Pyridoxine Source: Integrative Medicine Communications; www.drkoop.com Vitamin B9 (Folic Acid) Alternative names: Folate, Folic Acid Source: Integrative Medicine Communications; www.drkoop.com Vitamin C Source: Healthnotes, Inc.; www.healthnotes.com Vitamin D Source: Healthnotes, Inc.; www.healthnotes.com Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com Vitamin K Alternative names: Menadione, Menaphthone, Menaquinone, Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com x

Minerals Acetyl-L-Carnitine Source: Healthnotes, Inc.; www.healthnotes.com Biotin Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Healthnotes, Inc.; www.healthnotes.com Calcium Source: Integrative Medicine Communications; www.drkoop.com Calcium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,884,00.html Calcium Acetate Source: Healthnotes, Inc.; www.healthnotes.com Calcium/Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,937,00.html Carnitine Source: Prima Communications, Inc.www.personalhealthzone.com Chromium Source: Healthnotes, Inc.; www.healthnotes.com Copper Source: Healthnotes, Inc.; www.healthnotes.com Fluoxetine Source: Healthnotes, Inc.; www.healthnotes.com Folate Source: Integrative Medicine Communications; www.drkoop.com Folate Source: Prima Communications, Inc.www.personalhealthzone.com Gabapentin Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Healthnotes, Inc.; www.healthnotes.com Iron Source: Prima Communications, Inc.www.personalhealthzone.com Lecithin and Choline Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10040,00.html Lecithin/Phosphatidylcholine/Choline Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com

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Magnesium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,890,00.html Naproxen/Naproxen Sodium Source: Healthnotes, Inc.; www.healthnotes.com Paroxetine Source: Healthnotes, Inc.; www.healthnotes.com Potassium-Sparing Diuretics Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Healthnotes, Inc.; www.healthnotes.com Selenium Source: Integrative Medicine Communications; www.drkoop.com Selenium Source: Prima Communications, Inc.www.personalhealthzone.com Selenium Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10055,00.html Vanadium Alternative names: Vanadate, Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Zinc Source: Healthnotes, Inc.; www.healthnotes.com x

Food and Diet Bluefish Source: Healthnotes, Inc.; www.healthnotes.com Coffee Source: Healthnotes, Inc.; www.healthnotes.com Fasting Diet Source: Healthnotes, Inc.; www.healthnotes.com Gluten-Free Diet Source: Healthnotes, Inc.; www.healthnotes.com Hypoglycemia Source: Healthnotes, Inc.; www.healthnotes.com

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Low-Fat Recipes Index Source: Healthnotes, Inc.; www.healthnotes.com Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Omega-3 Fatty Acids Source: Integrative Medicine Communications; www.drkoop.com Omega-3 Fatty Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Pain Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Seeds Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Seeds Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,176,00.html Salmon Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/foods_view/0,1523,102,00.html

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CHAPTER 3. ALTERNATIVE MEDICINE AND DEPRESSIVE DISORDERS Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to depressive disorders. At the conclusion of this chapter, we will provide additional sources.

The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “depressive disorders” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: x

S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease Source: Rockville, MD: Agency for Healthcare Research and Quality. 2002. 6 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D175. Summary: This evidence report/technology assessment summary from the Agency for Healthcare Research and Quality (AHRQ) provides a review of the published literature on the use of S-adenosyl-L-methionine (SAMe) for the treatment of osteoarthritis, depression, and liver disease (cholestasis of pregnancy). The literature review is used to evaluate evidence for the efficacy of SAMe. The summary includes a description of the

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methodology, including the search strategy; selection criteria; and data collection and analysis. The findings are then discussed followed by an overview of future research on the topic. Information is also given on when and where the full report will be available. 1 reference. x

St. John's Wort and the Treatment for Depression Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2002. 8 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D005. Summary: This fact sheet discusses the use of St. John's wort for depression to help consumers make informed decisions about whether to use this complementary and alternative medicine (CAM) therapy. It includes a section on key facts about St. John's wort, a section on safety in using this therapy, and a questions and answers section. Information is provided about what St. John's wort is and the purposes for which it is used, what depression is, why St. John's wort is used as a CAM for depression, whether St. John's wort works, how widely it is used, how it is sold, and the risks and possible problems of this therapy. It also lists contacts where consumers can go for more information. 7 references.

x

Questions and Answers: A Trial of St. John's Wort (Hypericum perforatum) for the Treatment of Major Depression Source: Gaithersburg, MD: National Center for Complementary and Alternative Medicine. 2002. 8 p. Contact: Available from National Center for Complementary and Alternative Medicine Clearinghouse. P.O. Box 7923, Gaithersburg, MD 20898. (888) 644-6226; INTERNATIONAL PHONE: (301) 519-3153; TTY: (866) 464-3615; FAX: (866) 464-3616; EMAIL: [email protected]. PRICE: Free. Publication Number: D145. Summary: This fact sheet, written in a question and answer format, provides information about a clinical trial on St. John's wort for the treatment of major depression. The questions are categorized into three sections: background on St. John's wort and depression, about the trial, and conclusions and future research. It includes information about the specifics of the trial, such as the characteristics of the trial participants, the types of drugs and doses used, and the main results. 6 references.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to depressive disorders and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “depressive disorders” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to depressive disorders:

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x

A double-blind, placebo-controlled study of the omega-3 fatty acid docosahexaenoic acid in the treatment of major depression. Author(s): Marangell LB, Martinez JM, Zboyan HA, Kertz B, Kim HF, Puryear LJ. Source: The American Journal of Psychiatry. 2003 May; 160(5): 996-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727707

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Add-on rTMS for treatment of depression: a pilot study using stereotaxic coilnavigation according to PET data. Author(s): Herwig U, Lampe Y, Juengling FD, Wunderlich A, Walter H, Spitzer M, Schonfeldt-Lecuona C. Source: Journal of Psychiatric Research. 2003 July-August; 37(4): 267-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765849

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An open-label pilot study of St. John's wort in juvenile depression. Author(s): Findling RL, McNamara NK, O'Riordan MA, Reed MD, Demeter CA, Branicky LA, Blumer JL. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 August; 42(8): 908-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12874492

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Association of depression, CD8+ T lymphocytes, and natural killer cell activity: implications for morbidity and mortality in Human immunodeficiency virus disease. Author(s): Cruess DG, Douglas SD, Petitto JM, Leserman J, Ten Have T, Gettes D, Dube B, Evans DL. Source: Current Psychiatry Reports. 2003 December; 5(6): 445-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14609499

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Association of obesity with anxiety, depression and emotional well-being: a community survey. Author(s): Jorm AF, Korten AE, Christensen H, Jacomb PA, Rodgers B, Parslow RA. Source: Aust N Z J Public Health. 2003; 27(4): 434-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705308

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Auditory event-related potential indices of increased distractibility in children with major depression. Author(s): Lepisto T, Soininen M, Ceponiene R, Almqvist F, Naatanen R, Aronen ET. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2004 March; 115(3): 620-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15036058

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Complementary therapies as adjuncts in the treatment of postpartum depression. Author(s): Weier KM, Beal MW.

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Source: Journal of Midwifery & Women's Health. 2004 March-April; 49(2): 96-104. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15010661 x

Coronary artery disease and depression. Author(s): Zellweger MJ, Osterwalder RH, Langewitz W, Pfisterer ME. Source: European Heart Journal. 2004 January; 25(1): 3-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683736

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Cross-national differences in diet, the outcome of schizophrenia and the prevalence of depression: you are (associated with) what you eat. Author(s): McIntosh A, Lawrie S. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2004 May; 184: 381-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123499

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Cross-sectional survey of users of Internet depression communities. Author(s): Powell J, McCarthy N, Eysenbach G. Source: Bmc Psychiatry [electronic Resource]. 2003 December 10; 3(1): 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14664725

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Developing a culture-specific tool to assess postnatal depression in the Indian community. Author(s): Mantle F. Source: British Journal of Community Nursing. 2003 April; 8(4): 176-80. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12732834

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Does pain relief during delivery decrease the risk of postnatal depression? Author(s): Hiltunen P, Raudaskoski T, Ebeling H, Moilanen I. Source: Acta Obstetricia Et Gynecologica Scandinavica. 2004 March; 83(3): 257-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14995921

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Effect of maternal docosahexaenoic acid supplementation on postpartum depression and information processing. Author(s): Llorente AM, Jensen CL, Voigt RG, Fraley JK, Berretta MC, Heird WC. Source: American Journal of Obstetrics and Gynecology. 2003 May; 188(5): 1348-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12748510

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Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Author(s): Nowak G, Siwek M, Dudek D, Zieba A, Pilc A.

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Source: Polish Journal of Pharmacology. 2003 November-December; 55(6): 1143-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730113 x

Effects of antidepressant pharmacotherapy after repetitive transcranial magnetic stimulation in major depression: an open follow-up study. Author(s): Schule C, Zwanzger P, Baghai T, Mikhaiel P, Thoma H, Moller HJ, Rupprecht R, Padberg F. Source: Journal of Psychiatric Research. 2003 March-April; 37(2): 145-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12842168

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Efficacy of repetitive transcranial magnetic stimulation in depression: a review of the evidence. Author(s): Aarre TF, Dahl AA, Johansen JB, Kjonniksen I, Neckelmann D. Source: Nordic Journal of Psychiatry. 2003; 57(3): 227-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12775299

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GABAergic functions and depression: from classical therapies to herbal medicine. Author(s): Leung JW, Xue H. Source: Curr Drug Targets Cns Neurol Disord. 2003 December; 2(6): 363-74. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14683464

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International variations in the outcome of schizophrenia and the prevalence of depression in relation to national dietary practices: an ecological analysis. Author(s): Peet M. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2004 May; 184: 404-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123503

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Is it time to introduce repetitive transcranial magnetic stimulation into standard clinical practice for the treatment of depressive disorders? Author(s): Fitzgerald P. Source: The Australian and New Zealand Journal of Psychiatry. 2003 February; 37(1): 511; Discussion 12-4. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12534650

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Is low dietary intake of omega-3 fatty acids associated with depression? Author(s): Hakkarainen R, Partonen T, Haukka J, Virtamo J, Albanes D, Lonnqvist J. Source: The American Journal of Psychiatry. 2004 March; 161(3): 567-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992986

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Is obesity associated with major depression? Results from the Third National Health and Nutrition Examination Survey. Author(s): Onyike CU, Crum RM, Lee HB, Lyketsos CG, Eaton WW.

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Source: American Journal of Epidemiology. 2003 December 15; 158(12): 1139-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14652298 x

Long-term effects of energetic healing on symptoms of psychological depression and self-perceived stress. Author(s): Shore AG. Source: Alternative Therapies in Health and Medicine. 2004 May-June; 10(3): 42-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15154152

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Methods of testing feasibility for sequenced treatment alternatives to relieve depression (STAR*D). Author(s): Wisniewski SR, Stegman D, Trivedi M, Husain MM, Eng H, Shores-Wilson K, Luther J, Biggs MM, Burroughs D, Ritz AL, Fava M, Quitkin F, Rush AJ; STAR*D Investigators. Source: Journal of Psychiatric Research. 2004 May-June; 38(3): 241-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003429

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Neurobehavioral aspects of omega-3 fatty acids: possible mechanisms and therapeutic value in major depression. Author(s): Logan AC. Source: Alternative Medicine Review : a Journal of Clinical Therapeutic. 2003 November; 8(4): 410-25. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14653768

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Neurobiological and psychological correlates of suicidal attempts and thoughts of death in patients with major depression. Author(s): Fountoulakis KN, Iacovides A, Fotiou F, Nimatoudis J, Bascialla F, Ioannidou C, Kaprinis G, Bech P. Source: Neuropsychobiology. 2004; 49(1): 42-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14730200

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Neurocognitive effects of repetitive transcranial magnetic stimulation in severe major depression. Author(s): Martis B, Alam D, Dowd SM, Hill SK, Sharma RP, Rosen C, Pliskin N, Martin E, Carson V, Janicak PG. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2003 June; 114(6): 1125-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804681

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No benefit derived from repetitive transcranial magnetic stimulation in depression: a prospective, single centre, randomised, double blind, sham controlled “add on” trial. Author(s): Hausmann A, Kemmler G, Walpoth M, Mechtcheriakov S, KramerReinstadler K, Lechner T, Walch T, Deisenhammer EA, Kofler M, Rupp CI, Hinterhuber H, Conca A.

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Source: Journal of Neurology, Neurosurgery, and Psychiatry. 2004 February; 75(2): 3202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14742619 x

Omega-3 polyunsaturated fatty acids for postpartum depression. Author(s): Chiu CC, Huang SY, Su KP. Source: American Journal of Obstetrics and Gynecology. 2004 February; 190(2): 582-3; Author Reply 583. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15002412

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Patient attitudes regarding causes of depression: implications for psychoeducation. Author(s): Srinivasan J, Cohen NL, Parikh SV. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 August; 48(7): 493-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12971021

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Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. Author(s): Tiemeier H, van Tuijl HR, Hofman A, Kiliaan AJ, Breteler MM. Source: The American Journal of Clinical Nutrition. 2003 July; 78(1): 40-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12816769

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Postpartum depression, culture and African-American women. Author(s): Amankwaa LC. Source: J Cult Divers. 2003 Spring; 10(1): 23-9. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12776544

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Prefrontal cortex transcranial magnetic stimulation does not change local diffusion: a magnetic resonance imaging study in patients with depression. Author(s): Li X, Nahas Z, Lomarev M, Denslow S, Shastri A, Bohning DE, George MS. Source: Cognitive and Behavioral Neurology : Official Journal of the Society for Behavioral and Cognitive Neurology. 2003 June; 16(2): 128-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12799599

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Recurrent episode in three older patients suffering from chronic depression: positive response to TMS treatment. Author(s): Januel D, Benadhira R, Saba G, Rocamora JF, Stamatiadis L, Kalalou K, Dumortier G. Source: International Journal of Geriatric Psychiatry. 2004 May; 19(5): 493-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156552

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Repetitive transcranial magnetic stimulation for depression. Author(s): Cooke RG.

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Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 September; 28(5): 400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14517581 x

Repetitive transcranial magnetic stimulation for the treatment of depression. Systematic review and meta-analysis. Author(s): Martin JL, Barbanoj MJ, Schlaepfer TE, Thompson E, Perez V, Kulisevsky J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 June; 182: 480-91. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12777338

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Serotonin, serotonin 5-HT(1A) receptors and dopamine in blood peripheral lymphocytes of major depression patients. Author(s): Fajardo O, Galeno J, Urbina M, Carreira I, Lima L. Source: International Immunopharmacology. 2003 September; 3(9): 1345-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12890432

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Some recommendations to assess depression in Chinese people in Australasia. Author(s): Chan B, Parker G. Source: The Australian and New Zealand Journal of Psychiatry. 2004 March; 38(3): 1417. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14961932

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St John's wort for the treatment of depression. Author(s): Shelton RC. Source: Lancet. Neurology. 2002 September; 1(5): 275. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12849421

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The efficacy and safety of bilateral rTMS in medication-resistant depression. Author(s): Cohen CI, Amassian VE, Akande B, Maccabee PJ. Source: The Journal of Clinical Psychiatry. 2003 May; 64(5): 613-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12755672

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The impact of religious practice and religious coping on geriatric depression. Author(s): Bosworth HB, Park KS, McQuoid DR, Hays JC, Steffens DC. Source: International Journal of Geriatric Psychiatry. 2003 October; 18(10): 905-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14533123

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Transcranial magnetic stimulation in the treatment of depression. Author(s): Gershon AA, Dannon PN, Grunhaus L. Source: The American Journal of Psychiatry. 2003 May; 160(5): 835-45. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12727683

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Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Author(s): Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J. Source: Archives of General Psychiatry. 2003 October; 60(10): 1002-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14557145

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Treating depression comorbid with anxiety--results of an open, practice-oriented study with St John's wort WS 5572 and valerian extract in high doses. Author(s): Muller D, Pfeil T, von den Driesch V. Source: Phytomedicine : International Journal of Phytotherapy and Phytopharmacology. 2003; 10 Suppl 4: 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12807339

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Treatment of mental depression due to liver-qi stagnancy with herbal decoction and by magnetic therapy at the acupoints--a report of 45 cases. Author(s): Zhang G, Ruan J. Source: J Tradit Chin Med. 2004 March; 24(1): 20-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15119163

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Treatment-resistant depression: new therapies on the horizon. Author(s): Trivedi MH. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 2003 March; 15(1): 59-70. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12839433

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Treatments for depression: wisdom imparted from treatments discarded. Author(s): Overholser JC. Source: International Journal of Psychiatry in Medicine. 2002; 32(4): 317-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12779182

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Two overlooked mood disorders in women: subsyndromal depression and prenatal depression. Author(s): Brown MA, Solchany JE. Source: Nurs Clin North Am. 2004 March; 39(1): 83-95. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15062729

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: x

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to depressive disorders; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: x

General Overview Age-Related Cognitive Decline Source: Healthnotes, Inc.; www.healthnotes.com AIDS and HIV Source: Integrative Medicine Communications; www.drkoop.com Alcohol Withdrawal Source: Healthnotes, Inc.; www.healthnotes.com Alcoholism Source: Integrative Medicine Communications; www.drkoop.com Alzheimer's Disease Source: Healthnotes, Inc.; www.healthnotes.com Alzheimer's Disease Source: Integrative Medicine Communications; www.drkoop.com Amenorrhea Source: Integrative Medicine Communications; www.drkoop.com Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com

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Anxiety Source: Healthnotes, Inc.; www.healthnotes.com Anxiety Source: Integrative Medicine Communications; www.drkoop.com Anxiety and Panic Attacks Source: Prima Communications, Inc.www.personalhealthzone.com Asthma Source: Healthnotes, Inc.; www.healthnotes.com Autism Source: Healthnotes, Inc.; www.healthnotes.com Bipolar Disorder Source: Healthnotes, Inc.; www.healthnotes.com Bone Loss Source: Integrative Medicine Communications; www.drkoop.com Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Bulimia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Burns Source: Integrative Medicine Communications; www.drkoop.com Candida/Yeast Hypersensitivity Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Cardiovascular Disease Overview Source: Healthnotes, Inc.; www.healthnotes.com Celiac Disease Source: Healthnotes, Inc.; www.healthnotes.com Chronic Candidiasis Source: Healthnotes, Inc.; www.healthnotes.com Chronic Fatigue Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Chronic Fatigue Syndrome Source: Integrative Medicine Communications; www.drkoop.com Chronic Obstructive Pulmonary Disease Source: Healthnotes, Inc.; www.healthnotes.com

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Colorectal Cancer Source: Integrative Medicine Communications; www.drkoop.com Constipation Source: Integrative Medicine Communications; www.drkoop.com Dementia Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Healthnotes, Inc.; www.healthnotes.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Dysphagia Source: Integrative Medicine Communications; www.drkoop.com Eating Disorders Source: Healthnotes, Inc.; www.healthnotes.com Epilepsy Source: Integrative Medicine Communications; www.drkoop.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Gastroesophageal Reflux Disease Source: Integrative Medicine Communications; www.drkoop.com Heartburn Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com High Cholesterol Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Source: Integrative Medicine Communications; www.drkoop.com HIV and AIDS Support Source: Healthnotes, Inc.; www.healthnotes.com Hypercholesterolemia Source: Integrative Medicine Communications; www.drkoop.com

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Hyperparathyroidism Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com Hypochondriasis Source: Integrative Medicine Communications; www.drkoop.com Hypoglycemia Source: Integrative Medicine Communications; www.drkoop.com Hypothyroidism Source: Healthnotes, Inc.; www.healthnotes.com Hypothyroidism Source: Integrative Medicine Communications; www.drkoop.com Inflammatory Bowel Disease Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Integrative Medicine Communications; www.drkoop.com Insomnia Source: Prima Communications, Inc.www.personalhealthzone.com Irritable Bowel Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Irritable Bowel Syndrome Source: Integrative Medicine Communications; www.drkoop.com Lactose Intolerance Source: Healthnotes, Inc.; www.healthnotes.com Low Back Pain Source: Integrative Medicine Communications; www.drkoop.com Low Blood Sugar Source: Integrative Medicine Communications; www.drkoop.com Lupus Source: Integrative Medicine Communications; www.drkoop.com Malabsorption Source: Healthnotes, Inc.; www.healthnotes.com Manic Depression Source: Integrative Medicine Communications; www.drkoop.com

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Menopausal Symptoms (Other Than Osteoporosis) Source: Prima Communications, Inc.www.personalhealthzone.com Menopause Source: Healthnotes, Inc.; www.healthnotes.com Menopause Source: Integrative Medicine Communications; www.drkoop.com Migraine Headaches Source: Healthnotes, Inc.; www.healthnotes.com Miscarriage Source: Integrative Medicine Communications; www.drkoop.com Osteoporosis Source: Integrative Medicine Communications; www.drkoop.com Parkinson's Disease Source: Healthnotes, Inc.; www.healthnotes.com Parkinson's Disease Source: Integrative Medicine Communications; www.drkoop.com Photodermatitis Source: Integrative Medicine Communications; www.drkoop.com PMS Source: Integrative Medicine Communications; www.drkoop.com PMS Alternative names: Premenstrual Stress Syndrome Source: Prima Communications, Inc.www.personalhealthzone.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com Premenstrual Syndrome Source: Healthnotes, Inc.; www.healthnotes.com Premenstrual Syndrome Source: Integrative Medicine Communications; www.drkoop.com Prostate Cancer Source: Integrative Medicine Communications; www.drkoop.com Prostatitis Source: Healthnotes, Inc.; www.healthnotes.com PTSD Source: Integrative Medicine Communications; www.drkoop.com

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Recurrent Ear Infections Source: Healthnotes, Inc.; www.healthnotes.com Schizophrenia Source: Healthnotes, Inc.; www.healthnotes.com Seasonal Affective Disorder Source: Healthnotes, Inc.; www.healthnotes.com Seizure Disorders Source: Integrative Medicine Communications; www.drkoop.com Senile Dementia Source: Integrative Medicine Communications; www.drkoop.com Serum Sickness Source: Integrative Medicine Communications; www.drkoop.com Sexual Dysfunction Source: Integrative Medicine Communications; www.drkoop.com Shingles and Postherpetic Neuralgia Source: Healthnotes, Inc.; www.healthnotes.com Sleeplessness Source: Integrative Medicine Communications; www.drkoop.com Spastic Colon Source: Integrative Medicine Communications; www.drkoop.com Spontaneous Abortion Source: Integrative Medicine Communications; www.drkoop.com Stress Source: Integrative Medicine Communications; www.drkoop.com Stroke Source: Integrative Medicine Communications; www.drkoop.com Sunburn Source: Integrative Medicine Communications; www.drkoop.com Systemic Lupus Erythematosus Source: Integrative Medicine Communications; www.drkoop.com Tension Headache Source: Healthnotes, Inc.; www.healthnotes.com Tension Headache Source: Integrative Medicine Communications; www.drkoop.com

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Ulcerative Colitis Source: Integrative Medicine Communications; www.drkoop.com Weight Loss and Obesity Source: Healthnotes, Inc.; www.healthnotes.com x

Alternative Therapy Acupuncture Source: Healthnotes, Inc.; www.healthnotes.com Acupuncture Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,663,00.html Aromatherapy Source: Integrative Medicine Communications; www.drkoop.com Aromatherapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,664,00.html Ayurveda Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,672,00.html Bach Flower Remedies Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,673,00.html Biofeedback Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,675,00.html Colon Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,682,00.html Color Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,683,00.html

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Crystal Healing Alternative names: crystal therapeutics crystal therapy crystal work Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/c.html Dance Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,687,00.html Detoxification Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10119,00.html Guided Imagery Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,699,00.html Herbal Medicine Source: Integrative Medicine Communications; www.drkoop.com Homeopathy Source: Integrative Medicine Communications; www.drkoop.com Homeopathy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,703,00.html Light Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,713,00.html Magnet Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,715,00.html Massage Source: Integrative Medicine Communications; www.drkoop.com Massage Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,716,00.html Meditation Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,717,00.html Music Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,719,00.html Native American Medicine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,721,00.html Naturopathy Source: Integrative Medicine Communications; www.drkoop.com Prayer Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,728,00.html Psychic Self-Defense Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/p.html Qigong Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,729,00.html Reiki Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,731,00.html Repressed Memory Therapy Alternative names: RMT Source: The Canoe version of A Dictionary of Alternative-Medicine Methods, by Priorities for Health editor Jack Raso, M.S., R.D. Hyperlink: http://www.canoe.ca/AltmedDictionary/r.html Tai Chi Source: Integrative Medicine Communications; www.drkoop.com Therapeutic Touch Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,739,00.html Writing Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,745,00.html Yoga Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,746,00.html x

Chinese Medicine Chenxiang Alternative names: Chinese Eaglewood Wood; Lignum Aquilariae Resinatum Source: Chinese Materia Medica Fuke Tongjing Wan Alternative names: Fuke Tongjing Pills Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Gansui Alternative names: Gansui Root; Radix Kansui Source: Chinese Materia Medica Hehuanhua Alternative names: Albizia Flower; Flos Albiziae Source: Chinese Materia Medica Mabo Alternative names: Puff-ball; Lasiosphaera seu Calvatia Source: Chinese Materia Medica Meihua Alternative names: Plum Flower; Flos Mume Source: Chinese Materia Medica Muli Alternative names: Oyster Shell; Concha Ostreae Source: Chinese Materia Medica Muxiang Alternative names: Slender Dutchmanspipe Root; Qingmuxiang; Radix Aristolochiae Source: Chinese Materia Medica Nanshashen Alternative names: Fourleaf Ladybell Root; Radix Adenophorae Source: Chinese Materia Medica

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Naolejing Alternative names: Naolejing Syrup Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Shixiang Zhitong Wan Alternative names: hixiang Zhitong Pills; Shixiang Zhitong Wan (Shi Xiang Zhi Tong Wan Source: Pharmacopoeia Commission of the Ministry of Health, People's Republic of China Tumuxiang Alternative names: Inula Root; Radix Inulae Source: Chinese Materia Medica Walengzi Alternative names: Arc Shell; Concha Arcae Source: Chinese Materia Medica Zhebeimu Alternative names: hunberg Fritillary Bulb; Zhebeimu (Zhe Bei Mu); Bulbus Fritillariae Thunbergi Source: Chinese Materia Medica Zhimu Alternative names: Common Anemarrhena Rhizome; Rhizoma Anemarrhenae Source: Chinese Materia Medica x

Homeopathy Actaea Racemosa Source: Healthnotes, Inc.; www.healthnotes.com Arsenicum Album Source: Healthnotes, Inc.; www.healthnotes.com Aurum Metallicum Source: Healthnotes, Inc.; www.healthnotes.com Calcarea Carbonica Source: Healthnotes, Inc.; www.healthnotes.com Causticum Source: Healthnotes, Inc.; www.healthnotes.com Cimicifuga Source: Healthnotes, Inc.; www.healthnotes.com Ignatia Source: Healthnotes, Inc.; www.healthnotes.com

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Kali Phosophoricum Source: Healthnotes, Inc.; www.healthnotes.com Natrum Carbonicum Source: Healthnotes, Inc.; www.healthnotes.com Natrum Muriaticum Source: Healthnotes, Inc.; www.healthnotes.com Phosphorus Source: Healthnotes, Inc.; www.healthnotes.com Pulsatilla Source: Healthnotes, Inc.; www.healthnotes.com Sepia Source: Healthnotes, Inc.; www.healthnotes.com Staphysagria Source: Healthnotes, Inc.; www.healthnotes.com x

Herbs and Supplements 5-HTP Source: Integrative Medicine Communications; www.drkoop.com 5-HTP (5-Hydroxytryptophan) Source: Prima Communications, Inc.www.personalhealthzone.com 5-Hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com Aesculus Alternative names: Horse Chestnut; Aesculus hippocastanum L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org ALA Source: Integrative Medicine Communications; www.drkoop.com Allopurinol Source: Healthnotes, Inc.; www.healthnotes.com Alpha-Linolenic Acid (ALA) Source: Integrative Medicine Communications; www.drkoop.com Amino Acids Overview Source: Healthnotes, Inc.; www.healthnotes.com

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Aminoglycosides Source: Integrative Medicine Communications; www.drkoop.com Antibiotic Combination: Sulfa Drugs Source: Integrative Medicine Communications; www.drkoop.com Anticonvulsants Source: Healthnotes, Inc.; www.healthnotes.com Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Antituberculosis Agents Source: Integrative Medicine Communications; www.drkoop.com Arnica Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,753,00.html Asian Ginseng Alternative names: Panax ginseng Source: Integrative Medicine Communications; www.drkoop.com Astragalus Mem Alternative names: Huang-Qi; Astragalus membranaceus Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Astragalus Sp Alternative names: Vetch, Rattlepod, Locoweed; Astragalus sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ava Source: Integrative Medicine Communications; www.drkoop.com Barbiturates Source: Integrative Medicine Communications; www.drkoop.com Berberis Alternative names: Barberry; Berberis sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Beta-Carotene Source: Prima Communications, Inc.www.personalhealthzone.com Bisphosphonate Derivatives Source: Integrative Medicine Communications; www.drkoop.com Black Cohosh Source: Prima Communications, Inc.www.personalhealthzone.com

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Black Cohosh Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10009,00.html Brahmi Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Brewer's Yeast Alternative names: Nutritional Yeast Source: Integrative Medicine Communications; www.drkoop.com Bupropion Source: Healthnotes, Inc.; www.healthnotes.com Caprylic Acid Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10111,00.html Cardiac Glycosides Source: Integrative Medicine Communications; www.drkoop.com Celecoxib Source: Healthnotes, Inc.; www.healthnotes.com Celery Seed Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Centella Source: Integrative Medicine Communications; www.drkoop.com Centella asiatica Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Cephalosporins Source: Integrative Medicine Communications; www.drkoop.com Chamaemelum Nobile Source: Integrative Medicine Communications; www.drkoop.com Chasteberry Source: Prima Communications, Inc.www.personalhealthzone.com

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Chasteberry Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,767,00.html Citalopram Source: Healthnotes, Inc.; www.healthnotes.com Clozapine Source: Healthnotes, Inc.; www.healthnotes.com Cyclosporine Alternative names: Neoral, Sandimmune Source: Prima Communications, Inc.www.personalhealthzone.com Damiana Alternative names: Turnera diffusa Source: Healthnotes, Inc.; www.healthnotes.com Damiana Source: Prima Communications, Inc.www.personalhealthzone.com Damiana Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone (DHEA) Source: Integrative Medicine Communications; www.drkoop.com DHA Source: Integrative Medicine Communications; www.drkoop.com DHEA Source: Integrative Medicine Communications; www.drkoop.com DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Diclofenac Source: Healthnotes, Inc.; www.healthnotes.com DMAE Source: Healthnotes, Inc.; www.healthnotes.com DMAE Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10023,00.html

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Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Docosahexaenoic Acid (DHA) Source: Integrative Medicine Communications; www.drkoop.com English Lavendar Source: Integrative Medicine Communications; www.drkoop.com Ephedra Alternative names: Ephedra sinensis, Ma huang Source: Integrative Medicine Communications; www.drkoop.com Ephedra (Ma huang) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,777,00.html Ephedra sinensis Source: Integrative Medicine Communications; www.drkoop.com Estrogens (Combined) Source: Healthnotes, Inc.; www.healthnotes.com Etodolac Source: Healthnotes, Inc.; www.healthnotes.com Eugenia Clove Alternative names: Cloves; Eugenia sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Flurbiprofen Source: Healthnotes, Inc.; www.healthnotes.com Fluvoxamine Source: Healthnotes, Inc.; www.healthnotes.com Forskolin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10025,00.html French Lavendar Source: Integrative Medicine Communications; www.drkoop.com GABA (Gamma-Amino Butyric Acid) Source: Healthnotes, Inc.; www.healthnotes.com Garcinia Cambogia Alternative names: Citrin, Gambooge Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org

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Gentamicin Source: Healthnotes, Inc.; www.healthnotes.com Ginger Alternative names: Zingiber officinale Source: Integrative Medicine Communications; www.drkoop.com Ginger Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Alternative names: Ginkgo biloba Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Ginkgo Source: Prima Communications, Inc.www.personalhealthzone.com Ginkgo Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Ginkgo Biloba Source: Healthnotes, Inc.; www.healthnotes.com Ginkgo Biloba Alternative names: Maidenhair Tree Source: Integrative Medicine Communications; www.drkoop.com Ginkgo Biloba Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,788,00.html Ginseng (Panax) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10029,00.html Glimepiride Source: Healthnotes, Inc.; www.healthnotes.com Glutamic Acid Source: Healthnotes, Inc.; www.healthnotes.com Glutamine Source: Prima Communications, Inc.www.personalhealthzone.com Glutamine Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10030,00.html

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Glutathione Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,854,00.html Gotu Kola Alternative names: Centella asiatica , Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Green Tea Alternative names: Camellia sinensis Source: Healthnotes, Inc.; www.healthnotes.com Histamine H2 Antagonists Source: Integrative Medicine Communications; www.drkoop.com Hops Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Hydantoin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Hydrocotyle Source: Integrative Medicine Communications; www.drkoop.com Hypericum Perforatum Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Ibuprofen Source: Healthnotes, Inc.; www.healthnotes.com Indapamide Source: Healthnotes, Inc.; www.healthnotes.com Indian Pennywort Source: Integrative Medicine Communications; www.drkoop.com Indomethacin Source: Healthnotes, Inc.; www.healthnotes.com Inositol Source: Healthnotes, Inc.; www.healthnotes.com Inositol Source: Prima Communications, Inc.www.personalhealthzone.com

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Jamaica Dogwood Alternative names: Piscidia erythrina, Piscidia piscipula Source: Integrative Medicine Communications; www.drkoop.com Kava Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,798,00.html Kava Kava Alternative names: Piper methysticum, Ava Source: Integrative Medicine Communications; www.drkoop.com Ketoprofen Source: Healthnotes, Inc.; www.healthnotes.com Ketorolac Source: Healthnotes, Inc.; www.healthnotes.com Klamathweed Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com Kochia Alternative names: Summer Cypress, Fireweed; Kochia scoparia (L.) Schrad Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Kola Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Lavandula Alternative names: Lavender; Lavandula sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Lavandula Angustifolia Source: Integrative Medicine Communications; www.drkoop.com Lavender Alternative names: Lavandula officinalis Source: Healthnotes, Inc.; www.healthnotes.com Lavender Alternative names: Lavandula angustifolia, English Lavendar, French Lavendar Source: Integrative Medicine Communications; www.drkoop.com Lavender Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Lavender Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com

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Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,799,00.html Lecithin Source: Prima Communications, Inc.www.personalhealthzone.com Lepidium Sp Alternative names: Cress; Lepidium sp. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Levodopa/Carbidopa Alternative names: Sinemet Source: Prima Communications, Inc.www.personalhealthzone.com Lithium Source: Healthnotes, Inc.; www.healthnotes.com Loop Diuretics Source: Integrative Medicine Communications; www.drkoop.com L-Tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Ma huang Source: Integrative Medicine Communications; www.drkoop.com Macrolides Source: Integrative Medicine Communications; www.drkoop.com Maidenhair Tree Alternative names: Ginkgo Biloba Source: Integrative Medicine Communications; www.drkoop.com Marsh Pennywort Alternative names: Centella asiatica, Centella, March Pennywort, Indian Pennywort, Hydrocotyle, Brahmi (Sanskrit), Luei Gong Gen (Chinese)(Note: Gotu kola should not be confused with kola nut.) Source: Integrative Medicine Communications; www.drkoop.com Matricaria Alternative names: Chamomile; Matricaria chamomilla Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Melaleuca Alternative names: Tea Tree Oil; Melaleuca alternifolia Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Melatonin Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Integrative Medicine Communications; www.drkoop.com

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Melatonin Source: Prima Communications, Inc.www.personalhealthzone.com Melatonin Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,804,00.html Melissa Source: Prima Communications, Inc.www.personalhealthzone.com Menadione Source: Integrative Medicine Communications; www.drkoop.com Menaphthone Source: Integrative Medicine Communications; www.drkoop.com Menaquinone Source: Integrative Medicine Communications; www.drkoop.com Mentha Alternative names: Pennyroyal; Mentha/Hedeoma pulegium Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Mentha X Piperita Source: Integrative Medicine Communications; www.drkoop.com Metoclopramide Source: Healthnotes, Inc.; www.healthnotes.com Milk Thistle Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10044,00.html Mirtazapine Source: Healthnotes, Inc.; www.healthnotes.com Mixed Amphetamines Source: Healthnotes, Inc.; www.healthnotes.com Nabumetone Source: Healthnotes, Inc.; www.healthnotes.com NADH Source: Healthnotes, Inc.; www.healthnotes.com NADH Source: Prima Communications, Inc.www.personalhealthzone.com Nefazodone Source: Healthnotes, Inc.; www.healthnotes.com

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Non-Steroidal Anti-Inflammatory Drugs Source: Healthnotes, Inc.; www.healthnotes.com Oat Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Oral Contraceptives Source: Healthnotes, Inc.; www.healthnotes.com Oxaprozin Source: Healthnotes, Inc.; www.healthnotes.com Panax Alternative names: Ginseng; Panax ginseng Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Panax Ginseng Source: Integrative Medicine Communications; www.drkoop.com Penicillin Derivatives Source: Integrative Medicine Communications; www.drkoop.com Peppermint Alternative names: Mentha x piperita Source: Integrative Medicine Communications; www.drkoop.com Perphenazine Source: Healthnotes, Inc.; www.healthnotes.com Phenelzine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Healthnotes, Inc.; www.healthnotes.com Phenylalanine Source: Integrative Medicine Communications; www.drkoop.com Phenylalanine Source: Prima Communications, Inc.www.personalhealthzone.com Phosphatidylserine Source: Healthnotes, Inc.; www.healthnotes.com Phosphatidylserine Source: Prima Communications, Inc.www.personalhealthzone.com Phosphatidylserine (PS) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,813,00.html

