MOOD
DISORDERS A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright 2004 by ICON Group International, Inc. Copyright 2004 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Mood Disorders: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84042-3 1. Mood Disorders-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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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 mood disorders. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes&Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON MOOD DISORDERS .................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Mood Disorders............................................................................. 4 E-Journals: PubMed Central ....................................................................................................... 66 The National Library of Medicine: PubMed ................................................................................ 68 CHAPTER 2. NUTRITION AND MOOD DISORDERS ........................................................................ 113 Overview.................................................................................................................................... 113 Finding Nutrition Studies on Mood Disorders ......................................................................... 113 Federal Resources on Nutrition ................................................................................................. 115 Additional Web Resources ......................................................................................................... 116 CHAPTER 3. ALTERNATIVE MEDICINE AND MOOD DISORDERS .................................................. 117 Overview.................................................................................................................................... 117 The Combined Health Information Database............................................................................. 117 National Center for Complementary and Alternative Medicine................................................ 118 Additional Web Resources ......................................................................................................... 119 General References ..................................................................................................................... 122 CHAPTER 4. DISSERTATIONS ON MOOD DISORDERS .................................................................... 123 Overview.................................................................................................................................... 123 Dissertations on Mood Disorders .............................................................................................. 123 Keeping Current ........................................................................................................................ 124 CHAPTER 5. CLINICAL TRIALS AND MOOD DISORDERS .............................................................. 125 Overview.................................................................................................................................... 125 Recent Trials on Mood Disorders .............................................................................................. 125 Keeping Current on Clinical Trials ........................................................................................... 137 CHAPTER 6. PATENTS ON MOOD DISORDERS............................................................................... 139 Overview.................................................................................................................................... 139 Patents on Mood Disorders........................................................................................................ 139 Patent Applications on Mood Disorders.................................................................................... 158 Keeping Current ........................................................................................................................ 170 CHAPTER 7. BOOKS ON MOOD DISORDERS .................................................................................. 173 Overview.................................................................................................................................... 173 Book Summaries: Federal Agencies............................................................................................ 173 Book Summaries: Online Booksellers......................................................................................... 176 The National Library of Medicine Book Index ........................................................................... 179 Chapters on Mood Disorders ..................................................................................................... 179 CHAPTER 8. MULTIMEDIA ON MOOD DISORDERS ....................................................................... 183 Overview.................................................................................................................................... 183 Video Recordings ....................................................................................................................... 183 Bibliography: Multimedia on Mood Disorders .......................................................................... 184 CHAPTER 9. PERIODICALS AND NEWS ON MOOD DISORDERS .................................................... 187 Overview.................................................................................................................................... 187 News Services and Press Releases.............................................................................................. 187 Newsletter Articles .................................................................................................................... 189 Academic Periodicals covering Mood Disorders........................................................................ 190 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 193 Overview.................................................................................................................................... 193 NIH Guidelines.......................................................................................................................... 193 NIH Databases........................................................................................................................... 195 Other Commercial Databases..................................................................................................... 197
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APPENDIX B. PATIENT RESOURCES ............................................................................................... 199 Overview.................................................................................................................................... 199 Patient Guideline Sources.......................................................................................................... 199 Finding Associations.................................................................................................................. 201 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 203 Overview.................................................................................................................................... 203 Preparation................................................................................................................................. 203 Finding a Local Medical Library................................................................................................ 203 Medical Libraries in the U.S. and Canada ................................................................................. 203 ONLINE GLOSSARIES................................................................................................................ 209 Online Dictionary Directories ................................................................................................... 209 MOOD DISORDERS DICTIONARY ........................................................................................ 211 INDEX .............................................................................................................................................. 279
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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 mood disorders is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about mood disorders, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to mood disorders, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on mood disorders. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to mood disorders, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on mood disorders. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON MOOD DISORDERS Overview In this chapter, we will show you how to locate peer-reviewed references and studies on mood disorders.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and mood disorders, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “mood disorders” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Mood Disorders in Rheumatic Disease: Evaluation and Management Source: Journal of Musculoskeletal Medicine. 16(11): 643-646,648-650. November 1999. Summary: This journal article provides health professionals with information on the diagnosis of mood disorders that commonly occur in people who have rheumatic diseases and the therapeutic strategies that may help patients better cope with the stress of chronic illness. Mood disorders are common in people who have rheumatic diseases such as fibromyalgia, rheumatoid arthritis, and systemic lupus erythematous. Altered mood tends to worsen as the illness becomes more severe. Major depression is particularly common. The presence of depressed mood, loss of interest or pleasure for 2 weeks or more, and at least five of nine established criteria such as weight change, fatigue, and indecisiveness is diagnostic. Other mood disorders that people who have a rheumatic disease may experience include minor depression, adjustment disorder with
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Mood Disorders
depressed mood, bereavement, bipolar disorder, and depressive disorder related to the general medical condition. Management includes a combination of biologic and interactive approaches. The goals of treatment are to restore normal mood, prevent suicide, and improve self esteem, productivity, and quality of life. Pharmacologic treatment of depression is an essential component of care and is usually successful. Psychopharmacologic agents include selective serotonin reuptake inhibitors, tricyclic antidepressants, monoamine inhibitors, psychostimulants, mood stabilizers, lithium, and newer agents such as bupropion. Electroconvulsive therapy is a treatment option commonly used for patients with severe, life threatening depression or psychotic depression and for patients in whom drug therapy is considered dangerous. Two major forms of psychotherapy are effective in treating patients who have major depression associated with rheumatic disease and other medical illness. Cognitive behavioral therapy deals with the relationship between cognition, affect, and behavior, whereas interpersonal therapy deals with interpersonal relationships and their effects on mood. Although many mood disorders can be managed satisfactorily within the primary care setting, referral is recommended for patients who are at significant risk for suicide or who have psychosis, psychotic depression, or full blown mania. 3 tables and 25 references. (AA-M).
Federally Funded Research on Mood Disorders The U.S. Government supports a variety of research studies relating to mood disorders. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to mood disorders. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore mood disorders. The following is typical of the type of information found when searching the CRISP database for mood disorders: •
Project Title: A BIOBEHAVIORAL RESEARCH TRAINING PROGRAM Principal Investigator & Institution: Schatzberg, Alan F.; Professor and Chair; Psychiatry and Behavioral Sci; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 30-SEP-1994; Project End 30-JUN-2004 Summary: This is an application for Competitive Renewal of an institutional training grant. The intent of this training program is to prepare MD's and PhD's for a career in clinical research. Physicians are eligible if they have completed the PGY 3 year of psychiatry training; psychologists if they have completed a clinical internship. The program is centered on three disease entities; mood disorders, anxiety disorders, and
2
Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
Studies
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eating disorders, reflecting the ongoing and long-standing research interests of the core faculty involved in the program. Fellows work with a mentor who is a member of the Stanford University faculty for a period of two years on projects related to the phenomenology, clinical biology, treatment, and outcome in the three major classes of disorders. The Program includes formal seminars in research methodology, and clinical research design. In addition, all Fellows are required to take a course focused on ethics in medical research. Trainees also have access to a wide array of more specialized course work. All Fellows are expected to design and conduct their own research projects. Assistance is given in preparing trainees to apply for their own funding to support their research post fellowship. Program oversight and continual review of both the program and the trainees progress is provided by an Executive Committee representing the principal areas of research and the training sites. The Program is now in its 4th year. Ten trainees have been entered into the program (five MD's and five PhD's), and seven Fellows are currently being trained. Thus, the program has been successful in recruiting both M.D.'s and PhD.s to the program, in filling all the funded positions available, and in retaining all Fellows accepted to the program. To date, one class has completed training. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADJUNCTIVE ACUPUNCTURE TO TREAT BIPOLAR DEPRESSION Principal Investigator & Institution: Suppes, Patricia; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-FEB-2001; Project End 31-JAN-2003 Summary: Complementary and alternative therapies for psychiatric disorders are increasingly popular despite the lack of rigorous scientific data addressing their safety, tolerability, or efficacy. The proposed study adds to a small but growing body of literature to evaluate acupuncture in the treatment of mood disorders. The primary aims are to evaluate the feasibility and efficacy of acupuncture treatment in conjunction with psychopharmacology alone. The study will replicate methods of acupuncture diagnosis and treatment designed in a previous NIMH- funded study. The role of subjects' expectancies for acupuncture treatment will be evaluated. Patients will be randomized to either acupuncture plus stable medications (ACUP N=15) on clinical outcome or non-specific acupuncture plus stable medications (NS ACUP N=15). Clinical contact with an acupuncturist will be equivalent for both groups (12 sessions, 8 weeks). Patients, raters, and psychiatrists will be blind to group assignment. The criteria for inclusion now require moderate (vs. mild) depression for study entry to minimize study confounds such as spontaneous improvement. Safety measures and procedures to maintain study retention have been strengthened. Acupuncture patients will meet weekly with an RA and psychiatrist to complete ratings (IDS-C, CGI-BP, YMRS, GAF) and to assess side effects and symptom severity. We will include a comparison group (TAU) of patients who met entry criteria but refused the acupuncture intervention. Those subjects will continue to receive pharmacological treatment, and retrospective chart audit will allow us to determine the degree of change expected from medication treatment alone in this sample. While clinical trials have addressed the efficacy of acupuncture treatment for unipolar depression, a unique opportunity exists to bring similar rigor to the study of acupuncture for depressive symptoms in bipolar disorder. A strength of this proposal is its replication of methodology developed and used by other researchers in a study of acupuncture in MDD. Should acupuncture demonstrate efficacy in the treatment of bipolar disorder, further studies will be proposed to evaluate its utility for maintenance and prevention.
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ADOLESCENT PATHWAYS TO MOOD DISORDER AND RISK OF SUICIDE Principal Investigator & Institution: Greenhill, Laurence L.; Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001 Summary: This application is for a five-year project that uses a high-risk design to study the familial transmission of early-onset suicidal behavior. The probands consist of 200 adolescents depressed suicide attempters and non-attempters who will be well characterized in studies at NYS Psychiatric Institute. We will recruit some of this group from a cohort of 100 individuals previously studied for serotonergic function by us under R01 MH47113 at which time they were adolescents with major depression and half were suicide attempters. For each proband, the biological parents and full siblings (age 10 and older) of adolescent/young adult attempters and non-attempters will also be studied. Probands and their biological first-degree relatives will be characterized as to Axis I and II disorder, suicide attempt history, tendency to impulsive aggression and family environment. Parents and siblings will be genotyped with polymorphic markers for tryptophan hydroxylase and other candidate genes per Projects 2 and 4. After initial assessment, the probands and their siblings 24 years old or less will be followed at one and years after intake to observe the development of aggression, psychopathology, and suicidal behavior. The project will test the following hypotheses: (1) first- degree relatives of adolescent attempters will have higher rates of suicide attempts than the offspring of non-attempters; (2) impulsive aggression will be greater in relative of attempters, and will predict development of suicide attempts in siblings, especially in those siblings who also develop Axis I disorders; (3) the familial transmission of suicide attempts will not be explained by the familial transmission of mood disorders alone; (4) familial transmission of suicide attempts will persist after controlling for the expected greater exposure to familial adversity in the offspring of attempters; and (5) polymorphism of the of the tryptophan hydroxylase gene and other genes related to central serotonergic function will be associated with impulsive aggression and suicide attempts among proband and their first-degree relatives. We will also acquire pilot data on the relationship of baseline serotonergic and clinical indices to long-term outcome in the 100 previously studied cases. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ADOLESCENT PROGRESSION OF NICTOINE DEPENDENCE Principal Investigator & Institution: Niaura, Raymond S.; Director of Research; Miriam Hospital Providence, Ri 02906 Timing: Fiscal Year 2001 Summary: (Applicant's Description) Little is known about individual differences in susceptibility to nicotine dependence among youth. While most adolescents experiment with tobacco, the majority do not go on to develop a pattern of habitual use and nicotine dependence. While both familial and biobehavioral factors are important in predicting cigarette use, little is known about; 1) the familial aggregation of smoking especially among adolescents and first degree relatives (parents and siblings); 2) the nicotine use and dependence phenotypes which are transmitted from parent to child; and 3) heritable biobehavioral substrates which may predispose toward nicotine dependence. Characteristics related to disruptive behavior disorders (e.g., attention deficit
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hyperactivity disorder, conduct disorder) and mood disorders (e.g. depression) are associated with smoking in both youth and adults. Maternal smoking during pregnancy increases the likelihood of youth smoking and young adult nicotine dependence, and is simultaneously associated with a variety of developmental and neurocognitive deficits (e.g., ADHD; conduct disorder) that may increase the likelihood of developing nicotine dependence by potentiating the reinforcing effects of nicotine. The aims of this proposal are to study associations between: (1) Adolescent comorbid disruptive behavioral disorders, mood disorders, and the progression of nicotine dependence; (2) Corresponding parental and sibling comorbid smoking, nicotine dependence, antisocial, ADHD, and mood disorders in relation to adolescents' progression of nicotine dependence; and (3) Effects of maternal smoking during pregnancy on incidence and trajectory of comorbid disruptive behavioral and mood disorders and nicotine dependence. Accordingly, 644 families (adolescents, siblings and parents) will be studied prospectively over 3 years to determine those factors which predict progression of nicotine dependence. This prospective family study will utilize both existing and new data gathered as part of the National Collaborative Perinatal Project (NCPP), whose New England cohort includes over 16,000 adults who have been followed since birth, whose early neurological, cognitive, and psychological functioning has been documented, and whose children are, on average, 14 years old, and will be 17 years old when the proposed study is complete. We propose to study comorbid disruptive behavioral and mood disorders in these children, their parents and siblings, and use this information to predict progression of nicotine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ANIMAL MODELS OF FEAR AND ANXIETY Principal Investigator & Institution: Davis, Michael; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: Five compounds (the CRH1 receptor antagonist SB723620, the NK1 antagonist G597599, the SSRI/5HT2A agonist Vilazodone, the antidepressant 8hydroxy-bupropion, and the type 4 phosphodiesterase inhbitor SB207499), provided by GlaxoSmithKline as part of The Emory-GSK-NIMH Collaborative Mood Disorders Initiative, will be evaluated for anti-fear and anxiolytic activity using fear-potentiated, light-enhanced, and CRH-enhanced startle paradigms (increased startle in the presence of cues that predict shock, during sustained illumination, or following i.c.v. corticotropin-releasing hormone infusions, respectively). Whereas light- and CRHenhanced startle (which are more akin to anxiety than to fear) are mediated by circuitry that includes the bed nucleus of the stria terminalis (BNST) but not the central nucleus of the amygdala (CeA), fear-potentiated startle is mediated by circuitry that includes the CeA but not the BNST. A central goal of the proposed studies will be to identify differing pharmacological vulnerabilities associated with BNST (anxiety) versus CeA (fear) dependent behaviors. In humans, anxiety disorders are more prevalent in women than in men and, in rats, light-enhanced startle is more robust in females than in males. Interestingly, the BNST is sexually dimorphic in both species. Thus, a second goal will be to compare the influence of gender on BNST- versus CeA-dependent responses, and to evaluate gender influences on drug responses in each model. These same compounds will be evaluated in other laboratories (separate applications) using different behavioral models and non-behavioral assays. It is hoped that this integrated effort will foster new approaches for the rapid evaluation of novel compounds with potential clinical utility. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: ASSESSMENT OF JUVENILLE BIPOLAR SPECTRUM DISORDERS Principal Investigator & Institution: Youngstrom, Eric A.; Psychology; Case Western Reserve University 10900 Euclid Ave Cleveland, Oh 44106 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Bipolar spectrum disorders (BPSD) are commonly misdiagnosed in community mental health settings, resulting in suboptimal treatment selection that can actually worsen the course of the disorder. Part of the difficulty in diagnosis is the current lack of consensus about the phenomenology of juvenile BPSD. At present, there also is no certainty about the base rate at which BPSD might present at a community mental health setting, nor is there an established set of instruments that could be used to screen a juvenile community sample for bipolar spectrum disorders. Such a screening protocol is sorely needed, given the long-term trajectory and serious consequences of untreated or mistreated BPSD, and the potential value of early intervention if juvenile cases could be identified. Preliminary evidence from this research group suggests that several measures perform well at distinguishing BPSD from unipolar depression, disruptive behavior disorders, and other disorders in children and adolescents (see Appendices). However, these findings were based on a sample presenting at an outpatient research clinic specializing in the treatment of juvenile mood disorders and psychopharmacology research. Thus, several factors prevent the immediate application of existing findings to a community setting, including the lack of soundly-established base rate of BPSD at community- based mental health centers, the unknown effects of potential ascertainment bias at a mood disorders clinic versus a community setting, changes in demographics or other sample characteristics that might interact with test performance, and the fact that test performance might degrade when exported from a research framework into a community context - much as therapeutic efficacy estimates usually exceed effectiveness findings. The purpose of the proposed study is to develop effective means of screening for bipolar spectrum disorders in a community mental health setting serving an ethnically and racially diverse population. This will be accomplished by determining the prevalence of bipolar disorders in a community sample, validating measures that have performed well in an academic clinical setting, and clarifying the features of early presentation of bipolar spectrum disorders along with their longitudinal course over 18 months. Particular attention is paid to identifying and validating diagnostic characteristics of youths with bipolar symptoms that do not meet full criteria for a bipolar diagnosis. These children, currently labeled "Bipolar- Not Otherwise Specified", may represent an early developmental precursor of later bipolar disorder, or they may manifest a developmentally different presentation and course. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISORDERS
BDNF
MUTANTS:
GENETIC
MODELS
FOR
DEPRESSIVE
Principal Investigator & Institution: Rios, Maribel; Anatomy and Cellular Biology; Tufts University Boston Boston, Ma 02111 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): Depressive disorders are debilitating conditions that affect millions of individuals and create an enormous burden on society. Close to 100 billion dollars per year are spent treating patients with severe and mild forms of depression in the United States alone. However, the underlying molecular mechanisms that trigger depression remain to be elucidated so that treatment alternatives for patients
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that are unresponsive to the current forms of therapy can be created. A potential target for the design of novel treatment strategies is brain derived neurotrophic factor (BDNF). Compelling evidence shows that BDNF modulates affective behavior but the specific role and the mechanism of action of this neurotrophin remain elusive. We recently generated conditional mutations of BDNF using the cre recombinase/IoxP system. These mice have a pre or postnatal depletion of BDNF in the central nervous system that does not compromise their viability as the global depletion of BDNF does. These mutants display dramatic changes in behavior including hyperaggression and hypersensitivity to stress, both of which are often symptoms of depression. We propose using these mutants, and others that we are currently generating, as genetic models of depressive disorders to dissect the role of BDNF in the regulation of behavior. Different lines of mutants that through genetic manipulation have depletion or over expression of BDNF in different regions of the brain associated with mood disorders will be tested using standard behavioral models for depression and aggression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIOR IN MOUSE TRYPTOPHAN HYDROXYLASE MUTANTS Principal Investigator & Institution: Patel, Paresh; Psychiatry; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2007 Summary: (provided by applicant): The candidate is a child and adolescent psychiatrist with experience in molecular biology and neuroscience. He holds a tenure track junior faculty appointment with 80 percent research time at the University of Michigan Medical Center. This career development award will serve to expand his skills to include the development of genetic animal models and their behavioral phenotyping. The skill base interdigitates with a commitment by the University of Michigan Mental Health Research Institute (MHRI) to apply novel molecular approaches to identify new candidate genes for major depression and undertake their anatomic, structural, and functional characterizations. It is expected that by the end of this grant, the candidate will have gained sufficient experience and generated several informative animal models for independent research and collaboration. The University of Michigan Medical Center is a thriving research community with ample resources for carrying out the proposed studies. A highly successful core facility is available for transgenic manipulation. Faculty in the MHRI bear expertise in the areas of genetic engineering, biochemistry, rodent anatomy, and animal behavior. The candidate is being supervised by a senior research scientist in the MHRI with consultative support from leaders in the field of mouse transgenics and behavior phenotyping. This project applies emerging molecular technology to expand understanding on the role of serotonin biosynthesis and neurotransmitter levels on nervous system development and behavior. The design employs neuron specific and tetracycline-inducible genetic elements to engineer transgenic mice permitting regulation of tryptophan hydroxylase (TPH) activity. TPH is the rate-limiting enzyme in serotonin biosynthesis, and is thereby critical to serotonin turnover. The recombinant animals will permit probing the effects of temporal and tissue-selective up- or down-regulation of brain serotonin on measures of anxiety, attention, learning, memory, aggression, appetite, drug preference, and other behaviors. The proposed research is central to the serotonin hypothesis of mood and anxiety disorders, and offers a model for studying the developmental effects of serotonin turnover on brain maturation. The candidate's long-term career plan is academic research integrating human clinical, genetic and animal model information for major mood disorders
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Mood Disorders
Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHILDREN OF BIPOLAR PARENTS: A HIGH RISK FOLLOW-UP STUDY Principal Investigator & Institution: Birmaher, Boris; Associate Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 20-AUG-2001; Project End 30-JUN-2006 Summary: Proposed is a 5-year longitudinal, high-risk study examining the psychopathological and functional status of 800 children and adolescents (age 7-18.0 years old) of 400 parents with bipolar disorder(BPD) and compare them with 300 children of 150 non-bipolar, community control parents, with frequency matched on age, ethnicity, and neighborhood. The parents with BPD will be ascertained through the Stanley Center Community control parents will be ascertained using Cole's reverse directory. Offspring will be assessed at intake and annually, alternating between face-toface and phone interviews, with standardized instruments to examine the differential incidence of psychopathology, dimensional measures of behavior and emotional psychiatric history. Offspring (an estimated 160 of 800) of BPD parents who at intake already have BPD (I, II, NOS and cycolthymia) will be followed through another grant Within the high-risk cohort, the investigators will examine the relationships between initial presentation and ultimate development of BPD and other mood disorders across different age groups. They hypothesize that offspring of BPD vs. offspring of control will show 1) Higher rates of incident BPD and other mood disorders and 2) Higher degree of behavior problems and mood dysregulation: 3) Within the offspring of BPD, incidence of BPD will be predicted by: early onset of parent's BPD, loaded pedigree for increased mood liability, increased exposure to familial and environmental negative events, and onset of puberty; and 4) Prepubertal onset vs. post-puberty onset BPD will show greater chronicity, frequency of mixed and rapid cycling presentations, and comorbid disruptive disorders. This unique prospective study will have important implications, and comorbid disruptive disorders. This unique prospective study will have important implications for early-detection, intervention, and prevention of childhood-onset of BPD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE NEUROSCIENCE RESEARCH UNIT Principal Investigator & Institution: Paulsen, Jane S.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001 Summary: Overall Aims 1. To define the fundamental cognitive deficits in patients with schizophrenia, using principles adapted from cognitive and experimental neuropsychology. 2. To examine the neural circuit hypotheses of schizophrenia by investigating cognition in other conditions with known neural mechanisms that can serve as "Model syndromes" such as Huntington's disease or patients with circumscribed lesions. 3. To study the relationships between disordered cognition and psychopathology using patients with mood disorders and/or with psychotic disorders. 4. To develop and apply new cognitive tasks to patients with schizophrenia, emphasizing tests found to be sensitive to brain areas considered abnormal (according to imaging and/or animal studies) in schizophrenia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COGNITIVE THERAPY FOR HIGH RISK & REFRACTORY DEPRESSION Principal Investigator & Institution: Jarrett, Robin B.; Professor; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2001; Project Start 01-DEC-1998; Project End 30-NOV-2003 Summary: This request for an Independent Scientist Award (KO2) fosters the candidate's research proficiency in personality disorders and treatment development within the context of three randomized clinical trials (RCTs) on the efficacy of cognitive therapy (CT) in reducing the likelihood of mood disorders in high risk or refractory outpatients. Project 1 (an ongoing R01) compares continuation phase CT (C-CT) to evaluation only (control) in reducing the risk of relapse during the first eight months following response to acute phase CT in outpatients with recurrent major depressive disorder (MDD). Approximately 156 male and female outpatients, aged 18-65, have entered 20 sessions of acute phase CT. Approximately 84 responders were randomized to either 8 months of: (a) 10 C-CT sessions, or (b) 10 evaluation only (control sessions); subjects are followed for an additional 16 months CT free. Relapse/recurrence (DSM IF MDD) is assessed by a blind evaluator using the LIFE at 4, 8, 12, and 24 months postacute phase CT and at suspected relapse/recurrence, or exit. Project 2 is a proposed, multi-site collaboration with University of Pittsburgh (Western Psychiatric Institute and Clinic; WPIC). This blinded, controlled RCT will evaluate the efficacy of and indications for eight months of C-CT, pharmacotherapy (the standard of care) (FLX: fluoxetine), and pill placebo (PBO: the control) in outpatients with recurrent MDD who are at higher risk for relapse/recurrence. "Higher risk" is a score >6 on the Hamilton Rating Scale for Depression (HRS-D) during the last six weeks of acute phase CT, while "lower risk" is defined as a score of 6 or less. The primary hypotheses is that higher risk patients who receive either C-CT or FLX have a longer time until relapse than higher risk patients who receive acute phase CT only plus PBO. The lower risk patients will be followed for 24 months without CT and are predicted to have a 20% relapse/recurrence rate in the first 8 months after acute phase CT. Project 3 is a proposed, multi-site collaboration with WPIC comparing the differential efficacy of a trial of: (a) FLX and (b) FLX plus CT in out- patients with recurrent MDD who were refractory to 20 sessions of acute phase CT. Blind evaluation of outcome will aid in testing the prediction that combination therapy is more efficacious for refractory depression than FLX alone. The KO2 focuses the candidate on (a) identifying the residual symptoms and social impairment remaining after CT and (b) designing treatment sequences to restore full functioning. These RCTs have great public health significance because they will help identify (a) when CT reduces the risk of relapse-recurrence for patients suffering from recurrent MDD, an illness with high morbidity and mortality, and (b) if refractory MDD is best treated with combination therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: COMORBID DEPENDENCE
DISORDERS
IN
TREATMENT
OF
OPIATE
Principal Investigator & Institution: Gonzalez-Haddad, Gerardo; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 01-JUL-2001; Project End 30-JUN-2006 Summary: (Provided by Applicant) This application is to study comorbid disorders that affect the treatment of opiate dependence. The specific aims of the proposed program of research are as follows: Study 1 will examine comorbid depression as a predictive factor
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Mood Disorders
