MAJOR
DEPRESSION 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., 1960Major Depression: 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: 0-497-00695-2 1. Major Depression-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.
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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 major depression. 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 MAJOR DEPRESSION ................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Major Depression.......................................................................... 7 E-Journals: PubMed Central ....................................................................................................... 67 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND MAJOR DEPRESSION ..................................................................... 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Major Depression ...................................................................... 113 Federal Resources on Nutrition ................................................................................................. 114 Additional Web Resources ......................................................................................................... 115 CHAPTER 3. ALTERNATIVE MEDICINE AND MAJOR DEPRESSION ............................................... 117 Overview.................................................................................................................................... 117 National Center for Complementary and Alternative Medicine................................................ 117 Additional Web Resources ......................................................................................................... 129 General References ..................................................................................................................... 131 CHAPTER 4. DISSERTATIONS ON MAJOR DEPRESSION ................................................................. 133 Overview.................................................................................................................................... 133 Dissertations on Major Depression ........................................................................................... 133 Keeping Current ........................................................................................................................ 134 CHAPTER 5. PATENTS ON MAJOR DEPRESSION ............................................................................ 135 Overview.................................................................................................................................... 135 Patents on Major Depression..................................................................................................... 135 Patent Applications on Major Depression................................................................................. 140 Keeping Current ........................................................................................................................ 147 CHAPTER 6. BOOKS ON MAJOR DEPRESSION................................................................................ 149 Overview.................................................................................................................................... 149 Book Summaries: Federal Agencies............................................................................................ 149 Chapters on Major Depression .................................................................................................. 151 CHAPTER 7. MULTIMEDIA ON MAJOR DEPRESSION ..................................................................... 155 Overview.................................................................................................................................... 155 Video Recordings ....................................................................................................................... 155 CHAPTER 8. PERIODICALS AND NEWS ON MAJOR DEPRESSION .................................................. 157 Overview.................................................................................................................................... 157 News Services and Press Releases.............................................................................................. 157 Newsletter Articles .................................................................................................................... 159 Academic Periodicals covering Major Depression ..................................................................... 159 CHAPTER 9. RESEARCHING MEDICATIONS .................................................................................. 161 Overview.................................................................................................................................... 161 U.S. Pharmacopeia..................................................................................................................... 161 Commercial Databases ............................................................................................................... 162 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 165 Overview.................................................................................................................................... 165 NIH Guidelines.......................................................................................................................... 165 NIH Databases........................................................................................................................... 167 Other Commercial Databases..................................................................................................... 169 APPENDIX B. PATIENT RESOURCES ............................................................................................... 171 Overview.................................................................................................................................... 171 Patient Guideline Sources.......................................................................................................... 171 Finding Associations.................................................................................................................. 173
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APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 175 Overview.................................................................................................................................... 175 Preparation................................................................................................................................. 175 Finding a Local Medical Library................................................................................................ 175 Medical Libraries in the U.S. and Canada ................................................................................. 175 ONLINE GLOSSARIES................................................................................................................ 181 Online Dictionary Directories ................................................................................................... 183 MAJOR DEPRESSION DICTIONARY ..................................................................................... 185 INDEX .............................................................................................................................................. 245
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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 major depression 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 major depression, 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 major depression, 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 major depression. 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 major depression, 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 major depression. 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 MAJOR DEPRESSION Overview In this chapter, we will show you how to locate peer-reviewed references and studies on major depression.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and major depression, 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 “major depression” (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: •
Dental Management of the Geriatric Patient with Major Depression Source: SCD. Special Care in Dentistry. 13(6): 249-253. November-December 1993. Summary: Major depression is a psychiatric disorder in which mood, thought content, and behavioral patterns are impaired, often for an extended period of time. In this article, the authors identify the adverse effects of depression on oral health and propose therapies for prevention and remediation. They note that the majority of antidepressant medications cause xerostomia and magnify the incidence of dental disease. Appropriate dental management of patients with the disorder necessitates the use of anti-caries agents containing fluoride, saliva substitutes, and special precautions when analgesics and local anesthetics are being prescribed or administered. 1 table. 60 references. (AAM).
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Major Depression
Recognizing and Recovering from Major Depression Source: Practical Diabetology. 20(4): 30. December 2001. Contact: Available from R.A. Rapaport Publishing, Inc. 150 West 22nd Street, New York, NY 10011. (212) 989-0200 or (773) 777-6801. Summary: Serious depressive illness is a common and critically important phenomenon among patients with diabetes. This fact sheet offers important information for patients about depression in diabetes. The fact sheet first reviews the symptoms of depression, which can include depressed, irritable or anxious mood; markedly diminished interest or pleasure in usual activities; significant weight loss or gain; inability to sleep or stay asleep, or sleeping more than usual; appearing agitated or slow to respond; fatigue or loss of energy; feeling worthless or excessively or inappropriately guilty; indecisiveness or impaired concentration; and recurrent thoughts about death or suicide. The fact sheet then briefly discusses treatment options, including psychotherapy (counseling), drug therapy, and self help groups. The fact sheet is published in the same issue as an article for health care providers on depression in people with diabetes.
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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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Lifetime Prevalence of Major Depression and Its Effects on Treatment Outcome in Obese Type II Diabetic Patients Source: Diabetes Care. 15(2): 253-255. February 1992. Summary: This article presents a short report of a study designed to assess the lifetime prevalence of major depression (MD) and its relation to glycemic control among a group of people with noninsulin-dependent diabetes (NIDDM) seeking obesity treatment. The researchers also hoped to determine whether a history of MD affected response to treatment. Sixty-six obese subjects with NIDDM (22 men, 44 women) completed the Inventory to Diagnose Depression-Lifetime Version, before a 52-week behavioral weight-control program. Weight, glycosylated hemoglobin, fasting blood glucose, and mood were assessed at pretreatment and posttreatment. Results show that a history of MD among NIDDM patients seeking obesity treatment was not related to pretreatment glycemic control but was associated with higher rates of attrition from treatment. Individuals with a history of MD who completed the program did not differ from those with no history of MD in response to treatment. 7 references. (AA-M).
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Prevalence and Costs of Major Depression Among Elderly Claimants With Diabetes Source: Diabetes Care. 26(2): 415-420. February 2003.
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Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reports on a study undertaken to compare the odds of major depression among Medicare claimants with and without diabetes and to test whether annual medical payments are greater for those with both diabetes and major depression than for those with diabetes alone. This retrospective analysis relies on claims data from the 1997 Medicare files. The authors statistically determined whether the odds of major depression are greater among elderly claimants with diabetes after controlling for age, race or ethnicity, and sex. The authors then used regression analysis on a sample of over 220,000 elderly claimants with diabetes to test whether payments for non-mental healthrelated services are greater for those with both diabetes and major depression (n = 4,203) than for those with diabetes alone. Results indicate that the odds of major depression are significantly greater among elderly Medicare claimants with diabetes than among those without diabetes. The authors also found that elderly claimants with both diabetes and major depression seek treatment for more services and spend more time in inpatient facilities, and as a result incur higher medical costs than claimants with diabetes but without major depression. These results hold even after excluding services related to mental health treatment. The authors conclude that treatment for major depression among claimants with diabetes may reduce total medical costs if treatment results in a decrease in utilization for general medical services in the future. 4 tables. 12 references. •
Olfactory Dysfunction Discriminates Probable Alzheimer's Dementia from Major Depression: A Cross-Validation and Extension Source: Journal of Neuropsychiatry and Clinical Neurosciences. 12(1): 29-33. Winter 2000. Summary: This journal article concerns the loss of the sense of smell (olfactory dysfunction) as an indicator of brain pathology, and a way to discriminate between persons with Alzheimer's disease (AD) and those with major depression. The entorhinal cortex, a major component of the olfactory system, is the first brain area affected by neurofibrillary tangles, one of the markers of AD. Forty people, 20 diagnosed with AD and 20 with major depression, all over age 55, were assessed with the 3-item Pocket Smell Test (PST), and with the Mini-Mental State Examination. The AD group had significantly lower scores than the depressed group on the PST. Results indicate that assessment of olfactory functioning can provide information for the clinician in the differential diagnosis of AD versus major depression in elderly patients. 4 tables, 28 references.
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Etiology: Clinicopathologic and Neurochemical Correlates of Major Depression and Psychosis in Primary Dementia Source: International Psychogeriatrics. 8(Supplement 3): 219-223. 1996. Summary: This journal article discusses the occurrence of major depression and psychosis in patients with dementia. It reviews strategies for diagnosing depression and psychosis in dementia patients, estimates of the prevalence of major depression and psychosis in Alzheimer's disease (AD), the natural history and prognostic significance of major depression and psychosis in AD, and response to treatment with antidepressant and antipsychotic medications. The article describes and compares the neuropathologic and neurochemical correlates of major depression and psychosis in primary dementia and notes that these two syndromes, along with delirium, produce considerable
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suffering and disability, interfere with caregiving, and precipitate institutionalization. Pharmacological treatment can help alleviate symptoms and relieve suffering. 1 table, 4 references. •
Neuropsychological Differentiation of Patients With Very Mild Alzheimer's Disease and/or Major Depression Source: Journal of the American Geriatrics Society. 43(11): 1256-1263. November 1995. Summary: This study evaluated the usefulness of standardized neuropsychological tests in the psychometric differentiation of patients with very mild or mild Alzheimer's disease (AD) and/or major depression. Researchers in England used a sample of 24 patients with a clinical diagnosis of AD (12 with major depression and 12 without), 12 patients with major depressive illness but without AD, and 12 healthy control subjects, all matched for age, sex, education, and estimates of intellectual potential. Measurements included the Mini-Mental State Examination (MMSE), Wechsler's Logical Memory (WLM), Visual Reproduction (WVR), Wechsler's Paired Associate Learning, Warrington's Recognition Memory for Faces, Kendrick's Object Learning Test (KOLT), and Digit Copying Test. Patients received a minimum 2-year followup diagnosis. Results suggest that, statistically, patients with very mild AD were distinguished clearly from those without AD on most tests of memory functions. According to the authors, only the KOLT and an index of retention on the WLM and WVR were specific enough to avoid false positives, a requirement for second-stage tools. The tests also proved sensitive enough to suggest their role as first-stage instruments when screening for primary dementia in high-functioning patients scoring above the cutpoint on the MMSE. 6 tables, 119 references. (AA-M).
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Prevalence and Correlates of Dysthymia and Major Depression Among Patients With Alzheimer's Disease Source: American Journal of Psychiatry. 152(1): 37-44. January 1995. Summary: This study examined the prevalence, risk factors, and correlates of depression among patients with Alzheimer's disease (AD). Researchers examined 103 patients with probable AD with a structured psychiatric interview and assessed them for the presence of cognitive impairments, deficits in activities of daily living, social functioning, and anosognosia. Results show that 51 percent of the patients had depression (28 percent with dysthymia and 23 percent with major depression). Women had a significantly higher prevalence of both major depression and dysthymia than men. Depressed and nondepressed patients had a similar frequency of family and personal histories of depression, a similar frequency of personality disorders before the onset of depression, and no significant differences in cognitive deficits and impairment in activities of daily living. Dysthymia usually started after the onset of dementia and was significantly more prevalent in the early stages of dementia; patients with dysthymia had a significantly better awareness of intellectual deficits than patients with major or no depression. However, patients with major depression had an earlier onset of depression (half of them before the onset of dementia), and the prevalence of major depression was similar across the different stages of the illness. 5 tables, 50 references. (AA-M).
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Prevalence and Incidence of Major Depression in Alzheimer's Disease Source: American Journal of Psychiatry. 151(7): 1006-1009. July 1994. Summary: This study examines the prevalence and incidence of major depressive disorder in Alzheimer's disease (AD). The authors retrospectively reviewed two large
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AD databases, one at the University of Texas Southwestern Medical Center in Dallas and the other at the Consortium to Establish a Registry for Alzheimer's Disease (CERAD). The Dallas series contained 264 cases of AD, of which 153 patients were followed up for an average of 3 years from initial evaluation. The CERAD database contained 1,095 cases and excluded patients with histories of depression at initial evaluation; 325 of these were followed up for at least 2 years. Most of the patients in these series were living in the community and had AD symptoms for approximately 4 years at the time of evaluation. In the Dallas series there was a 1.5 percent prevalence and a zero percent incidence of major depression. In the CERAD series there was a 1.3 percent 2- year incidence of major depression. The low prevalence and incidence of major depression in these patients suggest that for the period of time the patients were followed, AD did not predispose to major depression. However, according to the authors, major depression may herald the subsequent onset of dementia, and depression in dementia should perhaps be diagnosed by different criteria. 3 tables, 30 references. (AA-M).
Federally Funded Research on Major Depression The U.S. Government supports a variety of research studies relating to major depression. 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 major depression. 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 major depression. The following is typical of the type of information found when searching the CRISP database for major depression: •
Project Title: A TWIN STUDY OF CHRONIC FATIGUE SYNDROME IN SWEDEN Principal Investigator & Institution: Pedersen, Nancy L.; Karolinska Institute Stockholm, 17177 Timing: Fiscal Year 2002; Project Start 15-AUG-2001; Project End 31-JUL-2004 Summary: Despite considerable research, fundamental questions about CFS remain at best partially answered. These questions include its definition, validity, the degree to which it results from genetic versus environmental factors, the nature of the substantial comorbidity observed with other conditions, and the basis of the female preponderance. The overarching aim of this project is to shed light on a number of basic questions about CFS via a large, population-based classical twin study. First, we will collect data on approximately 32,000 adults aged 42-65 years (13,000 complete twin pairs) who are members of the population- based Swedish Twin Registry for persistent fatigue, several
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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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overlapping conditions (fibromyalgia, irritable bowel syndrome, tension headache, allergy/eczema, generalized anxiety disorder, and major depression), and a detailed medical history. Second, the medical records of all twins who appear to have CFS-like illness and a subset of those with "CFS-explained" will be requested via an efficient national retrieval system. Following expert review, these individuals will be classified in regard to the CDC CFS criteria. Obtaining these unique data will allow us to address a set of critical questions regarding CFS. First, we will estimate the prevalence of CFS and its common comorbidities (fibromyalgia, irritable bowel syndrome, tension headache, allergy/eczema, generalized anxiety disorder, and major depression) in one of the largest samples yet studied. Second, we will use a variety of multivariate techniques to derive an empirical typology of prolonged fatigue and to assess how this typology compares to the CFS definition. Third, we will quantify the genetic and environmental sources of variation for CFS and its comorbid conditions. Fourth, critically, we will examine the influence of gender on these sources of variation. Finally, we will analyze the patterns of comorbidity between CFS and fibromyalgia, irritable bowel syndrome, tension headache, allergy/eczema, generalized anxiety disorder, and major depression using multivariate twin analyses and thereby to estimate the extent of overlap between the shared and unique genetic and environmental sources of variation. In concert with other twin studies being conducted by the investigators and their collaborators, we hope to hasten progress in understanding the etiology of CFS by parallel studies in multiple populations. The current proposal has several unique aims and represents a costeffective means to extend this work in an epidemiological sample that is arguably the best twin registry in the world. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREGNANCY
ACUPUNCTURE
TREATMENT
OF
DEPRESSION
DURING
Principal Investigator & Institution: Manber, Rachel; Acting Associate Professor; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2002; Project Start 30-SEP-1998; Project End 31-AUG-2007 Summary: (TAKEN FROM APPLICANT): Objective: The aim of the proposed randomized controlled study is to assess the efficacy and effectiveness of acupuncture treatment of depression during pregnancy. Significance: Depression is, unfortunately common during pregnancy and it has significant deleterious effects on mother and infant, including low birth weight, preterm delivery, and continued depression into postpartum. Few medically acceptable treatments are available for the treatment of depression during pregnancy. Our preliminary work provides evidence that acupuncture may be a safe and acceptable treatment option for depression. Specific aims: 1) to evaluate the efficacy of brief 8-week treatment with SPEC acupuncture for major depression during pregnancy relative to the two control treatments; 2) to evaluate the efficacy and clinical significance (pregnancy outcome) of continued treatment with SPEC acupuncture relative to the two control treatments; and 3) to evaluate the differential impact of treatment with SPEC acupuncture for major depression on the incidence of postpartum depression. Participants. Design: To test the efficacy of acupuncture designed specifically to address depressive symptomatology during pregnancy (SPEC) it will be compared, using random assignment, to the following 2 control conditions: 1) valid acupuncture that does not directly address depressive symptoms (NSPEC), thus controlling for the belief in the efficacy of the treatment; and 2) prenatal massage (MSSG), thus controlling for attention, physical contact, relaxation and respite from daily stress. The study includes three phases, acute,
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continuation and follows up. Participants: 180 participants meeting western diagnostic criteria for Major Depression with a score >: 14 on the first 17 items of the 24-item Hamilton Depression Rating Scale (HRSD) will be randomized. The ethnic distribution of the sample will be representative of the ethnic distribution in the San Francisco Bay Area. Treatments: The acute phase of treatment consists of 16 half-hour treatment sessions delivered over 8 weeks. To consolidate treatment gains and to prevent post partum depression, participants who have full or partial response at the end of the acute phase will continue to receive the same, but less frequent, treatment until 10 weeks post partum, and will be followed up for 6 more months. Main Outcome Measure(s): The primary outcome measures are the HRSD and the depression portion of the SCID-IV, to be administered monthly during the treatment phases and at 3 and 6 months follow up. Other important measures include the Beck Depression Inventory (weekly), expectations (of the participants and the providers), and delivery and infant measures. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ACUTE PHARMACOTHERAPY OF UNIPOLAR PSYCHOTIC DEPRESSION Principal Investigator & Institution: Flint, Alastair J.; Uhn Toronto General Hospital 200 Elizabeth St, Ccrw1-800 Toronto, On Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Psychotic depression (PD) is a severe disorder that is present in 20% of mixed-age inpatients and in more than 40% of elderly inpatients hospitalized for the treatment of major depression. Acutely, PD is associated with a greater level of depression severity, functional impairment, and resistance to antidepressant treatment than nonpsychotic depression. Longitudinally, PD is associated with a greater likelihood of recurrence, a shorter symptom-free interval, greater disability, and an increased long-term risk of suicide. Among elderly patients, PD has also been associated with a high one year mortality rate. Although electroconvulsive therapy (ECT) is a highly effective treatment for PD, pharmacotherapy is more easily administered and generally preferred by many patients and psychiatrists. Furthermore, ECT is less available to, and less frequently used by minority ethnic groups, patients with low incomes, and those residing in rural areas. In the early 1980's a landmark NIMH randomized controlled trial demonstrated that a combination of high doses of both a tertiary amine tricyclic and a conventional antipsychotic was more efficacious than monotherapy with either medication. However, this combination has been associated with a high incidence of significant side effects, particularly in elderly patients. This collaborative U01 project builds on findings from the four sites principal investigators and others. Based on preliminary studies suggesting that sertraline, a serotonin-reuptake-inhibitor (SSRI) and olanzapine, an atypical antipsychotic, may be effective in the acute treatment of PD, this study uses a two-armed randomized doubleblind parallel-group design to compare the efficacay and tolerability of combining these two medications to olanzapine alone. By blocking recruitment of subjects age greater than or equal to 60 on a 1:1 basis the study will determine the relationship between older age and remission, time to remission and tolerability. A 12-week acute phase efficacy study is followed by a 20-week continuation trial during which subjects who achieved partial remission enter a placebo-controlled augmentation trial that is based on their initial assignment. Remitted subjects are also followed during stabilization to determine the stability of remission and predictors of clinical and functional deterioration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: AGMATINE, NEUROPROTECTION AND DEPRESSION Principal Investigator & Institution: Zhu, Meng-Yang; 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=6673599;P20RR Decreased hippocampal volume and reduced glial cell number in the cortex have been documented in major depression. Based largely on animal studies, stress-induced hypercortisolemia, leading to neurotoxicity and/or Active Cell Death (apoptosis) is the probable cause of the hippocampal volume loss in depression. Active Cell Death is known to involve NMDA glutamate receptor (NMDAR) activation and nitric oxide overproduction. Agmatine, an endogenous polyamine derived from decarboxylation of arginine and mainly stored in synaptic vesicles of neurons, has been found to antagonize both NMDA-R and Nitric Oxide synthase, and thereby to possess natural neuroprotective properties (i.e., shown against hypoxic ischemia). Hippocampal volume loss has been well-established to occur in animal models of chronic stress. Agmatine is normally abundant in the hippocampus where it may normally be co-released with glutamate to protect from excito-neurotoxicity through a polyamine site in the NMDA-R of normal rats. We hypothesize that in subjects suffering from major depression, agmatine becomes depleted as a consequence of long term release under prolonged stress, and therefore the hippocampal neurons become exposed to neuronal damage. The goal of my proposal is to examine the neuroprotective properties of agmatine against neurotoxicity induced by excitotoxins or higher concentrations of glucocorticoids as have been detected in patients with major depression. To address this goal, the neuroprotective effects of agmatine will be measured in 1) cultured fetal rat hippocampal neurons exposed to glutamate as well as related chemicals, or high concentrations of glucocorticoids in vitro which mimic conditions found in depressed patients in vivo, 2) the hippocampi of rats treated with excitotoxins, and 3) the hippocampi of rats after undergoing chronic mild stress. Concentrations of endogenous agmatine in hippocampi will be correlated with the extent of structural injury to neurons and glial cells in the hippocampal primary culture and in the hippocampus in vivo of treated rats and the rat chronic mild stress model. This research is designed to elucidate the functional significance of agmatine as an endogenous neuroprotective agent of relevance to the effects of chronic stress as occurs in depression. Clarification of structural and biochemical changes in the hippocampus of the chronic mild stress animal model will add to evidence of hippocampal neuron loss in depression, and hopefully suggest ways to augment agmatine's natural neuroprotective effects. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ALCOHOLISM AND SUICIDE Principal Investigator & Institution: Conner, Kenneth R.; Assistant Professor; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2003 Summary: (provided by applicant): Alcoholism is a potent risk factor for suicide and attempted suicide, yet there is a paucity of controlled data on the factors that distinguish alcoholics who take their own lives or make medically serious suicide attempts. To address this gap in knowledge, the investigators will conduct secondary analyses on a dataset gathered in the Canterbury region of New Zealand between 1991 and 1994 for the Canterbury Suicide Project (CSP). The CSP identified and collected data on adult suicide victims (N=193) and medically serious suicide attempters (N=240) and a
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community control group (N=984). Diagnostic data using best-estimate methods including DSM-III-R alcohol dependence (past month) are available. Data on other diagnoses (mood, psychotic, antisocial personality, drug use disorders), stressful life events, and personality traits were also gathered. In Aim 1, two predisposing factors, major depression and antisocial personality disorder (ASP), will be investigated as potential moderators (effect modifiers) of the association between alcoholism and suicidal behavior. In Aim 2, two precipitating factors, conjugal disruptions and other stressful life events, will be evaluated as potential mediators (intermediate effects) of the relationship between alcoholism and suicidal behavior, and between ASP and suicidal behavior. Primary analyses will be based on polytmous regression models and specifically, unordered logistic regression models with two case groups (suicides, serious attempts) and a reference group (community controls). This will allow for direct comparisons between each case group and the reference group as well as between the case groups. Results will be expressed in terms of odds ratios and asymmetric confidence intervals. Goodness-of-fit will be assessed using standard procedures. Secondary analyses will include estimates of relative risk and population attributable risk for suicide and serious attempts associated with alcohol dependence and other diagnostic conditions, and explore potential gender differences in risk factors for suicidal behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANTIDEPRESSANT ADHERENCE IN LATE LIFE DEPRESSION Principal Investigator & Institution: Bungay, Kathleen M.; Assistant Professor; New England Medical Center Hospitals 750 Washington St Boston, Ma 021111533 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): This application requests a Mentored PatientOriented Research Career Development Award (K23) to study and evaluate ways to overcome barriers to treatment of depression in the elderly. The applicant is a Doctor of Pharmacy specializing in the pharmacotherapy of psychiatric disorders at Tufts New England Medical Center who proposes to develop research skills for treatment of depression in community dwelling elderly patients. Although major depression is widely recognized to cause significant morbidity and mortality in the geriatric population, the ever increasing population of community dwelling elderly are at particular risk of having recognized and unrecognized depression. Even in those with diagnosed depression, willingness to take antidepressant medications is suboptimal. Little is known about what the barriers to treatment are, and how these barriers may be overcome. The candidate's research and educational plan will focus on innovative research methodology including: a) advanced study design and statistical methodology to develop skills to address complex problems relevant to medication adherence assessment, b) qualitative research methods that permit exploration and definition of research questions regarding medication adherence behaviors, and c) mentored, integrated and interdisciplinary research experience under Tufts faculty in health services research, psychiatry, medicine, health policy and geriatrics. To achieve these goals, the candidate will compare trends in antidepressant (AD) use over time using data from an NIMH study of a longitudinal pharmacist intervention in depressed primary care patients. Second, explore reasons why depressed patients refuse to take AD treatment as prescribed in this cohort. Lastly, develop assessment tools to evaluate willingness to take AD medications in an NIA funded cohort of home bound elderly and an patients of an inner city geriatrics ambulatory care practice. The specific aims of the proposed research are: 1) to determine if reasons for not taking antidepressant
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medications as prescribed are different in the elderly compared with young adults; 2) to evaluate how and why community dwelling elderly refuse to take antidepressant treatment as prescribed. This research has potential to improve treatment of depression in the elderly, improve outcomes, quality of life and functioning to enable older individuals to maintain their independence outside an institutional setting. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BIOBEHAVIORAL MECHANISMS OF DEPRESSION IN WOMEN Principal Investigator & Institution: Cyranowski, Jill M.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 20-AUG-2001; Project End 31-JUL-2006 Summary: (provided by applicant): This Mentored Research Scientist Development Award (MRSDA) is designed to promote the Candidate's long-term goal of becoming a women's health researcher with expertise in the etiology and treatment of depression in women. The training and research activities described in this MRSDA will facilitate the Candidate's training in the methods of acute stress research and neurohormonal assessment techniques, and the integration of these techniques within her own background in depression intervention research. This interdisciplinary training will provide the Candidate with the skills and experience needed to pursue an independent program of research testing biobehavioral mechanisms of stress sensitivity, depression vulnerability, and ultimately, depression treatment outcomes in women. Post-pubertal females are twice as likely as males to experience a lifetime episode of major depression, and are particularly likely to become depressed when faced with stressful life events. This gender-linked health disparity persists throughout women's reproductive lives, carrying deleterious consequences for both the woman herself and the children under her care. We (Cyranowski et al., 2000) have theorized that women's sensitivity to interpersonal life stress is mediated, in part, by the hypothalamic neurohormone, oxytocin. Oxytocin is known to play a key role in female reproductive processes. A growing body of animal research indicates that oxytocin is critically regulated by female reproductive hormones, and that oxytocin serves to facilitate female affiliative behaviors and down-regulate the hypothalamic-pituitary-adrenal (HPA) stress axis. The proposed pilot study was designed to provide a preliminary examination of the role of oxytocin in women's stress sensitivity and depression vulnerability. Twenty-two normal cycling, depressed females aged 21-40 and 22 agematched never-depressed controls will be recruited to participate in a 3-hour laboratory experiment designed to stimulate, measure and compare peripheral oxytocin release and basal oxytocin concentrations within and between groups, and to examine whether peripheral oxytocin release is associated with a down-regulation of the HPA stress axis following an acute stress task. Subjects will also complete self-report measures of depression, anxiety, interpersonal function, trauma history, and recent life stress. Subjects will then be retested with the laboratory paradigm at 18 weeks follow-up, or for depressed subjects, following a course of interpersonal psychotherapy (IPT). The skills, training, and pilot data obtained from this MRSDA will subsequently be used to support the Candidate's development of an R0l 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: CALCIUM FOR PREVENTION OF POSTPARTUM DEPRESSION Principal Investigator & Institution: Hatton, Daniel C.; Behavioral Neuroscience; Oregon Health & Science University Portland, or 972393098
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Timing: Fiscal Year 2002; Project Start 08-FEB-2002; Project End 31-JAN-2005 Summary: (provided by applicant): Post-partum depression causes maternal suffering and can have a lasting negative influence on the child's cognitive and emotional development. Interventions that prevent or reduce the incidence of post-partum depression would be of significant value to society. Preliminary studies indicate that dietary calcium supplementation during pregnancy may provide an inexpensive, safe, and effective protection against postpartum depression while at the same time providing a number of other health benefits for the mother and child. We will conduct a rigorous test of the hypothesis that supplemental calcium during pregnancy reduces the incidence of post-partum depression in a randomized, double-blind, placebo-controlled clinical trial of a 2 g/day oral calcium supplement in 238 women at risk for postpartum depression as a consequence of a positive history of depression. Supplementation will begin between weeks 16 and 20 of gestation and continue through 12-weeks post partum. Women will be recruited by newspaper advertisements and clinic referrals. Prior to randomization, a computerized version of the SCID followed by a psychiatric diagnostic interview will be used to determine baseline clinical status. Those currently suffering from major depression, active substance abuse, active psychosis, schizophrenia, bipolar disorder or are on antidepressant medication, will be referred for treatment and will not be included in the study. Prior history of postpartum depression and parity will be controlled for during randomization. The antenatal version of the Edinburgh Postnatal Depression Scale (EPDS) will be used to screen for depression at 26, 32 and 38 weeks of gestation and the postnatal version will be used at 6 and 12 weeks postpartum. Those with a positive change score of 30 percent or a score greater than 16 on the EPDS at any screening visit will be evaluated using a psychiatric interview. Those suffering from major depression will be referred for treatment. The proportion of women in the calcium supplemented group who experience a first episode of major depression since entry into the study in the postpartum period, either at 6 or 12 weeks, will be compared to the proportion in the placebo condition. A significantly smaller proportion in the calcium group will be taken as evidence in support of the hypothesis. Positive results from this trial will provide a strong foundation for a multicenter intervention trial. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHILDREN AT RISK FOR ANXIETY DISORDERS:A FOLLOW UP STUDY Principal Investigator & Institution: Rosenbaum, Jerrold F.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 01-MAY-1993; Project End 31-MAR-2009 Summary: (provided by applicant): The proposed study is a 12-year follow-up of a large cohort (N=446) of offspring at risk for panic disorder (PD), and comparison offspring at risk for major depression (MD) or without vulnerability for mood or anxiety disorders. The children were originally recruited in toddler hood and early childhood, were reassessed in middle childhood (at Year 6), and will enter adolescence during the next wave. This sample is unique in that a) children were characterized extensively at Baseline, using laboratory measures of behavioral inhibition (BI) and assessments of nascent symptomatology well before they entered the period of risk for childhood anxiety disorders; b) proband parents underwent comprehensive assessments of their adult and childhood psychopathology, with careful attention to delineating episodes to which offspring might have been exposed; and c) to our knowledge, it represents the largest sample of children at risk for anxiety followed longitudinally to date. Our study
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is also unique in that it has spawned offshoots in several promising directions, including studies of the genetic bases of BI and of an early intervention for young children at risk for anxiety. Our ongoing goals have been to study whether it is possible to predict the development and sequence of anxiety disorders among children of parents with PD, as well as to identify risk factors for childhood psychopathology, including temperamental (behavioral inhibition or disinhibition [BD]), parental comorbidity, and psychosocial adversity factors which might influence or moderate risk. We have already identified increased risks in middle childhood for PD, agoraphobia, and multiple anxiety disorders in offspring of PD parents, for a range of anxiety, mood and disruptive behavior disorders in offspring of MD parents, for social anxiety in BI youngsters, and for disruptive behavior disorders in children with BD. We have also noted associations between risk for anxiety disorders and perinatal and psychosocial risk factors. Now, as the children enter adolescence, a period of heightened risk for onset of social phobia, PD, and MD, as well as alcohol and substance abuse, peer difficulties, and other psychosocial problems, we are in the exciting and unique position to answer questions about the specific vulnerabilities conferred by parental PD, parental MD, BI or BD, and pre-existing childhood disorders. We are also able to begin to ask why and how the risk factors we have identified early in childhood influence psychopathology or resiliency in adolescence, and in what ways they combine with protective factors in predicting outcome. These research questions are straightforward, yet they carry broad implications. Studies of high-risk children and adolescents are of the utmost major public health relevance, since the identification of predictors of psychopathology and substance use disorders can set the stage for targeted primary or secondary prevention programs. The identification of such predictors, whether constitutional or environmental, is essential if we are to understand why some children with biological or psychosocial risk factors remain healthy during adolescence and successfully negotiate developmental tasks of this period while others develop psychopathology or derailments in functioning. Careful articulation of the mechanisms by which such factors operate would enable the design of specific, efficient, and cost-effective interventions to prevent poor outcomes in adolescence, and would permit the targeting of scarce societal resources for populations most likely to benefit from such programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CLASSIFICATION OF EARLY ONSET DYSTHMIA Principal Investigator & Institution: Klein, Daniel N.; Professor; Psychology; State University New York Stony Brook Stony Brook, Ny 11794 Timing: Fiscal Year 2002; Project Start 01-APR-1991; Project End 31-MAR-2004 Summary: (Adapted from Applican't Abstract): Dysthymic Disorder (DD) is a fairly prevalent condition with substantial social costs. As a nosological construct, it is defined and distinguished from Major Depressive Disorder (MDD) primarily on the bases of longitudinal course. Ironically, however, prospective data on the long-term course of DD are extremely limited. The present proposal seeks funding to complete the last five years of a then-year naturalistic follow-up study of DD, with follow-up evaluations being completed at 30 months intervals. Subjects include 97 outpatients who met DSMIII-R criteria for primary, early-onset dysthymia at entry into the study, and a comparison group of 45 outpatients with non-chronic (or episodic) major depression. Baseline and follow-up assessments include structured diagnostic interviews assessing Axis I and Axis II disorders conducted blind to the baseline evaluation, a comprehensive battery of self-report inventories, interviews with knowledgeable informants, and review of medical records. Attrition over the first five years of follow-up has been
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relatively low. The study addresses five major issues: (1) the diagnostic stability of DD; (2) the long-term naturalistic course of DD; (3) clinical, Psychosocial, and familial predictors of course and outcome; (4) the stability of comorbid anxiety and personality disorders, and their relationship with DD over time; and (5) the long-term course of social adjustment in DD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: COLLABORATIVE DEPRESSION STUDY Principal Investigator & Institution: Coryell, William H.; Professor; Psychiatry; University of Iowa Iowa City, Ia 52242 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
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Project Title: COMPARING THREE ELECTRODE PLACEMENTS TO OPTIMIZE ECT Principal Investigator & Institution: Rasmussen, Keith G.; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 16-SEP-2002; Project End 31-MAY-2006 Summary: (provided by applicant): Electroconvulsive therapy remains an important treatment for severely depressed patients who do not respond adequately to, or are intolerant of, antidepressant medication. As the prevalence of major depression increases, particularly in the geriatric population, the need for effective treatments is an urgent public health concern. Despite refinements in technique, the cognitive impairment associated with ECT remains a serious concern for many patients. Traditionally, ECT has been administered with one of two standard techniques: 1) bilateral (bitemporal) electrode placement or 2) right unilateral electrode placement. Bilateral electrode placement has greater efficacy but causes more cognitive impairment, while right unilateral electrode placement is less effective for some patients but causes less cognitive impairment. Recently, two innovative techniques have shown promise in preliminary studies: 1) right unilateral ECT administered at much higher electrical dose, which may achieve efficacy equivalent to bilateral ECT and 2) a novel electrode placement (bifrontal) which may combine the beneficial properties of both bilateral and
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unilateral ECT. We propose a double blind, randomized, controlled clinical trial comparing the standard technique of bilateral ECT with two novel techniques - highdose unilateral ECT and bifrontal ECT. The primary aims of the study are to compare the three treatments in terms of 1) antidepressant efficacy and 2) cognitive effects during and at the end of the treatment course, and over a two-month naturalistic follow-up period. An additional aim is to compare the treatments in terms of quality of life over two months. In this study, 360 patients with major depression are randomized over 4 years at 4 sites. Assessments are the Hamilton Rating Scale for Depression (HRSD), a comprehensive neuropsychological test battery, and quality of life outcome measures. Provisions are made for assuring the ongoing quality of treatments and assessments. The investigators are experienced ECT providers and researchers who are now successfully collaborating on an ongoing NIMH-funded trial of continuation ECT vs. pharmacotherapy. The proposed study will be the first direct comparison of the three types of ECT and will inform psychiatrists about the optimal technique of ECT. The results of this study will promote more effective and safer treatment of the most severely ill depressed patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CONTROLLED TRIAL OF SERTRALINE FOR DEPRESSION AFTER TBI Principal Investigator & Institution: Bombardier, Charles H.; Associate Professor; Rehabilitation Medicine; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 20-SEP-2000; Project End 31-MAY-2005 Summary: Persons with traumatic brain injury (TBI) experience high rates of depression, especially during the first six months following their injuries. Neurological and psychosocial factors appear to contribute to depression in this population. Depression following TBI is associated with poor cognitive, behavioral, and functional outcomes. Preliminary studies suggest that people with TBI and major depression may not respond to antidepressant treatment in the same way as depressed persons without TBI, post TBI depression may respond well to selective serotonin reuptake inhibitor (SSRI) antidepressants, that and effective antidepressant treatment is associated with improvements in health status, neuropsychological function, and post-concussive symptoms. No large randomized placebo-controlled studies have been conducted and basic questions remain about the treatment and outcomes of major depression among persons with traumatic injury. As a consequence, depression is not usually assessed after traumatic brain injury, and optimal rehabilitation guidelines for identifying and treating depression have not been established. To address this gap, the proposed study would follow a large consecutive sample of persons hospitalized for moderate to severe TBI to identify those who develop major depression. With those who develop major depression, a 12-week, randomized, double-blind, controlled trial of sertraline would be conducted. The trial would test the hypothesis that sertraline reduces depression related symptoms, as measured by the Hamilton Rating Scale for Depression. Secondary hypotheses to be tested include whether sertraline leads to greater improvement in neuropsychological test performance, post-concussive symptoms and self-reported health status as measured by the SF 36. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COST EFFICIENT TREATMENT OF GERIATRIC DEPRESSION Principal Investigator & Institution: Mcdonald, William M.; Associate Professor; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 10-APR-1998; Project End 31-JAN-2004 Summary: (Applicant's abstract): The annual cost of depression in the United States has been estimated to be greater than 40 billion dollars, and includes the direct costs of treatment and indirect costs related to lost productivity. The elderly are particularly prone to increased disability from depression. Prospective studies demonstrate that up to two-thirds of elderly depressed patients have a poor outcome in one year, and over one-fourth are re-hospitalized in the year following the acute depressive episode. Yet the current public policy debates have focused on the cost of entitlement programs such as Medicare and have ignored the complex relationship between the cost of the initial treatment, efficacy and long term benefit in reducing overall healthcare costs. The primary aim of the present proposal is to develop practical guidelines for the acute and prophylactic therapy of treatment resistant geriatric major depression. In this proposal, severely depressed elderly patients will be evaluated, treated with either medication or electroconvulsive therapy (ECT) and followed for 18 months. The data generated will be used to develop statistical models of the most clinically effective and cost-efficient acute, continuation and maintenance treatments for severe geriatric depression,. 360 patients meeting DSM-IV criteria for Major Depression, severe (approximately half with psychotic features) and the American Psychiatric Association guidelines for ECT will be randomized to either an acute trial of ECT or a 6 week prospective medication trial. Medicare costs, neuropsychological, sociodemographic and clinical data will be analyzed to determine both the costs of an additional medication trial, and the patient characteristics which are associated with a response to medication/ECT. Patients who fail the prospective medication trial will be administered an acute course of ECT. The second and third phases of the study will evaluate alternative prophylactic therapies after an acute response to ECT. Patient who are severely depressed and respond to ECT. Patients who are severely depressed and respond to an acute course of ECT have extremely high healthcare costs and attendant morbidity and mortality. The risk of relapse in 6 months in these patients is unacceptably high (50-70%) using the conventional strategy of placing the patient on continuation antidepressant medication. The 180 patients who respond to an acute course of ECT or fail the prospective medication trial and then respond to an acute course of ECT and will be randomized to either 6 months of continuation strategies. In the third phase, 160 patients will be followed for an additional year in order to examine the long term benefits of alternative continuation strategies (i.e., ECT vs. medication) on measures of mood stability, neuropsychological function and total healthcare costs. The data from these studies will be used to develop a clinical checklist which can be used in general psychiatric practice to assist clinicians in making clinically effective and cost-efficient treatment decisions. 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
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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 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 •
Project Title: DEPRESSION AND CHRONIC PAIN IN MARRIAGE Principal Investigator & Institution: Cano, Annmarie; Psychology; Wayne State University 656 W. Kirby Detroit, Mi 48202 Timing: Fiscal Year 2003; Project Start 01-AUG-2003; Project End 31-JUL-2008 Summary: (provided by applicant): The principal investigator (PI) is requesting five years of funding through the Scientist Development Award for New Minority Faculty (K01). The career development goals described in this application include testing an integrative model of depression and chronic pain developed by the applicant and training in theoretical and conceptual issues, advanced longitudinal statistical methods, objective interview assessment of life events, observational research methods with couples, and the responsible conduct of research with ethnic minorities. These activities are expected to build on the Pl's strong research and clinical background in marriage and enhance her ability to produce sophisticated scholarly work. Major depression and chronic pain are costly public health problems in the United States that are highly comorbid with each other. Although research suggests that marital variables may contribute to depression, researchers have yet to integrate existing theory and empirical
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findings into a comprehensive model that accounts for the interrelationships between marital functioning, chronic pain, and depression. Building on the career development activities described in the application, the PI will test an integrative model of the comorbidity of chronic pain and depression in which marital functioning plays a key role. The long-term objective of the study is to develop marital treatments for individuals experiencing both depression and chronic pain. The specific aims of the study include examining how changes in general marital functioning (e.g., marital satisfaction, affect expressed in a marital interaction, marital stressors), pain-specific marital functioning (e.g., spouse responses to pain, affect expressed in a marital interaction related to the impact of pain on the couple), and pain factors (e.g., pain severity, disability) relate to changes in depression over time. Participants will be 160 married couples in the community in which one spouse has a chronic musculoskeletal pain problem. Participant couples will complete surveys, a diagnostic interview for major depression, a life events interview, and two videotaped marital interactions. Participants will also take part in 6- and 12-month follow-ups in which they will complete the same instruments. Participants will be paid upon completion of each phase of the study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION IN HIV+ WOMEN: EFFECT ON NK CELLS Principal Investigator & Institution: Wahid, Zia; Meharry Medical College 1005-D B Todd Blvd Nashville, Tn 37208 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2009 Summary: Depressive symptoms are common in HIV patients and warrant thorough assessment and intervention. However, this may be made more critical by findings with regard to the effects of depression on immune function. Depression has been shown to adversely affect immune function; as well it may also accelerate the course of HIV disease progression. There is now evidence that depression not only influences key components of cellular immunity, but may increase the likelihood of disease progression. There is also very recent evidence that depression may alter the function of innate immunity among HIV+ women. Clearly, the impact of depression on immune function, particularly in HIV+ women, is clearly warranted. The central hypothesis of our study is that HIV-seropositive women who are diagnosed with major depression have a decreased function of natural killer (NK) cells and other cytotoxic effector cells, and that treatment with serotonin-specific reuptake inhibitors (SSRIs) reverses this decline. Further, we hypothesize that antidepressants will directly effect NK cell function. This accounts, at least in part for the recovery of function following treatment. If the hypotheses are supported, this could lead to an improved outcome for women with HIV disease. This project is intended to: 1. Determine the immune status especially the functional capacity of NK and cytotoxic T cells in women infected with HIV with and without co-morbid major depression 2. Determine the NK and T cell function from depressed women before and after treatment with an SSRI. 3. Study possible mechanisms by which treatment of depression in HIV infected women with an SSRI modulates NK cell function. The relationship between the modulation of NK function and improvement with an SSRI will be investigated. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION IN LATE LIFE AND CAUSES OF DEATH Principal Investigator & Institution: Gallo, Joseph J.; Associate Professor; Family Practice and Cmty Med; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104
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Major Depression
Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2007 Summary: (provided by applicant): The overarching goal of this study is to assess mortality of depressive syndromes in older adults in relation to overall death rates as well as in relation to deaths from specific causes, especially cardiovascular disease, while accounting for baseline and time-varying cardiovascular risk factors and other potentially influential personal and clinical characteristics. We will compare death rates among a representative sample of older persons who participated in an intervention trial designed to increase the number of older adults who receive appropriate depression treatment, such as antidepressant medications and psychotherapy. The study sample is enriched with older primary care patients with major and minor depression (n = 719) participating in an intervention trial, making it possible to study the impact of treatment on mortality risk associated with depression. Specific aims of this study are: (1) to estimate the relative risk of all-cause mortality among older primary care patients with major depression and clinically significant minor depression compared to patients without significant depression after a 3-year follow-up interval, accounting for potentially influential personal and clinical characteristics; and, (2) to assess whether varying intensity of depression treatment is associated with different allcause mortality after a 3-year follow-up interval. To accomplish these aims, we will capitalize on screening, clinical assessment, treatment, and follow-up assessments which have occurred for up to 2 years in PROSPECT (the "Prevention of Suicide in Primary Care Elderly: Collaborative Trial"). PROSPECT is a collaborative multi-site intervention study funded by the NIMH in primary care practices have been randomized into one of two treatment conditions: (1) treatment as usual (n = 597 patients); and (2) a guideline management intervention (n = 620 patients). In all, 1,217 patients, including all patients who screened positive for depression and a random sample of patients who screened negative, have been enrolled in the 2-year longitudinal study and clinically evaluated for DSM-IV major depression, minor depression, and dysthymia. In PROSPECT, 719 patients met criteria for depression treatment. The adequacy of depression treatment is assessed for all 1,217 patients regardless of diagnosis. Our proposal seeks support for identifying the follow-up vital status of the participants (using the National Death Index) and, for the persons who have died, determining primary and underlying causes of death using data from NDI Plus and primary care medical records. What we learn from this follow-up will help design interventions that are specifically targeted to decrease mortality among older adults with depression that is frequently associated with concurrent medical conditions such as diabetes mellitus and hypertension. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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.
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21
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) 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 •
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.