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Phylloquinone Source: Integrative Medicine Communications; www.drkoop.com Piper Methysticum Source: Integrative Medicine Communications; www.drkoop.com Piper Nigrum Alternative names: Black Pepper Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Piroxicam Source: Healthnotes, Inc.; www.healthnotes.com Piscidia Erythrina Source: Integrative Medicine Communications; www.drkoop.com Piscidia Piscipula Source: Integrative Medicine Communications; www.drkoop.com PMS Herbal Combination Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,947,00.html Pregnenolone Source: Healthnotes, Inc.; www.healthnotes.com Pregnenolone Source: Prima Communications, Inc.www.personalhealthzone.com Progesterone Source: Healthnotes, Inc.; www.healthnotes.com Pumpkin Alternative names: Cucurbita pepo, Cucurbita maxima Source: Healthnotes, Inc.; www.healthnotes.com Quinolones Source: Integrative Medicine Communications; www.drkoop.com Rofecoxib Source: Healthnotes, Inc.; www.healthnotes.com Roman Chamomile Alternative names: Chamaemelum nobile Source: Integrative Medicine Communications; www.drkoop.com Rosemary Alternative names: Rosmarinus officinalis Source: Integrative Medicine Communications; www.drkoop.com

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Rosemary Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Rosmarinus Officinalis Source: Integrative Medicine Communications; www.drkoop.com Ruta Alternative names: Rue; Ruta graveolens L. Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com Salsalate Source: Healthnotes, Inc.; www.healthnotes.com SAMe Source: Healthnotes, Inc.; www.healthnotes.com SAMe Source: Integrative Medicine Communications; www.drkoop.com SAMe (S-Adenosylmethionine) Source: Prima Communications, Inc.www.personalhealthzone.com SAMe (S-Adenosylmethionine) Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,818,00.html Selegiline Source: Healthnotes, Inc.; www.healthnotes.com Sertraline Source: Healthnotes, Inc.; www.healthnotes.com St. John’s Wort Alternative names: Hypericum perforatum Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Alternative names: Hypericum perforatum Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com St. John's Wort Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca

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St. John's Wort Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,824,00.html Sulindac Source: Healthnotes, Inc.; www.healthnotes.com Terminalia Alternative names: Myrobalans; Terminalia arjuna Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tetracycline Derivatives Source: Integrative Medicine Communications; www.drkoop.com Thioridazine Source: Healthnotes, Inc.; www.healthnotes.com Trazodone Source: Healthnotes, Inc.; www.healthnotes.com Tricyclic Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com Tyrosine Source: Integrative Medicine Communications; www.drkoop.com Tyrosine Source: Prima Communications, Inc.www.personalhealthzone.com Valeriana Alternative names: Valerian; Valeriana officinalis Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Valproic Acid Source: Healthnotes, Inc.; www.healthnotes.com Vanadate Source: Integrative Medicine Communications; www.drkoop.com Vanadyl Source: Integrative Medicine Communications; www.drkoop.com Venlafaxine Source: Healthnotes, Inc.; www.healthnotes.com Vervain Alternative names: Verbena officinalis Source: Healthnotes, Inc.; www.healthnotes.com

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Wild Indigo Source: The Canadian Internet Directory for Holistic Help, WellNet, Health and Wellness Network; www.wellnet.ca Yohimbe Alternative names: Pausinystalia yohimbe Source: Healthnotes, Inc.; www.healthnotes.com Yohimbe Source: Prima Communications, Inc.www.personalhealthzone.com Zingiber Alternative names: Ginger; Zingiber officinale Roscoe Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Zingiber Officinale Source: Integrative Medicine Communications; www.drkoop.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON DEPRESSIVE DISORDERS Overview In this chapter, we will give you a bibliography on recent dissertations relating to depressive disorders. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “depressive disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on depressive disorders, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Depressive Disorders ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to depressive disorders. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: x

A test of the tripartite model of anxiety and depression in adolescents by Ahnberg, Jamie Lynn, PhD from UNIVERSITY OF CALGARY (CANADA), 2003, 128 pages http://wwwlib.umi.com/dissertations/fullcit/NQ87011

x

Correlates and course of diagnosed and subthreshold depression in older adults by Wyman, Mary Frances, PhD from INDIANA UNIVERSITY, 2003, 91 pages http://wwwlib.umi.com/dissertations/fullcit/3094125

x

Endocrine dysfunction in primary depressive disorders in the mentally retarded and its behavioral correlates by PAWLARCZYK, DOUGLAS JOSEPH, PHD from THE UNIVERSITY OF NORTH DAKOTA, 1984, 174 pages http://wwwlib.umi.com/dissertations/fullcit/8507632

x

Relationships of multidimensional locus-of-control, depression and hopelessness in depressive disorders by VENTIMIGLIA, JOSEPH A., DSW from ADELPHI UNIVERSITY, SCHOOL OF SOCIAL WORK, 1986, 150 pages http://wwwlib.umi.com/dissertations/fullcit/8615944

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x

Self-esteem and depression in rural poor women by FULLER, CLAIRE ELLEN, PHD from UNIVERSITY OF VIRGINIA, 1996, 293 pages http://wwwlib.umi.com/dissertations/fullcit/9615967

x

Utilization of art therapy techniques to evidence latent bipolar disorders in adolescents diagnosed with depressive disorders: An application in differentiating depressive episodes of bipolar disorders and depressive disorders and predicting risk for dev by Prager, Jennifer Chiyoko, PhD from ALLIANT INTERNATIONAL UNIVERSITY, LOS ANGELES, 2003, 128 pages http://wwwlib.umi.com/dissertations/fullcit/3087087

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 5. PATENTS ON DEPRESSIVE DISORDERS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “depressive disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on depressive disorders, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Depressive Disorders By performing a patent search focusing on depressive disorders, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. 8Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Depressive Disorders

The following is an example of the type of information that you can expect to obtain from a patent search on depressive disorders: x

Anticonvulsant derivatives useful for the treatment of depression Inventor(s): Bacaltchuk; Josue (Sao Paulo, BR), Plata-Salaman; Carlos R. (Ambler, PA), Prado-Lima; Pedro A. S. (Alegre, BR) Assignee(s): Ortho-McNeil Pharmaceutical, Inc. (Raritan, NJ) Patent Number: 6,627,653 Date filed: July 27, 2001 Abstract: Anticonvulsant derivatives useful for treating depression as monotherapy or combination therapy are disclosed. Excerpt(s): The present invention is directed to anticonvulsant derivatives useful in the treatment of depression, specifically unipolar depression, treatment-refractory depression, resistant depression, anxious depression and dysthymia. The present invention is further directed to the treatment of depression comprising administration of one or more anticonvulsant derivatives in combination with one or more compounds selected from mono-amine oxidase inhibitors, tricyclics, serotonin reuptake inhibitors, serotonin noradrenergic reuptake inhibitors, noradrenergic and specific serotonergic agents, noradrenaline reuptake inhibitors, natural products, dietary supplements, neuropeptides, compounds targeting neuropeptide receptors or hormones. are structurally novel antiepileptic compounds that are highly effective anticonvulsants in animal tests (MARYANOFF, B. E, NORTEY, S. O., GARDOCKI, J. F., SHANK, R. P. AND DODGSON, S. P. J. Med. Chem. 1987, 30, 880-887; MARYANOFF, B. E., COSTANZO, M. J., SHANK, R. P., SCHUPSKY, J. J., ORTEGON, M. E., AND VAUGHT J. L. Bioorg. Med. Chem. Lett. 1993, 3, 2653-2656; SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., MARYANOFF, B. E. Epilepsia 1994, 35, 450-460; MARYANOFF B E, COSTANZO M J, NORTEY S O, GRECO M N, SHANK R P, SCHUPSKY J J, ORTEGON M P, VAUGHT J L. J. Med. Chem. 1998, 41, 1315-1343). These compounds are covered by three U.S. Pat. Nos.: 4,513,006, 5,242,942, and 5,384,327. One of these compounds 2,3:4,5-bis-O-(1-methylethylidene)-.beta.-D-fructopyranose sulfamate, known as topiramate, has been demonstrated in clinical trials of human epilepsy to be effective as adjunctive therapy or as monotherapy in treating simple and complex partial seizures and secondarily generalized seizures (E. FAUGHT, B. J. WILDER, R. E. RAMSEY, R. A. REIFE, L D. KRAMER, G. W. PLEDGER, R. M. KARIM et. al., Epilepsia 1995, 36 (S4), 33; S. K. SACHDEO, R. C. SACHDEO, R. A. REIFE, P. LIM and G. PLEDGER, Epilepsia 1995, 36 (S4), 33; T. A. GLAUSER, Epilepsia 1999, 40 (S5), S71-80; R. C. SACHDEO, Clin. Pharmacokinet. 1998, 34, 335-346), and is currently marketed for the treatment of seizures in patients with simple and complex partial epilepsy and seizures in patients with primary or secondary generalized seizures in the United States, Europe and most other markets throughout the world. Compounds of Formula I were initially found to possess anticonvulsant activity in the traditional maximal electroshock seizure (MES) test in mice (SHANK, R. P., GARDOCKI, J. F., VAUGHT, J. L., DAVIS, C. B., SCHUPSKY, J. J., RAFFA, R. B., DODGSON, S. J., NORTEY, S. O., and MARYANOFF, B. E., Epilepsia 1994, 35, 450-460). Subsequent studies revealed that Compounds of Formula I were also highly effective in the MES test in rats. Topiramate was also found to effectively block seizures in several rodent models of epilepsy (J. NAKAMURA, S. TAMURA, T. KANDA, A. ISHII, K. ISHIHARA, T. SERIKAWA, J. YAMADA, and M.

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SASA, Eur. J. Pharmacol. 1994, 254, 83-89), and in an animal model of kindled epilepsy (A. WAUQUIER and S. ZHOU, Epilepsy Res. 1996, 24, 73-77). Web site: http://www.delphion.com/details?pn=US06627653__ x

Apparatus and method for transcranial magnetic brain stimulation, including the treatment of depression and the localization and characterization of speech arrest Inventor(s): Davey; Kent R. (New Smyrna Beach, FL), Epstein; Charles M. (Atlanta, GA) Assignee(s): Emory University (Atlanta, GA) Patent Number: 6,425,852 Date filed: January 18, 2000 Abstract: An apparatus and method for transcranial magnetic brain stimulation. The apparatus allows transcranial stimulation at higher power efficiency and lower heat generation than prior available magnetic stimulator coils without an iron core. Use of the apparatus allows an improved method for active localization of language function. The device can also be used in rapid rate transcranial magnetic stimulation for the treatment of depression. Excerpt(s): The present invention relates to an apparatus for transcranial magnetic brain stimulation. The invention also relates to methods for localizing and characterizing speech arrest, and for treatment of depression using transcranial magnetic stimulation. Magnetic stimulation of neurons has been heavily investigated over the last decade. Almost all magnetic stimulation work has been done in vivo. The bulk of the magnetic stimulation work has been in the area of brain stimulation. Cohen has been a rather large contributor to this field of research (See e.g., T. Kujirai, M. Sato, J. Rothwell, and L. G. Cohen, "The Effects of Transcranial Magnetic Stimulation on Median Nerve Somatosensory Evoked Potentials", Journal of Clinical Neurophysiology and Electro Encephalography, Vol. 89, No. 4, 1993, pps. 227-234, the disclosure of which is fully incorporated herein by reference.) This work has been accompanied by various other research efforts including that of Davey, et al. and that of Epstein (See, K. R. Davey, C. H. Cheng, C. M. Epstein "An Alloy--Core Electromagnet for Transcranial Brain Stimulation", Journal of Clinical Neurophysiology, Volume 6, Number 4, 1989; and, Charles Epstein, Daniel Schwartzberg, Kent Davey, and David Sudderth, "Localizing the Site of Magnetic Brain Stimulation in Humans", Neurology, Volume 40, April 1990, pps. 666-670, the disclosures of which are fully incorporated herein by reference). Web site: http://www.delphion.com/details?pn=US06425852__

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Combined use of pramipexole and sertraline for the treatment of depression Inventor(s): Maj; Jerzy (Kracau, PL) Assignee(s): Boehringer Ingelheim Pharma KG (Ingelheim, DE) Patent Number: 6,255,329 Date filed: July 6, 1999 Abstract: The present invention relates to the use of 2-amino-4,5,6,7-tetrahydro-6-npropylamino-benzothiazole (pramipexole), the (+)- or (-)- enantiomer thereof, or one of the pharmacologically acceptable salts thereof, in conjunction with sertraline for the improved treatment of depression and depressive states.

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Excerpt(s): The present invention relates to an agent with an antidepressant activity containing 2-amino-4,5,6,7-tetrahydro-6-n-propylamino-benzothiazole, the (+) or (-) enantiomer thereof, the pharmacologically acceptable acid addition salts thereof and a conventional antidepressant. The combination of pramipexole and sertraline is of particular interest. Pramipexole--(-)-2-amino-6-n-propylamino-4,5,6,7-tetrahydrobenzothiazole-- is a dopamine-D.sub.3 /D.sub.2 agonist, the synthesis of which is described in European Patent 186 087 and U.S. Pat. No. 4,886,812. Pramipexole is known primarily for treating schizophrenia and particularly for the treatment of Parkinson's disease. German Patent Application DE 38 43 227 discloses that pramipexole lowers the prolactin serum level, and it is also known from German Patent Application DE 39 33 738 to use pramipexole to lower high TSH levels. Its transdermal administration is disclosed in U.S. Pat. No. 5,112,842, and WO Patent Application PCT/EP93/03389 describes the use of pramipexole as an antidepressant. Details of the preparation of the title compound can be found in EP-A 85 116 016, and reference is hereby made specifically to the literature cited therein. Web site: http://www.delphion.com/details?pn=US06255329__ x

Depression container Inventor(s): Chen; Jen-Fu (No. 835, Yuan Huan East Road, Feng Yuan City, Taichung Hsien, TW) Assignee(s): none reported Patent Number: 6,662,831 Date filed: August 29, 2002 Abstract: A depression container comprises a vessel including a compartment and a cover for enclosing and thus sealing the compartment. An air pump draws air out of the compartment and a pressure-activated switch controls on/off of the air pump. The pressure-activated switch detects an internal pressure in the compartment. The air pump is turned on when the internal pressure is higher than a predetermined first pressure value. The air pump is turned off when the internal pressure is lower than a predetermined second pressure value. In an alternative embodiment, the pressureactivated switch detects a pressure difference resulting from a closing motion of the cover on the vessel and turns the air pump on to thereby draw air out of the compartment of the vessel. The air pump is turned off when an internal pressure in the compartment detected by the pressure-activated switch is lower than a predetermined pressure value. Excerpt(s): The present invention relates to a depression container that is capable of maintaining the internal pressure under a predetermined value, and more particularly to a depression container equipped with an air pump that can be activated when the internal pressure in the depression container is below a predetermined value. A typical depression container includes a one-way valve and a user may manually operate a hand air pump to draw air out of the container via the one-way valve. The internal pressure of the container is thus reduced to a relatively low valve (almost vacuum). This reduces the risk of the articles in the container from being wetted or contaminated by dust or bacteria, thereby lengthening the preserve time. It is, however, troublesome and laborintensive for the user to reciprocatingly operate the hand air pump for many times. In addition, the user cannot know the exact internal pressure in the depression container. Furthermore, the depression container cannot provide an absolute sealing effect such that the internal pressure in the depression container may rise after a period of time and

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thus adversely affect preservation of the articles in the depression container. It is an object of the present invention to provide a depression container that may automatically draw air out of the depression container after a cover is attached to enclose an open end of the depression container. The internal pressure of the depression container is reduced to a predetermined value. Web site: http://www.delphion.com/details?pn=US06662831__ x

Device for judging normal operation of brake system based upon correlation of pedal depression stroke and master cylinder pressure Inventor(s): Onuma; Yutaka (Susono, JP) Assignee(s): Toyota Jidosha Kabushiki Kaisha (Toyota, JP) Patent Number: 6,129,425 Date filed: March 5, 1999 Abstract: In a device for judging a normal operation of a brake system of a vehicle such as an automobile by judging if the stroke of the brake pedal depression detected by a stroke sensor and the master cylinder pressure detected by a pressure sensor are correlated with one another within a range determined for a judgment of a normal operation of the brake system, the device detects speed of change of at least one of the stroke and the pressure, and refrains from executing the judgment when at least one of the stroke change speed and the pressure change speed is not smaller than a threshold value determined therefor. Excerpt(s): The present invention related to a device for judging a normal operation of a brake system of a vehicle such as an automobile, and more particularly, to such a brake system normal operation judging device that is improved not to make a mistake in the detection of the normal operation of the brake system due to variations of actuation thereof by drivers. In Japanese Patent Laid-open Publication 5-184007 (1993) there is proposed a device for judging a normal operation of a brake system which judges that the brake system is not normally operating when an output of a brake depression sensor is higher than a predetermined value under an off state of a brake lamp switch. In view of the above-mentioned problems, it is a primary object of the present invention to provide a device for judging a normal operation of a brake system of a vehicle such as an automobile, improved not to make a mistake in the judging of the normal operation of the brake system due to variations of actuation thereof by drivers. Web site: http://www.delphion.com/details?pn=US06129425__

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Kainate receptor subunit GLUR7 polymorphisms for determining predispositions to recurrent unipolar and bipolar II depressive disorders Inventor(s): Heinemann; Stephen F. (La Jolla, CA), Schiffer; Hans H. (San Diego, CA) Assignee(s): The Salk Institute (La Jolla, CA) Patent Number: 6,664,055 Date filed: May 11, 2001 Abstract: Provided are methods for determining the predisposition of a subject to a mood disorder by determining in a biological sample of a subject, the presence of a kainate receptor subunit GluR7 allelic genotype or allelic phenotype associated with

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predisposition to a mood disorder. The allelic genotype is homozygosity for a thymine containing nucleotide at position 928 (928T/T) or homozygosity for a guanine containing nucleotide position 928 (928G/G). In addition, a predominant expression of one GluR7 allele over the other allele in a heterozygous individuals also predicts predisposition to a mood disorder. The present invention also includes a method of treating or preventing a mood disorder and methods for identifying a compound useful for treatment. Transgenic non-human animals that express only a particular human GluR7 allele at nucleotide position 928 also are provided as a model of a human mood disorder. Excerpt(s): The present invention relates generally to the identification of cell receptors and encoding genes that are involved in neurological disease and the identification of receptors and encoding genes involved in mono and bipolar mood disorders. Mood disorders rank among the top ten causes of disability worldwide. Unipolar depressive disorder and bipolar disorder are mood disorders with high prevalence in the population and an enormous impact on the life of affected individuals and society (Oruc et al., (1998a) Med. Arch., 52:107-112; Craddock and Jones, (1999) Am. J. Psychiatry, 149443-454; Oruc et al., (1998b) Med. Arch, 52:167-173; Doris et al., (1999) Lancet, 354:1369-1375). Disability and suffering from a mood disorder even extends beyond the patient to their spouses, children, parents, siblings, and friends, who experience frustration, guilt, anger, financial hardship and, on occasion, physical abuse, all in their attempts to assuage or cope with the depressed person's suffering. A large portion of health care expenditures go to treating individuals having depression. Paradoxically, much of treatment does not address the mood disorder because individuals try to seek treatment for other problems in order to avoid the stigma associated with having a mood disorder diagnosis. Consequently, patients with depression undergo extensive and expensive diagnostic procedures of no benefit while their mood disorder goes undiagnosed. The genetics of mood disorders appears complex and it has been proposed that anticipation and/or genomic imprinting of candidate genes contribute to the observed mode of inheritance (Grigoroiu-Serbanescu (1992) Rom J Neural Psychiatry, 30,265-277. Grigoroiu-Serbanescu (1995) Acta Psychiatr Scand, 92, 365-370.; McMahon, et al. (1995) Am J Hum Genet, 56, 1277-1286; Kato, et al. (1996) Am J Med Genet, 67, 546-550; Grigoroiu-Serbanescu, et al.(1997) Br J Psychiatry, 170, 162-166). Researchers have identified genes generally involved in neurodegenerative disease such as genes of serotonergic, catecholaminergic or GABAergic neurotransmitter systems as well as the genes of the glutamate receptor system. Despite these intensive research efforts, the specific genes involved in mood disorder pathology remain to be identified. Web site: http://www.delphion.com/details?pn=US06664055__ x

Method for treatment of anxiety and depression Inventor(s): Dunbar; Geoffrey C. (Middleton, CT), Molinoff; Perry B. (Weston, CT) Assignee(s): Bristol-Myers Squibb Company (Princeton, NJ) Patent Number: 6,312,717 Date filed: June 14, 1999 Abstract: An improved method of treatment for anxiety and/or depression provides a quicker and more robust anxiolytic/antidepressant activity to a patient suffering from depression. The method comprises the concurrent administration of effective doses of certain azapirones, such as buspirone, given in a manner that suppresses formation of

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the 1-(2-pyrimidinyl)piperazine metabolite; and a 5-HT1A autosomal receptor antagonist, such as pindolol. Excerpt(s): The present invention relates to an improved method for treating anxious and/or depressed patients. Concurrent administration of certain azapirones with a 5HT1A autosomal receptor antagonist provides faster onset of anxiolytic and antidepressant actions. By administering the azapirone in such a manner that formation of the 1-(2-pyrimidinyl)piperazine metabolite (1-PP) is minimized, a more robust therapeutic effect is achieved. These particular azapirones containing the pyrimidinylpiperazine moiety as an integral part of their molecular structure give rise to 1-(2-pyrimidinyl)piperazine (1-PP) as their major metabolite. This metabolite is seen in greatest abundance following oral administration. The most studied and well-known member of this compound class is buspirone, an important antianxiety agent first approved for use in anxious patients in 1986. Although buspirone has been disclosed as having antidepressant properties by Robinson, et al., J. Clin. Psychopharmacol. , 1990, 10:675-765; it has not been generally considered to be as efficacious as classical antidepressant agents. However, Blier, et al. in Neuropsychopharmacol. , 1997, 16:333338; reported that buspirone exhibited both an efficacy and onset of action that was superior to classical antidepressants when the buspirone was combined with the 5HT1A autosomal receptor blocker, pindolol. Both agents were administered separately by the oral route to a group of depressed patients in the study described by Blier. Web site: http://www.delphion.com/details?pn=US06312717__ x

Method for treatment of depression Inventor(s): Tyers; Michael Brian (Ware, GB) Assignee(s): Glaxo Group Limited (GB) Patent Number: 6,221,878 Date filed: March 10, 1995 Abstract: The invention relates to the use of compounds which act as antagonists of 5hydroxytryptamine (5-HT) at 5-HT.sub.3 receptors for the treatment of depression. Excerpt(s): This invention relates to a new medical use for certain chemical compounds and pharmaceutical compositions containing them. In particular it relates to the use in the treatment of depression of compounds which act as antagonists of 5hydroxytryptamine (5-HT) at receptors known in the art as 5-HT.sub.3, 5-HT`M` or 5HT `M'-like` receptors. Such receptors have been described for example by Fozard et al., Eur. J. Pharmacol., 1979, 59, 195-210; Ireland, Straughan and Tyers, Br. J. Pharmacol., 1982, 75, 16P; Humphrey, Neuropharm., 1984, 23, 1503-1570; Richardson et al., Nature, 1985, 316, 126-131; and Bradley et al., Neuropharm., 1986, 25, 563-576. Receptors of this type are now designated as 5-HT.sub.3 receptors. 5-HT receptors of this type are located, for example, on the terminals of afferent sensory neurones, in the isolated guinea-pig ileum preparation and are also present in the central nervous system. Compounds which act as antagonists of 5-HT at 5-HT.sub.3 receptors may be identified using standard tests, for example, in vitro by measuring their inhibition of the depolarising effect of 5-HT on the rat or rabbit isolated vagus nerve, or the tachycardia produced by 5-HT in the rabbit isolated heart or the contraction produced by 5-HT in the guinea-pig isolated ileum, or in vivo by measuring their effect on the Von Bezold-Jarisch reflex (induced by 5-HT) as described, for example, in the above-mentioned references. A variety of compounds which act as antagonists of 5-HT at 5-HT.sub.3 receptors have

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been described in the art. These compounds are generally azabicyclo derivatives and/or benzoic acid derivatives, or imidazole derivatives. The azabicyclo derivatives include compounds containing a bridged piperidyl group, such as a tropyl, pseudotropyl, homotropyl or quinoclidinyl group, and they preferably contain a carbocyclic or heterocyclic aromatic group linked, for example as an ester or amide, to the azabicyclic ring. The aromatic group may be for example an optionally substituted phenyl, indolyl, benzofuranyl, benzothienyl, benzisoxazolyl, indazolyl or pyrimidinyl group. Web site: http://www.delphion.com/details?pn=US06221878__ x

Method of treating depression using 1-threo-methylphenidate Inventor(s): Kumar; Vijai (Morris Plains, NJ), Midha; Kamal K. (Hamilton, BM), Teicher; Martin (Waltham, MA) Assignee(s): Pharmaquest Limited (Hamilton, BM) Patent Number: 6,395,752 Date filed: August 11, 2000 Abstract: A method of treating dysphoria or depression is disclosed in a patient which comprises the step of administering orally or non-orally to said patient, a therapeutically effective amount of 1-threo-methylphenidate or a pharmaceutically acceptable acid addition salt thereof. Excerpt(s): This invention relates to a method of treating depression in a patient by oral or non-oral administration of 2S,2'S-methyl 2-phenyl-2-(2'-piperidyl) acetate, commonly known as 1-threo-methylphenidate, hereinafter referred to as 1-MPH and to pharmaceutical compositions containing 1-MPH designed to deliver 1-MPH to the central nervous system. More particularly the method of treatment is designed to provide relief to a depressed patient who is awaiting the onset of the antidepressive action of an antidepressant such as a selective serotonin re-uptake inhibitor, or any other class of antidepressant that requires administration over 2 to 6 weeks to demonstrate therapeutic effect. Orally administered racemic d1-threo-methylphenidate (d1-MPH) is widely used in the treatment of Attention-Deficit Hyperactivity Disorder (ADHD) in children and adults and also in the treatment of depression in patients suffering from cancer or AIDS, compulsive shopping disorder, narcolepsy, and hypersomnia. It is known that the therapeutic effect of d1-MPH in the treatment of ADHD in children is attributable to d-MPH (Srinivas et al, Clin. Pharmacol. Therap. 52, 561 to 568, 1992). Until recently, however, little was known about the potential pharmacological and/or therapeutic roles of 1-MPH because concentrations of 1-MPH in plasma and brain are very low due to extensive enantioselective first pass metabolism of 1-MPH after oral administration of d1-MPH (Srinivas et al, Pharm. Res. 10, 14 to 21, 1993). After intravenous administration of d1-MPH, however, both enantiomers of threomethylphenidate are taken up into the brain although their patterns of distribution are different (Ding et al, Psychopharmacology 131, 71 to 78, 1997). The use of oral stimulants such as dextroamphetamine or d1-MPH in the treatment of severe depressive disorders in the elderly or terminally ill depressed patients has been the subject of many studies over the years. After reviewing 85 publications on the subject, Satel and Nelson (J. Clin. Psychiat. 50, 241 to 249, 1989) were critical of the fact that many of the studies reported were methodologically unsophisticated and/or uncontrolled. They concluded that while stimulants are no more effective than a placebo in the treatment of primary depression, stimulants may be of value in the treatment of refractory patients and medically ill patients. Similarly, Chiarello and Cole (Arch. Gen. Psychiat. 44, 276 to 285, 1997)

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reviewed 81 publications and concluded that many of the older studies are inadequate although there was some evidence to support the use of psychostimulants in selected clinical instances. Emptage and Smith (Annals of Pharmacotherapy, 30, 151 to 157, 1996) reviewed 43 studies published from 1986 to 1995 and concluded that oral--MPH appears to be a safe and effective treatment for depressed, medically ill, elderly patients to provoke a rapid onset of antidepressant activity. Recently Wallace and co-workers (Am. J. Psychiat. 152, 929 to 931, 1995) conducted what they termed the first placebocontrolled double blind trial to demonstrate the efficacy of oral d1-MPH in older, medically ill depressed patients. The benefit of oral d1-MPH was statistically and clinically significant despite the small number of patients in the study (n=16). Depressive symptoms decreased markedly in 7 subjects (Hamilton depression scale decreased by >55%), moderately in a further 3 subjects (Hamilton depression scale decreased by 30 to 55%), minimally in 3 subjects (Hamilton depression scale decreased by <30%) and three patients were dropped from the study. Web site: http://www.delphion.com/details?pn=US06395752__ x

Method of treating manic depression by brain infusion Inventor(s): Rise; Mark T. (7745 Aetna Ave. NE., Monticello, MN 55432) Assignee(s): none reported Patent Number: 6,176,242 Date filed: April 30, 1999 Abstract: Techniques using one or more drugs, electrical stimulation or both to treat depression or manic depression by means of an implantable signal generator and electrode and/or an implantable pump and catheter. A catheter is surgically implanted in selected sites in the brain to infuse the drugs, and one or more electrodes are surgically implanted in the brain at selected sites to provide electrical stimulation. Excerpt(s): This invention relates to nerve tissue stimulation and infusion techniques, and more particularly relates to such techniques for treating depression and manic depression. A persons immediate emotional state is referred to as their affective state. Two normal emotions or affective states are eurphoria and depression. These affective states are experienced transiently by all persons in response life situations. For some individuals however, these normal emotional responses may become sustained for long periods of time. The general affective state may not reflect the momentary expeiences of the individual. Two affective disorders involving the emotions of eurphoria and depression are unipolar or major depression and bipolar depression or manic depression. Unipolar depression manifests as episodes of dysphoria (unpleasant mood) and anhedonia (inability to experience pleasure) which may last for months. Symptoms may include a loss of energy, changes in weight (most often weight loss but possibly weight gain) insomnia or sometimes oversleeping, restlessness, and inability to concentrate, loss of sex drive, negative thoughts, feelings of worthlessness and suicidal ideation. Unipolar depression is characterized by subtypes. The estimates are that there may be as many as 4 million people in the United States suffering from depression. Web site: http://www.delphion.com/details?pn=US06176242__

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Method of treating schizophrenia, depression and other neurological conditions Inventor(s): Kelly; John S. (Edinburgh, GB), Marston; Hugh M. (East Lothian, GB) Assignee(s): Fujisawa Pharmaceutical Co., Ltd. (Osaka, JP) Patent Number: 6,284,760 Date filed: June 24, 1999 Abstract: This application relates to the use of aminopiperazine derivatives for the treatment of schizophrenia, depression, and other neurological conditions. Excerpt(s): The aminopiperazine derivatives used in this invention are known as described in PCT International Publication No. WO 91/01979 that said aminopiperazine derivatives possess the potentiation of the cholinergic activity and are useful in the treatment of disorders in the central nervous system for human beings, and more particularly in the treatment of amnesia, dementia, senile dementia and the like. The present invention relates to a new use of aminpiperazine derivatives and pharmaceutically acceptable salts thereof for the treatment and/or prevention of schizophrenia, depression, stroke, head injury, nicotine withdrawal, spinal cord injury, anxiety, pollakiuria, incontinence of urine, myotonic dystrophy, attention deficit hyperactivity disorder, excessive daytime sleepiness (narcolepsy), Parkinson's disease or autism for mammals. Accordingly, this invention is to provide a new use of aminopiperazine derivatives and pharmaceutically acceptable salts thereof for treating and/or preventing schizophrenia, depression, stroke, head injury, nicotine withdrawal, spinal cord injury, anxiety, pollakiuria, incontinence of urine, myotonic dystrophy, attention deficit hyperactivity disorder, excessive daytime sleepiness (narcolepsy), Parkinson's disease or autism. Web site: http://www.delphion.com/details?pn=US06284760__

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Methods for reducing respiratory depression and attendant side effects of mu opioid compounds Inventor(s): Bishop; Michael J. (Durham, NC), Chang; Kwen-Jen (Chapel Hill, NC), McNutt, Jr.; Robert W. (Durham, NC), Pettit; Hugh O. (Cary, NC) Assignee(s): Delta Pharmaceuticals, Inc. (Durham, NC) Patent Number: 6,300,332 Date filed: July 12, 1999 Abstract: A method of reducing, treating or preventing drug-mediated respiratory depression, muscle rigidity, or nausea/vomiting in an animal, incident to the administration to said animal of a mixed delta/mu opioid agonist or a respiratory depression-mediating drug, comprising administering to the animal receiving said drug an effective amount of a delta receptor agonist compound. Excerpt(s): This invention relates generally to methods for reducing, treating, reversing or preventing drug-mediated respiratory depression, such as may be directly or indirectly caused by use of various bioactive compositions, including anaesthetics, barbiturates, analgesics, etc. The invention further relates to diarylmethyl piperazine compounds and diarylmethyl piperidine compounds, and pharmaceutical compositions thereof, having utility in medical therapy especially for reducing respiratory depression associated with certain analgesics, such as mu opiates. This invention additionally relates to diarylmethyl piperazine compounds and diarylmethyl piperidine compounds

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having utility in assays for determining the respiratory reducing characteristics of other bioactive compounds, including other diarylmethyl piperazine compounds and other diarylmethyl piperidine compounds. In the study of opioid biochemistry, a variety of endogenous opioid compounds and non-endogenous opioid compounds has been identified. In this effort, significant research has been focused on understanding the mechanism of opioid drug action, particularly as it relates to cellular and differentiated tissue opiate receptors. Opioid drugs typically are classified by their binding selectivity in respect of the cellular and differentiated tissue receptors to which a specific drug species binds as a ligand. These receptors include mu (.mu.), delta (.delta.), sigma (.sigma.) and kappa (.kappa.) receptors. Web site: http://www.delphion.com/details?pn=US06300332__ x

Methods for treating depression and other disorders using optically pure (-)bupropion Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,451,860 Date filed: February 19, 2002 Abstract: Methods are disclosed utilizing the optically pure (-)-isomer of bupropion, which is a potent drug for treating depression, Parkinson's disease, obesity, weight gain and other disorders. Excerpt(s): This invention relates to methods of treatment and pharmaceutical compositions employing the compound (-)-bupropion. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of plane-polarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes (+) and (-) or d and l are employed to designate the sign of rotation of planepolarized light by the compound, with (-) or l meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 16 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the Lform of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06451860__

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Osanetant in the treatment of depression and depressive disorders Inventor(s): Emonds-Alt; Xavier (Combaillaux, FR), Soubrie; Philippe (Valflaunes, FR), Steinberg; Regis (Prades le Lez, FR) Assignee(s): Sanofi-Synthelabo (Paris, FR) Patent Number: 6,420,388 Date filed: October 5, 2001

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Abstract: The invention relates to a method for the treatment of mood disorders utilizing osanetant or a pharmaceutically acceptable salt thereof. Excerpt(s): The subject of the present invention is a novel use of osanetant. This compound and its pharmaceutically acceptable salts are described in European Patent Application EP 673 928. These compounds are described as being selective antagonists of the human NK.sub.3 receptor which are useful for the treatment of disorders associated with dysfunction of the dopaminergic and noradrenergic systems. Web site: http://www.delphion.com/details?pn=US06420388__ x

Paroxetine in the treatment of depression associated with withdrawal from heroin abuse and post-traumatic stress disorder Inventor(s): Gleason; Maurice (Newbury, GB) Assignee(s): SmithKline Beecham plc (Brentford, GB) Patent Number: 6,121,291 Date filed: February 11, 1999 Abstract: This invention relates to the use of paroxetine or a pharmaceutically acceptable salt thereof for the treatment of post-traumatic stress disorder and depression associated with withdrawal from heroin abuse. Excerpt(s): The present invention relates to the treatment and/or prevention of specific types of depression. U.S. Pat. No. 4,007,196 discloses the compound, (-)-trans-4-(4'fluorophenyl)-3-(3'4'-methylenedioxy-phenoxymethyl) piperidine, and, in Example 2, a process by which it can be prepared. The compound, which is referred to herein by its common name, paroxetine, is described in the patent as an inhibitor of 5hydroxytryptamine uptake and, therefore, is of use in the treatment of depression in general. It has now been surprisingly discovered that paroxetine has particularly effective therapeutic utility for treating and/or preventing specific types of depression. Web site: http://www.delphion.com/details?pn=US06121291__

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Remediation of depression through computer-implemented interactive behavioral training Inventor(s): Blake; David T. (San Francisco, CA), Merzenich; Michael M. (San Francisco, CA) Assignee(s): Scientific Learning Corporation (Berkeley, CA), The Regents of the University of California (Oakland, CA) Patent Number: 6,165,126 Date filed: September 15, 1998 Abstract: A computer-implemented technique for remediating depression in a person which includes assessing, using a computer-implemented interactive behavioral assessment regime, a depression index for the person. If the depression index is above a predefined benchmark, the computer-implemented technique includes periodically reassessing the depression index by waiting for at least a predefined period of time, and performing the above assessing step after the predefined period of time expires. If the depression index is below the predefined benchmark, treating the person by

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administering computer-implemented interactive behavioral training to the person. The computer-implemented interactive behavioral training is sufficiently intensive during each training day to create a permanent change in modulatory functions of neurotransmitters of one of norepinephrine and serotonin in the person. Excerpt(s): The present invention relates to computer-implemented interactive training techniques for treating depression. More specifically, the present invention relates to intensive computer-implemented behavioral training techniques that effectively remediate symptoms of clinical depression and of depressive personality disorders. Depression in its manifold specific forms is the most common form of diagnosed mental illness. Although the symptoms may vary in different individuals, a common distinction between depressives differentiates `unipolar` from `bipolar` individuals. The former have a single-polar (depressed) disorder of mood. The latter swing alternatively (commonly with a cycle period of days to weeks in duration) between depression and mania. Within these simple distinctions and under the broad umbrella term `depression` fall many depression subtypes and an overlapping classification of an often-milder `depressive personality`. There are many thousands of published reports on the epidemiology, neurology, and treatment of this commonly occurring illness, and many thousands more publications relate to the study of its underlying neurology. Generally speaking, there are two primary treatment strategies that have been effective for very large populations of depressives. These two primary treatment strategies involve phamacological therapies and psychological therapies. Generally speaking, there are three primary treatment strategies that have been effective for large populations of depressives. These three treatments are pharmacotherapy, psychotherapy, and electroconvulsive therapy. Web site: http://www.delphion.com/details?pn=US06165126__ x