in treatment with desipramine and contingency management of cocaine abusing opiate dependent subjects maintained on buprenorphine by secondary data analysis of a completed randomized clinical trial. Study 2 will evaluate the efficacy of sertraline in the treatment of cocaine dependent patients with comorbid depression in a recently started double-blind randomized clinical trial. Study 3 will determine changes of health care cost after treatment of opiate dependence in the Veterans Affairs health delivery system using existing administrative databases. It will determine whether confounding factors, especially comorbid depression and cocaine dependence, may affect changes in costs. The overall aim of the proposal is to provide me with a supervised patient oriented research and educational experience that will enable me to become an independent investigator in substance abuse. My specific career development goals are to: (1) Acquire in-depth knowledge of the neuropharmacology of cocaine and opiate dependence, and of substance induced mood disorders. (2) Develop expertise in clinical research and management of cocaine and opiate dependence, and current pharmacotherapies. (3) Develop skills in Mental Health Service research related to substance abuse. The proposed career development plan utilizes the collaboration of Thomas Kosten, MD in developing expertise executing randomized clinical trials, Robert Rosenheck, MD in developing skills in mental health services research and Kevin Sevarino, MD, PhD in clinical management of opiate dependence. The educational experience includes a four year period of formal coursework at the Interdepartmental Neuroscience Program at the Yale School of Medicine and at the Yale School of Epidemiology and Public Health. This K23 research career award will enable me to start an academic career focusing on research in cocaine and opiate dependence and to develop a bridge between clinical trials and services research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--CHRONOBIOLOGY LABORATORY Principal Investigator & Institution: Campbell, Scott S.; Professor; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2002 Summary: The Chronobiology Core is guided by the overriding hypothesis that the onset, course and outcome of geriatric mood disorders are associated with various state and trait variables that can be measured by some of the same techniques and methodologies used to examine sleep and biological rhythms in healthy subjects. By assessing these variables prior to and during the course of treatment, and relating them to clinical measures, it is hypothesized that a better understanding can be gained as possible mechanisms of action of various treatment modalities, as well as potential physiological predictors of susceptibility to and recovery from late-life depression. The Core will carry out the scientific mandate of the nature CRC by testing specific hypotheses concerning outcomes, mechanisms, and treatment of geriatric affective disorders. Outcomes. Physiological measures, including waking quantitative EEG (qEEG) and 24-hour sex hormone levels, will be investigated by our Core to determine if they can predict the occurrence of, as well as the time to clinical recovery. Both baseline and longitudinal assessments will be combined with corresponding data from other CRC Cores to evaluate whether there are qEEG or sex hormone correlates of outcomes such as dementia, disability, chronicity, recurrence relapse, or mortality. Mechanisms. The Chronobiology Core will characterize age-related changes in circadian rhythmicity in healthy older individuals. These efforts will lay the groundwork for elucidating putative mechanisms involved in increasing the vulnerability to geriatric mood disorders. Treatment. By continuing to test hypothesis concerning the chronobiological
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effects of electroconvulsive therapy, and relating these effects to treatment efficacy, the Chronobiology Core seeks to further the understanding of how chronobiological principles may mediate this treatment of geriatric depression, and perhaps outline other means by which chronobiological principles may enhance treatments of geriatric depression. Measurement of qEEG, sex hormone levels, and circadian rhythm variables add a unique scientific dimension to this CRC. The integration of these data with services provided by the Pathophysiology, Psychosocial and Clinical Psychopharmacology Cores is expected to generate additional testable concepts to facilitate our understanding of the etiology and treatment of geriatric mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--FUNCTIONAL BRAIN IMAGING Principal Investigator & Institution: Mathis, Chester A.; Professor; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001 Summary: The Functional Brain Imaging Core will provide the scientific environment, imaging resources, and data analysis support to conduct three novel pilot investigators of late-life mood disorders using functional imaging. Each imaging study will examine a specific biological hypotheses related to late-life mood disorders using functional imaging method that share two or more of the following innovative attributes: a) measurement of the change in regional brain function during a pharmacological or sensory probe; b) examination of the remitted patient to allow focus on potential traitrelated attributes; or c) examination of a specific receptor system putatively related to the manifestion of mood disorders in the elderly. Objectives of the three proposed pilot projects are; Study 1: Identify circadian timing system abnormalities in remitted late-life depressed patients using a bright light stimulus. Study 2: Determine the relationships between the regional brain serotonin-mediated responses to a serotonergic challenge, CSF 5-HIAA as a measure of overall serotonin innervation, and suicidality and hopelessness in late-life depressed patients. Study 3; Identify changes in regional serotonin reuptake )serotonin transporter) sites in elderly depressed patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--HEALTH AND BEHAVIOR Principal Investigator & Institution: Schulz, Richard; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2002; Project Start 01-MAR-2002; Project End 28-FEB-2003 Summary: The Health and Behavior Core (formerly the Psychosocial Core) focuses on the social psychological, and behavioral factors relevant to understanding the interactive nature of physical illness and depression and their treatment. This core has 3 service aims and 3 scientific aims. The service aims are (1) to provide consultation to the IRC regarding the conceptualization and measurement of health and behavioral factors as they may account for the health-mood disorder relationship. (2) "Provide guidance in the selection and application of social and behavioral intervention methods and technologies that can be applied to the prevention and treatment of late-life mood disorders." (3) Consult with IRC training sectors on scientific aspects of Health and Behavior issues. The scientific aims are: (1) Develop and test interventions for primary care and specific-illness patients. (2) Facilitate future intervention research through broadening research populations (including family members) across different health-
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Mood Disorders
care settings. (3) "Explore the phenomenology and health-behavioral correlates of latelife mood disorders." Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CORE--MEDICAL Principal Investigator & Institution: Williams-Russo, Pamela; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001 Summary: Geriatric depression is rarely found without at least some medical comorbidity and/or impatient in physical functioning. Not only do these conditions complicate the study of geriatric depression, but evidence from the Developing CRC suggests that they are important indicators of heterogeneity in late life mood disorders and contribute to their outcomes; for example in depressed CRC subjects, medical burden predicts chronicity of depression and delayed recovery is associated with increased mortality. The Medical Core is newly added to the CRC and developed from collaborative relationships between investigators in the Departments of Psychiatry and Internal Medicine at Cornell. Addition of the Medical Core uniquely contributes to the CRC's investigation of heterogeneity of late life mood disorders by rigorous and extensive study of medical illness, functional impairment and depression course and outcome. The Medical Core expands the CRC's resource by providing: 1. funded medical investigators with extensive experience conducting longitudinal studies of comorbidity in medical setting patients and having central roles in the CRC; 2. access to a large population of elderly medical patients accustomed to receiving care in a research environment; 3. training and supervision in the administration of carefully selected instruments to assess longitudinal variation in medical morbidity and functional performance; (4) investigations of depression in post-operative depression in subjects enrolled in funded longitudinal studies of coronary bypass surgery and hip fracture repair. The Medical Core will work with the Clinical Core in screening and recruiting elderly patients from primary care settings for assessments and longitudinal follow-up, including subjects with major depression (N=50), minor depression (N=50) and nondepressed. These patients will contribute to the overall CRC database, yielding a sample of depressed elderly subjects ranging widely in severity and type of medical comorbidity and functional status, and followed longitudinally with extensive clinical, neuropsychological and psychosocial ratings. As part of its mission, the Medical Core will take advantage of these data to test cross-core hypotheses concerning the reciprocal relationships of depression and medical illness over time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: CORE--PATHOPHYSIOLOGY LABORATORY Principal Investigator & Institution: Van Gorp, Wilford; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001 Summary: The Pathophysiology Core (PA Core) has evolved from the Neuropsychology Core as a consequence of CRC findings of the previous funding period. We have identified evidence of at least two clinically and biologically meaningful subgroups of geriatric depression: 1. A group with predominant frontal systems impairment which is characterized by a distinct clinical presentation and a chronic course; and 2. A group with predominant memory impairment which is responsive to antidepressant treatment but at high risk for dementia (Alzheimer's or vascular). We argue that these subtypes are
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relevant to the pathophysiology of geriatric depression rather than randomly occurring comorbid states. The mission of the PA Core is to orchestrate for the CRC a program of targeted investigations into the above hypothesis using the science and techniques of four specialized laboratories: 1. neuropsychology; 2. evoked potentials; 3. structural MR neuroimaging; and 4. functional neuroimaging. Conceptual and operational integration of these laboratories provides a coordinated plan using complementary techniques to pursue biological hypothesis in a way that would be difficult, if not impossible to do, outside a CRC environment. Finally, the shared scientific goal of the PA Core provides its laboratories a coherent strategy for development of investigative methodology so that they can continue to make essential contributions to the pathophysiology of geriatric mood disorders. The findings and assessments of the PA Core will be sued by other Cores of the CRC in hypotheses examining heterogeneity in outcomes, mechanisms, and treatment of geriatric mood disorders. To accomplish its mission, the PA Core takes advantages of a unique geriatric population with a wide range of cognitive and medical morbidity necessary for testing the CRC hypotheses. Moreover, the PA Core draws upon the expertise and measures of other CRC Cores, such as Chronobiology, Psychopharmacology, and Psychosocial, to widen its scope. The PA Core will remain a central training resource in biological theory and techniques for senior and junior investigators of the CRC and for the research training programs of the Department of Psychiatry and the Medical College, including an NIMH research fellowship in geriatric mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CRC/GERIATRIC MOOD DISORDERS Principal Investigator & Institution: Alexopoulos, George S.; Professor and Vice Chair; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 30-SEP-1992; Project End 30-APR-2003 Summary: The Developing CRC was funded in October 1992 in order to form a multidisciplinary center of scientific excellence for studies and training in geriatric mood disorders. Mood disorders are highly prevalent and chronic in elderly populations and contribute to cognitive impairment, disability and mortality. The CRC's organizing principle has been that geriatric mood disorders are heterogenous syndromes best studied by clinical and biological investigations using outcomes as the principle validating parameter. This approach has yielded scientific evidence of subtypes of mood disorders with distinct clinical and biological characteristic and illness course. Beyond their heuristic value, these CRC findings have direct applicability to clinical practice. Fundamental to our success has been the CRC's achievement in recruitment (our goal was met) of a sample (N=235) with low attrition (total of 9.75 over 4 years), development of a well-managed database, and availability of advanced statistical support. Following the recommendations of the NIMH Study Section and its own external Advisory Committee the CRC has successfully created an atmosphere conductive to discovery and growth as evidenced by substantial increase in external funding (600%) in the past 4 years (12 R01 and R03 awards, 1 R24 grant for development of a Mental Health Services Research Program, 6 NIMH Career Development Awards and 4 Minority Supplements and Women's Studies grants). This application builds on these achievements and focuses on 3 over- arching themes: 1. long-term outcomes; 2. mechanisms, and 3. treatment of heterogenous geriatric mood disorders. The CRC has attracted new senior and junior investigators who enrich the scientific investigation and training. The Neuropsychology Core has added expertise in evoked potentials, structural and functional imaging. Medical and Psychosocial Cores are new to the CRC. We will
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Mood Disorders
expand the CRC sample by 400 subjects, including patients from medical (N=150), as well as psychiatric settings. These developments augment the CRC's histological strengths making possible integrative study of biology, medical co-morbidity, psychosocial characteristics, and both clinical and psychosocial outcomes in geriatric mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CYTOKINE INDUCED DEPRESSION Principal Investigator & Institution: Miller, Andrew H.; Professor; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: Depression in the medically ill occurs 5-10 times more often than depression in the general population and has a significant impact on treatment adherence, quality of life, and morbidity and mortality. New developments in the conceptualization of depression in the medically ill have focused on the potential role of immune activation/inflammation and the associated release of proinflammatory cytokines. Proinflammatory cytokines have been found to influence neurobiologic function and induce a depressive syndrome that has overlapping features with major depression. The long term objective of the proposed work is to further understand the pathophysiology and treatment of this cytokine-induced depression as it relates to depression in the medically ill. To accomplish this goal, we plan to develop an animal model of cytokineinduced depression using rhesus monkeys administered the cytokine, interferon (IFN) alpha. IFN alpha is a potent inducer of proinflammatory cytokines (especially interleukin 6) and leads to depressive symptoms in 30-50% of patients depending on dose. In addition, IFN alpha activates corticotropin releasing factor (CRF) pathways and has been shown to lead to monoamine depletion in laboratory animals (including rhesus monkeys). In addition, IFN alpha has been shown to alter fronto-striatal neurocircuitry in humans and induce REM sleep changes (decreased REM latency, increased REM percentage) consistent with depression in both humans and rhesus animals. Thus, IFN alpha treatment provides a unique model system to further understand the pathophysiology and treatment of cytokine-induced mood disorders. The specific aims of the proposed work are 1) to characterize neuroendocrine, monoamine, immune and behavioral responses of rhesus monkeys to IFN alpha and 2) to examine the therapeutic efficacy (capacity to reverse IFN alpha-induced neuroendocrine, monoamine, immune and behavioral changes) of pharmacologic compounds that antagonize activation of the cytokine network (NK-1 antagonists), antagonize CRF, or increase the activity of neurotransmission in monoamine neurocircuits. Relevant techniques to be used to accomplish these aims will include repeated blood and CSF sampling, telemetric polysomnography, microPET, and behavioral analysis of fear potentiated startle and social interactions. Results from these studies will identify novel targets as well as pharmacologic strategies for treatment of mood disorders in the medically ill. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DEPRESSION IN HUNTINGTON'S DISEASE Principal Investigator & Institution: Nehl, Carissa R.; Psychiatry; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002; Project Start 06-SEP-2002; Project End 31-JUL-2006 Summary: (provided by applicant): The proposed study will examine depression in presymptomatic Huntington's disease (HD). Presymptomatic individuals will be
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recruited through the NIH-funded PREDICT-HD study. This training proposal consists of two distinct stages. During the first stage, data collected during the PREDICT-HD study will be analyzed. The relationship between reported depression symptom severity, approximate nearness to disease onset, verbal memory, working memory, and visuospatial ability will be assessed. Additional information will be collected during the second stage of this proposal: a subgroup of individuals participating in PREDICT-HD will be assessed for mood disorders using the SCID and will complete a measure of relationship distress. This study will assess the relationship between mood disorders, nearness to disease onset, relationship distress, working, memory, and visuospatial ability. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DYSTHYMIC DISORDER IN YOUTH Principal Investigator & Institution: Waslick, Bruce D.; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-AUG-1998; Project End 31-JUL-2003 Summary: (Adapted from Applicant's Abstract): The purpose of this Mentored Clinical Scientist Development Award (MCSDA-K08) grant is to allow the applicant to develop a research program in the study of Dysthymic Disorder in children and adolescents and to develop the skills necessary to test the hypotheses that dysthymia in this age group is: 1) a neurobiologically mediated mood disorder that is amenable to psychopharmacologic intervention, and 2) a familial disorder in which risk factors for the development of the disorder are at least in part genetically transmitted. Building on the work of several investigators who have studied chronic depression in adults, and using several of these researchers in adult psychiatry as mentors and consultants to the Principal Investigator, this program will assess the validity of the classification of Dysthymic Disorder in youth as a mood disorder using clinical samples of subjects recruited into a treatment protocol. Research studies using methodologies that have contributed to the understanding of the disorder in adult subjects are proposed. The core study to be conducted during the period of this grant is a placebo-controlled, double-blind efficacy study of Fluoxetine in the short-term treatment of Dysthymic Disorder in children and adolescents. The project described will also develop a systematic approach to studying the familiarity of chronic depression in children and adolescents, culminating in controlled family studies of pediatric-age probands in comparison to controls. Preliminary studies investigating the role of Molecular Genetics studies in contributing to the understanding of the etiology of the disorder are also proposed. The Principal Investigator, having completed clinical training and preliminary research training, is pursuing a career devoted to clinical research and, proposes to train in the research techniques of Genetic Epidemiology and Molecular Genetics as a means of enhancing its capacity to conduct future research in the chronic mood disorders of childhood and adolescence. A program of systematic didactic education, supplemented by laboratory experience, mentored supervision and independent research projects, is proposed. This MCSDA will provide the Principal Investigator with further experience in the study of chronic mood disorders in children and adolescents and foster his growth toward conducting independent clinical research. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: EARLY INTERVENTIONS FOR ANXIOUS CHILDREN Principal Investigator & Institution: Bernstein, Gail A.; Associate Professor; Psychiatry; University of Minnesota Twin Cities 200 Oak Street Se Minneapolis, Mn 554552070
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Timing: Fiscal Year 2003; Project Start 01-DEC-2002; Project End 30-NOV-2005 Summary: (provided by applicant): This R21 application is in response to Program Announcement #PA-99-134 Exploratory/Development Grants for Mental Health Intervention Research. This project focuses on early identification of anxious children and pilot testing of school-based group interventions for anxious youth. Anxiety disorders are among the most prevalent psychiatric disorders in children. These disorders are strongly associated with risk for later developing mood disorders and other psychiatric disorders, academic failure, substance abuse problems, and other significant health problems. Up to 10-15% of the general youth population has an anxiety disorder. Anxiety disorders are associated with functional impairment and substantial morbidity. Longitudinal studies have demonstrated that untreated anxiety disorders in children may continue for years. For all these reasons, early identification and intervention are critical for preventing anxiety disorders and returning anxious children to the normal developmental trajectory. This R21 will employ a multiple gating procedure to identify children (ages 7-11) with features or diagnoses of separation anxiety disorder, generalized anxiety disorder, or social phobia. Schools will be randomly assigned to one of three conditions: (1) group cognitive-behavioral therapy (CBT) for children, (2) group CBT for children plus parent training, or (3) treatment as usual. Treatment as usual will consist of whatever the school would normally recommend for a child identified as anxious. Active treatments will utilize the FRIENDS Manual and will be provided at school. The FRIENDS manual will be expanded to provide a more intensive parent training component (i.e., parental anxiety management, understanding the child's anxiety in the family context, contracting and contingency management). All children will be followed prospectively with assessments at 3 months and 6 months post-treatment. Outcome measures will evaluate symptom severity, level of functioning, remission of baseline anxiety disorders, and incidence of new anxiety disorders. Data from this study will guide a large-scale school-based investigation of group interventions for anxious youth. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: INITIATIVE
EMORY-GSK-NIMH
COLLABORATIVE
MOOD
DISORDERS
Principal Investigator & Institution: Nemeroff, Charles B.; Reunette W. Harris Professor and Chair; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 11-AUG-2003; Project End 30-JUN-2008 Summary: This application, in response to RFA: MH-03-008 (National Cooperative Drug Discovery Groups for the Treatment of Mood Disorders or Nicotine Addiction, NC 336MD/NA), proposes the creation of"The Emory-GSK-NIMH Collaborative Mood Disorders Initiative." This unique opportunity to accererate antidepressant drug development brings together expertise of three complementary research groups: the Emory University School of Medicine Department of Psychiatry and Behavioral Sciences, the Mood and Anxiety Disorders Program at NIMH and the Center for Excellence in Drug Discovery (CEDD) in Psychiatry of GlaxoSmithKline (GSK), one of the largest multinational pharmaceutical companies. The two major goals of the current application are the development of innovative new models for basic and clinical research in mood disorders and the intensive scrutiny of 5 novel GSK antidepressant candidates in preclinical and clinical paradigms. In addition to an Administrative and Animal/Assay Core, 7 research projects are proposed. Of these, two are based in the intramural NIMH program; Neurogenesis, Synaptic Plasticity and Signal Transduction
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(Husseni Manji, M.D., PI) and Clinical Models to Assess Novel Antidepressants (Dennis S. Charney, M.D., PI). The remainder are based at Emory University led by established investigators including Jay M. Weiss, Ph.D. (Animal Models of Depression), Michael Davis, Ph.D. (Animal Models of Fear and Anxiety), Clinton D. Kilts, Ph.D. and Mark Goodman, Ph.D., (Functional Brain Imaging, with a focus on new PET ligand development), Michael J. Owens, Ph.D. and Charles B. Nemeroff, M.D., Ph.D. (Ex Vivo Assessment of Neurotransmitter Receptor and Transporter Occupancy of Antidepressants), and Andrew H. Miller, MD (Cytokine Induced Depression: A Rhesus Monkey Model). In conjunction with GSK, 5 novel GSK antidepressant candidates and others that become available via GSK Drug Discovery within the lifetime of the grant will be intensively scrutinized to synergize with the in-house GSK effort. This proposal encompasses virtually all of the major goals outlined in the RFA, namely, development of new neurochemical tools including novel PET ligands, exploration of new models of drug development and facilitation of a partnership between academia, NIMH and industry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: ESTROGEN AND CAM KINASE IV IN THE LIMBIC SYSTEM Principal Investigator & Institution: Cohen, Rochelle S.; Professor; Anatomy and Cell Biology; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 31-AUG-2007 Summary: (provided by applicant): Clinical studies have shown that estrogen (E2) can ameliorate symptoms of mood disorders in women, including severe depression. The presence of symptoms may represent an abnormal response to normal hormonal changes, thereby implicating contextual factors in the brain in the etiology of these symptoms. Some of these factors include second messenger systems that lead to the production of neurotrophic agents, including brain-derived neurotrophic factor (BDNF). Chronic stress results in deleterious effects on neurons and synapses which, in turn, may be related to alterations in affective behavior. Because of its involvement in cellular and synaptic growth and/or function, BDNF may counteract these negative effects and restore the appropriate behavioral responses. The gene transcription factor cyclic AMP response element-binding protein (CREB), has been shown to be a target of antidepressant and E2 action. Activation of CREB can lead to transcription of the BDNF gene. We propose that the Ca2+/calmodulin-dependent protein kinase IV (CaMK IV) pathway, "CaMK IV - CREB - phosphorylated CREB (pCREB) - BDNF," mediates some of the effects of long-term E2 treatment on behavior. Long-term E2 treatment results in the persistence of these messengers, even after two weeks. E2 may regulate CaMK IV and BDNF via alterations in their mRNAs; we will perform in situ hybridization to address the hypothesis that E2 regulates levels of CaMK IV mRNA and BDNF mRNA. We will also determine if E2 decreases relevant phosphatases, including protein phosphatase 2A and the calcineurin pathway, negative regulators of CaMK IV and pCREB, respectively. To determine if CaMK IV, CREB and/or BDNF mediate E2 effects in the forced swim test, a test for the efficacy of antidepressants in rodents, antisense oligodeoxynucleotides (ODNs) to CaMK IV, CREB or BDNF will be infused into the amygdala or hippocampus and animals will be subjected to the test conditions. Infusion of these antisense ODNs may interfere with the positive effects of E2 on forced swim. We will also determine if infusions of BDNF protein with the antisense ODNs to CaMK IV and CREB reverse the actions of the ODNs on behavior. These experiments will give insight to the molecular effects of E2 in areas of the brain related to affective processing
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Mood Disorders
and will uncover mechanisms that may allow hormonal intervention for the amelioration of female-related mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAMILIAL RISKS FOR MOOD DISORDERS IN ADULT OFFSPRING Principal Investigator & Institution: Giles, Donna E.; Professor; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 31-AUG-2003 Summary: (Verbatim from the Applicant's Abstract) The proposed project is a revised new R01 project, MH 60350. We propose to: 1) determine whether EEG sleep abnormalities and early onset independently predict lifetime affective morbidity in the offspring of families identified by depressed probands; 2) estimate the additive effects of early onset and abnormal EEG sleep in lifetime risk for depression; 3) establish cohort of offspring at risk for depression for prospective assessment of predictors of affective morbidity. We have compelling evidence that EEG sleep abnormalities cosegregate in families, are associated with increased lifetime risk for major depression, and double the risk of new-onset depression in at-risk relatives. Early onset of depression in the proband independently conferred increased familial risk for depression. These findings hold for two generations of relatives ascertained through unipolar depressed proband identified as part of MH39531 to the PI. By extending our well-characterized twogeneration pedigrees to include the third generation we will specify, in a definitive and cost-effective manner, independent sources of familial risk for depression and morbidity associated with early onset and with abnormal sleep physiology. Young adult offspring are an ideal resource to evaluate the cumulative or interactive influence of these distinct sources of risk. Lifetime psychiatric disorders and EEG sleep have been studied in parent and grandparent generations. Offspring targeted for this proposal have not been studies as part of MH39531. Unipolar depressed probands who defined our families had onset of depression before age 45 and 63 percent had their first episode by age 25 (early onset). Data on EEG sleep and clinical history in these offspring can be critically informative in describing physiological characteristics that cosegregate with the disorder and build on observations from two well-characterized generations to identify pathophysiologically important characteristics in adult offspring. Effects of age, sex, illness and medication will be controlled to generate information that is relevant across generations and across time. The proposed study creates a cohort that spans three generations, provides the framework for longitudinal, prospective predictions and identifies maximally informative families who can then be studied using molecular and/or genetic techniques. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAMILIAL TRANSMISSION DISORDERS, AGGRESSION/IMPULSIVITY
OF
SUICIDAL
ACTS,
MOOD
Principal Investigator & Institution: Mann, J John.; Chief; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2001 Summary: This two-site study, based at New York State Psychiatric Institute (NYPSI, the site of this CCNMD) and Western Psychiatric Institute and Clinic examine the familial transmission of early-onset suicidal behavior. The probands are adult depressed suicide attempters and depressed non- attempters well-characterized in previously interrelated studies in New York and Pittsburgh. In New York, 350 offspring of 90 attempters and 70
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non-attempters and in Pittsburgh, approximately 160 offspring of 35 attempters and 25 non-attempters will be studied. Because clinical and demographic characteristics of the probands in New York and Pittsburgh are similar, it is likely that the data can be pooled across sites. Probands, biological offspring over the age of 10, and the other biological parent will be characterized as to Axis I and II disorder, suicide attempt history, aggression, impulsivity, and family environment. Probands will be genotyped with polymorphic markers for tryptophan hydroxylase and other candidate genes, mostly related to central serotonergic metabolism. After the initial assessment, offspring will be followed up at one and two years after intake to observe the development of aggression., impulsivity, psychopathology, and suicidal behavior. We predict that the confluence of aggression and impulsivity, psychopathology, and suicidal behavior. We predict that the confluence of aggression and impulsivity, "impulsive aggression", the tendency to impulsively respond to provocation or frustration with anger or overt aggression, is central to the familial transmission of suicidal behavior. The project will test the following hypotheses: (1) offspring of attempters will have higher rates of suicide attempts than the offspring of non-attempters; (2) aggression, impulsivity, and the dimension of impulsive aggression will be greater in offspring of attempters, and will predict development of suicide attempts, especially in those who also develop mood disorders; (3) the familial transmission of suicide attempts will not be explained by the familial transmission of mood disorder alone; (4) there will be evidence of familial transmission of the suicide attempt even after controlling for the expected greater exposure to family adversity in the offspring of attempters; and (5) polymorphisms of the tryptophan hydroxylase gene and other genes related to central serotonergic function will be associated with impulsive aggression and suicide attempts among probands. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAMILY PSYCHOEDUCATION: EFFICACY IN CHILD MOOD DISORDERS Principal Investigator & Institution: Fristad, Mary A.; Professor; Psychiatry; Ohio State University 1960 Kenny Road Columbus, Oh 43210 Timing: Fiscal Year 2001; Project Start 01-MAY-2001; Project End 30-APR-2006 Summary: Mood disorders and suicide in youth represent major health concerns. Clinicians working with these youth need effective intervention strategies. However, there are no well established psychosocial interventions for prepubertal children with depression or manic-depression. Existing literature suggests that reducing expressed emotion (EE) via family psychoeducation improves outcome for adults with mood disorders, but similar studies in children are lacking. We developed an eight session, manual-driven, multi-family psychoeducation group therapy program (MFPG) designed to serve as an adjunct to the ongoing medication management and individual/family psychotherapy a child receives. Preliminary studies suggest MFPG is associated with multiple improvements for families, including: increased knowledge about mood disorders and improved coping skills in parents; improved family climate; increased perceptions of social support for parents and children; and increased effective treatment utilization. However, these studies have had significant methodologic limitations. In the proposed study, we hope to rigorously test the efficacy of MFPG with 165 mood disordered children aged 8 to 11. Participants will be recruited from multiple settings to obtain variability in socioeconomic status (SES), ethnicity, prior treatment history, and typical access to mental health services. Children and their primary and secondary parents/caregivers will complete pre-treatment assessment batteries at Time
22
Mood Disorders
1, then will be randomized into immediate MFPG plus treatment-as-usual (TAU) or a wait-list condition (WLC) plus TAU. All will be reassessed at Time 2 (approximately 3 months after study entry), Time 3 (7 months), and Time 4 (12 months). After the Time 4 assessment, WLC+TAU families will receive MFPG. A final assessment (Time 5, 15 months) will occur post-treatment. Hypotheses are: 1) MFPG+TAU families will function better than WLC+TAU families at Times 2, 3 and 4; 2) all families will improve functioning from immediately pre-treatment to immediately post-treatment; 3) several baseline variables (healthier child and parent functioning, higher caregiver concordance regarding treatment, and greater access to services) will be associated with better outcome for all participants; and 4) differences in gender and ethnicity will be unrelated to outcome. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FAMILY PSYCHOPATHOLOGY IN CHILD BIPOLARITY Principal Investigator & Institution: Geller, Barbara; Professor of Psychiatry; Psychiatry; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001; Project Start 01-FEB-1999; Project End 31-JAN-2003 Summary: Given mounting evidence for prepubertal-specific manifestations of DSM- IV mania, establishing continuities/discontinuities of bipolarity (BP) across the lifespan is crucial. Because family studies are paramount among validating methodologies, the paucity of family study data from prepubertal BP probands is striking. An especially compelling opportunity to fill this gap in family study knowledge exists in our research unit because of ongoing phenomenologic, naturalistic course, and molecular genetic investigations. These ongoing studies are conducted on a population of 270 nonadopted probands aged 7-16 years old at baseline entry into the phenomenology project. These 270 subjects comprise 90 with BP (with or without ADHD), 90 with ADHD (without BP or other major mood disorders), and 90 community controls (without BP, other major mood disorders or ADHD) who were ascertained to optimize future family genetic studies. Thus, the family study proposed in this application will use an already established pediatric aged proband population and will include probands' first degree relatives, who already participate in molecular genetic investigations. In the proposed work, first degree relatives (mothers, fathers and siblings aged seven or older) will be directly assessed by blind raters to establish DSM-IV diagnoses. Data on deceased or otherwise unavailable relatives will be obtained by family history from two informants, to increase caseness. Incorporation of the proposed family study with ongoing interrelated and interlocking phenomenology, naturalistic course, and molecular-genetic investigations will provide crucial data on differentiating prepubertal BP from ADHD and on establishing continuities/discontinuities between prepubertal versus adult onset mania. This application is a second revision to NIMH R01 MH57451. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FAMILY TREATMENT OF CHILDHOOD ONSET DEPRESSIVE DISORDERS Principal Investigator & Institution: Tompson, Martha C.; Professor; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2001; Project Start 15-AUG-1999; Project End 31-JUL-2003 Summary: While recent research has yielded advances in the psycho-social treatment of depression among adults, few studies have addressed adolescent depression and none have specifically targeted depressed pre-adolescents. Given that earlier onset may be
Studies
23