22
Major Depression
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION
DEPRESSION,
EPINEPHRINE,
SEROTONIN,
&
PLATELET
Principal Investigator & Institution: Musselman, Dominique L.; Assistant Professor; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 04-FEB-2002; Project End 31-JAN-2006 Summary: Several studies have shown that major depression and associated symptoms, such as hopelessness, are a major independent risk factor in development of ischemic heart disease (IHD), and for death after an index myocardial infarction. Not only do platelets play a central role in hemostasis, atherosclerosis, and acute coronary syndromes, but patients with major depression exhibit increased numbers of the functional platelet GPIIb/IIIa receptor, the receptor for fibrinogen and other ligands, and the final common pathway by which platelet aggregation and adhesion occurs. The overall goal is to determine in patients with major depression, the specific molecular pathways, and relative contributions of these pathways, whereby the platelet GPIIb/IIIa receptor is converted from a low- affinity to high-affinity conformation. To accomplish this goal, we will scrutinize in men with unipolar, recurrent, major depression, not only depression severity and platelet GPIIb/IIIa receptors, but characterize platelet autocrine "feed forward" pathways via: platelet serotonin (5HT) and 5HT2 receptors, platelet adenosine triphosphate (ATP) release, and urinary excretion of 11-dehydrothromboxane beta2: (1) under controlled basal conditions, (2) after the Trier Social Stress Test (a sustained mental stressor which will stimulate platelet function via peripheral release of the platelet agonist epinephrine). Moreover we will determine the molecular mechanisms whereby antidepressant treatment reduces numbers of high-affinity GPIIb/IIIa receptors, using randomized, double-blind, treatment with paroxetine (a selective 5HT reuptake inhibitor) in comparison to desipramine (a noradrenergic tricyclic). State-of- the-art techniques will be used, including fluorescence activated flow cytometry (FAFC), platelet calcium mobilization, and evaluation of in vitro antidepressant direct "drug effects" of upon platelet function. Novel information will be gleaned regarding not only the biological basis for the increased vulnerability of depressed patients to IHD, but also potential thrombovascular targets whereby psychopharmacologic interventions might reduce the future risk of heart attack and sudden death in patients with major depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION, SLEEP DISORDERS AND CORONARY HEART DISEASE Principal Investigator & Institution: Carney, Robert M.; Professor of Medical Psychology; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 30-SEP-2000; Project End 31-JUL-2005 Summary: Description (adapted from the investigator's abstract): Clinical depression is a risk factor for mortality and morbidity after acute myocardial infarction (MI), yet little is known about the underlying mechanisms that account for this. The purpose of this study is to examine a potential mechanism, cardiovascular response to disordered sleep. Three months after an MI, 75 patients who meet the DSM-IV criteria for major depression will be selected and matched for gender, age, BMI to patients without
Studies
23
depression. Polysomnography will be performed to determine the frequency and severity of cardiac responses to sleep disordered breathing and sleep architecture measures. The following hypotheses will be tested: 1) patients with depression have greater cardiac response to episodes of sleep apnea than non-depressed patients; 2) patients with depression without sleep disordered breathing have shorter REM latency, increased REM density, reduced slow wave sleep and worse sleep efficiency; 3) increased cardiac response to sleep disordered breathing, a shorter REM latency, increased REM density, decreased slow wave sleep are associated with electro cardiographic abnormalities predictive of cardiac events in post MI patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION, STRESS & HEALTH: ROLE OF ANABOLIC HORMONES Principal Investigator & Institution: Epel, Elissa S.; Langley Porter Psychiatric Institute; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2002; Project Start 05-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): The objective of the proposed Mentored Clinical Scientist Development Award (K08) is to promote the candidate's development as an independent behavioral science researcher, with a focus on neuroendocrine responses to stress, and their effects on mental and physical health. During the five-year career development period, the candidate will engage in formal and informal training in psychoneuroendocrinology and stress and coping, complete three research projects, build collaborations, and address basic questions about relationships between stress, hormones, and risk for depression and cardiovascular disease. Chronic psychological stress contributes strongly to depression and cardiovascular disease, but the mechanisms are unclear. Most research in this area has focused on the deleterious effects of catabolic stress hormones like cortisol. Although hypercortisolemia turned out to be a weak biological marker of depression, it may be more revealing when examined in combination with anabolic hormones, such as dehydroepiandrosterone (DHEA) and growth hormone (GH), which can buffer the damaging effects of cortisol. The long-term goal of the current research program is to examine whether anabolic and catabolic hormones, as well as their levels relative to each other (anabolic balance) serve as a mediating pathway from stress to depression and to risk factors for cardiovascular disease (insulin resistance, visceral fat, and atherosclerosis). Studies 1 and 2 will examine whether history of chronic stress predicts low anabolic balance, depression, and risk for disease in longitudinal cohorts of younger adults (N = 1000) and older adults (N = 1000). Study 3 will assess whether chronic stress alone and with major depression is related to basal and reactive measures of anabolic balance and disease risk in caregivers, who serve as a unique model of chronic stress. If warranted, future research will compare effects of stress reduction and hormonal supplementation on mood and disease risk. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
•
Project Title: DEPRESSION/DESIRE FOR DEATH IN TERMINAL CANCER PATIENTS Principal Investigator & Institution: Breitbart, William; Professor and Chief; SloanKettering Institute for Cancer Res New York, Ny 100216007 Timing: Fiscal Year 2002; Project Start 01-SEP-2000; Project End 31-MAY-2004
24
Major Depression
Summary: A clinically important mental health issue in palliative care concerns desire for death and its relationship to depression. Research focused on desire for death provides a link to understanding why patients might want to end their lives or request physician-assisted suicide (PAS) in the face of terminal illness. There have been several recent studies of patients with cancer or AIDS, demonstrating the central role of depression in desire for death and hypothetical interest in PAS. With one exception, these studies have not directly assessed desire for death among terminally ill patients, and no research has attempted to answer the question of whether treatment for depression has a significant impact on desire for death. This project aims to describe desire for death among patients with end-stage cancer, determine its correlates, and assess the impact of treatment for major depression on desire for death. Specifically, the research would assess the prevalence, severity, stability, and medical/psychosocial correlates of desire for death among terminally ill cancer patients hospitalized in a palliative care facility. It will examine the relationship between desire for death and a clinical diagnosis of Major Depressive Episode. Desire for death will then be monitored in a group of patients who receive a standardized pharmacological treatment for depression, as well as in patients who do not receive any intervention. This study is expected to provide a direct evaluation of desire for death in terminally ill cancer patients, and to ascertain whether a pharmacological treatment for depression influences desire for death. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
Studies
25
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 •
Project Title: DEVELOPMENT AND APPLICATIONS OF NOVEL SERT PET LIGANDS Principal Investigator & Institution: Goodman, Mark M.; Professor of Radiology; Radiology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 19-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): Considerable evidence accrued over the last two decades have convincingly implicated decreased serotonin transporter (SERT) binding in the pathophysiology of major depression and suicide. Although a tremendous amount of information regarding the SERT and its role in depression and suicide has been obtained, this supporting evidence has, however, been indirect in being derived almost exclusively from the study of postmortem tissue and animal and peripheral cell models of transporter cell function and pharmacology. The mechanisms responsible for decreased brain SERT binding in depression and suicide are still unknown. We propose to develop fluorine-18 and bromine-76 imaging agents as tools to the exploration of the mechanism of major depression by assessing the functional status of SERT using Positron Emission Tomography (PET). This application wide focus on the development of positron emitting analogs of 2beta-carbomethoxy-3 beta-(4'-(Z-2iodoethenyl)phenyl)nortropane (ZIENT) that show high selectivity and affinity for the SERT and low nonspecific binding. Our recent preliminary data with iodine-123 labeled ZIENT indicate that structural features unique to ZIENT permit in vivo measurement of SERT density in cortical brain regions suggesting ZIENT is a suitable lead compound for PET radiotracer development. Two goals of this proposal are: 1) conduct a structure activity relationship study (SAR) to identify a sutiable fluorine-18 and bromine-76 radiotracer for in vivo imaging of the SERT in atients with mood disorders; the SAR study will involve: (a) the development of synthetic methods for the preparation of new 18F- and 76Br-labeled 2beta-carboalkoxy-3beta-(4'-(Z-2-haloethenyl)phenyl)nortropanes, (b) the in vitro determination of relative affinity of 18F- and 76Br- candidates (c) ex vivo estimation of brain penetrance and regional distribution in rats. (d) microPET studies defining time- activity curves for specific and nonspecific binding in brain regions-ofinterest in rhesus monkeys. (e) ligand metabolite studies performed on arterial samples (f ) microPET studies of in vivo binding site selectivity assessed by "chase" competition in rhesus monkeys. (g) Graphical analysis of cerebral SERT site binding using microPET in non-human primates with the lead radiolabeled analog; 2) To conduct toxicity studies on an optimized ligand that will support the submission of an RDRC and an IND application. Our hypotheses include: 1) the introduction of fluorine onto an alkyl group in the 2P-carboakoxy- position of ZIENT and replacement of iodine with bromine on the 3beta-(4'-(Z-2-haloethenyl)phenyl) group will generate a PET ligand with imaging characteristics equivalent to ZIENT; 2) A 18F- and 76Br-analog of ZIENT provides substantial temporal and logistical benefits for SERT imaging as compared to a SERT [11C] radiotracer due to the longer half-life of fluorine-18 (t1/2=110 min) and bromine76 (t 1/2= 16 h) compared to carbon (tlI2=20min). After the best novel PET SERT ligand is identified, it will be applied in humans to define the relationship between brain SERT binding and depression and suicidal behavior. We will also begin to define SERT alterations in dimensional traits that are related to suicide, such as aggression,
26
Major Depression
impulsivity and anxiety. The relationship between SERT 5-HTTLPR promoter region and in vivo SERT expression will be explored. Once SERT binding is determined in depressed patients, we will be able to assess the relationship of SERT binding and treatment response to SSRIs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT SYMPTOMATOLOGY
OF
AN
INVENTORY
OF
DEPRESSIVE
Principal Investigator & Institution: Rush, Augustus J.; Betty Jo Hay Professor & Chair in Mh; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2003; Project Start 07-AUG-2003; Project End 31-JUL-2006 Summary: (provided by applicant): This application is a collaborative R01 submitted by Duke University, the University of Texas Southwestern Medical Center, and the University of Texas at Arlington in response to RFA 03-002. We plan to further develop and evaluate the 30-item Inventory of Depressive Symptomatology, which is available in clinician-rated (IDS30) and self-reported (IDS-SR30) forms, and to further develop and evaluate a shortened version (the Quick IDS), which is available in a 16-item selfreport (QIDS-SR16) and a clinician-rated (QIDS-C16) format. The properties of each of these four instruments as both screens for depression in general medical and psychiatric populations, and as measures of symptomatic change will be evaluated. We will analyze data that have been or that are now being collected from "ongoing" studies. We will also acquire and analyze new data from "prospective" studies to be conducted at Duke and at UT Southwestern. These studies will evaluate the performance of each measure to screen for major and minor depression, defined by a structured interview to render DSM-IV diagnoses - DIS (elderly), by SCID (adults), or by the K-SADS- PL (children/adolescents). We will evaluate concurrent validity with the Montgomery Asberg Depression Rating Scale (MADRS), the 17-item Hamilton Depression Rating Scale (HRSD1T), or Children's Depression Rating Scale (CDRS) as outcome measures in adolescent, adult, and older/elderly populations. Classic psychometric properties (e.g., factor analyses, Cronbach's alpha, and concurrent validity) will be established for each of these four measures (IDS-SR30, IDS-C30, QIDS-SR16, QIDS-C16). We will determine whether an anxiety subscale of the IDS-C3o or IDS-SR30 can be identified and compare the potential items against the Spielberger State Anxiety Inventory. We will create equivalence tables using Item Response Theory analysis to translate total scores on the IDS or QIDS to total scores on the HRSD17, MADRS, and CDRS. We will provide benchmark scores for depressive symptom severity by IDS/QIDS ratings to identify minimal, mild, moderate, and severe levels of impaired daily function, as measured by the Sheehan Disability Scale (DIS), SF-12, SF-36, or Social Adjustment Scale-Self-Report (SAS-SR). The result will be a matched self-report and clinician rating scale to assess only the core criterion symptoms of major depression (i.e., the QIDS-C and SR), and more expanded scales capable of assessing both core and associated symptoms (e.g., anxiety, irritability) (IDS-C and SR) that are in the public domain for use with patients across the age spans seen in practice and in research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DOUBLE-BLIND STUDY OF SAME VS ESCITALOPRAM IN MDD Principal Investigator & Institution: Price, Lawrence H.; Professor of Psychiatry; Butler Hospital (Providence, Ri) 345 Blackstone Blvd Providence, Ri 02906 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2009
Studies
27
Summary: (provided by applicant): Major depressive disorder (MDD) is a common, typically recurrent and disabling disorder, costing the U.S. over $44 billion/year in direct and indirect costs, and with point prevalence rates estimated at 5%-9% for women, and 2%-3% for men. More than one third of patients suffering from MDD appear to use alternative therapies in the U.S. Routinely prescribed in Europe for nearly 30 years and released four years ago in the U.S. as an over-the-counter dietary supplement, s-adenosyl-l-methionine (SAMe) has gained significant popularity as an agent marketed for improving mood and emotional well being. A number of relatively small double-blind studies have shown that parenteral or oral preparations of SAMe, compared with a number of standard tricyclic antidepressants, were generally equally effective, and tended to produce fewer side effects A relatively smaller number of studies have also examined the efficacy of SAMe compared to placebo, with the majority of these studies showing a significant advantage of SAMe over placebo. The recent report of the Southern California Evidence-Based Practice Center for the U.S. Department of Health and Human Services [Agency for Healthcare Research and Quality (AHRQ Publication 2002; http://www.ahrq.gov) ] states that "The results of these studies justify additional randomized clinical trials to evaluate the efficacy and tolerability of SAMe for treatment of depression." No adequately powered placebocontrolled study of SAMe in depression has ever been conducted in the U.S. We therefore propose a five-year, placebo-controlled, two-site study to assess the efficacy and safety of SAMe and of a standard selective serotonin reuptake inhibitor (SSRI), escitalopram in outpatients with MDD. This proposal is a parallel comparison of the efficacy and safety of SAMe, escitalopram, and placebo, with a crossover phase during which non-responders to any of these three treatments receive open-label treatment with the combination of escitalopram and SAMe. It is important to assess the efficacy of this combination therapy because patients frequently self-medicate with SAMe during standard antidepressant treatment. The primary aim of the proposed study is to test the acute antidepressant efficacy and tolerability of both SAMe and escitalopram, each compared to placebo, for the treatment of MDD. Secondary aims are to assess the acute effects of SAMe or escitalopram vs. placebo on remission rates, quality of life, and psychosocial functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: EFFECTS OF DEPRESSION ON SHORT-TERM RECOVERY FROM MI Principal Investigator & Institution: Freedland, Kenneth E.; Professor of Medical Psychology; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2004; Project Start 01-SEP-2004; Project End 31-AUG-2008 Summary: (provided by applicant): After more than a decade of research on the prognostic importance and treatment of depression after acute MI, surprisingly little is known about vulnerability to depressive disorders, the characteristics and short-term course of depression, and whether key cardiovascular risk markers covary with depression during post-MI recovery. The first 6 months after acute MI is the period of highest risk for reinfarction or mortality, yet we know little about the course and effects of depression during this interval. This study will yield a detailed account of depression and its effects during this critical period. The DISH depression interview will be administered to a series of hospitalized patients within 1 week of an acute MI; a blood sample for 5-HTTLPR genotyping will also be drawn at this time. Enrollment in the longitudinal phase will continue until 400 patients have been enrolled (100 with major depression, 100 with minor depression, 100 currently non-depressed but with a history
28
Major Depression
of major depression, 100 never depressed.) The DISH will be administered in person at baseline and at 3-month and 6-month follow-up sessions, and by telephone at interim assessments (weekly through Month 3 and monthly through Month 6). Additional interview modules and questionnaires will be administered at these times to assess depression, anxiety, perceived stress, stressful life events, health behaviors, and perceived social support. At baseline, 3too, and 6mo, blood samples will be drawn for inflammatory and procoagulant markers, and 24 hr ECGs will be obtained for heart rate variability analysis. Planned analyses will identify independent predictors of post-MI depression, differentiate between rapidly remitting vs. persistent cases, and model the relationships among change over time in depression and change in cardiovascular risk markers. The effects of depression on reinfarction and survival will be examined in exploratory analyses. The results will clarify the early course of post-MI depression and the mechanisms linking depression to cardiac events, and they will inform efforts to develop more efficacious treatments. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ELECTROACUPUNCTURE FOR MAJOR DEPRESSION: A PILOT STUDY Principal Investigator & Institution: Mulsant, Benoit H.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2003; Project Start 08-SEP-2003; Project End 31-MAY-2005 Summary: (provided by applicant): Major depression is a common and serious mental illness. It is associated with a markedly lower quality of life, significant functional impairment, and premature death due to suicide or comorbid physical illness. Over the past 50 years, effective and safe treatments for major depression have been developed, including antidepressant pharmacotherapy, psychotherapy, and electroconvulsive therapy. However, many Americans who suffer from a depressive disorder either do not accept to receive one of these conventional treatments or do not complete an adequate course of treatment. A growing number of Americans with depression are choosing to be treated with complementary and alternative therapies. Acupuncture, in particular, is increasingly being used to treat depression even though only limited data support its safety and efficacy. The proposed pilot study builds upon the complementary expertise of a group of investigators of conventional antidepressant treatments and a group of practitioners of alternative medicine. It will use a randomized parallel-group design to compare the safety, efficacy, and tolerability of electroacupuncture (EA) and sham electroacupuncture (SA) for the treatment of major depression. Over a 15-month period, 60 adult outpatients with a major depressive disorder of mild or moderate severity (as defined by the DSM-IV) will be randomized to either 12 sessions of EA or SA to be provided over 6 weeks. Safety and symptomatic improvement (as measured with the Hamilton Rating Scale for Depression) will constitute the primary outcome measures. Tolerability and functional improvement will constitute secondary outcome measures. The data generated by this pilot project will be used to support the feasibility of conducting, and inform the design of, a large multicenter study comparing the efficacy of two forms of acupuncture with a conventional treatment for depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
Studies
•
Project Title: DEPRESSION
ELUCIDATING
THE
NEUROBIOLOGY
OF
29
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 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 •
Project Title: FETAL REACTIVITY AND MATERNAL PSYCHOPATHOLOGY Principal Investigator & Institution: Emory, Eugene K.; Professor; Psychology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2007 Summary: (provided by applicant): This research will study the effects of maternal depression, psychosocial stress, and psychotropic medication on fetal/infant neurobehavioral development. Participants will include pregnant women diagnosed with: major depressive disorder who are prescribed antidepressant medications (i.e., SSRIs) (n = 40); major depressive disorder who are not prescribed SSRIs (n = 40), and a control group of pregnant women without a psychiatric diagnosis (n = 80) who are matched to the depressed groups on race, age, and SES. Actocardiographic technology will assess fetal behavioral and heart rate response to mild vibratory stimulation at 26-28 weeks gestation and again, between 32-34 weeks gestation. At each visit maternal psychiatric/stress symptoms will be measured with the Beck Depression and Anxiety Inventories, the Schedule of Recent Life Events and the Perceived Stress Scale. Maternal coping skills will be measured with the Coping Responses Inventory. Maternal urine samples will be assayed for prescribed medication and/or illicit drugs. Maternal saliva will be assayed for cortisol. Medical ultrasound records will be examined for physical length, head circumference and presence of abnormalities. During labour, fetal heart
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Major Depression
rate will be monitored and umbilical cord blood will be assayed for cortisol. On the first postnatal day, a behavioral observation will be obtained from neonates, they will be administered the BNBAS, salivary cortisol samples will be gathered and obstetrical/postnatal complications documented. In addition, another psychometric assessment will be made of each mother and saliva and urine samples obtained. A onemonth follow-up will consist of another behavioral observation of the infant, readministration of the BNBAS, obtaining mother/infant salivary cortisol samples, as well as a final maternal psychometric assessment and urine sample. Parametric statistical analyses and regression modeling will examine the relationships between maternal psychiatric symptoms, antidepressant medication, psychosocial stress and maternal coping, fetal and postpartum behavior and maternal/fetal/infant cortisol. It is predicted that fetal/infant physiological, behavioral, and hormonal patterns will vary with maternal diagnosis, degree of psychosocial stress and maternal coping strategy, and medication status and that with the amelioration of depressive symptoms via SSRIs, fetal/infant developmental profiles among the depressed women will more closely approximate those of the non-depressed control group. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GROUP TREATMENT FOR DEPRESSION IN HEART FAILURE Principal Investigator & Institution: Friedman, Michael A.; Psychology; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2003; Project Start 14-FEB-2003; Project End 31-JAN-2006 Summary: (provided by applicant): The overall aim of this research is to develop an efficacious group psychotherapy for the treatment of major depression among individuals with congestive heart failure. Both major depression and heart failure are associated with severe loss of functioning and increased mortality, and this co-morbid condition is particularly debilitating. While treating depression among heart failure patients has the potential to improve functioning and prolong life in this population, there are currently no empirically-supported treatments for depression among heart failure patients. Among the several well-validated psychosocial treatments, group cognitive-behavioral therapy (CBT) has been proposed as efficacious, and has established feasibility among heart failure patients. Group CBT may be particularly efficacious among CHF patients with depression due to the potential for increasing patient social support. Initial research suggests that there are several ways in which current group CBT could be improved to treat major depression among CHF patients, including: (1) the use of an "open" group format that allows for immediate patient care, (2) integration of individual interventions to individually tailor treatment goals and improve adherence to treatment, and (3) family-based interventions within the group CBT format to mobilize patient social support. The proposed integrated cognitivebehavioral therapy program includes group, individual, and family treatment (GIFT) for depression among individuals with CHF (GIFT-CHF). The current proposal is designed to develop the GIFT-CHF program. The proposal consists of three phases: a Development, Pilot, and Revision Phase. During the Development phase of the GIFTCHF, the goal of the research will be to: (a) develop an integrative group therapy program for depressed patients with heart failure (GIFT-CHF); (b) develop a therapist training program; and (c) develop and test the reliability and validity of competence and adherence rating scales. During the Pilot phase of the GIFT-CHF program, the goal will be to conduct a small pilot trial investigating the short-term efficacy of the GIFT-CHF program in comparison to a Standard Medical Care/Wait-List control group, and determine effect size. Finally, during the Revision phase of the GIFT-CHF program, the
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goal of the research will be based on the results of the Development and Pilot phases, to revise the GIFT-CHF program and treatment manual. This treatment development grant will lay the groundwork for a large-scale treatment outcome study of the GIFT-CHF program for depressed individuals with congestive heart failure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HIV IN WOMEN: DEPRESSION AND IMMUNITY Principal Investigator & Institution: Evans, Dwight L.; Professor and Chair; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2003; Project Start 25-JUL-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Psychiatric morbidity has been associated with HIV disease since the beginning of the AIDS epidemic. Most of the clinical literature to date has focused on psychiatric issues in men who are HIV seropositive. There has been little data regarding the prevalence of psychiatric disorders in HIV infected women, despite the fact that HIV remains among the leading causes of death for US women between the ages of 25 and 44. HIV also is the leading cause of death among African American women in this age group. We found that the proportion of women with current major depression was four times higher in HIV positive women compared to HIV seronegative women. This high rate of major depression coupled with the recent and largest epidemiology study to date indicating that depression is associated with increased mortality in HIV-infected women, underscores the need for studies to ascertain the relationship of major depression, immunity, and HIV disease progression in HIV infected women. The potential immune mechanisms by which depression may influence HIV disease progression and mortality remain to be understood. In our studies of HIV infected men, we have found depression associated alterations of immune cytotoxic cells suggesting that killer lymphocytes might mediate the effects of depression on HIV disease progression. Although previous studies have focused almost exclusively on HIV infected men, we have recently found that women with depression exhibit significant reductions in natural killer cell activity as well as increases in activated CD8 lymphocytes and viral load. The proposed study of HIV seropositive women, largely of minority representation, is designed to provide important information on 1) the underlying immune mechanisms by which depression my influence HIV-1 replication and thereby HIV disease progression; and 2) three potential mechanisms of action whereby depression my influence immunity and HIV disease progression. The present study may also help determine whether conventional antidepressants (SSRIs) as well as novel antidepressant pharmacotherapies (substance P antagonists and glucocorticoid antagonists) might benefit HIV-infected individuals and extend survival with HIV infection. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HMO COLLABORATIVE CARE TREATMENT FOR DEPRESSED YOUTH Principal Investigator & Institution: Clarke, Gregory N.; Senior Investigator; Kaiser Foundation Research Institute 1800 Harrison St, 16Th Fl Oakland, Ca 946123433 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: This randomized, controlled effectiveness trial will test the effectiveness of a short-term, collaborative care model of cognitive- behavioral therapy for depression (CC-CBT) as an adjunct to anti- depressant medication treatment of adolescent major depression in primary care (principally pediatricians). The CC-CBT model, which is
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Major Depression
based on the co-management of a patient's treatment by a mental health specialist. and a primary care physician, has been developed and positively evaluated by coinvestigators Von Korff, Lin, Ludman and Bush in a sample of depressed adults. In the first quarter of the initial study year we will pilot and revise the CC-CBT therapy manual for use with adolescents and families, prior to the randomized, controlled trial (RCT) in study years 01 to 03, with final follow-up completed halfway through Year 04. The RCT will be conducted in four major primary care clinics in the Northwest Division of the Kaiser Permanente (KP) health maintenance organization (HMO), with an overall membership of approximately 420,000, of whom approximately 47,590 (11.3%) are adolescents aged 12 to 18 (inclusive). We will enroll 150 consenting adolescents in this age range receiving incident (first time) pharmacotherapy for major depression from a KP primary care provider. Subjects will be randomly assigned to either (a) usual care depression pharmacotherapy as typically delivered by HMO providers; or (b) usual care pharmacotherapy plus six to eight individual sessions of CC-CBT delivered in a consult fashion by a trained mental health therapist (not the HMO pharmacotherapy provider). CC-CBT sessions are scheduled to occur in association with regular medication check visits, whenever possible. We anticipate that CC-CBT subjects will exhibit higher initial depression recovery rates, greater medication regime adherence, greater satisfaction with services, better social and academic functioning, lower subsequent depression relapse/remission. We predict that while initial HMO health care utilization and costs will be higher for the CC-CBT intervention will be more cost effective (e.g., units of improvement per unit of cost) compared to usual care. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEPRESSION
HORMONE
RHYTHMS:
METABOLIC
SIGNIFICANCE
IN
Principal Investigator & Institution: Rubin, Robert T.; Professor; Allegheny-Singer Research Institute 320 E North Ave Pittsburgh, Pa 15212 Timing: Fiscal Year 2002; Project Start 01-DEC-1985; Project End 31-JUL-2006 Summary: (adapted from applicant's abstract) This renewal application, for years 23-27, is to continue studies of the neuroendocrinology of major depression. The studies planned herein build upon more than 20 years of systematic exploration of the HPA axis in major depression, supported by this grant. In previous years, we conducted several large studies of patients with major depression vs normal controls, the results of which have led to our current focus on the hypothalamo-pituitary-adrenal cortical (HPA) axis. This axis is mildly to moderately hyperactive in 30-50 percent of depressed patients, most likely on the basis of increased corticotropin releasing hormone (CRH) and arginine vasopressin (AVP) secretion from the hypothalamus. Our most recent studies have revealed an unexpected and very interesting finding, the HPA axis responds differently to cholinergic challenge not only in depressed patients vs normal controls but also in women vsmen. Our extension of this to the study of laboratory rats has revealed similar findings between female and male animals. This is an emerging area of CNS neuropharmacology, with only a few prior studies that have considered neuroendocrine responses, other than the hypothalamo-pituitary-gonadal axis, by sex. Specific aims include: 1) Continued analysis of data from earlier studies. 2) Continued detailed study of sex differences in cholinergic regulation of the HPA axis in patients with major depression vs normal controls, in depressed patients during illness vsafter successful treatment, and in women us men. This specific aim forms the major thrust of this renewal application. 3) Completion of HPA axis studies at the adrenal and pituitary levels. 4) Continuation of animal studies of sexual diergism of cholinergic regulation of
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the HPA axis in female and male rats. The human studies will be used to inform planning of the studies in laboratory animals, and vice versa. The significance of the planned studies lies in their furthering our understanding of HPA axis regulation by CNS cholinergic mechanisms in major depression, as well as what we hypothesize to be adaptive changes to increased CNS stimulation of the axis at the pituitary and adrenal levels. In particular, understanding sex differences in cholinergic regulation of the HPA axis may help elucidate biological mechanisms underlying the greater incidence of major depression in women vsmen. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMPACT OF DEPRESSION & FUNCTION ON HEALTHCARE USE & COST Principal Investigator & Institution: Friedman, Bruce; Community and Prev Medicine; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 01-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): The purpose of this Mentored Research Scientist Career Development Award (KO1) is to become an independent researcher prepared to make a unique and significant contribution to our understanding of the impact of depression and functional impairment on health services use and expenditures among older adults (age 65+). Three themes characterize my background: (a) work-related positions with an exclusive or major focus on the aged; (b) exposure to and involvement with late life mental health; and (c) expertise in crosssectional analysis of healthcare use and expenditures. My past scientific history has focused on innovative intervention studies of elderly patients. I will receive the needed training and conduct mentored research at the University of Rochester, with additional study at the University of Michigan and training and mentored research at Cornell University. Presently little is known about the impact of depression and functional impairment on healthcare use and expenditures among most categories of elderly patients (e.g., primary care patients, home care patients, and community-dwelling high users of medical care). The Training Objectives of my Research Career Development Plan are to: (1) Improve my knowledge base in relation to affective illness, cognitive dysfunction, and chronic illness comorbidity and disability in elderly persons; (2) Increase my knowledge of mental health oriented community-based interventions and public health models; (3) Add to my knowledge and skills in longitudinal data analysis; (4) Become more familiar with the requirements for responsible conduct of research involving human subjects; and (5) Plan, organize, and carrying out a systematic research program adding knowledge of geriatric mental health and function to my expertise and skills in Health Services Research and community-based geriatric interventions. The Specific Aims of the Research Plan are: (Aim 1) To better understand the impact of major and subsyndronml depression on certain specific types of healthcare use and expenditures; (Aim 2) To better understand the effect of functional impairment (deficits in activities of daily living, instrumental activities of daily living, and ambulation/-mobility) on certain specific types of healthcare use and expenditures; and (Aim 3) To study the role of depression as a mediator between functional impairment and use/expenditures, and functional impairment as a mediator between depression and use/expenditures. The Analytic Plan consists of (a) bivariate associations, (b) regression analyses, (c) an examination of direct and indirect effects, and (d) longitudinal analyses applied to data from 3 studies: (1) the Medicare Primary and Consumer-Directed Care Demonstration (2) the Depression Outcome in Primary Care Elderly study, and (3) the Depression in Elderly Medical Homecare Patients study. Given the expected continuing rise in
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Major Depression
healthcare costs and the high prevalence of depression and functional impairment among the chronically ill aged, understanding the impact of depression and functional impairment on healthcare use and expenditures is of particular public health importance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INTEGRATED CARE FOR DEPRESSION AND CHRONIC BACK PAIN Principal Investigator & Institution: Von Korff, Michael R.; Senior Investigator; Center for Health Studies Seattle, Wa 98101 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-JUL-2006 Summary: (provided by applicant): Research Goal: Our long-term goal is to improve the functional, symptom and cost of care outcomes among patients with co-morbid depression and chronic pain. This proposal seeks support for a pilot study of an integrated intervention for depression and chronic back pain. The proposed pilot study will accomplish the following specific aims: Aim 1: Develop an integrated intervention for chronic back pain patients with major depression. This research will develop an integrated, biopsychosocial intervention for chronic back pain patients with major depression. The integrated intervention incorporates proven interventions for major depression (Problem-Solving Therapy and/or antidepressant medications depending on patient preferences) with brief cognitive-behavioral interventions for chronic back pain, also of proven effectiveness. Aim 2: Develop methods for inducing and assessing intervention fidelity. We will assess the delivery, receipt and enactment of the integrated intervention with multiple methods (provider ratings, patient ratings, patient logs, and independent ratings of audiotapes). We will assess the inter-rater reliability of independent ratings of audiotapes, the convergent validity of fidelity measures obtained from different sources, and the correlation of different components of intervention fidelity. Aim 3: Conduct a pilot test of the integrated intervention for depressed chronic back pain patients. We will conduct a pilot test of the integrated intervention with 50 intervention and 50 care as usual control patients. The pilot RCT will assess screening completion and eligibility rates; participation in the integrated intervention among patients randomly assigned to the intervention arm; the fidelity of provider delivery and patient receipt of the intervention; levels of patient enactment of the intervention as assessed by measures of patient adherence with pharmacologic and behavioral treatments; acceptability of the integrated intervention to participating primary care physicians; and intervention effect size at 6 months for pain, depression and functional outcomes. We will assess the incremental benefit of integrated management of depression and chronic back pain relative to brief cognitive-behavioral intervention for back pain alone (through comparison of intervention patients to historical controls receiving only a cognitive-behavioral intervention for chronic back pain). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION
INTERVENTION
TO
PREVENT
POST-STROKE
MAJOR
Principal Investigator & Institution: Whyte, Ellen M.; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2004; Project Start 01-JAN-2004; Project End 31-DEC-2008 Summary: (provided by candidate): This is a resubmission of an application for a Mentored Patient-Oriented Research Career Development Award (K23). The candidate
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is a geriatric psychiatrist and post-doctoral research fellow at the University of Pittsburgh. She proposes to become an expert in clinical mental-health prevention research. This proposal focuses on post-stroke major depression (PSMD) as this illness is a model of geriatric depression and is an illness ready for preventive intervention research. To develop the skills needed to conduct clinical mental-health prevention research, the candidate will learn from the related fields of epidemiology, public health prevention research, and traditional mental-health pharmacologic intervention research. She will gain the skills needed (1) to design and conduct prevention studies, and (2) to select at-risk populations that would benefit from preventive interventions through the identification and modeling of risk factors. In addition, the candidate will develop the skills needed to assess psychiatric and functional outcomes in subjects with neurological illness. The candidate will also learn about biostatistical analysis pertinent to prevention trials and the ethical issues involved in clinical research. Funding of this award will provide time and resources necessary for the candidate to develop into an independent investigator capable of conducting psychiatric prevention and intervention trials in impaired elderly depressed patients. Studies of stroke survivors indicate that Major Depression is common after stroke and is associated with poorer rehabilitation outcomes, increased disability, and increased mortality. While the response rate in treatment trials of PSMD is typically 65%, it is unclear whether successful treatment of PSMD translates into improved rehabilitation outcomes. Therefore, preventing the onset of PSMD may be a more beneficial approach in terms of both mental and physical health. The proposed research is a pilot double-blind placebo controlled trial of citalopram in the prevention of PSMD in stroke survivors at high-risk for developing PSMD. The proposed activities will take place at the University of Pittsburgh under the auspices of the NIMH-funded Intervention Research Center for Late Life Mood Disorders, directed by the candidate's sponsor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IS INSOMNIA A MODIFIABLE RISK FACTOR FOR MDD? Principal Investigator & Institution: Perlis, Michael L.; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2007 Summary: (provided by applicant): Recent studies have shown that insomnia may represent a vulnerability factor for Major Depression (MDD). These findings suggest that if remitted patients with recurrent MDD received treatment for their insomnia, this intervention might prevent or delay relapse/recurrence, or at least diminish the intensity of subsequent episodes. We propose to evaluate this hypothesis by undertaking a preliminary study on the effects of Behavioral treatment for insomnia on the clinical course of patients with remitted recurrent MDD. Specifically, we propose to randomly assign 45 patients with remitted recurrent Major Depression to one of two conditions behavioral treatment for insomnia (n=30) or to a contract control monitor only group (n=15) behavior therapy was selected because this treatment modality has demonstrated efficacy with respect to insomnia yet is not likely to have direct antidepressant effects. Sleep and depression symptoms will be monitored on a weekly basis prior to treatment initiation (3-4 weeks), during active treatment (8 weeks), and for a period of up to 33 months. Monitoring will require that subjects complete daily sleep diaries, weekly Beck Depression Inventories (BDI), and monthly clinical interviews. The BDI will be used to ascertain when subjects exhibit a worsening of their depressive symptoms and will serve as a prompt for a clinical evaluation to determine whether there has been a relapse/recurrence. Weekly diaries will be used to determine 1) the
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Major Depression
acute effects of the insomnia treatment, 2) the long term efficacy of the behavioral intervention, and 3) the extent to which sleep related complaints are prodromal to new onset episodes. Monthly interviews will be used to monitor and confirm clinical state. In addition, polysomnographic (PSG) data will be acquired prior to and following treatment. These data will be used to rule out occult sleep disorders (e.g., sleep apnea and PLMs), to objectively assess severity of insomnia symptoms prior to and following treatment, and to explore, in a preliminary way, the extent to which sleep architecture variables (e.g. reduced REM latency) independently predict treatment outcome, clinical course, and/or how these measures interact with self report sleep continuity measures. It is hypothesized that behavioral treatment for insomnia in patients with remitted MDD will be associated with less depressive symptomatology during remission, longer periods of remission, less severe new onset episodes and better responses to treatment for recurrent episodes Data for each of these hypotheses will be used to calculate effect sizes and to conduct power estimates. These analyses, if they provide good feasibility data, will be used as the foundation for a R01 level application. Ultimately, If one or more of these hypotheses are borne out in the larger follow up study, this will strongly suggest that 1) CBT for insomnia may be an important strategy for the management of recurrent MDD, and 2) insomnia is not only a symptom of MDD, but also a factor in the development of the disease. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LATE LIFE DEPRESSION OUTCOME & MEDICAL ILLNESS SEVERITY Principal Investigator & Institution: Lyness, Jeffrey M.; Associate Professor; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 10-FEB-2001; Project End 31-JAN-2006 Summary: The public health significance of later life depressive conditions in primary care settings is well recognized. In particular, the cross-sectional morbidity of depressive symptoms not meeting diagnostic criteria for major depression is greater than that of major depression alone. However, it is not known whether such conditions persist, lead to more severe depressive conditions, or have other long term morbidity. Accordingly, this revised R01 application proposes to test the hypothesis that patients with operationally defined minor/subsyndromal depression will have an intermediate 3-4 year outcome (as compared to non-depressed controls and to patients with major depression) in the following domains: depressive symptoms and diagnoses, medical illness severity, mortality, functional status, and health care utilization and costs. Also, the investigation will test hypotheses regarding the associations of specific theoretically based variables with the above outcomes. The predictors range across the biopsychosocial spectrum, including cerebrovascular risk factors, overall medical burden, functional status, the Five Factor Model of personality traits, social support, religiousness, and life events. The Study investigators Will recruit and follow 1000 subjects, age >= 65 years, from a variety of primary care sites serving the Monroe County, NY population. Study assessments will be derived from medical chart reviews and HCFA data as well as semi-structured patient interviews using validated measures such as the Structured Clinical Interview for DSM-IV and the Longitudinal Interval Follow-up Evaluation. Analysis of covariance will be used to examine group differences in outcomes. Multiple regression techniques will be used to determine the independent association of hypothesized predictors with outcomes. The results will directly inform future research, including identifying subjects for interventions as well as identifying theoretical models of depression pathogenesis that merit more definitive testing.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: LIFE STRESS AND COGNITIVE BIASES IN MAJOR DEPRESSION. Principal Investigator & Institution: Monroe, Scott M.; Professor; Psychology; University of Oregon Eugene, or 97403 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2005 Summary: Depressed individuals have been found consistently to report a higher incidence of recent severe stress than nondepressed people. Further, compared with patients without a recent severe life event, depressed patients with severe stress may have more severe symptoms, a different clinical course, and different rates of remission. Collectively, these findings suggest that the presence of recent severe stress represents a marker of potentially important individual differences in depression. Because not all people who encounter severe stress develop depression, however, information on other risk factors is required to understand individual differences in vulnerability to depression in the face of life stress. The construct of cognitive biases has been prominent in major theories of depression, and has been postulated to be important in relation to life stress and depression. Despite the obvious relevance of research that integrates information across social (life stress) and psychological (cognitive) domains, such inquiry has proven difficult to undertake. The methodological intricacies within each domain present a number of practical and logistic obstacles. Moreover, there are conceptual difficulties that have hindered this integration. Longitudinal empirical work, guided by theoretical insights and based on state-of-the-art methods from each domain, is required to advance understanding of multifactorial, integrative research. The primary goal of the present project is to investigate life stress and cognitive information processing biases for depression within the conceptual scheme afforded by diathesisstress theory. The present research has three specific aims. First, we test the relationship between life stress and cognitive bias within a well-differentiated conceptual scheme afforded by diathesis-stress theory and informed by attention to the issue of etiologic heterogeneity of depression; state-of-the-art methods will be used to assess life stress and cognitive vulnerability. Second, we test the predictive utility of stress, cognitive bias, and their interaction for clinical features and treatment course of depression. Third, we test differential activation of cognitive biases in remitted depressives as a function of preonset life stress with a laboratory mood priming paradigm to address questions of cognitive vulnerability. Secondary aims include testing: (1) other forms of life stress in relation to cognitive vulnerability; (2) life stress measurement issues; and (3) associations between stress-cognition interactions and other clinically relevant (e.g., attrition, treatment-seeking, post-recovery course) phenomena. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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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
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Major Depression
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 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 •
Project Title: MAJOR DEPRESSION FOLLOWING MINOR INJURY Principal Investigator & Institution: Richmond, Therese S.; None; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-APR-2002; Project End 31-MAR-2007 Summary: (provided by applicant): The cost of injury is considerable, estimated at $260 billion for fiscal year 1995. The primary costs are morbidity costs -- the value of goods and services not produced because of injury. Preliminary findings indicate that psychological distress is a significant predictor of post-injury disability and that symptoms of depression often accompany injury, appearing out of proportion to the severity of physical injury. The purpose of this study is to follow up on these findings, and in particular, to examine the public health impact of the development of major depression following minor injury. The majority of all injuries are minor, defined as injuries of sufficient import that individuals seek urgent medical care in an emergency department, but which do not threaten loss of life or limb. The primary aims of this study are to: determine the frequency of major depression (& related mood disorders) following minor physical injury; and determine the extent to which developing major depression (& related mood disorders) contribute to increased disability and reduced quality of life following minor physical injury. The secondary aims are to: compare the effect of developing depression and related psychiatric disorders (anxiety & stress-
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related disorders) on outcomes following minor physical injury; and describe the onset and course of developing depression and related psychiatric disorders in the year following minor physical injury. 250 patients presenting to the emergency department at the Hospital of the University of Pennsylvania with minor injury will be enrolled. Minor injury will be defined by the Injury Severity Score for anatomic severity and the triageRevised Trauma Score for physiologic severity. Intake information includes injury data, pre-injury disability and quality of life. A comprehensive, structured psychiatric diagnostic evaluation will be conducted 72 hours after the minor injury has occurred, documenting psychiatric baseline (excluding patients with existing depression at time of injury or major DSM IV Axis I psychotic disorders). Participants will be followed by systematic, longitudinal follow-up evaluations (3, 6, & 12 months) to determine the development of major depression and its effect on post-injury disability and quality of life. The quasi-experimental design, in which each participant serves as his/her own control, will enable an accurate and comprehensive profile of developing major depression (and related mood disorders) following minor injury. Further, this design, using comprehensive psychiatric evaluation, will allow a critical analysis of the influence of major depression and related psychiatric disorders on outcomes following minor injury. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MAJOR MENTAL DISORDERS AND HIV--HEALTH SERVICES USE Principal Investigator & Institution: Crystal, Stephen; Research Professor; None; Rutgers the St Univ of Nj New Brunswick Asb Iii New Brunswick, Nj 08901 Timing: Fiscal Year 2002; Project Start 20-AUG-2000; Project End 31-JUL-2005 Summary: This study will investigate the provision of health care services to a statewide population of HIV-positive Medicaid participants whose service needs are complicated by major psychiatric comorbidities, particularly schizophrenia and schizoaffective disorder. The overall objective is to generate much-needed knowledge about care of these persons so that policies and programs, which have largely been developed on the basis of findings from inpatient samples, can better address their complex needs. The research will use a unique database created by merging multiple New Jersey Medicaid administrative and claims records with HIV/AIDS Registry data, covering the years 1988-1999 for 8,996 individuals, including (according to preliminary classifications) 577 who received at least one inpatient or two outpatient diagnoses with schizophrenia or schizoaffective disorder, with a mean of 55 encounters with schizophrenia diagnoses. We will also examine, as a secondary focus, individuals diagnosed with mood disorders including bipolar disorder and recurrent major depressive disorder, and will explore the association between combinations of psychiatric and substance abuse comorbidities and use of health care services. The study will examine the types and combinations of psychiatric diagnoses reported by health care providers during health care encounters with HIV+ persons on Medicaid; refine claims-based diagnostic classifications; explore the impact of psychiatric conditions on the types and amounts of health care services used over the course of HIV; analyze receipt of mental health services and the type and consistency over time of psychotropic use; and examine the relationship between comorbid major mental disorders, with and without comorbid substance abuse, and patterns of antiretroviral therapy including type of regimen, incidence of use, consistency of use over time, and dropout from treatment. Results of these analyses will provide an important information base for the development of policies and programs to improve the care of this under-studied group within the population living with HIV. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Major Depression
Project Title: MAMAS Y BEBES: PREVENTION INTERVENTION DEVELOPMENT Principal Investigator & Institution: Munoz, Ricardo F.; Langley Porter Psychiatric Institute; University of California San Francisco 3333 California Street, Suite 315 San Francisco, Ca 941430962 Timing: Fiscal Year 2002; Project Start 01-MAY-2000; Project End 31-MAR-2004 Summary: (adapted from investigator's abstract): The University of California, San Francisco/San Francisco General Hospital Latino Mental Health Research Program is launching research efforts to reduce the number of new cases of major depression in high-risk, low-income, Spanish-and English-speaking pregnant women. The program, called Mamas y Bebes (Mothers and Babies/Mood and Health Project) is intended to benefit the mother-to-be and the infant by sparing them the pain and dysfunction associated with major depression, and reducing the sequelae of being raised by a clinically depressed mother. The long-term goal is to carry out a randomized controlled trial to test this preventive intervention. This proposal is to develop the trial protocol in Spanish and English for use with young (18-to 25-year old) pregnant women. The Depression Prevention Course, a group cognitive-behavioral intervention, will be adapted to address the experiences most salient during pregnancy, birth, and the first year of motherhood. The Course teaches participants methods to regulate their emotions to prevent full-blown major depressive episodes (MDE). Obstetrics patients will be screened for MDE. Those who meet criteria for MDE or other major psychiatric disorders will be referred for treatment and screened out of the study. Those who do not meet criteria for major psychiatric disorders but are at high risk for MDE will be offered entry into this part of the study. The study will evaluate recruitment and retention methods into the study, training technology, protocol adherence and instructor proficiency measures, and carry out three cycles of implementation and revision of the protocols. Effect sizes on changes in depressive symptoms and their cognitive and behavioral mediators will be obtained for power calculations for the randomized trials. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MEASUREMENT OF MAJOR STRESSFUL EVENTS OVER LIFE COURSES Principal Investigator & Institution: Dohrenwend, Bruce P.; Professor; Epidemiology; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 05-FEB-2001; Project End 31-JAN-2006 Summary: (Applicant's abstract): Powerful research designs for studying the roles of heredity and environment in the etiology of psychiatric disorders have outstripped our ability to measure the relevant variables. Major stressful life events as important environmental variables are a case in point. There are problems of conceptualization and measurement with even the best of the self-report checklist approaches and with the more labor- intensive interview and rating approaches. The proposed research will address these problems, taking a major step toward the long-term goal of obtaining reliable and valid measures of the important objective general and specific characteristics of major, stressful life events over the life course. The general characteristics and dimensions to be investigated include valence, fatefulness, predictability, centrality, magnitude, and potential to exhaust the individual physically. Examples of specific facets of particular events are atrocities in military combat, loss of younger versus older spouses in bereavement, and victimization by acquaintances versus strangers in rape. The specific aims are: (1) To review the Literature on case studies of important types major individual events in order to locate and define their
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specific dimensions in the context of their general objective dimensions; (2) to investigate how types of events, specific dimensions of events, and measures of some of their general dimensions vary with developmental stage, gender, ethnic/racial background, and socioeconomic background (SES); (3) to apply the event-specific ratings developed in I and 2 and the ratings of general dimensions to narratives of major events extracted from five completed case/control studies of the onset or adverse course of schizophrenia, major depression, antisocial personality, substance use disorders including alcoholism, and post-traumatic stress disorder (PTSD); (4) to investigate the extent to which the inclusion of measures of these group-specific and event-specific dimensions require expanded questioning and probing procedures to obtain the relevant narrative information; (5) to test the extent to which the ratings of event-specific dimensions increase the explanatory power of major negative events as risk factors in the five case/control studies; (6) to develop procedures for making these labor-intensive measures more economical by screening for major events to be intensively probed and rated; (7) to develop a manual for mapping major events over the life course; and (8) to develop plans for future research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR NEUROBIOLOGY OF DEPRESSION Principal Investigator & Institution: Shelton, Richard C.; Psychiatry; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: This is a request for five years of salary support via the Midcareer Investigator Award in Patient-Oriented Research (K24). Throughout my career I have sought to bridge basic neurobiological and clinical domains, with special emphasis on mood disorders. By the early 1990's, I began to redirect my energies toward the development of a series of studies using newer molecular biological methods to investigate the causes and possible treatments for depression. Using a fibroblast cell culture model, my collaborators and I have discovered that melancholic major depressives have a reduction of cyclic AMP binding to the regulatory subunit of protein kinase A (PKA) linked to beta adrenoceptors. This results in a concomitant reduction in phosphorylation activity (including that of CREB) and altered gene expression. We also have shown an altered expression of a specific nuclear phosphatase gene using the differential display reverse transcription polymerase chain reaction methodology with cPCR. Herein, I have outlined these findings along with plans for related projects over the next five years. I also have described briefly two other project areas that stand in the mid-ground between basic and clinical investigations. One is an investigation of mood regulation using new clinical ratings instruments (developed, in part by our research group) to measure components of mood under conditions of pharmacological manipulation. The second represents a novel therapeutic intervention in refractory major depression. Drawing from a set of basic laboratory observations, I have conducted a successful trial of the combination of olanzapine and fluoxetine in refractory depressives. Together, these study areas demonstrate my capacity to bridge from basic laboratory findings, on the one hand, to clinical phenomenology and treatment, on the other. Finally, consistent with the goals of the K24, I have a long trackrecord of mentorship of new investigators from a number of disciplines. However, an increasing burden of administrative and clinical responsibilities threatens my research productivity and mentorship. This award will relieve me of many of these demands and will allow me to: 1.Develop further expertise in basic molecular biological methods; 2.