Sheet metal component with depression Inventor(s): Laut; Marvin (Dracut, MA) Assignee(s): 3Com Corporation (Santa Clara, CA) Patent Number: 6,281,432 Date filed: May 25, 1999 Abstract: A process is provided for providing a metal element and removing portions of the metal at a series of location at a section of the metal element. By removing portions of the metal element a plurality of webs are provided separating the holes where the material has been removed. The webs are subsequently pressed to allow the webs to expand into the region of the holes and to form a depressed region based on the depressed surfaces of each of the webs relative to the surrounding web seat. The resulting product provides a metal piece such as a sheet metal element wherein a groove or depression is formed on one side without any extension or protrusion on the other side. A system is also provided using the metal element in combination with a gasket element and another component. This system provides an effective EMI barrier. Excerpt(s): The present invention relates generally to metal components and more particularly to electronic device housings made of sheet metal and sheet and support elements used for electronic devices, especially used for electronic devices operating at high frequencies. Support structures and housings made for electronic components are often made of sheet metal. The sheet metal structures can include support elements, housings as well as shielding elements, e.g. elements provided to shield various devices

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as to electromagnetic emissions that cause electromagnetic interference (EMI). Electronic devices are being used which operate at very high frequencies. This leads the designer of housings and support structures to increasingly provide systems and components for reducing EMI problems. Web site: http://www.delphion.com/details?pn=US06281432__ x

Substrate assembly having a depression suitable for an integrated circuit configuration and method for its fabrication Inventor(s): Hofmann; Franz (Munchen, DE), Schlosser; Till (Dresden, DE), Willer; Josef (Riemerling, DE) Assignee(s): Infineon Technologies AG (Munich, DE) Patent Number: 6,608,340 Date filed: March 30, 2001 Abstract: A depression extends from a main surface of the substrate to the inside of said substrate and has an upper area and an adjacent lower area. A cross-section of the upper area, parallel to the main surface, is provided with at least one corner. A cross-section of the lower area, parallel to the main surface, matches the cross-section of the upper area, particularly in the vicinity the upper area, with the following difference: each corner is rounded, whereby the cross section of the lower area is smaller than the cross-section of the upper area. In order to produce the indentation, the upper area is provided with an auxiliary spacer that is rounded by isotropic etching. The lower area is produced by selectively etching the substrate to form an auxiliary spacer. Excerpt(s): The invention relates to a substrate having a depression suitable for an integrated circuit configuration and to a method for its fabrication. In K. Yamada et al. "A deep-trenched capacity technology for 4 megabit dynamic RAM", IEDM (1985) 702, a capacitor disposed in a depression in a substrate is described. In the depression, a capacitor dielectric is produced on surfaces that have no edges. A photolithographic process initially produces the depression with a square cross section. In order to round off the edges, a thermal oxide about fifty nanometers (50 nm) thick is grown and then removed. The capacitor dielectric is then grown by thermal oxidation. The rounding of the edges reduces leakage currents. This is because if a thermal oxide is grown onto a surface which has an edge, the oxide at the edge turns out to be particularly thin, so that leakage currents therefore occur in the region of the edge. Commonly owned German patent 195 19 160 (which correspond to U.S. Pat. No. 5,817,552) describes a DRAM cell configuration. In this DRAM configuration, a storage capacitor is disposed underneath a transistor. A gate electrode of the transistor and a storage node of the capacitor are disposed in a depression having a square cross section. A surface on which the capacitor dielectric is disposed has edges. Web site: http://www.delphion.com/details?pn=US06608340__

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Treating depression with alcohol extracts of tobacco Inventor(s): Burton; Harold R. (Lexington, KY), Delorenzo; Robert J. (Richmond, VA), Williams; Jonnie R. (Manakin-Sabot, VA) Assignee(s): Regent Court Technologies (Town and Country, MI) Patent Number: 6,350,479 Date filed: June 4, 1999 Abstract: The present invention provides a group of tobacco alkaloids, tobacco extract, Yerbamate extract, and an extract of chewing gum and lozenges which are modulators of monoamine oxidase (MAO) activity (i.e., compounds and substances which inhibit MAO enzyme and prevent its biological activity). The MAO inhibitors of the present invention can cause an increase in the level of norepinephrine, dopamine, and serotonin in the brain and other tissues, and thus can cause a wide variety of pharmacological effects mediated by their effects on these compounds. The MAO inhibitors of the present invention are useful for a variety of therapeutic applications, such as the treatment of depression, disorders of attention and focus, mood and emotional disorders, Parkinson's disease, extrapyramidal disorders, hypertension, substance abuse, smoking substitution, antidepression therapy, eating disorders, withdrawal syndromes, and the cessation of smoking. Excerpt(s): The present invention relates to the novel use of compounds and substances which are capable of modulating monoamine oxidase (MAO) activity by inhibiting the MAO enzyme. The present invention also relates to MAO inhibitors and their therapeutic use as a drug or dietary supplement in the treatment of various conditions or disorders, including psychiatric and neurological illnesses. More particularly, the present invention relates to the therapeutic use of tobacco alkaloids, Yerbamate (Ilex paraguariensis) extract, or tobacco extracts to inhibit MAO activity to provide a treatment for various disorders or conditions. By inhibiting MAO activity, MAO inhibitors can regulate the level of mono amines and their neurotransmitter release in different brain regions and in the body (including dopamine, norepinephrine, and serotonin). Thus, MAO inhibitors can affect the modulation of neuroendocrine function, respiration, mood, motor control and function, focus and attention, concentration, memory and cognition, and the mechanisms of substance abuse. Inhibitors of MAO have been demonstrated to have effects on attention, cognition, appetite, substance abuse, memory, cardiovascular function, extrapyramidal function, pain and gastrointestinal motility and function. The distribution of MAO in the brain is widespread and includes the basal ganglia, cerebral cortex, limbic system, and mid and hind-brain nuclei. In the peripheral tissue, the distribution includes muscle, the gastrointestinal tract, the cardiovascular system, autonomic ganglia, the liver, and the endocrinic system. It has been suggested that cigarette smoke may have irreversible inhibitory effect towards monoamine oxidase (MAO). A. A. Boulton, P. H. Yu and K. F. Tipton, "Biogenic Amine Adducts, Monoamine Oxidase Inhibitors, and Smoking," Lancet, 1(8577): 114-155 (Jan. 16, 1988), reported that the MAO-inhibiting properties of cigarette smoke may help to explain the protective action of smoking against Parkinson's disease and also observed that patients with mental disorders who smoke heavily do not experience unusual rates of smoking-induced disorders. It was suggested that smoking, as an MAO inhibitor, may protect against dopaminergic neurotoxicity that leads to Parkinson's disease and that the MAO-inhibiting properties of smoking may result in an antidepressive effect in mental patients. Web site: http://www.delphion.com/details?pn=US06350479__

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Treatment of depression Inventor(s): Sanchez; Connie (Glostrup, DK) Assignee(s): H. Lundbeck A/S (Valby-Copenhagen, DK) Patent Number: 6,358,966 Date filed: March 15, 2001 Abstract: The compound 1'-[4-[1-(4-fluorophenyl)-1H-indole-3-yl]-1-butylspiro[isobenzo-furan-1(3 H,4'-piperidine] is active in models predictive of antidepressant effects and is useful for the preparation of a medicament for the treatment of depression or diseases associated with depressive symptoms. Excerpt(s): The present invention relates to the use of the compound 1'-[4-[1-(4fluorophenyl)-1H-indole-3-yl]-1-butyl]-spiro[isobenzofuran-1(3 H),4'-piperidine] or a pharmaceutically acceptable salt thereof for the preparation of medicaments for the treatment of depression. International Patent Publication No. WO 92/22554 describes a series of sigma receptor ligands considered useful for the treatment of a range of psychic and neurological disorders. The structure activity relationship of these compounds has been further investigated by Perregaard, J. et al., J. Med. Chem., 1995, 38, 11, p. 19982008. which is the subject of the present invention. This compound was shown in Perregaard, J. et al., J Med. Chem., 1995, 38, 11, p. 1998-2008 to be a potent and selective sigma ligand, in particular a sigma.sub.2 ligand. Furthermore, the anxiolytic potential of the compound was tested in the black/white exploration test in rats, which is an animal model predictive for effect in the treatment of generalised anxiety disorder. It was found to be active over a large dose range. Results of further tests in generalised anxiety disorder models are reported in J Pharmacol. Exp. Ther., 1997, 283, No. 2. Web site: http://www.delphion.com/details?pn=US06358966__

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Treatment of depression and pharmaceutical preparations therefor Inventor(s): Coppen; Alec James (Epsom, GB) Assignee(s): Scarista Limited (Douglas, GB) Patent Number: 6,191,133 Date filed: June 24, 1998 Abstract: It has been found that the treatment of depression using known serotonin reuptake inhibitors (SRIs) and noradrenaline reuptake inhibitors (NRIs) may be improved by the administration therewith of folic acid or a precursor which produces folate in the patient. The daily dose of NRI or SRI is as prescribed for treatment of depression in the usual way. The daily dose of the folic acid or precursor should be such as to provide a folate dosage of 300-5000 micrograms/day. Excerpt(s): This invention relates to the treatment of depression, and to pharmaceutical preparations for use therein. Depression is one of the most important health care problems, especially in developed countries. At some time in their lives, about 5-10% of the population goes through a major depressive illness while minor depressive episodes may affect 25% or more of the population. The World Health Organisation has estimated that depression causes more global distress than any other illness. Depression seriously disrupts people's lives, rendering existence both at home and at work difficult. Depression is the commonest reason for suicide. Depression is also associated with other illnesses, particularly cardiovascular diseases. People with a history of major

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depression were over four times more likely to have a myocardial infarction than normal individuals, even after allowing for known coronary disease risk factors (L A Pratt et al, Circulation 1996; 3123-3129). After a myocardial infarction, people with major depression are 3.5 times more likely to die than those who are not depressed (N Frasure-Smith et al, JAMA 1993; 1819-1825). There is therefore a particular need for effective treatments for depression which may be applied in particular to people with cardiovascular problems. Web site: http://www.delphion.com/details?pn=US06191133__ x

Treatment of depression with kappa receptor antagonists Inventor(s): Carlezon, Jr.; William A. (Belmont, MA) Assignee(s): The McLean Hospital Corporation (Belmont, MA) Patent Number: 6,528,518 Date filed: December 20, 2001 Abstract: The invention features the treatment of depression using kappa opioid receptor antagonists. Excerpt(s): The mesolimbic dopamine system, which originates in the ventral tegmental area and projects to the nucleus accumbens (NAc), is involved in the pleasurable (hedonic) and rewarding effects of a variety of substrates, including drugs of abuse, food, and sexual behavior. Drugs of abuse cause complex neuroadaptations in this system, some of which are associated with altered drug sensitivity. One neuroadaptation involves cAMP response element-binding protein (CREB), a transcription factor that is activated in striatal regions by psychostimulants. CREB in the NAc appears to regulate the rewarding and aversive effects of cocaine. Stimulation of cAMP-dependent protein kinase A (PKA), which activates CREB, in the NAc decreases cocaine reward. Similarly, elevation of CREB expression in the NAc decreases cocaine reward and makes low doses of the drug aversive. Conversely, blockade of PKA activity or overexpression of a dominant-negative CREB, which functions as a CREB antagonist, in the NAc increase cocaine reward. These findings suggest that CREB activation in the NAc counteracts drug reward and increases drug aversion. Cocaine alters neuronal excitability and neurotransmitter levels in the brain, particularly the mesolimbic dopamine system. Cocaine withdrawal is accompanied by signs of depression and other mood disorders in humans. The biological basis of mood disorders like depression is not understood, but may be caused by genetic and environmental factors. Physically and emotionally stressful events can also influence the etiology of depression, possibly causing subtle brain changes and alterations in gene expression. Thus, depression may have an important acquired component, caused by neuroadaptations in response to environment and experience. The therapeutic actions of antidepressants appear to involve neuroadaptations. Most antidepressant treatments (including tricyclic and atypical antidepressants, selective serotonin reuptake inhibitors, electroconvulsive therapy) have common actions on components of the cAMP pathway. Common actions include activation of PKA and the transcription factor CREB in the hippocampus, a brain region associated with emotion. CREB plays a critical role in the expression of numerous genes. Understanding causal relations among CREB function, gene expression, and the therapeutic effects of antidepressants might provide explanations for why antidepressants require sustained treatment for effectiveness. Additionally, because some genes regulated by CREB may be therapeutic while others may be

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pathophysiological, a more general understanding of the role CREB in behavior might help to elucidate the biological basis of depressive syndromes. Web site: http://www.delphion.com/details?pn=US06528518__ x

Treatment of mental conditions including depression Inventor(s): Renshaw; Perry F. (Arlington, MA) Assignee(s): The McLean Hospital Corporation (Belmont, MA) Patent Number: 6,258,794 Date filed: October 17, 2000 Abstract: The invention provides methods of treating a patient suffering from depression by increasing circulating adenosine levels in the patient. The invention also features diagnostic methods for depression which involve measuring purine or NTP resonance intensity. Excerpt(s): Major depression has been associated with both global and regional decreases in cerebral blood flow and glucose metabolism, assessed using emission tomography methods (reviewed in 1). In parallel, single voxel phosphorus-31 MRS has been used to document decreased levels of beta and total NTP in the basal ganglia (2; 16% and -6%) and the bilateral frontal lobes (3; -17% and -8%). Although these results are somewhat surprising, they are consistent with observations obtained from the cerebral cortex of polysubstance abusers (5; -10% and -7%) and decline in beta NTP in the basal ganglia of schizophrenics (4; -11%), disorders which have also been associated with sustained cerebral hypometabolism. Over the last several years, van Zijl and colleagues (6,7,8) have clearly demonstrated that a.sup.1 H MRS resonance which arises from purines may be detected in the range 7.8-8.8 PPM using short echo times. This resonance arises primarily from adenosine phosphates, with a smaller contribution from NAA at 7.8-8.0 PPM. We have reanalyzed the low field purine resonance in short echo time STEAM spectra acquired from the basal ganglia of depressed and healthy subjects (9). As a subset of these subjects also participated in a.sup.31 P MRS study (2), the relationship between the.sup.1 H MRS purine-resonance and the.sup.31 PNTP resonance was assessed. Finally, as all of the depressed study subjects were enrolled in a standardized clinical trial,.sup.1 H MRS purine measures were correlated with the clinical response to treatment. Web site: http://www.delphion.com/details?pn=US06258794__

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Use of (+)-.alpha.-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl) piperidinemethanol in treating depressive disorders and bipolar disorders

ethyl]-4-

Inventor(s): Mondadori; Cesare (Basking Ridge, NJ) Assignee(s): Aventis Pharmaceuticals Inc. (Bridgewater, NJ) Patent Number: 6,380,216 Date filed: October 30, 2000 Abstract: The present invention is directed to the use of (+)-.alpha.-(2,3dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine methanol in treating Depressive Disorders and Bipolar Disorders.

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Excerpt(s): The present invention is directed to the use of compound (+)-.alpha.-(2,3dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidine methanol or its pharmaceutically acceptable acid addition salts in a method of treating Depressive Disorders and Bipolar Disorders in patients in need of such therapy. The compound (+)isomer of.alpha.-(2,3-dimethoxyphenyl)-1-[2-(4-fluorophenyl)ethyl]-4-piperidinemeth anol is generically described by U.S. Pat. No. 5,169,096 and specifically described in U.S. Pat. No. 5,134,149, both of which are hereby incorporated by reference. This compound is described therein as a 5HT.sub.2A receptor antagonist. It has since been discovered that this compound is useful in the treatment of Depressive Disorders and Bipolar Disorders. The compound of the present invention solves the complicated problem of treating patients for Depression Disorders of Bipolar Disorders through an unusual compound profile. It is a highly selective 5HT.sub.2A receptor antagonist having subnanomolar affinity for the 5HT.sub.2A receptor versus affinities of greater than 100 nM for the 5HT.sub.2C, D.sub.1 (dopamine), D.sub.2 (dopamine), and.alpha.-1 receptors in in vitro models. Web site: http://www.delphion.com/details?pn=US06380216__ x

Use of NK-1 receptor antagonists for treating major depressive disorders Inventor(s): Baker; Raymond (Dursley, GB), Curtis; Neil Roy (Puckeridge, GB), Elliott; Jason Matthew (Felsted, GB), Harrison; Timothy (Great Dunmow, GB), Hollingworth; Gregory John (Basildon, GB), Jackson; Philip Stephen (Harlow, GB), Kulagowski; Janusz Jozef (Sawbridgeworth, GB), Rupniak; Nadia Melanie (Bishops Stortford, GB), Seward; Eileen May (Bishops Stortford, GB), Swain; Christopher John (Duxford, GB), Williams; Brian John (Great Dunmow, GB) Assignee(s): Merck Sharp & Dohme Limited (Hoddesdon) Patent Number: 6,613,765 Date filed: June 11, 1998 Abstract: The present invention provides methods for the treatment of major depressive disorders comprising oral administration of an orally active, long acting, CNS-penetrant NK-1 receptor antagonist and pharmaceutical compositions comprising such a NK-1 receptor antagonist. Excerpt(s): This invention relates to the treatment or prevention of certain depressive disorders by the administration of a specific class of NK-1 receptor antagonists. A major depressive episode has been defined as being a period of at least two weeks during which, for most of the day and nearly every day, there is either depressed mood or the loss of interest or pleasure in all, or nearly all activities. The individual may also experience changes in appetite or weight, sleep and psychomotor activity; descreased energy; feelings of worthlessness or guilt; difficulty thinking, concentrating or making decisions; and recurrent thoughts of death or suicidal ideation, plans or attempts. One or more major depressive episodes may give rise to a diagnosis of major depressive disorder (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, American Psychiatric Association, 1994). Treatment regimens commonly include the use of tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), some psychotropic drugs, lithium carbonate, and electroconvulsive therapy (ECT) (see R. J. Baldessarini in Goodman & Gilman's The Pharmacological Basis of Therapeutics, 9th Edition, Chapter 19, McGraw-Hill, 1996 for a review). More recently, new classes of antidepressant drugs are being developed including selective serotonin reuptake

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inhibitors (SSRIs), specific monoamine reuptake inhibitors and 5-HT.sub.1A receptor agonists and antagonists. Web site: http://www.delphion.com/details?pn=US06613765__

Patent Applications on Depressive Disorders As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to depressive disorders: x

3-Imino-2-indolones for the treatement of depression and/or anxiety Inventor(s): Konkel, Michael; (Garfield, NJ), Talisman, Jamie; (New York, NY), Wetzel, John M.; (Fairlawn, NJ) Correspondence: John P. White; Cooper & Dunham Llp; 1185 Avenue OF The Americas; New York; NY; 10036; US Patent Application Number: 20040082615 Date filed: August 7, 2003 Abstract: This invention is directed to indolone derivatives which are selective antagonists for the GalR3 receptor. The invention provides a pharmaceutical composition comprising a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a pharmaceutical composition made by combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention further provides a process for making a pharmaceutical composition comprising combining a therapeutically effective amount of a compound of the invention and a pharmaceutically acceptable carrier. This invention also provides a method of treating a subject suffering from depression and/or anxiety which comprises administering to the subject an amount of a compound of the invention effective to treat the subject's depression and/or anxiety. This invention also provides a method of treating depression and/or anxiety in a subject which comprises administering to the subject a composition comprising a pharmaceutically acceptable carrier and a therapeutically effective amount of a GalR3 receptor antagonist. Excerpt(s): Throughout this application, various publications are referenced in parentheses by author and year. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entireties are hereby incorporated by reference into this application to describe more fully the art to which this invention pertains. Depression is the most common of mental disorders and yet is often underdiagnosed and undertreated, inflicting substantial morbidity and psychosocial impairment on its sufferers. Depression is mainly characterized by sadness, flatness, loss of feeling, anhedonia (lack of pleasure), tearfulness, agitation or retardation, thoughts of guilt and worthlessness; in severe cases, suicide, hallucinations and delusions. Depression can be mainly categorized into bipolar disorders, identifying wide swings of mood; major depressive illness, marked by severe depressive symptoms but without manic swings; and less

9

This has been a common practice outside the United States prior to December 2000.

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defined milder forms of bipolar disorder and major depression that fall short of the specific diagnostic criteria, e.g. dysthymic disorder (formerly called depressive neurosis). The symptomatology and diagnostic criteria for depression are set out in the Diagnostic and Statistical Manual of Mental Disorders, 4.sup.th edition. Although many patients have single episodes of major depressive illness, the condition also can be repetitive, and this recurrent condition is frequently called unipolar depressive illness. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women Inventor(s): Comings, David E.; (Duarte, CA), MacMurray, James P.; (Loma Linda, CA) Correspondence: Rothwell, Figg, Ernst & Manbeck, P.C.; 1425 K Street, N.W.; Suite 800; Washington; DC; 20005; US Patent Application Number: 20030087267 Date filed: June 11, 2002 Abstract: The present invention relates to the observation that women having an A.fwdarw.T 1890 polymorphism in the 3' UTR of the cholinergic muscarinic receptor 2 (CHRM2) gene have an increased risk for developing major depression. The present invention provides diagnostic, screening and therapeutic methods based on that observation. Excerpt(s): The present application is related to U.S. provisional application Ser. No. 60/298,108 filed Jun. 15, 2001, incorporated herein by reference. Not applicable. The present invention relates to screening patients to determine their risk for having major depression. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Carnitine in the treatment of depression Inventor(s): Gershon, Samuel; (Fox Chapel, PA), Pettegrew, Jay W.; (Pittsburgh, PA) Correspondence: Nixon & Vanderhye, PC; 1100 N Glebe Road; 8th Floor; Arlington; VA; 22201-4714; US Patent Application Number: 20040009926 Date filed: February 7, 2003 Abstract: Geriatric depression is treated with L-carnitine or an alkanoyl L-carnitine, desirably acetyl L-carnitine thereby avoiding unwanted side-effects exhibited by conventional antidepressant agents. Excerpt(s): This application claims benefit under 35 U.S.C.sctn.119(e) of Provisional Application Serial No. 60/354,323 filed Feb. 7, 2002. This invention relates to the treatment of depression, particularly geriatric subjects. The clinical response to antidepressant treatment in later life follows a variable temporal response, with a median time to remission of 12 weeks. Newer antidepressants still demonstrate a disturbing side-effect profile in this fragile patient population. Thus, there is a need for the development of newer antidepressants. One such candidate is acetyl-L-carnitine, a molecule that is naturally present in human brain demonstrating only few side effects.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Combination therapy for treatment of refractory depression Inventor(s): Tollefson, Gary Dennis; (Indianapolis, IN) Correspondence: Eli Lilly And Company; Patent Division; P.O. Box 6288; Indianapolis; IN; 46206-6288; US Patent Application Number: 20030212060 Date filed: May 10, 2002 Abstract: The invention provides methods and ocmpositions for the treatment of depressive states refractory to treatment with traditional anti-depressive therapies alone. These methods and compositions employ a compound having activity as an atypical antipsychotic and a serotonin reuptake inhibitor. This invention also provides methods of providing rapid onset treatments of major depression which employing a compound having activity as an atypical antipsychotic and a serotonin reuptake inhibitor. Excerpt(s): The present invention belongs to the fields of pharmacology, medicine and medicinal chemistry, and provides methods and compositions for treating refractory depression or partial responders. Depression in its many variations has recently become much more visible to the general public than it has previously been. It is now recognized as an extremely damaging disorder, and one that afflicts a surprisingly large fraction of the population. Suicide is the most extreme symptom of depression, but millions of people, not quite so drastically afflicted, live in misery and partial or complete uselessness, and afflict their families as well by their affliction. The introduction of fluoxetine, a serotonin reuptake inhibitor (SRI), was a breakthrough in the treatment of depression, and depressives are now much more likely to be diagnosed and treated than they were only a decade ago. Depression is often associated with other diseases and conditions, or caused by such other conditions. For example, it is associated with Parkinson's disease; with HIV infection; with Alzheimer's disease; and with abuse of anabolic steroids. Depression may also be associated with abuse of any substance, or may be associated with behavioral problems resulting from or occurring in combination with head injuries, mental retardation or stroke. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Depression cap for a bottle Inventor(s): Chen, Jen-Fu; (Feng yuan City, TW) Correspondence: Rosenberg, Klein & Lee; 3458 Ellicott Center Drive-Suite 101; Ellicott City; MD; 21043; US Patent Application Number: 20030047219 Date filed: August 28, 2001 Abstract: A depression cap comprises a first end and a second end, the second end having a compartment defined therein for engaging with a nose of a bottle. An air pump is provided for drawing air out of the bottle. A pressure-activated switch is provided for controlling on/off of the air pump. The pressure-activated switch is capable of detecting an internal pressure in the bottle. The air pump is turned on when the internal pressure

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is higher than a predetermined first pressure value. The air pump is turned off when the internal pressure is lower than a predetermined second pressure value that is smaller than the predetermined first pressure value. Excerpt(s): The present invention relates to a depression cap for a bottle such as a wine bottle, the depression cap being capable of maintaining the internal pressure of the bottle under a predetermined value. In particular, the present invention relates to a depression cap that is mounted to a bottle and equipped with an air pump that can be activated when the internal pressure in the bottle is below a predetermined value. It has been found that a little wine may help with the blood circulation of human being and it is common to use the original cap or cork to reseal the wine bottle that still has wine left inside. However, the sealing effect of the cap or cork was found unsatisfactory such that air leaks into the bottle and causes deterioration of the wine. In addition, the cork might be expelled from the bottle when the interior pressure in the bottle exceeds a certain value. It is a primary object of the present invention to provide a depression cap that may automatically draw air out of a bottle after the depression cap is mounted to the bottle. The internal pressure of the bottle is reduced to a predetermined value. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Depression switch and multidirectional input device Inventor(s): Kitagawa, Tsuyoshi; (Osaka, JP) Correspondence: Armstrong, Kratz, Quintos, Hanson & Brooks, Llp; 1725 K Street, NW; Suite 1000; Washington; DC; 20006; US Patent Application Number: 20040040826 Date filed: August 20, 2003 Abstract: To obtain a comfortable feeling of click at the time of depression operation and to provide a depression switch and a multidirectional input device with excellent operability.A depression switch 700 in a multidirectional input device A comprises a key top 710 which is provided below an operating member 400 so as to penetrate a bottom plate portion 211 of a lower case 220 and to be movable in a vertical direction, an elastically deformable dome-shaped movable contact piece 720 abutting the key top 710 moved downward, one fixed electrode 731 provided below an end portion 721 of the movable contact piece 720 on a substrate 100, the other fixed electrode 732 provided at the position of contacting a central portion 722 of the elastically deformed movable contact piece 720 on the substrate 100 and a spacer 740 for electrically connecting the end portion 721 of the movable contact piece 720 to the one fixed electrode 731. Excerpt(s): The present invention relates to a depression switch which inputs various types of signals by being depressed and a multidirectional input device. The depression switch conventionally includes a key top which is provided below the operating member so as to penetrate a bottom plate portion of the case and to be movable in a vertical direction, a dome-shaped movable contact piece which is placed below the key top and is elastically deformed when being depressed by the key top descending in accordance with the depression operation of the operating member and a fixed electrode which is a contact piece formed on the substrate and in which an end portion of the movable contact piece is fixed and the central portion of the elastically deformed movable contact piece contact (see Patent Publication 1). In accordance with the depression switch, the end portion of the movable contact piece is directly fixed to the fixed electrode, and thus a stroke for the movable contact piece to be elastically

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deformed cannot be made long. For this reason, the depression switch has drawbacks such as uncomfortable feeling of click and thus inferior operability of depression operation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Drug combination for the treatment of depression and related disorders comprising mirtazapine Inventor(s): Andrews, John Stuart; (Dorpstraat Schilde, BE), Drinkenburg, Wilhelmus; (Molenschot, NL), Ward, Nicholas Matthew; (Scotland, GB) Correspondence: William M Blackstone; Akzo Nobel; Patent Department Intervet Inc; 405 State Street; Millsboro; DE; 19966; US Patent Application Number: 20030105083 Date filed: October 8, 2002 Abstract: The invention relates to a combination comprising an amount of mirtazapine, or a pharmaceutically acceptable salt or solvate thereof, and an amount of gepirone, or a pharmaceutically acceptable salt or solvate thereof, optionally in association with one or more pharmaceutically acceptable carriers, whereby the amount of gepirone and the amount of mirtazapine are such that the effect of the composition is more favourable than the added effects of the amounts of each drug separately. This combination can be used in the treatment of depression and related disorders, whereby the invention also provides for a new method of treatment of depression and related disorders. Excerpt(s): The invention relates to a combination comprising mirtazapine, to a package containing dosage units comprising mirtazapine, and to a method of treatment of depression and related disorders. Disorders of the central nervous system, such as depression and anxiety are illnesses that affect people of all ages. Although there are many effective drugs available for treatment of these diseases, the currently available methods of treatment are often still not adequate. Most noteworthy is that there are no positive treatment results in about one third of all subjects with depression or anxiety and recovery in the effectively treated group is slow, with an onset of effect at the earliest two weeks after the start of drug treatment. Mirtazapine (Org 3770; disclosed in U.S. Pat. No. 4,062,848), or the newly introduced drug gepirone (disclosed in U.S. Pat. No. 4,423,049), are examples of modern drugs for the treatments of depression and anxiety with favourable side effect profiles and very low risks for a lethal overdose. For more effective treatment there is hope that the different mechanisms of action of drugs enables complementary use, in the sense that patients not responding to one drug, may turn out to be responsive to another drug. Sometimes, drugs with the same therapeutic indication are prescribed as combination therapy in order to profit from such a mutually supplementary effect although it is generally not recommended to combine antidepressant drugs in view of risks for cumulative side effects or synergistic toxic interactions (Schweitzer and Tuckwell, in Drug Safety, Vol. 19, pp 455-464, 1998). Usually, if a seemingly positive effect of a known drug combination occurs in an individual patient, the positive effect is due to only one of the drugs in the combination. More desirable is a truly synergistic effect of two drugs with the same indication, in the sense that the effect of the combination is superior over an additive effect of the effects of both drugs in an individual patient. There are only very few synergistic therapeutic drug interactions known which have found acceptance in the area of treatment of central nervous system diseases. Most information is available on so-called augmentation therapy of treatment resistant depression by addition of lithium to anti-

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depressant drugs. The use of such a combination is viewed with caution in view of the side effects of lithium (Hardy et al., Journal Clin. Psychopharmacology, vol. 17, pp 2226, 1997). The results of a combination of lithium with mirtazapine has been disclosed with favourable results, but the augmentation is not so strong that this combination would be selected as first choice treatment of depressive disorders (Bruijn et al., Journal Clin. Psychiatry, Vol. 59, pp 657-663, 1998). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Inflectional therapy for mental depression and anxiety Inventor(s): Cobble, Daniel L.; (Louisville, KY) Correspondence: Daniel L. Cobble; STE. 12; 3401 Lesway CT.; Louisville; KY; 40220; US Patent Application Number: 20030208243 Date filed: May 1, 2002 Abstract: A therapeutic process, called inflectional therapy, is essentially a single-person process for diminishing the mental ailments of depression and anxiety. As the sufferer, being said single person, experiences such an ailment, [she]/he commences to record his thoughts and feelings by verbal expression onto a recording medium, such as an audio tape recorder. This is called a session, and the ensuing recording is called a recorded session. Typically, multiple sessions comprise adequate therapy for depression, but a single session usually diminishes a bout of anxiety. In circumstances where the sufferer does not have ready access to his recorder at the time of the ailment, he may commence recording his thoughts and feelings of the "prior" ailment when he eventually has access. Also, the sufferer may include positive, verbal expressions of encouragement during a session. A person may even record those thoughts and feelings when he is not undergoing a current ailment, such as inflecting upon happiness and other positive thoughts, or aspects of a personality disorder. Then, as desired, he listens to the recorded sessions for examining his ailment from the objective, recorded format, for the self-observation that leads to self-objectivity. But more significant, therapeutic value lies in the act(s) of expressing one's thoughts and feelings within the session(s) through the mental "focal point" of the recording medium.--For these matters, inflectional therapy may be utilized in institutional environments, such as hospitals, businesses, the military, etc., to treat patients, and to calm personnel during situations of conflict. Excerpt(s): The present invention comprises a process of "self-therapy" for diminishing mental depression and anxiety. For this specification, mental depression is defined as debilitating psychological orientation, trauma, and mental abuse that leads respectively to feelings of low self-esteem, disillusionment, fear, and feelings of inadequacy. The present invention may also be appropriate for conditions of mental depression as may be caused by chemical imbalance or bi-polar disorders. Also for this specification, anxiety is defined as varying degrees of emotional disturbance arising from one's environment, or, one's internally mental tension brought on by stress. Causes of anxiety include insomnia, despair, grief, distress, sadness, anguish, anger, fear, rejection, embarrassment, and worry. For centuries, sufferers of depression and anxiety have agonized over the problems of receiving adequate therapy that would provide suitable relief Of course, the ideal situation would be a cure. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Key depression detection apparatus for keyboard instrument Inventor(s): Sato, Shigeaki; (Hamamatsu-shi, JP) Correspondence: Dickstein Shapiro Morin & Oshinsky Llp; 1177 Avenue OF The Americas (6th Avenue); 41 ST FL.; New York; NY; 10036-2714; US Patent Application Number: 20030202834 Date filed: February 26, 2003 Abstract: A key depression detection apparatus is constituted by a sensor case incorporating key sensors, which can be easily adjusted in positions relative to an arrangement of keys on a keyboard frame (or a keybed) in a keyboard instrument such as a piano. The sensor case has a case body incorporating a key sensor and is affixed to a base member that is fixed to the keyboard frame by using a fixing member, which is constituted by a lower member and a pair of upper members. The legs of the case body are securely held by the fixing member between the lower member and upper members, which are connected together using screws accompanied with springs. Thus, an operator can easily adjust the sensor case in position relative to an arrangement of keys by manually controlling screws. Excerpt(s): This invention relates to key depression detection apparatuses that detect depressing operations of keys (or key depressions) in keyboard instruments such as acoustic pianos and electronic keyboard instruments. In acoustic pianos, vibrations of strings are transmitted to soundboards to cause sound radiation (or emission). Pianos having silencing functions use sensors for detecting operations of keys and operations of hammers interlocked with keys, based on which musical tone signals are correspondingly produced. Operators (e.g., users and players) may use headphone sets to listen to musical tones corresponding to amplified musical tone signals, so that they can enjoy playing pianos and the like without disturbing their neighborhoods. Acoustic pianos may include grand pianos, upright pianos, and the like. In the case of a grand piano, for example, three strings are stretched under tension and tuned with respect to each of middle pitch sounds and high pitch sounds, so that the three strings are simultaneously struck by a single hammer upon depression of a key. When an operator depresses a soft pedal, an action (or a keyboard assembly) interlocked with a key is slightly shifted in position in a key arrangement direction (i.e., a horizontal direction or operator's left-hand-right-hand direction), so that a hammer strikes only two strings among three strings to lessen tone volume. The action is supported on a keybed by means of a keyboard frame, which is one type of a key frame for mounting the action interlocked with the key and which performs reciprocating motion being interlocked with the soft pedal in the key arrangement direction. In order to smoothly perform such operation, the aforementioned keyboard frame has a specific structure using a frame member extending in a direction perpendicular to the key arrangement direction. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Materials and methods for the treatment of depression Inventor(s): Druzgala, Pascal; (Santa Rosa, CA) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030078284 Date filed: October 18, 2002

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Abstract: The subject invention provides compounds which are easily metabolized by the metobolic drug detoxification systems. Particularly, fluvoxamine analogs which have been designed to include esters within the structure of the compounds are taught. Also provided are methods of treating depression and affective disorders, such as obsessive compulsive disorder. Pharmaceutical compositions of the fluvoxamine analogs are also taught. Excerpt(s): This application is a continuation of U.S. Ser. No. 09/841,749, filed Apr. 24, 2001; which claims priority from provisional patent application U.S. Ser. No. 60/199,343, filed Apr. 24, 2000. Major depression represents one of the most common mental illness, affecting between 5- 10% of the population. The disease is characterized by extreme changes in mood which may also be associated with psychoses. It has generally been found that most antidepressant agents exert significant effects on the regulation of monoamine neurotransmitters, including serotonin. A number of types of antidepressants have been developed in recent years. Many of these compounds regulate serotonin (5-hydroxytryptamine; 5-HT). Trazodone controls the actions of 5-HT while fluoxetine is a potent and selective inhibitor of 5-HT reuptake. 3Chloroimipramine which inhibits both 5-HT and norepinephrine reuptake has been extensively used as an antidepressant in Europe and Canada. Other compounds which are of current interest or have been examined as antidepressants include fluvoxamine, citalopram, zimeldine, sertraline, bupropion and nomifensine. Fluvoxamine facilitates serotoninergic neurotransmission via potent and selective inhibition of scrotonin reuptake into presynaptic neurons. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Medicament for combating respiratory depression Inventor(s): Chizh, Boris; (Cambridge, GB), Christoph, Thomas; (Aachen, DE), Zimmer, Oswald; (Wuerselen, DE) Correspondence: Perman & Green; 425 Post Road; Fairfield; CT; 06824; US Patent Application Number: 20030130203 Date filed: November 21, 2002 Abstract: The invention relates to the use of at least one compound of general formula (I) and/or one of its diastereomers and/or one of its enantiomers and/or one of the corresponding physiologically compatible salts for producing a medicament for combating respiratory depression, with the exception of medicaments for combating respiratory depression as a cause of sleep apnea. Excerpt(s): The present invention relates to the use of at least one compound of general formula I and/or one of its diastereoisomers and/or one of its enantiomers and/or one of the corresponding physiologically acceptable salts for the preparation of a medicament for combating respiratory depression, with the exception of medicaments for combating respiratory depression as a cause of sleep apnoea. The occurrence of respiratory depression, e.g. when administering compounds with opioid activity, in states of shock, when administering psychotropic drugs or in cases of central respiratory regulation disorders, is a situation which arises relatively frequently in clinical practice and is not uncommonly life-threatening for the patient. There is therefore a worldwide need for effective therapies for combating respiratory depression, as documented in the large number of scientific papers which have recently appeared in this field from the sectors of both clinical practice and fundamental research. The object of the invention