associated with longer time to recovery and greater family history of affective disorders, development of effective treatments for depression in pre-adolescents children is critical. The goal of this project is to adapt family-focused intervention strategies, which have proven efficacy with adult mood disorders, to target school-aged children with depression. The project would consist of two phases. In the first phase, 10 children (ages 8-13) with a diagnosis of major depressive and/or dysthymic disorder (assessed using the Schedule for Affective Disorders and Schizophrenia for School-Aged Children) and their parents would participate in a treatment development phage, in which they would receive 8-10 sessions of a family based treatments using a preliminary treatment manual. Goals of treatment development include evaluating the utility of specific treatment components, designing flexible strategies for age-developmental level, developing specific procedures for addressing diagnostic co-morbidity, and determining appropriate treatment length. In the second phase, 24 children with major depressive and/or dysthymic disorders and their parents would participate in a small clinical trial and be randomly assigned to either family-focused treatment or a wait-list control group (to receive family-focused treatment after a three-month interval). Goals in Phase 2 include evaluating the relative efficacy of the new treatment (as compared to the control condition), assessing its impact on psycho-social functioning, and identifying variables potentially mediating treatment effects At study entry, immediately post-treatment (3 months) and at 6- and 12- month follow-up points, participants in both phases would undergo intensive evaluation of clinical state. Psycho-social functioning, cognitive processes, family functioning and environmental context. It is hypothesized that children receiving the family-focused intervention will demonstrate greater improvement in symptoms and psycho-social functioning and be more likely to recover from their depressive episodes than children in the comparison condition. Exploratory analyses will examine changes on potential mediating variables, particularly measures of family functioning. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHILDREN
FLUVOXAMINE
THERAPY
OF
ANXIETY
DIOSRDERS
IN
Principal Investigator & Institution: Labellarte, Michael; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: Although anxiety disorders are relatively common in children & adolescents, there are no controlled studies that have demonstrated efficacy of any treatment, either pharmacologic or psychosocial, for children & adolescents with anxiety disorders. Fluvoxamine is an SSRI that is marketed in the US for the treatment of obsessive compulsive disorder (OCD) in adults. Fluvoxamine has been used extensively throughout the world to treat a variety of anxiety & mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FLUVOXAMINE TREATMENT OF ANXIETY DISORDERS IN CHILDREN AND ADOLESCENTS Principal Investigator & Institution: Riddle, Mark A.; Professor; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: Although anxiety disorders are relatively common in children & adolescents, there are no controlled studies that have demonstrated efficacy of any treatment, either
24
Mood Disorders
pharmacologic or psychosocial, for children & adolescents with anxiety disorders. Fluvoxamine is an SSRI that is marketed in the US for the treatment of obsessive compulsive disorder (OCD) in adults. Fluvoxamine has been used extensively throughout the world to treat a variety of anxiety & mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTION & STRUCTURE ADAPTATION IN FOREBRAIN DEVELOPMENT Principal Investigator & Institution: Levitt, Pat R.; Director; Biomedical Informatics; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The migration of cells from their birthplace in embryonic proliferative zones of the forebrain to their final resting position is a key event in brain development. Cell migration requires initiation of movement, guidance through a complex terrain, and cessation at the appropriate time and place to integrate into developing circuits. Cell migration defects in the forebrain may contribute to mental retardation, epilepsy and neuropsychiatric disorders. Converging anatomical and genetic evidence supports the origin of neocortical GABAergic interneurons in the basal forebrain. These neurons arise from the ventrally located ganglionic eminence (GE) and migrate trans-telencephalically into the neocortex and hippocampus. From a developmental perspective, it is particularly important to define the molecular cues that regulate interneuron migration out of the GE into the neocortex, as disruption of this process could lead to significant changes in either the number or distribution of GABAergic neurons throughout the forebrain. In the context of altered function, there has been a longstanding interest in understanding impaired GABAergic transmission as an underlying component of mood disorders, for example anxiety and depression. We initiated studies of a complex signaling system that includes hepatocyte growth factor/scatter factor (HGF), a pleiotrophic molecule which, by signaling through its receptor, MET, induces motogenic, mitogenic, chemoattractive and differentiation activities in both neural and non-neural tissues. Our initial studies showed that HGF is a key molecular constituent in guiding interneuron migration out of the GE to the neocortex. Because genetic deletion of either Hgf or MET results in midgestional lethality, we have analyzed mice with a mutation of the gene encoding the urokinasetype plasminogen activator receptor (u-PAR), a component of the HGF-MET signaling system that activates HGF. In these mice, which survive into adulthood, interneuron migration is disrupted severely, providing evidence for HGF mediation of this process. Adult u-PAR-/- mice exhibit a substantial depletion of cortical interneurons and disruption of circuit function, expressed in the form of an altered anxiety state and spontaneous, intermittent seizures. These findings raise a number of important issues, which we propose to address in three specific aims. Morphological, molecular and behavioral analyses of the u-PAR-/- mice will be performed to define the adaptations in GABA function and interneuron development that may account for abnormal anxiety levels and altered excitability. We will examine the role of u-PAR signaling in mediating HGF-dependent interneuron development, using molecular and biochemical approaches to investigate the dynamic interactions between the HGF/MET and uPA/u-PAR signaling systems. Finally, we will dissect genetically the HGF and MET signaling pathways in the forebrain by creating and analyzing new mouse lines in which regionally-selected deletions of each gene are accomplished by crossing existing lines carrying floxed alleles with forebrain promoter-driven Cre mice. The characterization of these mouse lines will provide novel models for investigations of
Studies
25
adaptations in cortical circuits induced by developmental defects in interneuron migration. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL IMPAIRMENT IN HIV-1 ASSOCIATED COGNITIVE MOTOR DISORDERS Principal Investigator & Institution: Albert, Stephen; Children's Memorial Hospital (Chicago) Chicago, Il 606143394 Timing: Fiscal Year 2001 Summary: This project will: (1) Determine the construct validity of alternative indicators of functional status in individuals with, or at risk for, HIV-1 associated neurocognitive disorders. We have intentionally included functional status indicators that vary by source(patient, clinician), scope(overall rating, specific domain ratings), modality(time use, reported difficulty, need for help, observed performance on standardized tasks, and time reference(prior month, 24 hour- period). No clear consensus currently exists on the value of these alternative assessment techniques in HIV research, or whether they can be rationally combined. (2) Examined the criterion validity of the different measures, that is, the relationship between the function indicators and indicators of disease severity(viral load and neuropsychological status). The validity of self- report measures, for example, may vary with self-reports less accurate (relative to severity indicators among subjects with cognitive impairment or mood disorders. (3) Examine the relationship between particular domains of neuropsychological performance and specific domains of function. For example, among the mildly impaired, deficits in planning may be associated with impairment in higher-order functions (i.e., medication management). At this point, it is still unclear which domains of neuropsychological performance best predict onset of different kinds of functional deficit. In such analyses, it is important to examine non-cognitive sources of functional deficit as well, including fatigue, medical status, direct effects of viral load (association between viral load and functional status controlling for neuropsychological status), and mood disorders. To accomplish these goals, this proposal will assess predictors of functional status in the entire cohort (n=460), including a performance function test. It will also examine the 170 subjects at the Columbia University site in more detail, with enriches assessments of function(time budgets, unmet needs), neuropsychological status (executive function tests), and psychiatric status(SCID, apathy, fatigue). This work extends prior research conducted as part of the Dana Consortium on Therapy for HIV Dementia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GABA B COMPOUNDS FOR DEPRESSION AND SMOKING CESSATION Principal Investigator & Institution: Markou, Athina; Associate Professor; Scripps Research Institute Tpc7 La Jolla, Ca 92037 Timing: Fiscal Year 2003; Project Start 24-SEP-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This application is in response to RFA MH-03-008 to form a National Cooperative Drug Discovery Group for the Treatment of Mood Disorders or Nicotine Addiction (NCDDG-MD/NA) to work or innovative drug discovery for these two disorders, and the development and validation of a putative new animal model of antidepressant activity. This project will involve an academic partner, The Scripps Research Institute, La Jolla, California, and an industrial partner, Novartis Pharma AG, Basel Switzerland. The pharmacological approach proposed is the
26
Mood Disorders
development of gamma-aminobutyric acid B (GABAB) receptor positive modulators as antidepressants and/or aids to smoking cessation. Specific Aim 1 will involve the synthesis and refinement of GABAB receptor positive modulators with good selectivity for the GABAB receptor. Specific Aim 2 will involve experiments characterizing these (GABAB positive modulators biochemically in human, rat and mouse GABAB receptor assays. Pharmacokinetics, brain penetration, and binding affinities for other receptors and channels will also be evaluated. Specific Aim 3 will assess the effects of these compounds in nicotine self-administration using both fixed-ratio and progressive ratio schedules of reinforcement in nicotine-dependent rats. Specific Aim 4 will assess the effects of the compounds in vivo and in animal models of depression. Initial studies will evaluate the potential side-effect profile of these compounds. Subsequent work will evaluate the effects of the compounds in 6 models of antidepressant activity: the forced swim test ill mice and rats, the tail suspension test in mice, the olfactory bulbectomy test in rats, and nicotine and amphetamine withdrawal in rats. The latter test will also provide information about potential therapeutic effects of the compounds on drug withdrawal hypothesized to contribute to relapse. Finally, Specific Aim 5 will attempt to develop and validate a new animal model of depression (7th model) involving olfactory bulbectomy as the inducing condition and brain reward thresholds as the dependent variable, and test putative antidepressant drugs. This integrated multidisciplinary research program focusing on both depression and smoking cessation and capitalizing on the expertise of both Scripps and Novartis scientists will be an innovative approach to the development of new therapeutics for these disorders. | Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC INVESTIGATION OF MOOD DISORDERS Principal Investigator & Institution: Mcinnes, L A.; Psychiatry; Mount Sinai School of Medicine of Nyu of New York University New York, Ny 10029 Timing: Fiscal Year 2001; Project Start 01-AUG-1999; Project End 31-JUL-2004 Summary: Major depression (MDD) is a common and potentially devastating illness which likely has many etiologies, environmental as well as genetic. Unfortunately, biochemical and physiological experiments have so far failed to provide unequivocal, objective diagnostic markers for the illness, or to delineate specific pathological processes that are rectified by pharmacological treatments. Genetic approaches may only partially elucidate the neurobiology of depression, but the discovery of even one rare MDD predisposing gene will help guide efforts to understand mood disorders in general. Obstacles to identifying genes for psychiatric disorders include the lack of objective criteria for defining the disease phenotype and extensive etiologic heterogeneity. However, recent technological advances in molecular genetics have facilitated processing of the large samples required to find genes of small effect. As well, it is now generally recognized that genetic heterogeneity can be reduced by defining only the most severe form of a particular phenotype as affected and, possibly, by studying genetically isolated populations. Thus, the candidate intends to identify genes predisposing to mood disorder by applying population genetic mapping methods to study subjects with early onset recurrent MDD collected from an isolated population in the Central Valley of Costa Rica. The candidate is a postdoctoral fellow in psychiatry and has spent the last three years investigating the genetics of bipolar disorder in the laboratory of Nelson Freimer MD at UCSF. Short term career goals are to remain in this laboratory as an adjunct assistant professor, to further develop her knowledge of statistical approaches to the genetics of complex traits and to characterize the phenotypes associated with the genes she discovers for mood disorders. The latter
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27
endeavor will aid and be aided by 20 percent time clinical work related to affective disorders. The candidate's long-term goal is to establish an independent academic career continuing her genetic investigation of psychiatric disorders. It is hoped this work will ultimately lead to better patient care, the revision of psychiatric nosology in terms of etiology rather than symptoms, and the elimination of some of the stigma that surrounds mental illness that persists, in part, because of our inability to characterize the biology of complex behaviors. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GENETIC LINKAGE OF SCHIZOPHRENIA AND RELATED STUDIES Principal Investigator & Institution: Levinson, Douglas F.; Associate Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 30-JUL-2001; Project End 30-JUN-2006 Summary: This is a revision of a competing renewal application for a Midcareer Investigator Award which was funded as an Independent Scientist Award (K02) in 1995, with this renewal requested under the K24 mechanism for patient related research. The research theme has been collaborative studies in the genetics of schizophrenia and (more recently) major mood disorders. The applicant is a psychiatrist who has pursued a career of research in the recruitment and clinical assessment of families for these studies, the application of advances in statistical genetics to the design of clinical studies, and the organization and coordination of large collaborations to collect new samples and to carry out multicenter linkage studies of existing samples. The applicant has moved to an institution with an outstanding research and research training environment. Career award support is needed to provide sufficient protected time to focus on the proposed program of patient- oriented research and active involvement in mentoring of beginning research trainees. The current award period has included completion of a genome scan of schizophrenia; organization of a series of linkage studies of schizophrenia candidate regions in very large multicenter samples; creation and initial testing of a new dimensional rating scale for psychotic disorders; pilot data collection of mood disorders in an inbred population; work on computer simulation studies; initiation of two large pedigree collections, one of major depression (as coordinator of a six-site collaboration) and one of schizophrenia (as PI of one of nine sites); and mentoring activities. The protected time made possible by the proposed award will permit development of a new research focus on dimensional approaches to measuring psychopathology in psychotic disorders, organization of new large collaborations based on advances in the field, career development activities to enhance knowledge of molecular and statistical genetics, and participation as a teacher and mentor in a funded Clinical Scholars Research Program for psychiatry residents in a four-year research training track. Other activities will include the funded multicenter pedigree collections and genome scans of major depression and schizophrenia; completing a previous schizophrenia genome scan project; collaborative efforts to identify specific susceptibility genes; coordinating a funded project to continue multicenter linkage and association studies of schizophrenia; and completion of the isolated population mood disorders data collection and development of related population simulation software and genetic analysis strategies. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: GENOMIC CHARACTERIZATION IN DEPRESSION AND SUICIDE. Principal Investigator & Institution: Sibille, Etienne L.; Psychiatry; Columbia University Health Sciences New York, Ny 10032
28
Mood Disorders
Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): Major depression is emerging as a disease of the central nervous system with a characteristic pathophysiology. For inpatients with major depression, the lifetime mortality due to suicide reaches 15%. Despite a global burden of neuropsychiatric disorders on individual mental health and society's productivity, little is known on mechanisms or molecules that are responsible for these diseases. Accordingly, the identification of the neurobiological underpinnings for mood disorders represents an important challenge in neuropsychiatric research. Complex polygenic mechanisms are likely, with environmental factors contributing to the development of depression and suicidal behavior. However, research efforts have been largely limited to components of brain biology that are affected by antidepressants and mood stabilizers. Microarray technology and genomic characterization represent new investigational developments that allow for unbiased identification of new molecular components and mechanisms of mood disorders. During the award period, the applicant aims to train in the application of microarrays to postmortem human brain studies, to initiate a genomic and molecular characterization of prefrontal cortex dysfunction in depressed patients who died by suicide, and to seek new mechanisms, genes and molecules that contribute to the development of the disease. Preliminary results indicate a rich potential for genomic approaches to psychiatric disorders and hints at a possible molecular classification of depression into unrecognized subtypes. The specific aims of the study are /) to characterize gene expression profiles in the prefrontal cortex of human subjects, ii) to assess the effect of major depression and suicide on gene expression, iii) to investigate genes and molecular pathways that were affected by the disease, and iv) to develop new understanding of biological mechanisms involved in depression and suicide, with possibilities for designing new genetic mouse models, and uncovering new molecular targets for treatment and prevention of mood disorders. The proposed training plan will enable the applicant to benefit from recent advances in genome sequencing and genomic technologies, and to develop expertise to bridge these approaches to the study of neuropsychiatric disorders. In particular, the applicant will receive valuable training in genomics, statistics and bioinformatics, and in clinical and basic science aspects of brain function. The training program proposes formal courses, supervised training and frequent interactions with several research groups involved in pioneering aspects of genomic research in mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: GLUCOCORTOID RESISTANCE IN MOOD DISORDERS Principal Investigator & Institution: Wang, Xiaohong; Psychiatry and Behavioral Scis; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by candidate): The long-term objective of this Scientist Development Award for New Minority Faculty is to prepare the candidate for a career as an independent investigator conducting preclinical and clinical research in the area of signal transduction as it relates to neuroendocrine-immune interactions in mood disorders. The training plan consists of an extensive curriculum of formal graduate level courses in psychoneuroimmunology, endocrinology, biostatistics, research methodology and ethical conduct in research. The candidate's research plan will focus on interactions between the neuroendocrine and immune systems, specifically, glucocorticoid and proinflammatory cytokine signal transduction pathways as they relate to the development of glucocorticoid resistance and the pathophysiology of mood disorders. Specific aims include 1) To determine the signal transduction pathways responsible for
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29
IL-1-induced impairment in glucocorticoid receptor (GR) function, 2) To examine the role of protein kinase A (PKA) in modulating IL-1-induced GR impairment, and 3) To determine whether chronic cytokine exposure in humans is associated with the development of impaired GR function. To accomplish these aims, the candidate will use cultured cell lines and primary human cells to investigate the role of mitogen-activated protein kinase (MAPK) pathways and protein-protein interactions (i.e., NF-B or AP-1 and GR mutual suppression) in IL-1-induced impairment of GR function. Given the capacity of PKA to enhance GR function and inhibit MAPK pathways, the candidate will also investigate the role of cAMP/PKA in restoring and enhancing GR function in the presence of IL-1. Finally, to support the hypothesis that chronic cytokine exposure leads to glucocorticoid resistance, blood samples will be obtained from 100 patients receiving interferon treatment for hepatitis C and in vitro glucocorticoid sensitivity of peripheral blood mononuclear cells (PBMC) will be determined. Results from this in vitro assay will be correlated with circulating and CSF concentrations of proinflammatory cytokines as well as the development of depression. In combining his expertise in steroid receptor signal transduction, his laboratory skills in basic cellular and molecular biology and solid clinical training, the candidate will be in a position to develop this award into an application for an independent research award over the 5year award period. Moreover, insights gained from the proposed research will contribute to the development of novel therapeutic targets for the treatment of mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IMAGING OF SEROTONIN TRANSPORTERS IN DEPRESSION Principal Investigator & Institution: Parsey, Ramin V.; Assistant Professor; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 29-MAY-2001; Project End 30-APR-2006 Summary: (Provided by Applicant): Structural and functional imaging studies have suggested a neurocircuitry of mood disorders that involves a limbicthalamic-cortical circuit (amygdala, thalamus, prefrontal cortex) and a limbic-striatal-pallidal-thalamiccortical circuit. Abnormalities in a component of these circuits may affect the regulation of mood. Serotonin has been implicated in the pathophysiology of depression. Reports of fewer platelet serotonin transporters in major depression have rarely been extended to postmortem brain studies and neuroreceptor imaging studies in vivo. Serotonin transporter binding in the brainstem of depressed patients measured by SPECT is reportedly lower. ["C]McN5652 is a PET radioligand with high affinity for the serotonin transporter. Our group has developed kinetic modeling methods with this ligand that allow quantification of the serotonin transporter in subcortical and to a lesser extent in some cortical structures. We propose an in vivo study of the neurocircuitry of the serotonergic system in major depression. We predict that transporter binding will be decreased in depressed subjects in the midbrain, thalamus, putamen, hippocampus, and amygdala. Symptoms of depression have been correlated to serotonergic measures, including suicidal ideation, psychomotor retardation, and anxiety. We will correlate these measures of psychopathology with ["C]McN5652 binding. Correlations will help refine the neurocircuitry model of depression. Several lines of evidence suggest that serotonin dysfunction in depression may be a trait marker. Consequently, we will study both currently depressed (n=40) and remitted depressed subjects (N=20) while off medication, and compare both groups to healthy volunteers (N=20). We predict remitted depressed will not differ from currently depressed subjects. These results will greatly enhance our knowledge of the pathophysiology of major depression and help in
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Mood Disorders
our diagnosis, treatment, and design of future studies. This application for a Mentored Clinical Scientist Development Award has been submitted with the goal of supporting the development of the applicant's career as a psychiatric researcher. This research plan is intended to build on the candidate's prior work with neuroreceptor imaging in mood disorders. This application delineates plans for training and mentoring in the areas of the neurobiology of depression, cell and molecular physiology, pharmacology, neuroanatomy, statistical analysis, clinical diagnosis and ratings, teaching, brain imaging, and mathematical modeling necessary to enable the applicant to pursue an independent career of scientific inquiry in psychiatry. These goals will be met by a combination of didactic I course work and supervision. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISORDERS
INTEGRATED
TREATMENT
FOR
COCAINE
AND
MOOD
Principal Investigator & Institution: Schmitz, Joy M.; Professor; Psychiatry and Behavioral Scis; University of Texas Hlth Sci Ctr Houston Box 20036 Houston, Tx 77225 Timing: Fiscal Year 2001; Project Start 01-JUN-1994; Project End 30-JUN-2004 Summary: (Applicant's Abstract) Major depression co-occurs commonly in the population of cocaine dependent patients. Despite high prevalence and negative consequences on illness course and prognosis, little is known about effective treatments for dual diagnosis. Traditional models treat each disorder separately, an approach that has proven ineffective. The proposed study provides a direct and logical extension of our previous research evaluating treatments that focus simultaneously on cocaine and mood disorders using integrated cognitive behavioral therapy (CBT) and antidepressant therapy. The study will employ a double-blind, placebo-controlled design in which depressed, cocaine-dependent patients will be randomized into one of four treatment conditions according to a full W factorial research design. Two levels of psychotherapy will compare integrated CBT and Clinical Management (CM) for depression and substance use. Two levels of pharmacotherapy will compare bupropion 400 mg/d and placebo. Dually-diagnosed subjects (N=140) will be treated for 12 weeks, then followed for 12 months. The design provides sufficient power to test both the independent and interactive effects of psychotherapy and pharmacotherapy. The integrated CBT is based on concepts and techniques shared by both Marlatt's Relapse Prevention model of substance abuse and Rehm's Self Control model of depression therapy. Data collected during the original funding period support the feasibility and potential utility of the integrated CBT approach and warrant progression to a larger-scale Stage II efficacy study. The CM approach adapted for this study will provide nonspecific elements of psychotherapy (e.g., support, education, empathy, and advice) and thus serve as an adequate psychotherapy-control condition. Our rationale for testing bupropion is based on its specific dopaminergic activity, efficacy as an antidepressant, low side-effect profile, and preliminary evidence of positive response in depressed cocaine-abusing patients. The study is technically rigorous, theoretically innovative, and scientifically significant. Careful screening and structured clinical interviewing will be used to collect information for making reliable and valid diagnostic judgments of cocaine dependence and current comorbid mood disorder based on DSM-IV criteria. Written therapy manuals, trained therapists, competency checks, and adherence rating scales will be used to verify treatment fidelity. Procedures to safeguard against adverse events will include initial medical evaluation, monitoring of medication plasma levels, daily recording of pill taking using an electronic medication dispensing unit, twice-weekly clinic visits, and regular contact with study psychiatrists. The assessment battery
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captures the domains of diagnoses, substance use patterns, mood symptomatology, addiction severity, and psychosocial functioning. Primary outcome measures will be cocaine use (via observed urine samples) and depression ratings (BDI, HDRS). Repeated assessments at 3-, 6-, 9-, and 12-months following treatment will be used to evaluate relapse rates, patterns, and predictors. This research will contribute important new theoretical and empirical information concerning efficacious treatment for cocaine dependent patients with comorbid mood disorders. Further, these studies will enhance our knowledge about the relation between dual disorders, the relative effects of treatment on mood and substance use outcomes, and the optimal combination of pharmacologic and psychotherapeutic treatments for this important subpopulation of patients. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: IRC FOR THE STUDY OF LATE-LIFE MOOD DISORDERS Principal Investigator & Institution: Reynolds, Charles F.; Professor; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260 Timing: Fiscal Year 2001; Project Start 01-MAR-1995; Project End 28-FEB-2005 Summary: This application requests support for an Intervention Research Center in Late-Life Mood Disorders (IRC/LLMD) (PAR-98-020) and is the competing continuation of P30 MH52247 (MHCRC for Late-Life Mood Disorders), funded since March 1, 1995. The IRC/LLMD consists of six cores: 1) Administrative, Data Management, and Information Dissemination; 2) Methodology; 3) Recruitment, Assessment and Follow- up; 4) Health and Behavior; 5) Geriatric Psychopharmacology; and 6) Functional Brain Imaging. The goal of the IRC/LLMD is to understand and reduce treatment response variability in geriatric depression and related disorders. This theme encompasses several broad issues: 1) what is treatment response in late-life depression? 2) how can treatment response by accelerated? 3) How can treatment response be maintained? 4) Why does age matter as a source of short- and long-term treatment-response variability? 5) How can the identification and management of treatment-resistant depression in later life be improved? And 6) What are the costs and benefits of combined treatment (either polypharmacy or medication plus psychotherapy) versus monotherapy? The IRC/LLMD will provide infrastructure support to a portfolio of research projects, career development, and training grant awards aimed at: 1) improving treatment of elderly patients in the general medical sector and ameliorating risk factors for suicide risk factors for resistance and developing strategies for improving response in such patients; 4) finding maintenance treatments with long term efficacy, especially for patients over age 70; 5) developing preventive interventions to reduce the liability to late-onset depression; 6) developing strategies for minimizing residual disability and facilitating full recovery; and 7) developing costbenefit information for combined treatments versus monotherapy. The growing significance of global illness burden attributable to depression and suicide over the next 20 years, as reported by the World Health Organization (1996), undergoes the central rationale for the IRC/LLMD: to develop clinical preventive strategies to reduce the incidence of geriatric expression; to develop treatment strategies to accelerate treatment response; to improve early recognition and management of treatment resistance; to maintain treatment response; to minimize residual disability; to improve quality of life in elderly persons afflicted with depressions. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: LATE-LIFE DEPRESSION Principal Investigator & Institution: Kumar, Anand; Professor in Residence; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 05-DEC-2000; Project End 30-NOV-2005 Summary: (Applicant's abstract) The primary objective of this Research Scientist Development award is to permit Anand Kumar (the candidate) to develop greater sophistication with magnetic resonance imaging (MRI) technique and to apply them to study the neurobiology of late-life and minor depression. More specifically, the candidate, who has conducted research into the neuroanatomical basis of late-life mood disorders for several years, proposes to strengthen his skills in regional MR morphometry and to acquire expertise in proton magnetic resonance spectroscopy (MRS) in order to more thoroughly investigate the anatomical and biochemical basis of mood disorders in late-life. He has developed a comprehensive career enhancement plan to accomplish both his career goals and scientific objective. This program consists of hands on experience with specific research projects enriched by the following mechanisms: 1) close interactions with consultants familiar with the application of modern neuroimaging techniques to psychiatric research; 2) attending relevant seminars, journal clubs and workshops, both within and outside the hoist institution and 3) visiting other centers of excellence in order to interact and learn from experts in his chosen area of interest. The proposed research studies and career development plan will serve as vehicles to help the candidate realize his full potential as a clinical investigator and contribute to our further understanding of the pathophysiology of mood disorders in late-life. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MAGNETIC STIMULATION FOR PARKINSON DISEASE Principal Investigator & Institution: Epstein, Charles M.; Professor; Neurology; Emory University 1784 North Decatur Road Atlanta, Ga 30322 Timing: Fiscal Year 2001; Project Start 01-SEP-2000; Project End 30-JUN-2005 Summary: The major aim of this study is to carry out a sequential Phase I trial of prefrontal transcranial disease (PD) and severe depression. Depression complicates PD in up to 50 percent of cases, leading to further deterioration of motor performance and quality of life; but antidepressant medication fails or produces intolerable side effects in 25-30 percent of patients. Case reports and uncontrolled trials suggest that ect is effective in ameliorating simultaneously the mood and motor symptoms of PD. Only a few small studies of ECT in PD have been prospective or randomized, the assessment protocols have been limited, and the results have been variable. TMS is a new, promising, alternative treatment for refractory depression, which appears to be easier and safer that ETC. Requiring no hospitalization, anesthesia, or recovery time, TMS is now being investigated as an alternative therapy for mood disorders. TMS has not been studied in depressed patients with PD or in other serious central nervous system diseases. This study extends our past and present research in PD, depression, ECT, and TMS. We will comprehensively evaluate the effects of left prefrontal TMS on mood, motor, and neuropsychological function together with quality of life indices in depressed PD patients. All patients will initially receive treatment with TMS. Those who fail to benefit will proceed to ETC. Comprehensive evaluation will be continued for another eight weeks in both the TMS-only and ECT groups. The key issues addressed by these studies include (1) the potential benefit of TMS on mood and movement in
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depressed PD patient, and (2) the tightness of the association between mood and motor function after TMS and ETC. Overall, these studies will provide important preliminary data on the relationships among mood, cognitive and motor function in PD, and their influence on quality of life. The results will help in directing future applications of TMS as an alternative therapy for brain disorders, and will further elucidate the relative benefits of both TMS and ECT in depressed PD patients. A positive effects from TMS should be an impetus towards randomized, placebo-controlled trials. 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 & stressrelated 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
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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 2001; Project Start 20-AUG-2000; Project End 31-JUL-2003 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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Project Title: MATERNAL NEUROBEHAVIOR
ANTIDEPRESSANT
USE
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FETAL
Principal Investigator & Institution: Salisbury, Amy L.; Women and Infants HospitalRhode Island 101 Dudley St Providence, Ri 02905 Timing: Fiscal Year 2002; Project Start 01-JUN-2002; Project End 31-MAY-2007 Summary: (provided by applicant): The overall goal of the proposed research career development program is to prepare the investigator, Dr. Amy Salisbury, for a career as an independent investigator in the areas of fetal behavioral development and maternal mental health. The investigator's focus in these areas represents a strong aspiration to understand the mechanisms and mediators in the development of childhood mental illness. As a first step in achieving the long-term goals, Dr. Salisbury will study fetal and newborn neurobehavior in women with Major Depressive Disorder (MDD), diagnosed by structured interview, with and without antidepressant (S SRI) exposure. This study will be executed with intensive training in methodologies with at-risk fetuses and newborns (Dr. Barry Lester), fetal monitoring techniques (Dr. Janet DiPietro), structured interview techniques (SCID, SADS) and ongoing didactic training and clinical supervision with top experts in the field of mood disorders and medication management in women (Dr. Katherine Wisner and Dr. Teri Pearistein), and maternal-