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Develop new projects oriented to future funding opportunities; and 3. Continue to mentor the next generation of investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOOD AND ANXIETY DISORDERS IN PREGNANCY AND LACTATION Principal Investigator & Institution: Stowe, Zachary N.; Associate Professor and Director; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-AUG-2007 Summary: The treatment of mental illness during pregnancy has gained considerable attention over the past decade. The majority of this attention has focused on antidepressants and major depression, with far less consideration of anxiety disorders and bipolar disorder. The treatment guidelines for mental illness during pregnancy and lactation remain empiric and continue to emphasize the risk/benefit assessment. The lack of data on the course of illness, the impact of pregnancy and lactation of the metabolism and distribution of pharmacological treatments, and the extent of fetal and neonatal medication exposure underscores the empiric nature and prematurity of such guidelines. The current project will enhance and extend the data derived from an ongoing collaborative R01 MH56555-01A2 (Stowe) focused on the relapse of major depression in pregnant women taking antidepressant proximate to conception and K23 MH 63507-01 (Newport) investigating psychosis during pregnancy. We will prospectively follow women with major depression (MID), bipolar disorder (BPD), panic disorder (PD), and obsessive-compulsive disorder (OCD) through pregnancy and the first postpartum year. Many of these women may chose to continue medications such as antidepressants, mood stabilizers, and antipsychotic medications either during pregnancy and/or take medications postpartum. Monthly serum sampling and GCRC admissions will provide novel data.regarding the metabolism, distribution, and fetal/neonatal exposure to these compounds. These PK/PD models will be expanded to include assessment of pharmacogenetic factors of metabolic capacity and protein binding. Similarly, prospective documentation of additional exposures, sex steroid concentrations, and psychosocial variables will further refine such models and provide preliminary assessment of factors (other than medication concentrations) that may influence the course of illness and obstetrical outcome. The current project will utilize the core components to address the deficits in the current literature, affords a diagnostically diverse group of women that may be germane to the results obtained in Project 2 with respect to co-morbidity and the use of similar medications in a nonepileptic population. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOOD MANAGEMENT TRAINING FOR ALCOHOL DEPENDENT SMOKERS Principal Investigator & Institution: Patten, Christi A.; Associate Professor of Psychology; Mayo Clinic Coll of Medicine, Rochester 200 1St St Sw Rochester, Mn 55905 Timing: Fiscal Year 2002; Project Start 01-FEB-1999; Project End 31-JAN-2004 Summary: This application will serve as the foundation on which the PI will build a major line of research dedicated to the area of alcohol and nicotine dependence treatment. Alcohol dependent smokers are at high risk for tobacco-related morbidity and mortality. Effective interventions are needed to reduce smoking prevalence in this population. Among smokers, a history of major depression has been identified as a
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major obstacle to smoking cessation. Individuals with a history of alcohol dependence and major depression may represent a population of especially treatment- resistant smokers. This new investigator proposal builds on our previous work and focuses on treatment of smokers with a history of both alcohol dependence and major depression. The theoretical framework on which this program of research is based is the social learning cognitive-behavioral model of relapse which emphasizes the role of situational variables and coping responses in addiction relapse. Our preliminary work suggests that a mood management intervention, designed to enhance coping with negative affect, may improve smoking outcomes for smokers with a history of alcohol dependence and depression. The first primary aim of this study is to evaluate the efficacy of a mood management intervention on 12-month smoking outcomes for 144 adult, abstinent alcoholic smokers with a history of major depression. A further aim is to examine mechanisms and processes of change associated with smoking treatment outcomes. The second primary aim is to examine the effect of the smoking treatments on alcohol abstinence and to identify factors associated with smoking and alcohol outcomes. The ultimate goal of this work is to develop effective interventions which will reduce tobacco-related morbidity and mortality in this high-risk population without adversely affecting alcohol outcomes. A randomized, two-group design will be used to evaluate the added benefit of a mood management intervention compared to a state-of-the-art smoking cessation treatment. The two conditions are: 1) Transdermal Nicotine Therapy and Behavioral Counseling (BC) and 2)BC plus Cognitive-Behavioral Mood Management Training (MM). Treatment will consist of 8 weekly group sessions. The major assessments will occur at end-of-treatment (week 8), and 1,3,6,and 12-month follow-up. Dependent measures include 7-day point prevalence smoking abstinence verified with expired air carbon monoxide and alcohol and drug abstinence verified with breathalyzer, urine drug screen and informant report. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MORPHOLOGIC/NEUROCHEMICAL DEPRESSION IN AD
CORRELATES
OF
Principal Investigator & Institution: Zubenko, George S.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-JUL-2004 Summary: (applicant's abstract): Emerging clinicopathological studies of major depression in Alzheimer's disease (AD+D) suggest that the development of this behavioral complication of AD is associated with degeneration of the brainstem aminergic nuclei and the relative preservation of the cholinergic bnM. The neuropathologic and related neurochemical correlates of AD+D appear to be relatively specific for this condition, and may explain aspects of the course and treatment responsiveness of major depression in this context. Family histories of major depression may also be more common for AD+D patients, suggesting an interaction between a preexisting familial vulnerability and key neurodegenerative events in the pathogenesis of AD+D. The Lewy body variant (ADLBV) has been reported to be accompanied by more aggressive degeneration of the brainstem aminergic nuclei and a higher prevalence of major depression than AD alone. If confirmed, the latter observations would strengthen the relationship of degeneration of the brainstem aminergic nuclei to the development of AD+D. We propose to continue our clinicopathologic studies of these relationships and to evaluate their generalizability using autopsy-confirmed AD/ADLBV cases and controls who were prospectively characterized by a consortium of four NIA-funded ADCs/ADRCs. Moreover. we will
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test the hypothesis that the severity/ chronicity of major depression in AD is correlated with the extent of degeneration of the brainstem aminergic nuclei. To assess the specificity of these findings for depression, we will also explore the morphologic and neurochemical correlates of psychosis and other behavioral abnormalities in AD. In addition to family history studies we will determine whether the emergence of AD+D is influenced by the APOE genotype of AD patients. We will also continue our investigation of the role of apoptosis in neuronal loss from the brainstem aminergic nuclei in AD. Our data suggest that AD+D patients have increased susceptibility to neuronal loss in the LC (and possibly the DR and SN) due to increased vulnerability of these cells to apoptosis. We hypothesize that this enhanced vulnerability to apoptotic cell death results from a reduction in cellular protective mechanisms as reflected by a reduced proportion of neurons that manifest the upregulation of Bcl-2. The long-term goals of the proposed research plan are to better define the biological substrates of AD+D, to facilitate the development of more effective treatments, and to provide additional insight into the clinical biology of depression in the elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEUROANATOMY AND PHARMACOTHERAPY OF OCD AND MAJOR DEPRES Principal Investigator & Institution: Saxena, Sanjaya; Psychiatry & Biobehav Sciences; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 10-JUN-1999; Project End 31-MAY-2004 Summary: This application proposes Sanjaya Saxena, M.D. for a Mentored PatientOriented Research Career Development Award. The overall goals are to provide him with the conceptual background and research skills necessary for him to conduct patient-oriented research on obsessive-compulsive disorder (OCD) and major depressive disorder (MDD). Under the guidance of his Primary Mentor and Expert Consultants, he will be trained in neuroanatomy, neuropsychopharmacology, functional neuroimaging, quantitative image analysis, biostatistics, research design, and research ethics. Building upon his prior work in functional brain imaging in OCD and MDD, as well as in pharmacotherapy for refractory OCD, his research during the Award period will include two main studies, proposed herein, on the functional neuroanatomy, pharmacotherapy, and differential time course of response to treatment of OCD and MDD, studying a total of 42 subjects: 1) Cerebral Metabolic Changes with Treatment of Concurrent OCD and MDD: This study will use [18F]-fluoro-deoxyglucose positron emission tomography (FDG-PET), to delineate the specific brain system mediation of OCD symptoms and MDD symptoms occurring simultaneously, in patients treated with paroxetine, a medication shown to be effective for both disorders. Differential metabolic changes occurring along parallel, frontal-subcortical circuits within the same brain will be measured after four weeks and again, after twelve weeks of treatment, and will be correlated with changes in specific symptoms. Understanding the mediation of OCD and MDD by frontal-subcortical circuits, as well as the differential time course of pharmacological effects on these circuits, may lead to improved treatments for both of these common disorders in the future. 2) Cerebral Metabolic Predictors of Response to Paroxetine and Risperidone in Refractory OCD: This study has the following specific aims: a) to identify cerebral metabolic patterns with FDG-PET that might predict response to paroxetine alone vs. paroxetine plus risperidone, b) to identify symptoms or other clinical variables, such as level of insight or delusionality, which might predict response to adjunctive risperidone, and c) to examine the efficacy of adjunctive
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risperidone for OCD patients who are refractory to paroxetine. With the additional skills and experience acquired during the Award period, Dr. Saxena will be well-prepared to compete for independent research support, and to conduct patient-oriented, neuroimaging and pharmacological research on OCD and MDD, with the long-term goal of improving treatment for these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: OPTIMIZATION OF ELECTROCONVULSIVE THERAPY Principal Investigator & Institution: Sackeim, Harold A.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from Applicant's Abstract): Patients treated with electroconvulsive therapy typically present with the most severe forms of major depression. Likely due to the increasing representation of medication-resistant patients, ECT response rates have diminished relative to earlier decades. This diminished response rate and early relapse following response are critical clinical problems in the use of ECT. Using the CSMD mechanism, this project addresses two key issues in the optimization of ECT in patients with major depression: whether patients treated with ECT should receive concurrent treatment with antidepressant medications (to enhance ECT outcome and/or prevent early relapse) and the role of electrode placement (high dosage right unilateral (RUL) ECT versus low dosage bilateral (BL) ECT) in maximizing short-term response and minimizing side effects. Patient enrollment, treatment, and evaluation will be conducted at Wake Forest University, Washington University, and the Western Psychiatric Institute and Clinic, with staff at the New York State Psychiatric Institute responsible for study coordination and monitoring. The study uses a random assignment, double-masked, parallel group design with two phases. In Phase 1, stratified by the classification of medication resistance, patients are randomized to concurrent treatment with nortriptyline (NT, n=210], venlafaxine (VEN, n=210) or placebo (PL, n=210), and simultaneously to high dosage (6 times threshold) RUL ECT (n=315) or low dosage (1.5 times threshold) BL ECT (n=315). Based on substantial preliminary data, the hypotheses will be tested that (1) compared to PL, concurrent NT or VEN results in superior symptomatic response, without a meaningful difference in side effects, and (2) RUL and BL ECT are equal in efficacy, but with significant advantages to high dosage RUL ECT in the magnitude of short- and long-term cognitive side effects. Support for these hypotheses in a large and diverse sample should have widespread ramifications for clinical practice. In the Phase 2 double-masked, 6-month continuation trial, remitters who received PL during ECT are randomized to NT and lithium (LI) or to VEN-LI. Patients who had been randomized to concurrent NT or VEN during ECT receive continuation treatment with NT-LI or VEN-LI, respectively. Standard practice involves the discontinuation of antidepressant medications prior to ECT, the abrupt discontinuation of ECT upon response, and then a switch to continuation pharmacotherapy. This practice likely diminishes response to ECT and heightens relapse in the first several weeks following ECT. Phase 2 of this study, centering on the comparison of patients treated with an antidepressant medication (NT or VEN) or placebo during ECT, will provide the very first data on whether starting an antidepressant medication from the beginning of the ECT course reduces the rate of early relapse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PARENT INTERVENTION IN CBT FOR DEPRESSED LATINO YOUTH Principal Investigator & Institution: Bernal, Guillermo; Professor; Psychology; University of Puerto Rico Rio Piedras San Juan, Pr 009311489 Timing: Fiscal Year 2004; Project Start 01-JUL-2004; Project End 31-MAY-2009 Summary: (provided by applicant): Despite progress in treating mental disorders in youth, little is known about these interventions with Latinos who are now the largest minority group in the United States. This study examines the impact of enhancing effective interventions through the involvement of parents in an 8 session of a psycho education intervention (PPI). This PPI will be incorporated into the 12-session CBT, a Cognitive Behavioral treatment method that has already been shown effective for the treatment of adolescent depression. This study will randomize 140 Latino adolescents with Major Depression to CBT with or without a PPI delivered in groups. Intake diagnoses will be obtained via structured diagnostic interviews (Diagnostic Interview Schedule for Children-DISC for adolescents and Composite International Diagnostic Interview-CIDI for parents). The study will focus on Puerto Rican adolescents and their parents. The primary aims address both the efficacy and effectiveness of the intervention and treatments. Efficacy questions focus on the comparison of the active treatment with and without the PPI for reducing depressive symptoms and diagnosis (DISC) after 12 weeks of treatment and for preventing relapse over the course of one year post-treatment (DISC). Effectiveness questions focus on the impact of the treatment with or without the PPI on broader functional outcomes. Patient functional outcomes include general functioning status, family functioning, school attendance, and attrition rates. The relative value of CBT with and without the adjunctive parent intervention for improved parent functioning regarding psychiatric distress and symptoms, burden of patient illness, and work attendance will be examined. We hypothesize that the active treatment with PPI will be superior to no PPI in reducing depression at post treatment. Because the PPI is designed to involve parents and thus impact other aspects of the family system, this treatment is expected to produce better outcomes in several of the functional domains. To test the theoretical assumptions of the intervention, we also aim to examine the contribution of hypothesized treatment-specific change mechanisms to mediate the short-term outcome and predict long-term relapse over one year. This study responds to NIH and NIMH initiatives on decreasing disparities in health and mental health care between minorities and White populations and will contribute to our knowledge base. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PLACEBO-CONTROLLED STUDY OF SAME VS.ESCITALOPRAM IN MDD Principal Investigator & Institution: Fava, Maurizio; Professor of Psychiatry Harvard Medical; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2004; Project Start 15-APR-2004; Project End 31-MAR-2009 Summary: (provided by applicant): Major depressive disorder (MDD) is a common, typically recurrent and disabling disorder, costing the U.S. over $44 billion/year in direct and indirect costs, and with point prevalence rates estimated at 5%-9% for women, and 2%-3% for men. More than one third of patients suffering from MDD appear to use alternative therapies in the U.S. Routinely prescribed in Europe for nearly 30 years and released four years ago in the U.S. as an over-the-counter dietary supplement, s-adenosyl-l-methionine (SAMe) has gained significant popularity as an
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agent marketed for improving mood and emotional well being. A number of relatively small double-blind studies have shown that parenteral or oral preparations of SAMe, compared with a number of standard tricyclic antidepressants, were generally equally effective, and tended to produce fewer side effects A relatively smaller number of studies have also examined the efficacy of SAMe compared to placebo, with the majority of these studies showing a significant advantage of SAMe over placebo. The recent report of the Southern California Evidence-Based Practice Center for the U.S. Department of Health and Human Services [Agency for Healthcare Research and Quality (AHRQ Publication 2002; http://www.ahrq.gov) ] states that "The results of these studies justify additional randomized clinical trials to evaluate the efficacy and tolerability of SAMe for treatment of depression." No adequately powered placebocontrolled study of SAMe in depression has ever been conducted in the U.S. We therefore propose a five-year, placebo-controlled, two-site study to assess the efficacy and safety of SAMe and of a standard selective serotonin reuptake inhibitor (SSRI), escitalopram in outpatients with MDD. This proposal is a parallel comparison of the efficacy and safety of SAMe, escitalopram, and placebo, with a crossover phase during which non-responders to any of these three treatments receive open-label treatment with the combination of escitalopram and SAMe. It is important to assess the efficacy of this combination therapy because patients frequently self-medicate with SAMe during standard antidepressant treatment. The primary aim of the proposed study is to test the acute antidepressant efficacy and tolerability of both SAMe and escitalopram, each compared to placebo, for the treatment of MDD. Secondary aims are to assess the acute effects of SAMe or escitalopram vs. placebo on remission rates, quality of life, and psychosocial functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREDICTING DEPRESSION OUTCOMES IN MEDICALLY ILL ELDERS Principal Investigator & Institution: Koenig, Harold G.; Associate Professor; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 15-AUG-1999; Project End 31-JUL-2004 Summary: Older adults with congestive heart failure (CHF) and chronic pulmonary disease (CPD) are increasing in number. Their lives and ability to function are greatly affected by these illnesses, which frequently lead to recurrent hospital admissions to manage exacerbations. We have found that 26 percent of older persons with CHF or CPD fulfill criteria for major depressive disorder when hospitalized. Depression is often prolonged, affects recovery, and increases use of health services. About one-third of these depressed patients, however, will go into full remission within three months of hospital discharge, often without specific treatment for depression. Many of these patients improve because their physical illness improves. The other two-thirds of depressed patients will have persistent depression, whether or not their health improves. Minor depression is even more common than major depression, being present in 32 percent of such patients, and while it may have a better prognosis than major depression, it is nevertheless associated with considerable disability and poorer quality of life. Research Questions: We are interested in studying four conjoint trajectories of depression-physical health outcome in the first six months after hospital discharge: depression and health both improve, depression improves but health does not, health improves but depression does not, and neither depression nor health improves. What proportion of patients follow each trajectory? What psychosocial and health characteristics predict which trajectory they will follow? What are the barriers to
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effective treatment, how is depression currently treated in these patients, and what are predictors of treatment intensity? Methods: 1000 older patients with CHF or CPD and major (n=500) or minor depression (n=500) will be recruited from the inpatient services of Duke Hospital and two community hospitals and followed for six months after discharge. Detailed assessments of depression and severity of medical illness will be conducted by a research nurse during telephone and in-person evaluations. Significance: Such information is necessary to determine which of the many patients with major or minor depression need specific treatment, and which patients will improve on their own after discharge as their medical illness improves or fails to improve. It will also provide important information to both guide future clinical trials and identify barriers to effective treatment of depression in these patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION FOR INFANTS OF LOW-INCOME DEPRESSED MOTHERS Principal Investigator & Institution: Cicchetti, Dante; Clinical/Social Psychology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2004; Project Start 01-FEB-2004; Project End 31-JAN-2009 Summary: (provided by applicant): This longitudinal investigation will evaluate the relative efficacy of two theoretically-informed approaches to preventing maladaptation, a depressotypic developmental organization, and emergent psychopathology in young offspring of low-income depressed mothers. Research participants will include 260 mothers and their infants; 195 mothers will have a current major depressive disorder and 65 demographically comparable mothers will have no lifetime history of mental disorder. All families will be at or below the federal poverty level. Depressed mothers and their infants will be randomly assigned to 1 of 3 treatment conditions: 1) Interpersonal Psychotherapy (IPT) for 4 months followed by an attention control for 8 months; 2)IPT for 4 months followed by Infant-Parent Psychotherapy (IPP) for 8 months; and 3) Enhanced Community Standard (ECS) treatment for depression, involving facilitated referrals for standard interventions in the community. Baseline assessments will be conducted when infants are 12 months old, with subsequent re-assessments when infants are 14, 16, 24, 36, and 48 months of age. Assessments will measure three major areas: 1) Maternal depressive symptomatology and Major Depressive Disorder (MDD) diagnosis, social role functioning, support, and home contextual features; 2) the quality of the mother-child relationship and affective features of parenting; and 3) child functioning, stage-salient issues, and stress-reactivity. Longitudinal comparisons of the two active preventive intervention groups (IPT and IPT/IPP) with the ECS and nondisordered groups will be used to determine: 1) whether IPT and IPT/IPP are efficacious in reducing maternal depressive symptomatology and MDD relapse through the child's age of four; 2) whether treatment targeted on maternal depression is sufficient to alter the developmental course in offspring; and 3) whether intervention directly focused on the mother-child relationship also is necessary to promote positive outcomes and reduce risk for maladaptation and psychopathology in young offspring of depressed mothers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PROCESS OF CHANGE IN DRUG ABUSE BY SCHIZOPHRENICS Principal Investigator & Institution: Bellack, Alan S.; Professor; Psychiatry; University of Maryland Balt Prof School Baltimore, Md 21201
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Timing: Fiscal Year 2002; Project Start 20-APR-1999; Project End 31-MAR-2004 Summary: Substance abuse by individuals with schizophrenia has reached epidemic proportions, yet little is known about why they use substances or how they can be helped to decrease use. The most widely accepted conceptualization of their substance abuse treatment needs is adapted from Prochaska and DiClemente's Transtheoretical Model (TTM). This model has proven to be quite robust in explaining the process of change in a variety of less impaired substance abusing populations, and several instruments have proven to be reliable and valid for assessing central components of the model. However, the TTM assumes intentional behavior change and full participation in the process of change by the substance abuser. Schizophrenia is marked by a number of symptomatic, neurocognitive, and psychosocial characteristics that would make it difficult for many individuals to successfully perform these complex activities, thereby raising questions about the applicability of the model for this population. Notably, patients with schizophrenia have significant impairments in cognitive function, including attention, memory, and higher level "executive" abilities, that may limit their ability to analyze the pros and cons of substance use, retain a focus on goals for decreased use over time, and form realistic efficacy expectations based on past experience. The disorder also is frequently associated with avolition and anhedonia, which may interfere with the ability to sustain motivation to reduce use. The overall purpose of this project is to examine attitudes about substance use, motivation to reduce use, and the process of change among schizophrenia patients who meet DSM-IV criteria for current Cocaine Dependence or are in Early Remission. The specific focus is the validity of the TTM for this population, and the adequacy of the standard measures of stages and processes of change developed for less impaired groups. Four groups of subjects will be assessed at Baseline, 3-, 6-, 9-, and 12-months: 70 Schizophrenia patients with current Cocaine Dependence, 70 Schizophrenia patients who are in Early Remission from Cocaine, 70 patients with Major Depression and current Cocaine Dependence, and 70 patients with Major Depression who are in Early Remission from Cocaine. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROSPECTIVE STUDY OF SUICIDAL BEHAVIOR IN BPD Principal Investigator & Institution: Stanley, Barbara; Professor of Psychology; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 100321098 Timing: Fiscal Year 2002; Project Start 08-FEB-2002; Project End 31-JAN-2007 Summary: (provided by applicant): Nearly 10 percent of all patients with BPD commit suicide and up to 75 percent make at least one suicide attempt. While many of these attempts are low in medical lethality, 50 percent of individuals with BPD have made at least one suicide attempt that is highly lethal. Despite this severity, the frequency of low lethality suicide attempts and non-suicidal self-injury in BPD leads clinicians to consider suicide attempts as merely "gestures," or manipulative and attention-seeking behaviors. Also, clinicians tend to treat suicidality in BPD by treating the symptoms of depression, when, in fact, impulsivity appears to be a stronger risk factor. We will examine clinical and neurobiological factors related to suicide attempts in subjects with borderline personality disorder using a prospective design. Through the administration of structured clinical interviews and lumbar puncture, we plan to measure various state and trait variables that pose risk for suicidal behavior in a cohort of 300 subjects: 200 with BPD (100 attempters, 100 non-attempters) between the ages of 18-35, the period of highest suicide risk in BPD and 100 attempters with Major Depression without an Axis II diagnosis. The specific aims are to: 1. examine clinical state and trait predictors of
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suicide attempts during a two year follow-up; and 2. examine serotinergic function (e.g., CSF-5HIAA) and other biological indices of suicide attempt behavior in BPD during a two year follow-up. Exploratory aims include: 1. identify the risk factors for high lethality versus low lethality attempts in BPD; 2. determine co-morbidity of Major Depression at time of attempts; 3. apply a stress-diathesis model to examine the interaction of state and trait factors in determining risk for suicidal behavior in BPD; 4. explore the relationship of self-mutilation and dissociation with suicidal acts, and with state and trait risk factors. The difficulty in predicting suicidal behavior in the treatment of BPD leads to either under-recognition of the seriousness of suicidal risk in BPD, or alternatively, over-utilization of hospitalization. These findings may have important clinical application for more accurate prediction of high lethality attempts within the context of frequent low lethality suicidal behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PST DYSFUNCTION
IN
GERIATRIC
DEPRESSION
WITH
EXECUTIVE
Principal Investigator & Institution: Alexopoulos, George S.; Professor and Vice Chair; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 15-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): This study proposes to compare the efficacy of Problem Solving Therapy (PST) to that of Supportive Therapy (ST) in non-demented elderly patients with major depression and cognitive impairment. Among them, we will focus on patients with major depression and executive dysfunction because this combination of symptoms (as defined in our preliminary studies) is prevalent, debilitating, and responds poorly to treatment with antidepressant agents. Therefore, we find it compelling to identify an effective treatment for these patients, who would otherwise remain depressed, debilitated, and demoralized during the last years of their lives. We selected PST because it can address depression as well as deficits in problem solving skills that impact on the patients' ability to negotiate their environment and contribute to their depression and disability. Moreover we now have empirical evidence suggesting that PST can reduce depressive symptoms and disability in cognitively unimpaired depressed elderly patients as well as elderly patients with major depression and executive dysfunction. The subjects will be 240 (120 from each Center) elderly (>64 years) patients with non-psychotic, unipolar major depression and executive dysfunction and will be randomly assigned to receive 12 sessions of PST or ST. The study is designed to test the hypotheses that the PST is more effective than ST in reducing depressive symptoms and disability. Furthermore, we hypothesize that these effects are mediated by improvement in generation of alternative solutions, decision making, and solution implementation. While we are aware of the methodological problems and confounds posed by studying a "sick and old population", we bring to this project two groups with complementary expertise in treatment studies and psychotherapy research, and experience in directing multicenter studies. Moreover, the project will be supported by the structures of the Cornell Intervention Research Center (IRC), whose principal objective is to develop treatment interventions targeting specific clinical and biological characteristics of geriatric depression. Accordingly, we are well positioned to meet the challenges inherent in this difficult but important area of research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PSYCHIATRIC DISORDERS IN ADULTS WITH DIABETES MELLITUS Principal Investigator & Institution: Lustman, Patrick J.; Professor of Psychiatry; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2002; Project Start 01-JUL-1985; Project End 31-MAR-2004 Summary: Diabetes increases the risks of maternal, fetal, and neonatal complications from pregnancy. Tight glycemic control during pregnancy reduces these risks but is difficult to achieve. Major depression is present in approximately 25 percent of diabetic women and is associated with significant deterioration in glycemic control. There has been no study in diabetic or nondiabetic subjects of depression treatment during pregnancy, and the effects of depression treatment on obstetric outcomes remain unknown. Recently, we showed that cognitive behavior therapy (CBT) was an effective nonpharmacologic treatment for depression in diabetes that produced durable improvements in glycemic control. In this study we plan to treat major depression in pregnant diabetic women with CBT and determine its effects on depression, glycemic control, and maternal and neonatal outcomes. We also plan to assess the relationship of diabetes during pregnancy and postpartum depression to neuropsychological development of the infants. 150 pregnant diabetic women will be recruited for study: 100 with and 50 without major depression. The nondepressed subjects function only as a comparison group in some of the statistical analyses. All subjects will be assessed serially during the 2nd and 3rd trimesters and the 1 year postpartum period while receiving the usual degree of intensive medical care for the diabetic pregnancy. Depressed patients will be assigned randomly to treatment with individual CBT (n =50) or supportive counseling (n =50). The pregnancy care team is informed of the depression status of all subjects and advised to give usual care for depression. The design blinds the pregnancy care team to treatment assignment, controls for nonspecific effects of attention and the influence of enhanced diabetes control on mood, provides a comparison group likely to remain depression free during gestation and the postpartum period, and is sensitive to human subject issues. We hypothesize that CBT will be superior to supportive counseling in terms of improving depression and glycemic control, and that the treatment-related improvements in glycemic control will reduce the adverse effects of diabetes in pregnancy, including c-section, macrosomia, neonatal hypoglycemia, and fetal hyperinsulinemia. We also expect that by improving glycemic control during pregnancy and reducing the risk of postpartum depression CBT will improve neuropsychological development in the offspring. The findings should demonstrate the relevance of depression treatment to maternal and neonatal outcomes of diabetic pregnancies and translate directly to the management of patients living with diabetes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CHILDREN
PSYCHOBIOLOGY
AND
TEMPERAMENT
IN
HIGH
RISK
Principal Investigator & Institution: Fairbanks, Janet M.; Psychiatry; Columbia University Health Sciences Po Box 49 New York, Ny 10032 Timing: Fiscal Year 2002; Project Start 01-MAY-1998; Project End 31-OCT-2003 Summary: (Adapted from applicant's abstract): This application for a Mentored Clinical Scientist Development Award has the long-term objective of developing the applicant's ability to conduct independent research in developmental psychopathology, specifically, temperamental risk factors and their biological correlates in children at risk for anxiety
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Major Depression
disorders. Rachel Klein, Ph.D., primary sponsor, will oversee training of the applicant in methodology, assessment and data interpretation. Jack Gorman, M.D. will supervise biological studies, and physiology training. Training will be accomplished by means of: 1) supervision with experienced researchers, 2) internships in cardiac physiology, respiratory physiology, and brain function, 3) formal instruction in statistics, and 40 implementation of the research project. Course work will provide the necessary background in biostatistics and epidemiology to conduct data analyses. Training in data collection processing and analysis will be obtained through carrying out the Research Plan. The purpose of the research is to further understanding of the developmental psychopathology of anxiety disorders through the study of early temperament. The goal is to conduct an in-depth examination of behaviorally inhibited temperament and its biological correlates in at-risk children. Specific aims are to examine the relationship between behavioral inhibition and 1) parental anxiety disorders, and 2) physiological function exploring the influence of parental diagnosis on these relationships. These aims will be addressed through a top-down, high-risk study of 3-5 year old offspring of adults with lifetime panic disorder, social phobia, or major depression, and offspring of normals. Behavioral inhibition will be qualified through direct observational protocols blind to parent diagnosis. Biological procedures examine autonomic dysregulation of cardiac function and skin temperature, asymmetries of brain electrical activation and skin temperature. HPA Axis, and respiratory function. Measures of autonomic function include: 1) heart rate (HR), 2) heart rate variability (HRV) and spectral analysis of HRF, 3) acceleration of HR, 4) blood pressure, and 5) skin temperature. Techniques of quantitative EEG measure brain activational asymmetry. Salivary cortisol measures HPA Axis dysregulation. Measures of respiratory function include end-tidal carbon dioxide, respiratory rate, tidal volume, and minute ventilation. These have been implicated in behavioral inhibition and anxiety disorders. The study of risk factors has important implications for early identification and ultimately prevention. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PUFA AUGMENTATION IN TREATMENT OF MAJOR DEPRESSION Principal Investigator & Institution: Gertsik, Lev G.; Cedars-Sinai Medical Center Box 48750, 8700 Beverly Blvd Los Angeles, Ca 900481804 Timing: Fiscal Year 2003; Project Start 15-JUL-2003; Project End 31-MAR-2005 Summary: (provided by applicant): This is a second revision of an Investigator-Initiated Exploratory/Developmental Research (R21) grant application to the National Center for Complementary and Alternative Medicine to explore the use of polyunsaturated fatty acids (PUFAs) as an augmentation strategy for the treatment of unipolar major depression. Major depression is a common mental disorder, and is associated with serious functional impairment, morbidity and mortality. Moreover, it also produces a significant financial burden on our society. Despite the availability of numerous pharmacologic and psychotherapeutic interventions, the current treatment of depression is not optimal. Even in patients who do respond to treatment, remission is rarely complete. In addition, the onset of action of antidepressants is delayed; the drugs usually must be taken for three weeks or more before improvement is clinically discernible. Accordingly, a number of augmentation strategies to hasten the onset of activity and increase the efficacy of traditional antidepressants have been proposed and tested, but many of these produce significant side-effects, and some patients still do not respond. PUFAs are found in high concentrations in the central nervous system, and they appear to be involved in many aspects of signal transduction. Recently, evidence has surfaced suggesting that the dietary intake of PUFAs might be related to depression,
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and the administration of PUFAs might reduce depressive symptomatology. In this application, we propose testing the hypothesis that administration of one of the PUFAs, eicosapentanoic acid (EPA), in combination with a selective serotonin reuptake inhibitor (SSRI) antidepressant will improve treatment outcome in unipolar major depression. In addition, we will determine whether the onset of antidepressant activity occurs more rapidly when EPA supplementation is combined with selective serotonin uptake inhibitor. The results of the proposed study might provide a new, economical, safe, and potentially important alternative approach to the treatment of unipolar major depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RELAPSE PREVENTION OF BIPOLAR TYPE-II DISORDER Principal Investigator & Institution: Amsterdam, Jay D.; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-FEB-2001; Project End 31-JAN-2006 Summary: (Adapted from applicant's abstract) Bipolar Type U (BP U) disorder affects 1.5-2.5 percent of the U.S. adult population and results in annual healthcare costs of about $20 billion. BP II disorder is characterized by a high recurrence of major depressive episodes (MDE) and is associated with substantial morbidity and mortality. The recognition of effective treatments for recurrent MDE is of critical importance. Unfortunately, relatively little attention has been given to its treatment. Concern over a "manic switch" during treatments of BP U MDE have impeded the development of effective antidepressive treatments and relapse prevention therapies for this illness. We have recently published pilot data demonstrating that fluoxetine may be a safe and effective monotherapy for the treatment of BP U MDE and for relapse-prevention treatment of BP II MDE. We propose to determine whether fluoxetine monotherapy is an effective treatment for both the initial and relapse-prevention treatment of BP II MDE. We will also determine whether fluoxetine monotherapy is associated with a low incidence of manic and hypomanic switch episodes in these patients. To answer these questions, 184 BP II patients will be recruited over 4 years from the Depression Research Unit (DRU)-which screens 400-500 new patients per year (of which about 25 percent meet DSM-IV criteria for BP II or NOS disorder). Patients will be treated initially with fluoxetine for 10 weeks and patients who remit from their MDE will be randomized, in a double-blind fashion, to receive one of the following relapse-prevention treatments for one year: i) fluoxetine monotherapy (20mg/daily) ii) lithium monotherapy (6001200mg/daily) iii) the combination of lithium (600-1200mg/daily) and fluoxetine (20mg/daily), or iv) placebo. We believe that our study has the potential to have a significant impact upon current clinical practice in the appropriate management of bipolar depressed patients; an extremely important public-health matter. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RELATIONAL GROUP INTERVENTION FOR POSTPARTUM DEPRESSION Principal Investigator & Institution: Clark, Roseanne; Associate Professor; Psychiatry; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 18-SEP-2001; Project End 31-JUL-2006 Summary: (provided by applicant): Major and minor depression in the postpartum period occurs in 10-15 percent of all new mothers, representing a significant public health problem. One of the major mechanisms by which PPD may influence infant
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Major Depression
outcomes is through its impact on the quality of the mother's affective and behavioral interactions during infancy, a critical time when physiological and emotional regulation and the capacity for human attachments are developing. Risk for disturbances in the mother-infant relationship as well as developmental delays and psychopathology in their infants represent significant areas of morbidity associated with postpartum depression and have not been addressed adequately by current intervention approaches. Therefore, the investigation of the efficacy of mother-infant relational treatment approaches for major depression during the postpartum period is warranted. The proposed study, representing a revision of the first R01 application by the principal investigator has four major aims: (1) To compare the efficacy of a manualized, relationally focused group treatment approach (M-ITG) for women with major depression in the postpartum period and their infants with a standard individual treatment (IPT) to ameliorate depressive symptoms and reduce recurrent episodes; (2) To compare the efficacy of M-ITG and IPT in improving the quality of mother-infant interactions; (3) To determine whether improvements in the mother-infant interaction mediate the impact of maternal depression on infant emotional, behavioral, and attention regulation; and (4) To examine the unique effects of depression severity and chronicity, comorbid anxiety and personality pathology on mother-infant interaction quality, and infant outcomes. Two hundred and eight women meeting criteria for major depression will be randomly assigned to one of two treatments for depression (1) MITG for mothers and their infants or (2) IPT. Assessments of mother, infant and motherinfant dyadic functioning, as well as parenting stress and marital conflict will be conducted at pre and post-treatment and at two follow-up points(l2 months posttreatment and when the infant is 24 months of age). Measures include diagnostic interviews, self and other report instruments and observational coding methods. The long-range objectives addressed by this research are to identify an effective intervention for postpartum depression that also reduces recurrences of depressive episodes in mothers, prevents subsequent psychopathology in their young children, and identifies key relational mechanisms that may inform the development of specifically targeted preventive interventions for high-risk dyads. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RISK AND PREDICTORS OF POSTPARTUM DEPRESSION Principal Investigator & Institution: Cohen, Lee S.; Associate Professor; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 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 •
Project Title: SELF SYSTEM THERAPY AND CHRONIC LOW BACK PAIN Principal Investigator & Institution: Keefe, Francis J.; Professor and Associate Director; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 15-JUN-2003; Project End 31-MAY-2007 Summary: (provided by applicant): Patients with chronic low back pain (CLBP) cope with numerous major life challenges associated with their disorder, including changes in their ability to work, as well as decrements in physical and emotional well being. These changes alter CLBP patients' ability to pursue and achieve important personal goals and live up to personal standards. As a result, CLBP patients are highly likely to experience substantial difficulties with self-regulation, i.e., the ongoing process of evaluating and regulating one's behaviors so as to meet important personal goals and standards. In turn, the inability to attain important goals and standards increases risk for depression. The long-range goal of this research is to reduce the depression, pain, psychological disability, and physical disability experienced by CLBP patients suffering from depression. The proposed study seeks to evaluate the efficacy of Self-System Therapy (SST), a new therapy for depression specifically targeting problems in selfregulation. A total of 174 CLBP patients who meet DSM-IV criteria for major depressive disorder will be randomly assigned to one of three conditions: 1) Self-System Therapy (SST) - a twelve-session version of SST adapted to the concerns of CLBP patients; 2) Back Pain Education - a comparison condition that provides patients with information on the nature and treatment of chronic low back pain; or, 3) Standard Care Condition - a control condition in which patients will receive care requested by them and made available to them by their health care provider. Assessment measures to be gathered before and after treatment and at 6- and 12-month follow-up will include depression, physical and psychosocial disability, pain and coping self-efficacy, self-regulatory focus, and self-discrepancies. Daily measures of pain, mood, goal activation/attainment, and stress will also be gathered. Converting basic knowledge about the causes and consequences of unsuccessful self-regulation to the diagnosis and treatment of depression in CLBP patients represents a promising avenue for identifying treatment options appropriate for these individuals. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Major Depression
Project Title: SERTRALINE FOR ALCOHOL DEPENDENCE AND DEPRESSION Principal Investigator & Institution: Pettinati, Helen M.; Director; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 30-SEP-1992; Project End 31-MAR-2004 Summary: This is a competing continuation proposal to extend results from a 5- year NIAAA-funded project on sertraline for depressed alcoholics. Comorbidity in substance abusers traditionally has been associated with a more severe clinical picture and a poorer prognosis for drinking outcome, compared to cases of uncomplicated alcoholism. In clinical populations, one-third to one-half of patients seeking alcohol treatment have a lifetime major depressive disorder. Persistent depression in abstinent alcoholics is both disabling and a risk factor for relapse to drinking, and further clinical deterioration that may result in suicide. Because we have effective, FDA-approved pharmacotherapy for alleviating depressive symptoms, it is important that we are fully informed about the advantages (or disadvantages) of treating primary or secondary depression in alcoholics with antidepressant medications. Results from our initial, project suggested that comorbidly depressed alcoholics appeared to have reduced antidepressant effects from sertraline and sertraline did not reduce their drinking (more than placebo). To address these results, we propose a study that will examine if we can achieve a more optimal outcome in comorbidly depressed alcoholics by directly treating the alcoholism with naltrexone, and combining this pharmacotherapy with the use of sertraline for treating depression. Thus, the primary aim of this proposal is to examine in depressed alcoholic outpatients whether combining naltrexone (an FDA-approved pharmacological intervention to reduce drinking) with sertraline (an FDA-approved pharmacological intervention to treat depression) will result in greater reductions in both drinking and depression over either medication alone or placebo. A secondary aim is to examine whether certain patient features, e.g., extent of pre-treatment drinking or severity of depression, will predict response to sertraline, naltrexone, or the combination. Patients who present to the University of Pennsylvania Treatment Research Center will be recruited for participation in this study over a 5-year period. There will be 160 males and females with a current DSM-IV diagnosis of alcohol dependence and also of major depression (via PRISM) who will be randomized to one of four treatment groups (40 per group): 1) the combination of 100mg/day naltrexone and 200mg/day sertraline, 2) 100mg/day naltrexone, 3) 200mg/day sertraline, or 4) placebo. Subjects will also receive once- weekly sessions of Cognitive Behavioral Therapy that has been adapted to include a medication compliance enhancement component. The treatment phase will last 16 weeks (includes a week of baseline, and a week of single-blind, placebo lead-in, and 14 weeks of double-blind pharmacotherapy). The follow-up phase includes two visits at 6 and 9 months post-treatment entry. Overall, this project will determine if combining pharmacotherapies results in a better response in comorbidly depressed alcoholics than either medication alone or placebo. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SIGNAL TRANSDUCTION MECHANISMS IN SUICIDE BRAIN Principal Investigator & Institution: Dwivedi, Yogesh; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2009 Summary: We and several other investigators have previously reported that neurotransmitter receptors, such as serotonergic and adrenergic, and specific effectors of these receptor-mediated signal transduction systems are altered in the postmortem
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brain of suicide victims. Recent investigations in our laboratory have revealed that the functional characteristics and the expression of transcription factor CREB, a common substrate for many neurotransmitter receptor systems implicated in the pathophysiology of suicide, and the expressions of its target gene BDNF and receptor for BDNF, i.e., TrkB, are significantly altered in the postmortem brain of suicide victims, suggesting that these molecules may be playing an important role in the pathophysiology of suicidal behavior. However, the significance and consequences of these alterations at the functional level in suicide brain are not clear. ERK-1/2 and PI3kinase cascades are the two most important signaling systems in the CNS that are activated by TrkB and mediate the physiological functions of BDNF. The major objective of the proposed research is to elucidate the cellular and the molecular mechanisms associated with suicide by examining whether abnormalities in BDNF and TrkB are associated with abnormalities further downstream in the ERK-1/2 and the PI3-kinase pathways, both at the level of kinases and at the functional level in the substrate molecules responsible for physiological actions in the brain. More specifically, in postmortem brain of suicide victims and well-matched nonpsychiatric control subjects, we will study the activation and the expression of upstream kinases Raf-1, MEK-1, ERK1, ERK-2, PI3-kinase, Akt-1, Akt-3, and of downstream substrates, transcription factors Elk-1 and FKHRL1, and regulatory proteins Bcl-2 and Bad, both at the molecular and the cellular level. These studies will be performed in prefrontal cortical and hippocampal brain areas utilizing quantitative RT-PCR, Western blot, immunoprecipitation, enzymatic assays, in-situ hybridization, and gold-immunolabeling techniques. Furthermore, to examine whether observed changes are restricted to depression, we will compare the findings in the proposed measures between suicide victims with a firm diagnosis of major depression and those diagnosed with other psychiatric disorders. We will also study whether there is coordinated regulation of the proposed measures (upstream kinases, downstream substrates, and regulatory proteins) of the two signaling pathways within the same brain by examining the correlational structure overall and individually within the group and by statistical path analysis. The proposed research is based on the central hypothesis that there may be abnormalities in the components of ERK-1/2 and PI-3 kinase signaling pathways in postmortem brain of suicide victims, which may be associated with abnormalities in activation and/or expression of the substrate molecules responsible for BDNF-elicited neuronal functions, and that these abnormalities may play an important role in the pathophysiology of suicidal behavior. Elucidation of the alterations in ERK-1/2 and PI3-kinase pathways in postmortem brain of suicide victims will yield important information on the neurobiology of suicide and will indicate possible novel sites for therapeutic interventions, which may eventually lead to better treatment and possibly prevention of suicidal behavior. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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.