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was therefore to provide medicaments suitable for combating respiratory depression, especially for combating respiratory depression when administering compounds with opioid activity, in states of shock, when administering psychotropic drugs or in cases of central respiratory regulation disorders. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Metal object forming method utilizing freezing point depression of molten metal Inventor(s): Aso, Noriyasu; (Kawasaki-shi, JP), Ishiduka, Masanobu; (Kawasaki-shi, JP), Kimura, Koichi; (Kawasaki-shi, JP), Nishii, Kouta; (Kawasaki-shi, JP) Correspondence: Armstrong,westerman & Hattori, Llp; 1725 K Street, NW.; Suite 1000; Washington; DC; 20006; US Patent Application Number: 20030034145 Date filed: August 2, 2002 Abstract: A metal object forming method includes a preliminary step and a metalinjecting step. At the preliminary step, flowability-improving material is put in a molding die. Then, at the metal-injecting step, molten metal is poured into the die for producing a casting. Due to the high temperature of the molten metal, the flowabilityimproving material melts into the molten metal, to cause the freezing point depression of the molten metal. Excerpt(s): The present invention relates to a metal object forming method which is advantageously used for producing a metal housing of portable electronic devices such as notebook computers and cell phones. The present invention also relates to a metal housing produced by the method. In portable electronic devices including notebook computers, cell phones, etc., the housing is often made of light metal (e.g., magnesium alloy or aluminum alloy) for attaining weight reduction and good heat dissipation. Such a metal housing, which often includes thin walls and complex shapes, can be produced by a die-casting technique. As is known, in die-casting, use is made of dies, or molds, that are designed to define a cavity corresponding to the desired shape. Molten metal is injected into the die cavity, in which the supplied metal hardens. Then, the die is opened, and the finished casting is ejected. A die-casting technique is disclosed in JP-A9(1997)-272945, for example. The conventional die-casting technique has found disadvantageous in the following respects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Method for constructing a membrane probe using a depression Inventor(s): Bayne, Michael A.; (Beaverton, OR), Gleason, Reed; (Portland, OR), Smith, Kenneth; (Portland, OR) Correspondence: Kevin L. Russell; Suite 1600; 601 SW Second AVE.; Portland; OR; 97204-3157; US Patent Application Number: 20030192183 Date filed: April 16, 2003 Abstract: A substrate, preferably constructed of a ductile material and a tool having the desired shape of the resulting device for contacting contact pads on a test device is brought into contact with the substrate. The tool is preferably constructed of a material

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that is harder than the substrate so that a depression can be readily made therein. A dielectric (insulative) layer, that is preferably patterned, is supported by the substrate. A conductive material is located within the depressions and then preferably lapped to remove excess from the top surface of the dielectric layer and to provide a flat overall surface. A trace is patterned on the dielectric layer and the conductive material. A polyimide layer is then preferably patterned over the entire surface. The substrate is then removed by any suitable process. Excerpt(s): The present invention relates to probe assemblies of the type commonly used for testing integrated circuits (IC) and, in particular, the present invention relates to a membrane probing assembly having contacts which scrub, in a locally controlled manner, across the respective input/output conductors of each device so as to reliably wipe clear the surface oxides that are normally found on those conductors thereby ensuring good electrical connection between the probing assembly and each device. The trend in electronic production has been toward increasingly smaller geometries particularly in integrated circuit technology wherein a very large number of discrete circuit elements are fabricated on a single substrate or "wafer." After fabrication, this wafer is divided into a number of rectangular-shaped chips or "dice" where each die presents a rectangular or other regular arrangement of metallized contact pads through which input/output connections are made. Although each die is eventually packaged separately, for efficiency sake, testing of the circuit formed on each die is preferably performed while the dies are still joined together on the wafer. One typical procedure is to support the wafer on a flat stage or "chuck" and to move the wafer in X, Y and Z directions relative to the head of the probing assembly so that the contacts on the probing assembly move from die to die for consecutive engagement with each die. Respective signal, power and ground lines are run to the probing assembly from the test instrumentation thus enabling each circuit to be sequentially connected to the test instrumentation. The problem with this type of probing assembly is that the needle-like tips, due to their narrow geometry, exhibit high inductance so that signal distortion is large in high frequency measurements made through these tips. Also, these tips can act in the manner of a planing tool as they wipe across their respective pads, thereby leading to excessive pad damage. This problem is magnified to the extent that the probe tips bend out of shape during use or otherwise fail to terminate in a common plane which causes the more forward ones of the tips to bear down too heavily on their respective pads. Also, it is impractical to mount these tips at less than 100 micron centerto-center spacing or in a multi-row grid-like pattern so as to accommodate the pad arrangement of more modern, higher density dies. Also, this type of probing assembly has a scrub length of the needle tips of 25 microns or more, which increases the difficulty of staying within the allowed probing area. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Method for the targeted treatment of depression Inventor(s): Metzner, Richard J.; (Sedona, AZ) Correspondence: Christie, Parker & Hale, Llp; P.O. Box 7068; Pasadena; CA; 91109-7068; US Patent Application Number: 20040015055 Date filed: July 19, 2002 Abstract: A method for determining the appropriate medication for a patient suffering from depression. A patient will take a questionnaire wherein the patient answers a

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number of questions with scaled responses concerning the degree to which the patient's mental state is affected by at least one or both of impaired modulation and impaired activation. Next, the patient's answers will be processed to arrive at scores for the at least one impaired modulation and impaired activation. Depending upon the patient's scores for demodulation and deactivation, at least one medication which affects the at least one impaired modulation and impaired activation is recommended. Excerpt(s): The invention relates to clinical depression, the leading cause of medical disability in the world, and more specifically to a method for determining what antidepressant regimen is best suited for a patient with depression. Presently, there are few guidelines for determining the appropriate agents to use in treating depressed patients. Traditional thinking holds that all antidepressants are the same except for sideeffects. This assumption is based on the fact that all antidepressants show approximately the same level of effectiveness (50-70%) in studies on undifferentiated depressed populations. However, recent investigations which differentiate between subtypes of depression indicate that matching antidepressants with specific subtypes can improve results. Unfortunately, none of the depression assessment tools currently available identify these subtypes (e.g., DSM-IV-TR, Hamilton, Beck, Montgomery-Asberg, Zung). Thus, many health professionals seeing such patients fail to make the proper diagnosis and, when they attempt to treat may not always use medications optimally. There accordingly remains a need for an improved method that permits even inexperienced providers to quickly, easily, inexpensively, and accurately determine which type of depression is present (e.g. whether the depression is primarily characterized by (1) impaired CNS modulation, with typical symptoms of anxiety, irritability, hostility, impulsivity, agitation, hypochondriasis, or suicidality; (2) impaired activation, with common symptoms of fatigue, apathy, anhedonia, hypersomnia, lack of initiative, inability to concentrate, and decreased productivity, or (3) a combination of both types) and to prescribe the treatment regimen that is most likely to lead to clinical improvement. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Method for treating depression Inventor(s): Oxenkrug, Gregory; (Newton, MA) Correspondence: Nixon Peabody Llp; Attention: David Resnick; 101 Federal Street; Boston; MA; 02110; US Patent Application Number: 20030176488 Date filed: March 18, 2003 Abstract: The present invention relates to a method and composition for the treatment of depression in a human being identified as having depression. This method comprises the administration of a therapeutically effective depression treatment amount of M-3 agonists, 5-MCA-NAT or an analog, to a human being identified as having depression. The 5-MCA-NAT and its analogs may be administered alone or in combination with other agents, e.g. Ca.sup.++ antagonists. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/559,609 filed on Apr. 27, 2000, the content of which is relied upon and incorporated by reference in its entirety, and benefit of priority under 35 USC.sctn. 120 in hereby claimed, which claims the benefit of U.S. Provisional Application No. 60/134,573 filed May 17, 1999. The present invention relates to the method of treatment of depression in

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a human being identified as having depression. This method comprises the administration of a therapeutically effective depression treatment amount of agonists of melatonin-type 3 receptors (MT-3); 5 MCA-NAT and its analogs. MT-3 agonists may be administered alone or in combination with other agents, e.g. Ca.sup.++ antagonists. Depression is a difficult mental disorder to treat. Patients having such a disorder are often reluctant to seek the medical attention necessary to diagnose the disorder. Such reluctance is often related to the patient's fear of the stigma associated with seeking psychiatric help or to the patient's feeling of worthlessness associated with depression. Moreover, once the patients seek competent psychiatric help, it is difficult to successfully treat the disorder through psychoanalytic approach alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Method of administering buprenorphine to treat depression Inventor(s): Kaiko, Robert F.; (Weston, CT), Sanchez, Ramiro; (Killingworth, CT) Correspondence: Darby & Darby P.C.; 805 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030181475 Date filed: March 20, 2003 Abstract: A method of treating depression using transdermal delivery of buprenorphine is described. In one embodiment, the method employs transdermal patches comprising buprenorphine, preferably escalating incrementally the buprenorphine dose to a level where one or more symptoms of depression are alleviated. The method is particularly suitable for patients suffering from refractory depression, or for patients suffering from both depression and pain. Excerpt(s): This application claims priority from U.S. Ser. No. 60/366,358, filed Mar. 20, 2002, which is hereby incorporated by reference in its entirety. The present invention contemplates a method of alleviating the symptoms of depression, particularly refractory depression, by administration of a buprenorphine in a transdermal dosage form. It is estimated that as many as one in ten Americans will suffer from depression at some point during their lifetime. The term "depression" covers a wide range of illnesses, from mild to moderate to severe, and even life-threatening forms. However, they all share common psychological, behavioral, cognitive, physical, and emotional manifestations. Differences between depression subtypes, such as those articulated in the Diagnostic and Statistical Manual of Mental Disorders, (4.sup.th Ed., Washington, D.C., American Psychiatric Association, 2000), depend upon the range of severity, frequency, and duration of these defining attributes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods and compounds for treating depression and other disorders Inventor(s): Balandrin, Manuel F.; (Sandy, UT), Moe, Scott T.; (Salt Lake City, UT), Mueller, Alan L.; (Salt Lake City, UT) Correspondence: Foley & Lardner; 402 West Broadway; 23rd Floor; San Diego; CA; 92101 Patent Application Number: 20040039014 Date filed: November 21, 2001

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Abstract: The present invention features compounds active at both the serotonin reuptake site and the N-methyl-D-aspartate (NMDA) receptor and the use of such compounds for treating different disorders. Compounds having activity at the serotonin reuptake site and the NMDA receptor ("multi-active compounds") can be used to treat different types of disorders such as depression, obsessive-compulsive disorders (OCD), sleep, disorders, sexual dysfunction, and eating disorders. Preferably, the multi-active compounds are used to treat depression. Excerpt(s): This application claims priority to U.S. provisional application serial No. 60/092,546. This invention relates to the use of compounds and pharmaceutical compositions for the treatment of depression and other disorders. More specifically, this invention relates to compounds that are active at monoamine reuptake sites, such as the serotonin reuptake site, and the NMDA receptor. The following description provides a summary of information relevant to the present invention. It is not an admission that any of the information provided herein is prior art to the presently claimed invention, nor that any of the publications specifically or implicitly referenced are prior art to the present invention. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Methods and kits for treating depression or preventing deterioration of cognitive function Inventor(s): Day, Wesley W.; (San Diego, CA), Lee, Andrew G.; (Old Lyme, CT), Petrie, Charles D.; (Cranston, RI), Thompson, David D.; (Gales Ferry, CT) Correspondence: Pfizer INC.; Patent Department, Ms8260-1611; Eastern Point Road; Groton; CT; 06340; US Patent Application Number: 20030092719 Date filed: April 24, 2002 Abstract: The present invention provides methods and kits for treating depression, perimenopausal depression, schizophrenia, anxiety, panic attacks, binge eating, social phobia, or preventing deterioration of cognitive function by administering to a patient in need thereof a therapeutically effect amount of an estrogen agonist/antagonist of formula I 1 Excerpt(s): This application claims priority of U.S. provisional application No. 60/286,433, filed Apr. 25, 2001. The present invention relates to the use of an estrogen agonist/antagonist for treating depression, perimenopausal depression, schizophrenia, anxiety, panic attacks, binge eating, social phobia, or preventing deterioration of cognitive function. Estrogen has been associated with affective disorders. Depression is an affective disorder in which a patient feels sadness of such a scope and/or duration as to be clinically distinguishable from normal sadness. Depressed patients can have an overwhelming sense of uselessness and can feel lethargic and possibly suicidal. Unlike normal depression due to causative factors such as a death or bad news, a patient with clinical depression is unable to adjust to the causative factors over time and can remain in the depressed state for long periods of time. Other types of affective disorders can occur at particular time periods in a patient's life. For example, perimenopausal depression can occur in women who are near menopause. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for improving the therapeutic response of humans having major depression and carrying the gene for apolipoprotein E4 Inventor(s): Murphy, Greer Marechal JR.; (Stanford, CA), Schatzberg, Alan F.; (Los Altos, CA) Correspondence: Intervet Inc; 405 State Street; PO Box 318; Millsboro; DE; 19966; US Patent Application Number: 20030105082 Date filed: December 3, 2001 Abstract: This invention relates to a method for improving the therapeutic response of a human patient with major depression, characterised by genotyping said patient to be a carrier of the gene for apolipoprotein E4 and adapting the further treatment of the person differentially depending on the presence or absence of the said gene in the patient. Excerpt(s): The present invention relates to methods for improving the therapeutic response of human patients with major depression, particularly those carrying the gene for apolipoprotein E4. Psychiatric diseases generally provide a unique set of complications for clinicians, patients, and care givers. Major depression, for instance, is a major health problem and poses a tremendous financial burden on society due to lost self-support of individuals suffering from depression. Such individuals are often simply unable to function in everyday life situations, in part because of feelings of extreme hopelessness and worthlessness. There is also a serious risk of suicide among such individuals. The various forms of depression are defined and are separately diagnosed according to criteria given in handbooks for psychiatry, for example in the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) published by the American Psychiatric Association, Washington, D.C. (1994). The diagnostic criteria for major depression are well known to those skilled in the art, and comprise the criteria set forth, for example, at DSM-IV 296.2 and 296.3. Major depression, defined in more detail below, is also known as major depressive disorder and is estimated to affect between 5 to 10% of the human population. Although treatments for different types of depression do exist, there is a continuous search for new methods of treatment of depression because existing methods still have disadvantages, such as the side effects of drugs, the long duration of treatments, and, more importantly, the partial efficacy (or inefficacy) of treatments. For example, there is wide variation in the response of patients with major depression to antidepressant pharmacotherapy. Some of this variation may be due to genetic differences among patients. Regardless, the result is that about 30% of patients with major depression who are treated with existing antidepressant drugs do not improve. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Methods for improving the treatment of major depression by genotyping for the gene for apolipoproteine e4 and for improving the terapeutic response of humans having major depression and carrying the gene for apolipoprotein e4 Inventor(s): Murphy, Greer M.; (Stanford, CA), Schatzberg, Alan F.; (Los Altos, CA) Correspondence: William P Ramey Iii; Akzo Nobel; PO Box 318; Millsboro; DE; 19966; US Patent Application Number: 20040106124 Date filed: February 2, 2004

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Abstract: This invention relates to methods for improving the treatment of major depression in a human patient by genotyping the patient for the gene for apolipoprotein E4 and adapting the further treatment of the patient accordingly depending on the presence or absence of the gene in the patient. The invention also relates to methods for improving the therapeutic response of human patients with major depression by determining the apolipoprotein E genotype of a human patient and administering a noradrenergic transmission enhancing anti-depressant drug, such as mirtazapine, in an amount effective to treat major depression, to those patients who are found to carry the gene for apolipoprotein E4. Also disclosed are methods for improving the therapeutic response of a human patient with major depression comprising administering mirtazapine, in an amount effective to treat major depression, to a human patient who is a carrier of the gene for apolipoprotein E4. Excerpt(s): The present invention relates to methods for improving the treatment of major depression-in a human patient by genotyping the patient for a specific gene and further relates to methods for improving the therapeutic response of human patients with major depression, particularly those carrying the gene for apolipoprotein E4. Psychiatric diseases generally provide a unique set of complications for clinicians, patients, and care givers. Major depression, for instance, is a major health problem and poses a tremendous financial burden on society due to lost self-support of individuals suffering from such depression. Such individuals are often simply unable to function in everyday life situations, in part because of feelings of extreme hopelessness and worthlessness. There is also a serious risk of suicide among such individuals. The various forms of depression are defined and are separately diagnosed according to criteria given in handbooks for psychiatry, for example in the Diagnostic and Statistical Manual of Mental Disorders 4th edition (DSM-IV) published by the American Psychiatric Association, Washington, D.C. (1994). The diagnostic criteria for major depression are well known to those skilled in the art, and comprise the criteria set forth, for example, at DSM-IV 296.2 and 296.3. Major depression, defined in more detail below, is also known as major depressive disorder and is estimated to affect between 5 to 10% of the human population. Although treatments for different types of depression do exist, there is a continuous search for new methods of treatment of depression because existing methods still have disadvantages, such as the side effects of drugs, the long duration of treatments, and, more importantly, the partial efficacy (or inefficacy) of treatments. For example, there is wide variation in the response of patients with major depression to antidepressant pharmacotherapy. Some of this variation may be due to genetic differences among patients. Regardless, the result is that about 30% of patients with major depression who are treated with existing antidepressant drugs do not improve. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Methods of treating and preventing depression using didesmethylsibutramine Inventor(s): Jerussi, Thomas P.; (Framingham, MA) Correspondence: Jones Day; 51 Louisiana Aveue, N.W; Washington; DC; 20001-2113; US Patent Application Number: 20040092481 Date filed: October 28, 2003 Abstract: Methods are disclosed for the treatment and prevention of disorders and conditions such as, but are not limited to: eating disorders; weight gain; obesity; irritable bowel syndrome; obsessive-compulsive disorders; platelet adhesion; apnea; affective

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disorders such as attention deficit disorders, depression, and anxiety; male and female sexual function disorders; restless leg syndrome; osteoarthritis; substance abuse including nicotine and cocaine addiction; narcolepsy; pain such as neuropathic pain, diabetic neuropathy, and chronic pain; migraines; cerebral function disorders; chronic disorders such as premenstrual syndrome; and incontinence.Pharmaceutical compositions and dosage forms are also disclosed which comprise a racemic or optically pure sibutramine metabolite and an optional additional pharmacologically active compound. Excerpt(s): This application is a continuation-in-part of U.S. application Ser. No. 09/662,135, filed Sep. 14, 2000, which is a continuation-in-part of U.S. application Ser. No. 09/372,158, filed Aug. 11, 1999, both of which are incorporated herein by reference in their entireties. The invention relates to methods of using and compositions comprising dopamine reuptake inhibitors such as racemic and optically pure metabolites of sibutramine, optionally in combination with other pharmacologically active compounds. Sibutramine, chemically named [N-1-[1-(4-chlorophenyl)cyclobutyl]3- -methylbutyl]-N,N-dimethylamine, is a neuronal monoamine reuptake inhibitor which was originally disclosed in U.S. Pat. Nos. 4,746,680 and 4,806,570. Sibutramine inhibits the reuptake of norepinephrine and, to a lesser extent, serotonin and dopamine. See, e.g., Buckett et al., Prog. Neuro-psychopharm. & Biol. Psychiat., 12:575-584, 1988; King et al., J. Clin. Pharm., 26:607-611 (1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Non-pharmacological method for treating depression, skin disorders, and improving overall health and wellness Inventor(s): Smith, Jack V.; (Arden, NC) Correspondence: Jack V. Smith; P.O. Box 156; Arden; NC; 28704; US Patent Application Number: 20030108618 Date filed: December 7, 2001 Abstract: The present invention is a method for manufacture and treatment of depression and health disorders using a non-pharmacologic stable negative ion solution. Excerpt(s): The present invention is a method that relates to a liquid stable solution of negative ions (to be referred to as "ions") and has been proven in research the ability to provide a non-pharmacologic therapy for the following health issues. Negative ions have been proven to have a positive affect on behavioral disorders (seasonal affective disorder (SAD)), relief of depression, relief from headaches, earaches, stuffy/snotty noses from hay-fever allergies and colds, for the treatment of asthma, bronchitis, thromboembolism, pain and peeling from sunburn and other bums, relief from itching from psoriasis, bug bites, and other skin irritations and improve memory, vitamin metabolism, sleep patterns and behavior. The ions solution can be applied directly, sprayed on, misted on skin, and can be inhaled. The ions solution can be placed in spray bottles, misters, humidifiers or other devices to disperse the solution into the air. The ions solution can also be used as a drink for internal intake. It is therefore an object of the present invention to provide a non-pharmacologic method for treating health and behavioral issues such as SAD, depression, headaches, earaches, stuffy/snotty noses from hay-fever allergies and colds, asthma, bronchitis, thromboembolism, pain and peeling from sunburn and other burns, itching form psoriasis, bug bites, and other skin

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irritations and a method for improving memory, vitamin metabolism, sleep patterns and behavior by subjecting a patient to an exposure of high density negative ions directly using a liquid stable solution of negative ions via bathing, spray or mist aerosols, humidifier, mister, inhaler, drinking or other mode of application to the skin or internally through breathing or drinking. A further object is to provide a method for the treatment of patients determined to have certain health and behavioral issues with exposure to high concentration of negative ions in a stable liquid matrix for a predetermined course of time. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Patient support device with shoulder depression device Inventor(s): Coppens, Daniel D.; (Avondale, PA), Crowell, John A.; (Wilmington, DE), Gearon, Gary; (Shohola, PA), Kirk, John Damon; (Ramsey, NJ), Rabeno, David M.; (Bear, DE), Simmons, David L.; (Ocean, NJ), Winward, Thomas R.; (New Castle, DE) Correspondence: Huntley & Associates; 1105 North Market Street; P.O. Box 948; Wilmington; DE; 19899-0948; US Patent Application Number: 20040123388 Date filed: May 30, 2003 Abstract: A patient support device with shoulder depression devices for accurately and repeatably positioning a patient on a treatment table. The patient support device includes a headrest frame and an adjustable shoulder depression device and optionally includes a torso positioning device and a buttock restraint device. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/428,029, filed Nov. 21, 2002 and U.S. Provisional Application, not yet numbered, filed Apr. 25, 2003. The present invention relates to a durable and adjustable patient support device with shoulder depression device for repeatably positioning a patient for treatment. The patient support device of the present invention has several applications where immobility of the head and neck is required and an unobstructed 360-degree treatment is desired. The present invention is uniquely adjustable and is capable of repeatably positioning a patient by immobilizing the patient's head, neck, shoulders and torso. A major application of the present invention can be for patients in treatment settings who require radiation treatment of cancer within the brain and neck. When a high energy beam is used for irradiation of the tumor, it is critical that the beam destroys the tumor but not the surrounding healthy tissue. In order to accomplish this objective with acceptable precision, it is critical that the head and neck be maintained in a precise and fixed position with no possibility of movement. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Pharmaceutical compositions for the treatment of depression or symptoms suggesting depression Inventor(s): Kovacs, Peter; (Debrecen, HU), Racz, Anna; (Budapest, HU), Varga, Csilla; (Nyiregyhaza, HU) Correspondence: The Firm OF Karl F Ross; 5676 Riverdale Avenue; PO Box 900; Riverdale (bronx); NY; 10471-0900; US Patent Application Number: 20040010021 Date filed: January 13, 2003 Abstract: The invention relates to the human therapeutic application of famotidine or its therapeutically acceptable salts for the treatment of depression or symptoms suggesting depression, including somatic depression, unipolar depression, functional diseases of psychic origin, atypical depression, dysthymia, bipolar affective disorders, seasonal depression and persistent mood disorder. The invention also relates to such application of a pharmaceutical composition and its manufacturing. Excerpt(s): The present invention relates to the administration of pharmaceutical preparations containing the active ingredient famotidine, in the treatment of depression or symptoms suggesting depression. Moreover, the invention also relates to cases with acid related diseases. It is also a widely known fact that the group of patients suffering in gastrointestinal diseases is much more prone to hazards relating to depression, in other words they often develop different forms of depression or symptoms suggesting depression (for example functional dyspepsia). These may counteract on the underlying disease, often impeding or preventing recovery. Therefore it could be desirable, if pharmaceutical preparations developed for gastrointestinal diseases also had a positive effect on complaints relating to depression, but at least they should not worsen the clinical case. Unfortunately, the applied preparations show a rather heterogeneous picture. Several publications--e.g. Hassan and Saieed (Eur. J. Pharm. Sci., 6, Suppl. 1, S88, 1998)--have dealt with the psychiatric effects of H.sub.2-receptor antagonistsie with a high sales record. The firstly developed member of the group, cimetidine, was found to have a marked depressant effect (see e.g. Mangla J. C., Clin. Res. 33., No. 2, Pt. 1, 323 A, 1985 or Rush P. J., Am. J. Med. Sci. 286, No.3, 31-34, 1983). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Remedial agent for anxiety neurosis or depression and piperazine derivative Inventor(s): Chaki, Shigeyuki; (Saitama-shi, JP), Ishii, Takaaki; (Saitama-shi, JP), Nakazato, Atsuro; (Satte-shi, JP), Ogawa, Shin-ichi; (Okegawa-shi, JP), Okubo, Taketoshi; (Asaka-shi, JP) Correspondence: Lorussso & Loud; 3137 Mount Vernon Avenue; Alexandria; VA; 22305; US Patent Application Number: 20030186992 Date filed: December 18, 2002 Abstract: There are provided a therapeutic preparation for anxiety neurosis or depression which comprises a MC.sub.4 receptor antagonist as an effective ingredient; and a piperazine derivative represented by Formula [1]: 1[wherein Ar.sup.1 is a phenyl group, a substituted phenyl group, a naphthyl group or a substituted naphthyl group; Ar.sup.2 is a naphthyl group, a substituted naphthyl group, a quinolyl group, a group

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represented by the formula: 2(wherein R.sup.4 is a hydrogen atom or a halogen atom; and X--Y is CH--NH, CH--O, CH--S or N--O) or a group represented by the formula: 3(wherein R.sup.5 is a hydrogen atom, a hydroxyl group or a C.sub.1-10 alkoxy group); R.sup.1 is a hydrogen atom, a C.sub.1-10 alkyl group, a C.sub.3-8 cycloalkyl group, a C.sub.3-10 alkenyl group, a phenyl group, a 1-cyanoethyl group, a pyrimidin-2-yl group or an amidyl group; R.sup.2 and R.sup.3 are the same or different, and are each a hydrogen atom or a C.sub.1-10 alkyl group; A-B is N--CH.sub.2, CH--CH.sub.2, C(OH)-CH.sub.2 or C.dbd.CH; T.sup.1 is a single bond, --N(R.sup.6)-- (wherein R.sup.6 is a hydrogen atom or a C.sub.1-10 alkyl group), --O--, --CH.dbd.CH-- or --C(.dbd.O)--; n is an integer of from 1 to 10 and when T.sup.1 is a single bond, --CH.dbd.CH-- or -C(.dbd.O)--, n is an integer of from 2 to 10 when T.sup.1 is --N(R.sup.6)-- or --O--], or a pharmaceutically acceptable salt thereof. Excerpt(s): The present invention relates to a therapeutic preparation for anxiety neurosis or depression which comprises a MC.sub.4 receptor antagonist as an effective ingredient, and relates to novel piperazine derivatives having a MC.sub.4 receptor antagonistic action. It is suggested by the recent progress of pathophysiology that stress is deeply pertinent to development mechanism of anxiety neurosis and depression. As an intracerebral reaction caused by stress, there has been known a functional abnormality of neuroendocrine system of which representative is the functional abnormality of hypothalamus-pituitary-ad- renal system. From such a background, the neuropeptides which locate in pituitary and affect neuroendocrine attract attention as a development reason of depression/anxiety. Among such neuropeptides are corticotropin releasing factors (CRF) and proopiomelanocortin (POMC). CRF is known to play the central role of stress reaction such as susceptibility of hypothalamuspituitary-adrenal system, and suggested to have relation to anxiety/depression. Melanocortins [adrenocorticotropic hormone (ACTH), melanocyte stimulating hormone (MSH)] produced from POMC are main neuropeptides in hypothalamus, but there is no report of the substances acting to melanocortin receptors relating to stress reaction and depression/anxiety neurosis. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Remedies for depression containing ep1 antagonist as the active ingredient Inventor(s): Maruyama, Takayuki; (Osaka, JP), Nonaka, Shigeyuki; (Osaka, JP) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue, N.W.; Suite 800; Washington; DC; 20037; US Patent Application Number: 20040082653 Date filed: September 12, 2003 Abstract: A pharmaceutical composition for the treatment and/or prevention of depression comprising a compound having an antagonistic activity for EP.sub.1 receptor which a prostaglandin E.sub.2 receptor subtype.EP.sub.1 antagonist is useful for the treatment of depression, for example, endogenous depression, reactive depression, weatherability depression, neurological depressed state, the depressed state of brain organic mental disorder. Excerpt(s): The present invention relates to a pharmaceutical composition for the treatment of depression comprising the EP.sub.1 antagonist as active ingredient. Prostaglandin E.sub.2 (PGE.sub.2) has been known as a metabolite in the arachidonic acid cascade. It has been known that PGE.sub.2 possesses cyto-protective activity, uterine contractile activity, a pain-inducing effect, a promoting effect on digestive peristalsis, an awaking effect, a suppressive effect on gastric acid secretion, hypotensive

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activity, and diuretic activity. In the recent study, it was found that PGE.sub.2 receptor was divided into some subtypes, which possesses different physical roles from each other. At present, four receptor subtypes are known and they are called EP.sub.1, EP.sub.2, EP.sub.3 and EP.sub.4 respectively [Negishi M. et al, J. Lipid Mediators Cell Signaling 12, 379-391 (1995)]. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Repair tool for depression in putting green on golf course Inventor(s): Noda, Takao; (Mishima-shi, JP) Correspondence: Wenderoth, Lind & Ponack, L.L.P.; 2033 K Street N. W.; Suite 800; Washington; DC; 20006-1021; US Patent Application Number: 20040082410 Date filed: October 20, 2003 Abstract: A repair tool for a depression formed in a putting green enables a golfer responsible for the repair of the depression to gather the earth surrounding the depression easily toward the center of the depression by using the tool just once and even enables the golfer to perform the repair while continuously standing without doing any harm to the roots of the turf grasses. In this repair tool, split projecting pieces 9 which are so disposed as to encompass the outer periphery of a depression D in a putting green and made to form inserting claw parts 10 on the lower terminal side thereof and tapered parts 11 on the outer wall side thereof are extended downward from the lower side of a grip part through a rod and the grip part is provided with a slide engaging member 14 which is vertically moved relative to the tapered parts 11 by the manipulation of the grip part. By the vertical motion of this slide engaging member 14, the inserting claw parts 10 are enabled to be moved toward and away from the central part of the depression D in the putting green. Excerpt(s): This invention relates to a repair tool for repairing a depression formed in a putting green by the use of a golf ball and more particularly to a repair tool for a depression in a putting green which repair tool enables the user thereof to repair easily the depression while continuously standing without doing any damage to the turf in a putting green. On a golf course, a golf ball shot by a golfer is fated to inflict a depression conforming with the contour of the ball on the putting green (hereinafter referred to "a depression in the putting green") and this depression in the putting green is supposed to be repaired by the player responsible for the depression during the course of the play. As the method for repairing the depression in the putting green, it has been heretofore customary for the golfer to do this repair by using the head of a hard club such as a putter or an iron or to effect the repair by manipulating a putting-green fork which is only a repair tool having a forked claw part formed at one end of a basal plate made of metal or resin. When the repair is made with the head of a hard club, it is not easily achieved by a player who is not particularly accustomed to the work, because of the contributory factor that the club is not exclusively intended for the repair work. When the repair is effected with the putting-green fork, the user encounters the trouble of having to repeat the operation of inserting the fork in the periphery of the depression and pulling the earth toward the center of the depression. This operation does not permit the golfer to perform it while continuously standing during the whole course thereof. Moreover, the player who is not accustomed to the use of this fork is liable to insert the fork obliquely and possibly scoop up the earth and consequently cut roots of turf grasses and damage the turf.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Secreted protein associated with depression, compositions and methods of use thereof Inventor(s): Allen, Keith D.; (Cary, NC), Phillips, Russell; (Menlo Park, CA), Reeder, Thadd C.; (San Carlos, CA) Correspondence: Deltagen, INC.; 740 Bay Road; Redwood City; CA; 94063; US Patent Application Number: 20030066098 Date filed: November 5, 2001 Abstract: The present invention relates to compositions and methods relating to the characterization of gene function. More particularly, the present invention relates to the role of secreted protein genes involved in neurobiological disorders, and in particular, depression. In addition, the present invention provides transgenic mice comprising mutations in a secreted protein gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions, including depression. Excerpt(s): This application claims priority to U.S. Provisional Application No. 60/245,852, filed Nov. 3, 2000. The present invention relates to compositions and methods relating to the characterization of gene function. Clinical depression is characterized by a combination of symptoms that interfere with the ability to work, study, sleep, eat, and enjoy once pleasurable activities. Symptoms include: persistent sad or anxious mood; feelings of hopelessness or pessimism; feelings of guilt, worthlessness or helplessness; loss of interest in pleasure activities; decreased energy; difficulty concentrating, remembering, or making decisions; sleep abnormalities (e.g. insomnia); appetite and/or weight loss; thoughts of death or suicide; restlessness; and irritability. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Test probe for electrical devices having low or no wedge depression Inventor(s): Kliman, Gerald Burt; (Niskayuna, NY), Lee, Sang-Bin; (Schenectady, NY), Mall, Waheed Tony; (Waterford, NY) Correspondence: General Electric Company; Crd Patent Docket RM 4a59; BLDG. K-1; P.O. Box 8; Schenectady; NY; 12301; US Patent Application Number: 20040100300 Date filed: November 20, 2003 Abstract: A probe for use in detecting abnormalities in an electrical device having a wedge depression of no more than 100 mils. The probe includes a solid core surrounded by a sense coil. The ends of the core are arranged in a contact-free, spaced relationship between and at least partially above opposed surfaces of adjacent lamination teeth of a stator. Air gaps are maintained between the ends of the probe core and the opposed surfaces. The total of the two air gaps is constant. The probe is supported on a carriage arrangement and moved along the teeth. Variations in leakage flux produced with the stator energized with an energization winding to produce a flux which is a few percent of a normal energization level, are monitored.

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Excerpt(s): This application is a continuation-in-part of prior application Ser. No. 10/270,326, filed Oct. 15, 2002, the entirety of which is incorporated herein by reference. The invention relates generally to the diagnosis and monitoring of the operation of electrical apparatus. More specifically, the present invention relates to a probe or sensor arrangement which facilitates the detection of flaws/imperfections in electrical apparatus, such as stator cores of large generators having low or no wedge depressions, and which requires the stator to be energized only to a low level for detection purposes. In the field of generating electricity on a commercial scale it is important that elements of the power generating system forming part of a 50-1000 MVA power generating arrangement, for example, remain fully functional over their expected working lives so that unexpected downtimes and/or catastrophic failures can be avoided. To avoid such problems it is important that elements, such as the large stators which form part of the above-mentioned generating systems, be carefully inspected and tested either during regular periodic maintenance or before being sold and installed in a power generating installation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html x

Treatment and prevention of depression secondary to pain (DSP) Inventor(s): Kranzler, Jay D.; (LaJolla, CA), Rao, Srinivas G.; (San Diego, CA) Correspondence: Patrea L. Pabst; Holland & Knight Llp; Suite 2000, One Atlantic Center; 1201 West Peachtree Street, N.E.; Atlanta; GA; 30309-3400; US Patent Application Number: 20040034101 Date filed: July 24, 2003 Abstract: Methods for the prevention or treatment of a typical depression secondary to pain (DSP) have been developed. The method generally involves administering an effective amount of a monoamine re uptake inhibitor to treat or prevent symptoms of DSP. In a preferred embodiment, a therapeutically effective amount of a dual serotonin norepinephrine reuptake inhibitor (SRNI) compound of a specific type, or a pharmaceutically acceptable salt thereof is administered. The most preferred SNRI compounds are non-tricyclic SNRIs, wherein serotonin reuptake inhibition is greater than norepinephrine reuptake inhibition; and NSRIs, wherein norepinephrine reuptake inhibition is greater than serotonin reuptake inhibition. The most preferred compound is milnacipran or a bioequivalent or pharmaceutically acceptable salt thereof. Other preferred compounds are duloxetine and venlafaxine or a bioequivalent or pharmaceutically acceptable salt thereof. In yet another embodiment, a therapeutically effective amount of a non-tricyclic triple reuptake inhibitor ("TRI") compound of a specific type, or a pharmaceutically acceptable salt thereof, is administered. The TRI compounds are characterized by their ability to block the reuptake (and, hence, increase central concentrations of) the three primary brain monoamines: serotonin, noradrenaline, and dopamine. Excerpt(s): This application is a continuation-in-part of U.S. Ser. No. 10/028,547 entitled "Method of Treating Fibromyalgia" filed Dec. 19, 2001, which is a continuation-in-part of U.S. Ser. No. 10/014,149 entitled "Method of Treating Chronic Fatigue Syndrome" filed Nov. 5, 2001, and also claims priority to U.S. S. No. 60/398,676 entitled "Treatment of Pain-Associated Depression (PAD)" filed Jul. 24, 2002 and to U.S. S. No. 60/443,035 entitled "Treatment of Pain-Associated Depression (PAD)" filed Jan. 28, 2003. The present invention is in the field of treating a typical depression associated with a chronic pain state. Chronic pain is thought to result in a high incidence of clinical

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depression with some estimates suggesting that almost two thirds of patients with chronic non-malignant pain have coexisting symptoms of depression or anxiety. One problem in treating chronic pain is that little is known about what causes the pain state. Acute pain occurs when an individual experiences an acute injury. Chronic pain is more complex because it often occurs in the absence of any ongoing illness or disease and is often intractable using conventional analgesics. Chronic pain usually occurs following an acute injury, but continues for an unknown reason after the injured area has healed. Chronic pain can also be caused by an ongoing condition like Chronic Fatigue Syndrome (CFS), Fibromyalgia syndrome (FMS), arthritis, or an illness like cancer or multiple sclerosis. The cause of pain cannot be removed or treated and the pain itself cannot be relieved. This gives rise to feelings of helplessness, decreased energy, low selfesteem and social support (Brown et al Br J Psychiatry 147, 612-22 (1985)). This pattern often leads to depression, anxiety and frustration which further exacerbate the pain. Chronic or intractable pain is often endured over many years or decades. Patients suffering from chronic pain often develop emotional problems which can lead to depression and in worst cases, attempted suicide. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Keeping Current In order to stay informed about patents and patent applications dealing with depressive disorders, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “depressive disorders” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on depressive disorders. You can also use this procedure to view pending patent applications concerning depressive disorders. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 6. BOOKS ON DEPRESSIVE DISORDERS Overview This chapter provides bibliographic book references relating to depressive disorders. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on depressive disorders include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

Book Summaries: Federal Agencies The Combined Health Information Database collects various book abstracts from a variety of healthcare institutions and federal agencies. To access these summaries, go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. You will need to use the “Detailed Search” option. To find book summaries, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer. For the format option, select “Monograph/Book.” Now type “depressive disorders” (or synonyms) into the “For these words:” box. You should check back periodically with this database which is updated every three months. The following is a typical result when searching for books on depressive disorders: x

Depressive Disorders and Immunity Contact: American Psychiatric Press, Inc., 1400 K St NW, Washington, DC, 20005, (800) 368-5777. Summary: This monograph presents principles of neural-immune integration. It focuses on understanding the immunology of depression to bring new insights into the current understanding of depression as a psychiatric disorder. The monograph explains why the study of the immune system is valuable when the primary interest is in the brain and behavior. It highlights major areas of investigation relating neuromotivation to immunity. The first area of interest is the relationship of immune function to the maintenance of health and the development of physical disease. The next area of interest is brain/immune system interactions, including the mechanisms of neural-immune integration and basic neuroimmunology. The final area of interest is the pathogenesis of psychiatric disorders as revealed through immune phenomena.