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fetal medicine (Dr. Stephen Carr). Dr. Lester will serve as the primary mentor of this program and resource provider throughout the award period. Additional skills will be attained through coursework on research design and regression analyses at Brown University as well as advanced obstetric ultrasound training. The proposed program of career development will build on Dr. Salisbury's established research and clinical skills in fetal and newborn behavior. The investigator has the full support of the Brown Medical School, Women & Infants' Hospital, and her sponsors to achieve the goals outlined in this career development program. The broad, long-term objective of the research plan is to determine if there are differential effects of SSRI exposure and MDD on fetal and newborn neurobehavioral development. The data will provide information about how the fetal CNS responds to the two maternal biological environments as well as contribute to the urgently needed information for treatment guidelines of mood disorders during pregnancy. The specific aims of the proposed research plan are 1. To determine the effect of maternal S SRI-treated MDD (euthymic) versus nonSSRI exposed active MDD on fetal neurobehavior and controls, 2. To determine the effect of maternal S SRI-treated MDD versus non-SSRI exposed active MDD on newborn neurobehavior and controls. A secondary aim of this study is to examine the stability of the individual differences of neurobehavioral measures from the fetal to newborn period. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MEDICATION ADHERENCE IN LATINOS Principal Investigator & Institution: Diaz, Esperanza; Associate Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 15-DEC-1999; Project End 30-NOV-2004 Summary: This is a request for a Mentored Patient-Oriented Research Development Award (K23). The overall aim of the proposal is to provide the candidate, Esperanza Diaz MD., with a supervised patient oriented research and educational experience that will enable her to become an independent investigator in mental health services research with focus on the Latino population and cultural issues. Dr. Diaz is an experienced, bilingual, bicultural clinician. A K23 will free her time from clinical duties to obtain the skills and experience of an independent researcher. Dr. Diaz has chosen a distinguished set of mentors Robert Rosenheck MD., Joyce Cramer BS., and Scott W. Woods MD., from Yale University and Janis H. Jenkins Ph.D., from Case Western Reserve University. They are active mental health services and cultural researchers with excellent records of successful mentorships. The first aim of the study is to determine the medication adherence rates and differences in attitudes to medications in patients treated for Schizophrenia and other Psychotic Disorders, Mood disorders, Anxiety Disorders, and Somatoform Disorders in three groups. 1) Latinos treated at a culturally competent Latino Clinic, 2) Latinos treated by non Latinos in a standard Community Mental Health Center and 3) non Latino groups treated at the same Community Mental Health Center. Analysis of the data will be used to identify the role of cultural factors and other attitudes in medication compliance in Latinos to formulate a culturally sensitive intervention for enhancing medication adherence in Latinos. The second aim of the project will compare a previously tested intervention to enhance adherence to medicines, the Medication Usage Skills for Effectiveness, (MUSE) among Latino patients receiving the MUSE intervention alone, Latino patients receiving the MUSE plus a culturally sensitive enhancement and Latino patients receiving a non specific counseling intervention. The control group will provide data on medication adherence and outcome. Dr. Diaz's training experience includes a three year period of intense coursework at the school of Epidemiology and Public Health and at Case Western
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Reserve University. The plan includes developing skills in Statistics, Biostatistics, Epidemiology, Health Policy, Mental Health Services Research, Analysis of Data, etc., leading to a Masters in Public Health. Dr. Diaz will also develop skills in descriptive and qualitative research, Data collection, Data analysis. Dr. Diaz will have an R01 proposal ready by the end of funding. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTAL DISORDERS AS RISK FACTORS FOR SUBSTANCE DISORDERS Principal Investigator & Institution: Kessler, Ronald C.; Professor; Health Care Policy; Harvard University (Medical School) Medical School Campus Boston, Ma 02115 Timing: Fiscal Year 2001; Project Start 15-JUL-1999; Project End 30-JUN-2004 Summary: (Applicant's Abstract) This proposal seeks support for a ten-year follow-up of the 5877 people who participated in Parts I and II of the National Comorbidity Survey (NCS; Kessler et al., 1994), a nationally representative survey of people in the age range 15-54 in the U.S. household population designed to estimate the prevalences and correlates of DSM-III-R mental and substance disorders. The focus of the follow-up survey will be on the relationship between temporally primary mental disorders and the subsequent onset and course of substance disorders. Specifically, we aim to use information about mental disorders collected in the baseline survey to predict the subsequent onset of substance use and the onset and course of substance disorders over the intervening decade. We also aim to use causal modeling to evaluate the effects of mediators and modifiers of these associations. There are two specific aims. The first is to evaluate the two overarching hypotheses that guide the proposed research: that temporally primary mental disorders assessed at baseline predict the subsequent first onset and progression of substance use and substance disorders over the intervening decade; and that co-occurring mental disorders among baseline respondents with substance disorders are significant predictors of continuation over the intervening decade. The second specific aim is to carry out more refined analyses to elucidate the mechanisms involved in the associations documented under the first aim. A large number of potentially important mediators and modifiers will be considered here, with a particular interest in modifiable risk factors that could be intervention targets associated with mental disorders. All of the work under this second aim will separately consider the subsample of respondents with primary conduct disorder and the subsample of respondents without conduct disorder who have primary anxiety-mood disorders. The processes involved in the onset and course of secondary substance disorders are anticipated to be considerably different in these two subsamples, with substance disorders strongly related to a broader pattern of unconventionality and risk taking in the subsample with primary conduct disorder and to self- medication in the subsample with primary anxiety-mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MENTAL HEALTH COMPUTERIZED ADAPTIVE TESTING Principal Investigator & Institution: Gibbons, Robert D.; Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 20-SEP-2002; Project End 31-JUL-2005 Summary: (provided by applicant): Mental health research relies heavily on antiquated systems of measurement. The construction of traditional mental health scales is based largely on subjective judgment, and at best, application of methods from classical test
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theory to determine a scale's psychometric properties. In this application we borrow strength from major advances in test construction and administration that have been developed in the fields of educational measurement and modem psychometric theory. In particular, we propose to use Item Response Theory (IRT) to calibrate a large item pool of 626 mood disorder items and then adaptively administer them such that a given subject can be evaluated on a small subset of the items to any practical degree of accuracy. The use of the IRT model allows us to evaluate the intensity of the mood disorder for different subjects who have taken potentially different numbers of items selected from the item pool. Using computerized adaptive testing (CAT) we can then adaptively select the most appropriate set of items for each subject based on his/her responses to previous items, beginning from a small screening set of items that characterize low to high levels of impairment. The net result is that large "item banks" can be developed that thoroughly characterize a particular disorder. Although it is not routinely possible for any one subject to be evaluated on all of the items, CAT permits each subject to be evaluated on a small subset of the total item pool, with minimal and controllable loss of information. A complication of applying IRT to mental health measurement problems is that unlike traditional ability testing (e.g., mathematics achievement) which are inherently unidimensional, mental health measurement scales are inherently multidimensional. Although multidimensional IRT models are available they have not been well studied in the Context of adaptive testing. Note that one of the primary reasons for the multidimensionality of mental health measurement scales is that the items are often sampled from multiple domains (e.g., various mood disorders), thereby violating the assumption of a unidimensional IRT model. To this end, Gibbons and Hedeker (1992) developed an "item bi-factor" model which allows each item to load on a primary dimension (e.g., depression) and one subdomain (e.g., sleep disturbance). In the context of mental health measurement, the advantage of the hi-factor model is that it yields a measure of overall impairment that can be the focus of adaptive testing. In this application, we propose to provide an in depth feasibility study of the use of CAT and IRT in the calibration and administration of mental health measurement instruments. Specifically, we propose to develop the statistical theory and software that is necessary, and to then apply it to the Mood-Anxiety Spectrum Disorders Scale. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MENTAL ILLNESS CURRICULUM FOR ADOLESCENTS Principal Investigator & Institution: Baker, Cynthia D.; Danya International, Inc. 8737 Colesville Rd, Ste 1200 Silver Spring, Md 20910 Timing: Fiscal Year 2003; Project Start 01-JUN-2003; Project End 29-FEB-2004 Summary: (provided by applicant): Danya International proposes to develop the Mental Illness Curriculum for Adolescents, a multimedia, modular curriculum package designed to educate adolescents, ages 13 to 15 in grades seven through nine, about mental illness. The curriculum consists of an interactive CD-ROM, teacher's resource guide, counselor's guide, parent newsletters, and posters. The curriculum will consist of four modules that cover the topics of Mood Disorders, Anxiety Disorders, Eating Disorders, and Attention Deficit Hyperactivity Disorder. During Phase I, Danya will develop the content of each module of the curriculum and program the Mood Disorders module of the CD-ROM curriculum. During the final two months of the Phase 1 period, a randomized experimental/control group feasibility study will be conducted to evaluate the effectiveness of the Mood Disorders module to influence knowledge and attitudes about mental illness in a group of students in the target age group. The Phase
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II project period will be devoted to refining and programming the CD-ROM and conducting a full-scale evaluation of the entire curriculum package. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MHCRC--NEUROSCIENCE OF MENTAL AND BEHAVIORAL DISORDERS Principal Investigator & Institution: Lieberman, Jeffrey A.; Professor and Vice Chairman; Psychiatry; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-1979; Project End 31-MAY-2002 Summary: Based at the University of North Carolina, this MHCRC is a multidisciplinary organization of scientists and support staff that includes important collaborators in other Departments and Centers intra and extramurally. The UNC-MHCRC supports studies of the Neuroscience of Mental and Behavioral Disorders focusing on the neurobiological bases and treatment of mood and psychotic disorders, and the psychopathological and physiological effects of stress. The aims of the MHCRC are 1) to generate and test hypotheses in thematic areas of interest; 2) to foster the integration of basic and clinical research; 3) to train young investigators within the research infrastructure of the MHCRC; and 40 to enhance faculty development and productivity by the coordination and facilitation of thematically linked research within the MHCRC's community of investigators. While this MHCRC began 17 years ago as a compendium of related projects focusing on psychoneuroendocrinology, it has matured into a core based center whose goal is to provide the infrastructure (both physical and intellectual) to facilitate state of the art thematically integrated neuroscience research in a costeffective manner. The health and dynamic nature of the MHCRC are reflected in the sustained evolution of the cores as its investigators' scientific interests and needs have developed. The MHCRC has 7 core units: 1) Administrative; 2) Clinical Assessment and Procedures; 3) Behavioral and Cognitive Neuroscience; 4) Neuro-imaging; 5) Analytical and Applied Neuroscience; 6) Data Management and Biostatistics; and 7) Information Technology. Through the functions of its cores and programs, the MHCRC focuses research around 4 themes: 1) neurobiology of mood disorders; 2) pathophysiology of stress transduction in mental and medical disorders; 3) neurobiology of psychotic disorders; and 4) psychopharmacology. The MHCRC continues its interest in children, as well as adults, across all themes, and supports research projects that focus on understanding the roles of both gender and race in mental health. A particular strength of this MHCRC is the close interaction of basic and clinical neuroscientists enabling translation of basic research findings into clinical investigations. The organizational structure and program of the MHCRC provide for the efficient operation and interaction of the cores, dissemination of information between investigators and across projects, the maintenance of rigorous methodologic and ethical standards, and quality control of the supported research. The importance of strong leadership of the MHCRC to achieve these ends was recognized by the recruitment during the last funding period of Jeffrey A. Lieberman to succeed Arthur J. Pranger, Jr., the founding Director of the UNCMHCRC. Dr. Lieberman's research interests and experience provide the ideal complement to the MHCRC at this point in its development. Together, Drs. Prange and Lieberman have led MHCRC scientists in developing a research plan for the next funding period that combines historical continuity with a vision of the scientific future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR AND POPULATION GENETICS OF BIPOLAR DISORDER Principal Investigator & Institution: Freimer, Nelson B.; Professor and Director; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2001; Project Start 01-SEP-1996; Project End 30-APR-2006 Summary: (Investigator's abstract): This application is for competitive renewal of an NIMH Research Scientist Development Award. The University of California, Los Angeles (UCLA) is the nominating institution and the site of most of the planned research and career development activities. The chief objective of the proposal is to foster the continued development of the P1 as an investigator working at the boundary between molecular human genetics and psychiatry. The P1's laboratory is mainly focused on the use of molecular and population genetics approaches to identify the chromosomal location of genes responsible for bipolar disorder (BP), to clone these genes and then to characterize their function. The proposal outlines these objectives and the plans for achieving them. The new goals represent a natural extension of those enunciated in the current award, and are based on developments in human genetics and genomics, as a whole, but particularly on work accomplished in the PI's laboratory during the past four years. Identifying genes responsible for BP will lead to reevaluation of the diagnostic categories that are currently in place for mood disorders. Mapping and cloning BP genes will be of great scientific significance and will likely also have important implications for clinical practice. The proposed population genetics studies aimed mainly at understanding factors governing the detection of linkage disequilibrium (LD) in the genome and on improving the methods available for LD analysis, will yield information that may be valuable in mapping loci for BP as well as other psychiatric disorders. Additionally, the P1's laboratory has developed a new project focused on pharmacogenetic studies of neurotransmitter transporter genes. The goal of these studies is to systematically identify sequence variants in these genes and then to determine if such variants are associated with treatment response to or side effects from psychopharmacologic agents, in particular antidepressant drugs. These studies may lead to more focused used of such agents in clinical practice. Some of the projects proposed in this application will be carried out in collaboration with investigators who have already contributed to the P1's development as a scientist, while other proposed projects will be carried out with new collaborators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOLECULAR GENETIC APPROACH TO EMOTIONAL STATES Principal Investigator & Institution: Hen, Rene; Associate Professor; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 01-SEP-2001; Project End 31-AUG-2002 Summary: The goal of this project is to identify some of the neural circuits and molecular substrates that underlie emotional states. Serotonin is a neuromodulator that has been implicated in normal mood control as well as in a number of mood disorders such as anxiety, depression and aggressiveness. To model such disorders the investigators have introduced mutations in various components of the serotonergic system. In particular, they have generated knockout mice that lack either the 5-HT1A or the 5-HT1B receptor. These mutant mice display a panoply of contrasting phenotypes. While the 5HT1B knockout mice appear to be more aggressive and less anxious than the wild types, the 5-HT1A knockout mice appear to be less aggressive and more anxious
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than wild types. In the present project the investigators propose to take advantage of these two mouse models to identify the neural circuits that are responsible for their opposite emotional states. They will characterize the molecular adaptations that might be responsible for variations in anxiety and aggressive behavior in these two knockout strains. Experiments will be conducted to address three specific aims. The first specific aim will be to identify the neural circuits that are differentially activated in 5-HT1A and 5-HT1B knockout mice. In a second specific aim, they will identify the neural circuits that are responsible for the changes in anxiety and aggressiveness found in 5-HT1A and 5-HT1B knockout mice and in a final specific aim they will identify the molecular adaptations that are associated with variable levels of anxiety and aggressiveness in 5HT receptor knockout mice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MOLECULAR GENETICS OF BIPOLAR DISORDER Principal Investigator & Institution: Baron, Miron; Psychiatry; Columbia University Health Sciences New York, Ny 10032 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-AUG-2004 Summary: (Adapted from investigator's abstract) This proposal is in response to RFA 98-010 entitled "Molecular Genetics of Mental Disorders," a research initiative based on recommendations of the National Advisory Mental Health Council and the NIMH Genetics Workgroup. The broad objective of the proposed research is to detect and localize susceptibility loci for bipolar and related mood disorders. This goal will be attained through a genome-wide search for linkage between the disease and marker loci in a large sample of multiplex pedigrees. The investigators propose a two-site international project is to collect the pedigree sample. Specifically, it is proposed to (1) collect a sample of 300 pedigrees, including about 400 affected sib pairs with bipolar I disorder and 60 to 75 extended high- density pedigrees; (2) evaluate subjects clinically using the DIGS and FIGS interviews, and obtain best estimate clinical diagnoses based on interview, family history, and medical records; (3) obtain blood samples from subjects informative for linkage analysis, for DNA extraction and creation of cell lines; (4) conduct a 10cM genome scan with 377 microsattelite markers; (5) analyze the clinical and genotypic data for evidence of linkage using various statistical methods; and (6) based on the linkage results, identify candidate genomic regions for further study. About 1,500 subjects will be studied. The investigators will make available to the scientific community the clinical and biological data to facilitate efforts to map and clone the disease genes. Long-term goals will include the identification and characterization of the disease genes using a gamut of molecular techniques; elucidation of geneenvironment, interaction, and characterization of cases with linked genes to identify and define homogenous subsets of the disorder. These long-term objectives will be considered in a renewal application. The availability of a unique series of pedigrees, coupled with recent advances in diagnostic procedures, molecular genetics techniques and linkage analysis methods, bode well for unraveling the genetic mechanisms that underlie some forms of bipolar disorder. This, in turn, may have important implications for the etiology, nosology, pathophysiology and, possibly, prevention and treatment of this disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOOD DISORDERS CLINICAL INTERVENTION TRAINING PROGRAM 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 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This training program will address the national shortage of skilled clinical intervention researchers in mood disorders. This application requests support for a three-year postdoctoral training program (2 fellows per year) in clinical intervention studies in mood disorders (e.g., bipolar or unipolar disorder) across the lifespan (juvenile, adult, geriatric mood disorders). The program is open to psychiatrists who have completed adult residency requirements or clinical psychologists who have been awarded their Ph.D. The program has three components: a core curriculum including didactic and workshop formats, three required supervised clinical research rotations that include research on juveniles or adults with bipolar or unipolar disorders, and a mentored multiyear experience designed to assist trainees in developing and implementing an independent clinical research project, which will lead to an application for independent research funding at the conclusion of this training program (e.g., K Award, R-01). The faculty has many years of experience in conducting research together, and in training students and fellows. The core training faculty has established track records in the study of a wide array of interventions including ECT, cognitive therapy, acupuncture, hypericum, antidepressant medications, and the combination of medications and psychotherapy. They are experienced in the conduct of early open label trials, single and multi site randomized trials, as well as in conducting efficacy and effectiveness trials in patients of all ages. Optional research training experiences are available (based on fellow desire) in intervention research in mood disorders associated with general medical, cognitive, and substance abuse disorders. This program will provide a formal training program with predictable support, and will provide trainees with knowledge and experience in the proper conduct of clinical intervention research, ethics, human subjects issues, consent procedures, clinical measurement of symptoms, function, quality of life, healthcare costs, as well as in research design, statistical analytic approaches, and preparation of peer-reviewed articles and research grant applications. This application also includes set-aside support for five minority medical student summer stipends to engage minority students between MSl and MSll years in clinical intervention research with core faculty, to address the national shortage of this group of investigators. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MOOD FLUCTUATIONS IN PARKINSON'S DISEASE Principal Investigator & Institution: Richard, Irene H.; Neurology; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2001; Project Start 27-SEP-2000; Project End 31-AUG-2005 Summary: (Adapted From The Applicant's Abstract): The candidate has a clinical background in neurology with an expertise in movement disorders and has completed a two year NIH-funded fellowship through the Department of Neurology in Experimental Therapeutics. This fellowship provided the candidate with both theoretical knowledge and practical experience pertaining to the design and conduct of clinical trials. She has focussed most of her efforts thus far on the understanding and treatment of the behavioral aspects of Parkinson's disease (PD) The candidate's short term goals include the following: 1) to increase her knowledge of basic pharmacology and gain experience
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using techniques relevant to pharmacologic mechanism oriented research, 2) to gain a better understanding of molecular medicine, 3) to obtain training in psychiatric assessment techniques, 4) to expand her knowledge of areas fundamental to clinical investigation including biostatistics, epidemiology and outcomes research. The focus of her research plan during this career development award will be understanding mood fluctuations in PD. Mood fluctuations have been reported in up to 2/3 of advanced PD patients who experience motor fluctuations. These can be frequent, dramatic and distressing. Research involving the phenomenology and underlying mechanisms of mood fluctuations in PD has been limited. The specific aims of this study are to: 1) better understand the phenomenology of mood fluctuations in PD (frequency, quality, magnitude), 2) better understand the relationship between mood fluctuations and more pervasive depressive disorders in PD, 3) clarify the temporal relationship between changes in mood and motor states in PD, 4) elucidate the neurobiological mechanisms of changing mood states in PD and to determine, in particular, whether mood fluctuations in PD are the result of dopamine dysregulation, and 5) gather preliminary information regarding the optimal treatment of mood disorders in PD. These findings may lead to the development of therapeutic interventions for patients with PD who suffer from these disabling fluctuations on a daily basis. It may also provide a better understanding of the mechanisms responsible for more pervasive forms of depression in PD, and perhaps even in primary psychiatric mood disturbances. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: MRNA REGULATION IN DEPRESSION--CANDIDATE AND ARRAY STUDIES Principal Investigator & Institution: Watson, Stanley J.; Co-Director/Research Scientist; University of California Irvine Irvine, Ca 926977600 Timing: Fiscal Year 2001 Summary: The genetic, molecular, and biochemical causes of mood disorders are still poorly understood. Disturbances in the limbic-hypothalamic- pituitary-adrenal (LHPA) stress axis and the serotonin system are commonly found in depression. However, the pathophysiology of mood disorders and the effectiveness (or lack thereof) of various antidepressants suggest that other neural systems may contribute to the primary or secondary changes in this disorder. The availability of brains from control and depressed subjects provides us with the opportunity to examine the molecular changes in depression in the context of known circuits. As described in the Center Overview, we will address the central hypothesis using two major approaches to the study of alterations in gene expression: 1) The "expression candidate approach" will rely on classical tools such as in situ hybridization to characterize known gene products in the context of circuits proposed to be involved in the regulation of stress emotional responsiveness and emotional executive function. It will also include preliminary genetic characterization of the DNA from control and depressed subjects for markers with known polymorphisms relevant to psychiatric diseases (i.e. serotonin transporter) (Specific Aim I). 2) The "expression array approach" will rely on the new microarray and DNA chip technologies to screen for known and unknown genes whose expression may be altered (either induced or repressed) in depression (see Dr. Cox's proposal). The opportunity to scan the expression levels of thousands of mRNA species for regulatory changes in important brain regions will clearly enhance our understanding of both stress and monoamine systems, and will also identify regulated genes in new neural pathways that are relevant to mood disorders. We may also detect highly regulated mRNA sequences from genes with unidentified functions, leading to new areas of
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study. The post-array analyses will include studies for validation of the regulation changes detected by microarray and DNA chip technologies using additional control and depressed brains. Validation studies will include comparison of mRNA values (and ratios) with those obtained via in situ hybridization of known mRNAs. Biological validation will include in situ hybridization analysis to identify the anatomical sties of expression of altered mRNAs and regulatory studies with rodent models (Specific Aim II). This work will rely on the effects of the Stanford site, and will integrate with the findings from UC site, in order to yield a more comprehensive view of the biological underpinnings of major depressive disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEGATIVE COGNITION DEPRESSION: ETIOLOGY AND COURSE Principal Investigator & Institution: Abramson, Lyn Y.; Professor; Psychology; University of Wisconsin Madison 750 University Ave Madison, Wi 53706 Timing: Fiscal Year 2002; Project Start 01-AUG-1990; Project End 31-DEC-2003 Summary: (provided by applicant): This competing continuation is part of a 2-site collaborative research grant with an identical application submitted concurrently by Dr. Lauren B. Alloy at Temple University. Prior research did not provide an adequate test of the hopelessness theory (HT) and Beck's theory (BT) of depression and may have been misleading about those cognitive theories' validity. Thus, the overarching goal of this project is to provide a more powerful test of HT's and BT's predictions about the etiology of depression and a validation of the Hopelessness Depression subtype. To this end, a large scale, 5.5-year prospective study was conducted at both sites. Initially nondepressed, non-psychopathological Ss (n=349) who were at either high or low cognitive risk for depression were followed prospectively with independent and blind self-report and interview assessments of stressful life events, cognitions, social support, coping, and psychiatric status/symptoms in order to predict onsets and subsequent recurrences of depression. Familial and developmental origins of cognitive vulnerability to depression also were examined, including assessment of the parents (n=335) of highrisk and low-risk Ss. In this renewal, differential predictors of first onsets vs. recurrences of depression, factors that increase resilience among high-risk Ss and promote depression among low-risk Ss, factors that contribute to and moderate change in cognitive vulnerability, and different models of cognitive vulnerability-stress relations also were investigated. This project contributes to: 1) the scientific understanding of the etiology and course of a subset of the mood disorders; 2) a more valid nosologv of the depressive disorders; 3) an understanding of the origins and continuity/change of cognitive vulnerability to depression; 4) an understanding of factors that promote resilience to depression; and 5) the development of interventions for treating and preventing depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NEGATIVE COGNITION DEPRESSION: ETIOLOGY AND COURSE Principal Investigator & Institution: Alloy, Lauren B.; Professor; Psychology; Temple University 406 Usb, 083-45 Philadelphia, Pa 19122 Timing: Fiscal Year 2002; Project Start 01-SEP-1990; Project End 31-DEC-2003 Summary: This competing continuation is part of a 2-site collaborative research grant with an identical application submitted concurrently by Dr. Lyn Y. Abramson at the University of Wisconsin. Prior research did not provide an adequate test of the hopelessness theory (HT) and Beck's theory (BT) of depression and may have been
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misleading about those cognitive theories' validity. Thus, the overarching goal of this project is to provide a more powerful test of HT's and BT's predictions about the etiology of depression and a validation of the Hopelessness Depression subtype. To this end, a large scale, 5.5-year prospective study was conducted at both sites. Initially nondepressed, non-psychopathological Ss (n=349) who were at either high or low cognitive risk for depression were followed prospectively with independent and blind self-report and interview assessments of stressful life events, cognitions, social support, coping, and psychiatric status/symptoms in order to predict onsets and subsequent recurrences of depression. Familial and developmental origins of cognitive vulnerability to depression were also examined, including assessment of the parents(n=335) of highrisk and low-risk Ss. In this renewal, differential predictors of first onsets vs. recurrences of depression, factors that increase resilience among high-risk Ss and promote depression among low-risk Ss, factors that mediate and moderate change in cognitive vulnerability, and different models of cognitive vulnerability-stress relations are also investigated. This project contributes to: 1) the scientific understanding of the etiology and course of a subset of the mood disorders; 2) a more valid nosology of the depressive disorders; 3) an understanding of the origins and continuity/change of cognitive vulnerability to depression; 4) an understanding of factors that promote resilience to depression; and 5) the development of interventions for treating and preventing depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURAL CORRELATES OF EMOTIONAL LEARNING AND BEHAVIOR Principal Investigator & Institution: Salzman, Daniel C.; Psychiatry; Stanford University Stanford, Ca 94305 Timing: Fiscal Year 2001; Project Start 10-MAY-2000; Project End 31-AUG-2001 Summary: Dysfunction in neural circuits within the limbic system has been implicated in the pathophysiology of many psychiatric diseases, such as mood disorders, anxiety disorders, and schizophrenia. Indeed, psychiatric illness is frequently in part characterized by patients' having abnormal emotional, or affective, responses to sensory stimuli, events, and memories. The primary goal of this research program is to study the manner in which sensory stimuli are endowed with affective significance to produce emotional behavior. Within the limbic system, the amygdala appears to play a prominent role in mediating emotional responses to sensory stimuli. The specific aim of this proposal investigates amygdala neural responses to visual stimuli that have acquired affective significance through Pavlovian conditioning in monkeys performing an emotional learning behavioral paradigm. In addition , psychophysiological recordings will be obtained during task measurements of psychophysiological parameters. In this manner, neural correlates of emotional learning and behavior will be sought. The second specific aim of this proposal involves recording the activity of neurons in area TE of inferotemporal cortex while monkeys perform the same emotional learning paradigm. Again, psychophysiological recordings will be obtained simultaneous to the neurophysiological recordings. Area TE is the primary source of unimodal visual inputs to the amygdala, and the amygdala sends back projects to TE. Previous studies in TE have suggested that it is involved in representing and remembering visual objects. A fundamental question in visual neurosciences to what extent affective value is inextricably linked to the basic representation of visual objects in the cortex. These experiments will address this question by determining the extent of affective signals present in TE. Ultimately, the experiments will address this question by
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determining the extent of affective signals present in TE. Ultimately, the approach taken in this project may provide the opportunity to improve understanding of psychiatric treatments by investigating how pharmacological interventions influence neural responses and emotional behavior in the alert monkey. The long-term career goal of the investigator is to establish a research program investigating the neural basis of emotions and emotional behavior. Stanford University and the laboratory of Dr. William Newsome, combined with the co-mentorship of Dr. Joseph LeDoux at New York University, provide a rich intellectual environment for the candidate to develop into an independent investigator. Participation in seminar, journal clubs, courses, scientific presentation sessions, and informal discussions with a large variety of faculty and trainees will form the basis of an intensive training program Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NEURONAL DYSFUNCTION IN PREMENSTRUAL DYSPHORIC DISORDER Principal Investigator & Institution: Epperson, Cynthia N.; Assistant Professor; Psychiatry; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2001; Project Start 05-DEC-1999; Project End 30-NOV-2004 Summary: After a year and a half on the faculty in the Departments of Psychiatry and Obstetrics and Gynecology, I find myself at a crossroads in my career development. I have been involved primarily in clinical postpartum mood disorders and obsessive compulsive disorders research. However, my clinical and scientific interests have shifted. During my tenure as the Director of the Yale Behavioral Gynecology Program, I have developed an appreciation for the complex interplay between neuroactive steroids and the neurochemistry involved in regulation of mood and cognition. In addition, I have developed basic skills in proton-magnetic resonance spectroscopy (1H-MRS), a novel, non-invasive method to quantify in vivo amino acid neurotransmitters. I have designed the K23 award to enable me to pursue a five-year comprehensive researchtraining plan. This plan will provide me with the skills necessary to become an independent investigator who can apply MRS techniques to determine the impact of neurosteroids on GABA and glutamate neurotransmission as they reltate to the pathophysiology and treatment of premenstrual dysphoric disorder (PMDD). Without support from a K23 award, I would be required to continue my significant administrative and clinical duties as the director of a busy clinical program and would not be afforded the opportunity to make this shift in my scientific career. We have obtained exciting pilot data using 1H-MRS demonstrating fluctuations in cortical GABA levels across the menstrual cycle of women with PMDD and health menstruating controls with between group differences in the fluctuation pattern. I propose to continue these investigations with three goals. 1) To conduct the first longitudinal (across the menstrual cycle) characterization of both frontal and occipital cortex GABAergic and glutamatergic systems in healthy menstruating women and those with PMDD. 2) To determine the relationship between neuroactive steroids and amino acid neurotransmitter levels across the menstrual cycle. Amd 3) To determine whether the selective serotonin reuptake inhibitor fluoxetine exert its therapeutic effect in the treatment of PMDD via modulation of neuroactive steroids and/or GABAergic and/or glutamateric function. I have identified several key areas where I will require additional training in order to advance the use of 1H-MRS techniques to the study of PMDD. These areas include; 1) nuclear magnetic resonance application of reproductive endocrinology to PMDD research, 3) neurochemistry and kinetic modeling, and 4) neuropharmacology and clinical trials methodologies. Under the mentorship of my Yale mentors Drs.