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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 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 •
Project Title: SOFTAD SUBSTANCE USE OUTCOMES FOLLOWING TAD Principal Investigator & Institution: Curry, John F.; Associate Professor; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAY-2008 Summary: (provided by applicant): Substance abuse is a major public health problem among adolescents in the United States, associated with serious negative outcomes including high-risk sexual behavior and the leading causes of adolescent death: accidents, homicide and suicide. Substance use disorders (SUD's) are one of the three most common forms of adolescent psychiatric disturbance. Prevention of such disorders is a public health priority. The National Institute on Drug Abuse (NIDA) and the National Institute of Mental Health (NIMH) recently released RFA: DA-03-007, calling for investigations into the impact of child psychopathology and childhood interventions on subsequent drug abuse. This project, Substance use Outcomes Following Treatment for Adolescent Depression (SOFTAD) is an extended follow-up of adolescents who have completed the NIMH Treatment for Adolescents with Depression Study (TADS). We developed and are coordinating TADS, a 12-site study comparing cognitive behavior therapy (CBT), fluoxetine (FLX), combined CBT and FLX acutely to one another and to placebo, and longitudinally to one another in 432 adolescents with Major Depressive Disorder (MDD). TADS is the first adolescent MDD treatment study to include measures of substance use and abuse. We propose to enhance the measurement of substance use outcomes and related family factors and to extend the follow-up period from TADS treatment to five years in order to address critical questions emphasized in RFA: DA-03-007. These include the impact of treating MDD (and of specific treatments) on subsequent substance use outcomes, the identification of moderators and mediators of successful outcome in the affective and substance use domains, and the longitudinal
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relationship between adolescent MDD and substance use or abuse in a clinical sample. Approximately 300 adolescents will be followed and assessed every six months. Selfreport, parent-report and diagnostic interview measures will be collected. The major hypothesis, that successful treatment of MDD will reduce subsequent substance use problems, and additional questions, will be tested using chi-square, logistic regression, and structural equation modeling. SOFTAD will be coordinated by the Duke Clinical Research Institute (DCRI), the same organization coordinating TADS, thus realizing substantial efficiencies and cost savings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL GENOMICS OF NOREPINEPHRINE TRANSPORTERS Principal Investigator & Institution: Blakely, Randy D.; Associate Professor; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): The antidepressant-sensitive norepinephrine (NE) transporters (NETs) constitute the major mode of synaptic inactivation of NE. Recent clinical genetic studies by our groups identified a coding mutation, A457P, in one NET allele of a proband with Orthostatic Intolerance (OI) presenting with reduced NE clearance, increased spillover and reduced intraneuronal NE metabolism. The A457P mutation was found to track with measures of postural tachycardia in the proband?s family and to correlate with altered synaptic NE metabolism. In Specific Aim 1, we propose to ascertain the functional impact of the A457P and other identified NET coding mutations in terms of transport and efflux, transporter trafficking and surface expression using heterologous expression systems. Evidence will be sought to support a dominant-negative interaction between mutant and wildtype subunits and whether homomultimeric complexes support NET function. In Specific Aim 2, we propose to extend our genetic evaluation of NET deficiency to evaluate additional subjects with OI and cardiomyopathy (CM) using high-throughput gene scanning techniques. These studies will focus on the NET coding exons and splice junctions and also include a recently identified intronic region that plays a critical role in NET gene expression. Methods will be implemented to allow for an evaluation of altered NET protein in biopsies tissue. Finally, attention and mood are dependent on proper noradrenergic signaling in the CNS and symptoms are present in our A457P probands indicating attention deficit, anxiety and hyperarousal. Thus, we propose in Specific Aim 3 to examine NET alleles with primary diagnoses of attention-deficit hyperactivity disorder (ADHD), attentional deficit (ADD) subtype and Major Depression, melancholic subtype, which is characterized by hyperarousal and anxiety. We will select subjects for analysis in both cases on the basis of comorbid tachycardia. Together these studies offer an opportunity for a better understanding of the molecular and behavioral manifestations of genetic NET variation. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TESTING COGNITIVE BEHAVIORAL THERAPY IN A PUBLIC SYSTEM Principal Investigator & Institution: Lopez, Molly Ann.; Psychologist; Texas State Dept of Mental Health & Mr Box 12668, 909 W 45Th St Austin, Tx 78711 Timing: Fiscal Year 2003; Project Start 05-AUG-2003; Project End 31-DEC-2004 Summary: The Texas Department of Mental Health and Mental Retardation (TDMHMR) is committed to incorporating empirically-supported interventions into a service array
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designed to meet the needs of the citizens of Texas with severe or persistent mental illness. As a part of this on-going effort, TDMHMR proposes to undergo a project designed to identify and implement an empirically-validated cognitive behavioral therapeutic approach for adults diagnosed with major depressive disorder. There is compelling research evidence that cognitive behavioral therapies are as effective as pharmacotherapy in improving depressive symptomatology and may be more effective in preventing relapse. The department has the long-range goal of identifying and implementing one or more validated psychotherapies throughout all community mental health centers in Texas. The current application has three primary aims: (1) to review empirically-validated, manualized, cognitive behavioral therapies for the treatment of major depression in adults and select a therapeutic approach that can best be transported into a community mental health system; (2) to create an implementation plan that includes a training module to maximize implementation and fidelity to the treatment model and addresses methods for reducing common barriers to implementation; and (3) to conduct a brief pilot study utilizing four to eight masterslevel clinicians currently employed within community mental health clinics to provide the manualized treatment to consumers deemed appropriate for the service. Providers will undergo training and supervision by an expert consultant. Adults with major depression referred for counseling will be recruited for the study. Changes in symptom severity during treatment will be measured, as well as each therapists' level of competence with the selected therapeutic approach. This small pilot study will provide preliminary information on the feasibility of implementing this approach within community mental health clinics and provide guidance for the future planning of a more comprehensive implementation effort. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TMS TREATMENT OF MAJOR DEPRESSION Principal Investigator & Institution: Avery, David H.; Professor; Psychiatry and Behavioral Scis; University of Washington Grant & Contract Services Seattle, Wa 98105 Timing: Fiscal Year 2002; Project Start 15-AUG-2000; Project End 31-JUL-2004 Summary: Repetitive Transcranial Magnetic Stimulation (Rtms) is a promising new treatment Major Depressive Disorder: some small controlled studies of high frequency rTMS electrical current is induced in the cortext of the brain by the magnetic field of a small electromagnetic coil placed on the scalp. Unlike electroconvulsive therapy (ETC), one of the most effective treatment for severe depression, rTMS gives a much smaller, subconvulsive stimulus and is more focal in its localization. Preliminary data suggest no disorientation, confusion, or memory disturbance associated with Rtms. We propose to study 86 drug-free patients with Major Depressive Disorder who have failed at least two trials of antidepressant medication either because of medication resistance and/or medication intolerance. The subjects will be randomized into one of two stimulations to the left DLPFC: 1) Rtms at 110 percent of motor threshold intensity at 10 Hz with 5 second trains (rTMS) or 2) Sham stimulation (the electromagnetic coil angled at 90 degrees so that the cortex is not stimulated) at 110 percent motor threshold intensity at 10 Hz for 5 seconds. Each subject will be given 10 sessions with 32 trains per session over a period of two weeks. Blind assessment of the depression will take place before the 1st Rtms session, after the 5th and 10th rTMS sessions and 1 week and 2 weeks after the 10 rTMS session. Neuropsychological measures fo attention, memory, language production, psychomotor speed, visual motor sequencing, cognitive flexibility, information processing speed and executive functioning will be administered by a trained examiner blind to treatment conditions at screening. Baseline, and following the
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last rTMS session. Additionally, measures of orientation, attention, and memory to monitor for post-rTMS confusion will be administered following each Rtms treatment session. We hypothesize that the rTMS stimulations will be significantly more efficacious than the sham stimulations. Ultimately, if Rtms is shown efficacious, safe and free from cognitive disturbance, rTMS could be an alternative treatment for depressed patients who have failed to respond to antidepressant medication trials. In a second phase of the study, we will place responders on maintenance antidepressant medication two weeks after the last rTMS session and evaluate them at follow-up visits 1 month, 2 month, 3 months, 4 months, 5 months, and 6 months after the last rTMS session. Nonresponders to sham stimulation will be offered rTMS. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TRAIT DEPRESSION
AND
STATE
FRONTAL
BRAIN
ASYMMETRY
IN
Principal Investigator & Institution: Allen, John J.; Professor; Psychology; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2004; Project Start 01-APR-2004; Project End 31-JAN-2009 Summary: (provided by applicant): Asymmetrical frontal brain activity holds promise as a marker of risk for depression. Over 40 studies suggest that resting frontal electroencephalographic (EEG) asymmetry may serve as an indicator of a trait-like diathesis to respond to emotional situations with a pattern of emotional negativity and behavioral withdrawal. Moreover, resting frontal EEG asymmetry distinguishes depressed individuals -- those currently symptomatic as well those as in remission -from never-depressed individuals. These findings suggest that frontal EEG asymmetry is more than a correlate of a depressive episode, potentially serving as a liability marker for the development of depression. Such a marker could have prognostic and etiological value, but superimposed on the trait-like stability are fluctuations that vary as a function of occasion of assessment or experimentally manipulated emotion. Estimates of the stability of frontal EEG asymmetry are in the range of.60, suggesting that trait factors are substantial, but that variation across assessments may limit the utility of asymmetrical frontal brain activity as a trait-like risk indicator for depression. Such factors may underlie the few inconsistent findings in this literature. The present proposal represents a necessary step in the programmatic investigation of frontal EEG asymmetry as a potential risk indicator for depression, by evaluating three distinct sources of variability in frontal EEG asymmetry: 1) Stable trait consistency across multiple assessments; 2) Occasion-specific fluctuations from one assessment to the next; and, 3) State-dependent changes within a single assessment. During four visits, trait resting as well as state manipulated frontal EEG asymmetry will be assessed in depressed and nondepressed subjects. This design will allow us to address several specific aims, including: 1) To assess the relative contributions of trait, occasion, and state variance in frontal EEG asymmetry; 2) To assess whether frontal EEG asymmetry has characteristics that suggest it may profitably serve as a marker of risk for major depressive disorder; and, 3) To assess the acute impact of a widely used selective serotonin reuptake inhibitor on frontal EEG asymmetry, as medication effects have been largely unexplored. Secondary aims address methodological and treatment-related questions, as well as assessing gender and menstrual cycle effects that may moderate the relationship between frontal EEG asymmetry and depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: HISTORIES
TREATING
DEPRESSED
WOMEN
WITH
SEXUAL
ABUSE
Principal Investigator & Institution: Talbot, Nancy L.; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 13-SEP-2002; Project End 31-AUG-2007 Summary: (provided by applicant): This Mentored Patient-Oriented Research Career Development Award will provide training in intervention research testing psychotherapeutic treatments for depression among patients with histories of childhood sexual abuse and other lifetime traumas. Depression and childhood sexual abuse are prevalent and exact enormous psychological and economic costs for women's mental health and physical health. Childhood sexual abuse amplifies risk for major depression in women; the affective illness that ensues often is more severe, chronic, and complex, and hence more difficult to treat. Individual psychotherapies with proven efficacy in other treatment contexts have not been systematically investigated among depressed women with abuse histories in community- based settings. The educational plan provides explicit instruction, training, and supervision to prepare the candidate as an independent investigator of psychotherapeutic treatments for depressed patients with histories of childhood sexual abuse and other lifetime traumas. Mentored career development and research activities are designed to develop expertise in (a) the assessment, moderators, and outcomes of depression; and (b) clinical interventions research design and methods. The research plan lays the foundations for a program of systematic research into treatments for this high-risk subset of women by comparing interpersonal psychotherapy (IPT), an established treatment for depression, to usual care provided in a community mental health center. The study will use a 2 (treatment) X4 (pretest, 8-week, post test, 3-month follow-up) repeated measures design. Seventy women with major depression (DSM-IV) will be randomly assigned to IPT or usual care. IPT is hypothesized to lead to greater improvements in depressive symptoms, and psychological and social functioning. Key variables that moderate good and poor outcomes will be identified. The acceptability of IPT will also be examined. Results will guide the next state of research, which is to refine treatment strategies to improve health outcomes in an often-underserved and understudied patient population from diverse socioeconomic backgrounds within community-based settings. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TREATMENT OF DEPRESSION IN PARENTS--IMPACT ON CHILDREN Principal Investigator & Institution: Garber, Judy; Professor; Psychology & Human Development; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 20-AUG-1998; Project End 31-JUL-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
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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 •
Project Title: TREATMENT OF LATE LIFE DEPRESSION COMPLICATED BY ALCOHOL Principal Investigator & Institution: Oslin, David W.; Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUN-1999; Project End 31-MAY-2004 Summary: The focus of this Mentored Clinical Scientist Development Award (MCSDA) is to enable David Oslin, MD to acquire academic and research expertise for the treatment of late life mental disorders including major depression and comorbid alcoholism. Dr. Oslin is currently an Assistant Professor of Psychiatry at the University of Pennsylvania with appointments in the Section of Geriatric Psychiatry and the Center for Studies on Addiction. His career goals include: 1) gaining expertise in study design and methodology for intervention research, 2) establishing independent research projects on the treatment of comorbid mental health disorders, 3) enhancing his clinical expertise in the prevention, recognition and treatment of late life mental illness, and 4) being a resource for the university community on the research and clinical care of older adults, especially those with comorbid mental health problems. The proposal for this application includes both formal and informal instruction in research design and methodology as well as an intervention development project that will have both educational and scientific significance. The research plan for this award includes an intervention development study for older adults with primary major depression complicated by alcohol dependence. The aim of the project is to evaluate the tolerability and efficacy of naltrexone compared to placebo as a treatment for alcoholism in combination with sertraline as a treatment for primary major depression. Focusing on older adults enhances the goal of examining primary depression and comorbid alcoholism as the literature suggests that alcoholism is more often secondary to major depression in older adults compared to younger adults. This research plan is seen as a step toward the design of future studies of comorbidity in late life major depression. A growing awareness of a strong association between depression and alcohol abuse/dependence, the need for safe and effective treatments for comorbidity, and everpresent problem of gaining patient compliance with treatment regimens all appear to be
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fertile ground for study in an older population. The MCSDA would provide an important vehicle via course work and mentoring to enable Dr. Oslin to advance his knowledge and experience in these areas, which in turn, may advance the field of psychiatry's understanding of these complex issues. Dr. Oslin's training in geriatric psychiatry and addictions also makes him a good candidate to conduct the proposed intervention study. Finally, proposed plans for this MCSDA are well coordinated with the research activities of the Section of Geriatric Psychiatry and the Center for Studies on Addiction. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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, 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
•
Project Title: TREATMENT OUTCOMES OF VASCULAR DEPRESSION Principal Investigator & Institution: Doraiswamy, Pudugramam Murali.; Director, Psychiatry Clinical Trial; Psychiatry; Duke University Durham, Nc 27710 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 31-MAR-2006
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Summary: (provided by applicant): The treatment of major depression in late life (LLD) is an important health problem with a large and growing number of affected individuals. A significant subset of patients with LLD, particularly those with cerebrovascular risk factors (VRF)s, have subcortical gray matter (SCGMH) or frontal deep white matter (FDWMH) hyperintensities on brain mRI scans. Naturalistic studies suggest that such changes may be associated with poor acute and long-term antidepressant treatment response. However, the prognostic significance of brain MRI findings has not been evaluated systematically in prospective treatment trials. Similarly, studies have indicated that LLD patients frequently have deficits in Initiation/Perseveration (IP) and other tests of frontal lobe function. An elegant longitudinal study with nortriptyline has demonstrated that frontal executive dysfunction is associated with poor acute response as well as a greater risk for relapse/recurrence in LLD. However, the generalizability of this important finding to other classes of antidepressants, such as the widely used SSRIs, is not known. The interaction between frontal brain lesions and executive function deficits in LLD is also not fully studied. The proposed study will be the first large-scale prospective trial to simultaneously test the effects of both specific neuroanatomical and neuropsychological factors on course of response, remission rate as well as on broader measures of health outcomes in LLD. We propose to conduct a collaborative 12-week acute treatment trial with sertraline in 320 elderly (age greater than 60) patients with major depression at Duke University Medical Center and Washington University Medical Center. In a sample chosen to balance generalizability and scientific rigor, we will test the hypotheses that: 1) greater lesion severity on MRI will predict reduced treatment response, and 2) greater lesions severity on MRI willbe correlated with frontal executive dysfunction. In secondary aims, we will test the effects of lesion volume/location and frontal executive dysfunction on treatment response. In addition, we will test the effect of interactions of MRI-lesions, vascular risk factors and executive dysfunction on treatment response. The proposed trial will provide information of value to the practitioner and also provide data to build a more comprehensive model of the prognostic impact of frontal-subcortical brain changes on the outcome of late-life depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
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 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
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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 •
Project Title: VENTILATORY PHYSIOLOGY IN CHILDREN AT RISK FOR ANXIETY Principal Investigator & Institution: Klein, Rachel G.; Professor; Psychiatry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2002; Project Start 28-SEP-1999; Project End 31-MAY-2004 Summary: The proposed investigation addresses the biology of risk for anxiety disorders. It derives from important parallel scientific concerns regarding the association between adult and child anxiety disorders, coupled with concerns regarding the mechanisms which underlie this association. The study specifically evolves from findings that link childhood separation anxiety disorder (SAD) and adult panic disorder (PD). These findings include: family studies noting elevated rates of SAD in offspring of adults with PD; longitudinal studies linking childhood SAD to adult PD; and biological studies finding CO2-hypersensitivity in children with SAD. CO2-hypersensitivity is also found in both adults with PD and non-ill adult relatives of patients with PD. Taken together, these findings point to the existence of a latent vulnerability to PD reflected in the respiratory system. We propose to examine respiratory function in children at high risk for panic disorder. Major hypotheses are that at risk children, compared to controls, exhibit more variable respiration and hypersensitivity to CO2 exposure as manifested by greater symptomatic and physiologic responses to the inhalation of 5 percent of CO2. We hypothesize that such abnormalities will occur among offspring even in the absence of an anxiety disorder. Aims are addressed through the study of ventilatory measures in offspring, ages nine-to-17, of adults with PD, as compared to offspring of adults with a) social phobia but not panic disorder, b) major depression but neither panic disorder nor social phobia, and c) no mental disorder. A total of nearly 350 children and their parents have been systematically assessed in an ongoing diagnostic study of children at highrisk for anxiety. In the proposed work, diagnosis will be updated with separate interviewers for each family member. Children will undergo a CO2 inhalation procedure in their home with a validated apparatus. Outcome measures consist of: i)
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pre-experimental respiratory variability, as well as ii) the symptomatic, and iii) physiological response to CO2. A series of studies conducted by the investigative team finds that these factors distinguish adults with PD and children with SAD from relevant contrast groups. Respiratory variables will be rated blind to parental and child diagnosis. The inclusion of offspring from pathological comparison groups, together with offspring of normals, provides a rigorous test of hypothesized diagnostic specificity in the relationship between respiratory factors and anxiety in both children and adults. The proposed study follows naturally from the investigative team's prior work and capitalizes on the availability of a well-characterized sample. 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 “major depression” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for major depression in the PubMed Central database: •
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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Comorbid Major Depression and Social Phobia. by Douglas S.; 2001 Aug; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=181185
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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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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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Incidence of major depression in Canada. by Patten SB.; 2000 Sep 19; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=80167
3 4
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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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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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 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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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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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
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 major depression, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “major depression” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for major depression (hyperlinks lead to article summaries): •
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A comparison of life events between suicidal adolescents with major depression and borderline personality disorder. Author(s): Horesh N, Sever J, Apter A. Source: Comprehensive Psychiatry. 2003 July-August; 44(4): 277-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12923705
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 longitudinal population-based study of treated and untreated major depression. Author(s): Wang J. Source: Medical Care. 2004 June; 42(6): 543-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15167322
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A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression. Author(s): van West D, Del-Favero J, Aulchenko Y, Oswald P, Souery D, Forsgren T, Sluijs S, Bel-Kacem S, Adolfsson R, Mendlewicz J, Van Duijn C, Deboutte D, Van Broeckhoven C, Claes S. Source: Molecular Psychiatry. 2004 March; 9(3): 287-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15094789
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A neuropathological study of periventricular white matter hyperintensities in major depression. Author(s): Thomas AJ, O'Brien JT, Barber R, McMeekin W, Perry R. Source: Journal of Affective Disorders. 2003 September; 76(1-3): 49-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943933
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A prospective trial of modafinil as an adjunctive treatment of major depression. Author(s): DeBattista C, Lembke A, Solvason HB, Ghebremichael R, Poirier J. Source: Journal of Clinical Psychopharmacology. 2004 February; 24(1): 87-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14709953
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A quantitative neuromotor predictor of antidepressant non-response in patients with major depression. Author(s): Caligiuri MP, Gentili V, Eberson S, Kelsoe J, Rapaport M, Gillin JC. Source: Journal of Affective Disorders. 2003 November; 77(2): 135-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607390
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A randomized, placebo-controlled trial of citalopram for the treatment of major depression in children and adolescents. Author(s): Wagner KD, Robb AS, Findling RL, Jin J, Gutierrez MM, Heydorn WE. Source: The American Journal of Psychiatry. 2004 June; 161(6): 1079-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15169696
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A review of antidepressant-induced hypomania in major depression: suggestions for DSM-V. Author(s): Chun BJ, Dunner DL. Source: Bipolar Disorders. 2004 February; 6(1): 32-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996139
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A test of the tripartite model's prediction of anhedonia's specificity to depression: patients with major depression versus patients with schizophrenia. Author(s): Joiner TE, Brown JS, Metalsky GI. Source: Psychiatry Research. 2003 August 1; 119(3): 243-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12914895
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Age of traumatisation as a predictor of post-traumatic stress disorder or major depression in young women. Author(s): Maercker A, Michael T, Fehm L, Becker ES, Margraf J. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2004 June; 184: 482-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15172941
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Alleles of a functional serotonin transporter promoter polymorphism are associated with major depression in alcoholics. Author(s): Nellissery M, Feinn RS, Covault J, Gelernter J, Anton RF, Pettinati H, Moak D, Mueller T, Kranzler HR. Source: Alcoholism, Clinical and Experimental Research. 2003 September; 27(9): 1402-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14506400
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An efficacy/effectiveness study of cognitive-behavioral treatment for adolescents with comorbid major depression and conduct disorder. Author(s): Rohde P, Clarke GN, Mace DE, Jorgensen JS, Seeley JR. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2004 June; 43(6): 660-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15167082
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An open-label study of nefazodone treatment of major depression in patients with congestive heart failure. Author(s): Lesperance F, Frasure-Smith N, Laliberte MA, White M, Lafontaine S, Calderone A, Talajic M, Rouleau JL. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 November; 48(10): 695-701. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14674053
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An open-label trial of riluzole in patients with treatment-resistant major depression. Author(s): Zarate CA Jr, Payne JL, Quiroz J, Sporn J, Denicoff KK, Luckenbaugh D, Charney DS, Manji HK. Source: The American Journal of Psychiatry. 2004 January; 161(1): 171-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702270
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Antidepressive treatment in patients with temporal lobe epilepsy and major depression: a prospective study with three different antidepressants. Author(s): Kuhn KU, Quednow BB, Thiel M, Falkai P, Maier W, Elger CE. Source: Epilepsy & Behavior : E&B. 2003 December; 4(6): 674-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14698701
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Arthritis and heart disease as risk factors for major depression: the role of functional limitation. Author(s): Dunlop DD, Lyons JS, Manheim LM, Song J, Chang RW. Source: Medical Care. 2004 June; 42(6): 502-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15167318
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Association between norepinephrine transporter gene polymorphism and major depression. Author(s): Ryu SH, Lee SH, Lee HJ, Cha JH, Ham BJ, Han CS, Choi MJ, Lee MS. Source: Neuropsychobiology. 2004; 49(4): 174-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15118352
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Augmentation of milnacipran by risperidone in treatment for major depression. Author(s): Tani K, Takei N, Kawai M, Suzuki K, Sekine Y, Toyoda T, Minabe Y, Mori N. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2004 March; 7(1): 55-8. Epub 2004 January 20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14731310
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Automatic and effortful information processing in unipolar major depression. Author(s): Hammar A. Source: Scandinavian Journal of Psychology. 2003 December; 44(5): 409-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15030106
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Balancing speed of response to ECT in major depression and adverse cognitive effects: role of treatment schedule. Author(s): Shapira B, Tubi N, Lerer B. Source: The Journal of Ect. 2000 June; 16(2): 97-109. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10868320
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Basal limbic system alteration in major depression: a hypothesis supported by transcranial sonography and MRI findings. Author(s): Becker G, Berg D, Lesch KP, Becker T. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2001 March; 4(1): 21-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11343626
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Baseline prolactin and L-tryptophan availability predict response to antidepressant treatment in major depression. Author(s): Porter RJ, Mulder RT, Joyce PR. Source: Psychopharmacology. 2003 January; 165(3): 216-21. Epub 2002 November 19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12439628
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Benefits from aerobic exercise in patients with major depression: a pilot study. Author(s): Dimeo F, Bauer M, Varahram I, Proest G, Halter U. Source: British Journal of Sports Medicine. 2001 April; 35(2): 114-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11273973
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Benefits from mianserin augmentation of fluoxetine in patients with major depression non-responders to fluoxetine alone. Author(s): Ferreri M, Lavergne F, Berlin I, Payan C, Puech AJ. Source: Acta Psychiatrica Scandinavica. 2001 January; 103(1): 66-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11202131
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Best practices: dissemination of guidelines for the treatment of major depression in a managed behavioral health care network. Author(s): Azocar F, Cuffel BD, Goldman W, McCulloch J. Source: Psychiatric Services (Washington, D.C.). 2001 August; 52(8): 1014-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11474040
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Beta-1-adrenergic receptor gene in major depression: influence on antidepressant treatment response. Author(s): Zill P, Baghai TC, Engel R, Zwanzger P, Schule C, Minov C, Behrens S, Bottlender R, Jager M, Rupprecht R, Moller HJ, Ackenheil M, Bondy B. Source: American Journal of Medical Genetics. 2003 July 1; 120B(1): 85-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12815745
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Beta-thromboglobulin and platelet factor 4 levels in post-myocardial infarction patients with major depression. Author(s): Kuijpers PM, Hamulyak K, Strik JJ, Wellens HJ, Honig A. Source: Psychiatry Research. 2002 March 15; 109(2): 207-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11927146
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Biological nature of depressive symptoms in borderline personality disorder: endocrine comparison to recurrent brief and major depression. Author(s): De la Fuente JM, Bobes J, Vizuete C, Mendlewicz J. Source: Journal of Psychiatric Research. 2002 May-June; 36(3): 137-45. Erratum In: J Psychiatr Res 2002 July-August; 36(4): 267-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886691
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Biophysical changes in normal-appearing white matter and subcortical nuclei in latelife major depression detected using magnetization transfer. Author(s): Kumar A, Gupta RC, Albert Thomas M, Alger J, Wyckoff N, Hwang S. Source: Psychiatry Research. 2004 February 15; 130(2): 131-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15033183
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Blood coagulation and platelet aggregation in major depression. Author(s): Maes M, Van der Planken M, Van Gastel A, Desnyder R. Source: Journal of Affective Disorders. 1996 September 9; 40(1-2): 35-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8882912
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Blunted adenosine A2a receptor function in platelets in patients with major depression. Author(s): Berk M, Plein H, Ferreira D, Jersky B. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 April; 11(2): 183-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11313166
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Blunted prolactin response to D-fenfluramine in post-stroke major depression. Author(s): Morris P, Hopwood M, Maguire K, Norman T, Schweitzer I. Source: Journal of Affective Disorders. 2003 September; 76(1-3): 273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943959
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Body dysmorphic disorder in outpatients with major depression. Author(s): Nierenberg AA, Phillips KA, Petersen TJ, Kelly KE, Alpert JE, Worthington JJ, Tedlow JR, Rosenbaum JF, Fava M. Source: Journal of Affective Disorders. 2002 May; 69(1-3): 141-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12103460
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Borderline personality disorder and age of onset in major depression. Author(s): Rothschild L, Zimmerman M. Source: Journal of Personality Disorders. 2002 April; 16(2): 189-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12004494
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Borderline personality disorder in major depression: symptomatology, temperament, character, differential drug response, and 6-month outcome. Author(s): Joyce PR, Mulder RT, Luty SE, McKenzie JM, Sullivan PF, Cloninger RC. Source: Comprehensive Psychiatry. 2003 January-February; 44(1): 35-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12524634
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Brain activation measured with fMRI during a mental arithmetic task in schizophrenia and major depression. Author(s): Hugdahl K, Rund BR, Lund A, Asbjornsen A, Egeland J, Ersland L, Landro NI, Roness A, Stordal KI, Sundet K, Thomsen T. Source: The American Journal of Psychiatry. 2004 February; 161(2): 286-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14754778
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Brain serotonin2 receptors in major depression: a positron emission tomography study. Author(s): Yatham LN, Liddle PF, Shiah IS, Scarrow G, Lam RW, Adam MJ, Zis AP, Ruth TJ. Source: Archives of General Psychiatry. 2000 September; 57(9): 850-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10986548
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Brain-derived neurotrophic factor: a bridge between major depression and Alzheimer's disease? Author(s): Tsai SJ. Source: Medical Hypotheses. 2003 July; 61(1): 110-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12781652
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Bupropion SR in the naturalistic treatment of elderly patients with major depression. Author(s): Steffens DC, Doraiswamy PM, McQuoid DR. Source: International Journal of Geriatric Psychiatry. 2001 September; 16(9): 862-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11571765
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Catechol-o-methyltransferase (COMT) and proline dehydrogenase (PRODH) mRNAs in the dorsolateral prefrontal cortex in schizophrenia, bipolar disorder, and major depression. Author(s): Tunbridge E, Burnet PW, Sodhi MS, Harrison PJ. Source: Synapse (New York, N.Y.). 2004 February; 51(2): 112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14618678
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Central monoamines and their role in major depression. Author(s): Elhwuegi AS. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2004 May; 28(3): 435-51. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15093950
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Cerebral metabolic correlates as potential predictors of response to anterior cingulotomy for treatment of major depression. Author(s): Dougherty DD, Weiss AP, Cosgrove GR, Alpert NM, Cassem EH, Nierenberg AA, Price BH, Mayberg HS, Fischman AJ, Rauch SL. Source: Journal of Neurosurgery. 2003 December; 99(6): 1010-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14705729
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Cerebrospinal fluid interleukin (IL)-6 in unipolar major depression. Author(s): Carpenter LL, Heninger GR, Malison RT, Tyrka AR, Price LH. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 285-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023509
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Cerebrovascular reactivity in major depression: a pilot study. Author(s): Neu P, Schlattmann P, Schilling A, Hartmann A. Source: Psychosomatic Medicine. 2004 January-February; 66(1): 6-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14747631
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Challenges in preventing relapse in major depression. Report of a National Institute of Mental Health Workshop on state of the science of relapse prevention in major depression. Author(s): Segal ZV, Pearson JL, Thase ME. Source: Journal of Affective Disorders. 2003 November; 77(2): 97-108. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14607387
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Changes in serum concentrations and in cytokine production by blood cell cultures of a patient with major depression--case report. Author(s): Dubas-Slemp H, Kaminska T, Marmurowska-Michalowska H, KandeferSzerszen M. Source: Ann Univ Mariae Curie Sklodowska [med]. 2002; 57(2): 496-504. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12898886
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Childhood and adolescent predictors of major depression in the transition to adulthood. Author(s): Reinherz HZ, Paradis AD, Giaconia RM, Stashwick CK, Fitzmaurice G. Source: The American Journal of Psychiatry. 2003 December; 160(12): 2141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14638584
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Chronic back pain and major depression in the general Canadian population. Author(s): Currie SR, Wang J. Source: Pain. 2004 January; 107(1-2): 54-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14715389
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Citalopram treatment of social anxiety disorder with comorbid major depression. Author(s): Schneier FR, Blanco C, Campeas R, Lewis-Fernandez R, Lin SH, Marshall R, Schmidt AB, Sanchez-Lacay JA, Simpson HB, Liebowitz MR. Source: Depression and Anxiety. 2003; 17(4): 191-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12820174
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Clinical and health services relationships between major depression, depressive symptoms, and general medical illness. Author(s): Katon WJ. Source: Biological Psychiatry. 2003 August 1; 54(3): 216-26. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893098
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Clinical and psychosocial factors associated with the outcome of unipolar major depression: a one year prospective study. Author(s): Ezquiaga E, Garcia-Lopez A, de Dios C, Leiva A, Bravo M, Montejo J. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 63-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023481
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Cluster C personality disorder and recovery from major depression: 24-month prospective follow-up. Author(s): Viinamaki H, Tanskanen A, Koivumaa-Honkanen H, Haatainen K, Honkalampi K, Antikainen R, Hintikka J. Source: Journal of Personality Disorders. 2003 August; 17(4): 341-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14521182
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Cognitive functioning in young and middle-aged unmedicated out-patients with major depression: testing the effort and cognitive speed hypotheses. Author(s): Den Hartog HM, Derix MM, Van Bemmel AL, Kremer B, Jolles J. Source: Psychological Medicine. 2003 November; 33(8): 1443-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672253
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Combined DEX/CRH test among Japanese patients with major depression. Author(s): Kunugi H, Urushibara T, Nanko S. Source: Journal of Psychiatric Research. 2004 March-April; 38(2): 123-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757325
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Comparative effects of mirtazapine and fluoxetine on sleep physiology measures in patients with major depression and insomnia. Author(s): Winokur A, DeMartinis NA 3rd, McNally DP, Gary EM, Cormier JL, Gary KA. Source: The Journal of Clinical Psychiatry. 2003 October; 64(10): 1224-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14658972
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Comparison of response to fluvoxamine in nondemented elderly compared to younger patients affected by major depression. Author(s): Zanardi R, Cusin C, Rossini D, De Ronchi D, Serretti A. Source: Journal of Clinical Psychopharmacology. 2003 December; 23(6): 535-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14624182
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Comparison of the suicidal behavior of adolescent inpatients with borderline personality disorder and major depression. Author(s): Horesh N, Orbach I, Gothelf D, Efrati M, Apter A. Source: The Journal of Nervous and Mental Disease. 2003 September; 191(9): 582-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504567
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Cost effectiveness of representatives of three classes of antidepressants used in major depression in the UK. Author(s): Lenox-Smith A, Conway P, Knight C. Source: Pharmacoeconomics. 2004; 22(5): 311-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15061681
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CRH, stress, and major depression: a psychobiological interplay. Author(s): Claes SJ. Source: Vitam Horm. 2004; 69: 117-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15196881
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Decrease of the D4 dopamine receptor messenger RNA expression in lymphocytes from patients with major depression. Author(s): Rocc P, De Leo C, Eva C, Marchiaro L, Milani AM, Musso R, Ravizza L, Zanalda E, Bogetto F. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1155-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452539
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Decreased cerebrospinal fluid neuropeptide Y (NPY) in patients with treatment refractory unipolar major depression: preliminary evidence for association with preproNPY gene polymorphism. Author(s): Heilig M, Zachrisson O, Thorsell A, Ehnvall A, Mottagui-Tabar S, Sjogren M, Asberg M, Ekman R, Wahlestedt C, Agren H. Source: Journal of Psychiatric Research. 2004 March-April; 38(2): 113-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757324
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Decreased thyrotropin-releasing hormone gene expression in the hypothalamic paraventricular nucleus of patients with major depression. Author(s): Alkemade A, Unmehopa UA, Brouwer JP, Hoogendijk WJ, Wiersinga WM, Swaab DF, Fliers E. Source: Molecular Psychiatry. 2003 October; 8(10): 838-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14515134
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Defense styles, impulsivity and suicide attempts in major depression. Author(s): Corruble E, Hatem N, Damy C, Falissard B, Guelfi JD, Reynaud M, Hardy P. Source: Psychopathology. 2003 November-December; 36(6): 279-84. Epub 2003 November 27. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14646450
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Deficits in hippocampal and anterior cingulate functioning during verbal declarative memory encoding in midlife major depression. Author(s): Bremner JD, Vythilingam M, Vermetten E, Vaccarino V, Charney DS. Source: The American Journal of Psychiatry. 2004 April; 161(4): 637-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056509
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Demonstration of the efficacy and safety of a novel substance P (NK1) receptor antagonist in major depression. Author(s): Kramer MS, Winokur A, Kelsey J, Preskorn SH, Rothschild AJ, Snavely D, Ghosh K, Ball WA, Reines SA, Munjack D, Apter JT, Cunningham L, Kling M, Bari M, Getson A, Lee Y. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 February; 29(2): 385-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14666114
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Depressed new neurons--adult hippocampal neurogenesis and a cellular plasticity hypothesis of major depression. Author(s): Kempermann G, Kronenberg G. Source: Biological Psychiatry. 2003 September 1; 54(5): 499-503. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946878
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Depression status, medical comorbidity and resource costs. Evidence from an international study of major depression in primary care (LIDO). Author(s): Chisholm D, Diehr P, Knapp M, Patrick D, Treglia M, Simon G; LIDO Group. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2003 August; 183: 121-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12893665
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Depression-free days as a summary measure of the temporal pattern of response and remission in the treatment of major depression: a comparison of venlafaxine, selective serotonin reuptake inhibitors, and placebo. Author(s): Mallick R, Chen J, Entsuah AR, Schatzberg AF. Source: The Journal of Clinical Psychiatry. 2003 March; 64(3): 321-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716275
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Development of a brief screening interview for adjustment disorders and major depression in patients with cancer. Author(s): Akizuki N, Akechi T, Nakanishi T, Yoshikawa E, Okamura M, Nakano T, Murakami Y, Uchitomi Y. Source: Cancer. 2003 May 15; 97(10): 2605-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12733160
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Dexamethasone suppression test findings in subjects with personality disorders: associations with posttraumatic stress disorder and major depression. Author(s): Grossman R, Yehuda R, New A, Schmeidler J, Silverman J, Mitropoulou V, Sta Maria N, Golier J, Siever L. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1291-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12832244
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Diagnosing major depression in medical outpatients: acceptability of telephone interviews. Author(s): Allen K, Cull A, Sharpe M. Source: Journal of Psychosomatic Research. 2003 October; 55(4): 385-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507551
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Differential expression of pentraxin 3 in fibroblasts from patients with major depression. Author(s): Shelton RC, Liang S, Liang P, Chakrabarti A, Manier DH, Sulser F. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 January; 29(1): 126-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603263
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Differential responses to psychotherapy versus pharmacotherapy in patients with chronic forms of major depression and childhood trauma. Author(s): 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. Source: Proceedings of the National Academy of Sciences of the United States of America. 2003 November 25; 100(24): 14293-6. Epub 2003 Nov 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14615578
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Differentiation of geriatric major depression from Alzheimer's disease with CSF tau protein phosphorylated at threonine 231. Author(s): Buerger K, Zinkowski R, Teipel SJ, Arai H, DeBernardis J, Kerkman D, McCulloch C, Padberg F, Faltraco F, Goernitz A, Tapiola T, Rapoport SI, Pirttila T, Moller HJ, Hampel H. Source: The American Journal of Psychiatry. 2003 February; 160(2): 376-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12562590
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Direct comparison of total sleep deprivation and late partial sleep deprivation in the treatment of major depression. Author(s): Giedke H, Klingberg S, Schwarzler F, Schweinsberg M. Source: Journal of Affective Disorders. 2003 September; 76(1-3): 85-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943937
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Distinguishing generalized anxiety disorder from major depression: prevalence and impairment from current pure and comorbid disorders in the US and Ontario. Author(s): Kessler RC, Berglund PA, Dewit DJ, Ustun TB, Wang PS, Wittchen HU. Source: International Journal of Methods in Psychiatric Research. 2002; 11(3): 99-111. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12459823
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Diurnal rhythms of free estradiol and cortisol during the normal menstrual cycle in women with major depression. Author(s): Bao AM, Ji YF, Van Someren EJ, Hofman MA, Liu RY, Zhou JN. Source: Hormones and Behavior. 2004 February; 45(2): 93-102. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15019795
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Double-blind comparison of fluoxetine and nortriptyline in the treatment of moderate to severe major depression. Author(s): Akhondzadeh S, Faraji H, Sadeghi M, Afkham K, Fakhrzadeh H, Kamalipour A. Source: Journal of Clinical Pharmacy and Therapeutics. 2003 October; 28(5): 379-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632962
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Early improvement under mirtazapine and paroxetine predicts later stable response and remission with high sensitivity in patients with major depression. Author(s): Szegedi A, Muller MJ, Anghelescu I, Klawe C, Kohnen R, Benkert O. Source: The Journal of Clinical Psychiatry. 2003 April; 64(4): 413-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12716243
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Early life menstrual characteristics and pregnancy experiences among women with and without major depression: the Harvard study of moods and cycles. Author(s): Harlow BL, Cohen LS, Otto MW, Spiegelman D, Cramer DW. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 167-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023491
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ECT in the management of major depression: implications of recent research. Author(s): Andrade C, Nelson AI, Fink M. Source: World J Biol Psychiatry. 2003 July; 4(3): 139-40; Author Reply 140-1. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872209
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Effect of major depression on cognitive performance among treatment-seeking adolescents. Author(s): Korhonen V, Laukkanen E, Antikainen R, Peiponen S, Lehtonen J, Viinamaki H. Source: Nordic Journal of Psychiatry. 2002; 56(3): 187-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12079570
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Effect on body weight of bupropion sustained-release in patients with major depression treated for 52 weeks. Author(s): Croft H, Houser TL, Jamerson BD, Leadbetter R, Bolden-Watson C, Donahue R, Metz A. Source: Clinical Therapeutics. 2002 April; 24(4): 662-72. Erratum In: Clin Ther. 2002 September; 24(9): 1481. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12017410
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Effects of glucocorticoids on declarative memory function in major depression. Author(s): Bremner JD, Vythilingam M, Vermetten E, Anderson G, Newcomer JW, Charney DS. Source: Biological Psychiatry. 2004 April 15; 55(8): 811-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15050862
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Effects of mirtazapine on sleep polygraphic variables in major depression. Author(s): Schittecatte M, Dumont F, Machowski R, Cornil C, Lavergne F, Wilmotte J. Source: Neuropsychobiology. 2002; 46(4): 197-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12566938
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Effects of rapid tryptophan depletion on mood and urge to drink in patients with comorbid major depression and alcohol dependence. Author(s): Pierucci-Lagha A, Feinn R, Modesto-Lowe V, Swift R, Nellissery M, Covault J, Kranzler HR. Source: Psychopharmacology. 2004 January; 171(3): 340-8. Epub 2003 September 10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13680073
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Efficacy and safety of venlafaxine ER vs. amitriptyline ER in patients with major depression of moderate severity. Author(s): Sauer H, Huppertz-Helmhold S, Dierkes W. Source: Pharmacopsychiatry. 2003 September; 36(5): 169-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14571350
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Efficacy and tolerability of oral and intramuscular S-adenosyl-L-methionine 1,4butanedisulfonate (SAMe) in the treatment of major depression: comparison with imipramine in 2 multicenter studies. Author(s): Delle Chiaie R, Pancheri P, Scapicchio P. Source: The American Journal of Clinical Nutrition. 2002 November; 76(5): 1172S-6S. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12418499
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Efficacy of venlafaxine in major depression resistant to selective serotonin reuptake inhibitors. Author(s): Saiz-Ruiz J, Ibanez A, Diaz-Marsa M, Arias F, Padin J, Martin-Carrasco M, Montes JM, Ferrando L, Carrasco JL, Martin-Ballesteros E, Jorda L, Chamorro L. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 October; 26(6): 1129-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452535
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Electroconvulsive therapy for patients with major depression and probable Lewy body dementia. Author(s): Rasmussen KG Jr, Russell JC, Kung S, Rummans TA, Rae-Stuart E, O'Connor MK. Source: The Journal of Ect. 2003 June; 19(2): 103-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12792460
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Elevated agonist binding to alpha2-adrenoceptors in the locus coeruleus in major depression. Author(s): Ordway GA, Schenk J, Stockmeier CA, May W, Klimek V. Source: Biological Psychiatry. 2003 February 15; 53(4): 315-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586450
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Elevated neuron number in the limbic thalamus in major depression. Author(s): Young KA, Holcomb LA, Yazdani U, Hicks PB, German DC. Source: The American Journal of Psychiatry. 2004 July; 161(7): 1270-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15229061
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Elevated platelet vesicular monoamine transporter density in untreated patients diagnosed with major depression. Author(s): Zucker M, Aviv A, Shelef A, Weizman A, Rehavi M. Source: Psychiatry Research. 2002 November 15; 112(3): 251-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12450634
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Epidemiology of major depression in a predominantly rural health region. Author(s): Patten SB, Stuart HL, Russell ML, Maxwell CJ, Arboleda-Florez J. Source: Social Psychiatry and Psychiatric Epidemiology. 2003 July; 38(7): 360-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12861441
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Evaluating the state dependency of the Temperament and Character Inventory dimensions in patients with major depression: a methodological contribution. Author(s): Hirano S, Sato T, Narita T, Kusunoki K, Ozaki N, Kimura S, Takahashi T, Sakado K, Uehara T. Source: Journal of Affective Disorders. 2002 May; 69(1-3): 31-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12103449
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Evidence that the SSRI dose response in treating major depression should be reassessed: a meta-analysis. Author(s): Baker CB, Tweedie R, Duval S, Woods SW. Source: Depression and Anxiety. 2003; 17(1): 1-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12577272
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Expression of cAMP response element-binding protein in major depression before and after antidepressant treatment. Author(s): Lai IC, Hong CJ, Tsai SJ. Source: Neuropsychobiology. 2003; 48(4): 182-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14673215
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Factor structure of the hospital anxiety and depression scale in older patients with major depression. Author(s): Flint AJ, Rifat SL. Source: International Journal of Geriatric Psychiatry. 2002 February; 17(2): 117-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11813272
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Factor validity of the temperament and character inventory in patients with major depression. Author(s): Sato T, Narita T, Hirano S, Kusunoki K, Goto M, Sakado K, Uehara T. Source: Comprehensive Psychiatry. 2001 July-August; 42(4): 337-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11458309
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Factors affecting return of symptoms 1 year after treatment in a 62-week controlled study of fluoxetine in major depression. Author(s): Reimherr FW, Strong RE, Marchant BK, Hedges DW, Wender PH. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 22: 16-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11599643
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Factors associated with being granted a pension among psychiatric outpatients with major depression. Author(s): Sorvaniemi M, Helenius H, Salokangas RK. Source: Journal of Affective Disorders. 2003 June; 75(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12781349
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Factors associated with outcome in major depression: a 6-month prospective study. Author(s): Ezquiaga E, Garcia A, Bravo F, Pallares T. Source: Social Psychiatry and Psychiatric Epidemiology. 1998 November; 33(11): 552-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9803823
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Factors associated with symptomatic improvement and recovery from major depression in primary care patients. Author(s): Brown C, Schulberg HC, Prigerson HG. Source: General Hospital Psychiatry. 2000 July-August; 22(4): 242-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10936631