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Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “depressive disorders” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “depressive disorders” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “depressive disorders” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): x

A Brotherhood of Tyrants: Manic Depression & Absolute Power by D. Jablow Hershman, et al; ISBN: 0879758880; http://www.amazon.com/exec/obidos/ASIN/0879758880/icongroupinterna

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A Life Worth Living: Practical Strategies for Reducing Depression in Older Adults by Pearl M., Ph.D. Mosher-Ashley, Phyllis W. Barrett; ISBN: 1878812033; http://www.amazon.com/exec/obidos/ASIN/1878812033/icongroupinterna

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An Inquiry into Schizophrenia and Depression (Animal Models of Psychiatric Disorders, Vol 2) by P. Simon, et al; ISBN: 3805547579; http://www.amazon.com/exec/obidos/ASIN/3805547579/icongroupinterna

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Anna's Fight for Hope: The Great Depression (Sisters in Time) by Joann A. Grote; ISBN: 1593102089; http://www.amazon.com/exec/obidos/ASIN/1593102089/icongroupinterna

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Anxiety and Depressive Disorders in the Medical Patient (Clinical Practice, No 4) by Leonard R. Derogatis, Thomas N. Wise; ISBN: 0880481595; http://www.amazon.com/exec/obidos/ASIN/0880481595/icongroupinterna

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Biology of Depressive Disorders: Subtypes of Depression and Comorbid Disorders ( The Depressive Illness Series, Vol 4) by J. John, M.D. Mann, David J., M.D. Kupfer; ISBN: 0306442965; http://www.amazon.com/exec/obidos/ASIN/0306442965/icongroupinterna

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Bipolar Disorder and Depression (Health Watch) by Susan Dudley Gold, Linda Zamvil; ISBN: 0766016544; http://www.amazon.com/exec/obidos/ASIN/0766016544/icongroupinterna

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Blow Away the Black Clouds: A Woman's Answer to Depression [LARGE PRINT] by Florence Littauer; ISBN: 0802726062; http://www.amazon.com/exec/obidos/ASIN/0802726062/icongroupinterna

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Breaking Free from Depression (Breaking Free) by Linda Mintle, Linda, Ph.D. Mintle; ISBN: 0884198936; http://www.amazon.com/exec/obidos/ASIN/0884198936/icongroupinterna

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Christmas After All: The Great Depression Diary of Minnie Swift, Indianapolis, Indiana, 1932 (Dear America) by Kathryn Lasky; ISBN: 0439219434; http://www.amazon.com/exec/obidos/ASIN/0439219434/icongroupinterna

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Clinical Depression During Addiction Recovery: Process, Diagnosis, and Treatment by Jerry S. Kantor, Marcel Dekker; ISBN: 0824796225; http://www.amazon.com/exec/obidos/ASIN/0824796225/icongroupinterna

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Clinical Guide to Depression in Children and Adolescents by Mohammad Shafii, Sharon Lee Shafii; ISBN: 0880483563; http://www.amazon.com/exec/obidos/ASIN/0880483563/icongroupinterna

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Conquering Depression and Anxiety Through Exercise by Keith Johnsgard; ISBN: 1591021928; http://www.amazon.com/exec/obidos/ASIN/1591021928/icongroupinterna

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Culture and Politics in the Great Depression (Charles Edmondson Historical Lectures, 20th) by Alan Brinkley; ISBN: 091895472X; http://www.amazon.com/exec/obidos/ASIN/091895472X/icongroupinterna

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Curing Depression Naturally with Chinese Medicine by Rosa N. Schnyer, Bob Flaws; ISBN: 0936185945; http://www.amazon.com/exec/obidos/ASIN/0936185945/icongroupinterna

x

Current perspectives on major depressive disorders in children (Clinical insights); ISBN: 0880480610; http://www.amazon.com/exec/obidos/ASIN/0880480610/icongroupinterna

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Depression Workbook: Guide for Living With Depression and Manic Depression by Mary Copeland; ISBN: 1879237334; http://www.amazon.com/exec/obidos/ASIN/1879237334/icongroupinterna

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Diagnosis and Treatment of Depression in Late Life: Results of the Nih Consensus Development Conference by Lon S., M.D. Schneider, et al; ISBN: 0880485566; http://www.amazon.com/exec/obidos/ASIN/0880485566/icongroupinterna

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Diagnosis of Depression (Perspectives in Psychiatry) by J. P. Feighner (Editor); ISBN: 0471928917; http://www.amazon.com/exec/obidos/ASIN/0471928917/icongroupinterna

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Dillinger, the Hidden Truth: A Tribute to Gangsters and G-Men of the Great Depression Era by Tony Stewart; ISBN: 1401053726; http://www.amazon.com/exec/obidos/ASIN/1401053726/icongroupinterna

x

Dining During the Depression : Strong Family Ties, Hard Work, and Good OldFashioned Cooking Sustained Folks Through the 1930s (Reminisce Books) by Mike Beno (Author), et al; ISBN: 0898211565; http://www.amazon.com/exec/obidos/ASIN/0898211565/icongroupinterna

x

Disciplined Hearts: Hearts, Identity and Depression in an American Indian Community by Theresa Deleane O'Nell; ISBN: 0520214463; http://www.amazon.com/exec/obidos/ASIN/0520214463/icongroupinterna

x

Does Your Man Have the Blues: Understanding Male Depression & How It Affects Your Relationship by David Hawkins, David, Dr Hawkins; ISBN: 0736913483; http://www.amazon.com/exec/obidos/ASIN/0736913483/icongroupinterna

x

Drugs and Depression (Drug Abuse Prevention Library) by Beth Wilkinson; ISBN: 0823930041; http://www.amazon.com/exec/obidos/ASIN/0823930041/icongroupinterna

x

Earl Mindell's New Herb Bible: A complete update of the bestselling guide to new and traditional herbal remedies - how they can help fight depression and anxiety, improve your sex life, prevent illness, and help you heal faster! by Earl Mindell; ISBN:

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0743225481; http://www.amazon.com/exec/obidos/ASIN/0743225481/icongroupinterna x

Elegant Glassware Of The Depression Era (ELEGANT GLASSWARE OF THE DEPRESSION ERA) by Florence Gene; ISBN: 1574324179; http://www.amazon.com/exec/obidos/ASIN/1574324179/icongroupinterna

x

Endangered Dreams: The Great Depression in California (Americans and the California Dream) by Kevin Starr; ISBN: 0195118022; http://www.amazon.com/exec/obidos/ASIN/0195118022/icongroupinterna

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Ending the Depression Cycle: A Step-By-Step Guide for Preventing Relapse by Peter J. Bieling, et al; ISBN: 1572243333; http://www.amazon.com/exec/obidos/ASIN/1572243333/icongroupinterna

x

Essential Papers on Depression (Essential Papers in Psychoanalysis) by James C. Coyne; ISBN: 0814713998; http://www.amazon.com/exec/obidos/ASIN/0814713998/icongroupinterna

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Fragments of My Life: A Journal About Manic Depression and Its Companion Illnesses by Carol›J Griffin; ISBN: 0595289053; http://www.amazon.com/exec/obidos/ASIN/0595289053/icongroupinterna

x

Freedom from Depression (Includes Bibliographical References) by Neil T. Anderson (Author), Hal Baumchen (Author); ISBN: 0830723285; http://www.amazon.com/exec/obidos/ASIN/0830723285/icongroupinterna

x

From Depression To Deliverance by Carole P Adkins; ISBN: 0595288804; http://www.amazon.com/exec/obidos/ASIN/0595288804/icongroupinterna

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From Depression To Wholeness : The Anatomy of Healing by Debbie Thurman; ISBN: 0967628903; http://www.amazon.com/exec/obidos/ASIN/0967628903/icongroupinterna

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Glass Candlesticks of the Depression Era: Identification and Value Guide by Gene Florence; ISBN: 1574321366; http://www.amazon.com/exec/obidos/ASIN/1574321366/icongroupinterna

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Hammer and Hoe: Alabama Communists During the Great Depression (Fred W. Morrison Series in Southern Studies) by Robin D.G. Kelley; ISBN: 0807842885; http://www.amazon.com/exec/obidos/ASIN/0807842885/icongroupinterna

x

Handbook of Depression and Anxiety (Medical Psychiatry, 21) by S. Kasper, et al; ISBN: 0824708725; http://www.amazon.com/exec/obidos/ASIN/0824708725/icongroupinterna

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Handbook of Depression and Anxiety: A Biological Approach (Medical Psychiatry, Vol 1) by Johan A. Boer, et al; ISBN: 0824788583; http://www.amazon.com/exec/obidos/ASIN/0824788583/icongroupinterna

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Have a Heart's Home: A Rest Stop from Depression and Suicidal Thoughts by Stephen Bernhardt; ISBN: 0595206719; http://www.amazon.com/exec/obidos/ASIN/0595206719/icongroupinterna

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Headin' for Better Times: The Arts of the Great Depression (People's History) by Duane Damon; ISBN: 0822517418; http://www.amazon.com/exec/obidos/ASIN/0822517418/icongroupinterna

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209

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Helping Students Overcome Depression and Anxiety: A Practical Guide by Kenneth W. Merrell; ISBN: 1572306173; http://www.amazon.com/exec/obidos/ASIN/1572306173/icongroupinterna

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Helping Your Child Cope with Depression and Suicidal Thoughts (The Jossey-Bass Psychology Series) by Tonia K. Shamoo, Philip G. Patros; ISBN: 0787908444; http://www.amazon.com/exec/obidos/ASIN/0787908444/icongroupinterna

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Heyday of American Communism: The Depression Decade by Harvey Klehr; ISBN: 0465029469; http://www.amazon.com/exec/obidos/ASIN/0465029469/icongroupinterna

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Historic Events for Students: The Great Depression (Historic Events for Students) by Richard C. Hanes; ISBN: 0787657018; http://www.amazon.com/exec/obidos/ASIN/0787657018/icongroupinterna

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Hitting Home: The Great Depression in Town and Country by Bernard Sternsher; ISBN: 0929587138; http://www.amazon.com/exec/obidos/ASIN/0929587138/icongroupinterna

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Interpersonal Psychotherapy of Depression (The Master Work Series) by Gerald L. Klerman; ISBN: 1568213506; http://www.amazon.com/exec/obidos/ASIN/1568213506/icongroupinterna

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John Vachon's America: Photographs and Letters from the Depression to World War II by John Vachon, Miles Orvell; ISBN: 0520223780; http://www.amazon.com/exec/obidos/ASIN/0520223780/icongroupinterna

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Lessons from the Great Depression (Lionel Robbins Lectures) by Peter Temin; ISBN: 0262700441; http://www.amazon.com/exec/obidos/ASIN/0262700441/icongroupinterna

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Living Longer Depression Free: A Family Guide to Recognizing, Treating, and Preventing Depression in Later Life [LARGE PRINT] by Mark D. Miller, Charles F. Reynolds; ISBN: 0801871697; http://www.amazon.com/exec/obidos/ASIN/0801871697/icongroupinterna

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Long-Term Treatment of Depression (PERSPECTIVES IN PSYCHIATRY) by S. A. Montgomery, F. Rouillon; ISBN: 0471928925; http://www.amazon.com/exec/obidos/ASIN/0471928925/icongroupinterna

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Major Depressive Disorder : The Latest Assessment and Treatment Strategies by Anton O. Tolman, Anton Tolman; ISBN: 1887537104; http://www.amazon.com/exec/obidos/ASIN/1887537104/icongroupinterna

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Manic Depression and Creativity by D. Jablow Hershman, Julian Lieb; ISBN: 1573922412; http://www.amazon.com/exec/obidos/ASIN/1573922412/icongroupinterna

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Mind Fall: Inside Major Depression : A Story of Survival & A Medical Perspective by Lynn Shahan, Anna-Lisa Stonehill; ISBN: 0927015218; http://www.amazon.com/exec/obidos/ASIN/0927015218/icongroupinterna

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Mood Genes: Hunting for Origins of Mania and Depression (Oxford Paperbacks) by Samuel H. Barondes; ISBN: 0195131061; http://www.amazon.com/exec/obidos/ASIN/0195131061/icongroupinterna

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My Naked Truth: Surviving Depression and Bulimia by Ximena Veliz; ISBN: 159299010X; http://www.amazon.com/exec/obidos/ASIN/159299010X/icongroupinterna

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Neuropsychological Assessment of Dementia and Depression in Older Adults: A Clinician's Guide by Martha Storandt, Gary R. Vandenbos; ISBN: 1557984379; http://www.amazon.com/exec/obidos/ASIN/1557984379/icongroupinterna

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New Results in Depression Research by H. Hippius, et al; ISBN: 0387157824; http://www.amazon.com/exec/obidos/ASIN/0387157824/icongroupinterna

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One Time One Place: Mississippi in the Depression : A Snapshot Album by Eudora Welty; ISBN: 0878058664; http://www.amazon.com/exec/obidos/ASIN/0878058664/icongroupinterna

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Overcoming Depression - Therapist Protocol (Best Practices for Therapy) by Gary Emery; ISBN: 1572241608; http://www.amazon.com/exec/obidos/ASIN/1572241608/icongroupinterna

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Overcoming Depression (Victory Over the Darkness Series) by Neil T. Anderson, Joanne Anderson; ISBN: 0830733515; http://www.amazon.com/exec/obidos/ASIN/0830733515/icongroupinterna

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Overcoming Depression One Step at a Time: The New Behavioral Activation Approach to Getting Your Life Back by Christopher R., Ph.D. Martell, Michael E., Ph.D Addis; ISBN: 1572243678; http://www.amazon.com/exec/obidos/ASIN/1572243678/icongroupinterna

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Patterns of Self Destruction: Depression and Suicide; Proceedings. by 12th, Veterans Administration Hospital, co Neuropsychiatric Institute; ISBN: 0398021104; http://www.amazon.com/exec/obidos/ASIN/0398021104/icongroupinterna

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Postpartum Depression and Child Development by Lynne Murray (Editor), Peter J. Cooper (Editor); ISBN: 1572305177; http://www.amazon.com/exec/obidos/ASIN/1572305177/icongroupinterna

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Practice Guidelines for the Treatment of Patients With Major Depressive Disorder (American Psychiatric Association Practice Guidelines) by American Psychiatric Association; ISBN: 0890423164; http://www.amazon.com/exec/obidos/ASIN/0890423164/icongroupinterna

x

Resource Depression and Intensification During the Late Holocene, San Francisco Bay: Evidence from the Emeryville Shellmound Vertebrate Fauna (Anthropological Records, V. 32) by Jack M. Broughton; ISBN: 0520098285; http://www.amazon.com/exec/obidos/ASIN/0520098285/icongroupinterna

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Rethinking the Great Depression (American Ways Series) by Gene Smiley; ISBN: 1566634717; http://www.amazon.com/exec/obidos/ASIN/1566634717/icongroupinterna

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Riding the Rails: Teenagers on the Move During the Great Depression (Images of America) by Errol Lincoln Uys; ISBN: 0415945755; http://www.amazon.com/exec/obidos/ASIN/0415945755/icongroupinterna

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Rousing the Nation: Radical Culture in Depression America by Laura Browder; ISBN: 1558491252; http://www.amazon.com/exec/obidos/ASIN/1558491252/icongroupinterna

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Rural Trends in Depression Years: A Survey of Village-Centered Agricultural Communities 1930-1936 (Poverty U.S.A. Historical Record) by Edmund D. Brunner, Irving Lorge; ISBN: 0405030959; http://www.amazon.com/exec/obidos/ASIN/0405030959/icongroupinterna

Books

211

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Sightlines: The View of a Valley Through the Voice of Depression (Middlebury Bicentennial Series in Environmental Studies) by Terry Osborne; ISBN: 1584650834; http://www.amazon.com/exec/obidos/ASIN/1584650834/icongroupinterna

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Situating Sadness: Women and Depression in Social Context (Qualitative Studies in Psychology Series) by Janet M. Stoppard, Linda M. McMullen; ISBN: 0814798012; http://www.amazon.com/exec/obidos/ASIN/0814798012/icongroupinterna

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Somatic manifestations of depressive disorders (International congress series); ISBN: 0444151354; http://www.amazon.com/exec/obidos/ASIN/0444151354/icongroupinterna

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SSRIs in Depression and Anxiety (Perspectives in Psychiatry) by Stuart A. Montgomery (Editor), J. A. den Boer (Editor); ISBN: 0470841362; http://www.amazon.com/exec/obidos/ASIN/0470841362/icongroupinterna

x

Standing In the Shadows : Understanding and Overcoming Depression in Black Men by JOHN HEAD; ISBN: 0767913531; http://www.amazon.com/exec/obidos/ASIN/0767913531/icongroupinterna

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Stop Depression Now: Sam-E : The Breakthrough Supplement That Works As Well As Prescription Drugs, in Half the Time.With No Side Effects by Richard Brown, et al; ISBN: 0425176436; http://www.amazon.com/exec/obidos/ASIN/0425176436/icongroupinterna

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Straight Talk on Depression : Overcoming Emotional Battles with the Power of God's Word! by Joyce Meyer; ISBN: 0446691518; http://www.amazon.com/exec/obidos/ASIN/0446691518/icongroupinterna

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Super Strength Letting Go of the Past/Up From Depression [ABRIDGED] by Robert E. Griswold; ISBN: 1558483047; http://www.amazon.com/exec/obidos/ASIN/1558483047/icongroupinterna

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Surviving the Crisis of Depression & Bipolar (Manic-Depression) Illness: Layperson's Guide to Coping With Mental Illness Beyond the Time of Crisis & Outside the Hospital by Mark A. Halebsky; ISBN: 1880793016; http://www.amazon.com/exec/obidos/ASIN/1880793016/icongroupinterna

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The Age of the Great Depression 1929-1941 by Dixon Wecter; ISBN: 0024249300; http://www.amazon.com/exec/obidos/ASIN/0024249300/icongroupinterna

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The Bible Cure for Depression and Anxiety (Fitness and Health) by Don Colbert, Donald, Md. Colbert; ISBN: 088419650X; http://www.amazon.com/exec/obidos/ASIN/088419650X/icongroupinterna

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The Childhood Depression Sourcebook by Jeffrey A. Miller; ISBN: 0737300019; http://www.amazon.com/exec/obidos/ASIN/0737300019/icongroupinterna

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The Depression and New Deal: A History in Documents (Pages from History) by Robert S. McElvaine; ISBN: 0195166361; http://www.amazon.com/exec/obidos/ASIN/0195166361/icongroupinterna

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The Depression Book: Depression As an Opportunity for Spiritual Growth by Cheri Huber, June Shiver; ISBN: 096362556X; http://www.amazon.com/exec/obidos/ASIN/096362556X/icongroupinterna

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The Great Depression (CORNERSTONES OF FREEDOM SECOND SERIES) by R. Conrad Stein; ISBN: 0516066684; http://www.amazon.com/exec/obidos/ASIN/0516066684/icongroupinterna

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The Great Depression (History Firsthand) by Dennis Nishi; ISBN: 0737704101; http://www.amazon.com/exec/obidos/ASIN/0737704101/icongroupinterna

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The Great Depression : Delayed Recovery and Economic Change in America, 19291939 (Studies in Economic History and Policy : The United States in The) by Michael A. Bernstein; ISBN: 0521379857; http://www.amazon.com/exec/obidos/ASIN/0521379857/icongroupinterna

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The Hungry Years: A Narrative History of the Great Depression in America by T. H. Watkins; ISBN: 0805065067; http://www.amazon.com/exec/obidos/ASIN/0805065067/icongroupinterna

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The Many Faces of Depression in Children and Adolescents (Review of Psychiatry Series, V. 21, No. 2.) by David Shaffer, Bruce D. Waslick; ISBN: 1585620718; http://www.amazon.com/exec/obidos/ASIN/1585620718/icongroupinterna

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The New Deal and the Great Depression in American History (In American History) by Lisa A. Wroble, Lisa Wroble; ISBN: 0766014215; http://www.amazon.com/exec/obidos/ASIN/0766014215/icongroupinterna

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The New Deal: America's Response to the Great Depression (Problems in American History) by Ronald Edsforth; ISBN: 1577181433; http://www.amazon.com/exec/obidos/ASIN/1577181433/icongroupinterna

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The New Deal: The Depression Years, 1933-40 by Anthony J. Badger; ISBN: 1566634539; http://www.amazon.com/exec/obidos/ASIN/1566634539/icongroupinterna

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The Tortured Mind: The Many Faces of Manic Depression ((Encyclopedia of Psychological Disorders)) by Ann Holmes; ISBN: 0791049000; http://www.amazon.com/exec/obidos/ASIN/0791049000/icongroupinterna

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Times of Sorrow & Hope Cmbk: Documenting Everyday Life in Pennsylvania During the Depression and World War II : A Photographic Record by Allen Cohen, et al; ISBN: 0271022523; http://www.amazon.com/exec/obidos/ASIN/0271022523/icongroupinterna

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Treasures of Very Rare Depression Glass: Identification and Value Guide by Gene Florence; ISBN: 1574323369; http://www.amazon.com/exec/obidos/ASIN/1574323369/icongroupinterna

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Treating Depression in Children and Adolescents; ISBN: 0080358756; http://www.amazon.com/exec/obidos/ASIN/0080358756/icongroupinterna

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Understanding Depression (Understanding Health and Sickness) by Patricia Ainsworth; ISBN: 1578061695; http://www.amazon.com/exec/obidos/ASIN/1578061695/icongroupinterna

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User's Guide to Natural Remedies for Depression (Basic Health Publications User's Guide) by Linda Knittel; ISBN: 1591200466; http://www.amazon.com/exec/obidos/ASIN/1591200466/icongroupinterna

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Very Rare Glassware Depression Years S (Very Rare Glassware of the Depression Years) by Gene Florence; ISBN: 0891455108; http://www.amazon.com/exec/obidos/ASIN/0891455108/icongroupinterna

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Warman's Depression Glass: A Value & Identification Guide (Warman's Depression Glass) by Ellen T. Schroy; ISBN: 0873496183; http://www.amazon.com/exec/obidos/ASIN/0873496183/icongroupinterna

Books

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When You're Down With the Blues: Ways to Overcome Depression and Create a Bright Future (Your Pocket Therapist Series) by David, Dr Hawkins; ISBN: 0781434734; http://www.amazon.com/exec/obidos/ASIN/0781434734/icongroupinterna

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Your Depression Map: Find the Source of Your Depression and Chart Your Own Recovery by Randy J., Ph.D. Paterson; ISBN: 1572243007; http://www.amazon.com/exec/obidos/ASIN/1572243007/icongroupinterna

Chapters on Depressive Disorders In order to find chapters that specifically relate to depressive disorders, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and depressive disorders using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “depressive disorders” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on depressive disorders: x

Differential Assessment of Dementia and Depression in Elderly People (Chapter 5) Source: in Safford, F.; Krell, G.I., eds. Gerontology for Health Professionals: A Practice Guide. Annapolis JCT, MD: National Association for Social Workers Press. 1992. p. 5167. Contact: Available from National Association for Social Workers Press. P.O. Box 431, Annapolis JCT, MD 20701. (800) 227-3590 or FAX (301) 206-7989. PRICE: $20.95 plus $3.00 shipping and handling. Summary: This book chapter examines the differential assessment of dementia and depression in elderly people. The first section highlights some of the obstacles to an accurate diagnosis in older people and provides a differential definition of three syndromes of mental impairment: dementia, delirium, and depression. The second section describes the cognitive, psychological, and behavioral symptoms that may appear in persons with mental impairment and that may help to identify the problem. The third section describes the individualized assessment to establish an accurate diagnosis of dementia or depression and to distinguish between the two disorders. This section discusses commonly used mental status examinations, distinguishing features of dementia versus depression, symptoms that are characteristic of depression in older people, diagnostic criteria for major depression, the classification of primary versus secondary depressive disorders, and medical problems and medications that may cause depression. The final section discusses the treatment of dementia and depression in older people. 31 references.

x

Epidemiology of Late-Life Depression and Dementia: A Comparative Study Source: in Tasman, A.; Goldfinger, S.M.; Kaufmann, C.A., eds. Review of Psychiatry, Volume 9. Washington, DC: American Psychiatric Press. 1990. p. 210-219. Contact: Available from American Psychiatric Press. 1400 K Street, NW, Washington, DC 20005. (202) 682-6262 or (800) 368-5777. PRICE: $54.95 plus $5.00 shipping and handling.

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Summary: This chapter discusses how depression and dementia reflect different patterns of prevalence and distribution among the elderly. Depression is not associated with increased age, whereas dementia is correlated with age after about the age of 55.The causes of depressive disorders and dementing illness are multiple, yet the epidemiologic evidence suggests that primary degenerative disease of the Alzheimer's type is an age-related disorder with primarily psychobiological etiology. In contrast, the prevalence of major depression is not associated with age, and psychosocial factors are important in the etiology. Major depression presents much as it does at other ages and requires a similar approach to diagnostics and therapeutics across the life cycle. Both disorders lead to an increased use of health services, yet dementia accounts for the major portion of the sizable long-term care cases in the United States. 42 references.

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CHAPTER 7. PERIODICALS AND NEWS ON DEPRESSIVE DISORDERS Overview In this chapter, we suggest a number of news sources and present various periodicals that cover depressive disorders.

News Services and Press Releases One of the simplest ways of tracking press releases on depressive disorders is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing.

PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “depressive disorders” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance.

Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to depressive disorders. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “depressive disorders” (or synonyms). The following was recently listed in this archive for depressive disorders: x

CORRECTION: Celexa safely curbs depression in the young Source: Reuters Health eLine Date: July 06, 2004

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Citalopram safely curbs depression in the young Source: Reuters Industry Breifing Date: July 05, 2004

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Zoloft helps prevent depression relapse Source: Reuters Health eLine Date: May 27, 2004

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Bilateral no better than unilateral magnetic stimulation for depression therapy Source: Reuters Medical News Date: February 24, 2004

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Prolonged depression reduces global cerebral gray matter volume Source: Reuters Medical News Date: November 19, 2003

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Watch for suicide with depression drugs, FDA says Source: Reuters Health eLine Date: October 27, 2003

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Eli Lilly says duloxetine cuts depression relapse risk Source: Reuters Industry Breifing Date: September 22, 2003

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Artery stiffening related to depression in elderly Source: Reuters Health eLine Date: August 20, 2003

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Arterial stiffness is related to depression in the elderly Source: Reuters Medical News Date: August 20, 2003

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Genome survey finds depression genes Source: Reuters Health eLine Date: July 02, 2003

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FDA advises against Glaxo's Paxil for major depression in children Source: Reuters Industry Breifing Date: June 19, 2003

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Chronic, fluctuating depression typifies natural course of bipolar II disorder Source: Reuters Medical News Date: March 17, 2003

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ECT provides effective short-term depression therapy Source: Reuters Medical News Date: March 06, 2003

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Wyeth depression drug approved for anxiety ailment Source: Reuters Industry Breifing Date: February 11, 2003

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Study looks at hepatitis drug, depression risk Source: Reuters Health eLine Date: November 25, 2002

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CORRECTION: Adolescent depression common, but reporting to physicians unlikely Source: Reuters Medical News Date: October 28, 2002

Periodicals and News

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Adolescent depression common, but reporting to physicians unlikely Source: Reuters Medical News Date: October 25, 2002

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Major depression associated with past alcohol dependence Source: Reuters Medical News Date: October 10, 2002

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Sertraline found safe, effective treatment for depression post-MI Source: Reuters Industry Breifing Date: August 13, 2002

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Rate of major depressive disorder high among HIV-positive women Source: Reuters Medical News Date: May 10, 2002

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Parent's depression ups kid's risk of anxiety Source: Reuters Health eLine Date: April 17, 2002

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Citalopram safely relieves depression in patients with hepatitis C Source: Reuters Industry Breifing Date: April 12, 2002

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Roots of juvenile-onset and adult-onset depression may differ Source: Reuters Medical News Date: April 10, 2002

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Genetic susceptibility loci for major depression exhibit sex specificity Source: Reuters Medical News Date: March 28, 2002

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Mom's depression linked to child's future problems Source: Reuters Health eLine Date: November 21, 2001

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History of depression increases risk of early-onset perimenopause Source: Reuters Medical News Date: October 05, 2001

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Study links depression and heart failure death Source: Reuters Medical News Date: August 14, 2001

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Treatment for depression in MS patients reduces interferon-gamma production Source: Reuters Medical News Date: July 27, 2001

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St. John's wort not effective for depression in large-scale trial Source: Reuters Industry Breifing Date: April 17, 2001

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Social anxiety ups depression risk in teens Source: Reuters Health eLine Date: March 16, 2001

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Diabetes and depression have a complex relationship Source: Reuters Medical News Date: November 03, 2000

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Early-onset depression in women linked to lower future earnings Source: Reuters Medical News Date: July 12, 2000

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Treating poststroke depression aids cognitive recovery Source: Reuters Industry Breifing Date: July 07, 2000

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ACP-ASIM release guidelines for pharmacologic management of depression in primary care Source: Reuters Medical News Date: May 02, 2000

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Sertraline superior to desipramine for treatment of depression plus OCD Source: Reuters Medical News Date: January 21, 2000

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Migraine with aura linked with depression risk Source: Reuters Medical News Date: July 27, 1999

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Breast cancer therapy tied to depression risk Source: Reuters Health eLine Date: June 30, 1999

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Adolescent depression persists into adulthood Source: Reuters Medical News Date: May 12, 1999

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Teen depression often recurs in adulthood Source: Reuters Health eLine Date: May 11, 1999

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Nefazodone safe, efficacious for treatment of major depression in HIV-positive patients Source: Reuters Medical News Date: April 30, 1999

The NIH Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine.

Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name.

Periodicals and News

219

Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “depressive disorders” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests.

Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “depressive disorders” (or synonyms). If you know the name of a company that is relevant to depressive disorders, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/.

BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “depressive disorders” (or synonyms).

Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “depressive disorders” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on depressive disorders: x

Acoustic Neuroma and Depression: An Update Source: ANA Notes. Number 67: 1, 6. September 1998. Contact: Available from Acoustic Neuroma Association (ANA). 600 Peachtree Parkway, Suite 108, Cumming, GA 30041-8211. (770) 205-8211. Fax (770 www.ANAUSA.org. Summary: Acoustic neuroma is a serious illness that, even after surgery, can leave multiple disabling symptoms and depression. This review focuses on depression after surgery for acoustic neuroma. The author notes that a 1993 article reviewed the available information on acoustic neuroma and depression and showed that up to 37 percent of

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acoustic neuroma patients experienced depression. The author of this 1998 article reports on research published in the past five years. The author also reviews the definitions of depressive disorders as they are outlined in the American Psychiatric Association's diagnostic manual. All of the depressive disorders can be helped by appropriate intervention. This intervention can include peer support, individual counseling, and anti-depressant medication. The author concludes by encouraging readers to use the support services offered by the Acoustic Neuroma Association (ANA). 8 references.

Academic Periodicals covering Depressive Disorders Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to depressive disorders. In addition to these sources, you can search for articles covering depressive disorders that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for depressive disorders. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a non-profit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with depressive disorders. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.).

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The following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to depressive disorders: Antidepressants, Monoamine Oxidase (MAO) Inhibitor x

MAO - U.S. Brands: Marplan; Nardil; Parnate http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202054.html

Antidepressants, Tricyclic x

Systemic - U.S. Brands: Anafranil; Asendin; Aventyl; Elavil; Endep; Norfranil; Norpramin; Pamelor; Sinequan; Surmontil; Tipramine; Tofranil; Tofranil-PM; Vivactil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202055.html

Ascorbic Acid (Vitamin C) x

Vitamin C - U.S. Brands: Ascorbicap; Cebid Timecelles; Cecon; Cecore 500; Cee500; Cemill; Cenolate; Cetane; Cevi-Bid; Flavorcee; Mega-C/A Plus; Ortho/CS; Sunkist http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202071.html

Bupropion x

Systemic - U.S. Brands: Wellbutrin; Wellbutrin SR; Zyban http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202098.html

Chlordiazepoxide and Amitriptyline x

Systemic - U.S. Brands: Limbitrol; Limbitrol DS http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202129.html

Citalopram x

Systemic - U.S. Brands: Celexa http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203653.html

Clomiphene x

Systemic - U.S. Brands: Clomid; Milophene; Serophene http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202151.html

Corticosteroids Glucocorticoid Effects x

Systemic - U.S. Brands: Acetocot; A-hydroCort; Amcort; A-MethaPred; Aristocort; Aristocort Forte; Aristopak; Aristospan; Articulose-50; ArticuloseL.A.; Celestone; Celestone Phosphate; Celestone Soluspan; Cinalone 40; Cinonide 40; Clinacort; Clinalog; Cordrol; Cortastat; Cortastat 10; Cortastat LA; Cortef; Cortone Acetate; Cotolone; Dalalone; Dalalone D.P.; Dalalone L.A.; Decadrol; Decadron; Decadron Elixir; Decadron Phosphate; Decadron-LA; Decaject; Decaject-LA; Delta-Cortef; Deltasone; DepMedalone 40; DepMedalone 80; Depoject-40; Depoject-80; Depo-Medrol; Depopred; Depo-Predate; Dexacorten; Dexacorten-LA; Dexamethasone Intensol; Dexasone; Dexasone L.A.; Dexone; Dexone 0.75; Dexone 1.5; Dexone 4; Dexone LA; Duralone-40; Duralone-80; Hexadrol; Hexadrol Phosphate; Hydrocortone; Hydrocortone Acetate; Hydrocortone Phosphate; Kenacort; Kenacort Diacetate; Kenaject-40; Kenalog-10; Kenalog-40; Ken-Jec 40; Key-Pred; Key-Pred SP; Liquid Pred; Med-Jec-40; Medralone 80; Medrol; Meprolone; Methacort 40; Methacort 80; Methylcotolone;

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Meticorten; Mymethasone; Nor-Pred T.B.A.; Orasone 1; Orasone 10; Orasone 20; Orasone 5; Orasone 50; Pediapred; Predacort 50; Predacorten; Predacorten 80; Predalone 50; Predalone T.B.A.; Predate S; Predate TBA; Predate-50; Predcor-25; Predcor-50; Predcor-TBA; Predicort-RP; Pred-Ject-50; Prednicot; Prednisone Intensol; Pred-Pak 45; Pred-Pak 79; Prelone; Primethasone; Robalog; Selestoject; Solu-Cortef; Solu-Medrol; Solurex; Solurex LA; Sterapred; Sterapred DS; Tac-3; Tramacort-D; Triam-A; Triam-Forte; Triamolone 40; Triamonide 40; Tri-Kort; Trilog; Trilone; Tristoject http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202018.html Escitalopram x

Systemic - U.S. Brands: Lexapro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/500409.html

Fluoxetine x

Systemic - U.S. Brands: Prozac; Prozac Weekly; Sarafem http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202247.html

Fluvoxamine x

Systemic - U.S. Brands: Luvox http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202919.html

Lithium x

Systemic - U.S. Brands: Cibalith-S; Eskalith; Eskalith CR; Lithane; Lithobid; Lithonate; Lithotabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202330.html

Loxapine x

Systemic - U.S. Brands: Loxitane; Loxitane C; Loxitane IM http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202333.html

Maprotiline x

Systemic - U.S. Brands: Ludiomil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202337.html

Methylphenidate x

Systemic - U.S. Brands: Concerta; Metadate CD; Ritalin; Ritalin-SR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202361.html

Mirtazapine x

Systemic - U.S. Brands: Remeron; Remeron SolTab http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203490.html

Nefazodone x

Systemic - U.S. Brands: Serzone http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203491.html

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Paroxetine x

Systemic - U.S. Brands: Paxil http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202717.html

Sertraline x

Systemic - U.S. Brands: Zoloft http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202651.html

Thiamine (Vitamin B 1) x

Vitamin B 1 - U.S. Brands: Biamine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202560.html

Trazodone x

Systemic - U.S. Brands: Desyrel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202573.html

Venlafaxine x

Systemic - U.S. Brands: Effexor; Effexor XR http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202764.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/.

PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter,

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Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: x

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

x

National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

x

National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

x

National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

x

National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

x

National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

x

National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

x

National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

10

These publications are typically written by one or more of the various NIH Institutes.

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x

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

x

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

x

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

x

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

x

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

x

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

x

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

x

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

x

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

x

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

x

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

x

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

x

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

x

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

x

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

x

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

x

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

x

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 x

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

x

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

x

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

x

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

x

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

x

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

x

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

x

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

x

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

x

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

x

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

11 Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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x

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

x

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “depressive disorders” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 44928 930 1020 199 153 47230

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “depressive disorders” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

16

The HSTAT URL is http://hstat.nlm.nih.gov/.

17

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: x

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

x

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

18 Adapted 19

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on depressive disorders can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.

Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to depressive disorders. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly.

The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below.

Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to depressive disorders. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “depressive disorders”:

236

x

Depressive Disorders

Guides on depressive disorders Postpartum Depression http://www.nlm.nih.gov/medlineplus/postpartumdepression.html

x

Other guides Bipolar Disorder http://www.nlm.nih.gov/medlineplus/bipolardisorder.html Mental Health http://www.nlm.nih.gov/medlineplus/mentalhealth.html Panic Disorder http://www.nlm.nih.gov/medlineplus/panicdisorder.html Seasonal Affective Disorder http://www.nlm.nih.gov/medlineplus/seasonalaffectivedisorder.html Suicide http://www.nlm.nih.gov/medlineplus/suicide.html

Within the health topic page dedicated to depressive disorders, the following was listed: x

Diagnosis/Symptoms Recognizing Postpartum Depression Source: National Mental Health Association http://www.nmha.org/children/ppd.pdf

x

Treatment Interpersonal Psychotherapy Effective for Treatment of Postpartum Depression Source: American Medical Association http://www.medem.com/MedLB/article_detaillb.cfm?article_ID=ZZZ4LE2OEFC &sub_cat=638 Medications Source: National Institute of Mental Health http://www.nimh.nih.gov/publicat/medicate.cfm

x

Coping Postpartum Coping: The Blues and Depression Source: Mayo Foundation for Medical Education and Research http://www.mayoclinic.com/invoke.cfm?id=HQ01243 Tips on Healthy Parenting for Mothers with Depression Source: National Mental Health Association http://www.nmha.org/infoctr/factsheets/HealthyParentingTips.pdf

x

Organizations National Institute of Mental Health http://www.nimh.nih.gov/

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National Mental Health Association http://www.nmha.org/ x

Statistics Depression in Women Source: National Mental Health Association http://www.nmha.org/infoctr/factsheets/23.cfm

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search.

The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on depressive disorders. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: x

Clinical depression and African Americans Source: Arlington, VA: National Alliance for the Mentally Ill. 1995. 17 items. Contact: Available from National Alliance for the Mentally Ill, 200 North Glebe Road, Suite 1015, Arlington, VA 22203-3754. Telephone: (703) 524-7600 or (800) 950-6264 or (703) 526-7991 TDD / fax: (703) 524-9094 / e-mail: [email protected] / Web site: http://www.nami.org. Summary: This information package contains fact sheets, consumer pamphlets, articles, and other information about depression in African Americans.

x

Depression: It's an illness, not a weakness Source: Alexandria, VA: National Mental Health Association. 1995. 11 items. Contact: Available from National Mental Health Association, 1021 Prince Street, Alexandria, VA 22314-2971. Telephone: (703) 684-7722 or (800) 969-NMHA / fax: (703) 684-5968 / Web site: http://www.nmha.org. Summary: This information package contains information about clinical depression in women, including fact sheets, resource lists, newsletters, and pamphlets for consumers.

x

Depression and women: Dispelling the myths Source: Staten Island, NY: Freedom from Fear. 1994. 30 pp., 1 videotape (14 minutes, VHS 1/2 inch).

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Contact: Available from Freedom from Fear, 308 Seaview Avenue, Staten Island, NY 10305. Telephone: (718) 351-1717 / fax: (718) 667-8893. $59.95. Summary: This notebook includes materials to use in organizing a health promotion program about women and depression. It contains a program planning and promotion manual, a depression questionnaire, fact sheets, and an educational videotape.

The National Guideline Clearinghouse™ The National Guideline Clearinghouse™ offers hundreds of evidence-based clinical practice guidelines published in the United States and other countries. You can search this site located at http://www.guideline.gov/ by using the keyword “depressive disorders” (or synonyms). The following was recently posted: x

Major depression in adults for mental health care providers Source: Institute for Clinical Systems Improvement - Private Nonprofit Organization; 1996 February (revised 2003 Sep); 49 pages http://www.guideline.gov/summary/summary.aspx?doc_id=4173&nbr=3198&a mp;string=depressive+AND+disorders

x

Pharmacologic treatment of acute major depression and dysthymia Source: American College of Physicians - Medical Specialty Society; 2000; 5 pages http://www.guideline.gov/summary/summary.aspx?doc_id=2547&nbr=1773&a mp;string=depressive+AND+disorders

x

Postnatal depression and puerperal psychosis. A national clinical guideline Source: Scottish Intercollegiate Guidelines Network - National Government Agency [Non-U.S.]; 2002 June; 28 pages http://www.guideline.gov/summary/summary.aspx?doc_id=3360&nbr=2586&a mp;string=depressive+AND+disorders

x

VHA/DOD clinical practice guideline for the management of major depressive disorder in adults Source: Department of Defense - Federal Government Agency [U.S.]; 1997 (updated 2000); Various pagings http://www.guideline.gov/summary/summary.aspx?doc_id=2585&nbr=1811&a mp;string=depressive+AND+disorders

The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to depressive disorders. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information

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for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.

Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: x

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

x

Family Village: http://www.familyvillage.wisc.edu/specific.htm

x

Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/

x

Med Help International: http://www.medhelp.org/HealthTopics/A.html

x

Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/

x

Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/

x

WebMDHealth: http://my.webmd.com/health_topics

Associations and Depressive Disorders The following is a list of associations that provide information on and resources relating to depressive disorders: x

Depression and Bipolar Support Alliance (DBSA) Telephone: (312) 642-0049 Toll-free: (800) 826-3632 Fax: (312) 642-7243 Web Site: http://www.dbsalliance.org/ Background: The National Depressive and Manic-Depressive Associatino (National DMDA) is the nation's largest patient-directed, illness-specific organization. Incorporated in 1986 and based in Chicago, it represents the voices of more than 23 million American adults living with depression and an additional 2.5 million adults living with manic-depression, also known as bipolar disorder. It is a not-for-profit organization that educates the public concerning the nature of depressioin and manicdepressive illnesses as treatable medical diseases. National DMDA has a grassroots network of mroe than 800 patient-run support groups that hold regular meetings across the United States and Canada.

x

Depression and Related Affective Disorders Association Telephone: (410) 955-4647 Fax: (410) 614-3241 Email: [email protected] Web Site: www.drada.org

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Background: The Depression and Related Affective Disorders Association (DRADA) is a nonprofit organization uniting the efforts of persons with affective disorders, family members, and mental health professionals. The mission of the organization is to provide information, assistance, and support to those with depression and manic depression by assisting self-help groups. In addition, the Association lends support to research programs. Educational materials produced by the Depression and Related Affective Disorders Association include a variety of pamphlets, books, and videos.

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to depressive disorders. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with depressive disorders.

The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about depressive disorders. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797.

Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “depressive disorders” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received your search results, click on the name of the organization for its description and contact information.

The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “depressive disorders”. Type the following hyperlink

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into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “depressive disorders” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “depressive disorders” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

21

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: x

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

x

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

x

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

x

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

x

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

x

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

x

California: Gateway Health Library (Sutter Gould Medical Foundation)

x

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

x

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

x

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

x

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

x

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

x

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

x

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

x

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

x

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

x

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

x

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

22

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

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x

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

x

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

x

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

x

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

x

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

x

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

x

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

x

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

x

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

x

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

x

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

x

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

x

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

x

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

x

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

x

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

x

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

x

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

x

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

x

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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x

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

x

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

x

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

x

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

x

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

x

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

x

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

x

Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

x

Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

x

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

x

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

x

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

x

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

x

Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

x

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

x

Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

x

National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

x

National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

x

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

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x

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

x

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

x

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

x

New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

x

New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

x

New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

x

New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

x

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

x

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

x

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

x

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

x

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

x

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

x

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

x

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

x

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

x

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

x

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

x

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

x

Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/

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x

South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp

x

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

x

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

x

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

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ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: x

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

x

MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

x

Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

x

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

x

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

x

Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

x

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on depressive disorders: x

Basic Guidelines for Depressive Disorders Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Depression - elderly Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001521.htm Depression - resources Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002177.htm Depression signs in teenagers Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001996.htm

x

Signs & Symptoms for Depressive Disorders Agitation Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003212.htm

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Change in appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Difficulty falling asleep Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Difficulty sleeping Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Discouragement Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Fatigue Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm High blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003082.htm Insomnia Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Loss of appetite Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003121.htm Memory loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003257.htm Sadness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Sleepiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm Sleeping difficulties Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Tiredness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Weariness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003088.htm Weight gain (unintentional) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003084.htm Weight loss (unintentional) Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm

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x

Diagnostics and Tests for Depressive Disorders Electroconvulsive therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003324.htm

x

Background Topics for Depressive Disorders Chronic Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002312.htm Exercise Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Physical activity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/001941.htm Physical examination Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002274.htm

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: x

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

x

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

x

Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

x

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

253

DEPRESSIVE DISORDERS DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Hydroxytryptophan: Precursor of serotonin used as antiepileptic and antidepressant. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] Absenteeism: Chronic absence from work or other duty. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acculturation: Process of cultural change in which one group or members of a group assimilates various cultural patterns from another. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acoustic: Having to do with sound or hearing. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjustment Disorders: Maladaptive reactions to identifiable psychosocial stressors occurring within a short time after onset of the stressor. They are manifested by either impairment in social or occupational functioning or by symptoms (depression, anxiety, etc.) that are in excess of a normal and expected reaction to the stressor. [NIH]

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Adolescence: The period of life beginning with the appearance of secondary sex characteristics and terminating with the cessation of somatic growth. The years usually referred to as adolescence lie between 13 and 18 years of age. [NIH] Adolescent Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders in individuals 13-18 years. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Glands: Paired glands situated in the retroperitoneal tissues at the superior pole of each kidney. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosols: Colloids with a gaseous dispersing phase and either liquid (fog) or solid (smoke) dispersed phase; used in fumigation or in inhalation therapy; may contain propellent agents. [NIH]

Affective Symptoms: Mood or emotional responses dissonant with or inappropriate to the behavior and/or stimulus. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Akathisia: 1. A condition of motor restlessness in which there is a feeling of muscular quivering, an urge to move about constantly, and an inability to sit still, a common extrapyramidal side effect of neuroleptic drugs. 2. An inability to sit down because of intense anxiety at the thought of doing so. [EU] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH]

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Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha Particles: Positively charged particles composed of two protons and two neutrons, i.e., helium nuclei, emitted during disintegration of very heavy isotopes; a beam of alpha particles or an alpha ray has very strong ionizing power, but weak penetrability. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Aluminum: A metallic element that has the atomic number 13, atomic symbol Al, and atomic weight 26.98. [NIH] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnesia: Lack or loss of memory; inability to remember past experiences. [EU]

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Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]

Anabolic: Relating to, characterized by, or promoting anabolism. [EU] Anabolic Steroids: Chemical derivatives of testosterone that are used for anabolic promotion of growth and repair of body tissues and the development of male sexual characteristics. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anaphylatoxins: The family of peptides C3a, C4a, C5a, and C5a des-arginine produced in the serum during complement activation. They produce smooth muscle contraction, mast cell histamine release, affect platelet aggregation, and act as mediators of the local inflammatory process. The order of anaphylatoxin activity from strongest to weakest is C5a, C3a, C4a, and C5a des-arginine. The latter is the so-called "classical" anaphylatoxin but shows no spasmogenic activity though it contains some chemotactic ability. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful

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situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Anisotropy: A physical property showing different values in relation to the direction in or along which the measurement is made. The physical property may be with regard to thermal or electric conductivity or light refraction. In crystallography, it describes crystals whose index of refraction varies with the direction of the incident light. It is also called acolotropy and colotropy. The opposite of anisotropy is isotropy wherein the same values characterize the object when measured along axes in all directions. [NIH] Anosognosia: Inability to recognize loss of function, disease, or defect in a part of one's own body. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressive Agents: Mood-stimulating drugs used primarily in the treatment of affective disorders and related conditions. Several monoamine oxidase inhibitors are useful as antidepressants apparently as a long-term consequence of their modulation of catecholamine levels. The tricyclic compounds useful as antidepressive agents also appear to act through brain catecholamine systems. A third group (antidepressive agents, secondgeneration) is a diverse group of drugs including some that act specifically on serotonergic systems. [NIH]

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Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antigen-Antibody Complex: The complex formed by the binding of antigen and antibody molecules. The deposition of large antigen-antibody complexes leading to tissue damage causes immune complex diseases. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiety Disorders: Disorders in which anxiety (persistent feelings of apprehension, tension, or uneasiness) is the predominant disturbance. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apathy: Lack of feeling or emotion; indifference. [EU] Aphasia: A cognitive disorder marked by an impaired ability to comprehend or express language in its written or spoken form. This condition is caused by diseases which affect the language areas of the dominant hemisphere. Clinical features are used to classify the various subtypes of this condition. General categories include receptive, expressive, and mixed forms of aphasia. [NIH] Apnea: A transient absence of spontaneous respiration. [NIH] Apnoea: Cessation of breathing. [EU] Applicability: A list of the commodities to which the candidate method can be applied as

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presented or with minor modifications. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Art Therapy: The use of art as an adjunctive therapy in the treatment of neurological, mental, or behavioral disorders. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Aspiration: The act of inhaling. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Ataxia: Impairment of the ability to perform smoothly coordinated voluntary movements. This condition may affect the limbs, trunk, eyes, pharnyx, larnyx, and other structures. Ataxia may result from impaired sensory or motor function. Sensory ataxia may result from posterior column injury or peripheral nerve diseases. Motor ataxia may be associated with cerebellar diseases; cerebral cortex diseases; thalamic diseases; basal ganglia diseases; injury to the red nucleus; and other conditions. [NIH] Atrial: Pertaining to an atrium. [EU] Atrioventricular: Pertaining to an atrium of the heart and to a ventricle. [EU] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU] Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Autoimmune disease: A condition in which the body recognizes its own tissues as foreign and directs an immune response against them. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Nervous System: The enteric, parasympathetic, and sympathetic nervous systems taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the central nervous system, especially the

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hypothalamus and the solitary nucleus, which receive information relayed from visceral afferents; these and related central and sensory structures are sometimes (but not here) considered to be part of the autonomic nervous system itself. [NIH] Autopsy: Postmortem examination of the body. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bacterial Physiology: Physiological processes and activities of bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturates: A class of chemicals derived from barbituric acid or thiobarbituric acid. Many of these are medically important as sedatives and hypnotics (sedatives, barbiturate), as anesthetics, or as anticonvulsants. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Basophils: Granular leukocytes characterized by a relatively pale-staining, lobate nucleus and cytoplasm containing coarse dark-staining granules of variable size and stainable by basic dyes. [NIH] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Behavioral Symptoms: Observable manifestions of impaired psychological functioning. [NIH]

Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bilateral: Affecting both the right and left side of body. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioequivalent: Having the same strength and similar bioavailability in the same dosage form as another specimen of a given drug substance. [EU] Biogenic Amines: A group of naturally occurring amines derived by enzymatic decarboxylation of the natural amino acids. Many have powerful physiological effects (e.g.,

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histamine, serotonin, epinephrine, tyramine). Those derived from aromatic amino acids, and also their synthetic analogs (e.g., amphetamine), are of use in pharmacology. [NIH] Biogenic Monoamines: Biogenic amines having only one amine moiety. Included in this group are all natural monoamines formed by the enzymatic decarboxylation of natural amino acids. [NIH] Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc. [NIH] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bipolar Disorder: A major affective disorder marked by severe mood swings (manic or major depressive episodes) and a tendency to remission and recurrence. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [NIH]

Body Fluids: Liquid components of living organisms. [NIH] Body Image: Individuals' personal concept of their bodies as objects in and bound by space, independently and apart from all other objects. [NIH] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the

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bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Brain Neoplasms: Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain. [NIH] Brain Stem: The part of the brain that connects the cerebral hemispheres with the spinal cord. It consists of the mesencephalon, pons, and medulla oblongata. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Bupropion: A unicyclic, aminoketone antidepressant. The mechanism of its therapeutic actions is not well understood, but it does appear to block dopamine uptake. The hydrochloride is available as an aid to smoking cessation treatment. [NIH] Burns: Injuries to tissues caused by contact with heat, steam, chemicals (burns, chemical), electricity (burns, electric), or the like. [NIH] Burns, Electric: Burns produced by contact with electric current or from a sudden discharge of electricity. [NIH] Buspirone: An anxiolytic agent and a serotonin receptor agonist belonging to the azaspirodecanedione class of compounds. Its structure is unrelated to those of the benzodiazepines, but it has an efficacy comparable to diazepam. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the

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alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiology: The study of the heart, its physiology, and its functions. [NIH] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carnitine: Constituent of striated muscle and liver. It is used therapeutically to stimulate gastric and pancreatic secretions and in the treatment of hyperlipoproteinemias. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheter: A flexible tube used to deliver fluids into or withdraw fluids from the body. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Caudate Nucleus: Elongated gray mass of the neostriatum located adjacent to the lateral

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ventricle of the brain. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Cycle: The complex series of phenomena, occurring between the end of one cell division and the end of the next, by which cellular material is divided between daughter cells. [NIH] Cell Division: The fission of a cell. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Diseases: Diseases of any component of the brain (including the cerebral hemispheres, diencephalon, brain stem, and cerebellum) or the spinal cord. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebellum: Part of the metencephalon that lies in the posterior cranial fossa behind the brain stem. It is concerned with the coordination of movement. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Cortex: The thin layer of gray matter on the surface of the cerebral hemisphere that develops from the telencephalon and folds into gyri. It reaches its highest development in man and is responsible for intellectual faculties and higher mental functions. [NIH] Cerebral hemispheres: The two halves of the cerebrum, the part of the brain that controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. The right hemisphere controls muscle movement on the left side of the body, and the left hemisphere controls muscle movement on the right side of the body. [NIH] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [EU]

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Chemotactic Factors: Chemical substances that attract or repel cells or organisms. The concept denotes especially those factors released as a result of tissue injury, invasion, or immunologic activity, that attract leukocytes, macrophages, or other cells to the site of infection or insult. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [NIH] Chloral Hydrate: A hypnotic and sedative used in the treatment of insomnia. The safety margin is too narrow for chloral hydrate to be used as a general anesthetic in humans, but it is commonly used for that purpose in animal experiments. It is no longer considered useful as an anti-anxiety medication. [NIH] Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [NIH]

Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chorea: Involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. Hypotonia and pendular reflexes are often associated. Conditions which feature recurrent or persistent episodes of chorea as a primary manifestation of disease are referred to as choreatic disorders. Chorea is also a frequent manifestation of basal ganglia diseases. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Disease: Disease or ailment of long duration. [NIH] Chronic Fatigue Syndrome: Fatigue caused by the combined effects of different types of prolonged fatigue. [NIH] Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clinical Medicine: The study and practice of medicine by direct examination of the patient. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Clomipramine: A tricyclic antidepressant similar to imipramine that selectively inhibits the uptake of serotonin in the brain. It is readily absorbed from the gastrointestinal tract and demethylated in the liver to form its primary active metabolite, desmethylclomipramine. [NIH]

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Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collagen disease: A term previously used to describe chronic diseases of the connective tissue (e.g., rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis), but now is thought to be more appropriate for diseases associated with defects in collagen, which is a component of the connective tissue. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colon: The long, coiled, tubelike organ that removes water from digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus. [NIH] Comorbidity: The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector

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not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Compliance: Distensibility measure of a chamber such as the lungs (lung compliance) or bladder. Compliance is expressed as a change in volume per unit change in pressure. [NIH] Compulsions: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [NIH] Computational Biology: A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized tomography. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Confounding: Extraneous variables resulting in outcome effects that obscure or exaggerate

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the "true" effect of an intervention. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Convulsive Therapy: The use of convulsive agents to influence favorably the course of a mental disorder. It is used primarily in the treatment of severe affective disorders and schizophrenia. [NIH] Coordination: Muscular or motor regulation or the harmonious cooperation of muscles or groups of muscles, in a complex action or series of actions. [NIH] Cor: The muscular organ that maintains the circulation of the blood. c. adiposum a heart that has undergone fatty degeneration or that has an accumulation of fat around it; called also fat or fatty, heart. c. arteriosum the left side of the heart, so called because it contains oxygenated (arterial) blood. c. biloculare a congenital anomaly characterized by failure of formation of the atrial and ventricular septums, the heart having only two chambers, a single atrium and a single ventricle, and a common atrioventricular valve. c. bovinum (L. 'ox heart') a greatly enlarged heart due to a hypertrophied left ventricle; called also c. taurinum and bucardia. c. dextrum (L. 'right heart') the right atrium and ventricle. c. hirsutum, c. villosum. c. mobile (obs.) an abnormally movable heart. c. pendulum a heart so movable that it seems to be hanging by the great blood vessels. c. pseudotriloculare biatriatum a congenital cardiac anomaly in which the heart functions as a three-chambered heart because of tricuspid atresia, the right ventricle being extremely small or rudimentary and the right atrium greatly dilated. Blood passes from the right to the left atrium and thence disease due to pulmonary hypertension secondary to disease of the lung, or its blood vessels, with

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hypertrophy of the right ventricle. [EU] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary Disease: Disorder of cardiac function due to an imbalance between myocardial function and the capacity of the coronary vessels to supply sufficient flow for normal function. It is a form of myocardial ischemia (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. [NIH] Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vessels: The veins and arteries of the heart. [NIH] Corpus: The body of the uterus. [NIH] Corpus Callosum: Broad plate of dense myelinated fibers that reciprocally interconnect regions of the cortex in all lobes with corresponding regions of the opposite hemisphere. The corpus callosum is located deep in the longitudinal fissure. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cotinine: 1-Methyl-5-(3-pyridyl)-2-pyrrolidinone antidepressant. Synonym: Scotine. [NIH]

fumarate.

Stimulant

proposed

as

Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH]

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Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cystitis: Inflammation of the urinary bladder. [EU] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Data Collection: Systematic gathering of data for a particular purpose from various sources, including questionnaires, interviews, observation, existing records, and electronic devices. The process is usually preliminary to statistical analysis of the data. [NIH] Deamination: The removal of an amino group (NH2) from a chemical compound. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Delusions: A false belief regarding the self or persons or objects outside the self that persists despite the facts, and is not considered tenable by one's associates. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

Dentate Gyrus: Gray matter situated above the gyrus hippocampi. It is composed of three layers. The molecular layer is continuous with the hippocampus in the hippocampal fissure. The granular layer consists of closely arranged spherical or oval neurons, called granule

Dictionary 271

cells, whose axons pass through the polymorphic layer ending on the dendrites of pyramidal cells in the hippocampus. [NIH] Dentists: Individuals licensed to practice dentistry. [NIH] Depersonalization: Alteration in the perception of the self so that the usual sense of one's own reality is lost, manifested in a sense of unreality or self-estrangement, in changes of body image, or in a feeling that one does not control his own actions and speech; seen in depersonalization disorder, schizophrenic disorders, and schizotypal personality disorder. Some do not draw a distinction between depersonalization and derealization, using depersonalization to include both. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Developed Countries: Countries that have reached a level of economic achievement through an increase of production, per capita income and consumption, and utilization of natural and human resources. [NIH] Dexamethasone: (11 beta,16 alpha)-9-Fluoro-11,17,21-trihydroxy-16-methylpregna-1,4diene-3,20-dione. An anti-inflammatory glucocorticoid used either in the free alcohol or esterified form in treatment of conditions that respond generally to cortisone. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextrorotatory: Turning towards the right hand. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diastolic: Of or pertaining to the diastole. [EU] Diathesis: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the person more than usually susceptible to certain diseases. [EU] Diencephalon: The paired caudal parts of the prosencephalon from which the thalamus, hypothalamus, epithalamus, and subthalamus are derived. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or

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concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrete: Made up of separate parts or characterized by lesions which do not become blended; not running together; separate. [NIH] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disparity: Failure of the two retinal images of an object to fall on corresponding retinal points. [NIH] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diurnal: Occurring during the day. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dominance: In genetics, the full phenotypic expression of a gene in both heterozygotes and homozygotes. [EU] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments,

Dictionary 273

pharmaceutical solutions, powders, tablets, etc. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Drinking Behavior: Behaviors associated with the ingesting of water and other liquids; includes rhythmic patterns of drinking (time intervals - onset and duration), frequency and satiety. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Design: The molecular designing of drugs for specific purposes (such as DNAbinding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dyspareunia: Painful sexual intercourse. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH] Dysphagia: Difficulty in swallowing. [EU] Dysphoria: Disquiet; restlessness; malaise. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Dystrophy: Any disorder arising from defective or faulty nutrition, especially the muscular dystrophies. [EU] Eating Disorders: A group of disorders characterized by physiological and psychological disturbances in appetite or food intake. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electric Conductivity: The ability of a substrate to allow the passage of electrons. [NIH] Electric shock: A dangerous patho-physiological effect resulting from an electric current passing through the body of a human or animal. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the

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treatment of severe affective disorders and schizophrenia. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electroencephalography: Recording of electric currents developed in the brain by means of electrodes applied to the scalp, to the surface of the brain, or placed within the substance of the brain. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Elementary Particles: Individual components of atoms, usually subatomic; subnuclear particles are usually detected only when the atomic nucleus decays and then only transiently, as most of them are unstable, often yielding pure energy without substance, i.e., radiation. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Enamel: A very hard whitish substance which covers the dentine of the anatomical crown of a tooth. [NIH] Encephalitis: Inflammation of the brain due to infection, autoimmune processes, toxins, and other conditions. Viral infections (see encephalitis, viral) are a relatively frequent cause of this condition. [NIH] Endemic: Present or usually prevalent in a population or geographical area at all times; said of a disease or agent. Called also endemial. [EU] Endocrine System: The system of glands that release their secretions (hormones) directly into the circulatory system. In addition to the endocrine glands, included are the chromaffin system and the neurosecretory systems. [NIH] Endocrinology: A subspecialty of internal medicine concerned with the metabolism, physiology, and disorders of the endocrine system. [NIH]

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Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endorphins: One of the three major groups of endogenous opioid peptides. They are large peptides derived from the pro-opiomelanocortin precursor. The known members of this group are alpha-, beta-, and gamma-endorphin. The term endorphin is also sometimes used to refer to all opioid peptides, but the narrower sense is used here; opioid peptides is used for the broader group. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] Energetic: Exhibiting energy : strenuous; operating with force, vigour, or effect. [EU] Enhancer: Transcriptional element in the virus genome. [NIH] Enkephalins: One of the three major families of endogenous opioid peptides. The enkephalins are pentapeptides that are widespread in the central and peripheral nervous systems and in the adrenal medulla. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [NIH] Environmental Exposure: The exposure to potentially harmful chemical, physical, or biological agents in the environment or to environmental factors that may include ionizing radiation, pathogenic organisms, or toxic chemicals. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Eosinophils: Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidemiologic Studies: Studies designed to examine associations, commonly, hypothesized causal relations. They are usually concerned with identifying or measuring the effects of risk factors or exposures. The common types of analytic study are case-control studies, cohort studies, and cross-sectional studies. [NIH] Epidemiological: Relating to, or involving epidemiology. [EU] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Epithalamus: The dorsal posterior subdivision of the diencephalon. The epithalamus is

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generally considered to include the habenular nuclei (habenula) and associated fiber bundles, the pineal body, and the epithelial roof of the third ventricle. The anterior and posterior paraventricular nuclei of the thalamus are included with the thalamic nuclei although they develop from the same pronuclear mass as the epithalamic nuclei and are sometimes considered part of the epithalamus. [NIH] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [NIH] Erythrina: A genus of leguminous shrubs or trees, mainly tropical, yielding certain alkaloids, lectins, and other useful compounds. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Estradiol: The most potent mammalian estrogenic hormone. It is produced in the ovary, placenta, testis, and possibly the adrenal cortex. [NIH] Estrogen: One of the two female sex hormones. [NIH] Estrogen Replacement Therapy: The use of hormonal agents with estrogen-like activity in postmenopausal or other estrogen-deficient women to alleviate effects of hormone deficiency, such as vasomotor symptoms, dyspareunia, and progressive development of osteoporosis. This may also include the use of progestational agents in combination therapy. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitation: An act of irritation or stimulation or of responding to a stimulus; the addition of energy, as the excitation of a molecule by absorption of photons. [EU] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] Expiratory Reserve Volume: The extra volume of air that can be expired with maximum effort beyond the level reached at the end of a normal, quiet expiration. Common abbreviation is ERV. [NIH] Extensor: A muscle whose contraction tends to straighten a limb; the antagonist of a flexor. [NIH]

External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU]

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Extravasation: A discharge or escape, as of blood, from a vessel into the tissues. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Family Practice: A medical specialty concerned with the provision of continuing, comprehensive primary health care for the entire family. [NIH] Family Relations: Behavioral, psychological, and social relations among various members of the nuclear family and the extended family. [NIH] Famotidine: A competitive histamine H2-receptor antagonist. Its main pharmacodynamic effect is the inhibition of gastric secretion. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fissure: Any cleft or groove, normal or otherwise; especially a deep fold in the cerebral cortex which involves the entire thickness of the brain wall. [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flatus: Gas passed through the rectum. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flush: Transient, episodic redness of the face and neck caused by certain diseases, ingestion of certain drugs or other substances, heat, emotional factors, or physical exertion. [EU] Fluvoxamine: A selective serotonin reuptake inhibitor. It is effective in the treatment of depression, obsessive-compulsive disorders, anxiety, panic disorders, and alcohol amnestic disorders. [NIH] Folate: A B-complex vitamin that is being studied as a cancer prevention agent. Also called folic acid. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Folic

Acid:

N-(4-(((2-Amino-1,4-dihydro-4-oxo-6-pteridinyl)methyl)amino)benzoyl)-L-

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glutamic acid. A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses. Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fourth Ventricle: An irregularly shaped cavity in the rhombencephalon, between the medulla oblongata, the pons, and the isthmus in front, and the cerebellum behind. It is continuous with the central canal of the cord below and with the cerebral aqueduct above, and through its lateral and median apertures it communicates with the subarachnoid space. [NIH]

Fractionation: Dividing the total dose of radiation therapy into several smaller, equal doses delivered over a period of several days. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Fumigation: The application of smoke, vapor, or gas for the purpose of disinfecting or destroying pests or microorganisms. [NIH] Functional magnetic resonance imaging: A noninvasive tool used to observe functioning in the brain or other organs by detecting changes in chemical composition, blood flow, or both. [NIH]

Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gait: Manner or style of walking. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH]

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Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetic Engineering: Directed modification of the gene complement of a living organism by such techniques as altering the DNA, substituting genetic material by means of a virus, transplanting whole nuclei, transplanting cell hybrids, etc. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Geriatric: Pertaining to the treatment of the aged. [EU] Gestation: The period of development of the young in viviparous animals, from the time of fertilization of the ovum until birth. [EU] Ginseng: An araliaceous genus of plants that contains a number of pharmacologically active agents used as stimulants, sedatives, and tonics, especially in traditional medicine. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid (glutamate) is the most common excitatory neurotransmitter in the central nervous system. [NIH]

Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Gonad: A sex organ, such as an ovary or a testicle, which produces the gametes in most multicellular animals. [NIH] Gonadal: Pertaining to a gonad. [EU] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Grasses: A large family, Gramineae, of narrow-leaved herbaceous monocots. Many grasses produce highly allergenic pollens and are hosts to cattle parasites and toxic fungi. [NIH] Guanine: One of the four DNA bases. [NIH]

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Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Gyrus Cinguli: One of the convolutions on the medial surface of the cerebral hemisphere. It surrounds the rostral part of the brain and interhemispheric commissure and forms part of the limbic system. [NIH] Habitat: An area considered in terms of its environment, particularly as this determines the type and quality of the vegetation the area can carry. [NIH] Hammer: The largest of the three ossicles of the ear. [NIH] Happiness: Highly pleasant emotion characterized by outward manifestations of gratification; joy. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Health Promotion: Encouraging consumer behaviors most likely to optimize health potentials (physical and psychosocial) through health information, preventive programs, and access to medical care. [NIH] Health Services: Services for the diagnosis and treatment of disease and the maintenance of health. [NIH] Health Status: The level of health of the individual, group, or population as subjectively assessed by the individual or by more objective measures. [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Hematoma: An extravasation of blood localized in an organ, space, or tissue. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion

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and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatitis D: Hepatitis caused by the hepatitis delta virus in association with hepatitis B. It is endemic in some European countries and is seen in drug users, hemophiliacs, and polytransfused persons. [NIH] Hepatitis Delta Virus: A defective virus, containing particles of RNA nucleoprotein in virion-like form, present in patients with acute hepatitis B and chronic hepatitis. Officially this is classified as a subviral satellite RNA. [NIH] Hepatocyte: A liver cell. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Heterozygotes: Having unlike alleles at one or more corresponding loci on homologous chromosomes. [NIH] Hippocampus: A curved elevation of gray matter extending the entire length of the floor of the temporal horn of the lateral ventricle (Dorland, 28th ed). The hippocampus, subiculum, and dentate gyrus constitute the hippocampal formation. Sometimes authors include the entorhinal cortex in the hippocampal formation. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Homosexuality: Sexual attraction or relationship between members of the same sex. [NIH] Homozygotes: An individual having a homozygous gene pair. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hospice: Institution dedicated to caring for the terminally ill. [NIH] Humidifier: A machine that puts moisture in the air. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result

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of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrocortisone: The main glucocorticoid secreted by the adrenal cortex. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthermia: A type of treatment in which body tissue is exposed to high temperatures to damage and kill cancer cells or to make cancer cells more sensitive to the effects of radiation and certain anticancer drugs. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypochondriasis: (DSM III-R) a mental disorder characterized by a preoccupation with bodily functions and the interpretation of normal sensations (such as heart beats, sweating, peristaltic action, and bowel movements) or minor abnormalities (such as a runny nose, minor aches and pains, or slightly swollen lymph nodes) as indications of highly disturbing problems needing medical attention. Negative results of diagnostic evaluations and reassurance by physicians only increase the patient's anxious concern about his health, and the patient continues to seek medical attention. Called also hypochondriacal neurosis. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypoglycemia: Abnormally low blood sugar [NIH] Hypoglycemic: An orally active drug that produces a fall in blood glucose concentration. [NIH]

Hypotension: Abnormally low blood pressure. [NIH] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothalamic: Of or involving the hypothalamus. [EU] Hypothalamus: Ventral part of the diencephalon extending from the region of the optic chiasm to the caudal border of the mammillary bodies and forming the inferior and lateral walls of the third ventricle. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in

Dictionary 283

the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Ileum: The lower end of the small intestine. [NIH] Imidazole: C3H4N2. The ring is present in polybenzimidazoles. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]

Immune function: Production and action of cells that fight disease or infection. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Implantable pump: A small device installed under the skin to administer a steady dose of drugs. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU]

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Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infectious Mononucleosis: A common, acute infection usually caused by the Epstein-Barr virus (Human herpesvirus 4). There is an increase in mononuclear white blood cells and other atypical lymphocytes, generalized lymphadenopathy, splenomegaly, and occasionally hepatomegaly with hepatitis. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]

Infuse: To pour (a liquid) into something. [EU] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inositol: An isomer of glucose that has traditionally been considered to be a B vitamin although it has an uncertain status as a vitamin and a deficiency syndrome has not been identified in man. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1379) Inositol phospholipids are important in signal transduction. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Insulator: Material covering the metal conductor of the lead. It is usually polyurethane or silicone. [NIH] Interferon: A biological response modifier (a substance that can improve the body's natural response to disease). Interferons interfere with the division of cancer cells and can slow tumor growth. There are several types of interferons, including interferon-alpha, -beta, and gamma. These substances are normally produced by the body. They are also made in the laboratory for use in treating cancer and other diseases. [NIH]

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Interferon-alpha: One of the type I interferons produced by peripheral blood leukocytes or lymphoblastoid cells when exposed to live or inactivated virus, double-stranded RNA, or bacterial products. It is the major interferon produced by virus-induced leukocyte cultures and, in addition to its pronounced antiviral activity, it causes activation of NK cells. [NIH] Intergenerational Relations: The interactions between individuals of different generations. These interactions include communication, caring, accountability, loyalty, and even conflict between related or non-related individuals. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intracranial Hemorrhages: Bleeding within the intracranial cavity, including hemorrhages in the brain and within the cranial epidural, subdural, and subarachnoid spaces. [NIH] Intracranial Hypertension: Increased pressure within the cranial vault. This may result from several conditions, including hydrocephalus; brain edema; intracranial masses; severe systemic hypertension; pseudotumor cerebri; and other disorders. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [EU]

Involuntary: Reaction occurring without intention or volition. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Kainate: Glutamate receptor. [NIH]

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Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratolytic: An agent that promotes keratolysis. [EU] Labile: 1. Gliding; moving from point to point over the surface; unstable; fluctuating. 2. Chemically unstable. [EU] Lactation: The period of the secretion of milk. [EU] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latency: The period of apparent inactivity between the time when a stimulus is presented and the moment a response occurs. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lectins: Protein or glycoprotein substances, usually of plant origin, that bind to sugar moieties in cell walls or membranes and thereby change the physiology of the membrane to cause agglutination, mitosis, or other biochemical changes in the cell. [NIH] Length of Stay: The period of confinement of a patient to a hospital or other health facility. [NIH]

Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Lethargy: Abnormal drowsiness or stupor; a condition of indifference. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number 3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

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Lithium Carbonate: A lithium salt, classified as a mood-stabilizing agent. Lithium ion alters the metabolism of biogenic monoamines in the central nervous system, and affects multiple neurotransmission systems. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localization: The process of determining or marking the location or site of a lesion or disease. May also refer to the process of keeping a lesion or disease in a specific location or site. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Locus Coeruleus: Bluish region in the superior angle of the fourth ventricle floor, corresponding to melanin-like pigmented nerve cells which lie lateral to the pontomesencephalic central gray (griseum centrale). It is also known as nucleus pigmentosus pontis. [NIH] Loneliness: The state of feeling sad or dejected as a result of lack of companionship or being separated from others. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Longitudinal study: Also referred to as a "cohort study" or "prospective study"; the analytic method of epidemiologic study in which subsets of a defined population can be identified who are, have been, or in the future may be exposed or not exposed, or exposed in different degrees, to a factor or factors hypothesized to influence the probability of occurrence of a given disease or other outcome. The main feature of this type of study is to observe large numbers of subjects over an extended time, with comparisons of incidence rates in groups that differ in exposure levels. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lumbar puncture: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a spinal tap. [NIH] Lutein Cells: The cells of the corpus luteum which are derived from the granulosa cells and the theca cells of the Graafian follicle. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph