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Krystal, Rothman, and Naftolin and my extra-mural mentors Drs. Rubinow and Schmidt, the career development program outlined in this program is certain to prepare me for a career as an neuroendocrinologist who can utilize MRS technology to study the impact of neuroactive steroids on brain neurochemistry. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NIA ACADEMIC CAREER LEADERSHIP AWARD Principal Investigator & Institution: Lachs, Mark S.; Associate Professor; Medicine; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2001; Project Start 30-SEP-1998; Project End 31-JUL-2003 Summary: This application proposes use of the NIA Academic Career Leadership Award to link renowned aging related programs at the New York Hospital- Cornell University Medical College by pairing the research methodology expertise of the candidate. Mark Lachs MD, MPH, a geriatrician, clinical epidemiologist, and health services researcher, with that of other gerontology program faculty in the mentorship of a fellow or junior faculty member in specific research projects for each year of the award. The newly appointed Chief of the Division of Geriatrics and Gerontology at the Medical College, Dr. Lachs has laid the foundation for leveraging Cornell's existing resources in the areas of geriatric medicine, psychiatry, mobility, sociology, and neurology in a way that will efficiently expand the aging research and training capabilities of the institution consistent with the goals of the RFA. These remarkable resources include: (1) An NIMH Research Center Grant on Mood Disorders under the direction of Dr. George Alexopoulos, (2) A NIAMS Multipurpose Arthritis and Musculoskeletal Disease Center Grant headed by Dr. Steven Paget, Chief of Rheumatology at Cornell and Physician-in-Chief of the Hospital for Special Surgery, (3) An NIA Roybal Social Gerontology Center Grant based at the Cornell Applied Geriatrics Research Institute headed by Dr. Karl Pillemer (the candidate's long-standing collaborator in studies of family violence committed against the elderly), (4) The Cornell Neurogeriatrics Program at Cornell Medical College and the Hebrew Home for the Aged in Riverdale, headed by Drs. Fred Plum and Norman Relkin, and (5) an AHCPR funded training program for physicians leading to a masters degree in clinical epidemiology and health services research from the Cornell's Graduate School of the Medical Sciences, headed by Drs. Mary Charlson and Pamela Williams-Russo, and on which the candidate serves as faculty. Additionally, in the spring of 1998, the institution will open the Irving Sherwood Wright Center on Aging, a 15,000 square foot community- based aging center, named in honor of pioneer in aging research and Cornell Professor Emeritus Irving Wright. A sample pilot project for year one is provided, the specific aim of which is to estimate the incidence of new or worsening depressive symptomatology and cognitive impairment in a group of "self-neglecting" older adults referred to adult protective services and who have been followed for over a decade as part of the New Haven EPESE cohort. This project pairs the candidate with two members of the geropsychiatry program (Dr. Martha Bruce, a Psychosocial Epidemiologist, and Dr. Robert Abrams, a geriatric psychiatrist with expertise in late life personality disorders) in the mentorship of Dr. Denis Keohane, a new faculty member in the Division of Geriatrics and Gerontology who has a scientific interest in prognostication in medical illness and a clinical interest in the homebound elderly. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: NOVEL NEURONAL NACHR-TARGETED PEPTIDES Principal Investigator & Institution: Mc Intosh, J M.; Psychiatry; University of Utah Salt Lake City, Ut 84102 Timing: Fiscal Year 2001; Project Start 30-SEP-1996; Project End 30-APR-2006 Summary: From applicant's abstract): Nicotinic acetyicholine receptors (nAChRs) modulate the release of a number of key neurotransmitters in the central nervous system (CNS). Pharmacological manipulation of the function of these receptors may be beneficial in the treatment of a variety of disorders that impact mental health including schizophrenia, Tourette's syndrome, attention deficit hyperactivity disorder, mood disorders, Alzheimer's disease and chronic pain. Venom from carnivorous marine snails of the genus Conus are an extraordinarily rich source of compounds (cx-conotoxins) that potently and selectively target specific nAChR subtypes. The aim of this proposal is to identify and characterize compounds from these venoms that discriminate among distinct ACh-binding subunit interfaces of neuronal nAChRs. This aim will be accomplished by using receptor-based assays to track the purification of active venom compounds. Genes encoding a-conotoxins also will be cloned to isolate new toxins. Peptides identified by either approach will be biochemically characterized and synthesized. These peptides will then be fully characterized with respect to receptor subtype specificity and used to examine the subunit composition of presynaptic nAChRs that mediate the release of neurotransmitters. A major thrust of current research is to identify the subunits in the different functional channel subtypes of nAChRs and to understand their roles in health and disease. The availability of selective probes for the nAChR subtypes will greatly facilitate these efforts and provide a platform for development of medications capable of modulating specific nAChRmediated functions in the nervous system. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: OFFSPRING OF OUTPATIENTS WITH DYSTHYMIC DISORDER: OUTCOMES AND MEDIATORS OF RISK Principal Investigator & Institution: Lizardi, Humberto; Herbert H. Lehman College Bedford Park Blvd W New York, Ny 10468 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2007 Summary: The NICHD has as one of its missions the support of projects that examine the effects of parental care on the social and emotional adjustment of children. This project is designed to address several aims that specifically fit this mission. There are several decades worth of literature examining major depressive disorder in parents as a risk factor for offspring maladjustment. However, the literature on outcomes in the children of parents with dysthymic disorder is limited. The proposed research is designed to address this gap in the literature. More specifically, the aims of this project are to compare outpatients with DSM-IV early-onset dysthymic disorder with concurrent major depressive disorder (double depression), DSM-IV early-onset dysthymic disorder without a concurrent major depressive disorder (pure dysthymic disorder), DSM-IV episodic major depressive disorder, and normal controls with no history of Axis I disorder on the following: 1) functioning in major role areas; 2) their parenting; 3) their cognitive processes; 4) rates of psychiatric disorders in their offspring; 5) functioning by their offspring in major role areas; 6) cognitive processes in their offspring; and 7) mediators of the risk for adverse outcomes in offspring. Participants will include 45 subjects in each group. The parent groups will be compared on both interview and self-report measures of social functioning. In addition, the offspring of the
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four groups will be compared on rates of psychopathology, as determined by a teamconsensus method, and on social and cognitive functioning. Offspring adjustment will be assessed blind to the diagnostic status of the parents. Mood disorders represent a significant public health problem in the United States. Research contributing to our understanding of the correlates of double depression and pure dysthymic disorder in parents and the mediators of risk for offspring maladjustment will enable us to identify vulnerable children and to develop effective intervention programs. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PATHWAYS TO DISTURED EMOTIONS, PERCEPTIONS AND BELIEFS Principal Investigator & Institution: Berenbaum, Howard; Associate Professor; Psychology; University of Illinois Urbana-Champaign Henry Administration Bldg Champaign, Il 61820 Timing: Fiscal Year 2001; Project Start 10-SEP-2001; Project End 31-AUG-2005 Summary: (provided by applicant): The proposed project has four major goals: (1) to examine in a large representative community sample the strength of the association between a history of psychological trauma and elevated levels of peculiar perceptions and beliefs, assessed by measuring symptoms of schizotypal personality disorder; (2) to examine whether the effects of neurodevelopmental factors and psychological trauma on vulnerability to peculiar perceptions and beliefs are additive or interactive; (3) to examine the relation between peculiar perceptions and beliefs and disturbances in emotional awareness and the processing and utilization of emotionally-valenced information; and (4) to examine psychological mechanisms (disturbances in emotional awareness and the processing and utilization of emotionally-valenced information, dissociation, absorption, and an intuitive-experiential thinking style) that may mediate the links between distal vulnerability factors, such as psychological trauma and neurodevelopmental factors, and the later development of elevated levels of peculiar perceptions and beliefs. The association between trauma history and schizotypal personality disorder will be examined in a telephone survey of 1500 individuals randomly selected from the community. The remaining goals will be addressed by conducting intensive laboratory/interview assessments of 300 individuals, recruited via telephone screening and newspaper advertising, intentionally oversampling individuals with high levels of schizotypal symptoms. The laboratory/interview assessments will include the assessment of minor physical anomalies, handedness, dermatoglyphic asymmetries, Cluster A personality disorders, childhood maltreatment as well as other traumas, and questionnaire and behavioral measures of the processing and utilization of emotionally-valenced information. The proposed project will improve our understanding of the nature and etiology of schizotypal, schizoid, and paranoid personality disorders. The proposed project will also provide clues concerning which psychological mechanisms might contribute to peculiar perceptions and beliefs across the psychiatric spectrum, such as the hallucinations and delusions exhibited by individuals with psychotic and mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: PET STUDIES OF REM/NREM SLEEP IN MOOD DISORDERS Principal Investigator & Institution: Nofzinger, Eric A.; Associate Professor of Psychiatry; Psychiatry; University of Pittsburgh at Pittsburgh 350 Thackeray Hall Pittsburgh, Pa 15260
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Timing: Fiscal Year 2001; Project Start 10-SEP-1997; Project End 24-SEP-2002 Summary: (Adapted from applicant's abstract): This is a revised submission of the Mentored Clinical Scientist Development Award application 1 K08 MH 01414-01. The biological basis of mood disorders has been clarified through alterations in REM and delta sleep across the clinical course of depression. Questions remain, however, regarding the pathophysiologic mechanisms of these EEG sleep alterations as well as regarding the specificity of these findings. Advances in the neurobiology of sleep suggest that the neuropharmacologic modulation of REM/NREM sleep states as well as regions of the brain found to be metabolically active during REM/NREM sleep have parallels with pathophysiologic mechanisms hypothesized for mood disorder patients. These include monoaminergic/cholinergic interactions involving the prefrontal cortex,and limbic and paralimbic cortical regions. Therefore, paradigms utilizing functional brain imaging during REM/NREM sleep states may clarify specific neuropathologic mechanisms in mood disorder patients. Within this background, this K08 Mentored Clinical Scientist Development Award proposal outlines: 1) the candidate's background in mood disorders, sleep disorders and psychiatric EEG sleep research; 2) a career development path describing new research training in the neurosciences and in PET imaging necessary for the successful completion of functional imaging studies of sleep; 3) a research paradigm combining EEG sleep and PET imaging methodologies to study waking, NREM, and REM sleep in 20 unipolar depressed patients and 20 age- and sex-matched healthy controls; and 4) directions for future proposals using similar methodologies in conjunction with longitudinal clinical trials and utilizing pharmacologic probes in limbic and paralimbic cortex in mood disorder patients over the course of illness. PET sleep pilot data in six unipolar depressed women and six age-matched healthy women demonstrate the feasibility of these methods. Preliminary data suggest that there are fundamental differences in relative and absolute cerebral glucose metabolism during REM sleep between depressed and control subjects. These changes involve neural systems which regulate affective and adaptive behavior. Mentors for this work include: Dr. Robert Moore (neurosciences), Dr. Wayne Drevets (PET), and Dr. Charles Reynolds, III (psychobiology and clinical trials), Drs. J. Christian Gillin and Richard Frackowiak will provide additional training in the neuropharmacology of sleep in mood disorders and in the design of PET studies utilizing pharmacologic modulation of cognitive activation, respectively. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHASE SHIFTING EFFECTS OF MELATONIN IN WINTER DEPRESSION Principal Investigator & Institution: Lewy, Alfred J.; Professor; Psychiatry; Oregon Health & Science University Portland, or 972393098 Timing: Fiscal Year 2001; Project Start 01-SEP-1997; Project End 30-APR-2004 Summary: We have concentrated all of our research efforts on the study of the role of biological rhythms in sleep and mood disorders. We have found that human nighttime melatonin production is suppressed by bright light. This discovery led to the use of bright light in the morning in order to cause a phase advance and in the evening to cause a phase delay. These findings have been applied in the treatment of circadian phase disorders, which include advanced and delayed sleep phase syndrome, jet lag and maladaptation to shift work. One of the most responsive disorders to bright light treatment is winter depression. However, it is not known whether or not this disorder has a significant biological rhythm component. We have proposed a biological rhythm hypothesis in order to further our knowledge of why these patients become depressed
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in the winter and how bright light exposure is antidepressant. The phase shift hypothesis states that winter depressives become phase delayed in response to the short natural photoperiod (the later dawn) at this time of year. It further states that bright light exposure should be most antidepressant when scheduled in the morning at which time it will cause a corrective circadian phase advance. Although the phase shift hypothesis is probably the most actively tested of the winter depression hypotheses, it is controversial: some studies show morning light to be more antidepressant than evening light, other studies show no difference. We have recently completed the largest single comparison of morning versus. evening light in this patient population, the results of which support the phase shift hypothesis. However, although morning light is more antidepressant than evening light, evening light depression ratings are lower than baseline ratings. Therefore, it is still possible that the antidepressant response to light is not dependent upon a phase advance. The present study proposes to determine whether or not a phase advance is a significant component of morning light's antidepressant effect. It is based on our recent discovery of a phase response curve for exogenous administration of melatonin in humans: administration of melatonin in the afternoon causes a phase advance similar to that caused by morning light exposure; administration of melatonin in the morning causes a phase delay similar to that caused by evening light. By causing circadian phase shifts through an entirely different phaseresetting agent, we can conduct an important test of the phase shift hypothesis. The proposed study should further our understanding of light melatonin and biological rhythms in winter depression. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PHENOTYPICAL EXPRESSION OF ANXIETY AND SLEEP Principal Investigator & Institution: Sanford, Larry D.; Associate Professor; Pathology and Anatomy; Eastern Virginia Medical School Norfolk, Va 23507 Timing: Fiscal Year 2001; Project Start 30-SEP-1999; Project End 31-MAY-2003 Summary: (adapted from the applicants' abstract) The long-term goal of this project is to further the understanding of how emotional factors influence sleep. Emotional state has a strong influence on sleep quality and amount. This statement can be attested to by almost everyone, and it is factually supported by the observed role of emotional factors in human sleep medicine, particularly sleep disorders related to a psychiatric condition. However, the role of emotion has virtually been ignored in basic sleep research, possibly because of the lack of a clear anatomical focus, or perhaps because of a lack of established models. It is now becoming increasingly apparent that the amygdala, the limbic center of emotion, has a strong modulatory role in the control of sleep. Inbred mouse strains are being examined in order to find models of anxiety and mood disorders. The investigators plan to study sleep in inbred mouse strains with differences in emotional reactivity in order to begin to understand how genetics and the environment interact in producing the effects of emotion on sleep. The investigators' strategy is to : 1) establish protocols for studying how emotion affects sleep in inbred mouse strains, 2) identify the anatomical regions that could account for strain differences in emotional reactivity as it affects sleep, and 3) determine the functional significance of these regions in the control of emotion and sleep. To accomplish these goals, the investigators will examine the effect of fear conditioning on sleep, identify the activated brain areas that affect sleep and examine the function of these regions by selectively preventing their activation in response to fear conditioning. These studies will help elucidate into how stress, emotion and environmental factors influence sleep. This work will advance the understanding of how stress and anxiety affect sleep and
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may give insight into sleep disorders such as insomnia and into mental disorders in which sleep is affected. The investigators findings may be especially relevant to posttraumatic stress disorder (PTSD), which is typically characterized by a prominent sleep disturbance in the aftermath of exposure to a psychologically traumatic stressor. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PKC SUBSTRATES & TRANSCRIPTION FACTORS IN MOOD DISORDERS Principal Investigator & Institution: Pandey, Ghanshyam N.; Professor; Psychiatry; University of Illinois at Chicago 1737 West Polk Street Chicago, Il 60612 Timing: Fiscal Year 2002; Project Start 01-MAR-1998; Project End 31-AUG-2007 Summary: (provided by applicant): Significant progress has been made in the understanding of the neurobiological abnormalities associated with depression and bipolar disorders. However, the specific sites of such abnormalities in these disorders are still unclear. Several studies indicate increased 5HT2A receptors and 5HT2A receptor linked phosphoinositide (PI) signaling activity in the brain and platelets of patients with mood disorder. The studies in the previous funding period, indicated that 5HT2A receptors and IP3 receptors are increased in the platelets of unipolar patients, PKC activity, PLC activity and selective isozymes of PKC and PLC are decreased and MARCKS, a substrate for PKC increased in the platelets of bipolar patients. In the proposed research, the main objective is to extend our findings and to study further downstream events in the PI signaling system, such as: PKC substrates and transcription factors in the platelets and neutrophils obtained in drug-free unipolar and bipolar patients. More specifically, we will study PKC, MARKCS and GAP43 the substrates for PKC, in the platelets of unipolar and bipolar patients, DNA binding activity of transcription factors AP-1, GRE, DNA binding activity, protein expression and mRNA levels of another transcription factor CREB in the neutrophils of unipolar and bipolar patients. In addition, we will study the activity, protein level and mRNA levels of GSK3B and protein levels of B-catenin, the two important components of the WNT pathway that appears to be related to and may be regulated by PKC and has been implicated to be abnormal in bipolar disorders. Our proposed studies are based on our central hypothesis that an abnormal PT signaling system in patients with mood disorders is associated with abnormality of several of its components leading to abnormality of transcription factors and gene expression.These studies will enhance our understanding of the involvement of transcription factors and PKC substrates in the pathophysiology of unipolar and bipolar disorders and may indicate if they may be possible sites for therapeutic action of antidepressants and mood stabilizing drugs, thus, may result in more appropriate and better treatment these disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: POSTPARTUM DEPRESSION IN A PEDIATRIC CLINIC Principal Investigator & Institution: Chaudron, Linda H.; Psychiatry; University of Rochester Orpa - Rc Box 270140 Rochester, Ny 14627 Timing: Fiscal Year 2002; Project Start 03-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): This K23 Award will allow the candidate to gain the skills and depth of knowledge required to become a leader in women's health with focused expertise in postpartum depression research and to address this critical problem through an approach that integrates clinical and public health perspectives. Postpartum depression (PPD) is a serious public health problem affecting 10-20% of American
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women. PPD has significant repercussions for the health and functioning of mothers and the welfare of their children. It remains a poorly detected disorder by both women and their clinicians, in part due to its inadequate clinical characterization. Consequently, effective detection strategies have yet to be developed. The proposed research addresses these issues by 1) characterizing the mood disorders, depressive symptomatology and co-morbid psychiatric disorders throughout the postpartum year, 2) identifying effective screening tools for its detection, 3) establishing the feasibility of conducting a prospective longitudinal study of women during the postpartum year, and 4) collecting pilot data to describe the natural course and clinical correlates of PPD. To facilitate the application of this research to clinical settings, it will be conducted in the context of pediatric outpatient services where mothers are seen regularly throughout the postpartum year. Because an even greater paucity of data exists about PPD in ethnic and minority populations, this project focuses on a primarily African-American population of young women. To achieve her research and career goals, the candidate will follow a career development plan that consists of: 1) academic coursework to further develop general and health services research skills and to enhance her knowledge of early life development, parent-child interactions, and health systems; 2) mentorship and consultation with nationally and internationally recognized experts in postpartum depression, maternal and child health, and pediatric health services research; 3) innovative research of postpartum depression in a pediatric clinic. PPD is a disorder that cuts across traditional discipline boundaries of epidemiology, psychiatry, women's health, pediatrics and public health. An integrated model can provide a greater contribution to the detection and prevention of PPD than any individual discipline can provide independently. The candidate and this research project will lead to the creation of such a model. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: POSTPARTUM DEPRESSION: OMEGA-3 FA VS PLACEBO Principal Investigator & Institution: Freeman, Marlene P.; Psychiatry; University of Arizona P O Box 3308 Tucson, Az 857223308 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Dr. Freeman is an Assistant Professor of Psychiatry at the University of Arizona and Director of the Women's Mental Health Program of the Department of Psychiatry. After receiving her M.D. from Northwestern University Medical School, she completed a psychiatry residency at the Harvard Longwood Psychiatry Residency Training Program and a Fellowship in Biological Psychiatry at the University of Cincinnati. Her immediate goals are: I) to obtain proficiency in clinical research methodology, with specific emphasis on gender-specific psychopharmacologic research, statistics, and ethical issues, and 2) to gain expertise in the research on mood disorders during pregnancy and the postpartum period. Long term goals are: 1) to become an independent investigator of mood disorders during pregnancy and postpartum, 2) to obtain an ROI award to support further study as an independent investigator, and 3) to serve as a mentor for junior investigators. The career development plan includes a structured didactic program designed to facilitate development to an independent investigator. Mentorship includes work with a primary mentor, Alan Gelenberg, M.D., and strong mentorship in the areas of women's psychiatry and omega-3 fatty acids. A multidisciplinary Advisory Committee will oversee the career development activities at the University of Arizona. The proposed research study is a double-blind, placebo-controlled 3-arm trial of omega-3 fatty acids (FA) in postpartum depression. Data suggest omega-3 fatty acids are efficacious in the
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treatment and prophylaxis of major depressive disorders. Omega-3 fatty acids may be especially relevant in the treatment of postpartum depression, due to the depletion of maternal omega-3 fatty acids that occurs during pregnancy. The purpose of this study is to determine the efficacy, as well as most effective dose, of omega-3 fatty acids for postpartum depression. Two omega-3 fatty acids in fish oil are eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Two different active arms are included in this protocol, one in which patients receive 2.8 g of EPA plus DHA (1.7 g EPA and 1.1 g DHA) and another in which patients receive I g EPA. The active arms were carefully chosen on the basis of pilot treatment data and epidemiological data; they should produce optimal tissue levels. These doses should provide an adequate test of the efficacy of omega-3 fatty acids while being safe for the mother and breastfeeding baby. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PREVENTION OF SUBSTANCE ABUSE IN HIGH RISK ADHD CHILDREN Principal Investigator & Institution: Greene, Ross W.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 15-MAY-2000; Project End 30-APR-2005 Summary: (Applicant's Abstract) This is an application for a Mentored Clinical Scientist Development Award with a focus on developing expertise in designing and evaluating early interventions for children with attention-deficit/hyperactivity disorder (ADHD) at risk for later substance use disorders (SUDs). While research has shown that children with ADHD are at heightened risk for SUDs, it has been difficult to identify characteristics of children with ADHD that are associated with subsequent SUDs. However, recent studies by the candidate and his colleagues have identified "social disability" as a major risk factor for later SUDs in children with ADHD (after controlling for well-known risk factors such as conduct disorder, mood disorders, aggression, and severity of ADHD). Thus, social disability provides a mechanism for early identification of children with ADHD at greatest risk for later SUDs and affords the opportunity for early prevention efforts. Research Plan: The candidate proposes to refine and test an intervention for 8-10 year old socially disabled children with ADHD for the purpose of preventing later substance use and abuse. The 12-week intervention is intended as a departure from traditional consequence-oriented approaches emphasizing compliance, and will instead focus on reducing adversarial parent-child interactions, improving family communication and problem-solving, and training children in lacking skills in a manner that is matched to each child's individual needs and conducted in a familytherapy context to promote maintenance and generalization. It will be tested in a randomized controlled trial with proximal (3-month) and long-term (3-year) follow-up assessment. Environment: The proposed study will be based at the Massachusetts General Hospital and will complement a program of training, and supervised research under the mentorship of Joseph Biederman, MD and Co-Sponsorship of Timothy E. Wilens, MD, with consultation from experts in the areas of social impairment, childhood psychopathology, and assessment and prevention of SUDs. Career development plan: The candidate proposes to develop further expertise in the assessment and prevention of substance use disorders, on assessment of child psychopathology and social dysfunction, and in statistical approaches for analysis of complex longitudinal data. Coursework at the Harvard School of Public Health and tutorials in intervention research design, statistical methods, and methodology for longitudinal follow-up will complement supervision by the consultants. The candidate hopes to develop a critical fund of knowledge in SUDs, social impairment, child psychopathgology. prevention
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research, and statistical methodology which will lav the foundation for future independent investigation of intervention strategies for high-risk children. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PROBING PREMENSTRUAL DYSPHORIC DISORDER WITH LIGHT Principal Investigator & Institution: Parry, Barbara L.; Professor; Psychiatry; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 92093 Timing: Fiscal Year 2002; Project Start 19-SEP-2002; Project End 30-JUN-2007 Summary: (provided by applicant): Depression is a major health problem, on a par with heart disease in its annual cost of $43.7 billion. Women, compared with men, have a 2 to 1 incidence of major depression and are prone to develop episodes at times of reproductive hormonal change. The focus of this revised application is premenstrual dysphoric disorder (PMDD), a depressive disorder in the DSM-1V. In a pilot study, we observed in PMDD, but not in normal control (NC) subjects, an abnormal direction and a decreased magnitude of phase-shift responses in melatonin offset time alter a morning bright light pulse. The abnormality occurred in the symptomatic luteal, but not the asymptomatic follicular, menstrual cycle phase. In this proposal, we aim to replicate and extend these findings to determine whether abnormal phase-shifts to light occur in PMDD at other times of day. We will test the hypothesis that abnormal phase-shift responses to light also occur in the late subjective evening (during a delay portion of the phase-response curve, PRC), and during the early subjective morning (during an advance portion of the PRC). To assess phase-shift responses, we will measure the effects of bright (about 6,000 lux), 3-hour (h) light pulses on the critical circadian parameters of rhythmic plasma melatonin secretion, sleep electroencephalogram (EEG), and core body temperature. Responses to light at 2 different times of day will be compared between the follicular and luteal phases in women with PMDD and in normal control subjects. Altered phase-shift responses may contribute to disturbances in internal temporal order, and thereby result in mood disorders in predisposed individuals. These investigations will provide further insight into the pathophysiology of PMDD and other depressive disorders in women, and serve as a basis for refining light treatment interventions in the future. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISORDERS
PSYCHIATRIC
SYMPTOMS
IN
NEURODEGENERATIVE
Principal Investigator & Institution: Margolis, Russell L.; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2001 Summary: An extremely powerful approach to understanding the neurobiology of psychiatric syndromes is to study the nature and frequency of these conditions in brain diseases in which the neuropathology is well-defined. For instance, studies of Alzheimer's disease, Parkinson's disease, and Huntington's disease have helped to implicate regions of the cerebral cortex and basal ganglia as potentially important to the pathophysiology of mood disorders. Preliminary evidence suggests that the cerebellum and related structures may also be relevant to such disorders. We now propose to test the hypothesis that the cerebellum and related structures have a role in affective and other psychiatric syndromes by examining the nature and frequency of these syndromes in patients with degenerative diseases of the cerebellum. Three lines of evidence support this hypothesis. First, it has long been emphasized that the cerebellum is an important
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modulator of movement, a functional role reflected in the connections the cerebellum makes to cortical and spinal regions that regulate movement. However, recent work has demonstrated that the cerebellum is anatomically connected to regions of the cerebral cortex (prefrontal, superior temporal, and posterior parietal) that regulate emotion and cognition rather than motor function. Second, the cerebellum and related structures appear to have a role in cognition, including learning, decision making, language, orientation in space and time, and attention. Third, preliminary studies have found evidence for prominent but short-live depression after cerebellar strokes, a higher overall rate of psychiatric illness among patients with ataxia (loosely defined) than in a control population, and a 12-14% rate of depression, euphoria, and impulsivity (all loosely defined) in patients with progressive ataxia. This evidence strongly suggests a link between the cerebellum and psychiatric phenomenology. However, to date no study has systematically used reliable and validated methods to examine psychiatric phenomenology in patients with cerebellar degeneration. We propose to remedy this oversight. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF SEPTOHIPPOCAMPAL PATHWAY Principal Investigator & Institution: Alreja, Meenakshi; Associate Professor; Yale University 47 College Street, Suite 203 New Haven, Ct 065208047 Timing: Fiscal Year 2002; Project Start 16-JUL-2002; Project End 30-JUN-2006 Summary: Mood disorders are often precipitated/worsened by stress, which decreases hippocampal neurogenesis, causes atrophy and decreases- derived neurotrophic factor (BDNF) mRNA. These effects may partly be mediated via an excess of glucocorticoids (GC) possibly due to decreased hippocampal hypothalamic-pituitary-adrenal (HOA) axis feedback. Anti-depressants up-regulated hippocampal (BDNF) aqnd neurogenesis. Functionally, hippocampal disruption may contribute to cognitive deficits in stressrelated disorders. Available evidence suggests that, similar to cognitive functions, hippocampal BDNF and HPA axis feedback are highly dependent on the septohippocampal pathway which provides the hippocampus with almost its entire ACh. Thus, rats with selective loss of septohippocampal cholinergic neurons are not only cognitively impaired, but have higher basal corticosterone (CORT) and higher CORT levels for a longer period after restrain stress. Muscarinic receptor antagonists mimic this effect, suggesting that hippocampal cognition, HPA axis feed back and BDNF are under a septohippocampal muscarinic tone. In turn, retrograde-transported hippocampal BDNF provides essential trophic support to the septohippocampal cholinergic neurons. Behavioral, neurochemical and molecular studies have demonstrated that septohippocampal cholinergic functions decline rapidly with stress. In our preliminary studies, conducted using electrophysiological recordings in rat brain slices, we have found that muscarinic tones, which reflects the availability of ACH that is synthesized by septohippocampal cholinergic neurons, is significantly reduced both in stressed rats as well as in BDNF null-mutant mice. Therefore, we hypothesize that 1) stress reduces septohippocampal functions by reducing the availability of ACh; 2) the decreased muscarinic tone impairs the hippocampal cognition and HPA axis feedback, and reduces BDNF and neurogenesis; 3) the reduced BDNF and elevated CORT further exacerbate cholinergic functions. Mechanistically, we hypothesize that 1) the effects of stress are mediated via septal GC receptors and/or CRF1 receptors; 2) GC and/or CRF enhance breakdown of available ACh by transcriptional activation of AChE; 3) antidepressants, by up-regulating hippocampal BDNF and enhancing monoamine levels, restore septohippocampal functions. The above hypothesis will be tested using