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False positives, false negatives, and the validity of the diagnosis of major depression in primary care. Author(s): Klinkman MS, Coyne JC, Gallo S, Schwenk TL. Source: Archives of Family Medicine. 1998 September-October; 7(5): 451-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9755738
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First-episode major depression in adolescents. Affective, cognitive and endocrine characteristics of risk status and predictors of onset. Author(s): Goodyer IM, Herbert J, Tamplin A, Altham PM. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2000 February; 176: 142-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10755051
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Fluoxetine and sertraline dosages in major depression. Author(s): Cantrell R, Gillespie W, Altshuler L. Source: Depression and Anxiety. 1999; 9(2): 78-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10207663
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Fluoxetine in adolescents with major depression and an alcohol use disorder: an open-label trial. Author(s): Cornelius JR, Bukstein OG, Birmaher B, Salloum IM, Lynch K, Pollock NK, Gershon S, Clark D. Source: Addictive Behaviors. 2001 September-October; 26(5): 735-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11676382
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Fluoxetine versus amitriptyline in the treatment of major depression with associated anxiety (anxious depression): a double-blind comparison. Author(s): Versiani M, Ontiveros A, Mazzotti G, Ospina J, Davila J, Mata S, Pacheco A, Plewes J, Tamura R, Palacios M. Source: International Clinical Psychopharmacology. 1999 November; 14(6): 321-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10565798
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Frontal cerebral perfusion after antidepressant drug treatment versus ECT in elderly patients with major depression: a 12-month follow-up control study. Author(s): Navarro V, Gasto C, Lomena F, Mateos JJ, Portella MJ, Massana G, Bernardo M, Marcos T. Source: The Journal of Clinical Psychiatry. 2004 May; 65(5): 656-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15163251
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Frontal cerebral perfusion dysfunction in elderly late-onset major depression assessed by 99MTC-HMPAO SPECT. Author(s): Navarro V, Gasto C, Lomena F, Mateos JJ, Marcos T. Source: Neuroimage. 2001 July; 14(1 Pt 1): 202-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11525329
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Frontal lobe dysfunction in obsessive-compulsive disorder and major depression: a clinical-neuropsychological study. Author(s): Cavedini P, Ferri S, Scarone S, Bellodi L. Source: Psychiatry Research. 1998 March 20; 78(1-2): 21-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579699
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Frontal systems impairment in major depression. Author(s): Royall DR. Source: Semin Clin Neuropsychiatry. 1999 January; 4(1): 13-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10229789
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Frontal white matter biochemical abnormalities in late-life major depression detected with proton magnetic resonance spectroscopy. Author(s): Kumar A, Thomas A, Lavretsky H, Yue K, Huda A, Curran J, Venkatraman T, Estanol L, Mintz J, Mega M, Toga A. Source: The American Journal of Psychiatry. 2002 April; 159(4): 630-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11925302
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Frontostriatal deficits in unipolar major depression. Author(s): Rogers MA, Bradshaw JL, Pantelis C, Phillips JG. Source: Brain Research Bulletin. 1998 November 1; 47(4): 297-310. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9886780
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Functional anatomical abnormalities in limbic and prefrontal cortical structures in major depression. Author(s): Drevets WC. Source: Prog Brain Res. 2000; 126: 413-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11105660
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Functional brain circuits in major depression and remission. Author(s): Sackeim HA. Source: Archives of General Psychiatry. 2001 July; 58(7): 649-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11448370
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Gabapentin leads to remission of somatoform pain disorder with major depression. Author(s): Maurer I, Volz HP, Sauer H. Source: Pharmacopsychiatry. 1999 November; 32(6): 255-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10599936
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Gender differences in severity, symptomatology and distribution of melancholia in major depression. Author(s): Hildebrandt MG, Stage KB, Kragh-Soerensen P; Danish University Antidepressant Group. Source: Psychopathology. 2003 July-August; 36(4): 204-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504455
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Gender differences in the genetic epidemiology of major depression. Author(s): Kendler KS. Source: J Gend Specif Med. 1998 October-November; 1(2): 28-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11281009
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Gene-based SNP genetic association study of the corticotropin-releasing hormone receptor-2 (CRHR2) in major depression. Author(s): Villafuerte SM, Del-Favero J, Adolfsson R, Souery D, Massat I, Mendlewicz J, Van Broeckhoven C, Claes S. Source: American Journal of Medical Genetics. 2002 March 8; 114(2): 222-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857585
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General medical and specialty mental health service use for major depression. Author(s): Burns BJ, Ryan Wagner H, Gaynes BN, Wells KB, Schulberg HC. Source: International Journal of Psychiatry in Medicine. 2000; 30(2): 127-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11001277
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Genetic epidemiology of major depression: review and meta-analysis. Author(s): Sullivan PF, Neale MC, Kendler KS. Source: The American Journal of Psychiatry. 2000 October; 157(10): 1552-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11007705
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Genetic linkage of region containing the CREB1 gene to depressive disorders in women from families with recurrent, early-onset, major depression. Author(s): Zubenko GS, Hughes HB 3rd, Maher BS, Stiffler JS, Zubenko WN, Marazita ML. Source: American Journal of Medical Genetics. 2002 December 8; 114(8): 980-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12457397
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Genetic polymorphism at the CLOCK gene locus and major depression. Author(s): Desan PH, Oren DA, Malison R, Price LH, Rosenbaum J, Smoller J, Charney DS, Gelernter J. Source: American Journal of Medical Genetics. 2000 June 12; 96(3): 418-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10898925
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Genetic risk factors for major depression in men and women: similar or different heritabilities and same or partly distinct genes? Author(s): Kendler KS, Gardner CO, Neale MC, Prescott CA. Source: Psychological Medicine. 2001 May; 31(4): 605-16. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11352363
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Genetic risk, number of previous depressive episodes, and stressful life events in predicting onset of major depression. Author(s): Kendler KS, Thornton LM, Gardner CO. Source: The American Journal of Psychiatry. 2001 April; 158(4): 582-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11282692
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Genetic segregation analysis of alcohol and other substance-use disorders in families with recurrent, early-onset major depression. Author(s): Maher BS, Marazita ML, Zubenko WN, Kaplan BB, Zubenko GS. Source: The American Journal of Drug and Alcohol Abuse. 2002 November; 28(4): 71131. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12492266
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Genetic segregation analysis of recurrent, early-onset major depression: evidence for single major locus transmission. Author(s): Maher BS, Marazita ML, Zubenko WN, Spiker DG, Giles DE, Kaplan BB, Zubenko GS. Source: American Journal of Medical Genetics. 2002 March 8; 114(2): 214-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11857584
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Genetic variation in the 5-HT5A receptor gene in patients with bipolar disorder and major depression. Author(s): Arias B, Collier DA, Gasto C, Pintor L, Gutierrez B, Valles V, Fananas L. Source: Neuroscience Letters. 2001 May 4; 303(2): 111-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11311505
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Genome survey for susceptibility loci for recurrent, early-onset major depression: results at 10cM resolution. Author(s): Zubenko GS, Hughes HB, Stiffler JS, Zubenko WN, Kaplan BB. Source: American Journal of Medical Genetics. 2002 May 8; 114(4): 413-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11992563
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Genome-wide linkage survey for genetic loci that influence the development of depressive disorders in families with recurrent, early-onset, major depression. Author(s): Zubenko GS, Maher B, Hughes HB 3rd, Zubenko WN, Stiffler JS, Kaplan BB, Marazita ML. Source: American Journal of Medical Genetics. 2003 November 15; 123B(1): 1-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14582139
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Genotype-controlled analysis of plasma dopamine beta-hydroxylase activity in psychotic unipolar major depression. Author(s): Cubells JF, Price LH, Meyers BS, Anderson GM, Zabetian CP, Alexopoulos GS, Nelson JC, Sanacora G, Kirwin P, Carpenter L, Malison RT, Gelernter J. Source: Biological Psychiatry. 2002 March 1; 51(5): 358-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904129
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Global functioning of inpatients with obsessive-compulsive disorder, schizophrenia, and major depression. Author(s): Calvocoressi L, Libman D, Vegso SJ, McDougle CJ, Price LH. Source: Psychiatric Services (Washington, D.C.). 1998 March; 49(3): 379-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9525801
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Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Author(s): Pariante CM, Miller AH. Source: Biological Psychiatry. 2001 March 1; 49(5): 391-404. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11274650
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Glycemic control and major depression in patients with type 1 and type 2 diabetes mellitus. Author(s): de Groot M, Jacobson AM, Samson JA, Welch G. Source: Journal of Psychosomatic Research. 1999 May; 46(5): 425-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10404477
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Group interpersonal psychotherapy for patients with major depression disorder pilot study. Author(s): Levkovitz Y, Shahar G, Native G, Hirsfeld E, Treves I, Krieger I, Fennig S. Source: Journal of Affective Disorders. 2000 November; 60(3): 191-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074107
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Headache and major depression: is the association specific to migraine? Author(s): Breslau N, Schultz LR, Stewart WF, Lipton RB, Lucia VC, Welch KM. Source: Neurology. 2000 January 25; 54(2): 308-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10668688
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Health-related quality of life among patients with major depression. Author(s): Saarijarvi S, Salminen JK, Toikka T, Raitasalo R. Source: Nordic Journal of Psychiatry. 2002; 56(4): 261-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12470316
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Heart rate and blood pressure in panic disorder, major depression, and comorbid panic disorder with major depression. Author(s): Townsend MH, Bologna NB, Barbee JG. Source: Psychiatry Research. 1998 June 15; 79(2): 187-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9705056
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Heart rate variability in patients with major depression. Author(s): Nahshoni E, Aravot D, Aizenberg D, Sigler M, Zalsman G, Strasberg B, Imbar S, Adler E, Weizman A. Source: Psychosomatics. 2004 March-April; 45(2): 129-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15016926
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High relapse rate after discontinuation of adjunctive medication for elderly patients with recurrent major depression. Author(s): Reynolds CF 3rd, Frank E, Perel JM, Mazumdar S, Dew MA, Begley A, Houck PR, Hall M, Mulsant B, Shear MK, Miller MD, Cornes C, Kupfer DJ. Source: The American Journal of Psychiatry. 1996 November; 153(11): 1418-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8890674
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Hippocampal apoptosis in major depression is a minor event and absent from subareas at risk for glucocorticoid overexposure. Author(s): Lucassen PJ, Muller MB, Holsboer F, Bauer J, Holtrop A, Wouda J, Hoogendijk WJ, De Kloet ER, Swaab DF. Source: American Journal of Pathology. 2001 February; 158(2): 453-68. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11159183
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Hippocampal atrophy in major depression: a result of depression-induced neurotoxicity? Author(s): Sheline YI. Source: Molecular Psychiatry. 1996 September; 1(4): 298-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9118352
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Hippocampal changes in patients with a first episode of major depression. Author(s): Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M, Leinsinger G, Bottlender R, Hahn K, Moller HJ. Source: The American Journal of Psychiatry. 2002 July; 159(7): 1112-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12091188
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Hippocampal synaptic pathology in schizophrenia, bipolar disorder and major depression: a study of complexin mRNAs. Author(s): Eastwood SL, Harrison PJ. Source: Molecular Psychiatry. 2000 July; 5(4): 425-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10889554
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Hippocampal volume in primary unipolar major depression: a magnetic resonance imaging study. Author(s): Vakili K, Pillay SS, Lafer B, Fava M, Renshaw PF, Bonello-Cintron CM, Yurgelun-Todd DA. Source: Biological Psychiatry. 2000 June 15; 47(12): 1087-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862809
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Hippocampal volume reduction in major depression. Author(s): Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS. Source: The American Journal of Psychiatry. 2000 January; 157(1): 115-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10618023
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Histopathology of the prefrontal cortex in major depression: what does it tell us about dysfunctional monoaminergic circuits? Author(s): Rajkowska G. Source: Prog Brain Res. 2000; 126: 397-412. Review. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11105659
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Hormonal evidence for altered responsiveness to social stress in major depression. Author(s): Young EA, Lopez JF, Murphy-Weinberg V, Watson SJ, Akil H. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2000 October; 23(4): 411-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10989268
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How does dysfunctional thinking decrease during recovery from major depression? Author(s): Sheppard LC, Teasdale JD. Source: Journal of Abnormal Psychology. 2004 February; 113(1): 64-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14992658
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How does the threshold score to enter a major depression trial influence the size of the available patient population for study? Author(s): Hawley CJ, Gale TM, Sivakumaran T. Source: Journal of Affective Disorders. 2002 September; 71(1-3): 181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12167514
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How long should the lithium augmentation strategy be maintained? A 1-year followup of a placebo-controlled study in unipolar refractory major depression. Author(s): Bschor T, Berghofer A, Strohle A, Kunz D, Adli M, Muller-Oerlinghausen B, Bauer M. Source: Journal of Clinical Psychopharmacology. 2002 August; 22(4): 427-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172345
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HPA axis dysfunction in major depression: relationship to 5-HT(1A) receptor activity. Author(s): Pitchot W, Herrera C, Ansseau M. Source: Neuropsychobiology. 2001; 44(2): 74-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11490174
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Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene. Author(s): Baghai TC, Schule C, Zwanzger P, Minov C, Zill P, Ella R, Eser D, Oezer S, Bondy B, Rupprecht R. Source: Neuroscience Letters. 2002 August 16; 328(3): 299-303. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12147330
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Hypothalamic-pituitary-thyroid system activity during lithium augmentation therapy in patients with unipolar major depression. Author(s): Bschor T, Baethge C, Adli M, Lewitzka U, Eichmann U, Bauer M. Source: Journal of Psychiatry & Neuroscience : Jpn. 2003 May; 28(3): 210-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12790161
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Immune dysregulation in major depression: a critical review of existing evidence. Author(s): Kronfol Z. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2002 December; 5(4): 333-43. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12466033
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Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. Author(s): Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD, Sequeira A, Kushwaha N, Morris SJ, Basak A, Ou XM, Albert PR. Source: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience. 2003 September 24; 23(25): 8788-99. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14507979
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Impairment across executive functions in recurrent major depression. Author(s): Stordal KI, Lundervold AJ, Egeland J, Mykletun A, Asbjornsen A, Landro NI, Roness A, Rund BR, Sundet K, Oedegaard KJ, Lund A. Source: Nordic Journal of Psychiatry. 2004; 58(1): 41-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985153
Studies
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Incidence and clinical course of major depression in patients with chronic hepatitis type C undergoing interferon-alpha therapy: a prospective study. Author(s): Horikawa N, Yamazaki T, Izumi N, Uchihara M. Source: General Hospital Psychiatry. 2003 January-February; 25(1): 34-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12583926
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Increased amygdala: hippocampal volume ratios associated with severity of anxiety in pediatric major depression. Author(s): MacMillan S, Szeszko PR, Moore GJ, Madden R, Lorch E, Ivey J, Banerjee SP, Rosenberg DR. Source: Journal of Child and Adolescent Psychopharmacology. 2003 Spring; 13(1): 65-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12804127
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Increased medial thalamic choline found in pediatric patients with obsessivecompulsive disorder versus major depression or healthy control subjects: a magnetic resonance spectroscopy study. Author(s): Smith EA, Russell A, Lorch E, Banerjee SP, Rose M, Ivey J, Bhandari R, Moore GJ, Rosenberg DR. Source: Biological Psychiatry. 2003 December 15; 54(12): 1399-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14675804
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Infection, treatment and immune response in patients with bipolar disorder versus patients with major depression, schizophrenia or healthy controls. Author(s): Hinze-Selch D. Source: Bipolar Disorders. 2002; 4 Suppl 1: 81-3. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479687
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Influence of gender and hemispheric lateralization on heat pain perception in major depression. Author(s): Bar KJ, Greiner W, Letsch A, Kobele R, Sauer H. Source: Journal of Psychiatric Research. 2003 July-August; 37(4): 345-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12765857
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Insight into illness in patients with mania, mixed mania, bipolar depression and major depression with psychotic features. Author(s): Dell'Osso L, Pini S, Cassano GB, Mastrocinque C, Seckinger RA, Saettoni M, Papasogli A, Yale SA, Amador XF. Source: Bipolar Disorders. 2002 October; 4(5): 315-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12479664
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Instability of symptoms in recurrent major depression: a prospective study. Author(s): Oquendo MA, Barrera A, Ellis SP, Li S, Burke AK, Grunebaum M, Endicott J, Mann JJ. Source: The American Journal of Psychiatry. 2004 February; 161(2): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14754774
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International differences in major depression prevalence: what do they mean? Author(s): Patten SB. Source: Journal of Clinical Epidemiology. 2003 August; 56(8): 711-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12954461
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Interpersonal dependence and major depression: aetiological inter-relationship and gender differences. Author(s): Sanathara VA, Gardner CO, Prescott CA, Kendler KS. Source: Psychological Medicine. 2003 July; 33(5): 927-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12877407
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Intra-episode hypomanic symptoms during major depression and their correlates. Author(s): Benazzi F. Source: Psychiatry and Clinical Neurosciences. 2004 June; 58(3): 289-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15149296
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Investigation of m1/m4 muscarinic receptors in the anterior cingulate cortex in schizophrenia, bipolar disorder, and major depression disorder. Author(s): Katerina Z, Andrew K, Filomena M, Xu-Feng H. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 March; 29(3): 619-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14694353
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Is the Beck Depression Inventory suitable for screening major depression in different phases of the disease? Author(s): Viinamaki H, Tanskanen A, Honkalampi K, Koivumaa-Honkanen H, Haatainen K, Kaustio O, Hintikka J. Source: Nordic Journal of Psychiatry. 2004; 58(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14985154
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Is the female preponderance in major depression secondary to a gender difference in specific anxiety disorders? Author(s): Parker G, Hadzi-Pavlovic D. Source: Psychological Medicine. 2004 April; 34(3): 461-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15259831
Studies
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Is there a SSRI dose response in treating major depression? The case for re-analysis of current data and for enhancing future study design. Author(s): Baker CB, Woods SW. Source: Depression and Anxiety. 2003; 17(1): 10-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12577273
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Is there evidence for a male depressive syndrome in inpatients with major depression? Author(s): Moller-Leimkuhler AM, Bottlender R, Strauss A, Rutz W. Source: Journal of Affective Disorders. 2004 May; 80(1): 87-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15094262
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It's about timing and change: pubertal transition effects on symptoms of major depression among African American youths. Author(s): Ge X, Kim IJ, Brody GH, Conger RD, Simons RL, Gibbons FX, Cutrona CE. Source: Developmental Psychology. 2003 May; 39(3): 430-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12760513
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Juvenile-onset major depression includes childhood- and adolescent-onset depression and may be heterogeneous. Author(s): Weissman MM. Source: Archives of General Psychiatry. 2002 March; 59(3): 223-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11879159
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Larger amygdala volumes in first depressive episode as compared to recurrent major depression and healthy control subjects. Author(s): Frodl T, Meisenzahl EM, Zetzsche T, Born C, Jager M, Groll C, Bottlender R, Leinsinger G, Moller HJ. Source: Biological Psychiatry. 2003 February 15; 53(4): 338-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586453
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Late onset dysthymic disorder and major depression differ from early onset dysthymic disorder and major depression in elderly outpatients. Author(s): Devanand DP, Adorno E, Cheng J, Burt T, Pelton GH, Roose SP, Sackeim HA. Source: Journal of Affective Disorders. 2004 March; 78(3): 259-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013252
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Learning and memory in bipolar and unipolar major depression: effects of aging. Author(s): Burt T, Prudic J, Peyser S, Clark J, Sackeim HA. Source: Neuropsychiatry, Neuropsychology, and Behavioral Neurology. 2000 October; 13(4): 246-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11186160
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Levels and variability of daily life cortisol secretion in major depression. Author(s): Peeters F, Nicolson NA, Berkhof J. Source: Psychiatry Research. 2004 April 15; 126(1): 1-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15081622
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Levels of disability in major depression: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS). Author(s): Kruijshaar ME, Hoeymans N, Bijl RV, Spijker J, Essink-Bot ML. Source: Journal of Affective Disorders. 2003 October; 77(1): 53-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14550935
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Levels of serum total cholesterol and LDL-cholesterol in patients with major depression in acute period and remission. Author(s): Rabe-Jablonska J, Poprawska I. Source: Medical Science Monitor : International Medical Journal of Experimental and Clinical Research. 2000 May-June; 6(3): 539-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11208367
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Life event dimensions of loss, humiliation, entrapment, and danger in the prediction of onsets of major depression and generalized anxiety. Author(s): Kendler KS, Hettema JM, Butera F, Gardner CO, Prescott CA. Source: Archives of General Psychiatry. 2003 August; 60(8): 789-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12912762
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Life events, number of social relationships, and twelve-month naturalistic course of major depression in a community sample of women. Author(s): Wildes JE, Harkness KL, Simons AD. Source: Depression and Anxiety. 2002; 16(3): 104-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12415534
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Life stress and the symptoms of major depression. Author(s): Monroe SM, Harkness K, Simons AD, Thase ME. Source: The Journal of Nervous and Mental Disease. 2001 March; 189(3): 168-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11277353
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Limbic-frontal circuitry in major depression: a path modeling metanalysis. Author(s): Seminowicz DA, Mayberg HS, McIntosh AR, Goldapple K, Kennedy S, Segal Z, Rafi-Tari S. Source: Neuroimage. 2004 May; 22(1): 409-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15110034
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Lithium augmentation increases post-dexamethasone cortisol in the dexamethasone suppression test in unipolar major depression. Author(s): Bschor T, Baethge C, Adli M, Eichmann U, Ising M, Uhr M, MullerOerlinghausen B, Bauer M. Source: Depression and Anxiety. 2003; 17(1): 43-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12577277
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Long-lasting cognitive impairment in unipolar major depression: a 6-month followup study. Author(s): Hammar A, Lund A, Hugdahl K. Source: Psychiatry Research. 2003 May 30; 118(2): 189-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12798984
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Long-term efficacy and therapeutic drug monitoring of sertraline in major depression. Author(s): Mauri MC, Fiorentini A, Cerveri G, Volonteri LS, Regispani F, Malvini L, Boscati L, Baido RL, Invernizzi G. Source: Human Psychopharmacology. 2003 July; 18(5): 385-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12858326
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Low-dose dexamethasone challenge in women with atypical major depression: pilot study. Author(s): Levitan RD, Vaccarino FJ, Brown GM, Kennedy SH. Source: Journal of Psychiatry & Neuroscience : Jpn. 2002 January; 27(1): 47-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11836976
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Lowered serum n-3 polyunsaturated fatty acid (PUFA) levels predict the occurrence of postpartum depression: further evidence that lowered n-PUFAs are related to major depression. Author(s): De Vriese SR, Christophe AB, Maes M. Source: Life Sciences. 2003 November 7; 73(25): 3181-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14561523
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Major depression and conduct disorder in youth: associations with parental psychopathology and parent-child conflict. Author(s): Marmorstein NR, Iacono WG. Source: Journal of Child Psychology and Psychiatry, and Allied Disciplines. 2004 February; 45(2): 377-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14982250
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Major depression and mental health care utilization in Canada: 1994 to 2000. Author(s): Patten SB. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2004 May; 49(5): 303-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15198466
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Major depression due to primary hyperparathyroidism: a frequent and correctable disorder. Author(s): Wilhelm SM, Lee J, Prinz RA. Source: The American Surgeon. 2004 February; 70(2): 175-9; Discussion 179-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15011923
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Major depression following traumatic brain injury. Author(s): Jorge RE, Robinson RG, Moser D, Tateno A, Crespo-Facorro B, Arndt S. Source: Archives of General Psychiatry. 2004 January; 61(1): 42-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14706943
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Major depression in outpatients attending a regional cancer centre: screening and unmet treatment needs. Author(s): Sharpe M, Strong V, Allen K, Rush R, Postma K, Tulloh A, Maguire P, House A, Ramirez A, Cull A. Source: British Journal of Cancer. 2004 January 26; 90(2): 314-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735170
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Major depression, adjustment disorders, and post-traumatic stress disorder in terminally ill cancer patients: associated and predictive factors. Author(s): Akechi T, Okuyama T, Sugawara Y, Nakano T, Shima Y, Uchitomi Y. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 2004 May 15; 22(10): 1957-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15143090
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Management of major depression in outpatients attending a cancer centre: a preliminary evaluation of a multicomponent cancer nurse-delivered intervention. Author(s): Sharpe M, Strong V, Allen K, Rush R, Maguire P, House A, Ramirez A, Cull A. Source: British Journal of Cancer. 2004 January 26; 90(2): 310-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14735169
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Minor depression: risk profiles, functional disability, health care use and risk of developing major depression. Author(s): Cuijpers P, de Graaf R, van Dorsselaer S. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023482
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Minor physical anomalies in non-familial unipolar recurrent major depression. Author(s): Tenyi T, Trixler M, Csabi G, Jeges S. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 259-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023504
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Monocytic parameters in patients with dysthymia versus major depression. Author(s): Schlatter J, Ortuno F, Cervera-Enguix S. Source: Journal of Affective Disorders. 2004 March; 78(3): 243-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013249
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Natural course and placebo response in short-term, placebo-controlled studies in major depression: a meta-analysis of published and non-published studies. Author(s): Storosum JG, Elferink AJ, van Zwieten BJ, van den Brink W, Huyser J. Source: Pharmacopsychiatry. 2004 January; 37(1): 32-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14750046
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Nefazodone treatment of comorbid alcohol dependence and major depression. Author(s): Hernandez-Avila CA, Modesto-Lowe V, Feinn R, Kranzler HR. Source: Alcoholism, Clinical and Experimental Research. 2004 March; 28(3): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15084901
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Negative mood, depressive symptoms, and major depression after smoking cessation treatment in smokers with a history of major depressive disorder. Author(s): Kahler CW, Brown RA, Ramsey SE, Niaura R, Abrams DB, Goldstein MG, Mueller TI, Miller IW. Source: Journal of Abnormal Psychology. 2002 November; 111(4): 670-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12428781
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Neuropsychological deficits among patients with late-onset minor and major depression. Author(s): Elderkin-Thompson V, Kumar A, Bilker WB, Dunkin JJ, Mintz J, Moberg PJ, Mesholam RI, Gur RE. Source: Archives of Clinical Neuropsychology : the Official Journal of the National Academy of Neuropsychologists. 2003 July; 18(5): 529-49. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14591448
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Neuroticism, major depression and gender: a population-based twin study. Author(s): Fanous A, Gardner CO, Prescott CA, Cancro R, Kendler KS. Source: Psychological Medicine. 2002 May; 32(4): 719-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12102386
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No Influence of a functional polymorphism within the serotonin transporter gene on partial sleep deprivation in major depression. Author(s): Baghai TC, Schule C, Zwanzger P, Zill P, Ella R, Eser D, Deiml T, Minov C, Rupprecht R, Bondy B. Source: World J Biol Psychiatry. 2003 July; 4(3): 111-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12872203
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Norepinephrine alters the expression of genes involved in neuronal sprouting and differentiation: relevance for major depression and antidepressant mechanisms. Author(s): Laifenfeld D, Klein E, Ben-Shachar D. Source: Journal of Neurochemistry. 2002 December; 83(5): 1054-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12437576
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Olfactory dysfunction discriminates probable Alzheimer's dementia from major depression: a cross-validation and extension. Author(s): McCaffrey RJ, Duff K, Solomon GS. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2000 Winter; 12(1): 29-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10678509
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On the role of menopause for sleep-endocrine alterations associated with major depression. Author(s): Antonijevic IA, Murck H, Frieboes RM, Uhr M, Steiger A. Source: Psychoneuroendocrinology. 2003 April; 28(3): 401-18. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12573305
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Open trial of bupropion SR in adolescent major depression. Author(s): Glod CA, Lynch A, Flynn E, Berkowitz C, Baldessarini RJ. Source: Journal of Child and Adolescent Psychiatric Nursing : Official Publication of the Association of Child and Adolescent Psychiatric Nurses, Inc. 2003 July-September; 16(3): 123-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14603988
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Open trial of interpersonal therapy in adolescents with moderate to severe major depression: effectiveness of novice IPT therapists. Author(s): Santor DA, Kusumakar V. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 February; 40(2): 236-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11211373
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Open trial of nefazodone among Hispanics with major depression: efficacy, tolerability, and adherence issues. Author(s): Sanchez-Lacay JA, Lewis-Fernandez R, Goetz D, Blanco C, Salman E, Davies S, Liebowitz M. Source: Depression and Anxiety. 2001; 13(3): 118-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11387731
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Open-label evaluation of venlafaxine sustained release in outpatients with generalized anxiety disorder with comorbid major depression or dysthymia: effectiveness, tolerability and predictors of response. Author(s): Perugi G, Frare F, Toni C, Ruffolo G, Torti C. Source: Neuropsychobiology. 2002; 46(3): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12422062
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Opioid peptides and immunodysfunction in patients with major depression and anxiety disorders. Author(s): Castilla-Cortazar I, Castilla A, Gurpegui M. Source: J Physiol Biochem. 1998 December; 54(4): 203-15. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10225412
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Outcome at 6 months for 50 adolescents with major depression treated in a health maintenance organization. Author(s): Hamilton JD, Bridge J. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 1999 November; 38(11): 1340-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10560219
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Paroxetine in major depression: correlating plasma concentrations and clinical response. Author(s): Normann C, Horn M, Hummel B, Grunze H, Walden J. Source: Pharmacopsychiatry. 2004 May; 37(3): 123-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15138896
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Partner violence and major depression in women: a community study of Chinese Americans. Author(s): Hicks MH, Li Z. Source: The Journal of Nervous and Mental Disease. 2003 November; 191(11): 722-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14614339
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Pharmacologic treatments of major depression: are two mechanisms really better than one? Author(s): Schatzberg AF. Source: The Journal of Clinical Psychiatry. 2004; 65 Suppl 4: 3-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15046535
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Pharmacological treatment of adolescent major depression. Author(s): Cohen D, Gerardin P, Mazet P, Purper-Ouakil D, Flament MF. Source: Journal of Child and Adolescent Psychopharmacology. 2004 Spring; 14(1): 19-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15142388
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Plasma glycine and serine levels in schizophrenia compared to normal controls and major depression: relation to negative symptoms. Author(s): Sumiyoshi T, Anil AE, Jin D, Jayathilake K, Lee M, Meltzer HY. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2004 March; 7(1): 1-8. Epub 2004 January 13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14720317
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Prevalence of major depression and stress indicators in the Danish general population. Author(s): Olsen LR, Mortensen EL, Bech P. Source: Acta Psychiatrica Scandinavica. 2004 February; 109(2): 96-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14725589
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Prognostic value of frontal functional neuroimaging in late-onset severe major depression. Author(s): Navarro V, Gasto C, Lomena F, Torres X, Mateos JJ, Portella MJ, Masana G, Marcos T. Source: The British Journal of Psychiatry; the Journal of Mental Science. 2004 April; 184: 306-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056574
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Prospective assessment of sexual function in women treated for recurrent major depression. Author(s): Cyranowski JM, Frank E, Cherry C, Houck P, Kupfer DJ. Source: Journal of Psychiatric Research. 2004 May-June; 38(3): 267-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15003432
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Psychopathology of seasonal affective disorder patients in comparison with major depression patients who have attempted suicide. Author(s): Pendse BP, Engstrom G, Traskman-Bendz L. Source: The Journal of Clinical Psychiatry. 2004 March; 65(3): 322-7; Quiz 452-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096070
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Pulmonary muscle strength, pulmonary function tests, and dyspnea in women with major depression. Author(s): Calikoglu M, Sahin G, Yazici AE, Yazici K, Ozisik S. Source: Journal of Women's Health (2002). 2004 January-February; 13(1): 93-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15006282
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QT dispersion in the surface electrocardiogram in elderly patients with major depression. Author(s): Nahshoni E, Aizenberg D, Strasberg B, Dorfman P, Sigler M, Imbar S, Weizman A. Source: Journal of Affective Disorders. 2000 November; 60(3): 197-200. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11074108
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Quality of life in elderly patients with recurrent major depression: a factor analysis of the General Life Functioning Scale. Author(s): Mazumdar S, Reynolds CF 3rd, Houck PR, Frank E, Dew MA, Kupfer DJ. Source: Psychiatry Research. 1996 July 31; 63(2-3): 183-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8878314
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Quantitative anatomic measures and comorbid medical illness in late-life major depression. Author(s): Kumar A, Miller D, Ewbank D, Yousem D, Newberg A, Samuels S, Cowell P, Gottlieb G. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 1997 Winter; 5(1): 15-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9169241
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Quantitative distribution of monoamine oxidase A in brainstem monoamine nuclei is normal in major depression. Author(s): Ordway GA, Farley JT, Dilley GE, Overholser JC, Meltzer HY, Balraj EK, Stockmeier CA, Klimek V. Source: Brain Research. 1999 November 13; 847(1): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10564737
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Recognition accuracy and response bias to happy and sad facial expressions in patients with major depression. Author(s): Surguladze SA, Young AW, Senior C, Brebion G, Travis MJ, Phillips ML. Source: Neuropsychology. 2004 April; 18(2): 212-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15099143
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Recurrence of bipolar disorders and major depression. A life-long perspective. Author(s): Angst J, Gamma A, Sellaro R, Lavori PW, Zhang H. Source: European Archives of Psychiatry and Clinical Neuroscience. 2003 October; 253(5): 236-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14504992
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Reduced anterior cingulate cortex glutamatergic concentrations in childhood major depression. Author(s): Mirza Y, Tang J, Russell A, Banerjee SP, Bhandari R, Ivey J, Rose M, Moore GJ, Rosenberg DR. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2004 March; 43(3): 341-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15076268
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Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression. Author(s): Frodl T, Meisenzahl EM, Zill P, Baghai T, Rujescu D, Leinsinger G, Bottlender R, Schule C, Zwanzger P, Engel RR, Rupprecht R, Bondy B, Reiser M, Moller HJ. Source: Archives of General Psychiatry. 2004 February; 61(2): 177-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14757594
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Regulation of platelet alpha 2A-adrenoceptors, Gi proteins and receptor kinases in major depression: effects of mirtazapine treatment. Author(s): Garcia-Sevilla JA, Ventayol P, Perez V, Rubovszky G, Puigdemont D, FerrerAlcon M, Andreoli A, Guimon J, Alvarez E. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 March; 29(3): 580-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14628003
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Remission in major depression with two antidepressant mechanisms: results from a naturalistic study. Author(s): Montes JM, Ferrando L, Saiz-Ruiz J. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 229-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023499
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Reporting of somatic symptoms as a screening marker for detecting major depression in a population of Japanese white-collar workers. Author(s): Nakao M, Yano E. Source: Journal of Clinical Epidemiology. 2003 October; 56(10): 1021-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14568635
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Response selection deficits in melancholic but not nonmelancholic unipolar major depression. Author(s): Rogers MA, Bellgrove MA, Chiu E, Mileshkin C, Bradshaw JL. Source: J Clin Exp Neuropsychol. 2004 April; 26(2): 169-79. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15202537
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Risk factors for depression at 12-month follow-up in adult primary health care patients with major depression: an international prospective study. Author(s): Barkow K, Maier W, Ustun TB, Gansicke M, Wittchen HU, Heun R. Source: Journal of Affective Disorders. 2003 September; 76(1-3): 157-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12943946
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Rural-urban differences in the prevalence of major depression and associated impairment. Author(s): Wang JL. Source: Social Psychiatry and Psychiatric Epidemiology. 2004 January; 39(1): 19-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15022042
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Selective impairment in effortful information processing in major depression. Author(s): Hammar A, Lund A, Hugdahl K. Source: Journal of the International Neuropsychological Society : Jins. 2003 September; 9(6): 954-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14632254
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Serotonin 5-HT1A, 5-HT1B, and 5-HT2A receptor mRNA expression in subjects with major depression, bipolar disorder, and schizophrenia. Author(s): Lopez-Figueroa AL, Norton CS, Lopez-Figueroa MO, Armellini-Dodel D, Burke S, Akil H, Lopez JF, Watson SJ. Source: Biological Psychiatry. 2004 February 1; 55(3): 225-33. Erratum In: Biol Psychiatry. 2004 March 15; 55(6): 660. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14744462
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Sertraline treatment of post-stroke major depression: an open study in patients with moderate to severe symptoms. Author(s): Spalletta G, Caltagirone C. Source: Funct Neurol. 2003 October-December; 18(4): 227-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15055748
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Short-term fluoxetine monotherapy for bipolar type II or bipolar NOS major depression - low manic switch rate. Author(s): Amsterdam JD, Shults J, Brunswick DJ, Hundert M. Source: Bipolar Disorders. 2004 February; 6(1): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14996144
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Should major depression with 'high normal' thyroid-stimulating hormone be treated preferentially with tricyclics? Author(s): Corruble E, Berlin I, Lemoine A, Hardy P. Source: Neuropsychobiology. 2004; 50(2): 144-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15292668
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Sleep quality and immune functions in rheumatoid arthritis patients with and without major depression. Author(s): Cakirbay H, Bilici M, Kavakci O, Cebi A, Guler M, Tan U. Source: The International Journal of Neuroscience. 2004 February; 114(2): 245-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14702212
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Socio-economic status, family disruption and residential stability in childhood: relation to onset, recurrence and remission of major depression. Author(s): Gilman SE, Kawachi I, Fitzmaurice GM, Buka L. Source: Psychological Medicine. 2003 November; 33(8): 1341-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14672243
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Subcortical and ventral prefrontal cortical neural responses to facial expressions distinguish patients with bipolar disorder and major depression. Author(s): Lawrence NS, Williams AM, Surguladze S, Giampietro V, Brammer MJ, Andrew C, Frangou S, Ecker C, Phillips ML. Source: Biological Psychiatry. 2004 March 15; 55(6): 578-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15013826
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Subtype-specific alterations of gamma-aminobutyric acid and glutamate in patients with major depression. Author(s): Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF. Source: Archives of General Psychiatry. 2004 July; 61(7): 705-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15237082
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Suicidal behavior and mild traumatic brain injury in major depression. Author(s): Oquendo MA, Friedman JH, Grunebaum MF, Burke A, Silver JM, Mann JJ. Source: The Journal of Nervous and Mental Disease. 2004 June; 192(6): 430-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15167407
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The genetic relationship of personality to major depression and schizophrenia. Author(s): Fanous AH, Kendler KS. Source: Neurotox Res. 2004; 6(1): 43-50. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15184104
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The interrelationship of neuroticism, sex, and stressful life events in the prediction of episodes of major depression. Author(s): Kendler KS, Kuhn J, Prescott CA. Source: The American Journal of Psychiatry. 2004 April; 161(4): 631-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15056508
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The relationship between interpersonal sensitivity, anxiety disorders and major depression. Author(s): Wilhelm K, Boyce P, Brownhill S. Source: Journal of Affective Disorders. 2004 April; 79(1-3): 33-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15023478
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The relationship of regional cerebral blood flow with subtypes of major depression. Author(s): Fountoulakis KN, Iacovides A, Gerasimou G, Fotiou F, Ioannidou C, Bascialla F, Grammaticos P, Kaprinis G. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2004 May; 28(3): 537-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15093962
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Thyroid function in clinical subtypes of major depression: an exploratory study. Author(s): Fountoulakis KN, Iacovides A, Grammaticos P, St Kaprinis G, Bech P. Source: Bmc Psychiatry [electronic Resource]. 2004 March 15; 4(1): 6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15113438
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Towards a dynamic description of major depression epidemiology. Author(s): Patten SB, Lee RC. Source: Epidemiol Psichiatr Soc. 2004 January-March; 13(1): 21-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15248391
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Treating major depression in children and adolescents: depressed adolescents may lose out. Author(s): Shenderey KD. Source: Bmj (Clinical Research Ed.). 2004 February 28; 328(7438): 525. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988210
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Treating major depression in children and adolescents: use of selective serotonin reuptake inhibitors needs urgent clarification. Author(s): Herxheimer A. Source: Bmj (Clinical Research Ed.). 2004 February 28; 328(7438): 525. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14988211
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Treatment of adolescents with major depression: contributions of a major trial. Author(s): Glass RM. Source: Jama : the Journal of the American Medical Association. 2004 August 18; 292(7): 861-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15316001
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Treatment of major depression in individuals with spinal cord injury. Author(s): Kemp BJ, Kahan JS, Krause JS, Adkins RH, Nava G. Source: J Spinal Cord Med. 2004; 27(1): 22-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15156933
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Underuse of antidepressants in major depression: prevalence and correlates in a national sample of young adults. Author(s): Druss BG, Hoff RA, Rosenheck RA. Source: The Journal of Clinical Psychiatry. 2000 March; 61(3): 234-7; Quiz 238-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10817113
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Untreated short-term course of major depression: a meta-analysis of outcomes from studies using wait-list control groups. Author(s): Posternak MA, Miller I. Source: Journal of Affective Disorders. 2001 October; 66(2-3): 139-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11578666
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Urinary free cortisol excretion in elderly persons with minor and major depression. Author(s): Oldehinkel AJ, van den Berg MD, Flentge F, Bouhuys AL, ter Horst GJ, Ormel J. Source: Psychiatry Research. 2001 October 10; 104(1): 39-47. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11600188
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Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo. Author(s): Stewart JW, Quitkin FM, McGrath PJ, Amsterdam J, Fava M, Fawcett J, Reimherr F, Rosenbaum J, Beasley C, Roback P. Source: Archives of General Psychiatry. 1998 April; 55(4): 334-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9554429
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Use of placebo control groups in evaluating efficacy of treatment of unipolar major depression. Author(s): Schatzberg AF, Kraemer HC. Source: Biological Psychiatry. 2000 April 15; 47(8): 736-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10773182
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Use of the Beck Depression Inventory for Primary Care to screen for major depression disorders. Author(s): Steer RA, Cavalieri TA, Leonard DM, Beck AT. Source: General Hospital Psychiatry. 1999 March-April; 21(2): 106-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10228890
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Using a computerized patient database to evaluate guideline adherence and measure patterns of care for major depression. Author(s): Chen RS, Rosenheck R. Source: The Journal of Behavioral Health Services & Research. 2001 November; 28(4): 466-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11732248
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Using elicitation techniques to estimate the value of ambulatory treatments for major depression. Author(s): Normand SL, Frank RG, McGuire TG. Source: Medical Decision Making : an International Journal of the Society for Medical Decision Making. 2002 May-June; 22(3): 245-61. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12058782
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Utility scores of symptom profiles in major depression. Author(s): Schaffer A, Levitt AJ, Hershkop SK, Oh P, MacDonald C, Lanctot K. Source: Psychiatry Research. 2002 June 1; 110(2): 189-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12057830
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Variability in the 5-HT(2A) receptor gene is associated with seasonal pattern in major depression. Author(s): Arias B, Gutierrez B, Pintor L, Gasto C, Fananas L. Source: Molecular Psychiatry. 2001 March; 6(2): 239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11317230
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Vasoconstrictor response to topical beclomethasone in major depression. Author(s): Cotter PA, Mulligan OF, Landau S, Papadopoulos A, Lightman SL, Checkley SA. Source: Psychoneuroendocrinology. 2002 May; 27(4): 475-87. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11912000
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Vasopressin, major depression, and hypothalamic-pituitary-adrenocortical desensitization. Author(s): Muller MB, Landgraf R, Keck ME. Source: Biological Psychiatry. 2000 August 15; 48(4): 330-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10960167
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Venlafaxine extended-release: a review of its use in the management of major depression. Author(s): Wellington K, Perry CM. Source: Cns Drugs. 2001; 15(8): 643-69. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11524036
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Venlafaxine versus placebo in the preventive treatment of recurrent major depression. Author(s): Montgomery SA, Entsuah R, Hackett D, Kunz NR, Rudolph RL; Venlafaxine 335 Study Group. Source: The Journal of Clinical Psychiatry. 2004 March; 65(3): 328-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15096071
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Violence and risk of PTSD, major depression, substance abuse/dependence, and comorbidity: results from the National Survey of Adolescents. Author(s): Kilpatrick DG, Ruggiero KJ, Acierno R, Saunders BE, Resnick HS, Best CL. Source: Journal of Consulting and Clinical Psychology. 2003 August; 71(4): 692-700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12924674
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Visuo-motor coordination is normal in patients with major depression. Author(s): Hocherman S, Dimant A, Schwartz M. Source: Parkinsonism & Related Disorders. 2003 August; 9(6): 361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12853236
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Vitamin D in schizophrenia, major depression and alcoholism. Author(s): Schneider B, Weber B, Frensch A, Stein J, Fritz J. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2000; 107(7): 839-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11005548
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Volumetric analysis of the prefrontal cortex, amygdala, and hippocampus in major depression. Author(s): Hastings RS, Parsey RV, Oquendo MA, Arango V, Mann JJ. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2004 May; 29(5): 952-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14997169
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Weekly dosing of fluoxetine for the continuation phase of treatment of major depression: results of a placebo-controlled, randomized clinical trial. Author(s): Burke WJ, Hendricks SE, McArthur-Miller D, Jacques D, Bessette D, McKillup T, Stull T, Wilson J. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 423-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10917403
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What does the Keane PTSD scale of the MMPI measure? Repeated measurements in a group of patients with major depression. Author(s): Wetzel RD, Murphy GE, Simons A, Lustman P, North C, Yutzy S. Source: Psychological Reports. 2003 June; 92(3 Pt 1): 781-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12841442
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What happens to patients after the end of a clinical trial? Systematic follow-up observational study of an open moclobemide trial in major depression. Author(s): Linden M, Baier D, Gothe H, Kohnen R. Source: Pharmacopsychiatry. 1997 January; 30(1 Suppl): 35-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9035226
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When should a trial of fluoxetine for major depression be declared failed? Author(s): Quitkin FM, Petkova E, McGrath PJ, Taylor B, Beasley C, Stewart J, Amsterdam J, Fava M, Rosenbaum J, Reimherr F, Fawcett J, Chen Y, Klein D. Source: The American Journal of Psychiatry. 2003 April; 160(4): 734-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12668363
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Which class of antidepressants is most effective and best tolerated by patients with major depression? Author(s): Sparano N. Source: The Journal of Family Practice. 2000 October; 49(10): 886, 947-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11052159
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Wolf-Hirschhorn (4p-)syndrome in a near adult with major depression; successful treatment with citalopram. Author(s): Verhoeven WM, Moog U, Wagemans AM, Tuinier S. Source: Genet Couns. 2002; 13(3): 297-301. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12416637
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Women's conceptions of coping with major depression in daily life: a qualitative, salutogenic approach. Author(s): Skarsater I, Dencker K, Bergbom I, Haggstrom L, Fridlund B. Source: Issues in Mental Health Nursing. 2003 June; 24(4): 419-39. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12746183
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Working memory and prefrontal cortex dysfunction: specificity to schizophrenia compared with major depression. Author(s): Barch DM, Sheline YI, Csernansky JG, Snyder AZ. Source: Biological Psychiatry. 2003 March 1; 53(5): 376-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12614990
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Working memory dysfunction in major depression: an event-related potential study. Author(s): Pelosi L, Slade T, Blumhardt LD, Sharma VK. Source: Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology. 2000 September; 111(9): 1531-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10964062
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Zalospirone in major depression: a placebo-controlled multicenter study. Author(s): Rickels K, Derivan A, Kunz N, Pallay A, Schweizer E. Source: Journal of Clinical Psychopharmacology. 1996 June; 16(3): 212-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8784652
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CHAPTER 2. NUTRITION AND MAJOR DEPRESSION Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and major depression.