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nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (magnetic resonance imaging). [NIH] Magnetoencephalography: The measurement of magnetic fields over the head generated by electric currents in the brain. As in any electrical conductor, electric fields in the brain are accompanied by orthogonal magnetic fields. The measurement of these fields provides information about the localization of brain activity which is complementary to that provided by electroencephalography. Magnetoencephalography may be used alone or together with electroencephalography, for measurement of spontaneous or evoked activity, and for research or clinical purposes. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Maprotiline: A bridged-ring tetracyclic antidepressant that is both mechanistically and functionally similar to the tricyclic antidepressants, including side effects associated with its use. [NIH] Marijuana Abuse: The excessive use of marijuana with associated psychological symptoms and impairment in social or occupational functioning. [NIH] Meatus: A canal running from the internal auditory foramen through the petrous portion of the temporal bone. It gives passage to the facial and auditory nerves together with the auditory branch of the basilar artery and the internal auditory veins. [NIH] Mecamylamine: A nicotinic antagonist that is well absorbed from the gastrointestinal tract and crosses the blood-brain barrier. Mecamylamine has been used as a ganglionic blocker in treating hypertension, but, like most ganglionic blockers, is more often used now as a research tool. [NIH] Mechanical ventilation: Use of a machine called a ventilator or respirator to improve the exchange of air between the lungs and the atmosphere. [NIH] Medial: Lying near the midsaggital plane of the body; opposed to lateral. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen

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with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Records: Recording of pertinent information concerning patient's illness or illnesses. [NIH] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Megaloblastic: A large abnormal red blood cell appearing in the blood in pernicious anaemia. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Memantine: Amantadine derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Memory Disorders: Disturbances in registering an impression, in the retention of an acquired impression, or in the recall of an impression. Memory impairments are associated with dementia; craniocerebraltrauma; encephalitis; alcoholism (see also alcohol amnestic disorder); schizophrenia; and other conditions. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Mental Health Services: Organized services to provide mental health care. [NIH] Mental Processes: Conceptual functions or thinking in all its forms. [NIH] Mental Retardation: Refers to sub-average general intellectual functioning which originated during the developmental period and is associated with impairment in adaptive behavior. [NIH]

Mentors: Senior professionals who provide guidance, direction and support to those persons desirous of improvement in academic positions, administrative positions or other career development situations. [NIH] Mesencephalic: Ipsilateral oculomotor paralysis and contralateral tremor, spasm. or choreic movements of the face and limbs. [NIH] Mesolimbic: Inner brain region governing emotion and drives. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions

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which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microglia: The third type of glial cell, along with astrocytes and oligodendrocytes (which together form the macroglia). Microglia vary in appearance depending on developmental stage, functional state, and anatomical location; subtype terms include ramified, perivascular, ameboid, resting, and activated. Microglia clearly are capable of phagocytosis and play an important role in a wide spectrum of neuropathologies. They have also been suggested to act in several other roles including in secretion (e.g., of cytokines and neural growth factors), in immunological processing (e.g., antigen presentation), and in central nervous system development and remodeling. [NIH] Micro-organism: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Moclobemide: A reversible inhibitor of monoamine oxidase type A (RIMA) that has antidepressive properties. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the

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same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Mononucleosis: The presence of an abnormally large number of mononuclear leucocytes (monocytes) in the blood. The term is often used alone to refer to infectious mononucleosis. [EU]

Monotherapy: A therapy which uses only one drug. [EU] Mood Disorders: Those disorders that have a disturbance in mood as their predominant feature. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multiple sclerosis: A disorder of the central nervous system marked by weakness, numbness, a loss of muscle coordination, and problems with vision, speech, and bladder control. Multiple sclerosis is thought to be an autoimmune disease in which the body's immune system destroys myelin. Myelin is a substance that contains both protein and fat (lipid) and serves as a nerve insulator and helps in the transmission of nerve signals. [NIH] Muscular Dystrophies: A general term for a group of inherited disorders which are characterized by progressive degeneration of skeletal muscles. [NIH] Myelin: The fatty substance that covers and protects nerves. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH]

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Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myotonic Dystrophy: A condition presenting muscle weakness and wasting which may be progressive. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Neoplastic: Pertaining to or like a neoplasm (= any new and abnormal growth); pertaining to neoplasia (= the formation of a neoplasm). [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nerve Endings: Specialized terminations of peripheral neurons. Nerve endings include neuroeffector junction(s) by which neurons activate target organs and sensory receptors which transduce information from the various sensory modalities and send it centrally in the nervous system. Presynaptic nerve endings are presynaptic terminals. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Networks: Pertaining to a nerve or to the nerves, a meshlike structure of interlocking fibers or strands. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuroendocrine: Having to do with the interactions between the nervous system and the endocrine system. Describes certain cells that release hormones into the blood in response to stimulation of the nervous system. [NIH] Neuroendocrinology: The study of the anatomical and functional relationships between the nervous system and the endocrine system. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of

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emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neurologic: Having to do with nerves or the nervous system. [NIH] Neurology: A medical specialty concerned with the study of the structures, functions, and diseases of the nervous system. [NIH] Neuroma: A tumor that arises in nerve cells. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neuropeptide: A member of a class of protein-like molecules made in the brain. Neuropeptides consist of short chains of amino acids, with some functioning as neurotransmitters and some functioning as hormones. [NIH] Neuropsychological Tests: Tests designed to assess neurological function associated with certain behaviors. They are used in diagnosing brain dysfunction or damage and central nervous system disorders or injury. [NIH] Neuropsychology: A branch of psychology which investigates the correlation between experience or behavior and the basic neurophysiological processes. The term neuropsychology stresses the dominant role of the nervous system. It is a more narrowly defined field than physiological psychology or psychophysiology. [NIH] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurotic: 1. Pertaining to or characterized by neurosis. 2. A person affected with a neurosis. [EU]

Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neurovegetative: Pertaining to the vegetative (autonomic) nervous system. [EU] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant

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tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [NIH] Niche: The ultimate unit of the habitat, i. e. the specific spot occupied by an individual organism; by extension, the more or less specialized relationships existing between an organism, individual or synusia(e), and its environment. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Nonverbal Communication: Transmission of emotions, ideas, and attitudes between individuals in ways other than the spoken language. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nuclear Family: A family composed of spouses and their children. [NIH] Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleus Accumbens: Collection of pleomorphic cells in the caudal part of the anterior horn of the lateral ventricle, in the region of the olfactory tubercle, lying between the head of the caudate nucleus and the anterior perforated substance. It is part of the so-called ventral striatum, a composite structure considered part of the basal ganglia. [NIH] Nutritional Status: State of the body in relation to the consumption and utilization of nutrients. [NIH] Observational study: An epidemiologic study that does not involve any intervention, experimental or otherwise. Such a study may be one in which nature is allowed to take its

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course, with changes in one characteristic being studied in relation to changes in other characteristics. Analytical epidemiologic methods, such as case-control and cohort study designs, are properly called observational epidemiology because the investigator is observing without intervention other than to record, classify, count, and statistically analyze results. [NIH] Obsessive-Compulsive Disorder: An anxiety disorder characterized by recurrent, persistent obsessions or compulsions. Obsessions are the intrusive ideas, thoughts, or images that are experienced as senseless or repugnant. Compulsions are repetitive and seemingly purposeful behavior which the individual generally recognizes as senseless and from which the individual does not derive pleasure although it may provide a release from tension. [NIH] Occult: Obscure; concealed from observation, difficult to understand. [EU] Occupational Therapy: The field concerned with utilizing craft or work activities in the rehabilitation of patients. Occupational therapy can also refer to the activities themselves. [NIH]

Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Omega-3 fatty acid: A type of fat obtained in the diet and involved in immunity. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Ophthalmoplegia: Paralysis of one or more of the ocular muscles due to disorders of the eye muscles, neuromuscular junction, supporting soft tissue, tendons, or innervation to the muscles. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Optic Chiasm: The X-shaped structure formed by the meeting of the two optic nerves. At the optic chiasm the fibers from the medial part of each retina cross to project to the other side of the brain while the lateral retinal fibers continue on the same side. As a result each half of the brain receives information about the contralateral visual field from both eyes. [NIH]

Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Ossicles: The hammer, anvil and stirrup, the small bones of the middle ear, which transmit the vibrations from the tympanic membrane to the oval window. [NIH] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis,

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especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Osteoporosis: Reduction of bone mass without alteration in the composition of bone, leading to fractures. Primary osteoporosis can be of two major types: postmenopausal osteoporosis and age-related (or senile) osteoporosis. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Ovary: Either of the paired glands in the female that produce the female germ cells and secrete some of the female sex hormones. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreatic: Having to do with the pancreas. [NIH] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Parent-Child Relations: The interactions between parent and child. [NIH] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH]

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Partial response: A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. [NIH] Particle: A tiny mass of material. [EU] Parturition: The act or process of given birth to a child. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathogenesis: The cellular events and reactions that occur in the development of disease. [NIH]

Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Pelvis: The lower part of the abdomen, located between the hip bones. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] Perimenopausal: The time of a woman's life when menstrual periods become irregular. Refers to the time near menopause. [NIH] Perinatal: Pertaining to or occurring in the period shortly before and after birth; variously defined as beginning with completion of the twentieth to twenty-eighth week of gestation and ending 7 to 28 days after birth. [EU] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that

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is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetics: Dynamic and kinetic mechanisms of exogenous chemical and drug absorption, biotransformation, distribution, release, transport, uptake, and elimination as a function of dosage, and extent and rate of metabolic processes. It includes toxicokinetics, the pharmacokinetic mechanism of the toxic effects of a substance. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacology, Clinical: The branch of pharmacology that deals directly with the effectiveness and safety of drugs in humans. [NIH] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phobia: A persistent, irrational, intense fear of a specific object, activity, or situation (the phobic stimulus), fear that is recognized as being excessive or unreasonable by the individual himself. When a phobia is a significant source of distress or interferes with social functioning, it is considered a mental disorder; phobic disorder (or neurosis). In DSM III phobic disorders are subclassified as agoraphobia, social phobias, and simple phobias. Used as a word termination denoting irrational fear of or aversion to the subject indicated by the stem to which it is affixed. [EU] Phobic Disorders: Anxiety disorders in which the essential feature is persistent and irrational fear of a specific object, activity, or situation that the individual feels compelled to avoid. The individual recognizes the fear as excessive or unreasonable. [NIH] Phosphates: Inorganic salts of phosphoric acid. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [NIH] Phototransduction: The transducing of light energy to afferent nerve impulses, such as takes place in the retinal rods and cones. After light photons are absorbed by the photopigments, the signal is transmitted to the outer segment membrane by the cyclic GMP second messenger system, where it closes the sodium channels. This channel gating ultimately generates an action potential in the inner retina. [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Pilot Projects: Small-scale tests of methods and procedures to be used on a larger scale if the

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pilot study demonstrates that these methods and procedures can work. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pitch: The subjective awareness of the frequency or spectral distribution of a sound. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Pituitary-Adrenal System: The interactions between the anterior pituitary and adrenal glands, in which corticotropin (ACTH) stimulates the adrenal cortex and adrenal cortical hormones suppress the production of corticotropin by the anterior pituitary. [NIH] Placenta: A highly vascular fetal organ through which the fetus absorbs oxygen and other nutrients and excretes carbon dioxide and other wastes. It begins to form about the eighth day of gestation when the blastocyst adheres to the decidua. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleomorphic: Occurring in various distinct forms. In terms of cells, having variation in the size and shape of cells or their nuclei. [NIH] Pneumonia: Inflammation of the lungs. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postmenopausal: Refers to the time after menopause. Menopause is the time in a woman's life when menstrual periods stop permanently; also called "change of life." [NIH] Postnatal: Occurring after birth, with reference to the newborn. [EU] Post-synaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Post-traumatic: Occurring as a result of or after injury. [EU] Post-traumatic stress disorder: A psychological disorder that develops in some individuals after a major traumatic experience such as war, rape, domestic violence, or accident. [NIH]

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Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practicability: A non-standard characteristic of an analytical procedure. It is dependent on the scope of the method and is determined by requirements such as sample throughout and costs. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prefrontal Cortex: The rostral part of the frontal lobe, bounded by the inferior precentral fissure in humans, which receives projection fibers from the mediodorsal nucleus of the thalamus. The prefrontal cortex receives afferent fibers from numerous structures of the diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Premenstrual Syndrome: A syndrome occurring most often during the last week of the menstrual cycle and ending soon after the onset of menses. Some of the symptoms are emotional instability, insomnia, headache, nausea, vomiting, abdominal distension, and painful breasts. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Private Sector: That distinct portion of the institutional, industrial, or economic structure of a country that is controlled or owned by non-governmental, private interests. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Problem Solving: A learning situation involving more than one alternative from which a selection is made in order to attain a specific goal. [NIH] Progesterone: Pregn-4-ene-3,20-dione. The principal progestational hormone of the body, secreted by the corpus luteum, adrenal cortex, and placenta. Its chief function is to prepare the uterus for the reception and development of the fertilized ovum. It acts as an antiovulatory agent when administered on days 5-25 of the menstrual cycle. [NIH]

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Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promoter: A chemical substance that increases the activity of a carcinogenic process. [NIH] Prone: Having the front portion of the body downwards. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Proteolytic: 1. Pertaining to, characterized by, or promoting proteolysis. 2. An enzyme that promotes proteolysis (= the splitting of proteins by hydrolysis of the peptide bonds with formation of smaller polypeptides). [EU] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psoriasis: A common genetically determined, chronic, inflammatory skin disease characterized by rounded erythematous, dry, scaling patches. The lesions have a predilection for nails, scalp, genitalia, extensor surfaces, and the lumbosacral region. Accelerated epidermopoiesis is considered to be the fundamental pathologic feature in psoriasis. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU]

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Psychiatry: The medical science that deals with the origin, diagnosis, prevention, and treatment of mental disorders. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychoactive: Those drugs which alter sensation, mood, consciousness or other psychological or behavioral functions. [NIH] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychopathology: The study of significant causes and processes in the development of mental illness. [NIH] Psychopharmacology: The study of the effects of drugs on mental and behavioral activity. [NIH]

Psychophysiology: The study of the physiological basis of human and animal behavior. [NIH]

Psychosis: A mental disorder characterized by gross impairment in reality testing as evidenced by delusions, hallucinations, markedly incoherent speech, or disorganized and agitated behaviour without apparent awareness on the part of the patient of the incomprehensibility of his behaviour; the term is also used in a more general sense to refer to mental disorders in which mental functioning is sufficiently impaired as to interfere grossly with the patient's capacity to meet the ordinary demands of life. Historically, the term has been applied to many conditions, e.g. manic-depressive psychosis, that were first described in psychotic patients, although many patients with the disorder are not judged psychotic. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Psychotropic Drugs: A loosely defined grouping of drugs that have effects on psychological function. Here the psychotropic agents include the antidepressive agents, hallucinogens, and tranquilizing agents (including the antipsychotics and anti-anxiety agents). [NIH] Puberty: The period during which the secondary sex characteristics begin to develop and the capability of sexual reproduction is attained. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right

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ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Pyramidal Tracts: Fibers that arise from cells within the cerebral cortex, pass through the medullary pyramid, and descend in the spinal cord. Many authorities say the pyramidal tracts include both the corticospinal and corticobulbar tracts. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH] Radioactive: Giving off radiation. [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Reality Testing: The individual's objective evaluation of the external world and the ability to differentiate adequately between it and the internal world; considered to be a primary ego

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function. [NIH] Reassurance: A procedure in psychotherapy that seeks to give the client confidence in a favorable outcome. It makes use of suggestion, of the prestige of the therapist. [NIH] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Recur: To occur again. Recurrence is the return of cancer, at the same site as the original (primary) tumor or in another location, after the tumor had disappeared. [NIH] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Red Nucleus: A pinkish-yellow portion of the midbrain situated in the rostral mesencephalic tegmentum. It receives a large projection from the contralateral half of the cerebellum via the superior cerebellar peduncle and a projection from the ipsilateral motor cortex. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relapse: The return of signs and symptoms of cancer after a period of improvement. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]

Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary,

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4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respirator: A mechanical device that helps a patient breathe; a mechanical ventilator. [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retrospective: Looking back at events that have already taken place. [NIH] Retrospective study: A study that looks backward in time, usually using medical records and interviews with patients who already have or had a disease. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Ribosome: A granule of protein and RNA, synthesized in the nucleolus and found in the cytoplasm of cells. Ribosomes are the main sites of protein synthesis. Messenger RNA attaches to them and there receives molecules of transfer RNA bearing amino acids. [NIH] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Rod: A reception for vision, located in the retina. [NIH] Rural Population: The inhabitants of rural areas or of small towns classified as rural. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a

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person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Seasonal Affective Disorder: A syndrome characterized by depressions that recur annually at the same time each year, usually during the winter months. Other symptoms include anxiety, irritability, decreased energy, increased appetite (carbohydrate cravings), increased duration of sleep, and weight gain. SAD (seasonal affective disorder) can be treated by daily exposure to bright artificial lights (phototherapy), during the season of recurrence. [NIH] Second Messenger Systems: Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Sedatives, Barbiturate: Those derivatives of barbituric or thiobarbituric acid that are used as hypnotics or sedatives. The structural class of all such derivatives, regardless of use, is barbiturates. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selection Bias: The introduction of error due to systematic differences in the characteristics between those selected and those not selected for a given study. In sampling bias, error is the result of failure to ensure that all members of the reference population have a known chance of selection in the sample. [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Care: Performance of activities or tasks traditionally performed by professional health care providers. The concept includes care of oneself or one's family and friends. [NIH] Self-Help Groups: Organizations which provide an environment encouraging social interactions through group activities or individual relationships especially for the purpose of rehabilitating or supporting patients, individuals with common health problems, or the elderly. They include therapeutic social clubs. [NIH]

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Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] Sensor: A device designed to respond to physical stimuli such as temperature, light, magnetism or movement and transmit resulting impulses for interpretation, recording, movement, or operating control. [NIH] Septal: An abscess occurring at the root of the tooth on the proximal surface. [NIH] Septal Nuclei: Neural nuclei situated in the septal region. They have afferent and cholinergic efferent connections with a variety of forebrain and brainstem areas including the hippocampus, the lateral hypothalamus, the tegmentum, and the amygdala. Included are the dorsal, lateral, medial, and triangular septal nuclei, septofimbrial nucleus, nucleus of diagonal band, nucleus of anterior commissure, and the nucleus of stria terminalis. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Sex Characteristics: Those characteristics that distinguish one sex from the other. The primary sex characteristics are the ovaries and testes and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]

Sibutramine: A drug used for the management of obesity that helps reduce food intake and is indicated for weight loss and maintenance of weight loss when used in conjunction with a reduced-calorie diet. It works to suppress the appetite primarily by inhibiting the reuptake of the neurotransmitters norepinephrine and serotonin. Side effects include dry mouth, headache, constipation, insomnia, and a slight increase in average blood pressure. In some patients it causes a higher blood pressure increase. [NIH] Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Sleep apnea: A serious, potentially life-threatening breathing disorder characterized by repeated cessation of breathing due to either collapse of the upper airway during sleep or

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absence of respiratory effort. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smoking Cessation: Discontinuation of the habit of smoking, the inhaling and exhaling of tobacco smoke. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Behavior: Any behavior caused by or affecting another individual, usually of the same species. [NIH] Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Social Support: Support systems that provide assistance and encouragement to individuals with physical or emotional disabilities in order that they may better cope. Informal social support is usually provided by friends, relatives, or peers, while formal assistance is provided by churches, groups, etc. [NIH] Social Work: The use of community resources, individual case work, or group work to promote the adaptive capacities of individuals in relation to their social and economic environments. It includes social service agencies. [NIH] Socialization: The training or molding of an individual through various relationships, educational agencies, and social controls, which enables him to become a member of a particular society. [NIH] Solitary Nucleus: Gray matter located in the dorsomedial part of the medulla oblongata associated with the solitary tract. The solitary nucleus receives inputs from most organ systems including the terminations of the facial, glossopharyngeal, and vagus nerves. It is a major coordinator of autonomic nervous system regulation of cardiovascular, respiratory, gustatory, gastrointestinal, and chemoreceptive aspects of homeostasis. The solitary nucleus is also notable for the large number of neurotransmitters which are found therein. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and

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types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spinal tap: A procedure in which a needle is put into the lower part of the spinal column to collect cerebrospinal fluid or to give anticancer drugs intrathecally. Also called a lumbar puncture. [NIH] Spontaneous Abortion: The non-induced birth of an embryo or of fetus prior to the stage of viability at about 20 weeks of gestation. [NIH] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Statistically significant: Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. [NIH] Steroids: Drugs used to relieve swelling and inflammation. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subiculum: A region of the hippocampus that projects to other areas of the brain. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally

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conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Substrate: A substance upon which an enzyme acts. [EU] Sulfur: An element that is a member of the chalcogen family. It has an atomic symbol S, atomic number 16, and atomic weight 32.066. It is found in the amino acids cysteine and methionine. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Support group: A group of people with similar disease who meet to discuss how better to cope with their cancer and treatment. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synaptosomes: Pinched-off nerve endings and their contents of vesicles and cytoplasm together with the attached subsynaptic area of the membrane of the post-synaptic cell. They are largely artificial structures produced by fractionation after selective centrifugation of nervous tissue homogenates. [NIH]

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Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Telencephalon: Paired anteriolateral evaginations of the prosencephalon plus the lamina terminalis. The cerebral hemispheres are derived from it. Many authors consider cerebrum a synonymous term to telencephalon, though a minority include diencephalon as part of the cerebrum (Anthoney, 1994). [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Terminal disease: Disease that cannot be cured and will cause death. [NIH] Testis: Either of the paired male reproductive glands that produce the male germ cells and the male hormones. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalamus: Paired bodies containing mostly gray substance and forming part of the lateral wall of the third ventricle of the brain. The thalamus represents the major portion of the diencephalon and is commonly divided into cellular aggregates known as nuclear groups. [NIH]

Theophylline: Alkaloid obtained from Thea sinensis (tea) and others. It stimulates the heart and central nervous system, dilates bronchi and blood vessels, and causes diuresis. The drug is used mainly in bronchial asthma and for myocardial stimulation. Among its more prominent cellular effects are inhibition of cyclic nucleotide phosphodiesterases and antagonism of adenosine receptors. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thromboxanes: Physiologically active compounds found in many organs of the body. They are formed in vivo from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. Thromboxanes are important mediators of the actions of polyunsaturated fatty acids transformed by cyclooxygenase. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU]

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Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroid Hormones: Hormones secreted by the thyroid gland. [NIH] Thyrotropin: A peptide hormone secreted by the anterior pituitary. It promotes the growth of the thyroid gland and stimulates the synthesis of thyroid hormones and the release of thyroxine by the thyroid gland. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Tonus: A state of slight tension usually present in muscles even when they are not undergoing active contraction. [NIH] Tooth Preparation: Procedures carried out with regard to the teeth or tooth structures preparatory to specified dental therapeutic and surgical measures. [NIH] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Torture: The intentional infliction of physical or mental suffering upon an individual or individuals, including the torture of animals. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tracheostomy: Surgical formation of an opening into the trachea through the neck, or the

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opening so created. [NIH] Tranquilizing Agents: A traditional grouping of drugs said to have a soothing or calming effect on mood, thought, or behavior. Included here are the anti-anxiety agents (minor tranquilizers), antimanic agents, and the antipsychotic agents (major tranquilizers). These drugs act by different mechanisms and are used for different therapeutic purposes. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, practicability, etc., of these interventions in individual cases or series. [NIH]

Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Triage: The sorting out and classification of patients or casualties to determine priority of need and proper place of treatment. [NIH] Tricuspid Atresia: Absence of the orifice between the right atrium and ventricle, with the presence of an atrial defect through which all the systemic venous return reaches the left heart. As a result, there is left ventricular hypertrophy because the right ventricle is absent or not functional. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tubercle: A rounded elevation on a bone or other structure. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Tyramine: An indirect sympathomimetic. Tyramine does not directly activate adrenergic receptors, but it can serve as a substrate for adrenergic uptake systems and monoamine oxidase so it prolongs the actions of adrenergic transmitters. It also provokes transmitter release from adrenergic terminals. Tyramine may be a neurotransmitter in some invertebrate nervous systems. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is

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also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx). [NIH] Valerian: Valeriana officinale, an ancient, sedative herb of the large family Valerianaceae. The roots were formerly used to treat hysterias and other neurotic states and are presently used to treat sleep disorders. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vasomotor: 1. Affecting the calibre of a vessel, especially of a blood vessel. 2. Any element or agent that effects the calibre of a blood vessel. [EU] VE: The total volume of gas either inspired or expired in one minute. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vegetative: 1. Concerned with growth and with nutrition. 2. Functioning involuntarily or unconsciously, as the vegetative nervous system. 3. Resting; denoting the portion of a cell cycle during which the cell is not involved in replication. 4. Of, pertaining to, or characteristic of plants. [EU] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venlafaxine: An antidepressant drug that is being evaluated for the treatment of hot flashes in women who have breast cancer. [NIH] Venter: Belly. [NIH] Ventilation: 1. In respiratory physiology, the process of exchange of air between the lungs and the ambient air. Pulmonary ventilation (usually measured in litres per minute) refers to the total exchange, whereas alveolar ventilation refers to the effective ventilation of the alveoli, in which gas exchange with the blood takes place. 2. In psychiatry, verbalization of one's emotional problems. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventral Tegmental Area: A region in the mesencephalon which is dorsomedial to the substantia nigra and ventral to the red nucleus. The mesocortical and mesolimbic

Dictionary 315

dopaminergic systems originate here, including an important projection to the nucleus accumbens. Overactivity of the cells in this area has been suspected to contribute to the positive symptoms of schizophrenia. [NIH] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH] Ventricular: Pertaining to a ventricle. [EU] Vertebrae: A bony unit of the segmented spinal column. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Villi: The tiny, fingerlike projections on the surface of the small intestine. Villi help absorb nutrients. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visceral Afferents: The sensory fibers innervating the viscera. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] War: Hostile conflict between organized groups of people. [NIH] Watchful waiting: Closely monitoring a patient's condition but withholding treatment until symptoms appear or change. Also called observation. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Windpipe: A rigid tube, 10 cm long, extending from the cricoid cartilage to the upper border of the fifth thoracic vertebra. [NIH] Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xanthine: An urinary calculus. [NIH] Xenograft: The cells of one species transplanted to another species. [NIH] Xerostomia: Decreased salivary flow. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

316

Depressive Disorders

X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH]

317

INDEX 5 5-Hydroxytryptophan, 118, 145, 253 A Abdominal, 253, 285, 296, 300 Abdominal Pain, 253, 285 Aberrant, 253, 266 Absenteeism, 29, 61, 253 Acceptor, 253, 296 Acculturation, 18, 253 Acetylcholine, 253, 265, 293, 294 Acoustic, 188, 219, 253 Activities of Daily Living, 7, 253 Adaptation, 62, 64, 253 Adenine, 253, 303 Adenosine, 180, 253, 262, 282, 298, 311 Adjunctive Therapy, 164, 253, 259 Adjustment, 40, 64, 81, 108, 253 Adjustment Disorders, 108, 253 Adolescence, 18, 21, 27, 50, 52, 53, 61, 79, 86, 106, 254 Adolescent Psychiatry, 53, 79, 82, 85, 86, 89, 106, 110, 127, 254 Adrenal Cortex, 254, 269, 276, 282, 299, 300 Adrenal Glands, 254, 299 Adrenal Medulla, 254, 263, 275, 294 Adrenergic, 106, 173, 254, 255, 257, 258, 272, 275, 301, 310, 313 Adverse Effect, 24, 254, 307 Aerosols, 198, 254 Affective Symptoms, 21, 52, 254 Afferent, 169, 254, 298, 300, 307 Affinity, 181, 254, 259, 271 Age of Onset, 15, 254, 262 Agonist, 166, 172, 194, 254, 262, 272, 294 Agoraphobia, 254, 283, 296, 298 Airway, 254, 307 Akathisia, 254, 258 Alertness, 254, 262 Algorithms, 255, 261 Alkaline, 255, 263, 296 Alkaloid, 255, 262, 266, 291, 294, 311 Alleles, 67, 255, 281 Allergen, 255, 271, 307 Allylamine, 255 Alpha Particles, 255, 303 Alpha-1, 255 Alternative medicine, 57, 219, 255

Aluminum, 190, 255 Alveoli, 255, 314 Amine, 45, 164, 177, 255, 261, 281 Amino acid, 62, 66, 255, 257, 259, 260, 261, 272, 279, 290, 293, 297, 299, 301, 305, 307, 310, 312, 313 Amitriptyline, 72, 222, 255 Ammonia, 255 Amnesia, 172, 255 Amnestic, 256, 277, 289 Amphetamine, 256, 261, 271 Ampulla, 256, 265 Amygdala, 45, 58, 256, 286, 307 Anabolic, 184, 256 Anabolic Steroids, 184, 256 Anaesthesia, 256, 283 Anal, 27, 60, 84, 90, 256, 275, 277, 287 Analgesic, 256, 262, 291, 295 Analog, 192, 256 Analogous, 256, 273, 313 Anaphylatoxins, 256, 267 Anatomical, 256, 259, 265, 274, 283, 290, 292, 306 Androgens, 254, 256, 269 Anemia, 256, 278 Anesthesia, 254, 256, 257 Anesthetics, 4, 256, 260, 275 Angina, 256, 301 Angina Pectoris, 256, 301 Animal model, 42, 44, 61, 75, 165, 178, 257 Anions, 257, 285 Anisotropy, 23, 257 Anosognosia, 11, 257 Antagonism, 257, 262, 311 Antiallergic, 257, 269 Anti-Anxiety Agents, 257, 302, 313 Antibacterial, 257, 309 Antibiotic, 146, 257, 309 Antibodies, 257, 280, 288 Antibody, 254, 257, 258, 266, 280, 281, 284, 285, 289, 291, 303, 307, 308, 316 Anticholinergic, 42, 255, 257 Anticonvulsant, 164, 257 Antidepressive Agents, 257, 302 Antiemetic, 258 Antiepileptic, 164, 253, 258 Antigen, 254, 257, 258, 267, 281, 282, 284, 288, 290, 307

318

Depressive Disorders

Antigen-Antibody Complex, 258, 267 Anti-inflammatory, 258, 269, 271, 279 Anti-Inflammatory Agents, 258, 269 Antineoplastic, 258, 269 Antipsychotic, 184, 258, 292, 305, 313 Anus, 256, 258, 262, 266 Anxiety Disorders, 17, 19, 21, 22, 31, 44, 46, 50, 71, 84, 103, 106, 258, 296 Anxiolytic, 168, 169, 178, 258, 262 Apathy, 10, 192, 258, 292 Aphasia, 11, 256, 258 Apnea, 196, 258 Apnoea, 189, 258 Applicability, 30, 258 Arachidonic Acid, 200, 259, 301 Arginine, 35, 62, 256, 259, 294 Art Therapy, 162, 259 Arterial, 216, 255, 259, 268, 282, 301, 311 Arteries, 259, 261, 269, 290, 291, 292, 303, 311 Artery, 57, 88, 128, 216, 259, 269, 274, 288, 303 Articular, 259, 286, 296 Aspartate, 194, 259 Aspiration, 26, 259 Astrocytes, 259, 290, 291 Ataxia, 259, 281 Atrial, 259, 268, 313 Atrioventricular, 259, 268 Atrium, 259, 268, 313, 315 Atypical, 179, 184, 199, 259, 284, 305 Auditory, 127, 259, 288, 300, 314 Aura, 218, 259 Autoimmune disease, 259, 291 Autonomic, 19, 177, 253, 258, 259, 278, 293, 294, 297, 308, 310 Autonomic Nervous System, 19, 259, 297, 308, 310 Autopsy, 46, 260 Autoradiography, 24, 260 B Bacteria, 166, 257, 258, 260, 270, 274, 290, 309, 312, 313, 314 Bacterial Physiology, 253, 260 Bacteriophage, 260, 313 Barbiturates, 146, 172, 260, 306 Basal Ganglia, 177, 180, 258, 259, 260, 262, 265, 286, 294 Basophils, 260, 286 Behavior Therapy, 260 Behavioral Symptoms, 10, 213, 260 Benign, 260, 262, 280, 303

Benzodiazepines, 76, 77, 260, 262 Benzoic Acid, 170, 260 Bilateral, 132, 180, 216, 260 Bile, 260, 287 Biliary, 260, 265 Bioavailability, 45, 260 Biochemical, 45, 62, 77, 78, 79, 100, 255, 260, 261, 286, 296, 307 Bioequivalent, 203, 260 Biogenic Amines, 44, 260 Biogenic Monoamines, 261, 287 Biological Markers, 19, 100, 261 Biological Transport, 261, 272 Biosynthesis, 259, 261 Biotechnology, 68, 72, 219, 231, 261 Bipolar Disorder, 12, 38, 43, 46, 135, 162, 168, 180, 181, 182, 206, 236, 239, 261 Bladder, 261, 267, 270, 283, 291, 314 Bloating, 261, 285 Blood Coagulation, 261, 263 Blood Glucose, 261, 280, 282 Blood Platelets, 261, 307 Blood pressure, 250, 261, 263, 264, 278, 282, 291, 303, 307 Blood vessel, 261, 263, 264, 265, 268, 275, 287, 308, 309, 311, 314 Blood-Brain Barrier, 261, 288 Blot, 24, 261 Body Fluids, 261, 273 Body Image, 27, 261, 271 Bone scan, 261, 305 Bowel, 137, 256, 262, 282, 284, 285, 309 Bowel Movement, 262, 282, 309 Brachytherapy, 262, 285, 303, 316 Bradykinin, 262, 294 Brain Neoplasms, 262, 281 Brain Stem, 262, 264 Bronchi, 262, 275, 311, 312 Bronchitis, 197, 262 Buprenorphine, 193, 262 Bupropion, 16, 17, 147, 173, 189, 222, 262 Burns, 98, 135, 197, 262 Burns, Electric, 262 Buspirone, 168, 169, 262 C Caffeine, 51, 262, 303 Calcium, 22, 62, 121, 122, 262, 263, 267 Calmodulin, 62, 263 Capsules, 263, 272 Carbohydrate, 263, 269, 306 Carbon Dioxide, 263, 270, 277, 278, 299, 304

319

Carcinogenic, 263, 301 Cardiac, 22, 58, 147, 255, 262, 263, 268, 269, 274, 275, 276, 292 Cardiology, 22, 263 Cardioselective, 263, 301 Cardiovascular, 22, 44, 59, 113, 135, 177, 178, 256, 263, 307, 308 Cardiovascular disease, 113, 178, 263 Cardiovascular System, 177, 263 Carnitine, 121, 122, 183, 263 Case report, 46, 263, 265 Case series, 263, 265 Catecholamine, 257, 263, 272, 298 Catheter, 171, 263 Cations, 263, 285 Caudal, 23, 263, 271, 282, 294, 299 Caudate Nucleus, 263, 294 Causal, 29, 44, 56, 179, 264, 275, 285 Cell Cycle, 264, 314 Cell Division, 260, 264, 289, 299, 301 Cell Respiration, 264, 305 Central Nervous System Diseases, 186, 264 Central Nervous System Infections, 264, 280, 281 Centrifugation, 264, 310 Cerebellum, 262, 264, 278, 304 Cerebral Cortex, 177, 180, 259, 264, 277, 303 Cerebral hemispheres, 260, 262, 264, 311 Cerebrospinal, 35, 70, 264, 281, 287, 309 Cerebrospinal fluid, 35, 70, 264, 281, 287, 309 Cerebrovascular, 11, 57, 96, 106, 263, 264 Cerebrum, 264, 311 Character, 256, 264, 270 Chemoreceptor, 258, 264 Chemotactic Factors, 265, 267 Chin, 133, 265, 289 Chloral Hydrate, 24, 265 Cholestasis, 125, 265 Cholesterol, 136, 260, 265, 269 Cholinergic, 37, 172, 183, 255, 258, 265, 294, 307 Chorea, 258, 265 Chromosome, 44, 265, 286 Chronic Disease, 70, 265, 266 Chronic Fatigue Syndrome, 99, 135, 203, 265 Citalopram, 14, 148, 189, 216, 217, 222, 265 Clinical Medicine, 265, 300 Clinical study, 38, 92, 265, 268

Clomipramine, 91, 265 Cloning, 44, 261, 266 Coca, 266 Cocaine, 32, 37, 48, 114, 179, 197, 266 Cognition, 25, 177, 266, 292 Cognitive behavior therapy, 39, 266 Cognitive Therapy, 10, 64, 266 Colitis, 140, 266, 284, 285 Collagen, 255, 266, 282, 299 Collagen disease, 266, 282 Collapse, 266, 307 Colon, 139, 140, 266, 284, 285 Comorbidity, 21, 22, 27, 37, 39, 48, 54, 59, 62, 66, 67, 71, 74, 81, 82, 84, 100, 104, 110, 266 Complement, 20, 63, 256, 266, 267, 279, 307 Complementary and alternative medicine, 125, 126, 159, 267 Complementary medicine, 126, 267 Compliance, 14, 50, 62, 82, 267 Compulsions, 267, 295 Computational Biology, 231, 267 Computed tomography, 267, 305 Computerized axial tomography, 267, 305 Concomitant, 6, 13, 15, 51, 267 Confounding, 59, 267 Congestion, 258, 268 Congestive heart failure, 6, 57, 268 Conjugated, 260, 268 Connective Tissue, 266, 268, 271, 277, 278, 287 Consciousness, 256, 257, 268, 270, 272, 302 Constipation, 136, 258, 268, 285, 307 Consultation, 17, 38, 46, 51, 57, 268 Contraindications, ii, 7, 268 Control group, 8, 22, 25, 268 Controlled clinical trial, 65, 268 Controlled study, 14, 113, 127, 128, 268 Convulsions, 257, 268, 273, 282 Convulsive, 175, 268, 274 Convulsive Therapy, 175, 268 Coordination, 53, 264, 268, 291 Cor, 35, 45, 70, 200, 268, 269, 299 Coronary, 22, 40, 57, 88, 128, 179, 257, 263, 269, 290, 291, 292 Coronary Disease, 179, 269 Coronary heart disease, 22, 263, 269 Coronary Thrombosis, 269, 290, 291, 292 Coronary Vessels, 269 Corpus, 23, 269, 287, 300 Corpus Callosum, 23, 269