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electrophysiological recordings in septohippocampal neurons in conjunction with immunocytochemical and in situ hybridization techniques. The proposed research will provide fresh insights into the mechanisms underlying stress-induced changes in brain functions and possibly treatment of associated cognitive deficits. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RELAPSE OF BIPOLAR DISORDER DURING PREGNANCY Principal Investigator & Institution: Viguera, Adele C.; Massachusetts General Hospital 55 Fruit St Boston, Ma 02114 Timing: Fiscal Year 2001; Project Start 28-SEP-1999; Project End 31-AUG-2004 Summary: This Mentored Patient-Oriented RCDA is a resubmission, designed to enhance clinical training and research expertise in the area of psychiatric disorders during pregnancy and the postpartum period. The research aim of this proposal includes a study to evaluate risk for recurrence among pregnant bipolar women. Following-up preliminary findings, morbid risk will be compared quantitatively in women who continue or discontinue mood-stabilizers; recurrence of a first new episode of DSM-IV mania or bipolar depression and its timing from initial assessment are primary outcome measures. Secondary considerations include analyses of associated clinical (demographic, social, prior morbidity) and pharmacological (drug-type, duration of use, mean dose and serum concentration, and rate of discontinuation) predictors of recurrence, as well as the neonatal outcome of infants born to the subjects. The design involves open and clinical, but prospective, single blind, longitudinal followup of parallel groups of women with DSM-IV bipolar disorders who become pregnant and continue vs. discontinue mood-stabilizing medications. The proposal also includes a rich training component. Close supervision is provided by Massachusetts General Hospital co-mentors Lee S. Cohen, M.D. and Ross J. Baldessarini, M.D., with frequent consultation with local and national experts in mood disorders and psychopharmacology research, perinatal psychiatry, obstetrics, reproductive endocrinology, teratology, research ethics, and formal coursework in statistics and research design aimed at satisfying requirements for the MPH degree at Harvard School of Public Health. The awardee is thus assured a critical fund of basic knowledge and practical research experience with clinical, qualitative and quantitative methods required for her research career in women's mental health in pregnancy and the postpartum period--a remarkably underdeveloped area of major clinical and public health significance. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: RESEARCH TRAINING IN CHILD AND ADOLESCENT MENTAL HEALTH Principal Investigator & Institution: Castellanos, Francisco X.; Professor; Psychiatry; New York University School of Medicine 550 1St Ave New York, Ny 10016 Timing: Fiscal Year 2003; Project Start 01-JUL-2003; Project End 30-JUN-2008 Summary: (provided by applicant): This is an application for an Institutional National Research Service Award to support Short-Term Research Training for medical students and to establish a two- to three-year postdoctoral traineeship in children's mental health research at the New York University Child Study Center. The NYU Child Study Center is a division within the Department of Psychiatry of the NYU School of Medicine that was established to facilitate children's mental health research, to disseminate research findings to clinicians, and to provide high-quality training across the professional
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spectrum. Available resources include faculty expertise in pharmacological and psychosocial intervention trials, neuroimaging, longitudinal studies, and assessment of child/adolescent psychopathology. These modalities are currently being applied to externally-supported research programs in anxiety and mood disorders, disruptive behavior disorders, Tourette's disorder, post-traumatic stress disorder, family-based prevention of conduct problems, service utilization for the severely ill and for children in foster care, and community outreach services. Research fellows will select mentors in a research modality as well as in content areas, and pursue their development of advanced research skills with the goal of becoming independent investigators. Trainees' research can take advantage of access to highly diverse patient populations at Bellevue Hospital Center and other clinical settings. We will initially recruit two trainees per year, one a Ph.D. psychologist and one a physician who completed residency training in child and adolescent psychiatry. In the third through fifth years, we will recruit two psychologists and two child and adolescent psychiatrists per year. The overall goals of the program are to train clinical scientists in psychiatry and clinical psychology to conduct empirical research on child mental health problems, and to advance these trainees to productive academic research careers. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: RISK AND PREDICTORS OF POSTPARTUM DEPRESSION Principal Investigator & Institution: Altshuler, Lori L.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2003; Project Start 11-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): The postpartum period is a time of heightened risk for the emergence of psychiatric illness, particularly in women who already have a history of mood disorder. Given the prevalence of depressive disorders during the childbearing years, it is crucial to identify women who are at highest risk for new onset or recurrence of depression during the postpartum period. Identification of those women at greatest risk for postpartum depression may allow for interventions that would limit maternal morbidity associated with untreated postpartum depression. This proposal outlines a multi-institutional collaborative research project (R01) in response to PA-00-074, in which risk for postpartum depression will be evaluated in women with histories of major depressive disorder. Subjects who have had at least one episode of DSM-IV major depression will be followed prospectively from late pregnancy (32-36 weeks gestation) up to six months after delivery using a series of standardized instruments. The primary aims of this investigation are (1) to identify clinical and psychosocial predictors of postpartum depression and functional impairment and (2) to 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
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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: RISK AND PREVENTION OF DEPRESSION IN YOUTH Principal Investigator & Institution: Garber, Judy; Professor; Psychology & Human Development; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 31-MAR-2008 Summary: (provided by applicant): This is a request for an NIH Independent Scientist Award (K02) to enhance the Pl's ability to contribute to the understanding of the processes underlying the development of depressive disorders in children and adolescents and to develop and test interventions aimed at preventing depression in youth. The Pl's research program has evolved from studying psychosocial risk factors that predict depression in children and adolescents, to examining the role of these risk factors as mediators of the link between parent and child psychopathology, to testing a prevention program that targets several of the risk factors identified in the earlier studies. This proposal describes three research programs involving five different but related studies. The first program includes two separate longitudinal studies that examine the contribution of varbus psychosocial factors (e.g., family dysfunction, social feedback, stress) to the development of negative cognitions and depressive disorders in children and adolescents. The second program is comprised of two different investigations of whether decreases in parents' depression as a result of treatment (cognitive-behavioral and/or pharmacotherapy) are associated with changes in their children's psychopathology and functioning, and whether these changes are mediated by improvements in parent-child relationships, negative cognitions, and/or decreases in stressful life events. The last project uses knowledge about risk factors learned from the first two research programs to test a cognitive-behavioral intervention for preventing depression in adolescents at risk for mood disorders due to their having a parent in treatment for depression, and themselves having either a past depressive ecandidatesode or current subsyndromal depressive symptoms. The goal of the career development plan is to expand the candidate's skills in two areas: quantitative methods and prevention science. Because most of the candidate's research is longitudinal, learning state-of-the-art statistical methods (e.g. latent growth curve, linear and nonlinear mixed effects models, survival analysis, structural equations modeling) will broaden the kinds of research questions that can be addressed with both existing and new data. In addition, she will update and expand her knowledge of preventive interventions, particularly cognitive-behavioral approaches, with the aim of further developing and testing the efficacy of programs for preventing depression in high-risk adolescents. This K award will allow the candidate to bridge emcandidaterical research with practice by using basic knowledge about etiology to address the practical problem of preventing the onset and recurrence of the serious public health condition of depression, particularly among those at greatest risk for the disorder. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: SELECTIVE SEROTONERGIC AGENTS Principal Investigator & Institution: Glennon, Richard A.; Professor; Medicinal Chemistry; Virginia Commonwealth University Richmond, Va 232980568
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Timing: Fiscal Year 2001; Project Start 15-FEB-2001; Project End 31-JAN-2005 Summary: Adapted from applicant's abstract): Serotonin (5-hydroxytryptamine; 5-HT) receptors have been implicated in a wide variety of neuropsychiatric disorders including schizophrenia, depression, anxiety, obsessive-compulsive behavior, and panic disorders. The diversity of these implications can be explained, at least in part, by the large number of 5-HT receptor populations that now have been identified: 5-HT1-5-HT7. Many of these seven populations have been shown to consist of subpopulations and at least 20 different subpopulations and splice variants of 5-HT receptors have been cloned. In some instances, the exact role(s) of these 5-HT populations is merely speculative due to the lack of selective sertonergic ligands. Indeed, very few truly subpopulation-selective agonists or antagonists have been developed. The purpose of the present investigation is to develop such agents. Specifically, we propose (a) to explain the 5-HT2A versus 5-HT2C selectivity of spiperone and to develop and test a comprehensive model that might eventually allow the de novo design and synthesis of novel 5-HT2A antagonists, (b) to exploit the first example of a 5-HT6-selective agonist, and (c) to explore a newly identified 5-HT1F ligand. 5-HT2A antagonists may be of value as atypical antipsychotics, there is evidence that 5-HT6 receptors may be involved in psychosis, depression, and mood disorders, and preliminary findings suggest that 5HT1F receptors may play a role in migraine. Although there may be clinical value in developing such agents, their exact utility is far from clear at this time. Hence, a more immediate goal of this application is to develop such agents as tools to further investigate the pharmacologic significance of these receptor populations and to study basic neurochemical mechanisms. We have already identified in the course of our preliminary investigations, (a) a 5-HT2A versus 5-HT2C antagonist (i.e., KML-010), (b) a 5-HT6-selective agonist (i.e., 2-MMT), and (c) a novel 5-HT1F ligand. New analogs of KML-010 will be synthesized and examined in radioligand binding and behavioral studies in order to test a hypothetical model we have formulated to account for the 5HT2A selectivity of spiperone and the lack of selectivity of ketanserin. The 5-HT6 agonist 2-MMT has not been thoroughly investigated, binds only with modest affinity, and likely will have difficulty in penetrating the blood-brain barrier due to its chemical composition. We propose to systematically exploit additional leads we have already identified in an attempt to optimize activity. Radioligand binding and functional assays will be conducted. The 5-HT1F ligand is not selective; we propose to explore its structure-activity relationships and functional activity in an attempt to develop a 5HT1F-selective ligand. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SLEEP AND CHRONOBIOLOGY OF LATE-LIFE DEPRESSION Principal Investigator & Institution: Szuba, Martin P.; Assistant Professor; Psychiatry; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2001; Project Start 15-SEP-1998; Project End 30-JUN-2002 Summary: This application proposes Martin P. Szuba, M.D. for a Mentored Clinical Scientist Development Award at the University of Pennsylvania. The aims of this program include: 1) to support his development into an independent research scientist 2) to support and enhance the applicant's development as an investigator in sleep and chronobiology in the elderly; 3) to develop him for a faculty leadership role in mood disorders at Penn; and 4) to enhance the study of late-life mood disorders at Penn, using a chronobiologic approach. These aims will be structured around a four-part plan: 1) A program of formal academic courses and tutorials aimed at enhancing his research skills. 2) Research training, supervised by Drs. David Dinges and Ira Katz. This training
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will include supervised participation in three ongoing studies of the Center for Sleep and Respiratory Neurobiology and the Clinical Research Center (CRC) in Depression in the Aged: Medical- Psychiatric Co-Morbidity (I. Katz, PI). 3) Performance of a separate research project: The first systematic randomized, double-blind, placebo-controlled treatment trial of the effects of exogenous melatonin administration on sleep, mood, and circadian rhythms in depressed elderly subjects. The specific aims of the study include a thorough evaluation in elderly depressed subjects with insomnia of subjective, behavioral, and physiological indices of sleep, in the laboratory and at home, as well as recording of circadian physiology during an unmasking protocol (constant routine), prior to and following treatment with melatonin or placebo. 4)Preparation, as Principal Investigator, of an independent research grant application. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: SSRI TREATMENT OF PRENATAL COCAINE-INDUCED 5HT DEFICITS Principal Investigator & Institution: Battaglia, George; Professor; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2001; Project Start 01-APR-1993; Project End 31-DEC-2004 Summary: (applicant's abstract): Various mood disorders are being increasingly diagnosed in offspring exposed to cocaine in utero. In humans, impairments in serotonin (5-HT) function are associated with disorders such as anxiety, depression and increased impulsivity and aggression. During the initial funding period, we identified long-term neurochemical and functional impairments in brain 5-HT systems in rat offspring exposed prenatally to cocaine. Thus, the long-term objective of this research is to determine the effectiveness of clinically prescribed serotonin-selective reuptake inhibitors (SSRIs) to treat mood disorders in offspring resulting from prenatal exposure to cocaine. The clinical efficacy of SSRIs is related to their ability to produce neuroadaptive changes in 5-HT systems. This renewal application will determine if clinically used SSRIs, such as paroxetine (Paxil), will be effective in reversing the serotonergic deficits in rats produced by prenatal cocaine exposure. Our HYPOTHESIS is that SSRIs will be effective in restoring brain 5-HT function and producing neuroadaptive changes in 5-HT receptor signal transduction in prenatal cocaineexposed offspring. This proposal will determine the mechanisms responsible for 5-HT impairments and the restoration of 5-HT function by SSRIs in offspring using biochemical, neurochemical and neuroendocrine measures to study pre- and postsynaptic components of 5-HT pathways. Each aim will study the mechanism of neuroadaptive changes in different components of the 5-HT signal transduction pathway due to prenatal cocaine and subsequent postnatal SSRI treatment. Aim 1 will focus on presynaptic 5-HT terminal function; aim 2 will investigate the sensitivity of somatodendritic 5-HT1A autoreceptors on 5-HT cell bodies; and aims 3 & 4 will investigate postsynaptic function of 5-HT1A and 5-HT2A receptor signal transduction systems, respectively. Because neuroendocrine challenge can also be used in humans, the correspondence between neurochemical changes in brain induced changes in 5-HTmediated neuroendocrine responses will provide the foundation to assess prenatal cocaine-induced changes in 5-HT function in human offspring. In addition, our studies will identify the mechanisms mediating SSRI-induced neuroadaptive changes in 5-HT systems in offspring impaired by prenatal cocaine. Data obtained from the proposed studies will be important in predicting the potential efficacy of SSRIs in treating disorders in individuals previously exposed to cocaine in utero. To our knowledge,
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these studies are the first to determine the utility of SSRIs to treat impairments in 5-HT function due to prenatal cocaine exposure. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: STRUCTURAL/TROPHIC HYPOTHESIS FOR ANTIDEPRESSANT ACTIONS Principal Investigator & Institution: Koliatsos, Vassilis E.; Professor; Pathology; Johns Hopkins University 3400 N Charles St Baltimore, Md 21218 Timing: Fiscal Year 2003; Project Start 10-SEP-2003; Project End 31-AUG-2005 Summary: (provided by applicant): Mechanisms of antidepressant drug actions are not clearly understood. In the present application, we propose that antidepressant drugs work via a classical trophic mechanism, i.e. proliferation of terminal branches (sprouting) of central monoamine axons in cortex and the limbic system. We also propose that the molecular signals mediating these structural effects are neurotrophins, e.g. for the serotonin system, the critical signal is brain-derived neurotrophic factor (BDNF). Our experimental design takes a stepwise approach using cellular and molecular methodologies, including transgenic mice. We first evaluate the ability of serotonin (5-HT)- and norepinephrine (NE)-promoting compounds to cause 5-HT and NE sprouting in selected areas of neocortex, hippocampus and the subcortical limbic system. In parallel, we evaluate the role of antidepressants in enhancing neurotrophin expression and transduction in the same areas, focusing on BDNF and 5-HT reuptake inhibitors/enhancersx We subsequently test whether strategies that abolish BDNF expression/binding (such as blocking BDNF with antibodies and scavenging peptides or partially eliminating BDNF with transgenic approaches) inhibit the effects of antidepressants on 5-HT fiber sprouting. Finally, we assess the significance of trophic mechanisms for the mediation of antidepressant effects using BDNF +/- mice in laboratory models of depression. In concert, our proposal pursues a novel hypothesis for the effects of antidepressant drugs which has implications for an understanding of mood disorders as disorders of blunted structural plasticity of central monoamine systems. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: THE CLASSIFICATION OF ANXIETY DISORDER Principal Investigator & Institution: Brown, Timothy A.; Research Associate Professor; Psychology; Boston University Charles River Campus 881 Commonwealth Avenue Boston, Ma 02215 Timing: Fiscal Year 2002; Project Start 01-APR-1984; Project End 30-NOV-2006 Summary: Most empirical evaluation of diagnostic systems of emotional disorders (e.g., DSM-IV) has occurred at the categorical/descriptive level (e.g., diagnostic reliability and comorbidity) or has examined categories in isolation of related disorders. These findings provide little information on the validity of our nosology and the validity of conceptual models of the etiology, nature, and course of emotional disorders. Expanding on our recent work, research in the next project phase will test hypotheses pertaining to structural models of anxiety and mood disorders and trait variables implicated in the etiology, comorbidity, expression, and course of these disorders. Over 1,750 patients will be assessed using the Anxiety Disorders Interview Schedule: Lifetime version and associated instruments of key features of anxiety and mood disorders and measures of core temperament and personality (e.g., negative affect, behavioral inhibition). Dimensional measures of DSM-IV disorder features and personality, collected cross-
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sectionally and longitudinally, will be submitted to structural equation modeling to test competing models of the latent structure of DSM-IV emotional disorders, trait personality constructs, and their interrelationships. These studies will provide the first large- scale comparative evaluations of models of trait vulnerability and the influence of such constructs on the course of emotional disorders. Further analyses will evaluate the generalizability of the DSM-IV structure and its relationships with higher-order personality dimensions across races, sexes, and ages. Longitudinal analyses will examine the covariation of disorder and personality constructs as a function of psychosocial treatment and across two-year follow-up. Collectively, findings will indicate: (a) the shared, and specific dimensions of anxiety and mood disorders; (b) the possible treatment resiliency of higher-order personality dimensions influencing the course of disorders; (c) important reconceptualizations of personality models of emotional disorders; (d) refinements to the diagnostic definitions of emotional disorders and their cross-cultural aspects in DSM-V. This work will enhance and complement biological approaches to these issues by suggesting a more valid and robust set of disorder and personality constructs on which to base investigations such as familial, genetic, and etiologic studies-these data will foster a fuller integration of biological and psychological approaches to the structure and pathogenesis of emotional disorders. Taxometric studies will be conducted on selected DSM-IV disorders and personality constructs to examine whether these phenomena operate on a continuum or as taxa. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TIME COURSE AND POTENTIATION OF FLUOXETIN ACTION Principal Investigator & Institution: Van De Kar, Louis D.; Professor; Pharmacol & Exper Therapeutics; Loyola University Medical Center Lewis Towers, 13Th Fl Chicago, Il 60611 Timing: Fiscal Year 2002; Project Start 14-JAN-2002; Project End 31-DEC-2004 Summary: (provided by applicant) The long-term goal of the proposed studies is to provide novel therapeutic approaches for the treatment of mood disorders that will work more rapidly and more effectively than the currently available medications. The introduction of selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) has revolutionized psychiatry. In addition to their effectiveness in the treatment of depression, SSRIs also have proven effective for the treatment of several mood disorders for which the older medications were ineffective. These disorders include anxiety, obsessive compulsive disorder, aggression, eating disorders and premenstrual syndrome. However, a lag time of about 2-3 weeks exists from the onset of medication until the first signs of improvement appear. This delayed onset of therapeutic effects is a severe problem. Some of the suicides of depressed patients occur during this lag time. Therefore, there is a great need to find therapeutic approaches that will work more rapidly. Studies supporting the parent grant indicate that treatment with SSRIs produces a delayed-onset, homologous desensitization of post-synaptic serotoninlA( 5HT1A) receptors in the hypothalamus. This desensitization is most likely mediated by increased levels of 5-HT in the synapse and the resulting over-activation of postsynaptic receptors. Studies in depressed patients indicate that the therapeutic effectiveness of SSRIs is dependent on maintaining high levels of 5-HT in the synaptic cleft. The 5-HT reuptake mechanism is the primary mechanism terminating the activation of post-synaptic receptors by 5-HT in the synaptic cleft. However, the release of 5-HT from the nerve terminals is highly regulated by inhibitory 5-HT1A autoreceptors on the soma and dendrites of the serotonergic cells in the raphe nuclei and by inhibitory 5-HT1B/1D autoreceptors on the serotonergic nerve terminals in forebrain
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regions. Thus, the overall hypothesis is that during SSRI therapy, the inhibitory influences of 5-HT autoreceptors must be overcome to allow SSRIs to increase the levels of 5-HT in the synaptic cleft. The proposed studies will use in vivo microdialysis approaches to investigate the time courses of changes in both 5-HT1A and 5-HT1B/1D autoreceptors, and thus determine whether these receptors contribute to the delay in onset of fluoxetine-induced increase in extracellular levels of 5-HT in several forebrain regions. In addition, the studies will investigate whether combining fluoxetine with selective 5-HT1A and/or 5-HT1B/1D antagonists will accelerate the fluoxetine-induced increase in extracellular levels of 5-HT. The results of the present studies will provide the scientific foundation for the use of specific autoreceptor antagonists as adjunctive therapy with SSRIs to produce a more rapid and effective therapy of mood disorders. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: TOPOGRAPHIC REGULATION OF RAPHE SEROTONIN CIRCUITS Principal Investigator & Institution: Beck, Sheryl G.; Associate Professor; University of Pennsylvania 3451 Walnut Street Philadelphia, Pa 19104 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The 5-hydroxytryptamine (5-HT, serotonin) neruotransmitter system is implicated in the etiology and treatment of psychiatric mood disorders such as anxiety and depression. Drugs used in the treatment of depression and anxiety are known to have effects on the 5-HT system, such as the serotonin selective reuptake inhibitors (SSRIs) and the azipirones, respectively. Also, the recent development of mice in which certain receptors of the 5-HT neurotransmitter system have been genetically eliminated has provided further evidence that the 5-HT system is important in mood disorders. Mice that have the 5-HT1A receptor eliminated by genetic engineering exhibit increased anxiety and antidepressant-like behavior. Selective "rescue" of forebrain 5-HT1A receptors using gene targeting technology relives the anxiolytic phenotype. The 5-HT system is composed of two primary groups of cell bodies, the dorsal raphe (DR) and median raphe (MR) nuclei. The DR and MR share many features, yet they are distinctive in many ways. Evidence from studies using microdialysis, receptor binding and extracellular recording techniques suggests that there are topographical differences in certain aspects of not only 5-HT synaptic transmission, but also noradrenergic and GABA synaptic transmission in these distinct DR and MR neural circuits. A working hypothesis for the mechanism of action of antidepressants that are serotonin selective reuptake inhibitors (SSRIs) and for the behavioral phenotypes seen in the 5-HT receptor knockout mice is that there is site selective regulation of receptor-mediated responses within the DR and MR circuits. Electrophysiology techniques in brain slice preparations will be used to test this hypothesis in the following Specific Aims. Aim I will identify differences in 5-HT, alpha1-adrenergic and GABA receptor-mediated responses in 5-HT containing cells of the DR and MR and the frontal cortex (DR projection site) and dorsal hippocampus (MR projection site) of the mouse. Aim 2 will compare 5-HT, alpha-adrenergic and GABA neurotransmission in the DR and MR circuits in genetically manipulated mice. Aim 3 will compare 5-HT, alpha-adrenergic and GABA neurotransmission in the DR and MR circuits in mice chronically treated with an SSRI. These experiments will provide important information about the topographical differences in the DR and MR neural circuits and how genetic deletion of 5-HT receptors or antidepressant treatment selectively alters these topographically differences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT OF ADOLESCENT SUICIDE ATTEMPTERS IN DALLAS Principal Investigator & Institution: Emslie, Graham J.; Professor, Chair, and Director; Psychiatry; University of Texas Sw Med Ctr/Dallas Dallas, Tx 753909105 Timing: Fiscal Year 2002; Project Start 12-AUG-2002; Project End 31-JUL-2007 Summary: (provided by applicant): This proposal is to establish an NIMH Research Unit for Pediatric Psychopharmacology and Psychosocial Interventions (RUPP-PI) in Dallas, Texas. Our site, UT Southwestern Medical Center at Dallas, is a major center for research in Affective Disorders, with expertise in the field of efficacy research in children and adolescents with psychiatric disorders. Our team of investigators have successfully worked together on pharmacotherapy (Graham Emslie, Russell Scheffer, Namrata Rao) and cognitive behavior therapy (Graham Emslie, Betsy Kennard, Sunita Stewart) trials with adolescents with mood disorders, and have consistently ranked at the top of recruitment on multi-site trials. The exemplary research protocol targets a major public health issue: although adolescents in this country suffer 2 million suicide attempts annually, no controlled intervention studies for this condition have been conducted. The proposed 5-year study will determine the effectiveness of a multi-modal treatment intervention to prevent additional suicide attempts in 480 depressed adolescents attempters, ages 12 to 18. Eligible subjects will be recruited, carefully assessed, and then randomized equally to two treatment conditions. The Experimental Group will receive a 12-week course of antidepressant medication management (MM); weekly cognitive behavioral therapy adapted for adolescent attempters (CBTASA), and enhanced clinical management (ECM). The Control Group will be referred to a community provider for standard clinical care with additional ECM. Both groups will be assessed at baseline, 4, 8, 12, 16, 20 and 24, 36 and 48 weeks by an independent evaluator blind to treatment assignment. The goal of this study is to determine if the number of suicide attempts, severity of depression, severity of suicidal ideation, and Clinical Global ImpressionsImproved scores differ between the 2 groups at outcome. This exemplary protocol stimulated the formation of a collaborative group of 8 RUPP-PI applicants. By creating the protocol, the group forged an ability to work together. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: TREATMENT OF DRUG DEPENDENCE AND PSYCHIATRIC ILLNESS Principal Investigator & Institution: Weiss, Roger D.; Professor of Psychiatry and Clinical Dir; Mc Lean Hospital (Belmont, Ma) Belmont, Ma 02478 Timing: Fiscal Year 2001; Project Start 20-APR-1997; Project End 31-MAR-2002 Summary: (Applicant's Abstract) The primary aim of this K02 application is to further the applicant's scientific development in the area of treatment of drug dependent patients, particularly those who are "dually diagnosed" with drug abuse and coexisting psychiatric illness. The major hypothesis guiding the applicant's current and planned research is that careful study of the relationship between substance use disorders and specific psychiatric disorders will inform and enhance treatment methods for dually diagnosed patients. This application is designed to strengthen the applicant's involvement in three MDA-funded projects (as PI or Co-PI), as well as several other funded projects as Co-Investigator or Consultant. The following funded projects are currently being pursued by the applicant: 1) a Stage 1 NIDA Behavioral Therapies Development Project to develop a relapse prevention group therapy manual for patients with coexisting bipolar disorder and substance use disorder (NIDA grant, PI); 2) the
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NIDA Collaborative Cocaine Treatment study, a multi-site randomized controlled trial, comparing 4 different behavioral treatments for cocaine dependent outpatients (NIDA grant, PI at the McLean/Massachusetts General Hospital site); and 3) a Stage 1 NIDA Behavioral Therapies Development study to develop and pilot-test a group cognitivebehavioral treatment manual for women with post-traumatic stress disorder and substance use disorder (NIDA grant, Co-PI). The applicant proposes to expand his research capabilities by integrating his clinical research with pre-clinical investigations conducted by investigators with complementary areas of research expertise. He will also be Co-Investigator or Consultant on other studies of comorbid substance use disorder and mood disorders, and consult at the Boston site of the NIDA/VA Medication Development project. Finally, the applicant will mentor young investigators who bring their expertise in other areas (e.g., neuroscience) to bear on drug abuse research projects. 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 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
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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: VULNERABILITY TO DRUG ABUSE IN HIGH RISK YOUTH Principal Investigator & Institution: Gerstein, Dean R.; Research Vice President; National Opinion Research Center 1155 E 60Th St Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 01-APR-1991; Project End 31-MAR-2003 Summary: (Applicant's Abstract) This proposed study is the continuation of a prospective five-year longitudinal study of offspring in families with substance-abusing parents, depressed parents, and parents without a diagnosable psychiatric disorder in the Minneapolis-St. Paul metropolitan area. The study collected annual data from parents and offspring since 1992, following sample recruitment and classification. The first funding cycle of this study concluded March 31, 1996, with a 97.3 % follow-up rate. We propose a continuation study using a four-wave prospective cohort design that follows the adolescents who participated in the first cycle but who will be 14 to 21 years of age in 1997. This proposed study has as its overall goal to develop and test models that assess the effects of parental substance abuse and depression, adolescent substance use and depression, and the mediating effects of personal resources, familial and extrafamilial factors on the trajectories, transitions, and turning points that define the movement from late adolescence to young adulthood. And by integrating these followup data with data from the first cycle, the study will examine developmental trajectories involving parental psychopathology, drug use, deviant behavior, and mental health among offspring from late childhood through the stages of adolescence into young adulthood. Self administered questionnaires will be completed by all adolescents (N=848 in 585 families) at approximately 12-month intervals during the first four years of the study, and by all parents (N=881 parents) during the first three years of the study. In addition, structured psychiatric interviews using UM-CIDI will be conducted with adolescents in Years 2 and 4, and with parents using the substance use disorder and mood disorders modules in Year 2. These diagnostic data, along with annual selfadministered questionnaires filled out by parents and adolescents that cover a wide range of topics (family and parent-child relations, experiences, and changes; peer behaviors and relations; life events and transitions, such as school and work experiences; drug and alcohol use, and criminal behavior; social support; coping mechanisms such as self-esteem and mastery; and depressive symptomatology) will provide abundant information with which to assess numerous life transitions-especially role transitions that accompany the movement to young adulthood--and adaptations, behavioral problems such as drug use or alcohol abuse, and psychiatric disorders in late adolescence and young adulthood. 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
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
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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 “mood disorders” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for mood disorders in the PubMed Central database: •