Finding Nutrition Studies on Major Depression 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 “major depression” (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 “major depression” (or a synonym): •
Growth hormone response to apomorphine in panic disorder: comparison with major depression and normal controls. Author(s): Psychiatric Unit, University Hospital of Liege, Belgium. Source: Pichot, W Hansenne, M Gonzalez Moreno, A Ansseau, M Eur-Arch-PsychiatryClin-Neurosci. 1995; 245(6): 306-8 0940-1334
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Moclobemide, imipramine, and placebo in the treatment of major depression (DSM III). Author(s): Institute of Psychiatry, Federal University of Rio de Janeiro, Brazil. Source: Versiani, M Nardi, A E Mundim, F D Alves, A B J-Neural-Transm-Suppl. 1989; 2865-75 0303-6995
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Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major depression medicated with trimipramine. Author(s): Psychiatric University Hospital Basle, Department of Depression Research, Sleep Medicine and Neurophysiology, Basle, Switzerland. Source: Hemmeter, U Annen, B Bischof, R Bruderlin, U Hatzinger, M Rose, U Holsboer Trachsler, E Pharmacopsychiatry. 2001 March; 34(2): 50-9 0176-3679
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Serotonergic function in major depression and effect of sertraline and paroxetine treatment. Author(s): Department of Psychiatry, Institution of Clinical Neuroscience, Karolinska Institute, St Goran's Hospital, Stockholm, Sweden.
[email protected] Source: Stain Malmgren, R Khoury, A E Aberg Wistedt, A Tham, A Int-ClinPsychopharmacol. 2001 March; 16(2): 93-101 0268-1315
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Treatment of resistant depression. Review on the efficacy of various biological treatments, specifically in major depression resistant to cyclic antidepressants. Author(s): Department of Biological Psychiatry, Psychiatric Centre Bloemendaal, Hague, The Netherlands. Source: Nolen, W A Haffmans, J Int-Clin-Psychopharmacol. 1989 July; 4(3): 217-28 02681315
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: •
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: •
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
The following is a specific Web list relating to major depression; 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: •
Vitamins Vitamin E Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND MAJOR DEPRESSION Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to major depression. At the conclusion of this chapter, we will provide additional sources.
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 major depression 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 “major depression” (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 major depression: •
“Diet pills” and major depression in the Canadian population. Author(s): Patten SB. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 June; 46(5): 438-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11441784
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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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A major depression of psychogenic origin in a five-year-old. Author(s): Giancotti A, Vinci G. Source: The American Journal of Orthopsychiatry. 1986 October; 56(4): 617-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3789108
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A randomized clinical trial of repetitive transcranial magnetic stimulation in the treatment of major depression. Author(s): Berman RM, Narasimhan M, Sanacora G, Miano AP, Hoffman RE, Hu XS, Charney DS, Boutros NN. Source: Biological Psychiatry. 2000 February 15; 47(4): 332-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10686268
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A randomized controlled comparison of electroconvulsive therapy and repetitive transcranial magnetic stimulation in severe and resistant nonpsychotic major depression. Author(s): Grunhaus L, Schreiber S, Dolberg OT, Polak D, Dannon PN. Source: Biological Psychiatry. 2003 February 15; 53(4): 324-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12586451
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Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression. Author(s): Szuba MP, O'Reardon JP, Rai AS, Snyder-Kastenberg J, Amsterdam JD, Gettes DR, Wassermann E, Evans DL. Source: Biological Psychiatry. 2001 July 1; 50(1): 22-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11457420
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Acute phase proteins in major depression. Author(s): Berk M, Wadee AA, Kuschke RH, O'Neill-Kerr A. Source: Journal of Psychosomatic Research. 1997 November; 43(5): 529-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9394269
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Alternative medicine use by individuals with major depression. Author(s): Wang JL, Patten SB, Russell ML. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 August; 46(6): 528-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11526809
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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.
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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 •
Charles Bonnet syndrome with major depression in a Chinese middle-aged man. Author(s): Fong SY, Wing YK. Source: The Australian and New Zealand Journal of Psychiatry. 1997 October; 31(5): 76971. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9400886
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Childhood experiences and adult behavior in a group of women with pain accounted for by psychological factors and a group recovered from major depression. Author(s): Zlot SI, Herrmann M, Hofer-Mayer T, Adler M, Adler RH. Source: International Journal of Psychiatry in Medicine. 2000; 30(3): 261-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11209993
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Circulating lymphocyte subsets in major depression and dysthymia with typical or atypical features. Author(s): Ravindran AV, Griffiths J, Merali Z, Anisman H. Source: Psychosomatic Medicine. 1998 May-June; 60(3): 283-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625215
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Comment on “Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial”. Author(s): Kellner CH, Husain M, Petrides G, Fink M, Rummans T. Source: Biological Psychiatry. 2002 November 15; 52(10): 1032-3; Discussion 1033. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12437944
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Course and severity of substance abuse among patients with comorbid major depression. Author(s): Westermeyer J, Kopka S, Nugent S. Source: The American Journal on Addictions / American Academy of Psychiatrists in Alcoholism and Addictions. 1997 Fall; 6(4): 284-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9398926
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Dichotic listening before and after fluoxetine treatment for major depression: relations of laterality to therapeutic response. Author(s): Bruder GE, Otto MW, McGrath PJ, Stewart JW, Fava M, Rosenbaum JF, Quitkin FM. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 1996 August; 15(2): 171-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8840353
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Does clinical response to repetitive prefrontal transcranial magnetic stimulation (r TMS) predict response to electroconvulsive therapy (ECT) in cases of major depression? Author(s): Eschweiler GW, Plewnia C, Batra A, Bartels M. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2000 November; 45(9): 845-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11143838
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Double-blind controlled investigation of bilateral prefrontal transcranial magnetic stimulation for the treatment of resistant major depression. Author(s): Loo CK, Mitchell PB, Croker VM, Malhi GS, Wen W, Gandevia SC, Sachdev PS. Source: Psychological Medicine. 2003 January; 33(1): 33-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12537034
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Double-blind controlled investigation of transcranial magnetic stimulation for the treatment of resistant major depression. Author(s): Loo C, Mitchell P, Sachdev P, McDarmont B, Parker G, Gandevia S. Source: The American Journal of Psychiatry. 1999 June; 156(6): 946-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10360138
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Effectiveness of St John's wort in major depression: a randomized controlled trial. Author(s): Shelton RC, Keller MB, Gelenberg A, Dunner DL, Hirschfeld R, Thase ME, Russell J, Lydiard RB, Crits-Cristoph P, Gallop R, Todd L, Hellerstein D, Goodnick P, Keitner G, Stahl SM, Halbreich U. Source: Jama : the Journal of the American Medical Association. 2001 April 18; 285(15): 1978-86. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11308434
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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 and safety of St. John's wort for the treatment of major depression. Author(s): Nangia M, Syed W, Doraiswamy PM. Source: Public Health Nutrition. 2000 December; 3(4A): 487-94. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11276296
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Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Author(s): Lecrubier Y, Clerc G, Didi R, Kieser M.
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Source: The American Journal of Psychiatry. 2002 August; 159(8): 1361-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12153829 •
Factors Influencing Response to Bilateral Electroconvulsive Therapy in Major Depression. Author(s): Kindler S, Shapira B, Hadjez J, Abramowitz M, Brom D, Lerer B. Source: Convuls Ther. 1991; 7(4): 245-254. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11941129
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Fatty acid composition in major depression: decreased omega 3 fractions in cholesteryl esters and increased C20: 4 omega 6/C20:5 omega 3 ratio in cholesteryl esters and phospholipids. Author(s): Maes M, Smith R, Christophe A, Cosyns P, Desnyder R, Meltzer H. Source: Journal of Affective Disorders. 1996 April 26; 38(1): 35-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8735157
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Fish consumption and major depression. Author(s): Hibbeln JR. Source: Lancet. 1998 April 18; 351(9110): 1213. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9643729
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Hearing loss and asymmetry in major depression. Author(s): Yovell Y, Sackeim HA, Epstein DG, Prudic J, Devanand DP, McElhiney MC, Settembrino JM, Bruder GE. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1995 Winter; 7(1): 82-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7711498
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Hypnosis in treating symptoms and risk factors of major depression. Author(s): Yapko M. Source: Am J Clin Hypn. 2001 October; 44(2): 97-108. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11591085
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Immunity, major depression, and panic disorder comorbidity. Author(s): Andreoli A, Keller SE, Rabaeus M, Zaugg L, Garrone G, Taban C. Source: Biological Psychiatry. 1992 May 1; 31(9): 896-908. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1637930
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Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. Author(s): Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R.
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Source: Journal of Affective Disorders. 1995 August 18; 34(4): 301-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8550956 •
Increased serum interleukin-1-receptor-antagonist concentrations in major depression. Author(s): Maes M, Vandoolaeghe E, Ranjan R, Bosmans E, Bergmans R, Desnyder R. Source: Journal of Affective Disorders. 1995 December 24; 36(1-2): 29-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8988262
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Influence of stimulation parameters on auditory stimulus processing in schizophrenia and major depression: an auditory evoked potential study. Author(s): Adler G, Adler J, Schneck M, Armbruster B. Source: Acta Psychiatrica Scandinavica. 1990 May; 81(5): 453-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2356768
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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. 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
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Is St. John's wort an effective treatment for major depression? Author(s): Tatum P, Lindbloom EJ. Source: The Journal of Family Practice. 2001 July; 50(7): 624. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11485714
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Left dorso-lateral repetitive transcranial magnetic stimulation affects cortical excitability and functional connectivity, but does not impair cognition in major depression. Author(s): Shajahan PM, Glabus MF, Steele JD, Doris AB, Anderson K, Jenkins JA, Gooding PA, Ebmeier KP. Source: Progress in Neuro-Psychopharmacology & Biological Psychiatry. 2002 June; 26(5): 945-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12369271
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Left prefrontal activation predicts therapeutic effects of repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Eschweiler GW, Wegerer C, Schlotter W, Spandl C, Stevens A, Bartels M, Buchkremer G. Source: Psychiatry Research. 2000 October 30; 99(3): 161-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11068197
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Magnetic seizure therapy of major depression. Author(s): Lisanby SH, Schlaepfer TE, Fisch HU, Sackeim HA. Source: Archives of General Psychiatry. 2001 March; 58(3): 303-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231838
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Major depression and somatic symptoms in a mind/body medicine clinic. Author(s): Nakao M, Yamanaka G, Kuboki T. Source: Psychopathology. 2001 September-October; 34(5): 230-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11799317
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Major depression in patients with substance use disorders: relationship to 12-Step self-help involvement and substance use outcomes. Author(s): Kelly JF, McKellar JD, Moos R. Source: Addiction (Abingdon, England). 2003 April; 98(4): 499-508. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12653819
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Major depression is associated with lower omega-3 fatty acid levels in patients with recent acute coronary syndromes. Author(s): Frasure-Smith N, Lesperance F, Julien P. Source: Biological Psychiatry. 2004 May 1; 55(9): 891-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15110732
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Methodological considerations in clinical studies of omega 3 fatty acids in major depression and bipolar disorder. Author(s): Stoll AL, Damico KE, Daly BP, Severus WE, Marangell LB. Source: World Review of Nutrition and Dietetics. 2001; 88: 58-67. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11935971
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Mitogen-stimulated lymphocyte proliferation and pituitary hormones in major depression. Author(s): Darko DF, Gillin JC, Risch SC, Bulloch K, Golshan S, Tasevska Z, Hamburger RN. Source: Biological Psychiatry. 1989 June; 26(2): 145-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2544231
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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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Occurrence of delusions during repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Zwanzger P, Ella R, Keck ME, Rupprecht R, Padberg F. Source: Biological Psychiatry. 2002 April 1; 51(7): 602-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11950462
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Omega-3 fatty acids in major depression. Author(s): Locke CA, Stoll AL. Source: World Review of Nutrition and Dietetics. 2001; 89: 173-85. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11530734
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Pain perception threshold in major depression. Author(s): Adler G, Gattaz WF. Source: Biological Psychiatry. 1993 November 15; 34(10): 687-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8292672
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Pharmacologic treatment of acute major depression and dysthymia. American College of Physicians-American Society of Internal Medicine. Author(s): Snow V, Lascher S, Mottur-Pilson C. Source: Annals of Internal Medicine. 2000 May 2; 132(9): 738-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10787369
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Plasma beta-endorphin and natural killer cell activity in major depression: a preliminary study. Author(s): Darko DF, Irwin MR, Risch SC, Gillin JC. Source: Psychiatry Research. 1992 August; 43(2): 111-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1410068
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Plasma concentrations of neuroactive steroids before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Padberg F, di Michele F, Zwanzger P, Romeo E, Bernardi G, Schule C, Baghai TC, Ella R, Pasini A, Rupprecht R. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 November; 27(5): 874-8. Erratum In: Neuropsychopharmacology. 2003 March; 28(3): 610-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12431862
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Polysomnographic effects of adjuvant ginkgo biloba therapy in patients with major depression medicated with trimipramine. Author(s): Hemmeter U, Annen B, Bischof R, Bruderlin U, Hatzinger M, Rose U, Holsboer-Trachsler E. Source: Pharmacopsychiatry. 2001 March; 34(2): 50-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11302564
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Preliminary evidence for a beneficial effect of low-frequency, repetitive transcranial magnetic stimulation in patients with major depression and schizophrenia. Author(s): Feinsod M, Kreinin B, Chistyakov A, Klein E. Source: Depression and Anxiety. 1998; 7(2): 65-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9614593
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Psychomotor retardation, anorexia, weight loss, sleep disturbances, and loss of energy: psychopathological correlates of hyperhaptoglobinemia during major depression. Author(s): Maes M, Meltzer HY, Scharpe S, Cooreman W, Uyttenbroeck W, Suy E, Vandervorst C, Calabrese J, Raus J, Cosyns P. Source: Psychiatry Research. 1993 June; 47(3): 229-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8372161
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Psycho-neuro-immunological treatment of hepatocellular carcinoma with major depression--a single case report. Author(s): Jozuka H, Jozuka E, Suzuki M, Takeuchi S, Takatsu Y. Source: Current Medical Research and Opinion. 2003; 19(1): 59-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12661782
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Rational treatment choices for non-major depressions in primary care: an evidencebased review. Author(s): Ackermann RT, Williams JW Jr. Source: Journal of General Internal Medicine : Official Journal of the Society for Research and Education in Primary Care Internal Medicine. 2002 April; 17(4): 293-301. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11972726
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Relation between responses to repetitive transcranial magnetic stimulation and partial sleep deprivation in major depression. Author(s): Padberg F, Schule C, Zwanzger P, Baghai T, Ella R, Mikhaiel P, Hampel H, Moller HJ, Rupprecht R. Source: Journal of Psychiatric Research. 2002 May-June; 36(3): 131-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11886690
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Repetitive transcranial magnetic stimulation (rTMS) in major depression: relation between efficacy and stimulation intensity. Author(s): Padberg F, Zwanzger P, Keck ME, Kathmann N, Mikhaiel P, Ella R, Rupprecht P, Thoma H, Hampel H, Toschi N, Moller HJ. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2002 October; 27(4): 638-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12377400
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Repetitive transcranial magnetic stimulation (rTMS) in pharmacotherapy-refractory major depression: comparative study of fast, slow and sham rTMS. Author(s): Padberg F, Zwanzger P, Thoma H, Kathmann N, Haag C, Greenberg BD, Hampel H, Moller HJ. Source: Psychiatry Research. 1999 November 29; 88(3): 163-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622338
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Repetitive transcranial magnetic stimulation as an antidepressant monotherapy in a patient with major depression, leucocytopenia and rhabdomyolysis. Author(s): Mobascher A, Boecker J, Malevani J, Arends M, Klimke A, Cordes J. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 2004 July 26 [epub Ahead of Print] http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15315718
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Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. Author(s): Rosenberg PB, Mehndiratta RB, Mehndiratta YP, Wamer A, Rosse RB, Balish M. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 2002 Summer; 14(3): 270-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12154150
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Repetitive transcranial magnetic stimulation versus electroconvulsive therapy for major depression: preliminary results of a randomized trial. Author(s): Janicak PG, Dowd SM, Martis B, Alam D, Beedle D, Krasuski J, Strong MJ, Sharma R, Rosen C, Viana M.
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Source: Biological Psychiatry. 2002 April 15; 51(8): 659-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11955466 •
Repetitive transcranial magnetic stimulation: a putative add-on treatment for major depression in elderly patients. Author(s): Mosimann UP, Schmitt W, Greenberg BD, Kosel M, Muri RM, Berkhoff M, Hess CW, Fisch HU, Schlaepfer TE. Source: Psychiatry Research. 2004 April 30; 126(2): 123-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15123391
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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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St John's wort and major depression. Author(s): Fugh-Berman A. Source: Jama : the Journal of the American Medical Association. 2001 July 4; 286(1): 43-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434819
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St john's wort and major depression. Author(s): Brenner R, Madhusoodanan S, Pawlowska M, Czobor P. Source: Jama : the Journal of the American Medical Association. 2001 July 4; 286(1): 43; Author Reply 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434818
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St John's wort and major depression. Author(s): Cohen HW, Marantz PR. Source: Jama : the Journal of the American Medical Association. 2001 July 4; 286(1): 42-3; Author Reply 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434817
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St John's wort and major depression. Author(s): Fomous CM, Cardellina JH 2nd. Source: Jama : the Journal of the American Medical Association. 2001 July 4; 286(1): 42; Author Reply 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434816
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St John's wort and major depression. Author(s): Cott JM, Rosenthal N, Blumenthal M.
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Source: Jama : the Journal of the American Medical Association. 2001 July 4; 286(1): 42; Author Reply 44-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11434815 •
The benefit from whole body acupuncture in major depression. Author(s): Roschke J, Wolf C, Muller MJ, Wagner P, Mann K, Grozinger M, Bech S. Source: Journal of Affective Disorders. 2000 January-March; 57(1-3): 73-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10708818
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The combined dexamethasone-CRH test before and after repetitive transcranial magnetic stimulation (rTMS) in major depression. Author(s): Zwanzger P, Baghai TC, Padberg F, Ella R, Minov C, Mikhaiel P, Schule C, Thoma H, Rupprecht R. Source: Psychoneuroendocrinology. 2003 April; 28(3): 376-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12573303
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The effect of a history of alcohol dependence in adult major depression. Author(s): Rae AM, Joyce PR, Luty SE, Mulder RT. Source: Journal of Affective Disorders. 2002 August; 70(3): 281-90. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12128240
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The immune system and major depression. Author(s): Anderson JL. Source: Advances in Neuroimmunology. 1996; 6(2): 119-29. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8876768
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Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. Author(s): Klein E, Kreinin I, Chistyakov A, Koren D, Mecz L, Marmur S, Ben-Shachar D, Feinsod M. Source: Archives of General Psychiatry. 1999 April; 56(4): 315-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10197825
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Thyroid hormone supplementation of fluoxetine in the treatment of major depression. Author(s): Gupta S, Masand P, Tanquary JF. Source: The British Journal of Psychiatry; the Journal of Mental Science. 1991 December; 159: 866-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1790460
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Use of alternative medicine in major depression. Author(s): Druss BG, Rohrbaugh R, Kosten T, Hoff R, Rosenheck RA.
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Source: Psychiatric Services (Washington, D.C.). 1998 November; 49(11): 1397. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9826237 •
Vagal tone as an indicator of treatment response in major depression. Author(s): Chambers AS, Allen JJ. Source: Psychophysiology. 2002 November; 39(6): 861-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12462513
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
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 major depression; 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: •
General Overview Breast Cancer Source: Healthnotes, Inc.; www.healthnotes.com Depression Source: Healthnotes, Inc.; www.healthnotes.com
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Depression Source: Integrative Medicine Communications; www.drkoop.com Depression (Mild to Moderate) Source: Prima Communications, Inc.www.personalhealthzone.com Fibromyalgia Source: Healthnotes, Inc.; www.healthnotes.com Post Traumatic Stress Disorder Source: Integrative Medicine Communications; www.drkoop.com PTSD Source: Integrative Medicine Communications; www.drkoop.com Seasonal Affective Disorder Source: Healthnotes, Inc.; www.healthnotes.com Shingles and Postherpetic Neuralgia Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Dehydroepiandrosterone (DHEA) Source: Healthnotes, Inc.; www.healthnotes.com DHEA (Dehydroepiandrosterone) Source: Prima Communications, Inc.www.personalhealthzone.com Docosahexaenoic Acid Source: Healthnotes, Inc.; www.healthnotes.com Melatonin Source: Healthnotes, Inc.; www.healthnotes.com S-Adenosylmethionine (SAMe) Source: Integrative Medicine Communications; www.drkoop.com SAMe Source: Healthnotes, Inc.; www.healthnotes.com SAMe Source: Integrative Medicine Communications; www.drkoop.com St. John's Wort Source: Prima Communications, Inc.www.personalhealthzone.com Tricyclic Antidepressants Source: Healthnotes, Inc.; www.healthnotes.com
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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 MAJOR DEPRESSION Overview In this chapter, we will give you a bibliography on recent dissertations relating to major depression. 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 “major depression” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on major depression, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Major Depression 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 major depression. 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: •
Disaggregating the relationship between stress and major depression in Chinese Americans by Hwang, Wei-Chin, PhD from UNIVERSITY OF CALIFORNIA, LOS ANGELES, 2003, 108 pages http://wwwlib.umi.com/dissertations/fullcit/3094257
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Dopaminergic activity in major depression and nicotine dependence by Cardenas, Laura, PhD from UNIVERSITY OF TORONTO (CANADA), 2003, 152 pages http://wwwlib.umi.com/dissertations/fullcit/NQ84813
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Personality and cognitive risk factors: An investigation of vulnerability for major depression and other diagnoses by Leather, Faith A., MA from YORK UNIVERSITY (CANADA), 2003, 102 pages http://wwwlib.umi.com/dissertations/fullcit/MQ82938
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The nature of major depression in youths: A taxometric analysis by Danielson, Carla Kmett, PhD from CASE WESTERN RESERVE UNIVERSITY, 2003, 141 pages http://wwwlib.umi.com/dissertations/fullcit/3092000
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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 MAJOR DEPRESSION 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 “major depression” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on major depression, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Major Depression By performing a patent search focusing on major depression, 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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The following is an example of the type of information that you can expect to obtain from a patent search on major depression: •
Duplications of human chromosome 15q24-25 and anxiety disorders, diagnostic methods for their detection Inventor(s): Estivill Palleja; Xavier (Barcelona, ES), Gratacos; Monica (Barcelona, ES), Nadal; Marga (Barcelona, ES), Pujana; Miguel Angel (Barcelona, ES), Volpini; Victor (Barcelona, ES) Assignee(s): Palleja, Zavier Estivell (Barcelona, ES) Patent Number: 6,225,057 Date filed: July 23, 1998 Abstract: A method for identifying a person at risk for developing an anxiety disorder, said anxiety disorder selected from the group consisting of agoraphobia, social phobia, panic attacks, panic disorders, simple phobia, mood disorders, major depression, schizophrenia, and hypermobility syndrome associated with duplication of a region of the genomic sequence of human chromosome 15q24-25 defined by boundaries D15S925 (proximal end) and DS15S736 (distal end). The method comprises identifying the presence of duplication in the region of the genomic sequence of human chromosome 15q24-25 defined by the boundaries D15S925 (proximal end) and DS15S736 (distal end) in said person. Excerpt(s): Panic disorder, agoraphobia, social phobia and other anxiety disorders affect 5-10% of the general population. There are no biochemical, cytological or molecular tools for the diagnosis of anxiety disorders. Moreover, the gene or genes predisposing to anxiety disorders have not yet been localised. We have studied the clinical association between panic/agoraphobia and joint hypermobility syndrome, and have identified several pedigrees in which these disorders cosegregate. We have detected a 10 centiMorgan (cM) duplication of human chromosome 15 (15q24-25) in the affected subjects of families with several members suffering from anxiety and depression disorders. The 15q24-25 duplication segregates with panic disorder, agoraphobia, social phobia, depression and joint hypermobility syndrome. The 15q24-25 duplication is strongly linked to panic disorder, agoraphobia, social phobia and joint hypermobility syndrome (lod score 4.9). Affected-only analysis for the phenotype defined only by the anxiety disorders gave a lod score of 3.36. All but one of the 45 subjects of these families with these anxiety disorders had the 15q24-25 duplication. Mosaicism was detected in 80% of the affected subjects, with 40-70% of their lymphocytes having the 15q24-25 duplication. We have also studied 50 unrelated non-familial cases of panic disorder and/or agoraphobia and all had the 15q24-25 duplication. The duplicated region contains 10 known genes of which NTRK3 and LOXL1 are likely to be involved in anxiety and joint hypermobility. We propose that this genomic mutation, which is present in 7% of the general population, is the major susceptibility mutation for panic disorder, agoraphobia, major depression and social phobia in familial and sporadic cases. We have developed cytological, cytogenetic and molecular methods for the specific diagnosis of the 15q24-25 duplication causing anxiety disorders. Anxiety disorders are neurotic alterations that include generalised anxiety disorder, phobic disorders, panic disorders (panic attacks, panic disorder and agoraphobia) and obsessive-compulsive disorders. The prevalence of this group of alterations is estimated in about 10% in the adult population and up to 5% in infantile patients. Several million people worldwide are affected by anxiety disorders, but the actual prevalence rates of these alterations are probably higher. Anxiety and panic disorders aggregate in families.
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The familial transmission of anxiety disorders has often been explained by common familial environmental factors. Twin studies of anxiety disorders have shown a high concordance among monozygotic twins. The mode of familial transmission of panic disorder is unclear, but it has been suggested that anxiety, panic attacks and agoraphobia have an autosomal dominant pattern of inheritance with incomplete penetrance. Although a major gene is supposed to be involved in panic disorder, multifactorial/polygenic inheritance has also been postulated. Web site: http://www.delphion.com/details?pn=US06225057__ •
Hand grip/filler neck recess for a tractor hood Inventor(s): Bowman; George E. (Country Club Hills, IL), Brandl; Michael C. (Westmont, IL), Kataoka; David T. (Berwyn, IL) Assignee(s): International Harvester Company (Chicago, IL) Patent Number: 4,279,320 Date filed: January 22, 1980 Abstract: The improvement of a hood of a tractor that has a filler neck passing through a neck aperture in the top surface of the hood. The neck aperture is transversely offset from the tractor's centerline. The improvement includes a downwardly projecting trough in the hood's top surface. The bottom of the trough is a major depression that is connected at four brake lines to the top surface by inner, outer, fore and aft sides. The major depression incorporates a pair of run-off apertures, with each run off aperture being adjacent one of the fore or aft sides. The neck aperture is located in the inner side of the trough, while the outer side of the trough contains a grip aperture. The improvement also includes a seal which resiliently and sealably connects the filler neck and the inner side of the trough. The improvement further includes a downwardly projecting hand grip that is sealably secured to the outer side of the trough in the grip aperture. The hand grip base is a primary depression with fore and aft ends connected by a surface that is substantially parallel to the tractor's centerline. The primary depression contains a pair of drain apertures that are each adjacent one of the fore or aft ends of the primary depression. Excerpt(s): This invention relates generally to tractor hoods and more particularly concerns tractor hoods which have a hand grip and are sealably connected to a filler neck. There is a recent trend in the agricultural industry to improve the efficiency of crop production by utilizing higher horsepower tractors on larger units of farm land. Although higher horsepower tractors are more efficient while working in the larger fields, their horsepower requirements result in high profiles for the tractors. The tractor's high profile will diminish their efficiency during servicing operations, because the high profile makes it more difficult for the operator to obtain access to the components that pass through the top of the elevated tractor hood, e.g. fuel tank and radiator filler necks. The operator's access is inhibited by his having to raise himself to the elevation of the top of the hood, and then stabilizing himself at the elevation as he performs the servicing operation on the components. Web site: http://www.delphion.com/details?pn=US04279320__
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Method of treating psychiatric disorders by electrical stimulation within the orbitofrontal cerebral cortex Inventor(s): Kopell; Brian H. (New York City, NY), Rezai; Ali R. (New York City, NY) Assignee(s): ElectroCore Techniques, LLC (Summit, NJ) Patent Number: 6,418,344 Date filed: February 24, 2000 Abstract: A method for treating psychiatric diseases such as Anxiety disorder (including General Anxiety Disorder, Obsessive Compulsive Disease, and Panic Disorder), Affective Disorder(including Major Depression and Bipolar Disorder) by neuromodulation (either chemical or electrical) of the frontal cerebral cortex, and in particular regions within the orbitofrontal cerebral cortex. The method includes the steps of determining a common group of patients, each suffering from a common specific diagnosis for a psychiatric disorder; determining which common regions of the patients' orbitofrontal cerebral cortex are involved in the pathogenesis of the abnormal electrical and chemical activity associated with the psychiatric disease; surgically implanting an electrode and/or catheter and electrical signal generating device and/or drug-delivery pump such that the electrode and/or catheter is positioned within the region of the frontal cerebral cortex known as the orbitofrontal cortex; and selectively adjusting the level of electrical and/or chemical stimulation in accordance with the specific effect of the stimulation of the patient. In particular, the region of the frontal cerebral cortex most frequently associated with psychiatric disorders is the orbitofrontal cortex. Excerpt(s): This invention relates generally to the treatment of psychiatric disorders by modulating the activity within appropriate regions of the cerebral prefrontal cortex, and more particularly to a method of modifying pathological electrical and chemical activity of the brain by electrical stimulation and/or direct placement of neuromodulating chemicals within the corresponding areas of the orbitofrontal cerebral cortex (OFC). The treatment of psychiatric disorders by neurosurgical techniques has an extensive history. In the early 1930's Fulton and Jacobsen first recongnized that an experimentally induced neurotic behavior in chimpanzees could be abolished by frontal lobectomy. Within a few years, Freeman and Watts developed the first psychosurgical procedure for humans known as the frontal lobotomy. As the inherent physiology of the frontal lobe became more evident, the original freehand procedure of Freeman and Watts became less and less extensive. By the late 1940's, the method of stereotaxis, in which the patient's brain is modeled in 3-dimensional space for exquisite targeting accuracy, merged with lesioning techniques resulting in an even more efficacious and safe psychosurgical procedure. Further developments of stereotactic equipment have combined with novel advancements in functional and anatomic imaging to encompass the state of the art in the neurosurgical treatment of psychiatric disorders today. However, the fundamental limitation of these lesioning techniques is that they are inherently irreverible and static in nature. There is no proverbial "off" switch to alleviate side effects and no way to adjust the desirable effects in response to a patient's developing symptom profile. Within the field of neurosurgery, the use of electrical stimulation for treating neurological disease, including such disorders as compulsive eating, chronic pain, movement disorders, has been widely discussed in the literature. It has been recognized that electrical stimulation holds significant advantages over alternative methods of treatment, for example lesioning, inasmuch as lesioning can only destroy neuronal activity. In many instances, the preferred effect is to stimulate or reversibly block neural signals. Electrical stimulation permits such stimulation of the target neural structures,
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and equally importantly, it does not require the destruction of the nervous tissue (it is a reversible process, which can literally be shut off or removed at will). Web site: http://www.delphion.com/details?pn=US06418344__ •
Methods for improving the therapeutic response of humans having major depression and carrying the gene for apolipoprotein E4 Inventor(s): Murphy, Jr.; Greer M. (Stanford, CA), Schatzberg; Alan F. (Los Altos, CA) Assignee(s): Akzo Nobel N.V. (NL) Patent Number: 6,399,310 Date filed: February 12, 2001 Abstract: This invention 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 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 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://www.delphion.com/details?pn=US06399310__
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Methods of neuroendocrine regulation of affective disorders Inventor(s): De Castro Paixao; Julio Licinio (Bethesda, MD), Flier; Jeffrey S. (West Newton, MA), Gold; Philip W. (Washington, DC), Wong; Ma-Li (Bethesda, MD) Assignee(s): Beth Israel Deaconess Medical Center (Boston, MA) Patent Number: 5,866,547 Date filed: January 20, 1998 Abstract: Methods of treating an affective disorder in an individual are disclosed. Affective disorders include major depression, melancholic and atypical subtypes, and dysthymia. Excerpt(s): Affective and mood disorders are included in a group of mental disorders characterized by neuroendocrine dysregulation and are characterized by a disturbance in the regulation of mood, behavior, and affect. Affective and mood disorders can have serious impact on an individual's functional ability, interpersonal relationships and behavior. Major depression and dysthymia are examples such disorders. Major depression is a syndromal, episodic and recurrent illness with both psychological and biological components. A diagnosis of bipolar disorder is given to those patients with recurring depression and mania. Those patients with recurrent depression alone have a unipolar pattern. Within the spectrum of depressive illness, there are two distinct subtypes: melancholic depression and atypical depression (Gold et al., N. Engl. J. Med., 319:348-353 (1988); and Gold et al., N. Engl. J. Med., 319:413-420 (1988)). Melancholic depression is equally common among those with a pattern of unipolar and bipolar depression. Melancholic depression is characterized by hyposomnia (early morning awakening), anorexia and diurnal variation in mood, and is associated with a state of hyperarousal in which patients are painfully preoccupied with personal inadequacy, loss, feelings of worthlessness, guilt and suicidal ideation (Licinio et al., Bailliere's Clin. Endocrin. Met., 5(1):51-58 (1991)). Web site: http://www.delphion.com/details?pn=US05866547__
Patent Applications on Major Depression 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 major depression: •
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
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This has been a common practice outside the United States prior to December 2000.
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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 •
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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Compositions and methods for diagnosing and treating mood disorders Inventor(s): Akil, Huda; (Ann Arbor, MI), Bunney, William E. JR.; (Laguna Hills, CA), Choudary, Prabhakara V.; (Davis, CA), Evans, Simon J.; (Milan, MI), Jones, Edward G.; (Winters, CA), Li, Jun; (Palo Alto, CA), Lopez, Juan F.; (Ann Arbor, MI), Myers, Richard; (Stanford, CA), Thompson, Robert C.; (Ann Arbor, MI), Tomita, Hiroaki; (Irvine, CA), Vawter, Marquis P.; (Niguel, CA), Watson, Stanley; (Ann Arbor, MI) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20040152111 Date filed: November 3, 2003 Abstract: The present invention provides methods for diagnosing mental disorders such as mood disorders, including bipolar disorder I and II and major depression. The invention also provides methods of identifying modulators of such mental disorders as well as methods of using these modulators to treat patients suffering from such mental disorders. Excerpt(s): The present application claims the benefit of U.S. S No. 60/423,247, filed Nov. 1, 2002 and U.S. S No. 60/431,454, filed Dec. 6, 2002, the disclosures of which are hereby incorporated by reference in their entirety for all purposes. Not applicable. Clinical depression, including both bipolar disorders and major depression disorders, is a major public health problem, affecting an estimated 9.5% of the adult population of the United States each year. While it has been hypothesized that mental disorders, including mood disorders such as major depression and bipolar disorder as well as psychotic disorders such as schizophrenia, have complex genetic roots, little progress has been made in identifying gene sequences and gene products that play a role in causing these disorders, as is true for many diseases with a complex genetic origin (see, e.g., Burmeister, Biol. Psychiatry 45:522-532 (1999)). Relying on the discovery that certain genes expressed in particular brain pathways and regions are likely involved in the development of mental disorders, the present invention provides methods for diagnosis and treatment of mental disorders, as well as methods for identifying compounds effective in treating mental disorders. 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 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
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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 •
Omega-3 fatty acids in the treatment of depression Inventor(s): Stoll, Andrew; (Lincoln, MA) Correspondence: Choate, Hall & Stewart; Exchange Place; 53 State Street; Boston; MA; 02109; US Patent Application Number: 20030012827 Date filed: February 27, 2002 Abstract: The present invention is directed to a method of treating patients with major depression by administering omega-3 fatty acids. These may be administered in a substantially purified form, as part of a pharmaceutical composition, or as part of a larger molecule, e.g., a triacylglycerol, which releases free fatty acid after ingestion by a patient.The present invention is also directed to triacylglycerols which are esterified at the gamma cardon of glycerol to phosphocholine and at either the alpha or beta carbon
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of glycerol to an omega-3 fatty acid. These "omega-3 phoshatidylcholines" are also used in the treatment of patients with major depression. Excerpt(s): This application is a continuation-in-part of U.S. Patent Application entitled "Omega-3 Fatty Acids and Omega-3 Phosphatidylcholine in the Treatment of Bipolar Disorder", filed Feb. 5, 2002, using Express Mail No.: ET796587916US, which is a continuation of U.S. Ser. No. 09/269,361, filed Mar. 22, 1999, now issued as U.S. Pat. No. 6,344,482, which claims priority from PCT/US97/06712, filed Apr. 23, 1997. The contents of all of these applications are incorporated herein by reference. The present invention relates to medical treatments for psychiatric disorders. More specifically, it is concerned with novel methods and compositions for treating patients with unipolar major depression. Major depression is a neuropsychiatric illness characterized by a persistently low mood or diminished interests in one's surroundings, accompanied by at least several of the following symptoms: Reduced energy and motivation, difficulty concentrating, altered sleep and appetite, and at times, suicidal ideation (American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, ed. 4. Washington, American Psychiatric Association, 1994). Major depression without a history of abnormally elevated mood and energy (mania) is termed "unipolar major depression."However, a sizeable proportion of depressed patients presenting for treatment have bipolar disorder (also known as manic depressive illness), where there is a history of mania, or a milder form of mood elevation known as hypomania (Goodwin F K, Jamison K R: Manic Depressive Illness. London, Oxford University Press, 1990). Whether part of a unipolar or a bipolar illness, major depression is associated with high rates of morbidity and mortality, with suicide rates of 10-25% (Kaplan H I, Sadock B J (eds): Synopsis of Psychiatry. Baltimore, Williams & Wilkins, 1998, p. 866). According to the World Health Organization (WHO), major depression is the fourth leading cause of vocational disability on earth (Murray C J L, Lopez A D (eds): The Global Burden of Disease. Geneva, World Health Organization, 1996, vol. 1). Furthermore, the incidence of major depression increased and the age of onset of depression decreased with each passing decade of the 20th century (Klerman G L, Weissman M M: Increasing rates of depression. JAMA 1989; 261:2229-2235). Effective psychotherapeutic and pharmacological antidepressant treatments for major depression exist, but each has shortcomings. Two modern forms of psychotherapy, cognitive-behavioral therapy and interpersonal therapy, have shown efficacy in controlled studies of major depression (Kaplan, 1998, pp. 885-931). However, for moderate or severe depression, antidepressant medication is generally more effective, rapidly acting, and less expensive than psychotherapy. The combination of psychotherapy and medications has recently been shown to be superior to either treatment modality (Keller M B, et al.: A comparison of nefazodone, the cognitive behavioral-analysis system of psychotherapy, and their combination for the treatment of chronic depression. N Engl J Med 2000; 342:14621470). There are more than 20 approved antidepressant drugs available in the United States. All of these medications have proven acute efficacy for major depression. The newer agents, such as the selective serotonin reuptake inhibitors (SSRIs), are far less toxic than the older classes of antidepressants, but even the SSRIs carry a substantial burden of side-effects, including sexual dysfunction, sleep disturbance, and weight gain (Kaplan, 1998). In addition, no currently available antidepressant is acutely effective in more than 60-70% of the patients who receive it. Furthermore, long-term data exists for only a few antidepressant drugs, and it appears that efficacy may diminish over time with some agents (Fredman S J, et al.: Partial response, nonresponse, and relapse with selective serotonin reuptake inhibitors in major depression: a survey of current "next-step" practices. J Clin Psychiatry; 2000, 61:403-408). Thus, there is a need for newer treatments, with greater efficacy and safety, as well as fewer side-effects.
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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Polymorphisms of the 5' region of the human 5-HT1A gene, associated proteins of the 5' region and a diagnostic test for major depression and related mental illnesses Inventor(s): Albert, Paul; (Ottawa, CA), Lemonde, Sylvie; (Cantley, CA) Correspondence: Sheridan Ross PC; 1560 Broadway; Suite 1200; Denver; CO; 80202 Patent Application Number: 20040171083 Date filed: August 5, 2003 Abstract: Clinical response to antidepressant compounds correlates with a selective down-regulation of presynaptic 5-HT1A receptors in serotonergic raphe neurons. Thus regulation of the 5-HT1A receptor gene could play a crucial role in the treatment or etiology of major depression. The promoter and repressor activities of the human 5HT1A receptor gene have been examined. The analysis of the 5'-flanking regions of the 5-HT1A receptor gene has revealed a segment located between about -3438 and about 393 bp upstream from the initiator ATG that mediates cell-specific repression of the gene that is greater in cells that do not express the 5-HT1A receptor. The sequence of part of this region in patients with major depression was examined and a polymorphic C-G change located at -1019 bp (numbered earlier as -1017) was identified, which is associated with major depression. Thus, this sequence can be used as a genetic marker for major depression and related mental illnesses. Proteins that bind to the DNA at the 1019 locus have been identified. Such proteins that bind to this DNA region, for example the transcription factors NUDR/DEAF-1/suppressin and HES-5, are important targets for the development of therapeutic compounds for the treatment of major depression and related mental illness that involve the serotonin system. In addition the promoter region from about -393 to the initiator ATG displays glucocorticoid-mediated repression. Excerpt(s): The present invention relates to a DNA sequence of the 5' flanking region of the 5-HT1A receptor gene, from about -3438 to about -393, wherein said sequence contains a polymorphism that results in a reduction of protein-DNA interactions. This invention further relates to proteins, which bind to this region and the use of said proteins, as targets, to develop therapeutics to treat depression and related illnesses that involve the serotonin system. This invention also relates to a diagnostic or prognostic test for mental illnesses, and other conditions that involve the serotonin system, using the novel DNA sequence as a genetic marker. This invention also relates to a glucocorticoid-responsive element located from about -393 to the ATG initiation codon of the 5-HT1A receptor gene. Serotonin (5-HT), a key neurotransmitter in the central nervous system, is believed to play a role in various cognitive functions such as sleep, pain perception, depression, learning and anxiety (Blier et al., 1990; Jacobs and Azmitia, 1992; Mongeau et al., 1997). Neurons of the raphe nuclei which release serotonin have project axons widely throughout the brain to innervate a variety of nuclei (Tork, 1990). The activity of the raphe nucleus is controlled in part by inhibitory somatodendritic 5HT1A autoreceptors. The serotonin 1A (5-HT1A) receptor belongs to the seventransmembrane G-protein coupled receptor superfamily (Hoyer et al., 1994). Its activation inhibits adenylyl cyclase activity, increases K+ conductance causing a decrease in action potential frequency, and decreases the opening of voltage-dependent calcium channels (Penington and Kelly, 1990; Penington et al., 1993; Zgombick et al., 1989). An important function of 5-HT1A autoreceptors in the raphe nuclei is thus to control the frequency of action potential firing. Increase in action potential frequency
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leads to serotonin release at the cell body, which activates the 5-HT1A receptor to decrease raphe firing and reduce the release of serotonin, as part of a negative feed-back loop (Albert et al., 1996). As longterm regulation of the 5-HT1A receptor is implicated in major depression, we have investigated the promoter of the human 5-HT1A receptor gene to characterize and identify specific loci associated with depression. Changes in gene expression persist for days to weeks, and could underlie the down-regulation of 5HT1A receptors by antidepressant compounds over the 2-week treatment period. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Use of cortisol-sequestering agents for the treatment of hypercortisolaemia related disorders Inventor(s): Hill, David Robert; (Sctoland, GB), Rees, David; (Cambridge, GB), Zhang, Mingqiang; (Kirkland, CA) Correspondence: William M Blackstone; Akzo Nobel Patent Department; Intervet Inc; 405 State Street; Millsboro; DE; 19966; US Patent Application Number: 20040048830 Date filed: September 2, 2003 Abstract: The invention relates to the use of sequestering agents for the preparation of a medicament for the treatment of hypercortisolaemia related disorders, especially for the treatment of major depression; to pharmaceutical compositions comprising a cortisolsequestering agent, and to the cortisol-sequestering agent 6-per-deoxy-6-per-(2,3dihydroxypropyl- thio)-.gamma.-cyclodextrin. Excerpt(s): The invention relates to the use of sequestering agents for the preparation of a medicament for the treatment of hypercortisolaemia related disorders, especially for the treatment of major depression. One of the most consistent findings in psychiatry is that patients with major depression present with hypercortisolaemia (Holsboer, F. et al., Cortisol, 11-deoxy-cortisol and ACTH concentrations after dexamethasone in depressed patients and healthy volunteers. Psychiatry Res. 11, 15-23, 1984)). This hypercortisolaemia can reach an order of magnitude and indicates a gross disturbance in the negative feedback mechanisms that normally strongly regulate the endocrine stress HPA (hypothalamo-pituitary-adrenal) axis. Although not all depressed patients have manifest hypercortisolaemia, patients who suffer the most severe types of monoamine-resistant depression are in majority those in whom high levels of the stress hormone cortisol are apparent. Further, in almost all cases they exhibit a clear inability to switch off endogenous cortisol release following exogenous challenge with the potent synthetic glucocorticoid dexamethasone (the so-called dexamethasone non-suppressors) (Gold P. W., et al., Clinical and biochemical manifestations of depression: relation to neurobiology of stress. New England J. Med. 319, 413-420, 1988). This `sub-group` of severely compromised patients are most often the ones in whom depression becomes a life-threatening illness that warrants hospitalisation. A prompt treatment strategy like electroconvulsive therapy (ECT) may be necessary in such patients. Another condition in which high cortisol levels are reported as a result of adrenal gland malfunction (due to a pituitary tumour or a secondary tumour, both producing the cortisol secretagogue ACTH) is the Cushing's syndrome. The depressive symptoms associated with Cushing's disappear relatively quickly once the underlying cause of the disease has been treated, with the return of cortisol levels to normal. Such treatment may involve removal of the offending tumour or treatment with cortisol synthesis inhibitors such as metyrapone,
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ketoconozole, or aminoglutethimide (Murpy, B. E. P., Steroids and Depression. J. Steroid Biochem & Mol. Biol. 38, 537-558, 1991). 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 major depression, 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 “major depression” (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 major depression. You can also use this procedure to view pending patent applications concerning major depression. 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 MAJOR DEPRESSION Overview This chapter provides bibliographic book references relating to major depression. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on major depression 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 “major depression” (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 major depression: •
Brain Facts: A Primer on the Brain and Nervous System Source: Washington, DC: Society for Neuroscience. 1993. 52 p. Contact: Society for Neuroscience. 11 Dupont Circle, NW, Suite 500, Washington, DC 20036. (202) 462-6688. PRICE: $6.00. Summary: This book briefly describes what is known about the brain and nervous system, brain disorders, and avenues of research that promise new therapies for many of the most devastating neurological and psychiatric diseases. Topics include brain development; what a neuron is and its function; and the brain's involvement in sensation and perception, learning and memory, movement, sleep, stress, and aging. This book examines advances in research on Parkinson's disease, pain, epilepsy, major depression, and manic-depressive illness in addition to neurological disorders such as addiction, Alzheimer's disease, Down syndrome, Gilles de la Tourette's syndrome, brain
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tumors, and multiple sclerosis. It explores recent advances in diagnostic methods such as positron emission tomography, magnetic resonance imaging, magnetic source imaging, and gene diagnosis; and discusses potential therapies using drugs and transplants. •
Neurobiology of Primary Dementia Source: Washington, DC: American Psychiatric Press, Inc. 1998. 418 p. Contact: American Psychiatric Press, Inc. 1400 K Street, NW, Washington, DC 20005. (800) 368-5777; (202) 682-6262. Internet access: http://www.appi.org. PRICE: $61.50. ISBN: 0880489154. Summary: This book for health care practitioners, service providers, and policy makers, presents findings from recent research into the neurobiology of Alzheimer's disease (AD) and other primary dementias. One chapter reviews the epidemiology of dementia, using data from an ethnically diverse registry of older people who use communitybased services. Chapters focusing on AD discuss such topics as the genetics of familial AD, the cellular production of amyloid beta-protein in AD, the regulation of betaamyloid metabolism in AD, beta-amyloid amyloidogenesis in model systems of AD, head trauma as a risk factor for AD, brain imaging in AD, and diagnostic markers for AD. Other dementias are addressed in chapters on prion diseases, dementia associated with poststroke major depression, vascular dementia, dementia pugilistica, and the acquired immunodeficiency syndrome dementia complex. The book also discusses potential pharmacological treatments for AD, the practical management of AD, genetic counseling in AD and Huntington's disease, ethical issues in dementia, and the prospects for health care reform.