320

Depressive Disorders

Cortex, 131, 269, 275, 300, 304 Cortical, 269, 276, 299, 300, 306 Corticosteroid, 72, 118, 269 Corticotropin-Releasing Hormone, 35, 70, 269 Cortisone, 269, 271 Cotinine, 45, 269 Cranial, 264, 269, 280, 285, 297, 314 Craniocerebral Trauma, 269, 280, 281 Curative, 270, 294, 311 Cyclic, 262, 263, 270, 280, 294, 298, 306, 311 Cystitis, 4, 270 Cytokine, 94, 270 Cytoplasm, 260, 270, 275, 291, 293, 305, 310 D Data Collection, 21, 126, 270 Deamination, 270, 291 Decarboxylation, 260, 261, 270, 281 Degenerative, 214, 270, 281, 295 Delirium, 6, 7, 213, 258, 270 Delusions, 6, 8, 10, 182, 270, 302 Dementia, 5, 6, 7, 8, 9, 10, 11, 18, 20, 83, 136, 139, 172, 210, 213, 214, 258, 270, 289 Dendrites, 270, 271, 293 Density, 77, 191, 198, 264, 270, 295 Dental Caries, 4, 270 Dentate Gyrus, 270, 281 Dentists, 4, 6, 271 Depersonalization, 271, 296, 306 Derealization, 271, 296 Dermis, 271, 313 Desensitization, 63, 271 Desipramine, 42, 99, 218, 271 Detoxification, 141, 189, 271 Deuterium, 271, 282 Developed Countries, 178, 271 Dexamethasone, 114, 222, 271 Dextroamphetamine, 170, 256, 271, 290 Dextrorotatory, 173, 271 Diagnostic procedure, 163, 168, 219, 271 Diarrhea, 271, 285 Diastolic, 271, 282 Diathesis, 19, 86, 271 Diencephalon, 264, 271, 275, 282, 300, 311 Diffusion, 23, 131, 261, 271 Digestion, 260, 262, 272, 273, 285, 287, 309 Dilation, 262, 272, 281 Dimethyl, 197, 272 Direct, iii, 43, 44, 49, 60, 221, 265, 266, 272, 304, 310

Discrete, 60, 191, 272 Discrimination, 56, 272 Disorientation, 270, 272 Disparity, 49, 272 Dissociation, 254, 272 Distal, 272, 274 Diuresis, 262, 272, 311 Diuretic, 201, 272 Diurnal, 8, 272 Dizziness, 272, 296 Dominance, 61, 272 Dopamine, 41, 132, 166, 177, 179, 181, 197, 203, 256, 258, 262, 266, 271, 272, 291, 293, 305 Dosage Forms, 197, 272 Double-blind, 16, 57, 73, 88, 90, 98, 99, 105, 127, 133, 273 Drinking Behavior, 59, 273 Drive, ii, vi, 23, 61, 74, 117, 171, 273 Drug Design, 44, 273 Drug Interactions, 186, 224, 273 Drug Tolerance, 273, 312 Duct, 190, 256, 273, 305 Dyskinesia, 258, 265, 273 Dyspareunia, 273, 276 Dyspepsia, 199, 273 Dysphagia, 26, 136, 273 Dysphoria, 170, 171, 273 Dysphoric, 107, 273 Dyspnea, 273, 296 Dystrophy, 172, 273 E Eating Disorders, 136, 177, 194, 196, 273 Effector, 253, 266, 273 Electric Conductivity, 257, 273 Electric shock, 25, 273 Electroconvulsive Therapy, 6, 87, 88, 179, 181, 273 Electrode, 171, 176, 185, 274 Electroencephalography, 274, 288 Electrolyte, 269, 270, 274, 290 Electrons, 273, 274, 285, 288, 296, 303 Electroshock, 97, 164, 274 Elementary Particles, 274, 288, 293, 301 Embolus, 274, 284 Embryo, 274, 283, 309 Empirical, 10, 17, 47, 62, 274 Emulsion, 260, 274, 277 Enamel, 270, 274 Encephalitis, 274, 289 Endemic, 274, 281 Endocrine System, 274, 292

321

Endocrinology, 32, 49, 51, 274 Endogenous, 35, 100, 173, 200, 272, 275 Endorphins, 275, 293 Endothelium, 275, 294 Endothelium-derived, 275, 294 Endotoxins, 267, 275 Energetic, 130, 275 Enhancer, 32, 275 Enkephalins, 275, 293 Entorhinal Cortex, 275, 281 Environmental Exposure, 261, 275 Environmental Health, 230, 232, 275 Enzymatic, 255, 260, 261, 263, 267, 270, 275, 281, 305 Enzyme, 76, 177, 261, 273, 275, 279, 280, 291, 301, 310, 315 Eosinophils, 275, 286 Epidemic, 23, 275 Epidemiologic Studies, 261, 275 Epidemiological, 11, 22, 60, 275 Epinephrine, 254, 261, 272, 275, 293, 294, 314 Epithalamus, 271, 275, 286 ERV, 109, 232, 276 Erythrina, 152, 156, 276 Erythrocytes, 89, 256, 276, 307 Estradiol, 88, 276 Estrogen, 49, 194, 276, 301 Estrogen Replacement Therapy, 49, 276 Ethanol, 265, 276 Eukaryotic Cells, 276, 283 Excitability, 179, 276 Excitation, 264, 276, 293 Excitatory, 45, 62, 276, 279 Exogenous, 275, 276, 298 Expiration, 276, 304 Expiratory, 276 Expiratory Reserve Volume, 276 Extensor, 276, 301 External-beam radiation, 276, 285, 303, 316 Extracellular, 23, 259, 268, 276, 290 Extracellular Space, 276, 290 Extrapyramidal, 177, 254, 258, 272, 276 Extravasation, 277, 280 F Family Planning, 30, 231, 277 Family Practice, 81, 84, 85, 118, 277 Family Relations, 24, 277 Famotidine, 199, 277 Fat, 124, 259, 268, 269, 274, 277, 286, 291, 295, 299

Fatigue, 4, 192, 204, 250, 265, 277, 280 Fetus, 277, 299, 300, 309, 314 Fibrosis, 255, 277, 306 Fissure, 269, 270, 277, 300 Fixation, 277, 307 Flatus, 277, 278 Fluoxetine, 62, 70, 73, 88, 91, 118, 122, 184, 189, 223, 277 Flush, 49, 277 Fluvoxamine, 70, 91, 149, 189, 223, 277 Folate, 91, 121, 122, 178, 277, 278 Fold, 18, 51, 52, 53, 277 Folic Acid, 120, 121, 178, 277 Forearm, 261, 278 Fourth Ventricle, 278, 287 Fractionation, 278, 310 Frontal Lobe, 180, 278, 300 Fumigation, 254, 278 Functional magnetic resonance imaging, 25, 36, 278 Fungi, 278, 279, 290, 314, 316 G Gait, 6, 7, 278 Ganglia, 177, 180, 253, 278, 292, 297, 310 Ganglionic Blockers, 278, 288 Gas, 45, 100, 255, 263, 271, 276, 277, 278, 282, 285, 294, 314 Gas exchange, 278, 314 Gastric, 200, 263, 272, 277, 278, 281 Gastric Acid, 200, 278 Gastrin, 278, 281 Gastrointestinal, 177, 199, 262, 265, 275, 276, 278, 288, 307, 308, 310 Gastrointestinal tract, 177, 265, 276, 278, 288, 307 Gene Expression, 24, 45, 179, 202, 278 Generator, 171, 279 Genetic Engineering, 261, 266, 279 Genetics, 66, 76, 92, 93, 168, 272, 279 Genotype, 8, 167, 196, 279, 298 Geriatric, 7, 8, 11, 23, 88, 105, 131, 132, 183, 279 Gestation, 54, 279, 297, 299, 309 Ginseng, 146, 150, 155, 279 Gland, 254, 269, 279, 287, 299, 306, 309, 312 Glucocorticoid, 23, 34, 222, 271, 279, 282 Glucose, 180, 261, 279, 280, 282, 284 Glutamate, 45, 93, 168, 279, 285 Glutamic Acid, 150, 278, 279, 293 Glutathione Peroxidase, 279, 306 Glycine, 255, 260, 279, 293

322

Depressive Disorders

Glycoprotein, 279, 286, 313 Gonad, 279 Gonadal, 32, 94, 279 Governing Board, 279, 300 Grade, 33, 279 Grasses, 201, 278, 279 Guanine, 168, 279, 303 Guanylate Cyclase, 280, 294 Gyrus Cinguli, 280, 286 H Habitat, 280, 294 Hammer, 188, 208, 280, 295 Happiness, 187, 280 Haptens, 254, 280 Headache, 82, 139, 262, 280, 281, 282, 300, 307 Headache Disorders, 280 Health Promotion, 238, 280 Health Services, 18, 24, 27, 29, 53, 214, 280 Health Status, 17, 59, 280 Heart attack, 40, 263, 280 Heart failure, 57, 217, 280 Hematoma, 6, 280 Hemoglobin, 256, 276, 280 Hemorrhage, 269, 280, 309 Hemostasis, 280, 307 Hepatic, 270, 281, 291 Hepatitis, 34, 216, 217, 281, 284 Hepatitis D, 216, 281 Hepatitis Delta Virus, 281 Hepatocyte, 265, 281 Heredity, 278, 279, 281 Heterogeneity, 19, 31, 94, 112, 254, 281 Heterozygotes, 272, 281 Hippocampus, 23, 179, 270, 281, 286, 307, 309 Histamine, 151, 256, 258, 261, 277, 281 Homeostasis, 62, 281, 308 Homologous, 255, 281, 307, 310 Homosexuality, 56, 281 Homozygotes, 272, 281 Hormonal, 49, 66, 269, 276, 281 Hormone, 23, 66, 89, 200, 261, 269, 275, 276, 278, 281, 300, 301, 306, 311, 312 Hospice, 26, 281 Humidifier, 198, 281 Hydrocephalus, 6, 281, 285 Hydrocortisone, 94, 282 Hydrogen, 200, 253, 255, 263, 271, 279, 282, 291, 293, 296, 301 Hydroxyproline, 255, 266, 282 Hyperglycemia, 25, 282

Hypersensitivity, 15, 135, 255, 271, 282, 307 Hypertension, 137, 177, 263, 282, 285, 288, 301 Hyperthermia, 44, 282 Hyperthyroidism, 66, 282, 301 Hypertrophy, 269, 282, 313 Hypnotic, 49, 265, 282 Hypochondriasis, 137, 192, 282 Hypoglycaemia, 270, 282 Hypoglycemia, 25, 123, 137, 282 Hypoglycemic, 25, 282 Hypotension, 258, 268, 278, 282 Hypotensive, 200, 282 Hypothalamic, 32, 34, 66, 94, 95, 282 Hypothalamus, 200, 260, 262, 269, 271, 282, 286, 299, 307 Hypoxanthine, 78, 282 Hypoxia, 270, 283 I Ileum, 169, 283 Imidazole, 170, 281, 283 Imipramine, 62, 92, 95, 98, 105, 265, 283 Immune function, 102, 205, 283 Immune response, 258, 259, 269, 280, 283, 307, 310, 315 Immune system, 34, 205, 283, 288, 291, 315 Immunization, 283, 307 Immunodeficiency, 127, 283 Immunology, 205, 254, 283 Immunosuppressive, 279, 283 Immunotherapy, 271, 283 Implant radiation, 283, 285, 303, 316 Implantable pump, 171, 283 In situ, 24, 283 In Situ Hybridization, 24, 283 In vitro, 35, 169, 181, 283 In vivo, 23, 35, 43, 165, 169, 283, 290, 311 Incision, 283, 285 Incontinence, 27, 172, 197, 281, 283 Induction, 25, 38, 256, 258, 274, 278, 283, 301 Infancy, 68, 284 Infarction, 179, 282, 284 Infection, 34, 98, 184, 265, 270, 274, 283, 284, 287, 288, 293, 309, 315 Infectious Mononucleosis, 284, 291 Inflammation, 258, 262, 266, 270, 274, 277, 281, 282, 284, 299, 309 Inflammatory bowel disease, 63, 104, 284 Infuse, 171, 284 Infusion, 171, 284

323

Ingestion, 66, 277, 284, 290, 299 Inhalation, 254, 284, 299 Innervation, 284, 295 Inositol, 151, 284, 306 Inotropic, 272, 284 Inpatients, 7, 85, 87, 108, 284 Insight, 58, 284 Insomnia, 13, 51, 58, 137, 171, 187, 202, 250, 265, 284, 300, 307 Insulator, 284, 291 Interferon, 34, 96, 217, 284, 285 Interferon-alpha, 284, 285 Intergenerational Relations, 13, 285 Intermittent, 285, 287 Internal radiation, 285, 303, 316 Interpersonal Relations, 24, 285 Interstitial, 4, 262, 276, 285, 304, 316 Intervention Studies, 22, 49, 285 Intestine, 262, 285, 297, 304, 308 Intoxication, 270, 285, 315 Intracellular, 62, 262, 284, 285, 294, 304, 306 Intracranial Hemorrhages, 281, 285 Intracranial Hypertension, 280, 281, 285 Intravenous, 170, 284, 285 Intrinsic, 254, 285 Invasive, 26, 285, 288 Involuntary, 265, 285, 292, 304, 308 Ions, 197, 263, 272, 274, 282, 285, 290 Irradiation, 198, 285, 316 Irritable Bowel Syndrome, 137, 196, 285 K Kainate, 167, 285 Kb, 230, 286 Keratolytic, 270, 286 L Labile, 266, 286 Lactation, 286, 301 Larynx, 286, 312, 314 Latency, 14, 37, 58, 286 Latent, 19, 55, 67, 162, 286, 300 Lectins, 276, 286 Length of Stay, 7, 286 Lesion, 62, 85, 286, 287, 311 Lethal, 186, 286 Lethargy, 281, 286 Leukocytes, 77, 260, 265, 275, 285, 286, 291, 293, 313 Life cycle, 30, 214, 278, 286 Ligaments, 269, 286 Ligands, 42, 178, 286 Limbic, 25, 96, 177, 256, 280, 286, 300

Limbic System, 96, 177, 256, 280, 286, 300 Linkage, 26, 67, 89, 92, 93, 286 Lipid, 22, 201, 286, 291 Lithium, 97, 118, 153, 181, 186, 223, 258, 286, 287 Lithium Carbonate, 181, 287 Liver, 125, 133, 177, 253, 259, 260, 263, 265, 274, 278, 281, 287, 291, 305 Liver scan, 287, 305 Localization, 165, 287, 288 Localized, 270, 277, 280, 284, 287, 291, 299 Locomotion, 287, 299 Locomotor, 45, 287 Locus Coeruleus, 45, 287 Loneliness, 111, 287 Longitudinal Studies, 39, 55, 287 Longitudinal study, 50, 60, 84, 287 Long-Term Care, 22, 51, 214, 287 Lumbar, 35, 287, 309 Lumbar puncture, 35, 287, 309 Lutein Cells, 287, 301 Lymph, 275, 282, 284, 287 Lymph node, 282, 287, 288 Lymphatic, 275, 284, 287 Lymphocyte, 95, 102, 106, 258, 288, 289 Lymphocyte Subsets, 102, 288 M Magnetic Resonance Imaging, 25, 131, 288, 305 Magnetic Resonance Spectroscopy, 78, 288 Magnetoencephalography, 51, 288 Malaise, 273, 288 Malignant, 204, 258, 262, 288, 303 Mania, 38, 175, 209, 288 Manic, 77, 97, 137, 171, 182, 206, 207, 208, 209, 211, 212, 239, 240, 258, 261, 286, 288, 302 Maprotiline, 91, 223, 288 Marijuana Abuse, 39, 288 Meatus, 288, 314 Mecamylamine, 44, 288 Mechanical ventilation, 26, 288 Medial, 23, 280, 288, 295, 307 Mediate, 13, 37, 41, 60, 272, 288 Mediator, 288, 307 Medical Records, 28, 289, 305 Medicament, 178, 189, 289 MEDLINE, 231, 289 Megaloblastic, 278, 289 Meiosis, 289, 310 Melanin, 287, 289, 314

324

Depressive Disorders

Memantine, 32, 289 Membrane, 190, 191, 259, 267, 276, 286, 289, 290, 291, 295, 298, 305, 310 Memory, 8, 9, 20, 23, 26, 36, 87, 142, 177, 197, 250, 255, 270, 289 Memory Disorders, 8, 9, 289 Meninges, 264, 269, 289 Menopause, 49, 118, 138, 194, 289, 297, 299, 301 Menstruation, 289 Mental Disorders, 18, 20, 27, 33, 56, 59, 61, 108, 177, 181, 182, 193, 195, 196, 254, 289, 302 Mental Health Services, iv, 12, 18, 20, 28, 49, 53, 73, 232, 289 Mental Processes, 272, 289, 302 Mental Retardation, 184, 289 Mentors, 17, 20, 22, 48, 49, 53, 289 Mesencephalic, 287, 289, 304 Mesolimbic, 179, 258, 289, 314 Meta-Analysis, 69, 88, 132, 289 Metabolite, 169, 197, 200, 265, 272, 290 Methanol, 180, 181, 290 Methionine, 57, 125, 272, 290, 310 Methylphenidate, 98, 170, 223, 290 MI, 40, 177, 217, 251, 290 Microbiology, 253, 259, 290 Microdialysis, 45, 290 Microglia, 259, 290, 291 Micro-organism, 270, 290 Migration, 17, 290 Mineralocorticoids, 254, 269, 290 Moclobemide, 72, 73, 94, 99, 102, 103, 290 Modeling, 32, 55, 64, 273, 290 Modification, 11, 255, 279, 290, 303 Molecular Structure, 169, 290, 313 Molecule, 173, 183, 258, 267, 272, 273, 275, 276, 290, 296, 303, 304, 314 Monitor, 10, 38, 291, 294 Monoamine, 66, 177, 181, 189, 194, 197, 203, 222, 256, 257, 271, 290, 291, 313 Monoamine Oxidase, 177, 181, 222, 256, 257, 271, 290, 291, 313 Monoclonal, 285, 291, 303, 316 Monocytes, 286, 291 Mononuclear, 77, 284, 291, 313 Mononucleosis, 99, 291 Monotherapy, 164, 291 Mood Disorders, 12, 15, 21, 24, 35, 37, 41, 42, 55, 57, 66, 133, 168, 174, 179, 291 Morphine, 262, 291, 292, 295 Motility, 177, 291, 307

Motion Sickness, 291, 292 Mucins, 291, 305 Mucosa, 291, 301 Multiple sclerosis, 96, 204, 291 Muscular Dystrophies, 273, 291 Myelin, 291 Myocardial infarction, 40, 179, 269, 290, 291, 292, 301 Myocardial Ischemia, 256, 269, 292 Myocardium, 257, 290, 291, 292 Myotonic Dystrophy, 172, 292 N Naltrexone, 32, 292 Narcolepsy, 170, 172, 197, 271, 290, 292 Narcotic, 291, 292 Nausea, 172, 258, 272, 292, 296, 300 Necrosis, 284, 290, 291, 292 Neoplastic, 282, 292 Nerve Endings, 292, 310 Nervous System, 14, 118, 169, 170, 172, 186, 253, 254, 256, 259, 262, 264, 266, 271, 278, 279, 287, 288, 290, 291, 292, 293, 297, 307, 310, 311, 313, 314 Networks, 29, 292 Neural, 25, 44, 76, 168, 205, 254, 271, 278, 290, 291, 292, 307 Neuroendocrine, 98, 99, 177, 200, 292 Neuroendocrinology, 34, 292 Neuroleptic, 254, 258, 292 Neurologic, 46, 257, 281, 293 Neurology, 8, 28, 40, 105, 112, 131, 132, 165, 175, 293 Neuroma, 219, 293 Neuromuscular, 253, 293, 295 Neuromuscular Junction, 253, 293, 295 Neuronal, 24, 45, 57, 62, 179, 197, 265, 293 Neurons, 45, 62, 165, 189, 266, 270, 276, 278, 292, 293, 294, 310 Neuropathy, 197, 293 Neuropeptide, 164, 269, 293 Neuropsychological Tests, 26, 293 Neuropsychology, 20, 293 Neurosis, 183, 199, 200, 282, 293, 298 Neurotic, 78, 99, 257, 293, 314 Neurotoxicity, 177, 293 Neurovegetative, 34, 293 Neutrons, 255, 285, 293, 303 Neutrophils, 286, 293 Niacin, 120, 293, 313 Niche, 108, 294 Nicotine, 16, 44, 65, 84, 172, 197, 294 Nitric Oxide, 62, 294

325

Nitrogen, 255, 256, 277, 294, 313 Nonverbal Communication, 294, 302 Norepinephrine, 42, 45, 77, 94, 100, 175, 177, 189, 197, 203, 254, 255, 271, 272, 293, 294, 307 Nuclear, 260, 274, 276, 277, 286, 292, 294, 311 Nuclear Family, 277, 294 Nuclei, 177, 255, 256, 274, 276, 279, 288, 293, 294, 299, 301, 307 Nucleic acid, 283, 294, 303 Nucleus Accumbens, 179, 294, 315 Nutritional Status, 46, 294 O Observational study, 99, 294 Obsessive-Compulsive Disorder, 194, 196, 277, 295 Occult, 4, 295 Occupational Therapy, 7, 295 Ocular, 295 Odds Ratio, 295, 304 Ointments, 272, 295 Omega-3 fatty acid, 46, 127, 129, 130, 295 Opacity, 270, 295 Ophthalmoplegia, 70, 295 Opiate, 32, 95, 173, 291, 295 Opium, 291, 295 Optic Chiasm, 282, 295 Oral Health, 295 Oral Hygiene, 4, 295 Orthostatic, 258, 295 Ossicles, 280, 295 Osteoarthritis, 125, 197, 295 Osteoporosis, 138, 276, 296 Outpatient, 8, 35, 36, 65, 296 Ovary, 276, 279, 296 Overdose, 186, 296 Ovum, 279, 286, 296, 300, 301 Oxidation, 176, 253, 279, 296 Oxides, 191, 296 Oxygen Consumption, 296, 305 P Palliative, 26, 296, 311 Pancreatic, 263, 296 Panic, 21, 46, 83, 100, 102, 104, 110, 118, 135, 194, 236, 277, 283, 296 Panic Disorder, 21, 46, 104, 110, 236, 277, 283, 296 Parent-Child Relations, 55, 64, 296 Paresthesias, 296 Parkinsonism, 258, 296 Paroxetine, 19, 43, 62, 123, 174, 224, 296

Paroxysmal, 256, 259, 280, 296 Partial remission, 296, 304 Partial response, 14, 296, 297 Particle, 297, 313 Parturition, 297, 301 Patch, 16, 297, 313 Pathogenesis, 43, 205, 297 Pathologic, 269, 282, 297, 301, 304 Pathophysiology, 23, 25, 44, 48, 51, 66, 200, 297 Patient Education, 237, 244, 246, 251, 297 Pelvis, 287, 297, 314 Peptide, 255, 297, 299, 301, 312 Perception, 25, 29, 271, 297, 306 Perimenopausal, 49, 88, 194, 297 Perinatal, 24, 55, 60, 297 Periodontal disease, 4, 297 Peripheral Nervous System, 275, 293, 297, 310 Peristalsis, 200, 297 Personality Disorders, 101, 111, 175, 297 Pharmaceutical Preparations, 178, 199, 276, 297 Pharmaceutical Solutions, 273, 297 Pharmacodynamic, 277, 297 Pharmacokinetics, 102, 273, 298 Pharmacologic, 9, 17, 32, 39, 40, 54, 55, 197, 218, 238, 256, 298, 312 Pharmacology, Clinical, 17, 298 Pharmacotherapy, 30, 38, 43, 55, 64, 65, 69, 77, 81, 100, 102, 118, 129, 171, 175, 195, 196, 298 Pharynx, 298, 314 Phenotype, 19, 66, 67, 167, 261, 298 Phenyl, 170, 199, 298 Phobia, 36, 194, 298 Phobic Disorders, 298 Phosphates, 180, 298 Phosphorous, 78, 298 Phosphorus, 78, 145, 180, 263, 298 Phototherapy, 298, 306 Phototransduction, 298, 306 Physiologic, 49, 254, 261, 289, 298, 304 Physiology, 34, 37, 49, 261, 263, 274, 286, 298 Pilot Projects, 30, 298 Pilot study, 14, 31, 65, 94, 127, 299 Pitch, 188, 299 Pituitary Gland, 269, 299 Pituitary-Adrenal System, 200, 299 Placenta, 276, 299, 300

326

Depressive Disorders

Plants, 255, 263, 266, 279, 294, 299, 312, 313, 314 Plasma, 17, 45, 66, 95, 103, 131, 170, 257, 280, 281, 290, 299 Platelet Aggregation, 256, 294, 299, 311 Platelets, 294, 299, 311 Pleomorphic, 294, 299 Pneumonia, 268, 299 Poisoning, 270, 285, 292, 299 Polymorphic, 67, 271, 299 Polymorphism, 8, 76, 183, 299 Polypeptide, 255, 266, 299, 301 Polyunsaturated fat, 131, 299, 311 Posterior, 256, 259, 264, 275, 299 Postmenopausal, 27, 276, 296, 299 Postnatal, 14, 128, 238, 299 Post-synaptic, 43, 299, 310 Post-traumatic, 51, 81, 174, 280, 299 Post-traumatic stress disorder, 51, 174, 299 Potentiates, 25, 271, 300 Potentiating, 255, 300 Potentiation, 172, 300 Practicability, 300, 313 Practice Guidelines, 210, 232, 238, 300 Preclinical, 23, 62, 300 Precursor, 178, 253, 259, 272, 273, 275, 294, 300, 313, 314 Predisposition, 51, 60, 167, 300 Prefrontal Cortex, 58, 300 Premenstrual Syndrome, 138, 197, 300 Prenatal, 15, 133, 274, 300 Presynaptic, 189, 292, 293, 300, 310 Private Sector, 86, 300 Probe, 37, 44, 190, 191, 202, 203, 290, 300 Problem Solving, 9, 71, 300 Progesterone, 156, 300, 301 Progression, 257, 301 Progressive, 26, 70, 270, 273, 276, 291, 292, 295, 301, 304 Projection, 294, 300, 301, 304, 315 Prolactin, 166, 301 Promoter, 76, 301 Prone, 22, 61, 199, 301 Prophase, 301, 310 Propranolol, 173, 301 Prospective study, 21, 26, 37, 40, 41, 42, 287, 301 Prostaglandins, 259, 301 Protein S, 261, 301, 305 Proteins, 45, 255, 258, 261, 266, 291, 294, 297, 299, 301, 304, 307, 314

Proteolytic, 255, 267, 301 Protocol, 17, 37, 58, 210, 301 Protons, 255, 282, 288, 301, 303 Psoriasis, 197, 301 Psychic, 142, 178, 199, 289, 293, 302, 306 Psychoactive, 302, 315 Psychogenic, 44, 76, 302 Psychomotor, 8, 26, 104, 181, 270, 293, 302 Psychopharmacology, 12, 16, 46, 72, 73, 75, 90, 91, 92, 95, 97, 105, 108, 110, 170, 187, 302 Psychophysiology, 68, 293, 302 Psychosis, 5, 8, 10, 38, 74, 106, 238, 258, 302 Psychotherapy, 10, 14, 24, 30, 63, 69, 80, 81, 109, 175, 209, 236, 266, 302, 304 Psychotomimetic, 256, 271, 302 Psychotropic, 181, 189, 302 Psychotropic Drugs, 181, 189, 302 Puberty, 50, 302 Public Health, 24, 29, 30, 33, 39, 42, 48, 50, 56, 59, 60, 112, 127, 232, 302 Public Policy, 231, 302 Publishing, 4, 68, 302 Pulmonary, 26, 135, 261, 268, 302, 303, 314, 315 Pulmonary Artery, 261, 302, 315 Pulmonary hypertension, 268, 303 Pulse, 291, 303 Purines, 180, 303 Pyramidal Tracts, 276, 303 Q Quality of Life, 4, 19, 21, 28, 30, 40, 51, 56, 58, 110, 303 R Race, 170, 173, 197, 290, 303 Racemic, 170, 173, 197, 303 Radiation, 188, 198, 256, 260, 274, 275, 276, 278, 282, 285, 303, 305, 315, 316 Radiation therapy, 276, 278, 285, 303, 316 Radioactive, 260, 261, 282, 283, 285, 287, 294, 303, 305, 316 Radiolabeled, 285, 303, 316 Radiopharmaceutical, 279, 303 Radiotherapy, 262, 285, 303, 316 Randomized, 12, 14, 17, 19, 24, 31, 35, 38, 50, 52, 54, 62, 63, 88, 273, 303 Randomized clinical trial, 24, 303 Reality Testing, 302, 303 Reassurance, 282, 304 Receptors, Serotonin, 304, 307

327

Rectum, 258, 262, 266, 277, 278, 283, 284, 304 Recur, 304, 306 Recurrence, 54, 56, 96, 261, 304, 306 Red Nucleus, 259, 304, 314 Refer, 1, 21, 266, 272, 275, 277, 278, 287, 291, 292, 293, 295, 302, 304, 312 Reflex, 169, 304 Refraction, 257, 304, 309 Refractory, 57, 164, 170, 184, 193, 304 Regimen, 87, 192, 273, 298, 304 Relapse, 13, 39, 55, 106, 208, 216, 304 Relative risk, 28, 304 Reliability, 5, 71, 96, 115, 304 Remission, 14, 36, 54, 59, 66, 183, 261, 304 Renal failure, 270, 304 Resorption, 281, 304 Respiration, 177, 258, 263, 264, 291, 304 Respirator, 288, 305 Respiratory Physiology, 305, 314 Response rate, 57, 305 Retina, 295, 298, 305 Retinal, 272, 295, 298, 305 Retrospective, 12, 20, 68, 305 Retrospective study, 68, 305 Ribose, 253, 305 Ribosome, 305, 313 Risperidone, 97, 305 Rod, 201, 305 Rural Population, 18, 305 S Saliva, 4, 305 Salivary, 4, 305, 315 Salivary glands, 305 Scans, 48, 305 Schizoid, 305, 315 Schizotypal Personality Disorder, 271, 306, 315 Sclerosis, 26, 266, 291, 306 Screening, 30, 50, 62, 69, 71, 82, 87, 108, 183, 265, 306 Seasonal Affective Disorder, 139, 197, 236, 306 Second Messenger Systems, 45, 306 Secretion, 200, 269, 277, 281, 286, 290, 291, 306 Sedative, 255, 265, 283, 306, 314 Sedatives, Barbiturate, 260, 306 Seizures, 164, 270, 296, 306 Selection Bias, 107, 306 Selenium, 118, 123, 306 Self Care, 253, 306

Self-Help Groups, 240, 306 Senile, 139, 172, 296, 307 Sensitization, 93, 307 Sensor, 167, 188, 203, 307 Septal, 286, 307 Septal Nuclei, 286, 307 Sertraline, 69, 92, 99, 157, 165, 166, 189, 217, 218, 224, 307 Serum, 139, 166, 256, 266, 290, 307, 313 Sex Characteristics, 254, 256, 302, 307, 311 Shock, 189, 274, 282, 307, 313 Sibutramine, 197, 307 Side effect, 7, 12, 42, 62, 172, 183, 186, 195, 196, 221, 254, 258, 265, 288, 307, 312 Signs and Symptoms, 4, 5, 6, 304, 307 Skull, 269, 307, 311 Sleep apnea, 189, 307 Small intestine, 281, 283, 285, 308, 315 Smoking Cessation, 16, 84, 262, 308 Smooth muscle, 255, 256, 262, 281, 291, 308, 310 Social Behavior, 61, 308 Social Environment, 303, 308 Social Support, 5, 23, 30, 41, 42, 54, 55, 58, 92, 204, 308 Social Work, 24, 54, 213, 308 Socialization, 34, 308 Solitary Nucleus, 260, 308 Solvent, 95, 276, 290, 297, 308 Soma, 308 Somatic, 21, 43, 66, 199, 211, 254, 286, 289, 297, 300, 308, 314 Soybean Oil, 299, 308 Spasm, 268, 289, 308 Spastic, 139, 285, 308 Specialist, 240, 272, 308 Species, 173, 275, 289, 290, 291, 303, 308, 309, 315 Specificity, 36, 60, 109, 217, 254, 308 Spectrum, 20, 74, 90, 290, 309 Sperm, 256, 265, 309 Sphincter, 26, 286, 309 Spinal cord, 172, 259, 262, 264, 265, 289, 292, 293, 297, 303, 304, 309, 310 Spinal tap, 287, 309 Spontaneous Abortion, 83, 139, 309 Staging, 305, 309 Statistically significant, 57, 309 Steroids, 32, 73, 269, 279, 309 Stimulant, 256, 262, 269, 271, 281, 290, 309 Stimulus, 254, 273, 274, 276, 284, 286, 296, 298, 304, 309, 311

328

Depressive Disorders

Stomach, 253, 278, 281, 292, 298, 308, 309 Stool, 266, 283, 285, 309 Striatum, 294, 309 Stroke, 6, 85, 104, 139, 167, 172, 184, 185, 230, 263, 309 Subacute, 284, 309 Subarachnoid, 278, 280, 285, 309 Subclinical, 284, 306, 309 Subiculum, 281, 309 Subspecies, 308, 309 Substance P, 290, 306, 310 Substrate, 62, 176, 185, 190, 191, 273, 310, 313 Sulfur, 290, 310 Supplementation, 128, 310 Support group, 10, 239, 310 Suppression, 114, 269, 310 Suppressive, 200, 310 Sympathetic Nervous System, 259, 310 Sympathomimetic, 256, 271, 272, 275, 294, 310, 313 Symptomatic, 30, 54, 72, 257, 310 Symptomatology, 5, 23, 34, 36, 76, 78, 92, 183, 310 Synapse, 79, 254, 271, 293, 300, 310, 313 Synaptic, 43, 45, 62, 293, 294, 310 Synaptic Transmission, 294, 310 Synaptosomes, 17, 310 Synergistic, 38, 40, 186, 301, 311 Systemic, 139, 222, 223, 224, 261, 266, 270, 275, 284, 285, 303, 311, 313, 316 Systolic, 282, 311 T Tachycardia, 169, 311 Tardive, 258, 265, 311 Telencephalon, 260, 264, 311 Temporal, 28, 41, 85, 183, 256, 280, 281, 288, 311 Temporal Lobe, 28, 85, 256, 311 Terminal disease, 26, 311 Testis, 276, 311 Testosterone, 118, 256, 311 Thalamus, 262, 271, 276, 286, 300, 311 Theophylline, 303, 311 Therapeutics, 40, 73, 141, 181, 214, 225, 291, 311 Thermal, 176, 257, 272, 293, 311 Thorax, 287, 311, 314 Threshold, 167, 276, 282, 311 Thrombosis, 301, 309, 311 Thromboxanes, 259, 311 Thrombus, 269, 284, 292, 299, 311

Thyroid, 66, 282, 312, 314 Thyroid Gland, 282, 312 Thyroid Hormones, 312, 314 Thyrotropin, 89, 312 Thyroxine, 88, 312 Tolerance, 25, 262, 312 Tomography, 22, 32, 42, 43, 48, 58, 180, 267, 288, 312 Tone, 188, 295, 312 Tonic, 25, 312 Tonus, 312 Tooth Preparation, 253, 312 Torsion, 284, 312 Torture, 17, 312 Toxic, iv, 186, 275, 279, 290, 293, 294, 298, 306, 312 Toxicity, 273, 312 Toxicology, 36, 61, 73, 232, 312 Toxin, 312 Trachea, 262, 286, 298, 312 Tracheostomy, 26, 312 Tranquilizing Agents, 302, 313 Transdermal, 166, 193, 313 Transduction, 23, 284, 313 Transfection, 261, 313 Translation, 71, 255, 313 Transmitter, 79, 253, 259, 272, 288, 294, 313 Trauma, 17, 23, 69, 187, 270, 292, 313 Treatment Outcome, 27, 29, 48, 65, 313 Trees, 276, 313 Triage, 53, 313 Tricuspid Atresia, 268, 313 Tricyclic, 42, 69, 82, 158, 179, 181, 203, 222, 255, 257, 265, 271, 283, 288, 313 Trigger zone, 258, 313 Tryptophan, 66, 266, 307, 313 Tubercle, 294, 313 Tumor Necrosis Factor, 35, 313 Tyramine, 261, 291, 313 Tyrosine, 153, 158, 272, 313 U Unconscious, 256, 314 Urethra, 314 Urinary, 27, 94, 270, 281, 283, 314, 315 Urine, 36, 172, 261, 272, 283, 314 Uterus, 269, 289, 300, 314 V Vaccines, 314, 315 Vagus Nerve, 169, 308, 314 Valerian, 133, 158, 314

329

Vascular, 7, 57, 255, 271, 275, 280, 284, 294, 299, 311, 312, 314 Vasodilator, 262, 272, 281, 314 Vasomotor, 276, 314 VE, 109, 132, 314 Vector, 313, 314 Vegetative, 11, 293, 314 Vein, 285, 294, 314 Venlafaxine, 32, 38, 39, 48, 114, 158, 203, 224, 314 Venter, 314 Ventilation, 26, 314 Ventral, 179, 282, 294, 314 Ventral Tegmental Area, 179, 314 Ventricle, 256, 259, 264, 268, 276, 281, 282, 294, 303, 311, 313, 315 Ventricular, 268, 281, 313, 315 Vertebrae, 309, 315 Veterinary Medicine, 231, 315 Villi, 281, 315 Viral, 274, 313, 315

Virus, 34, 127, 260, 264, 275, 279, 281, 284, 285, 313, 315 Viscera, 308, 315 Visceral, 260, 286, 314, 315 Visceral Afferents, 260, 314, 315 Vitro, 315 Vivo, 43, 45, 315 W Wakefulness, 58, 270, 315 War, 209, 212, 299, 315 Watchful waiting, 54, 315 White blood cell, 257, 284, 286, 288, 315 Windpipe, 298, 312, 315 Withdrawal, 134, 172, 174, 177, 179, 270, 315 X Xanthine, 78, 315 Xenograft, 257, 315 Xerostomia, 4, 315 X-ray, 267, 285, 294, 303, 305, 315, 316 X-ray therapy, 285, 316 Y Yeasts, 278, 298, 316

330

Depressive Disorders

331

332

Depressive Disorders

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