Detection and Sequence Analysis of Borna Disease Virus p24 RNA from Peripheral Blood Mononuclear Cells of Patients with Mood Disorders or Schizophrenia and of Blood Donors. by Iwata Y, Takahashi K, Peng X, Fukuda K, Ohno K, Ogawa T, Gonda K, Mori N, Niwa SI, Shigeta S.; 1998 Dec; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=110530
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Fine-scale mapping of a locus for severe bipolar mood disorder on chromosome 18p11.3 in the Costa Rican population. by McInnes LA, Service SK, Reus VI, Barnes G, Charlat O, Jawahar S, Lewitzky S, Yang Q, Duong Q, Spesny M, Araya C, Araya X, Gallegos A, Meza L, Molina J, Ramirez R, Mendez R, Silva S, Fournier E, Batki SL, Mathews CA, Neylan T, Glatt CE, Escamilla MA, Luo D, Gajiwala P, Song T, Crook S, Nguyen JB, Roche E, Meyer JM, Leon P, Sandkuijl LA, Freimer NB, Chen H.; 2001 Sep 25; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=58756
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Glial reduction in the subgenual prefrontal cortex in mood disorders. by Ongur D, Drevets WC, Price JL.; 1998 Oct 27; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=23786
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Increasing sophistication of the pharmacotherapy of mood disorders. by Joffe RT.; 2002 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161637
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Mood Disorders in Women. by Calhoun L.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161737
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The Mood Disorder Questionnaire improves recognition of bipolar disorder in psychiatric care. by Isometsa E, Suominen K, Mantere O, Valtonen H, Leppamaki S, Pippingskold M, Arvilommi P.; 2003; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=169168
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Thyroid hormone treatment for lithium-induced thyroid dysfunction in mood disorder. by Ramasubbu R.; 2003 Mar; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161734
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Treating mood disorders. by Joffe RT.; 2003 Jan; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=161721
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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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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 mood disorders, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “mood disorders” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for mood disorders (hyperlinks lead to article summaries): •
A clinical monitoring form for mood disorders. Author(s): Sachs GS, Guille C, McMurrich SL. Source: Bipolar Disorders. 2002 October; 4(5): 323-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12479665&dopt=Abstract
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A comparison of individual and family psychology of adolescents with chronic fatigue syndrome, rheumatoid arthritis, and mood disorders. Author(s): Gray D, Parker-Cohen NY, White T, Clark ST, Seiner SH, Achilles J, McMahon WM. Source: Journal of Developmental and Behavioral Pediatrics : Jdbp. 2001 August; 22(4): 234-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11530896&dopt=Abstract
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A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. Author(s): Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA, Luckenbaugh DA, Cora-Ocatelli G, Leverich GS, Post RM. Source: Journal of Clinical Psychopharmacology. 2000 December; 20(6): 607-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11106131&dopt=Abstract
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A slow wave investigation of working memory biases in mood disorders. Author(s): Deldin PJ, Deveney CM, Kim AS, Casas BR, Best JL. Source: Journal of Abnormal Psychology. 2001 May; 110(2): 267-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11358021&dopt=Abstract
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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 spectrum model for mood disorders: a useful approach in clinical psychiatry in search of an assessment methodology. Author(s): Cassano GB, Pini S. Source: Epidemiol Psichiatr Soc. 2000 July-September; 9(3): 156-62. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11094837&dopt=Abstract
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Aetiology and pathogenesis of mood disorders. Author(s): Sher L. Source: Qjm : Monthly Journal of the Association of Physicians. 2003 April; 96(4): 309-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12651976&dopt=Abstract
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Aggression and violence in mood disorders. Author(s): Weisbrot DM, Ettinger AB. Source: Child Adolesc Psychiatr Clin N Am. 2002 July; 11(3): 649-71, Xi. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12222088&dopt=Abstract
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Altered levels of Reelin and its isoforms in schizophrenia and mood disorders. Author(s): Fatemi SH, Kroll JL, Stary JM. Source: Neuroreport. 2001 October 29; 12(15): 3209-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711858&dopt=Abstract
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Altered levels of the synaptosomal associated protein SNAP-25 in hippocampus of subjects with mood disorders and schizophrenia. Author(s): Fatemi SH, Earle JA, Stary JM, Lee S, Sedgewick J. Source: Neuroreport. 2001 October 29; 12(15): 3257-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11711867&dopt=Abstract
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Anticonvulsants in the treatment of mood disorders: assessing current and future roles. Author(s): Gilmer WS. Source: Expert Opinion on Pharmacotherapy. 2001 October; 2(10): 1597-608. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11825302&dopt=Abstract
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Antidepressant drugs and cytokines in mood disorders. Author(s): Nishida A, Hisaoka K, Zensho H, Uchitomi Y, Morinobu S, Yamawaki S. Source: International Immunopharmacology. 2002 November; 2(12): 1619-26. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12469936&dopt=Abstract
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Anxiety disorders comorbidity in mood disorder subgroups: data from a mood disorders clinic. Author(s): Yerevanian BI, Koek RJ, Ramdev S. Source: Journal of Affective Disorders. 2001 December; 67(1-3): 167-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869764&dopt=Abstract
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Association analysis of a functional G protein beta3 subunit gene polymorphism (C825T) in mood disorders. Author(s): Lin CN, Tsai SJ, Hong CJ. Source: Neuropsychobiology. 2001; 44(3): 118-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11586049&dopt=Abstract
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Association study of C825T polymorphism of the G-protein b3 subunit gene with schizophrenia and mood disorders. Author(s): Kunugi H, Kato T, Fukuda R, Tatsumi M, Sakai T, Nanko S. Source: Journal of Neural Transmission (Vienna, Austria : 1996). 2002 February; 109(2): 213-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12075862&dopt=Abstract
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Association study of MAO-A, COMT, 5-HT2A, DRD2, and DRD4 polymorphisms with illness time course in mood disorders. Author(s): Cusin C, Serretti A, Lattuada E, Lilli R, Lorenzi C, Smeraldi E. Source: American Journal of Medical Genetics. 2002 May 8; 114(4): 380-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992560&dopt=Abstract
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Association study of the short tandem repeat in the 5' upstream region of the cholecystokinin gene with mood disorders in the Japanese population. Author(s): Hattori E, Yamada K, Ebihara M, Toyota T, Nankai M, Shibuya H, Yoshikawa T. Source: American Journal of Medical Genetics. 2002 July 8; 114(5): 523-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116188&dopt=Abstract
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Borna disease virus-specific circulating immune complexes, antigenemia, and free antibodies--the key marker triplet determining infection and prevailing in severe mood disorders. Author(s): Bode L, Reckwald P, Severus WE, Stoyloff R, Ferszt R, Dietrich DE, Ludwig H. Source: Molecular Psychiatry. 2001 July; 6(4): 481-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11443538&dopt=Abstract
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Bupropion in the long-term treatment of cyclic mood disorders: mood stabilizing effects. Author(s): Wright G, Galloway L, Kim J, Dalton M, Miller L, Stern W. Source: The Journal of Clinical Psychiatry. 1985 January; 46(1): 22-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2856918&dopt=Abstract
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Changes in the regression slope correlating between urinary contents of alpha-1microglobulin and ulinastatin and its relation to severity in mood disorders. Author(s): Shikimi T, Uegaki J, Inagaki T, Mitsuoka S. Source: Nursing & Health Sciences. 2001 June; 3(2): 95-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11882184&dopt=Abstract
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Changing perspectives on mood disorders in children. Author(s): Volkmar FR. Source: The American Journal of Psychiatry. 2002 June; 159(6): 893-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12042173&dopt=Abstract
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Chronobiological basis of female-specific mood disorders. Author(s): Parry BL, Newton RP. Source: Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology. 2001 November; 25(5 Suppl): S102-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682284&dopt=Abstract
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Clinical significance of plasma levels of clomipramine, its hydroxylated and desmethylated metabolites: prediction of clinical outcome in mood disorders using discriminant analysis of therapeutic drug monitoring data. Author(s): Noguchi T, Shimoda K, Takahashi S. Source: Journal of Affective Disorders. 1993 December; 29(4): 267-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8126313&dopt=Abstract
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Color sensitivity and mood disorders: biology or metaphor? Author(s): Barrick CB, Taylor D, Correa EI. Source: Journal of Affective Disorders. 2002 February; 68(1): 67-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869784&dopt=Abstract
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Combining genetic and genomic approaches to study mood disorders. Author(s): Sibille E, Hen R. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2001 December; 11(6): 413-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11704418&dopt=Abstract
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Comorbid anxiety and mood disorders among persons with social anxiety disorder. Author(s): Erwin BA, Heimberg RG, Juster H, Mindlin M. Source: Behaviour Research and Therapy. 2002 January; 40(1): 19-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11762424&dopt=Abstract
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Comorbid mood disorders and medical illness: a Food and Drug Administration perspective. Author(s): Laughren TP. Source: Biological Psychiatry. 2003 August 1; 54(3): 195-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893095&dopt=Abstract
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Comorbid substance use reduces the health care contacts of suicide attempters with schizophrenia spectrum or mood disorders. Author(s): Suominen KH, Isometsa ET, Lonnqvist JK. Source: Schizophrenia Bulletin. 2002; 28(4): 637-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12795496&dopt=Abstract
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Continuation and maintenance pharmacotherapy for unipolar and bipolar mood disorders. Author(s): Solomon DA, Bauer MS. Source: The Psychiatric Clinics of North America. 1993 September; 16(3): 515-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8415235&dopt=Abstract
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Coping style of substance-abuse patients: effects of anxiety and mood disorders on coping change. Author(s): Franken IH, Hendriks VM, Haffmans PM, van der Meer CW. Source: Journal of Clinical Psychology. 2001 March; 57(3): 299-306. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11241361&dopt=Abstract
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Corticosteroid-induced psychotic and mood disorders: diagnosis defined by DSM-IV and clinical pictures. Author(s): Wada K, Yamada N, Sato T, Suzuki H, Miki M, Lee Y, Akiyama K, Kuroda S. Source: Psychosomatics. 2001 November-December; 42(6): 461-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815680&dopt=Abstract
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Creativity and mood disorders in nineteenth-century asylum patients. Author(s): King LJ, Eckerman NL. Source: J Med Biogr. 2001 August; 9(3): 167-74. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11466518&dopt=Abstract
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CSF thyrotropin-releasing hormone concentrations differ in patients with schizoaffective disorder from patients with schizophrenia or mood disorders. Author(s): Sharma RP, Martis B, Rosen C, Jonalagadda J, Nemeroff CB, Bissette G. Source: Journal of Psychiatric Research. 2001 September-October; 35(5): 287-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11591431&dopt=Abstract
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Current and lifetime comorbidity of the DSM-IV anxiety and mood disorders in a large clinical sample. Author(s): Brown TA, Campbell LA, Lehman CL, Grisham JR, Mancill RB. Source: Journal of Abnormal Psychology. 2001 November; 110(4): 585-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11727948&dopt=Abstract
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Decreased cerebral haemodynamic response to cognitive and physiological tasks in mood disorders as shown by near-infrared spectroscopy. Author(s): Matsuo K, Kato N, Kato T. Source: Psychological Medicine. 2002 August; 32(6): 1029-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12214784&dopt=Abstract
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Depression and Bipolar Support Alliance consensus statement on the unmet needs in diagnosis and treatment of mood disorders in late life. Author(s): Charney DS, Reynolds CF 3rd, Lewis L, Lebowitz BD, Sunderland T, Alexopoulos GS, Blazer DG, Katz IR, Meyers BS, Arean PA, Borson S, Brown C, Bruce ML, Callahan CM, Charlson ME, Conwell Y, Cuthbert BN, Devanand DP, Gibson MJ, Gottlieb GL, Krishnan KR, Laden SK, Lyketsos CG, Mulsant BH, Niederehe G, Olin JT, Oslin DW, Pearson J, Persky T, Pollock BG, Raetzman S, Reynolds M, Salzman C, Schulz R, Schwenk TL, Scolnick E, Unutzer J, Weissman MM, Young RC; Depression and Bipolar Support Alliance. Source: Archives of General Psychiatry. 2003 July; 60(7): 664-72. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860770&dopt=Abstract
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Detecting mood disorders in men diagnosed with cancer who seek semen cryopreservation: a chance to improve service. Author(s): Roopnarinesingh R, Keane D, Harrison R. Source: Ir Med J. 2003 April; 96(4): 104, 106-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793470&dopt=Abstract
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Detection and sequence analysis of borna disease virus p24 RNA from peripheral blood mononuclear cells of patients with mood disorders or schizophrenia and of blood donors. Author(s): Iwata Y, Takahashi K, Peng X, Fukuda K, Ohno K, Ogawa T, Gonda K, Mori N, Niwa S, Shigeta S. Source: Journal of Virology. 1998 December; 72(12): 10044-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9811743&dopt=Abstract
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Developing novel treatments for mood disorders: accelerating discovery. Author(s): Tamminga CA, Nemeroff CB, Blakely RD, Brady L, Carter CS, Davis KL, Dingledine R, Gorman JM, Grigoriadis DE, Henderson DC, B Innis RB, Killen J, Laughren TP, McDonald WM, M Murphy GM Jr, Paul SM, Rudorfer MV, Sausville E, Schatzberg AF, Scolnick EM, Suppes T. Source: Biological Psychiatry. 2002 September 15; 52(6): 589-609. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361670&dopt=Abstract
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Development and natural history of mood disorders. Author(s): Costello EJ, Pine DS, Hammen C, March JS, Plotsky PM, Weissman MM, Biederman J, Goldsmith HH, Kaufman J, Lewinsohn PM, Hellander M, Hoagwood K, Koretz DS, Nelson CA, Leckman JF. Source: Biological Psychiatry. 2002 September 15; 52(6): 529-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361667&dopt=Abstract
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Diagnosis and treatment of mood disorders in patients with rheumatic disease. Author(s): Alpay M, Cassem EH. Source: Annals of the Rheumatic Diseases. 2000 January; 59(1): 2-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10627418&dopt=Abstract
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Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Author(s): Gianfrancesco F, Grogg A, Mahmoud R, Wang RH, Meletiche D. Source: Clinical Therapeutics. 2003 April; 25(4): 1150-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12809963&dopt=Abstract
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Differential prevalence of cigarette smoking in patients with schizophrenic vs mood disorders. Author(s): Diwan A, Castine M, Pomerleau CS, Meador-Woodruff JH, Dalack GW. Source: Schizophrenia Research. 1998 September 7; 33(1-2): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9783351&dopt=Abstract
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Differentiating childhood-onset schizophrenia from psychotic mood disorders. Author(s): Calderoni D, Wudarsky M, Bhangoo R, Dell ML, Nicolson R, Hamburger SD, Gochman P, Lenane M, Rapoport JL, Leibenluft E. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2001 October; 40(10): 1190-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589532&dopt=Abstract
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Disability in schizophrenia and mood disorders in a developing country. Author(s): Rahman MB, Indran SK. Source: Social Psychiatry and Psychiatric Epidemiology. 1997 October; 32(7): 387-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9383969&dopt=Abstract
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Do adverse life events and mood disorders influence delayed presentation of breast cancer? Author(s): Burgess CC, Ramirez AJ, Smith P, Richards MA. Source: Journal of Psychosomatic Research. 2000 February; 48(2): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10719134&dopt=Abstract
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Dopamine D2 receptor gene not associated with symptomatology of mood disorders. Author(s): Serretti A, Smeraldi E. Source: American Journal of Medical Genetics. 1999 August 20; 88(4): 294-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10402492&dopt=Abstract
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Dopamine receptor D2 and D4 genes, GABA(A) alpha-1 subunit genes and response to lithium prophylaxis in mood disorders. Author(s): Serretti A, Lilli R, Lorenzi C, Franchini L, Di Bella D, Catalano M, Smeraldi E. Source: Psychiatry Research. 1999 July 30; 87(1): 7-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512150&dopt=Abstract
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Dopamine receptor D4 gene is associated with delusional symptomatology in mood disorders. Author(s): Serretti A, Macciardi F, Cusin C, Lattuada E, Lilli R, Smeraldi E. Source: Psychiatry Research. 1998 August 17; 80(2): 129-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754691&dopt=Abstract
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Duration between onset and time of obtaining initial treatment among people with anxiety and mood disorders: an international survey of members of mental health patient advocate groups. Author(s): Christiana JM, Gilman SE, Guardino M, Mickelson K, Morselli PL, Olfson M, Kessler RC. Source: Psychological Medicine. 2000 May; 30(3): 693-703. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10883723&dopt=Abstract
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Eating and mood disorders in young children. Author(s): DiNicola VF, Roberts N, Oke L. Source: The Psychiatric Clinics of North America. 1989 December; 12(4): 873-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2690030&dopt=Abstract
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ECT for the treatment of mood disorders in cancer patients. Author(s): Beale MD, Kellner CH, Parsons PJ. Source: Convuls Ther. 1997 December; 13(4): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9437566&dopt=Abstract
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Elevated sorbitol concentration in the cerebrospinal fluid of patients with mood disorders. Author(s): Regenold WT, Kling MA, Hauser P. Source: Psychoneuroendocrinology. 2000 August; 25(6): 593-606. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10840171&dopt=Abstract
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Epidemiology of mood disorders: a community survey in Florence. Author(s): Faravelli C, Guerrini Degl'Innocenti B, Aiazzi L, Incerpi G, Pallanti S. Source: Journal of Affective Disorders. 1990 October; 20(2): 135-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2148328&dopt=Abstract
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First isolates of infectious human Borna disease virus from patients with mood disorders. Author(s): Bode L, Durrwald R, Rantam FA, Ferszt R, Ludwig H. Source: Molecular Psychiatry. 1996 July; 1(3): 200-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9118344&dopt=Abstract
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Inverse relationship of peripheral thyrotropin-stimulating hormone levels to brain activity in mood disorders. Author(s): Marangell LB, Ketter TA, George MS, Pazzaglia PJ, Callahan AM, Parekh P, Andreason PJ, Horwitz B, Herscovitch P, Post RM. Source: The American Journal of Psychiatry. 1997 February; 154(2): 224-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9016272&dopt=Abstract
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Lithium in the treatment of mood disorders. Author(s): Stern R. Source: The New England Journal of Medicine. 1995 January 12; 332(2): 127-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7990900&dopt=Abstract
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Lithium in the treatment of mood disorders. Author(s): Price LH, Heninger GR. Source: The New England Journal of Medicine. 1994 September 1; 331(9): 591-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8047085&dopt=Abstract
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Lithium-treated mood disorders, paroxysmal rhinorrhea, and mesial temporal lobe epilepsy. Author(s): Berner J. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1999 Summer; 11(3): 414-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440025&dopt=Abstract
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Longitudinal course of mood disorders following traumatic brain injury. Author(s): Robinson RG, Jorge R. Source: Archives of General Psychiatry. 2002 January; 59(1): 23-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11779277&dopt=Abstract
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Long-term treatment of mood disorders in schizophrenia. Author(s): Azorin JM. Source: Acta Psychiatrica Scandinavica. Supplementum. 1995; 388: 20-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7541599&dopt=Abstract
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Long-term use of benzodiazepines: tolerance, dependence and clinical problems in anxiety and mood disorders. Author(s): Michelini S, Cassano GB, Frare F, Perugi G. Source: Pharmacopsychiatry. 1996 July; 29(4): 127-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8858711&dopt=Abstract
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Lower serum albumin levels in patients with mood disorders. Author(s): Huang TL. Source: Chang Gung Med J. 2002 August; 25(8): 509-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12392362&dopt=Abstract
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Lowest serum cholesterol values are associated with depressive symptoms but not with mood disorders. Author(s): Rozzini R, Sabatini T, Trabucchi M. Source: International Journal of Geriatric Psychiatry. 2003 May; 18(5): 457-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766924&dopt=Abstract
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Modern tricyclic antidepressant drugs are hardly distinguishable in efficacy or safety for treatment of depressive mood disorders in controlled clinical trials. Author(s): Glassman AH, Davis JM. Source: Journal of Clinical Psychopharmacology. 1993 August; 13(4): 296-9. Erratum In: J Clin Psychopharmacol 1994 Aug; 14(4): 293. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8376622&dopt=Abstract
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Molecular analysis, mutation screening, and association study of adenylate cyclase type 9 gene (ADCY9) in mood disorders. Author(s): Toyota T, Hattori E, Meerabux J, Yamada K, Saito K, Shibuya H, Nankai M, Yoshikawa T. Source: American Journal of Medical Genetics. 2002 January 8; 114(1): 84-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11840511&dopt=Abstract
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Mood disorders among mothers of infants admitted to a mothercraft hospital. Author(s): Barnett B, Lockhart K, Bernard D, Manicavasagar V, Dudley M. Source: Journal of Paediatrics and Child Health. 1993 August; 29(4): 270-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8373672&dopt=Abstract
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Mood disorders and allostatic load. Author(s): McEwen BS. Source: Biological Psychiatry. 2003 August 1; 54(3): 200-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893096&dopt=Abstract
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Mood disorders and cancer: a National Cancer Institute perspective. Author(s): Croyle RT, Rowland JH. Source: Biological Psychiatry. 2003 August 1; 54(3): 191-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893094&dopt=Abstract
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Mood disorders and chronic obstructive pulmonary disease: current research and future needs. Author(s): Clary GL, Palmer SM, Doraiswamy PM. Source: Current Psychiatry Reports. 2002 June; 4(3): 213-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003685&dopt=Abstract
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Mood disorders and medical illness: a major public health problem. Author(s): Evans DL, Charney DS. Source: Biological Psychiatry. 2003 August 1; 54(3): 177-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893090&dopt=Abstract
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Mood disorders and suicide. Author(s): Nierenberg AA, Gray SM, Grandin LD. Source: The Journal of Clinical Psychiatry. 2001; 62 Suppl 25: 27-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11765092&dopt=Abstract
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Mood disorders following traumatic brain injury. Author(s): Jorge R, Robinson RG. Source: Neurorehabilitation. 2002; 17(4): 311-24. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12547979&dopt=Abstract
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Mood disorders in children and adolescents: an epidemiologic perspective. Author(s): Kessler RC, Avenevoli S, Ries Merikangas K. Source: Biological Psychiatry. 2001 June 15; 49(12): 1002-14. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430842&dopt=Abstract
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Mood disorders in children and adolescents: an NIMH perspective. Author(s): Hyman SE. Source: Biological Psychiatry. 2001 June 15; 49(12): 962-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430838&dopt=Abstract
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Mood disorders in children and adolescents: psychopharmacological treatment. Author(s): Emslie GJ, Mayes TL. Source: Biological Psychiatry. 2001 June 15; 49(12): 1082-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11430850&dopt=Abstract
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Mood disorders in late life: a patient's perspective. Author(s): Reynolds MM. Source: Biological Psychiatry. 2002 August 1; 52(3): 148-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12182920&dopt=Abstract
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Mood disorders in patients with epilepsy: epidemiology and management. Author(s): Harden CL, Goldstein MA. Source: Cns Drugs. 2002; 16(5): 291-302. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994019&dopt=Abstract
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Mood disorders. Effective management of major depressive disorder in the geriatric patient. Author(s): Evers MM, Marin DB. Source: Geriatrics. 2002 October; 57(10): 36-40; Quiz 41. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12391798&dopt=Abstract
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Mood disorders: review of current diagnostic systems. Author(s): Paykel ES. Source: Psychopathology. 2002 March-June; 35(2-3): 94-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12145491&dopt=Abstract
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Mood disorders: treatment-induced changes in brain neurochemistry and structure. Author(s): Glitz DA, Manji HK, Moore GJ. Source: Semin Clin Neuropsychiatry. 2002 October; 7(4): 269-80. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382209&dopt=Abstract
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Mood disorders--new definitions, treatment directions, and understanding. Author(s): Grof P. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 March; 47(2): 123-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926073&dopt=Abstract
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Mortality of patients with mood disorders: follow-up over 34-38 years. Author(s): Angst F, Stassen HH, Clayton PJ, Angst J. Source: Journal of Affective Disorders. 2002 April; 68(2-3): 167-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12063145&dopt=Abstract
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National Depressive and Manic-Depressive Association consensus statement on the use of placebo in clinical trials of mood disorders. Author(s): Charney DS, Nemeroff CB, Lewis L, Laden SK, Gorman JM, Laska EM, Borenstein M, Bowden CL, Caplan A, Emslie GJ, Evans DL, Geller B, Grabowski LE, Herson J, Kalin NH, Keck PE Jr, Kirsch I, Krishnan KR, Kupfer DJ, Makuch RW, Miller FG, Pardes H, Post R, Reynolds MM, Roberts L, Rosenbaum JF, Rosenstein DL, Rubinow DR, Rush AJ, Ryan ND, Sachs GS, Schatzberg AF, Solomon S; Consensus Development Panel. Source: Archives of General Psychiatry. 2002 March; 59(3): 262-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11879164&dopt=Abstract
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Natural history and preventative treatment of recurrent mood disorders. Author(s): Frank E, Thase ME. Source: Annual Review of Medicine. 1999; 50: 453-68. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10073289&dopt=Abstract
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Neuroimaging abnormalities in the amygdala in mood disorders. Author(s): Drevets WC. Source: Annals of the New York Academy of Sciences. 2003 April; 985: 420-44. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12724175&dopt=Abstract
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Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders. Author(s): Drevets WC, Ongur D, Price JL. Source: Molecular Psychiatry. 1998 May; 3(3): 220-6, 190-1. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9672897&dopt=Abstract
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Neuroimaging and neuropathological studies of depression: implications for the cognitive-emotional features of mood disorders. Author(s): Drevets WC. Source: Current Opinion in Neurobiology. 2001 April; 11(2): 240-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11301246&dopt=Abstract
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Neuroimaging in late-life mood disorders. Author(s): Kumar A, Miller D. Source: Clin Neurosci. 1997; 4(1): 8-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9056117&dopt=Abstract
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Neuroimaging studies of mood disorders. Author(s): Drevets WC. Source: Biological Psychiatry. 2000 October 15; 48(8): 813-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063977&dopt=Abstract
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Neurological hard signs in schizophrenia and major mood disorders. Author(s): Kinney DK, Yurgelun-Todd DA, Woods BT. Source: The Journal of Nervous and Mental Disease. 1993 March; 181(3): 202-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8445381&dopt=Abstract
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Neuronal nicotinic receptor inhibition for treating mood disorders: preliminary controlled evidence with mecamylamine. Author(s): Shytle RD, Silver AA, Sheehan KH, Sheehan DV, Sanberg PR. Source: Depression and Anxiety. 2002; 16(3): 89-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12415531&dopt=Abstract
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Neuronal plasticity and survival in mood disorders. Author(s): Duman RS, Malberg J, Nakagawa S, D'Sa C. Source: Biological Psychiatry. 2000 October 15; 48(8): 732-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063970&dopt=Abstract
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Neuroplasticity and cellular resilience in mood disorders. Author(s): Manji HK, Moore GJ, Rajkowska G, Chen G. Source: Molecular Psychiatry. 2000 November; 5(6): 578-93. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11126389&dopt=Abstract
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Neuropsychologic impairments in bipolar and unipolar mood disorders on the CANTAB neurocognitive battery. Author(s): Sweeney JA, Kmiec JA, Kupfer DJ. Source: Biological Psychiatry. 2000 October 1; 48(7): 674-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032979&dopt=Abstract
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Neurotransmitter receptor-mediated activation of G-proteins in brains of suicide victims with mood disorders: selective supersensitivity of alpha(2A)-adrenoceptors. Author(s): Gonzalez-Maeso J, Rodriguez-Puertas R, Meana JJ, Garcia-Sevilla JA, Guimon J. Source: Molecular Psychiatry. 2002; 7(7): 755-67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12192620&dopt=Abstract
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Newer anticonvulsants: dosing strategies and cognition in treating patients with mood disorders and epilepsy. Author(s): Meador KJ. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 8: 30-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892539&dopt=Abstract
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No association between serotonin-2A receptor gene polymorphism and psychotic symptomatology of mood disorders. Author(s): Serretti A, Lilli R, Lorenzi C, Smeraldi E. Source: Psychiatry Research. 1999 June 30; 86(3): 203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10482339&dopt=Abstract
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No association of two missense variations of the benzodiazepine receptor (peripheral) gene and mood disorders in a Japanese sample. Author(s): Kurumaji A, Nomoto H, Yamada K, Yoshikawa T, Toru M. Source: American Journal of Medical Genetics. 2001 March 8; 105(2): 172-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11304832&dopt=Abstract
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Norepinephrine and selective norepinephrine reuptake inhibitors in depression and mood disorders: their pivotal roles. Author(s): Blier P. Source: Journal of Psychiatry & Neuroscience : Jpn. 2001; 26 Suppl: S1-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11590963&dopt=Abstract
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Nosology of chronic mood disorders. Author(s): First MB, Donovan S, Frances A. Source: The Psychiatric Clinics of North America. 1996 March; 19(1): 29-39. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8677218&dopt=Abstract
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Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS). Author(s): George MS, Nahas Z, Li X, Kozel FA, Anderson B, Yamanaka K, Chae JH, Foust MJ. Source: Semin Clin Neuropsychiatry. 2002 October; 7(4): 293-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382211&dopt=Abstract
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Nuclear magnetic resonance spectroscopy: new insights into the pathophysiology of mood disorders. Author(s): Soares JC, Krishnan KR, Keshavan MS. Source: Depression. 1996; 4(1): 14-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9160650&dopt=Abstract