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Memory Functioning in Dementia Source: New York, NY: Elsevier Science Publishing Co. 1992. 299 p. Contact: Available from Elsevier Science Publishing Co. P.O. Box 882, Madison Square Station, New York, NY 10059. (212) 633-3965. PRICE: $131.50. Summary: This book reviews and synthesizes recent research on memory impairment in Alzheimer's disease and other kinds of dementia. Section one, on episodic memory in Alzheimer's disease, includes four articles, discussing patterns of short-term memory impairment; the multiple causes of episodic memory deficits; forgetting; and use of cognitive support to improve episodic memory. Section two discusses different kinds of non-episodic memories, including semantic memory, priming, and skill learning, semantic knowledge and degradation, and motor and procedural memory. The third section examines research comparing persons with Alzheimer's disease and other persons with memory disturbances. This section discusses memory dysfunction in subcortical dementias, and the interaction of language and memory in major depression and Alzheimer's disease. In section four, the progression of dementia is explored. The final section reviews research that uses subjective information to assess memory in persons with dementia. 27 references.
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Concise Guide to Geriatric Psychiatry. 2nd ed Source: Washington, DC: American Psychiatric Press, Inc. 1997. 326 p. Contact: American Psychiatric Press, Inc. 1400 K Street, NW, Washington, DC 20005. (800) 368-5777; (202) 682-6262. Internet access: http://www.appi.org. PRICE: $21.00. ISBN: 0880487968. Order Number: INET8796.
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Summary: This handbook is intended to assist geriatric psychiatrists in the diagnosis and treatment of mental disorders that often are seen in later life. The book provides background information about contemporary issues in aging and health care, barriers to geriatric mental health care, and strategies for working effectively with older patients. It includes an overview of the process of normal aging and the cognitive, personality, and physical changes that occur as people age. It discusses the diagnosis and treatment of major depression and bipolar mood disorder, Alzheimer's disease (AD) and other dementias, delirium, anxiety disorders, late-onset psychosis, sleep disorders, substance abuse, sexual dysfunction, and other psychiatric illnesses. The chapter on AD discusses the diagnosis, epidemiology, clinical presentation, pathogenesis, diagnostic criteria, clinical evaluation, and treatment. An appendix includes various clinical assessment instruments with scoring instructions or ordering information.
Chapters on Major Depression In order to find chapters that specifically relate to major depression, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and major depression 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 “major depression” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on major depression: •
Current Understandings of Construct Source: in Emery, V.O.B. Pseudodementia: A Theoretical and Empirical Discussion. Cleveland, OH: Western Reserve Geriatric Education Center, Case Western Reserve University School of Medicine. 1988. 74 p. Contact: This publication may be available from your local medical library. Call for information. Summary: This book chapter describes a study and presentation of data pertaining to memory and language processing in the populations of depressive pseudodementia, major depression/unipolar, senior dementia Alzheimer's type, and normal elderly. Seventy-two demographically equivalent elderly persons were administered eight measures of memory, nine measures of oral language, two measures of reading, and two non-verbal measures. Memory and language patterning were examined in the research populations with special interest in how to differentiate depressive pseudodementia from senile dementia Alzheimer's type. A combination of measures helped to discriminate between depressive pseudodementia and comparison groups. In terms of the variables of clinical behavior, patients with depressive pseudodementia often complained of cognitive deterioration, whereas patients with Alzheimer's disease complained little of cognitive loss and approached their own deterioration in a vague manner. Patients in early to moderate stages of Alzheimer's disease rely on notes and other methods of self-reminding, and social skills often remain intact long after dysfunction in other areas. In contrast, the loss of social skills is early and conspicuous in depressive pseudodementia.
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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.
•
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. 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.
•
Chronic Tinnitus Following Electroconvulsive Therapy Source: in Hazell, J., ed. Proceedings of the Sixth International Tinnitus Seminar. London, England: Tinnitus and Hyperacusis Centre. 1999. p. 243-245. Contact: Available from Tinnitus and Hyperacusis Centre. 32 Devonshire Place, London, W1N 1PE, United Kingdom. Fax 44 + (0) 207 486 2218. E-mail:
[email protected]. Website: www.tinnitus.org. PRICE: Contact publisher for price. ISBN: 0953695700. Also available on CD-ROM.
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Summary: Tinnitus can be caused by almost any pathology involving the auditory system and can also result from head trauma, a variety of medications, and electrical shock, including lightning strikes. This article is from a lengthy document that reprints the proceedings of the Sixth International Tinnitus Seminar, held in Cambridge, United Kingdom, in September 1999 and hosted by the British Society of Audiology. In this article, the authors report a case study of chronic tinnitus that began immediately following electroconvulsive therapy (ECT). A 43 year old female with a 27 year history of obsessive compulsive disorder and major depression had previously been treated with psychotherapy, antidepressant and antipsychotic medications. Because these treatments were minimally effective and because the frequency and duration of her depressive episodes continued to increase, the patient was scheduled to undergo a series of ECT procedures. The patient received four ECT treatments during one week. Stimulating current was delivered through a unilateral electrode to the right frontotemporal region of the head. EEG seizures occurred during each of the ECT procedures. After the patient recovered from anesthesia, she complained of headaches, muscle pain, amnesia, and, after the fourth ECT, she reported a ringing sound in her right ear. Audiometric testing the day after the fourth ECT revealed a slight increase in threshold for 8000 Hz tones in her right ear. The authors conclude that it is likely that current delivered during the fourth ECT treatment triggered the perception of tinnitus for this patient. The unique organization of this patient's central nervous and auditory systems combined with her particular pharmacological history might have predisposed her to developing this symptom.
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CHAPTER 7. MULTIMEDIA ON MAJOR DEPRESSION Overview In this chapter, we show you how to keep current on multimedia sources of information on major depression. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on major depression is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “major depression” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, 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 “Videorecording (videotape, videocassette, etc.).” Type “major depression” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on major depression: •
Neuropsychiatric Aspects of HIV/AIDS Contact: University of Washington, Northwest AIDS Education and Training Center, 901 Boren Ave Ste 1100, Seattle, WA, 98104-3596, (800) 677-4799, http://depts.washington.edu/nwaetc/. Summary: This videorecording is a lecture by Dr. Terence C. Gayle, a clinical assistant professor at the University of Washington/Harborview Medical Center. Aimed at firstyear residents in psychiatry, it covers neuropsychological disorders commonly found in Human immunodeficiency virus (HIV) disease. He begins his lecture by discussing the epidemiology of Acquired immunodeficiency syndrome (AIDS). He then examines, in detail, the three types of neurological disorders: Organic problems such as delirium and dementia, psychoses, and mood disorders such as mania and major depression. The majority of the lecture focuses on AIDS Dementia Complex, with detailed information on early and late stage signs and symptoms, possible causes, and types of treatment. He delves into the ethical dilemmas of caring for a patient who has a pressing need for
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treatment, but may die soon. Gayle then goes on to take less detailed looks at psychoses and depression.
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CHAPTER 8. PERIODICALS AND NEWS ON MAJOR DEPRESSION Overview In this chapter, we suggest a number of news sources and present various periodicals that cover major depression.
News Services and Press Releases One of the simplest ways of tracking press releases on major depression 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 “major depression” (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 major depression. 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 “major depression” (or synonyms). The following was recently listed in this archive for major depression: •
FDA advises against Glaxo's Paxil for major depression in children Source: Reuters Industry Breifing Date: June 19, 2003
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Morning light therapy alleviates major depression during pregnancy Source: Reuters Medical News Date: April 26, 2002 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. 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 “major depression” (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 “major depression” (or synonyms). If you know the name of a company that is relevant to major depression, 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 “major depression” (or synonyms).
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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 “major depression” (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 major depression: •
ECT for Agitation in Patients With Dementia Source: American Association for Geriatric Psychiatry Newsletter. 11(11): 15-16. September-October 1990. Contact: Available from American Association for Geriatric Psychiatry, Central Office. P.O. Box 376A, Greenbelt, MD 20768. (301) 220-0952. PRICE: Call for price information. Summary: This newsletter article for the geriatric psychiatrist examines the use of electroconvulsive therapy (ECT) for agitated depressive symptoms in patients who are not responsive to tricyclics, heterocyclic antidepressants, neuroleptics, or benzodiazepines. ECT generally produces a good outcome and is looked upon as the treatment of choice for delusional depression which is often accompanied by an agitated state. However, it has not been established as to whether ECT is indicated for used in agitation associated with dementia without a depressive component. ECT has not been definitely indicated for chronic organic brain syndromes without a depressive component. A problem in assessment and treatment of agitation in patients with dementia but without major depression is obtaining the special informed consent needed for ECT use. Assessment of the patient's ability to provide informed consent as well as a conference with the patient and family can assist in determining the use of ECT. 20 references.
Academic Periodicals covering Major Depression Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to major depression. In addition to these sources, you can search for articles covering major depression 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 9. 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 major depression. 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 nonprofit 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 major depression. 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 major depression: Lithium •
Systemic - U.S. Brands: Cibalith-S; Eskalith; Eskalith CR; Lithane; Lithobid; Lithonate; Lithotabs http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202330.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, 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: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
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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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National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
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National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
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National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
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National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
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National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
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National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
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National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
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National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
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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
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National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
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National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
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Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
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National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
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National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
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Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
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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 •
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
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HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
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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
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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/
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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
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
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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/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
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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
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Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
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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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Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
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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 “major depression” (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 11839 54 337 102 161 12493
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 “major depression” (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 17
The HSTAT URL is http://hstat.nlm.nih.gov/.
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: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
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 major depression 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 major depression. 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 major depression. 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 “major depression”:
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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 Postpartum Depression http://www.nlm.nih.gov/medlineplus/postpartumdepression.html Seasonal Affective Disorder http://www.nlm.nih.gov/medlineplus/seasonalaffectivedisorder.html Suicide http://www.nlm.nih.gov/medlineplus/suicide.html 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 major depression. 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: •
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.
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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 “major depression” (or synonyms). The following was recently posted: •
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=major+AND+depression 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 major depression. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information 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: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/specific.htm
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Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
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Med Help International: http://www.medhelp.org/HealthTopics/A.html
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Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
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Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
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WebMDHealth: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to major depression. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with major depression.
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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 major depression. 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 “major depression” (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 “major depression”. Type the following hyperlink 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 “major depression” (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 “major depression” (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: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
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Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
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Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
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California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
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California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
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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
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California: Gateway Health Library (Sutter Gould Medical Foundation)
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California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
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California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
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California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
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California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
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California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
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California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
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California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
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California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
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Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
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Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
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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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•
Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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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
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
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Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
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Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
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Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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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
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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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
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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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/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
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New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
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Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
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Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
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Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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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: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
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
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On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
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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 major depression: •
Basic Guidelines for Major Depression Major depression Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000945.htm Major depression with psychotic features Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000933.htm
•
Signs & Symptoms for Major Depression Dejection Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003213.htm Depression 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
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Hallucinations Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003258.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 Seizure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003200.htm Sleep disturbances Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003210.htm Stress Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003211.htm Weakness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003174.htm Weight loss Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003107.htm •
Diagnostics and Tests for Major Depression ECT Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003324.htm Electroconvulsive therapy Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003324.htm Serotonin Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003562.htm
•
Background Topics for Major Depression Central nervous system Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002311.htm Depression - support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002177.htm Incidence Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002387.htm Support group Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002150.htm
Online Glossaries 183
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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MAJOR DEPRESSION DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 3-dimensional: 3-D. A graphic display of depth, width, and height. Three-dimensional radiation therapy uses computers to create a 3-dimensional picture of the tumor. This allows doctors to give the highest possible dose of radiation to the tumor, while sparing the normal tissue as much as possible. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [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 fat: Fat (adipose tissue) that is centrally distributed between the thorax and pelvis and that induces greater health risk. [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] Abortion: 1. The premature expulsion from the uterus of the products of conception - of the embryo, or of a nonviable fetus. The four classic symptoms, usually present in each type of abortion, are uterine contractions, uterine haemorrhage, softening and dilatation of the cervix, and presentation or expulsion of all or part of the products of conception. 2. Premature stoppage of a natural or a pathological process. [EU] Absenteeism: Chronic absence from work or other duty. [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] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Actin: Essential component of the cell skeleton. [NIH] Activities of Daily Living: The performance of the basic activities of self care, such as dressing, ambulation, eating, etc., in rehabilitation. [NIH] Adaptability: Ability to develop some form of tolerance to conditions extremely different from those under which a living organism evolved. [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
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microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenocarcinoma: A malignant epithelial tumor with a glandular organization. [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] Adenosine Triphosphate: Adenosine 5'-(tetrahydrogen triphosphate). An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter. [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] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [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] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Aerobic Exercise: A type of physical activity that includes walking, jogging, running, and dancing. Aerobic training improves the efficiency of the aerobic energy-producing systems that can improve cardiorespiratory endurance. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
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
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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] Agmatine: Decarboxylated arginine, isolated from several plant and animal sources, e.g., pollen, ergot, herring sperm, octopus muscle. [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] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] 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-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] Alveoli: Tiny air sacs at the end of the bronchioles in the lungs. [NIH] Ambulatory Care: Health care services provided to patients on an ambulatory basis, rather than by admission to a hospital or other health care facility. The services may be a part of a hospital, augmenting its inpatient services, or may be provided at a free-standing facility. [NIH]
Amine: An organic compound containing nitrogen; any member of a group of chemical
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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] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Aminoglutethimide: An anticancer drug that belongs to the family of drugs called nonsteroidal aromatase inhibitors. Aminoglutethimide is used to decrease the production of sex hormones (estrogen or testosterone) and suppress the growth of tumors that need sex hormones to grow. [NIH] 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] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [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]
Amyloid: A general term for a variety of different proteins that accumulate as extracellular fibrils of 7-10 nm and have common structural features, including a beta-pleated sheet conformation and the ability to bind such dyes as Congo red and thioflavine (Kandel, Schwartz, and Jessel, Principles of Neural Science, 3rd ed). [NIH] Amyloid beta-Protein: A 4 kD protein, 39-43 amino acids long, expressed by a gene located on chromosome 21. It is the major protein subunit of the vascular and plaque amyloid filaments in individuals with Alzheimer's disease and in aged individuals with trisomy 21 (Down syndrome). The protein is found predominantly in the nervous system, but there have been reports of its presence in non-neural tissue. [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]
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Anal: Having to do with the anus, which is the posterior opening of the large bowel. [NIH] Analgesics: Compounds capable of relieving pain without the loss of consciousness or without producing anesthesia. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] 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] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]
Anomalies: Birth defects; abnormalities. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Anosognosia: Inability to recognize loss of function, disease, or defect in a part of one's own body. [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] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [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
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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] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] 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] Antiviral: Destroying viruses or suppressing their replication. [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] Apnea: A transient absence of spontaneous respiration. [NIH] Apomorphine: A derivative of morphine that is a dopamine D2 agonist. It is a powerful emetic and has been used for that effect in acute poisoning. It has also been used in the diagnosis and treatment of parkinsonism, but its adverse effects limit its use. [NIH] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Applicability: A list of the commodities to which the candidate method can be applied as presented or with minor modifications. [NIH] Approximate: Approximal [EU] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Aromatase: An enzyme which converts androgens to estrogens by desaturating ring A of the steroid. This enzyme complex is located in the endoplasmic reticulum of estrogen-
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producing cells including ovaries, placenta, testicular Sertoli and Leydig cells, adipose, and brain tissues. The enzyme complex has two components, one of which is the CYP19 gene product, the aromatase cytochrome P-450. The other component is NADPH-cytochrome P450 reductase which transfers reducing equivalents to P-450(arom). EC 1.14.13.-. [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] Articulation: The relationship of two bodies by means of a moveable joint. [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] 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] Atrophy: Decrease in the size of a cell, tissue, organ, or multiple organs, associated with a variety of pathological conditions such as abnormal cellular changes, ischemia, malnutrition, or hormonal changes. [NIH] 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] 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] Autopsy: Postmortem examination of the body. [NIH] Autoreceptors: Transmitter receptors on or near presynaptic terminals (or varicosities) which are sensitive to the transmitter(s) released by the terminal itself. Receptors for the hormones released by hormone-releasing cells are also included. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [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
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important. [NIH] Basal Ganglia: Large subcortical nuclear masses derived from the telencephalon and located in the basal regions of the cerebral hemispheres. [NIH] Beclomethasone: An anti-inflammatory, synthetic glucocorticoid. It is used topically as an anti-inflammatory agent and in aerosol form for the treatment of asthma. [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]
Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [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] Bereavement: Refers to the whole process of grieving and mourning and is associated with a deep sense of loss and sadness. [NIH] Beta-Endorphin: A peptide consisting of amino acid sequence 61-91 of the endogenous pituitary hormone beta-lipotropin. The first four amino acids show a common tetrapeptide sequence with methionine- and leucine enkephalin. The compound shows opiate-like activity. Injection of beta-endorphin induces a profound analgesia of the whole body for several hours. This action is reversed after administration of naloxone. [NIH] Beta-pleated: Particular three-dimensional pattern of amyloidoses. [NIH] Bewilderment: Impairment or loss of will power. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [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]
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Blastocyst: The mammalian embryo in the post-morula stage in which a fluid-filled cavity, enclosed primarily by trophoblast, contains an inner cell mass which becomes the embryonic disc. [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] Blot: To transfer DNA, RNA, or proteins to an immobilizing matrix such as nitrocellulose. [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 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] 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 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] Bromine: A halogen with the atomic symbol Br, atomic number 36, and atomic weight 79.904. It is a volatile reddish-brown liquid that gives off suffocating vapors, is corrosive to the skin, and may cause severe gastroenteritis if ingested. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [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] Calcium: A basic element found in nearly all organized tissues. It is a member of the 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] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and
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the N-, P-, Q-, & R-types are located in neuronal tissue. [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] Carcinoma: Cancer that begins in the skin or in tissues that line or cover internal organs. [NIH]
Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardiorespiratory: Relating to the heart and lungs and their function. [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] 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] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Causal: Pertaining to a cause; directed against a cause. [EU] Cause of Death: Factors which produce cessation of all vital bodily functions. They can be analyzed from an epidemiologic viewpoint. [NIH] 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 Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Division: The fission of a cell. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral
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proteins are embedded to varying degrees. [EU] 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] Cell Size: The physical dimensions of a cell. It refers mainly to changes in dimensions correlated with physiological or pathological changes in cells. [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 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] 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] 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] 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] 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] Choline: A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. [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]
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Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [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] 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 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] 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] Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Diseases: Diseases of the cochlea, the part of the inner ear that is concerned with hearing. [NIH] Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (codon, terminator). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, transfer) complementary to all codons. These codons are referred to as unassigned codons (codons, nonsense). [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] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2.
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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] Community Mental Health Centers: Facilities which administer the delivery of psychologic and psychiatric services to people living in a neighborhood or community. [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 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
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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] Conception: The onset of pregnancy, marked by implantation of the blastocyst; the formation of a viable zygote. [EU] Concomitant: Accompanying; accessory; joined with another. [EU] Confidence Intervals: A range of values for a variable of interest, e.g., a rate, constructed so that this range has a specified probability of including the true value of the variable. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [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] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constitutional: 1. Affecting the whole constitution of the body; not local. 2. Pertaining to the constitution. [EU] Constriction: The act of constricting. [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]
Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [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]
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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 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 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] 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] Corticotropin-Releasing Hormone: A neuropeptide released by the hypothalamus that stimulates the release of corticotropin by the anterior pituitary gland. [NIH] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [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] Cost Savings: Reductions in all or any portion of the costs of providing goods or services. Savings may be incurred by the provider or the consumer. [NIH] 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] Criterion: A standard by which something may be judged. [EU] 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
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compounds that contain a ring of atoms in the nucleus. [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] Cytotoxic: Cell-killing. [NIH] 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] Decision Making: The process of making a selective intellectual judgment when presented with several complex alternatives consisting of several variables, and usually defining a course of action or an idea. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Dehydroepiandrosterone: DHEA. A substance that is being studied as a cancer prevention drug. It belongs to the family of drugs called steroids. [NIH] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] 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] Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [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
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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 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] Deoxyglucose: 2-Deoxy-D-arabino-hexose. An antimetabolite of glucose with antiviral activity. [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] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU] Derealization: Is characterized by the loss of the sense of reality concerning one's surroundings. [NIH] Dermatitis: Any inflammation of the skin. [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] 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] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [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]
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Digestion: The process of breakdown of food for metabolism and use by the body. [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] 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] Dissociative Disorders: Sudden temporary alterations in the normally integrative functions of consciousness. [NIH] 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] 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] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Monitoring: The process of observing, recording, or detecting the effects of a chemical substance administered to an individual therapeutically or diagnostically. [NIH] Duct: A tube through which body fluids pass. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or
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incomplete movements. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Dyspnea: Difficult or labored breathing. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Effector cell: A cell that performs a specific function in response to a stimulus; usually used to describe cells in the immune system. [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] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electroacupuncture: A form of acupuncture using low frequency electrically stimulated needles to produce analgesia and anesthesia and to treat disease. [NIH] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electroconvulsive Therapy: Electrically induced convulsions primarily used in the 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] 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] 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] Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryo Transfer: Removal of a mammalian embryo from one environment and replacement in the same or a new environment. The embryo is usually in the pre-nidation phase, i.e., a blastocyst. The process includes embryo or blastocyst transplantation or transfer after in vitro fertilization and transfer of the inner cell mass of the blastocyst. It is not used for transfer of differentiated embryonic tissue, e.g., germ layer cells. [NIH] Embryology: The study of the development of an organism during the embryonic and fetal stages of life. [NIH] Emetic: An agent that causes vomiting. [EU] Emollient: Softening or soothing; called also malactic. [EU]
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Empiric: Empirical; depending upon experience or observation alone, without using scientific method or theory. [EU] Empirical: A treatment based on an assumed diagnosis, prior to receiving confirmatory laboratory test results. [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] 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] Enkephalin: A natural opiate painkiller, in the hypothalamus. [NIH] Entorhinal Cortex: Cortex where the signals are combined with those from other sensory systems. [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] 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] 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 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] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a
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fungus. [NIH] ERV: The expiratory reserve volume is the largest volume of gas that can be expired from the end-expiratory level. [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] 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] Ethnic Groups: A group of people with a common cultural heritage that sets them apart from others in a variety of social relationships. [NIH] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Exons: Coding regions of messenger RNA included in the genetic transcript which survive the processing of RNA in cell nuclei to become part of a spliced messenger of structural RNA in the cytoplasm. They include joining and diversity exons of immunoglobulin genes. [NIH]
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] External radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external-beam radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. [NIH] Extrapyramidal: Outside of the pyramidal tracts. [EU] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [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.
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[NIH]
Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fertilization in Vitro: Fertilization of an egg outside the body when the egg is normally fertilized in the body. [NIH] Fetal Heart: The heart of the fetus of any viviparous animal. It refers to the heart in the postembryonic period and is differentiated from the embryonic heart (heart/embryology) only on the basis of time. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules. [NIH] Filler: An inactive substance used to make a product bigger or easier to handle. For example, fillers are often used to make pills or capsules because the amount of active drug is too small to be handled conveniently. [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] Flow Cytometry: Technique using an instrument system for making, processing, and displaying one or more measurements on individual cells obtained from a cell suspension. Cells are usually stained with one or more fluorescent dyes specific to cell components of interest, e.g., DNA, and fluorescence of each cell is measured as it rapidly transverses the excitation beam (laser or mercury arc lamp). Fluorescence provides a quantitative measure of various biochemical and biophysical properties of the cell, as well as a basis for cell sorting. Other measurable optical parameters include light absorption and light scattering, the latter being applicable to the measurement of cell size, shape, density, granularity, and stain uptake. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluorescent Dyes: Dyes that emit light when exposed to light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags. They are used as markers in biochemistry and immunology. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [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] 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] Forearm: The part between the elbow and the wrist. [NIH]
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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]
Free Radicals: Highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenteritis: An acute inflammation of the lining of the stomach and intestines, characterized by anorexia, nausea, diarrhoea, abdominal pain, and weakness, which has various causes, including food poisoning due to infection with such organisms as Escherichia coli, Staphylococcus aureus, and Salmonella species; consumption of irritating food or drink; or psychological factors such as anger, stress, and fear. Called also enterogastritis. [EU] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [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] Genetic Counseling: Advising families of the risks involved pertaining to birth defects, in order that they may make an informed decision on current or future pregnancies. [NIH] Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [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] Geriatric Psychiatry: A subspecialty of psychiatry concerned with the mental health of the aged. [NIH] Gestation: The period of development of the young in viviparous animals, from the time of
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fertilization of the ovum until birth. [EU] Gestures: Movement of a part of the body for the purpose of communication. [NIH] Ginkgo biloba: Exclusive species of the genus Ginkgo, family Ginkgoacea. It produces extracts of medicinal interest. Ginkgo may refer to the genus or species. [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] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [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]
Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [NIH]
Glycerophospholipids: Derivatives of phosphatidic acid in which the hydrophobic regions are composed of two fatty acids and a polar alcohol is joined to the C-3 position of glycerol through a phosphodiester bond. They are named according to their polar head groups, such as phosphatidylcholine and phosphatidylethanolamine. [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] Gravidity: Pregnancy; the condition of being pregnant, without regard to the outcome. [EU] 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] Guideline Adherence: Conformity in fulfilling or following official, recognized, or institutional requirements, guidelines, recommendations, protocols, pathways, or other standards. [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
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the limbic system. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [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 Behavior: Behaviors expressed by individuals to protect, maintain or promote their health status. For example, proper diet, and appropriate exercise are activities perceived to influence health status. Life style is closely associated with health behavior and factors influencing life style are socioeconomic, educational, and cultural. [NIH] Health Care Reform: Innovation and improvement of the health care system by reappraisal, amendment of services, and removal of faults and abuses in providing and distributing health services to patients. It includes a re-alignment of health services and health insurance to maximum demographic elements (the unemployed, indigent, uninsured, elderly, inner cities, rural areas) with reference to coverage, hospitalization, pricing and cost containment, insurers' and employers' costs, pre-existing medical conditions, prescribed drugs, equipment, and services. [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] Heartbeat: One complete contraction of the heart. [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
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carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Heparin: Heparinic acid. A highly acidic mucopolysaccharide formed of equal parts of sulfated D-glucosamine and D-glucuronic acid with sulfaminic bridges. The molecular weight ranges from six to twenty thousand. Heparin occurs in and is obtained from liver, lung, mast cells, etc., of vertebrates. Its function is unknown, but it is used to prevent blood clotting in vivo and vitro, in the form of many different salts. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocellular: Pertaining to or affecting liver cells. [EU] Hepatocellular carcinoma: A type of adenocarcinoma, the most common type of liver tumor. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [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]
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] Histology: The study of tissues and cells under a microscope. [NIH] Homicide: The killing of one person by another. [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] 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] Hybridomas: Cells artificially created by fusion of activated lymphocytes with neoplastic cells. The resulting hybrid cells are cloned and produce pure or "monoclonal" antibodies or T-cell products, identical to those produced by the immunologically competent parent, and continually grow and divide as the neoplastic parent. [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] Hydrogenation: Specific method of reduction in which hydrogen is added to a substance by
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the direct use of gaseous hydrogen. [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] 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] 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]
Hypomania: An abnormality of mood resembling mania (persistent elevated or expansive mood, hyperactivity, inflated self-esteem, etc.) but of lesser intensity. [EU] Hypotension: Abnormally low blood pressure. [NIH] 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] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hypoxic: Having too little oxygen. [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] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunoglobulin: A protein that acts as an antibody. [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]
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Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implantation: The insertion or grafting into the body of biological, living, inert, or radioactive material. [EU] 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] 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] Infancy: The period of complete dependency prior to the acquisition of competence in walking, talking, and self-feeding. [NIH] Infantile: Pertaining to an infant or to infancy. [EU] 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]
Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Initiation: Mutation induced by a chemical reactive substance causing cell changes; being a step in a carcinogenic process. [NIH] Initiator: A chemically reactive substance which may cause cell changes if ingested, inhaled or absorbed into the body; the substance may thus initiate a carcinogenic process. [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] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of
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glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [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] 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] Interleukin-1: A soluble factor produced by monocytes, macrophages, and other cells which activates T-lymphocytes and potentiates their response to mitogens or antigens. IL-1 consists of two distinct forms, IL-1 alpha and IL-1 beta which perform the same functions but are distinct proteins. The biological effects of IL-1 include the ability to replace macrophage requirements for T-cell activation. The factor is distinct from interleukin-2. [NIH] Interleukin-2: Chemical mediator produced by activated T lymphocytes and which regulates the proliferation of T cells, as well as playing a role in the regulation of NK cell activity. [NIH] Interleukin-6: Factor that stimulates the growth and differentiation of human B-cells and is also a growth factor for hybridomas and plasmacytomas. It is produced by many different cells including T-cells, monocytes, and fibroblasts. [NIH] Intermediate Filaments: Cytoplasmic filaments intermediate in diameter (about 10 nanometers) between the microfilaments and the microtubules. They may be composed of any of a number of different proteins and form a ring around the cell nucleus. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interpersonal Relations: The reciprocal interaction of two or more persons. [NIH] Intervention Studies: Epidemiologic investigations designed to test a hypothesized causeeffect relation by modifying the supposed causal factor(s) in the study population. [NIH] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [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 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] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU]
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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]
Iodine: A nonmetallic element of the halogen group that is represented by the atomic symbol I, atomic number 53, and atomic weight of 126.90. It is a nutritionally essential element, especially important in thyroid hormone synthesis. In solution, it has anti-infective properties and is used topically. [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] 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] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] 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] Kinetics: The study of rate dynamics in chemical or physical systems. [NIH] Lactation: The period of the secretion of milk. [EU] 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] Laterality: Behavioral manifestations of cerebral dominance in which there is preferential use and superior functioning of either the left or the right side, as in the preferred use of the right hand or right foot. [NIH] Least-Squares Analysis: A principle of estimation in which the estimates of a set of parameters in a statistical model are those quantities minimizing the sum of squared differences between the observed values of a dependent variable and the values predicted by the model. [NIH] Lesion: An area of abnormal tissue change. [NIH] Lethal: Deadly, fatal. [EU] Leucine: An essential branched-chain amino acid important for hemoglobin formation. [NIH] 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] Likelihood Functions: Functions constructed from a statistical model and a set of observed data which give the probability of that data for various values of the unknown model parameters. Those parameter values that maximize the probability are the maximum likelihood estimates of the parameters. [NIH]
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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] Linear Models: Statistical models in which the value of a parameter for a given value of a factor is assumed to be equal to a + bx, where a and b are constants. The models predict a linear regression. [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]
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] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [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] 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] Lod: The lowest analyte content which, if actually present, will be detected with reasonable statistical certainty and can be identified according to the identification criteria of the method. If both accuracy and precision are constant over a concentration range. [NIH] Lod Score: The total relative probability, expressed on a logarithmic scale, that a linkage relationship exists among selected loci. Lod is an acronym for "logarithmic odds." [NIH] Logistic Models: Statistical models which describe the relationship between a qualitative dependent variable (that is, one which can take only certain discrete values, such as the presence or absence of a disease) and an independent variable. A common application is in epidemiology for estimating an individual's risk (probability of a disease) as a function of a given risk factor. [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
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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] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [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 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 Count: A count of the number of lymphocytes in the blood. [NIH] Lymphocyte Subsets: A classification of lymphocytes based on structurally or functionally different populations of cells. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system 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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]
Mania: Excitement of psychotic proportions manifested by mental and physical
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hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] 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 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] 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] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Lipids: Lipids, predominantly phospholipids, cholesterol and small amounts of glycolipids found in membranes including cellular and intracellular membranes. These lipids may be arranged in bilayers in the membranes with integral proteins between the layers and peripheral proteins attached to the outside. Membrane lipids are required for active transport, several enzymatic activities and membrane formation. [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] 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]
Mercury: A silver metallic element that exists as a liquid at room temperature. It has the
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atomic symbol Hg (from hydrargyrum, liquid silver), atomic number 80, and atomic weight 200.59. Mercury is used in many industrial applications and its salts have been employed therapeutically as purgatives, antisyphilitics, disinfectants, and astringents. It can be absorbed through the skin and mucous membranes which leads to mercury poisoning. Because of its toxicity, the clinical use of mercury and mercurials is diminishing. [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 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] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyltransferase: A drug-metabolizing enzyme. [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] Mianserin: A tetracyclic compound with antidepressant effects. It may cause drowsiness and hematological problems. Its mechanism of therapeutic action is not well understood, although it apparently blocks alpha-adrenergic, histamine H1, and some types of serotonin receptors. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [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] Microtubule-Associated Proteins: High molecular weight proteins found in the microtubules of the cytoskeletal system. Under certain conditions they are required for tubulin assembly into the microtubules and stabilize the assembled microtubules. [NIH] Microtubules: Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein tubulin. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative
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procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] 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 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] 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] 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] Mother-Child Relations: Interaction between the mother and the child. [NIH] Motility: The ability to move spontaneously. [EU] Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Multicenter Studies: Controlled studies which are planned and carried out by several cooperating institutions to assess certain variables and outcomes in specific patient populations, for example, a multicenter study of congenital anomalies in children. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]
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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] Mutilation: Injuries to the body. [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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [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] 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] Neocortex: The largest portion of the cerebral cortex. It is composed of neurons arranged in six layers. [NIH] Neonatal: Pertaining to the first four weeks after birth. [EU] Neoplasm: A new growth of benign or malignant tissue. [NIH] 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] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [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] Neuroanatomy: Study of the anatomy of the nervous system as a specialty or discipline. [NIH]
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] Neurofibrillary Tangles: Abnormal structures located in various parts of the brain and composed of dense arrays of paired helical filaments (neurofilaments and microtubules). These double helical stacks of transverse subunits are twisted into left-handed ribbon-like filaments that likely incorporate the following proteins: (1) the intermediate filaments:
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medium- and high-molecular-weight neurofilaments; (2) the microtubule-associated proteins map-2 and tau; (3) actin; and (4) ubiquitin. As one of the hallmarks of Alzheimer disease, the neurofibrillary tangles eventually occupy the whole of the cytoplasm in certain classes of cell in the neocortex, hippocampus, brain stem, and diencephalon. The number of these tangles, as seen in post mortem histology, correlates with the degree of dementia during life. Some studies suggest that tangle antigens leak into the systemic circulation both in the course of normal aging and in cases of Alzheimer disease. [NIH] Neurofilaments: Bundle of neuronal fibers. [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 emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] 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] 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] Neurosis: Functional derangement due to disorders of the nervous system which does not affect the psychic personality of the patient. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [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] Niacin: Water-soluble vitamin of the B complex occurring in various animal and plant tissues. Required by the body for the formation of coenzymes NAD and NADP. Has pellagra-curative, vasodilating, and antilipemic properties. [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
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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] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [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] 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] 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 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] 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] 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]
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Operon: The genetic unit consisting of a feedback system under the control of an operator gene, in which a structural gene transcribes its message in the form of mRNA upon blockade of a repressor produced by a regulator gene. Included here is the attenuator site of bacterial operons where transcription termination is regulated. [NIH] Opiate: A remedy containing or derived from opium; also any drug that induces sleep. [EU] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [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] Orthostatic: Pertaining to or caused by standing erect. [EU] 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] Ovum: A female germ cell extruded from the ovary at ovulation. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocin: A nonapeptide posterior pituitary hormone that causes uterine contractions and stimulates lactation. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [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] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus. [NIH]
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Parity: The number of offspring a female has borne. It is contrasted with gravidity, which refers to the number of pregnancies, regardless of outcome. [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]
Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] 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] 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] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Pathophysiology: Altered functions in an individual or an organ due to disease. [NIH] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [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] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [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] Peripheral blood: Blood circulating throughout the body. [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] Personality Disorders: A major deviation from normal patterns of behavior. [NIH] Pharmacist: A person trained to prepare and distribute medicines and to give information about them. [NIH]
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Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] 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] Phospholipids: Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides; glycerophospholipids) or sphingosine (sphingolipids). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. [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] Phosphorylated: Attached to a phosphate group. [NIH] Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. [NIH] Phototherapy: Treatment of disease by exposure to light, especially by variously concentrated light rays or specific wavelengths. [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 study: The initial study examining a new method or treatment. [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 Hormones: Hormones secreted by the anterior and posterior lobes of the pituitary gland and the pars intermedia, an ill-defined region between the two. Their secretion is regulated by the hypothalamus. [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]
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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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [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] Plasticity: In an individual or a population, the capacity for adaptation: a) through gene changes (genetic plasticity) or b) through internal physiological modifications in response to changes of environment (physiological plasticity). [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] Platelet Factor 4: A high-molecular-weight proteoglycan-platelet factor complex which is released from blood platelets by thrombin. It acts as a mediator in the heparin-neutralizing capacity of the blood and plays a role in platelet aggregation. At high ionic strength (I=0.75), the complex dissociates into the active component (molecular weight 29,000) and the proteoglycan carrier (chondroitin 4-sulfate, molecular weight 350,000). The molecule exists in the form of a dimer consisting of 8 moles of platelet factor 4 and 2 moles of proteoglycan. [NIH]
Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [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] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polygenic Inheritance: A phenotypic outcome that is determined by more than one gene, such as a variety of physical characteristics or diseases. [NIH] Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for
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the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [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] Post partum: After childbirth, or after delivery. [EU] 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-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] Postural: Pertaining to posture or position. [EU] 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] 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] Precipitating Factors: Factors associated with the definitive onset of a disease, illness, accident, behavioral response, or course of action. Usually one factor is more important or more obviously recognizable than others, if several are involved, and one may often be regarded as "necessary". Examples include exposure to specific disease; amount or level of an infectious organism, drug, or noxious agent, etc. [NIH] 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] Predictive factor: A situation or condition that may increase a person's risk of developing a certain disease or disorder. [NIH] 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
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diencephalon, mesencephalon, and limbic system as well as cortical afferents of visual, auditory, and somatic origin. [NIH] Pregnancy Outcome: Results of conception and ensuing pregnancy, including live birth, stillbirth, spontaneous abortion, induced abortion. The outcome may follow natural or artificial insemination or any of the various reproduction techniques, such as embryo transfer or fertilization in vitro. [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] Presynaptic Terminals: The distal terminations of axons which are specialized for the release of neurotransmitters. Also included are varicosities along the course of axons which have similar specializations and also release transmitters. Presynaptic terminals in both the central and peripheral nervous systems are included. [NIH] 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] Prion: Small proteinaceous infectious particles that resist inactivation by procedures modifying nucleic acids and contain an abnormal isoform of a cellular protein which is a major and necessary component. [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] 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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [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] 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] Protein Binding: The process in which substances, either endogenous or exogenous, bind to
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proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [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] Proteoglycan: A molecule that contains both protein and glycosaminoglycans, which are a type of polysaccharide. Proteoglycans are found in cartilage and other connective tissues. [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] Pruritic: Pertaining to or characterized by pruritus. [EU] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] 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] 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
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primarily by verbal or nonverbal communication. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [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 ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [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] Pyrimidines: A family of 6-membered heterocyclic compounds occurring in nature in a wide variety of forms. They include several nucleic acid constituents (cytosine, thymine, and uracil) and form the basic structure of the barbiturates. [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] 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] Random Allocation: A process involving chance used in therapeutic trials or other research
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endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the trochlear nucleus in the midbrain to the hypoglossal area in the medulla oblongata. [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 function. [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] Recovery of Function: A partial or complete return to the normal or proper physiologic activity of an organ or part following disease or trauma. [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] Refer: To send or direct for treatment, aid, information, de decision. [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] Regional cancer: Refers to cancer that has grown beyond the original (primary) tumor to nearby lymph nodes or organs and tissues. [NIH] Regression Analysis: Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see linear models) the relationship is constrained to be a straight line and least-squares analysis is used to determine the best fit. In logistic regression (see logistic models) the dependent variable is qualitative rather than continuously variable
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and likelihood functions are used to find the best relationship. In multiple regression the dependent variable is considered to depend on more than a single independent variable. [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] Repressor: Any of the specific allosteric protein molecules, products of regulator genes, which bind to the operator of operons and prevent RNA polymerase from proceeding into the operon to transcribe messenger RNA. [NIH] Reproduction Techniques: Methods pertaining to the generation of new individuals. [NIH] Research Support: Financial support of research activities. [NIH] 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, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory Physiology: Functions and activities of the respiratory tract as a whole or of any of its parts. [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Response rate: The percentage of patients whose cancer shrinks or disappears after treatment. [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] Rhabdomyolysis: Necrosis or disintegration of skeletal muscle often followed by
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myoglobinuria. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [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] Riluzole: A glutamate antagonist that has reported anticonvulsant activity. It has been shown to prolong the survival of patients with amyotrophic lateral sclerosis and has been approved in the United States to treat patients with ALS. [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] Rural Health: The status of health in rural populations. [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] Saponins: Sapogenin glycosides. A type of glycoside widely distributed in plants. Each consists of a sapogenin as the aglycon moiety, and a sugar. The sapogenin may be a steroid or a triterpene and the sugar may be glucose, galactose, a pentose, or a methylpentose. Sapogenins are poisonous towards the lower forms of life and are powerful hemolytics when injected into the blood stream able to dissolve red blood cells at even extreme dilutions. [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 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
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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] 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] Segregation: The separation in meiotic cell division of homologous chromosome pairs and their contained allelomorphic gene pairs. [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] 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] Senile: Relating or belonging to old age; characteristic of old age; resulting from infirmity of old age. [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] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [NIH] Sequester: A portion of dead bone which has become detached from the healthy bone tissue, as occurs in necrosis. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [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]
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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]
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] Skeletal: Having to do with the skeleton (boney part of the body). [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 absence of respiratory effort. [NIH] Sleep Deprivation: The state of being deprived of sleep under experimental conditions, due to life events, or from a wide variety of pathophysiologic causes such as medication effect, chronic illness, psychiatric illness, or sleep disorder. [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] 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] 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] 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
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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 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] 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] Sporadic: Neither endemic nor epidemic; occurring occasionally in a random or isolated manner. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stabilization: The creation of a stable state. [EU] 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]
Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [NIH] Stereotactic: Radiotherapy that treats brain tumors by using a special frame affixed directly to the patient's cranium. By aiming the X-ray source with respect to the rigid frame, technicians can position the beam extremely precisely during each treatment. [NIH] Stereotaxis: Use of a computer and scanning devices to create three-dimensional pictures. This method can be used to direct a biopsy, external radiation, or the insertion of radiation implants. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stillbirth: The birth of a dead fetus or baby. [NIH] 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]
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Stool: The waste matter discharged in a bowel movement; feces. [NIH] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] 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] Subcutaneous: Beneath the skin. [NIH] Subiculum: A region of the hippocampus that projects to other areas of the brain. [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] Sudden death: Cardiac arrest caused by an irregular heartbeat. The term "death" is somewhat misleading, because some patients survive. [NIH] 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] 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,
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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] Synaptic Vesicles: Membrane-bound compartments which contain transmitter molecules. Synaptic vesicles are concentrated at presynaptic terminals. They actively sequester transmitter molecules from the cytoplasm. In at least some synapses, transmitter release occurs by fusion of these vesicles with the presynaptic membrane, followed by exocytosis of their contents. [NIH] 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] Temperament: Predisposition to react to one's environment in a certain way; usually refers to mood changes. [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] 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] Thalamic: Cell that reaches the lateral nucleus of amygdala. [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]
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]
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Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombocytes: Blood cells that help prevent bleeding by causing blood clots to form. Also called platelets. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [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] 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] Tinnitus: Sounds that are perceived in the absence of any external noise source which may take the form of buzzing, ringing, clicking, pulsations, and other noises. Objective tinnitus refers to noises generated from within the ear or adjacent structures that can be heard by other individuals. The term subjective tinnitus is used when the sound is audible only to the affected individual. Tinnitus may occur as a manifestation of cochlear diseases; vestibulocochlear nerve diseases; intracranial hypertension; craniocerebral trauma; and other conditions. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] 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] Tonus: A state of slight tension usually present in muscles even when they are not
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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] Topical: On the surface of the body. [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] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process. [NIH] 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]
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] Trimipramine: Tricyclic antidepressant similar to imipramine, but with more antihistaminic
Dictionary 241
and sedative properties. [NIH] Trisomy: The possession of a third chromosome of any one type in an otherwise diploid cell. [NIH]
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] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [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 also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ubiquitin: A highly conserved 76 amino acid-protein found in all eukaryotic cells. [NIH] Umbilical Arteries: Either of a pair of arteries originating from the internal iliac artery and passing through the umbilical cord to carry blood from the fetus to the placenta. [NIH] Umbilical Cord: The flexible structure, giving passage to the umbilical arteries and vein, which connects the embryo or fetus to the placenta. [NIH] Umbilical cord blood: Blood from the placenta (afterbirth) that contains high concentrations of stem cells needed to produce new blood cells. [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] Uterine Contraction: Contraction of the uterine muscle. [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]
Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vector: Plasmid or other self-replicating DNA molecule that transfers DNA between cells in nature or in recombinant DNA technology. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH]
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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] 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] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Vestibulocochlear Nerve: The 8th cranial nerve. The vestibulocochlear nerve has a cochlear part (cochlear nerve) which is concerned with hearing and a vestibular part (vestibular nerve) which mediates the sense of balance and head position. The fibers of the cochlear nerve originate from neurons of the spiral ganglion and project to the cochlear nuclei (cochlear nucleus). The fibers of the vestibular nerve arise from neurons of Scarpa's ganglion and project to the vestibular nuclei. [NIH] Vestibulocochlear Nerve Diseases: Diseases of the vestibular and/or cochlear (acoustic) nerves, which join to form the vestibulocochlear nerve. Vestibular neuritis, cochlear neuritis, and acoustic neuromas are relatively common conditions that affect these nerves. Clinical manifestations vary with which nerve is primarily affected, and include hearing loss, vertigo, and tinnitus. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Viral Load: The quantity of measurable virus in the blood. Change in viral load, measured in plasma, is used as a surrogate marker in HIV disease progression. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] 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 fat: One of the three compartments of abdominal fat. Retroperitoneal and subcutaneous are the other two compartments. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation
Dictionary 243
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] 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] 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] 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] Zygote: The fertilized ovum. [NIH] Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
245
INDEX 3 3-dimensional, 138, 185 A Abdomen, 185, 193, 213, 215, 224, 236, 239, 242 Abdominal, 185, 207, 214, 223, 242 Abdominal fat, 185, 242 Abdominal Pain, 185, 207, 214 Aberrant, 185, 196 Abortion, 185, 228 Absenteeism, 25, 185 Acetylcholine, 185, 195, 221 Acquired Immunodeficiency Syndrome, 150, 185 Actin, 185, 221 Activities of Daily Living, 6, 33, 185 Adaptability, 185, 194 Adaptation, 63, 185, 226 Adenine, 186, 230 Adenocarcinoma, 186, 210 Adenosine, 22, 73, 186, 225 Adenosine Triphosphate, 22, 186, 225 Adjustment, 15, 26, 62, 79, 98, 185, 186 Adjustment Disorders, 79, 98, 186 Adjuvant, 114, 125, 186, 207 Adolescence, 13, 186 Adrenal Cortex, 186, 199, 205, 228 Adrenal Medulla, 186, 194, 204, 222 Adrenergic, 56, 72, 186, 188, 190, 202, 204, 218, 237, 241 Adverse Effect, 3, 51, 186, 190, 235 Aerobic, 72, 186 Aerobic Exercise, 72, 186 Aerosol, 186, 192 Affective Symptoms, 15, 186 Afferent, 186, 227, 234 Affinity, 22, 25, 186, 187, 191, 201 Age of Onset, 73, 144, 187, 241 Agmatine, 10, 187 Agonist, 22, 82, 187, 190, 202, 221 Agoraphobia, 14, 136, 187, 211, 223, 225 Airway, 187, 235 Akathisia, 187, 190 Algorithms, 187, 192 Alimentary, 187, 223 Alkaline, 187, 188, 193 Alkaloid, 187, 219, 221 Alleles, 59, 70, 187
Allergen, 187, 201 Allylamine, 187, 188 Alpha-1, 187, 188 Alternative medicine, 28, 118, 128, 158, 187 Alveoli, 187, 242 Ambulatory Care, 11, 187 Amine, 9, 187, 210 Amino Acid Sequence, 188, 189, 192 Aminoglutethimide, 147, 188 Amitriptyline, 82, 85, 188 Ammonia, 188 Amnesia, 153, 188 Amnestic, 188, 206 Amygdala, 93, 95, 110, 188, 215, 234, 238 Amyloid, 150, 188 Amyloid beta-Protein, 150, 188 Anabolic, 23, 141, 188 Anabolic Steroids, 141, 188 Anaesthesia, 188, 212 Anal, 33, 58, 189, 215 Analgesics, 3, 189 Analog, 25, 189 Anatomical, 86, 189, 191, 195, 212, 218, 220, 234 Anesthesia, 153, 187, 189, 203 Anesthetics, 3, 189, 204 Animal model, 10, 189 Annealing, 189, 226 Anomalies, 99, 189, 219 Anorexia, 125, 140, 189, 207 Anosognosia, 6, 189 Antibacterial, 189, 236 Antibiotic, 189, 236 Antibodies, 189, 209, 210, 216 Antibody, 187, 189, 197, 209, 210, 211, 212, 217, 230, 236 Anticholinergic, 188, 189 Anticoagulant, 189, 229 Anticonvulsant, 189, 233 Antiemetic, 189, 190 Antigen, 186, 189, 197, 210, 211, 212, 217, 218 Anti-infective, 190, 214 Anti-inflammatory, 190, 192, 201, 208 Antimetabolite, 190, 201 Antipsychotic, 5, 9, 42, 141, 153, 190, 221, 233
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Major Depression
Antiviral, 190, 201, 213 Anus, 189, 190, 197 Anxiety Disorders, 13, 42, 52, 66, 68, 94, 101, 107, 136, 151, 190, 223 Apnea, 190 Apomorphine, 114, 190 Apoptosis, 10, 44, 90, 190 Applicability, 49, 190 Approximate, 30, 190 Arginine, 10, 32, 69, 187, 190, 221 Aromatase, 188, 190 Arterial, 25, 187, 191, 199, 211, 229, 238 Arteries, 191, 193, 199, 218, 220, 230, 241 Artery, 191, 199, 230, 241 Articulation, 14, 191 Astrocytes, 191, 218, 219 Atrial, 191, 199, 240 Atrioventricular, 191, 199 Atrium, 191, 199, 240, 242 Atrophy, 90, 191 Atypical, 9, 97, 119, 140, 141, 191, 222, 233 Auditory, 118, 122, 153, 191, 228 Autoimmune disease, 191, 220 Autonomic, 52, 185, 190, 191, 222, 224, 237 Autopsy, 43, 191 Autoreceptors, 145, 191 Axons, 145, 191, 201, 228 B Back Pain, 34, 55, 75, 191 Bacteria, 189, 190, 191, 201, 218, 236, 240, 241 Bacterial Physiology, 186, 191 Bacteriophage, 191, 226, 240 Basal Ganglia, 190, 192, 195, 215 Beclomethasone, 109, 192 Behavior Therapy, 35, 192 Behavioral Symptoms, 152, 192 Benign, 192, 209, 220 Benzene, 192 Benzodiazepines, 159, 192 Bereavement, 40, 192 Beta-Endorphin, 124, 192 Beta-pleated, 188, 192 Bewilderment, 192, 198 Bilateral, 15, 45, 120, 121, 192 Bile, 192, 215, 236 Biochemical, 10, 86, 136, 146, 187, 190, 192, 206, 234 Biopsy, 192, 236 Biosynthesis, 192, 234 Biotechnology, 67, 68, 158, 167, 192
Bipolar Disorder, 13, 38, 39, 42, 69, 74, 88, 90, 93, 94, 104, 105, 106, 123, 138, 140, 142, 144, 172, 192 Bladder, 192, 197, 212, 220, 241 Blastocyst, 193, 198, 203, 225 Bloating, 193, 214 Blood Coagulation, 193, 239 Blood Glucose, 4, 193, 209, 211, 213 Blood Platelets, 193, 226, 234 Blood pressure, 52, 89, 193, 194, 195, 211, 219, 230 Blood vessel, 193, 194, 195, 199, 204, 214, 215, 224, 237, 239, 241 Blot, 57, 193 Bone scan, 193, 233 Bowel, 8, 189, 193, 213, 237 Bradykinin, 193, 221 Brain Stem, 193, 221 Bromine, 25, 193 Bronchi, 193, 204, 240 Bupropion, 74, 81, 100, 193 C Calcium, 13, 22, 145, 193, 197 Calcium Channels, 145, 193 Capsules, 194, 206, 207 Carbohydrate, 194, 208, 234 Carbon Dioxide, 52, 194, 200, 207, 225, 232 Carcinogenic, 192, 194, 212, 228, 236 Carcinoma, 194 Cardiac, 23, 28, 52, 187, 194, 199, 203, 204, 205, 220, 236, 237 Cardiomyopathy, 59, 194 Cardiorespiratory, 186, 194 Cardiovascular, 20, 22, 23, 27, 57, 193, 194, 234 Cardiovascular disease, 20, 23, 194 Case report, 75, 125, 194, 196 Case series, 194, 196 Catecholamine, 194, 202, 225 Catheter, 138, 194 Caudal, 194, 201, 211, 227 Causal, 24, 194, 213 Cause of Death, 31, 194 Cell Death, 10, 44, 190, 194, 220 Cell Division, 191, 194, 217, 218, 226, 228, 234 Cell membrane, 193, 194, 225 Cell Respiration, 195, 232 Cell Size, 195, 206 Central Nervous System, 52, 145, 185, 192, 193, 195, 207, 208, 209, 218, 219, 220, 221, 234
247
Central Nervous System Infections, 195, 209 Cerebral Cortex, 138, 195, 205, 206, 220 Cerebrospinal, 68, 75, 77, 195, 216, 236 Cerebrospinal fluid, 68, 75, 77, 195, 216, 236 Cerebrovascular, 36, 65, 75, 194, 195 Cerebrum, 195, 238 Character, 73, 83, 84, 195, 200 Chemoreceptor, 190, 195 Chin, 133, 195, 217 Cholesterol, 96, 192, 195, 199, 217, 236 Choline, 93, 195 Cholinergic, 32, 43, 140, 141, 188, 190, 195, 221, 234 Chorea, 190, 195 Chromatin, 190, 196 Chromosome, 136, 188, 196, 215, 234, 241 Citalopram, 35, 69, 76, 111, 196 Clinical study, 38, 196, 198 Clinical trial, 7, 38, 48, 111, 167, 172, 196, 198, 202, 219, 229, 231 Cloning, 192, 196 Cochlear, 196, 239, 242 Cochlear Diseases, 196, 239 Codon, 145, 196 Cognition, 18, 37, 122, 196, 221 Cognitive behavior therapy, 51, 58, 196 Cognitive Therapy, 62, 196 Colitis, 196, 214 Collagen, 188, 196, 206, 207, 226, 228 Collapse, 196, 235 Colon, 196, 197, 214 Community Mental Health Centers, 60, 197 Comorbidity, 7, 14, 19, 33, 56, 63, 68, 78, 110, 121, 197 Complement, 197 Complementary and alternative medicine, 117, 131, 197 Complementary medicine, 117, 197 Compliance, 56, 197 Compulsions, 197, 222 Computational Biology, 167, 197 Computed tomography, 198, 233 Computerized axial tomography, 198, 233 Conception, 42, 185, 198, 206, 228 Concomitant, 41, 198 Confidence Intervals, 11, 198 Confusion, 60, 198, 202, 211, 221 Congestion, 190, 198 Congestive heart failure, 30, 47, 70, 198
Consciousness, 189, 198, 200, 202, 229 Constipation, 190, 198, 214 Constitutional, 14, 198 Constriction, 198, 214, 241 Consultation, 38, 198 Contraindications, ii, 198 Control group, 11, 18, 29, 30, 108, 109, 198, 231 Controlled clinical trial, 13, 16, 198 Controlled study, 8, 27, 47, 84, 91, 117, 128, 198 Conventional therapy, 198 Conventional treatment, 28, 198 Convulsions, 189, 198, 203, 211 Coordination, 45, 110, 199, 220 Cor, 32, 68, 87, 199 Coronary, 22, 123, 194, 199, 218, 220 Coronary heart disease, 194, 199 Coronary Thrombosis, 199, 218, 220 Cortex, 10, 60, 94, 104, 138, 199, 204, 227 Cortical, 25, 32, 57, 86, 106, 122, 199, 228, 234 Corticotropin-Releasing Hormone, 68, 87, 199 Cortisol, 23, 29, 52, 80, 96, 97, 108, 146, 199 Cortisone, 199, 201 Cost Savings, 59, 199 Cranial, 199, 209, 213, 224, 242 Craniocerebral Trauma, 199, 209, 239 Criterion, 26, 199 Curative, 199, 221, 238 Cyclic, 41, 114, 199, 208, 222 Cytokine, 75, 200 Cytoplasm, 190, 194, 200, 205, 219, 221, 233, 238 Cytotoxic, 19, 31, 200 D Data Collection, 15, 52, 200 Deamination, 200, 219 Decarboxylation, 10, 200, 210 Decision Making, 50, 109, 200 Degenerative, 152, 200, 210 Dehydroepiandrosterone, 23, 130, 200 Deletion, 92, 190, 200 Delirium, 5, 151, 152, 155, 190, 200 Delusions, 124, 200, 229 Dementia, 5, 6, 7, 82, 100, 150, 151, 152, 155, 159, 185, 190, 200, 221 Denaturation, 200, 226 Dendrites, 200, 201, 221 Density, 23, 25, 83, 200, 206, 222 Dental Caries, 200, 206
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Major Depression
Dentate Gyrus, 201, 210 Dentists, 4, 201 Deoxyglucose, 44, 201 Depersonalization, 201, 223, 233 Deprivation, 80, 201 Derealization, 201, 223 Dermatitis, 201, 203 Desensitization, 110, 201 Desipramine, 22, 201 Dexamethasone, 79, 97, 128, 146, 201 Diabetes Mellitus, 20, 201, 208, 209 Diagnostic procedure, 135, 158, 201 Diarrhea, 201, 214 Diastolic, 201, 211 Diathesis, 37, 50, 61, 201 Diencephalon, 201, 204, 211, 221, 228, 238 Digestion, 187, 192, 193, 202, 213, 215, 236 Direct, iii, 11, 16, 17, 22, 24, 27, 33, 35, 46, 52, 58, 80, 138, 161, 196, 202, 211, 231, 236, 238 Discrete, 58, 202, 215 Disorientation, 60, 198, 200, 202 Disparity, 12, 202 Dissociation, 50, 186, 202 Dissociative Disorders, 202 Distal, 136, 202, 203, 228 Diurnal, 80, 140, 202 Dizziness, 202, 223 Dominance, 202, 214 Dopamine, 77, 88, 127, 190, 193, 202, 219, 221, 233 Double-blind, 9, 13, 16, 22, 27, 35, 47, 53, 56, 80, 85, 117, 120, 128, 202 Drug Interactions, 162, 202 Drug Monitoring, 97, 202 Duct, 202, 233 Dyes, 188, 202, 206 Dyskinesia, 190, 196, 202 Dysphoric, 201, 203 Dyspnea, 103, 203, 223 E Eczema, 8, 203 Effector, 19, 185, 197, 203 Effector cell, 19, 203 Elective, 105, 203 Electroacupuncture, 28, 203 Electrocardiogram, 103, 203 Electroconvulsive Therapy, 9, 17, 28, 45, 60, 118, 119, 120, 121, 126, 146, 152, 153, 159, 203 Electrode, 15, 45, 138, 153, 203 Electrolyte, 200, 203
Electrons, 203, 214, 216, 230 Elementary Particles, 203, 216, 229 Emaciation, 185, 203 Embryo, 185, 193, 203, 212, 226, 228, 236, 241 Embryo Transfer, 203, 228 Embryology, 203, 206 Emetic, 190, 203 Emollient, 203, 208 Empiric, 42, 204 Empirical, 8, 18, 37, 50, 151, 204 Endemic, 204, 236 Endocrine System, 204, 220 Endocrinology, 29, 204 Endogenous, 10, 146, 192, 202, 203, 204, 228, 240 Endorphins, 204, 221 Endothelium, 204, 221 Endothelium-derived, 204, 221 Enkephalin, 192, 204 Entorhinal Cortex, 5, 204, 210 Environmental Health, 166, 168, 204 Enzymatic, 57, 188, 193, 197, 200, 204, 210, 217, 226, 232 Enzyme, 92, 190, 203, 204, 208, 218, 219, 226, 229, 237, 239, 242, 243 Epidemic, 31, 49, 204, 236 Epidemiological, 8, 204 Epinephrine, 22, 186, 202, 204, 221, 222, 241 Epithalamus, 201, 204, 215 Ergot, 187, 204 ERV, 168, 205 Estradiol, 80, 205 Estrogen, 188, 190, 205, 228 Ethanol, 196, 205 Ethnic Groups, 9, 205 Evoke, 205, 236 Excitability, 122, 205 Excitation, 195, 205, 206, 221 Exogenous, 146, 203, 204, 205, 228, 241 Exons, 59, 205 Expiration, 205, 232 Expiratory, 205 Expiratory Reserve Volume, 205 External radiation, 205, 236 Extracellular, 188, 191, 205, 206 Extracellular Matrix, 205, 206 Extrapyramidal, 187, 190, 202, 205 F Facial, 104, 106, 205 Facial Expression, 104, 106, 205
249
Family Planning, 167, 205 Fat, 185, 199, 205, 215, 220, 222, 227, 233 Fatigue, 4, 7, 181, 205, 209 Fenfluramine, 73, 206 Fertilization in Vitro, 206, 228 Fetal Heart, 29, 206 Fetus, 185, 206, 225, 228, 236, 241 Fibrinogen, 22, 206, 239 Fibroblasts, 79, 206, 213 Filler, 137, 206 Fissure, 201, 206, 227 Flow Cytometry, 22, 206 Fluorescence, 22, 206 Fluorescent Dyes, 206 Fluorine, 25, 206 Fluoxetine, 41, 53, 58, 68, 72, 76, 80, 84, 85, 106, 108, 111, 119, 128, 141, 206 Fluvoxamine, 68, 77, 206 Forearm, 193, 206 Fourth Ventricle, 207, 215 Free Radicals, 202, 207 Frontal Lobe, 65, 138, 207, 227 G Ganglia, 185, 207, 220, 224, 237 Gas, 188, 194, 205, 206, 207, 210, 214, 221, 222, 230, 232, 242 Gas exchange, 207, 232, 242 Gastrin, 207, 210 Gastroenteritis, 193, 207 Gastrointestinal, 193, 204, 205, 207, 234, 237 Gastrointestinal tract, 205, 207, 234 Gelatin, 207, 208, 239 Gene Expression, 41, 59, 78, 146, 207 Genetic Counseling, 150, 207 Genetic testing, 207, 227 Genetics, 72, 87, 88, 150, 202, 207 Genotype, 44, 88, 139, 143, 207, 225 Geriatric, 3, 11, 15, 17, 33, 35, 50, 63, 74, 80, 83, 103, 150, 151, 159, 207 Geriatric Psychiatry, 63, 74, 83, 103, 150, 159, 207 Gestation, 13, 29, 51, 54, 207, 224, 225, 236 Gestures, 49, 208 Ginkgo biloba, 114, 125, 208 Gland, 146, 186, 199, 208, 216, 223, 225, 234, 236, 239 Glucocorticoid, 31, 89, 90, 145, 146, 192, 201, 208 Glucose, 193, 201, 208, 209, 211, 212, 233 Glucose Intolerance, 201, 208 Glutamate, 10, 106, 208, 233
Glutamic Acid, 208, 221, 228 Glycerol, 143, 208, 225 Glycerophospholipids, 208, 225 Glycine, 102, 188, 208, 221, 234 Glycoprotein, 206, 208, 239 Gonad, 208 Gonadal, 29, 32, 208, 236 Governing Board, 208, 227 Gravidity, 208, 224 Guanylate Cyclase, 208, 222 Guideline Adherence, 109, 208 Gyrus Cinguli, 208, 215 H Habitual, 195, 209 Half-Life, 25, 209 Haptens, 187, 209 Headache, 8, 89, 209, 211 Headache Disorders, 209 Health Behavior, 28, 209 Health Care Reform, 150, 209 Health Services, 11, 21, 24, 33, 47, 76, 109, 152, 209 Health Status, 16, 57, 209 Heart attack, 22, 194, 209 Heart failure, 30, 209 Heartbeat, 209, 237 Hemoglobin, 4, 209, 214 Hemorrhage, 199, 209, 237 Hemostasis, 22, 209, 234 Heparin, 210, 226 Hepatic, 200, 210, 219 Hepatitis, 93, 210 Hepatocellular, 125, 210 Hepatocellular carcinoma, 125, 210 Hepatocytes, 210 Heredity, 40, 207, 210 Heterogeneity, 37, 187, 210 Hippocampus, 10, 110, 201, 210, 215, 221, 234, 237 Histamine, 190, 210, 218 Histology, 210, 221 Homicide, 58, 210 Homologous, 187, 210, 234, 238 Hormonal, 23, 30, 91, 191, 210 Hybridomas, 210, 213 Hydrogen, 188, 194, 200, 210, 219, 229 Hydrogenation, 192, 210 Hydroxyproline, 188, 196, 211 Hyperglycemia, 18, 211 Hypersensitivity, 66, 187, 201, 211, 233 Hypertension, 20, 194, 211, 213 Hypertrophy, 199, 211, 240
250
Major Depression
Hypoglycaemia, 200, 211 Hypoglycemia, 18, 51, 211 Hypoglycemic, 18, 211 Hypomania, 69, 144, 211 Hypotension, 190, 198, 211 Hypothalamic, 12, 29, 78, 92, 110, 211 Hypothalamus, 32, 199, 201, 204, 211, 215, 225, 234 Hypoxia, 200, 211 Hypoxic, 10, 211 I Imipramine, 82, 114, 211, 240 Immune function, 19, 106, 211 Immune response, 93, 186, 189, 191, 199, 209, 211, 237, 242 Immune system, 128, 203, 211, 216, 220, 243 Immunodeficiency, 155, 185, 211 Immunodeficiency syndrome, 155, 211 Immunoglobulin, 189, 205, 211 Immunology, 186, 206, 211 Immunosuppressive, 208, 211 Immunotherapy, 201, 211 Impairment, 6, 9, 15, 28, 33, 50, 52, 54, 80, 85, 92, 97, 105, 150, 152, 186, 192, 200, 202, 212, 217, 229 Implantation, 198, 212 In vitro, 10, 22, 25, 203, 212, 226 In vivo, 10, 25, 210, 212 Incontinence, 20, 212 Induction, 38, 190, 212, 228 Infancy, 54, 212 Infantile, 136, 212 Infarction, 212 Infection, 31, 93, 141, 185, 200, 207, 211, 212, 216, 223, 233, 237, 243 Informed Consent, 159, 212 Ingestion, 66, 143, 212, 226 Inhalation, 66, 186, 212, 226 Initiation, 35, 65, 145, 212, 240 Initiator, 145, 212 Inotropic, 202, 212 Inpatients, 9, 77, 89, 95, 212 Insight, 44, 93, 212 Insomnia, 35, 76, 212 Insulator, 212, 220 Insulin, 23, 212, 213, 241 Insulin-dependent diabetes mellitus, 213 Interferon, 93, 213 Interferon-alpha, 93, 213 Interleukin-1, 122, 213 Interleukin-2, 121, 213
Interleukin-6, 121, 213 Intermediate Filaments, 213, 220 Intermittent, 213, 216 Interpersonal Relations, 140, 213 Intervention Studies, 33, 213 Intervertebral, 213, 216 Intervertebral Disk Displacement, 213, 216 Intestine, 193, 213, 231, 235 Intoxication, 200, 213, 243 Intracellular, 212, 213, 217, 222, 231 Intracranial Hypertension, 209, 213, 239 Intramuscular, 82, 213, 223 Intravenous, 213, 223 Intrinsic, 187, 213 Invasive, 214, 216 Iodine, 25, 214 Ions, 193, 202, 203, 210, 214, 219 Irritable Bowel Syndrome, 8, 214 Ischemia, 10, 191, 214 K Kb, 166, 214 Kinetics, 193, 214 L Lactation, 42, 214, 223, 228 Latency, 23, 36, 214 Latent, 66, 214 Laterality, 119, 214 Least-Squares Analysis, 214, 231 Lesion, 65, 214, 215, 238 Lethal, 49, 214 Leucine, 192, 214 Leukocytes, 213, 214, 219 Life cycle, 152, 214 Ligaments, 199, 214 Ligands, 22, 214 Likelihood Functions, 214, 232 Limbic, 71, 83, 86, 96, 188, 209, 215, 228 Limbic System, 71, 188, 209, 215, 228 Linear Models, 215, 231 Linkage, 18, 87, 88, 215 Lipid, 195, 208, 213, 215, 220 Lithium, 45, 53, 91, 92, 97, 162, 190, 215 Liver, 185, 192, 210, 215, 219, 233 Liver scan, 215, 233 Lobe, 85, 138, 215 Localization, 60, 215 Localized, 200, 212, 215, 219, 226 Locus Coeruleus, 82, 215 Lod, 136, 215 Lod Score, 136, 215 Logistic Models, 215, 231
251
Longitudinal Studies, 38, 66, 215 Longitudinal study, 20, 58, 65, 215 Long-Term Care, 152, 216 Loop, 146, 216 Low Back Pain, 55, 216 Lumbar, 49, 191, 213, 216, 236 Lumbar puncture, 49, 216, 236 Lutein Cells, 216, 228 Lymph, 204, 216, 231 Lymph node, 216, 231 Lymphatic, 204, 212, 216 Lymphocyte, 119, 123, 185, 190, 216, 217 Lymphocyte Count, 185, 216 Lymphocyte Subsets, 119, 216 M Macrophage, 213, 216 Magnetic Resonance Imaging, 18, 91, 150, 216, 233 Magnetic Resonance Spectroscopy, 86, 93, 216 Malignant, 185, 186, 216, 220 Malnutrition, 191, 216 Mania, 38, 93, 140, 144, 155, 211, 216, 217 Manic, 53, 106, 144, 149, 190, 192, 215, 217, 229 Manifest, 44, 146, 217 Medial, 93, 208, 217, 223, 234 Mediate, 31, 46, 54, 57, 58, 202, 217 Mediator, 33, 213, 217, 226, 234 Medical Records, 8, 14, 20, 21, 217 Medicament, 146, 217 MEDLINE, 167, 217 Meiosis, 217, 238 Melanin, 215, 217, 241 Membrane, 191, 194, 197, 205, 217, 219, 225, 238 Membrane Lipids, 217, 225 Memory, 6, 18, 49, 60, 78, 81, 95, 112, 149, 150, 151, 182, 188, 189, 200, 217 Meninges, 195, 199, 217 Menopause, 100, 217, 227 Menstruation, 217 Mental Disorders, 39, 46, 57, 63, 139, 140, 142, 143, 144, 151, 217, 229 Mental Health Services, iv, 7, 21, 39, 168, 217 Mental Processes, 202, 217, 229 Mental Retardation, 59, 141, 217 Mercury, 206, 217 Mesencephalic, 215, 218 Mesolimbic, 190, 218 Meta-Analysis, 83, 87, 99, 108, 218
Metabolite, 25, 218, 222 Methionine, 27, 46, 82, 192, 218, 237 Methyltransferase, 74, 218 MI, 22, 27, 142, 183, 218 Mianserin, 72, 218 Microbe, 218, 240 Microbiology, 186, 191, 218 Microglia, 191, 218, 219 Microtubule-Associated Proteins, 218, 221 Microtubules, 213, 218, 220 Mitosis, 190, 218 Mobility, 33, 218 Mobilization, 22, 218 Moclobemide, 111, 114, 219 Modeling, 29, 30, 35, 59, 63, 96, 219 Modification, 188, 219, 230 Molecular Structure, 219, 240 Molecule, 143, 190, 197, 202, 203, 204, 205, 219, 226, 229, 231, 241 Monitor, 35, 61, 96, 219, 222 Monoamine, 65, 83, 103, 146, 219, 241 Monoamine Oxidase, 103, 219, 241 Monocytes, 213, 214, 219 Monotherapy, 9, 53, 106, 126, 219 Mood Disorders, 15, 25, 35, 38, 39, 41, 55, 65, 136, 140, 142, 155, 219 Morphine, 190, 219, 220 Mother-Child Relations, 48, 219 Motility, 219, 234 Mucins, 219, 233 Mucosa, 219, 228 Multicenter Studies, 50, 82, 219 Multicenter study, 28, 112, 219 Multiple sclerosis, 150, 220 Mutilation, 50, 220 Myelin, 220 Myocardial infarction, 22, 72, 199, 218, 220 Myocardium, 218, 220 N Naltrexone, 56, 63, 220 Narcotic, 219, 220 Nausea, 189, 190, 207, 220, 223 Necrosis, 190, 212, 218, 220, 232, 234 Neocortex, 220, 221 Neonatal, 42, 51, 220 Neoplasm, 220, 241 Nerve, 186, 188, 189, 191, 195, 200, 215, 217, 219, 220, 234, 236, 240, 242 Nervous System, 149, 182, 186, 188, 195, 217, 220, 221, 224, 237, 238, 241 Neural, 106, 110, 114, 138, 186, 188, 201, 218, 219, 220, 234
252
Major Depression
Neuroanatomy, 44, 215, 220 Neuroendocrine, 23, 32, 140, 220 Neuroendocrinology, 32, 220 Neurofibrillary Tangles, 5, 220 Neurofilaments, 220, 221 Neuroleptic, 187, 190, 221 Neuronal, 10, 44, 57, 100, 138, 194, 196, 221 Neurons, 10, 44, 78, 145, 200, 201, 207, 220, 221, 231, 237, 238, 242 Neuropeptide, 77, 199, 221 Neuropsychological Tests, 6, 18, 221 Neurosis, 221, 225 Neurosurgery, 75, 138, 221 Neurotic, 136, 138, 221 Neurotoxicity, 10, 90, 221 Neurotransmitter, 56, 65, 145, 185, 186, 188, 193, 202, 208, 210, 221, 222, 237, 238, 241 Niacin, 221, 241 Nicotine, 42, 133, 221 Nitric Oxide, 10, 221 Nitrogen, 187, 222, 241 Nonverbal Communication, 222, 230 Norepinephrine, 59, 71, 100, 186, 188, 201, 202, 221, 222 Nortriptyline, 45, 65, 80, 222 Nuclear, 41, 192, 203, 215, 220, 222, 238 Nuclei, 43, 73, 103, 145, 188, 203, 204, 205, 216, 218, 222, 229, 234, 242 Nucleic acid, 222, 228, 230 O Observational study, 111, 222 Obsessive-Compulsive Disorder, 42, 44, 85, 89, 93, 136, 206, 222 Occult, 36, 222 Odds Ratio, 11, 222, 232 Omega-3 fatty acid, 117, 123, 124, 143, 222 Opacity, 200, 222 Operon, 223, 232 Opiate, 192, 204, 219, 223 Opportunistic Infections, 185, 223 Optic Chiasm, 211, 223 Oral Health, 3, 223 Orthostatic, 59, 190, 223 Outpatient, 39, 223 Ovary, 205, 208, 223, 226 Ovum, 208, 214, 223, 228, 243 Oxygen Consumption, 223, 232 Oxytocin, 12, 223 P Palliative, 24, 223, 238
Pancreas, 185, 212, 223 Panic, 13, 42, 52, 66, 89, 114, 121, 136, 138, 172, 206, 211, 223 Panic Disorder, 13, 42, 52, 66, 89, 114, 121, 136, 138, 172, 206, 211, 223 Parent-Child Relations, 63, 223 Parenteral, 27, 47, 223 Paresthesias, 223 Parity, 13, 224 Parkinsonism, 110, 190, 224 Paroxetine, 22, 44, 80, 101, 114, 224 Partial remission, 9, 224, 232 Partial response, 9, 144, 224 Particle, 224, 240 Parturition, 224, 228 Pathogenesis, 36, 43, 138, 151, 224 Pathologic, 190, 192, 199, 211, 224, 241 Pathologic Processes, 190, 224 Pathophysiology, 25, 57, 65, 89, 224 Patient Compliance, 63, 224 Patient Education, 172, 176, 178, 183, 224 Pelvis, 185, 216, 224 Peptide, 188, 192, 224, 227, 229, 239 Perception, 24, 93, 124, 145, 149, 153, 201, 224, 233 Perfusion, 85, 211, 224 Perinatal, 14, 55, 58, 224 Peripheral blood, 213, 224 Peripheral Nervous System, 221, 224, 228, 237 Personality Disorders, 6, 15, 73, 76, 79, 224 Pharmacist, 11, 224 Pharmacologic, 34, 35, 52, 55, 102, 124, 173, 189, 209, 225, 240 Pharmacotherapy, 9, 11, 16, 28, 32, 44, 45, 56, 60, 62, 64, 67, 79, 120, 126, 139, 143, 225 Phenotype, 65, 136, 225 Phenyl, 25, 225 Phobia, 14, 52, 66, 67, 136, 225 Phobic Disorders, 136, 225 Phospholipids, 121, 205, 217, 225 Phosphorus, 193, 225 Phosphorylated, 80, 225 Phosphorylation, 41, 225 Phototherapy, 225, 234 Physiologic, 39, 66, 187, 192, 209, 217, 225, 231 Physiology, 52, 76, 138, 204, 225 Pilot study, 12, 28, 34, 60, 64, 72, 75, 89, 97, 225 Pituitary Gland, 199, 225
253
Pituitary Hormones, 123, 225 Placenta, 191, 205, 225, 228, 241 Plants, 187, 194, 195, 208, 222, 226, 227, 233, 240 Plaque, 188, 226 Plasma, 66, 88, 101, 102, 121, 124, 125, 189, 194, 206, 207, 208, 209, 210, 226, 242 Plasticity, 78, 226 Platelet Aggregation, 22, 73, 221, 226 Platelet Factor 4, 72, 226 Platelets, 22, 73, 222, 226, 239 Platinum, 216, 226 Pneumonia, 198, 226 Poisoning, 190, 200, 204, 207, 213, 218, 220, 226 Pollen, 187, 226 Polygenic Inheritance, 137, 226 Polymerase, 41, 66, 226, 232 Polymerase Chain Reaction, 41, 66, 226 Polymorphic, 145, 201, 227 Polymorphism, 70, 71, 77, 87, 92, 100, 104, 141, 145, 227 Polypeptide, 188, 196, 206, 227, 228, 243 Polyunsaturated fat, 52, 97, 227 Post partum, 9, 13, 227 Posterior, 189, 191, 204, 223, 225, 227 Postmenopausal, 20, 227 Postnatal, 13, 30, 227, 236 Post-traumatic, 41, 70, 98, 209, 227 Post-traumatic stress disorder, 41, 70, 98, 227 Postural, 59, 227 Potentiates, 201, 213, 227 Potentiating, 188, 227 Practicability, 227, 240 Practice Guidelines, 168, 173, 227 Precipitating Factors, 11, 209, 227 Precursor, 195, 202, 203, 204, 222, 227, 241 Predictive factor, 98, 227 Prefrontal Cortex, 74, 91, 110, 112, 138, 227 Pregnancy Outcome, 8, 228 Prenatal, 8, 203, 228 Presynaptic, 145, 191, 221, 228, 238 Presynaptic Terminals, 191, 228, 238 Prion, 150, 195, 228 Problem Solving, 50, 68, 228 Progesterone, 228, 236 Progression, 19, 31, 150, 189, 228, 242 Progressive, 200, 220, 228, 232, 241 Projection, 222, 227, 228 Prolactin, 72, 73, 228 Proline, 74, 196, 211, 228
Promoter, 26, 70, 145, 146, 228 Prone, 17, 228 Prophase, 228, 238 Prospective study, 15, 71, 76, 84, 93, 94, 105, 215, 228 Protein Binding, 42, 228 Protein C, 145, 188, 191, 196, 229 Protein S, 188, 192, 229, 233 Proteoglycan, 226, 229 Proteolytic, 187, 197, 206, 229 Protocol, 40, 229 Protons, 210, 216, 229, 230 Pruritic, 203, 229 Psychic, 217, 221, 229, 234 Psychoactive, 229, 243 Psychogenic, 118, 229 Psychomotor, 18, 60, 125, 200, 221, 229 Psychopathology, 13, 48, 51, 54, 58, 63, 78, 86, 97, 103, 123, 229 Psychosis, 5, 13, 38, 42, 44, 151, 190, 229 Psychotherapy, 4, 12, 20, 28, 30, 48, 50, 62, 67, 79, 89, 144, 153, 196, 229 Psychotropic, 29, 39, 230 Public Health, 14, 15, 18, 24, 33, 35, 36, 38, 53, 57, 58, 120, 142, 168, 230 Public Policy, 17, 167, 230 Publishing, 4, 67, 150, 230 Pulmonary, 47, 103, 193, 199, 230, 232, 242 Pulmonary Artery, 193, 230, 242 Pulmonary hypertension, 199, 230 Pulmonary Ventilation, 230, 232 Pulse, 219, 230 Purines, 230, 234 Pyrimidines, 230, 234 Q Quality of Life, 12, 16, 21, 27, 28, 38, 47, 89, 230 R Race, 5, 29, 230 Radiation, 185, 203, 205, 206, 207, 230, 233, 236, 243 Radiation therapy, 185, 205, 230 Radioactive, 193, 209, 210, 212, 215, 222, 230, 233 Radiolabeled, 25, 230 Random Allocation, 230, 231 Randomization, 13, 231 Randomized clinical trial, 27, 47, 111, 118, 231 Raphe Nuclei, 145, 231 Reality Testing, 229, 231 Receptors, Serotonin, 231, 234
254
Major Depression
Recovery of Function, 19, 231 Rectum, 190, 197, 207, 212, 231 Recur, 231, 234 Recurrence, 9, 35, 53, 54, 65, 104, 106, 192, 231, 234 Refer, 1, 197, 202, 204, 208, 215, 221, 229, 231 Refraction, 231, 236 Refractory, 41, 44, 77, 91, 126, 141, 231 Regimen, 39, 203, 224, 225, 231 Regional cancer, 98, 231 Regression Analysis, 5, 231 Relapse, 17, 32, 35, 42, 43, 45, 46, 48, 53, 55, 56, 60, 65, 75, 90, 108, 144, 232 Relative risk, 11, 20, 21, 232 Reliability, 30, 34, 68, 232 Remission, 9, 27, 32, 36, 37, 47, 49, 52, 61, 65, 66, 79, 80, 86, 96, 104, 106, 192, 231, 232 Renal failure, 200, 232 Repressor, 145, 223, 232 Reproduction Techniques, 228, 232 Research Support, 45, 232 Respiration, 66, 190, 194, 195, 219, 232 Respiratory Physiology, 52, 232, 242 Respiratory System, 66, 232 Response rate, 35, 45, 232 Retinal, 202, 223, 232 Retrospective, 5, 232 Rhabdomyolysis, 126, 232 Rheumatism, 233 Rheumatoid, 106, 233 Rheumatoid arthritis, 106, 233 Ribose, 186, 233 Ribosome, 233, 240 Riluzole, 70, 233 Risperidone, 44, 71, 233 Rural Health, 83, 233 Rural Population, 233 S Saliva, 3, 29, 233 Salivary, 30, 52, 233, 243 Salivary glands, 233 Saponins, 233, 236 Scans, 65, 233 Schizoid, 233, 243 Schizotypal Personality Disorder, 201, 233, 243 Sclerosis, 220, 233, 234 Screening, 6, 13, 20, 34, 41, 60, 79, 94, 98, 105, 141, 196, 234
Seasonal Affective Disorder, 103, 130, 172, 234 Secretion, 32, 96, 210, 213, 214, 218, 219, 225, 234 Sedative, 188, 211, 234, 241 Segregation, 88, 234 Seizures, 153, 200, 234 Self Care, 185, 234 Senile, 151, 234 Septal, 215, 234 Septal Nuclei, 215, 234 Sequencing, 60, 227, 234 Sequester, 234, 238 Serine, 102, 234 Sertraline, 9, 16, 56, 63, 65, 67, 85, 97, 105, 114, 234 Serum, 42, 75, 96, 97, 122, 197, 234 Sex Characteristics, 186, 235, 238 Shock, 153, 235, 240 Side effect, 9, 27, 45, 47, 138, 139, 143, 161, 186, 187, 190, 196, 235, 240 Signs and Symptoms, 155, 232, 235 Skeletal, 232, 235 Skull, 199, 235, 238 Sleep apnea, 23, 36, 235 Sleep Deprivation, 80, 100, 126, 235 Small intestine, 210, 213, 235 Smoking Cessation, 43, 99, 193, 235 Social Environment, 230, 235 Social Support, 28, 30, 36, 55, 235 Solvent, 192, 205, 208, 235 Soma, 235 Somatic, 15, 66, 105, 123, 186, 215, 217, 218, 224, 228, 235 Soybean Oil, 227, 235 Spastic, 214, 235 Specialist, 32, 174, 235 Species, 204, 207, 208, 217, 218, 230, 235, 242, 243 Specificity, 44, 67, 70, 112, 187, 193, 236 Spectrum, 36, 140, 218, 236 Sperm, 187, 196, 226, 236 Spinal cord, 108, 191, 193, 195, 217, 220, 221, 224, 236, 237 Spinal tap, 216, 236 Spontaneous Abortion, 228, 236 Sporadic, 136, 236 Sprains and Strains, 216, 236 Stabilization, 9, 236 Staging, 233, 236 Stem Cells, 236, 241 Stereotactic, 138, 236
255
Stereotaxis, 138, 236 Steroid, 42, 147, 190, 199, 233, 236 Stillbirth, 228, 236 Stimulus, 60, 122, 186, 203, 205, 214, 223, 225, 236, 239 Stomach, 185, 207, 210, 220, 235, 236 Stool, 197, 212, 214, 237 Strand, 226, 237 Stroke, 35, 73, 105, 141, 166, 194, 237 Subacute, 212, 237 Subarachnoid, 207, 209, 237 Subclinical, 212, 234, 237 Subcutaneous, 223, 237, 242 Subiculum, 210, 237 Substance P, 218, 234, 237 Substrate, 57, 237, 241 Sudden death, 22, 237 Sulfur, 218, 237 Supplementation, 13, 23, 53, 128, 237 Support group, 182, 237 Suppression, 79, 97, 237 Sympathetic Nervous System, 221, 237 Sympathomimetic, 202, 204, 222, 237, 241 Symptomatic, 26, 28, 45, 49, 61, 66, 84, 237 Symptomatology, 8, 13, 26, 36, 48, 53, 60, 73, 86, 237 Synapse, 74, 186, 201, 228, 237, 238, 240 Synaptic, 10, 59, 90, 221, 238 Synaptic Transmission, 221, 238 Synaptic Vesicles, 10, 238 Synergistic, 228, 238 Systemic, 162, 193, 200, 204, 212, 213, 221, 230, 238, 240 Systolic, 211, 238 T Tachycardia, 59, 238 Tardive, 190, 196, 238 Telencephalon, 192, 195, 238 Temperament, 52, 73, 83, 84, 238 Temporal, 21, 25, 71, 79, 188, 209, 210, 238 Temporal Lobe, 21, 71, 188, 238 Testis, 205, 238 Testosterone, 188, 238 Thalamic, 93, 204, 238 Thalamus, 83, 201, 204, 215, 227, 238 Therapeutics, 80, 81, 145, 152, 162, 219, 238 Thermal, 202, 226, 238 Thoracic, 191, 239, 243 Thorax, 185, 216, 239 Threonine, 80, 234, 239
Threshold, 45, 60, 91, 124, 153, 205, 211, 239 Thrombin, 206, 226, 229, 239 Thrombocytes, 226, 239 Thrombomodulin, 229, 239 Thrombosis, 229, 237, 239 Thrombus, 199, 212, 226, 239 Thyroid, 92, 106, 107, 118, 128, 214, 239, 241 Thyroid Gland, 239 Thyroid Hormones, 239, 241 Thyrotropin, 78, 239 Thyroxine, 239 Tinnitus, 152, 153, 239, 242 Tomography, 25, 29, 44, 74, 150, 198, 216, 239 Tone, 129, 239 Tonus, 239 Tooth Preparation, 185, 240 Topical, 109, 205, 240 Toxic, iv, 144, 192, 221, 240 Toxicity, 25, 202, 218, 240 Toxicology, 168, 240 Toxins, 190, 193, 212, 240 Trace element, 206, 240 Trachea, 193, 239, 240 Transcription Factors, 57, 145, 240 Transduction, 52, 56, 240 Transfection, 192, 240 Translation, 68, 188, 240 Transmitter, 185, 191, 202, 217, 222, 238, 240, 241 Trauma, 12, 39, 67, 79, 150, 153, 200, 220, 231, 240 Treatment Outcome, 4, 12, 21, 24, 31, 36, 43, 53, 64, 240 Triage, 39, 240 Tricuspid Atresia, 199, 240 Tricyclic, 9, 22, 27, 47, 130, 188, 196, 201, 211, 240 Trigger zone, 190, 240 Trimipramine, 114, 125, 240 Trisomy, 188, 241 Tryptophan, 65, 72, 82, 196, 234, 241 Tumour, 146, 241 Type 2 diabetes, 89, 241 Tyramine, 219, 241 Tyrosine, 202, 241 U Ubiquitin, 221, 241 Umbilical Arteries, 241 Umbilical Cord, 30, 241
256
Major Depression
Umbilical cord blood, 30, 241 Unconscious, 189, 241 Urethra, 241 Urinary, 20, 22, 108, 212, 241 Urine, 29, 43, 192, 212, 241 Uterine Contraction, 185, 223, 241 V Vaccines, 241, 242 Vascular, 65, 150, 187, 188, 204, 209, 212, 221, 225, 239, 241 Vasoconstriction, 204, 241 Vasodilator, 193, 202, 210, 241 Vector, 240, 241 Vein, 213, 222, 241 Venlafaxine, 45, 79, 82, 101, 110, 242 Venter, 242 Ventilation, 52, 242 Ventral, 106, 211, 242 Ventricle, 188, 191, 199, 204, 210, 211, 230, 238, 240, 242 Ventricular, 199, 240, 242 Vertebrae, 213, 236, 242 Vesicular, 83, 242 Vestibulocochlear Nerve, 239, 242 Vestibulocochlear Nerve Diseases, 239, 242
Veterinary Medicine, 167, 242 Viral, 31, 240, 242 Viral Load, 31, 242 Virulence, 240, 242 Virus, 155, 185, 191, 195, 213, 226, 240, 242 Viscera, 235, 242 Visceral, 23, 215, 242 Visceral fat, 23, 242 Vitro, 210, 242 Vivo, 10, 25, 243 W Wakefulness, 200, 243 War, 227, 243 White blood cell, 189, 214, 216, 243 Windpipe, 239, 243 Withdrawal, 61, 200, 243 X Xenograft, 189, 243 Xerostomia, 3, 243 X-ray, 198, 206, 222, 230, 233, 236, 243 Y Yeasts, 225, 243 Z Zygote, 198, 243 Zymogen, 229, 243