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Obsessive compulsive disorder and mood disorders: a family study. Author(s): Sciuto G, Pasquale L, Bellodi L. Source: American Journal of Medical Genetics. 1995 December 18; 60(6): 475-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8825883&dopt=Abstract
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Olanzapine for corticosteroid-induced mood disorders. Author(s): Budur K, Pozuelo L. Source: Psychosomatics. 2003 July-August; 44(4): 353. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832608&dopt=Abstract
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Olanzapine therapy in treatment-resistant psychotic mood disorders: a long-term follow-up study. Author(s): Narendran R, Young CM, Valenti AM, Pristach CA, Pato MT, Grace JJ. Source: The Journal of Clinical Psychiatry. 2001 July; 62(7): 509-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11488360&dopt=Abstract
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Olanzapine treatment of corticosteroid-induced mood disorders. Author(s): Goldman LS, Goveas J. Source: Psychosomatics. 2002 November-December; 43(6): 495-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444234&dopt=Abstract
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Online empathy for mood disorders: patients turn to internet support groups. Author(s): Lamberg L. Source: Jama : the Journal of the American Medical Association. 2003 June 18; 289(23): 3073-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813097&dopt=Abstract
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Onset of binge eating, dieting, obesity, and mood disorders among subjects seeking treatment for binge eating disorder. Author(s): Mussell MP, Mitchell JE, Weller CL, Raymond NC, Crow SJ, Crosby RD. Source: The International Journal of Eating Disorders. 1995 May; 17(4): 395-401. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7620480&dopt=Abstract
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Organic solvent exposure, mood disorders, and cancer risk. An hypothesis. Author(s): Frentzel-Beyme R. Source: Med Lav. 1995 May-June; 86(3): 284-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7565295&dopt=Abstract
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Outcome for adjustment disorder with depressed mood: comparison with other mood disorders. Author(s): Jones R, Yates WR, Williams S, Zhou M, Hardman L. Source: Journal of Affective Disorders. 1999 September; 55(1): 55-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10512607&dopt=Abstract
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Overview of mood disorders: diagnosis, classification, and management. Author(s): Fawcett J. Source: Clinical Chemistry. 1994 February; 40(2): 273-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8313608&dopt=Abstract
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Oxcarbazepine for mood disorders. Author(s): Nasr S. Source: The American Journal of Psychiatry. 2002 October; 159(10): 1793. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12359694&dopt=Abstract
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Pharmacogenetics of lithium prophylaxis in mood disorders: analysis of COMT, MAO-A, and Gbeta3 variants. Author(s): Serretti A, Lorenzi C, Lilli R, Mandelli L, Pirovano A, Smeraldi E. Source: American Journal of Medical Genetics. 2002 May 8; 114(4): 370-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992559&dopt=Abstract
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Pharmacologic treatment of mood disorders in acquired immune deficiency syndrome (AIDS). Author(s): Klesmer J, Badescu R. Source: Current Psychiatry Reports. 2002 June; 4(3): 222-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003686&dopt=Abstract
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Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders. Author(s): Bellivier F, Szoke A, Henry C, Lacoste J, Bottos C, Nosten-Bertrand M, Hardy P, Rouillon F, Launay JM, Laplanche JL, Leboyer M. Source: Biological Psychiatry. 2000 August 15; 48(4): 319-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10960164&dopt=Abstract
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Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Author(s): Rajkowska G. Source: Biological Psychiatry. 2000 October 15; 48(8): 766-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11063973&dopt=Abstract
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Predicting mood disorders in breast cancer patients. Author(s): Morasso G, Costantini M, Viterbori P, Bonci F, Del Mastro L, Musso M, Garrone O, Venturini M. Source: European Journal of Cancer (Oxford, England : 1990). 2001 January; 37(2): 21623. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11166149&dopt=Abstract
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Predicting response to lithium in mood disorders: role of genetic polymorphisms. Author(s): Serretti A, Artioli P. Source: American Journal of Pharmacogenomics : Genomics-Related Research in Drug Development and Clinical Practice. 2003; 3(1): 17-30. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562213&dopt=Abstract
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Predictions and associations of fatigue syndromes and mood disorders that occur after infectious mononucleosis. Author(s): White PD, Thomas JM, Kangro HO, Bruce-Jones WD, Amess J, Crawford DH, Grover SA, Clare AW. Source: Lancet. 2001 December 8; 358(9297): 1946-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747919&dopt=Abstract
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Predictors of psychosocial outcomes for patients with mood disorders: the effects of self-help group participation. Author(s): Powell TJ, Yeaton W, Hill EM, Silk KR. Source: Psychiatric Rehabilitation Journal. 2001 Summer; 25(1): 3-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529450&dopt=Abstract
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Predictors of response to treatment in children and adolescents with mood disorders. Author(s): Emslie GJ, Mayes TL, Laptook RS, Batt M. Source: The Psychiatric Clinics of North America. 2003 June; 26(2): 435-56. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12778842&dopt=Abstract
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Preliminary assessment of intrahemispheric QEEG measures in bipolar mood disorders. Author(s): Oluboka OJ, Stewart SL, Sharma V, Mazmanian D, Persad E. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2002 May; 47(4): 368-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12025436&dopt=Abstract
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Premenstrual exacerbations of mood disorders. Author(s): Miller MN, Miller BE. Source: Psychopharmacology Bulletin. 2001 Summer; 35(3): 135-49. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397883&dopt=Abstract
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Prevalence of depressive symptoms and mood disorders in primary care: a Spanish rural study. Author(s): Ruiz-Doblado S. Source: The International Journal of Social Psychiatry. 1999 Autumn; 45(3): 180-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10576084&dopt=Abstract
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Prevalence of mood disorders and relationship to asthma severity in patients at an inner-city asthma clinic. Author(s): Nejtek VA, Brown ES, Khan DA, Moore JJ, Van Wagner J, Perantie DC. Source: Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology. 2001 August; 87(2): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11527244&dopt=Abstract
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Prevalence of mood disorders and utility of the PRIME-MD in patients undergoing radiation therapy. Author(s): Leopold KA, Ahles TA, Walch S, Amdur RJ, Mott LA, Wiegand-Packard L, Oxman TE. Source: International Journal of Radiation Oncology, Biology, Physics. 1998 December 1; 42(5): 1105-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9869236&dopt=Abstract
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Prevalence, diagnosis, and pharmacological treatment of mood disorders in HIV disease. Author(s): Cruess DG, Evans DL, Repetto MJ, Gettes D, Douglas SD, Petitto JM. Source: Biological Psychiatry. 2003 August 1; 54(3): 307-16. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893106&dopt=Abstract
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Progress in the psychotherapy of mood disorders: studies from the Western Psychiatric Institute and Clinic. Author(s): Frank E, Novick D. Source: Epidemiol Psichiatr Soc. 2001 October-December; 10(4): 245-52. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11917698&dopt=Abstract
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Progress in the therapy of mood disorders: scientific support. Author(s): Frank E, Kupfer DJ. Source: The American Journal of Psychiatry. 2003 July; 160(7): 1207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12832231&dopt=Abstract
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Psychiatrists' referrals to self-help groups for people with mood disorders. Author(s): Powell TJ, Silk KR, Albeck JH. Source: Psychiatric Services (Washington, D.C.). 2000 June; 51(6): 809-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10828116&dopt=Abstract
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Psychotic and mood disorders associated with the perimenopausal period: epidemiology, aetiology and management. Author(s): Robinson GE. Source: Cns Drugs. 2001; 15(3): 175-84. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11463126&dopt=Abstract
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Pursuit tracking impairments in schizophrenia and mood disorders: step-ramp studies with unmedicated patients. Author(s): Sweeney JA, Luna B, Haas GL, Keshavan MS, Mann JJ, Thase ME. Source: Biological Psychiatry. 1999 September 1; 46(5): 671-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472419&dopt=Abstract
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Questionnaire survey on the prescribing practice of Japanese psychiatrists for mood disorders. Author(s): Oshima A, Higuchi T, Fujiwara Y, Iida M, Iwanami A, Kanba S, Motohashi N, Uchitomi Y, Yamada K, Yamawaki S. Source: Psychiatry and Clinical Neurosciences. 1999 October; 53 Suppl: S67-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10560902&dopt=Abstract
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Questions & answers. My daughter has been recovering from a manic episode in the hospital. I m relieved that she is responding to her medicines because her doctors said she might have needed ECT. Could you please tell me what place ECT has in the treatment of mood disorders in case this suggestion comes up in the future? Author(s): Miller MC. Source: The Harvard Mental Health Letter / from Harvard Medical School. 2003 August; 20(2): 8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12936873&dopt=Abstract
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Quetiapine alone and added to a mood stabilizer for serious mood disorders. Author(s): Sajatovic M, Brescan DW, Perez DE, DiGiovanni SK, Hattab H, Ray JB, Bingham CR. Source: The Journal of Clinical Psychiatry. 2001 September; 62(9): 728-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11681770&dopt=Abstract
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Rash in multicenter trials of lamotrigine in mood disorders: clinical relevance and management. Author(s): Calabrese JR, Sullivan JR, Bowden CL, Suppes T, Goldberg JF, Sachs GS, Shelton MD, Goodwin FK, Frye MA, Kusumakar V. Source: The Journal of Clinical Psychiatry. 2002 November; 63(11): 1012-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444815&dopt=Abstract
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Readmission rates for adjustment disorders: comparison with other mood disorders. Author(s): Jones R, Yates WR, Zhou MH. Source: Journal of Affective Disorders. 2002 September; 71(1-3): 199-203. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167517&dopt=Abstract
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Recognizing and meeting the needs of patients with mood disorders and comorbid medical illness: a consensus conference of the Depression and Bipolar Support Alliance. Author(s): Lewis L; Depression and Bipolar Support Alliance. Source: Biological Psychiatry. 2003 August 1; 54(3): 181-3. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893091&dopt=Abstract
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Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Author(s): Lambert G, Johansson M, Agren H, Friberg P. Source: Archives of General Psychiatry. 2000 August; 57(8): 787-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10920468&dopt=Abstract
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Reduced volume of limbic system-affiliated basal ganglia in mood disorders: preliminary data from a postmortem study. Author(s): Baumann B, Danos P, Krell D, Diekmann S, Leschinger A, Stauch R, Wurthmann C, Bernstein HG, Bogerts B. Source: The Journal of Neuropsychiatry and Clinical Neurosciences. 1999 Winter; 11(1): 71-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9990559&dopt=Abstract
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Reelin mutations in mouse and man: from reeler mouse to schizophrenia, mood disorders, autism and lissencephaly. Author(s): Fatemi SH. Source: Molecular Psychiatry. 2001 March; 6(2): 129-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11317213&dopt=Abstract
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Regional cerebral blood flow in mood disorders, V.: Effects of antidepressant medication in late-life depression. Author(s): Nobler MS, Roose SP, Prohovnik I, Moeller JR, Louie J, Van Heertum RL, Sackeim HA. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2000 Fall; 8(4): 289-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069268&dopt=Abstract
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Regional cerebral blood flow in mood disorders. II. Comparison of major depression and Alzheimer's disease. Author(s): Sackeim HA, Prohovnik I, Moeller JR, Mayeux R, Stern Y, Devanand DP. Source: Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine. 1993 July; 34(7): 1090-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8315484&dopt=Abstract
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Regional specificity of brain glucocorticoid receptor mRNA alterations in subjects with schizophrenia and mood disorders. Author(s): Webster MJ, Knable MB, O'Grady J, Orthmann J, Weickert CS. Source: Molecular Psychiatry. 2002; 7(9): 985-94, 924. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12399952&dopt=Abstract
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Rehabilitation therapists' recognition of cognitive and mood disorders in geriatric patients. Author(s): Ruchinskas R. Source: Archives of Physical Medicine and Rehabilitation. 2002 May; 83(5): 609-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11994799&dopt=Abstract
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Relations of tripartite dimensions of emotion to childhood anxiety and mood disorders. Author(s): Chorpita BF, Plummer CM, Moffitt CE. Source: Journal of Abnormal Child Psychology. 2000 June; 28(3): 299-310. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10885687&dopt=Abstract
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Relationship between mood disorders and coronary artery disease: possible role of the immune system and infection. Author(s): Sher L. Source: Journal of Affective Disorders. 2001 July; 65(2): 195-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11417519&dopt=Abstract
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Relationships between serum magnesium levels and clinical background factors in patients with mood disorders. Author(s): Imada Y, Yoshioka S, Ueda T, Katayama S, Kuno Y, Kawahara R. Source: Psychiatry and Clinical Neurosciences. 2002 October; 56(5): 509-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12193239&dopt=Abstract
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Reliability of DSM-IV anxiety and mood disorders: implications for the classification of emotional disorders. Author(s): Brown TA, Di Nardo PA, Lehman CL, Campbell LA. Source: Journal of Abnormal Psychology. 2001 February; 110(1): 49-58. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11261399&dopt=Abstract
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Response of cortical metabolic deficits to serotonergic challenge in familial mood disorders. Author(s): Kegeles LS, Malone KM, Slifstein M, Ellis SP, Xanthopoulos E, Keilp JG, Campbell C, Oquendo M, Van Heertum RL, Mann JJ. Source: The American Journal of Psychiatry. 2003 January; 160(1): 76-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505804&dopt=Abstract
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Review of the role of progesterone in the management of postnatal mood disorders. Author(s): Granger AC, Underwood MR. Source: Journal of Psychosomatic Obstetrics and Gynaecology. 2001 March; 22(1): 49-55. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11317610&dopt=Abstract
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Risk factors and outcome of mood disorders in epilepsy: a case-control study. Author(s): Jagadheesan K, Garg AK, Nizamie SH. Source: Seizure : the Journal of the British Epilepsy Association. 2003 March; 12(2): 1215. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566237&dopt=Abstract
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Risperidone for young children with mood disorders and aggressive behavior. Author(s): Schreier HA. Source: Journal of Child and Adolescent Psychopharmacology. 1998; 8(1): 49-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9639079&dopt=Abstract
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Role of estrogen in the aetiology and treatment of mood disorders. Author(s): Halbreich U, Kahn LS. Source: Cns Drugs. 2001; 15(10): 797-817. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11602005&dopt=Abstract
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Role of norepinephrine in the pathophysiology and treatment of mood disorders. Author(s): Ressler KJ, Nemeroff CB. Source: Biological Psychiatry. 1999 November 1; 46(9): 1219-33. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10560027&dopt=Abstract
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S100B is increased in mood disorders and may be reduced by antidepressive treatment. Author(s): Schroeter ML, Abdul-Khaliq H, Diefenbacher A, Blasig IE. Source: Neuroreport. 2002 September 16; 13(13): 1675-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352625&dopt=Abstract
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Serotonin transporter gene associated with lithium prophylaxis in mood disorders. Author(s): Serretti A, Lilli R, Mandelli L, Lorenzi C, Smeraldi E. Source: The Pharmacogenomics Journal. 2001; 1(1): 71-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913731&dopt=Abstract
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Serotonin transporter promoter genotype and illness recurrence in mood disorders. Author(s): Smeraldi E, Benedetti F, Zanardi R. Source: European Neuropsychopharmacology : the Journal of the European College of Neuropsychopharmacology. 2002 February; 12(1): 73-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11788243&dopt=Abstract
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Serotonin(1A) receptors in mood disorders: a combined genetic and genomic approach. Author(s): Sibille E, Hen R. Source: Behavioural Pharmacology. 2001 November; 12(6-7): 429-38. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11742136&dopt=Abstract
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Serum cholesterol levels in mood disorders associated with physical violence or suicide attempts in Taiwanese. Author(s): Huang TL. Source: Chang Gung Med J. 2001 September; 24(9): 563-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11725626&dopt=Abstract
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Signaling networks in the pathophysiology and treatment of mood disorders. Author(s): Gould TD, Manji HK. Source: Journal of Psychosomatic Research. 2002 August; 53(2): 687-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12169343&dopt=Abstract
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Skating to where the puck is going to be: a plan for clinical trials and translation research in mood disorders. Author(s): Frank E, Rush AJ, Blehar M, Essock S, Hargreaves W, Hogan M, Jarrett R, Johnson RL, Katon WJ, Lavori P, McNulty JP, Niederehe G, Ryan N, Stuart G, Thomas SB, Tollefson GD, Vitiello B. Source: Biological Psychiatry. 2002 September 15; 52(6): 631-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12361672&dopt=Abstract
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Sleep disturbances and mood disorders: an epidemiologic perspective. Author(s): Ford DE, Cooper-Patrick L. Source: Depression and Anxiety. 2001; 14(1): 3-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11568977&dopt=Abstract
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Social and economic burden of mood disorders. Author(s): Simon GE. Source: Biological Psychiatry. 2003 August 1; 54(3): 208-15. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893097&dopt=Abstract
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SPECT and PET imaging in mood disorders. Author(s): George MS, Ketter TA, Post RM. Source: The Journal of Clinical Psychiatry. 1993 November; 54 Suppl: 6-13. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8270597&dopt=Abstract
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Stress and mood disorders during pregnancy: implications for child development. Author(s): Monk C. Source: The Psychiatric Quarterly. 2001 Winter; 72(4): 347-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11525082&dopt=Abstract
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Suicide in mood disorders. Author(s): Sanchez LE, Le LT. Source: Depression and Anxiety. 2001; 14(3): 177-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11747127&dopt=Abstract
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Switch to mania upon discontinuation of antidepressants in patients with mood disorders: a review of the literature. Author(s): Ali S, Milev R. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2003 May; 48(4): 258-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12776393&dopt=Abstract
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Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins. Author(s): Eastwood SL, Harrison PJ. Source: Brain Research Bulletin. 2001 July 15; 55(5): 569-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11576753&dopt=Abstract
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Synaptic plasticity and mood disorders. Author(s): Duman RS. Source: Molecular Psychiatry. 2002; 7 Suppl 1: S29-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986993&dopt=Abstract
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The combination of olanzapine and fluoxetine in mood disorders. Author(s): Shelton RC. Source: Expert Opinion on Pharmacotherapy. 2003 July; 4(7): 1175-83. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12831342&dopt=Abstract
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The hypothalamic-pituitary-gonadal axis in mood disorders. Author(s): Young EA, Korszun A. Source: Endocrinology and Metabolism Clinics of North America. 2002 March; 31(1): 6378. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12055991&dopt=Abstract
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The neuroanatomy of mood disorders. Introduction. Author(s): Blumberg HP, Charney DS. Source: Semin Clin Neuropsychiatry. 2002 October; 7(4): 221-2. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382204&dopt=Abstract
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The recognition and management of mood disorders as a comorbidity of epilepsy. Author(s): Barry JJ. Source: Epilepsia. 2003; 44 Suppl 4: 30-40. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12823567&dopt=Abstract
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Thyroid hormones in treatment of mood disorders. Author(s): Chakrabarti S, Malhotra. Source: Indian Journal of Medical Sciences. 2001 September; 55(9): 501-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11887301&dopt=Abstract
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Topiramate in the treatment of severe bulimia nervosa with comorbid mood disorders: a case series. Author(s): Barbee JG. Source: The International Journal of Eating Disorders. 2003 May; 33(4): 468-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12658677&dopt=Abstract
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Toward molecular diagnostics of mood disorders in psychiatry. Author(s): Avissar S, Schreiber G. Source: Trends in Molecular Medicine. 2002 June; 8(6): 294-300. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067616&dopt=Abstract
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Trauma-related distress and mood disorders in the early stage of an acute traumatic hand injury. Author(s): Gustafsson M, Amilon A, Ahlstrom G. Source: Journal of Hand Surgery (Edinburgh, Lothian). 2003 August; 28(4): 332-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12849944&dopt=Abstract
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Treated prevalence, incidence, and pharmacotherapy of child and adolescent mood disorders in an HMO. Author(s): DeBar LL, Clarke GN, O'Connor E, Nichols GA. Source: Mental Health Services Research. 2001 June; 3(2): 73-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109840&dopt=Abstract
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Treatment-emergent tardive dyskinesia with quetiapine in mood disorders. Author(s): Sharma V. Source: Journal of Clinical Psychopharmacology. 2003 August; 23(4): 415-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920421&dopt=Abstract
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Understanding the genetic basis of mood disorders: where do we stand? Author(s): Reus VI, Freimer NB. Source: American Journal of Human Genetics. 1997 June; 60(6): 1283-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9199547&dopt=Abstract
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Undue mood elevation in unipolar patients following cessation of lithium augmentation treatment: implications for the understanding of mood disorders. Author(s): Hoaken PC, Hoaken P. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 1996 February; 41(1): 46-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8919423&dopt=Abstract
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Unipolar-bipolar dichotomy of mood disorders is supported by noradrenergic brainstem system morphology. Author(s): Baumann B, Danos P, Krell D, Diekmann S, Wurthmann C, Bielau H, Bernstein HG, Bogerts B. Source: Journal of Affective Disorders. 1999 July; 54(1-2): 217-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403168&dopt=Abstract
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Use of atypical antipsychotics in mood disorders. Author(s): Weizman R, Weizman A. Source: Curr Opin Investig Drugs. 2001 July; 2(7): 940-5. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11757795&dopt=Abstract
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Use of placebo in clinical trials of mood disorders. Author(s): Lewis L. Source: Journal of the American Academy of Child and Adolescent Psychiatry. 2003 August; 42(8): 883. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12874487&dopt=Abstract
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Using item response theory to understand comorbidity among anxiety and unipolar mood disorders. Author(s): Krueger RF, Finger MS. Source: Psychological Assessment. 2001 March; 13(1): 140-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281035&dopt=Abstract
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Validity of a five-minute speech sample for the measurement of expressed emotion in the families of Japanese patients with mood disorders. Author(s): Shimodera S, Mino Y, Fujita H, Izumoto Y, Kamimura N, Inoue S. Source: Psychiatry Research. 2002 November 15; 112(3): 231-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12450632&dopt=Abstract
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Validity of seasonal pattern as a modifier for recurrent mood disorders for DSM-IV. Author(s): Bauer MS, Dunner DL. Source: Comprehensive Psychiatry. 1993 May-June; 34(3): 159-70. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8339533&dopt=Abstract
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Valproate and mood disorders: perspectives. Introduction. Author(s): Potter WZ, Bowden CL. Source: Journal of Clinical Psychopharmacology. 1992 February; 12(1 Suppl): 2S-6S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1541714&dopt=Abstract
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Velo-cardio-facial syndrome: Implications of microdeletion 22q11 for schizophrenia and mood disorders. Author(s): Arnold PD, Siegel-Bartelt J, Cytrynbaum C, Teshima I, Schachar R. Source: American Journal of Medical Genetics. 2001 May 8; 105(4): 354-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11378850&dopt=Abstract
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Volumetric asymmetries in late-onset mood disorders: an attenuation of frontal asymmetry with depression severity. Author(s): Kumar A, Bilker W, Lavretsky H, Gottlieb G. Source: Psychiatry Research. 2000 November 20; 100(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090724&dopt=Abstract
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Volumetric brain imaging findings in mood disorders. Author(s): Beyer JL, Krishnan KR. Source: Bipolar Disorders. 2002 April; 4(2): 89-104. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071514&dopt=Abstract
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Volumetric MRI studies of mood disorders: do they distinguish unipolar and bipolar disorder? Author(s): Strakowski SM, Adler CM, DelBello MP. Source: Bipolar Disorders. 2002 April; 4(2): 80-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12071513&dopt=Abstract
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Weight gain in the treatment of mood disorders. Author(s): Aronne LJ, Segal KR. Source: The Journal of Clinical Psychiatry. 2003; 64 Suppl 8: 22-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12892538&dopt=Abstract
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What the doctor ordered? Referrer satisfaction with a mood disorders unit. Author(s): Eyers K, Brodaty H, Roy K. Source: The Australian and New Zealand Journal of Psychiatry. 1994 September; 28(3): 498-504. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7893246&dopt=Abstract
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Which temperamental characteristics are associated with substance use in subjects with psychotic and mood disorders? Author(s): Liraud F, Verdoux H. Source: Psychiatry Research. 2000 February 14; 93(1): 63-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10699229&dopt=Abstract
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Women and mood disorders. Menarche to menopause. Author(s): Pariser SF. Source: Annals of Clinical Psychiatry : Official Journal of the American Academy of Clinical Psychiatrists. 1993 December; 5(4): 249-54. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8312982&dopt=Abstract
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CHAPTER 2. NUTRITION AND MOOD DISORDERS Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and mood disorders.
Finding Nutrition Studies on Mood Disorders The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “mood disorders” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “mood disorders” (or a synonym): •
Divalproex sodium to treat concomitant substance abuse and mood disorders. Author(s): Department of Psychiatry, University of Maryland, 20 Courthouse Square, #217, Baltimore, MD 20852, USA. Source: Hertzman, M J-Subst-Abuse-Treat. 2000 June; 18(4): 371-2 0740-5472
•
Homatropine eyedrops change sleep and mood disorders in depressive patients. Source: Stojek, A Bilikiewicz, A Bartkiewicz, T Morstyn, J Psychiatr-Pol. 1987 May-June; 21(3): 239-45 0033-2674
•
Kleptomania, mood disorder and lithium. Author(s): Hospital das Clinicas, Universidade Federal de Minas Gerais, Brasil. Source: Rocha, F L Rocha, M E Arq-Neuropsiquiatr. 1992 December; 50(4): 543-6 0004282X
•
Lamotrigine update and its use in mood disorders. Author(s): College of Pharmacy, Idaho State University, Pocatello, ID, USA.
[email protected] Source: Hurley, S C Ann-Pharmacother. 2002 May; 36(5): 860-73 1060-0280
•
lithium for maintenance treatment of mood disorders. Author(s): Department of Psychiatry, University of Oxford, Oxford, UK, OX3 7JX.
[email protected] Source: Burgess, S Geddes, J Hawton, K Townsend, E Jamison, K Goodwin, G CochraneDatabase-Syst-Revolume 2001; (3): CD003013 1469-493X
•
Lithium long-term treatment in mood disorders: clinical and genetic predictors. Author(s): Department of Psychiatry, Istituto Scientifico H San Raffaele, Vita-Salute University, San Raffaele Institute, via Stamira D'Ancona 20, 20127 Milan, Italy.
[email protected] Source: Serretti, A Pharmacogenomics. 2002 January; 3(1): 117-29 1462-2416
•
Maintaining remission in mood disorders. Source: Livingston, M Practitioner. 1989 April 8; 233(1466): 497-9 0032-6518
•
Mood disorder with mixed features due to vitamin B(12) and folate deficiency. Author(s): Dept. of Psychiatry, Athens University Medical School, Athens, Greece. Source: Fafouti, Mata Paparrigopoulos, Thomas Liappas, John Mantouvalos, Vassilis Typaldou, Rika Christodoulou, George Gen-Hosp-Psychiatry. 2002 Mar-April; 24(2): 106-9 0163-8343
•
Mood disorders: treatment-induced changes in brain neurochemistry and structure. Author(s): Neuropsychiatric Research Unit, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA. Source: Glitz, D A Manji, H K Moore, G J Semin-Clin-Neuropsychiatry. 2002 October; 7(4): 269-80 1084-3612
•
Neuronal nicotinic receptor inhibition for treating mood disorders: preliminary controlled evidence with mecamylamine. Author(s): Center for Aging and Brain Repair, Department of Neurosurgery, University of South Florida College of Medicine, 12901 Bruce B. Downs Boulevard, Tampa, FL 33613, USA.
[email protected] Source: Shytle, R D Silver, A A Sheehan, K H Sheehan, D V Sanberg, P R DepressAnxiety. 2002; 16(3): 89-92 1091-4269
Nutrition
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Prodromal symptoms and intermittent drug medication in mood disorders. Author(s): Department of Psychology, University of Bologna, Italy. Source: Fava, G A Molnar, G Grandi, S Sonino, N Pharmacopsychiatry. 1991 January; 24(1): 28-30 0176-3679
•
Psychotic and mood disorders associated with the perimenopausal period: epidemiology, aetiology and management. Author(s): Women's Mental Health Program, The University Health Network, and Department of Psychiatry, University of Toronto, Ontario, Canada. Source: Robinson, G E CNS-Drugs. 2001; 15(3): 175-84 1172-7047
•
Role of estrogen in the aetiology and treatment of mood disorders. Author(s): BioBehavioral Program, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Buffalo, New York, USA.
[email protected] Source: Halbreich, U Kahn, L S CNS-Drugs. 2001; 15(10): 797-817 1172-7047
•
Serotonin transporter gene associated with lithium prophylaxis in mood disorders. Author(s): Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan, Italy.
[email protected] Source: Serretti, A Lilli, R Mandelli, L Lorenzi, C Smeraldi, E Pharmacogenomics-J. 2001; 1(1): 71-7 1470-269X
•
Subclinical symptoms in mood disorders: pathophysiological and therapeutic implications. Author(s): Department of Psychology, University of Bologna, Italy. Source: Fava, G A Psychol-Med. 1999 January; 29(1): 47-61 0033-2917
•
The role of dopamine in mood disorders. Author(s): Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213. Source: Diehl, D J Gershon, S Compr-Psychiatry. 1992 Mar-April; 33(2): 115-20 0010440X
•
Thyroid hormones in treatment of mood disorders. Author(s): Dept. of Psychiatry, PGIMER, Chandigrah.
[email protected] Source: Chakrabarti, S Malhotra Indian-J-Med-Sci. 2001 September; 55(9): 501-7 00195359
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
•
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/
•
Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
•
Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
•
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
•
Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
•
Google: http://directory.google.com/Top/Health/Nutrition/
•
Healthnotes: http://www.healthnotes.com/
•
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
•
WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to mood disorders; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Minerals Naproxen/Naproxen Sodium Source: Healthnotes, Inc.; www.healthnotes.com
•
Food and Diet Omega-3 Fatty Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,992,00.html Omega-6 Fatty Acids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,1037,00.html
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CHAPTER 3. DISORDERS
ALTERNATIVE MEDICINE AND MOOD
Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to mood disorders. At the conclusion of this chapter, we will provide additional sources.
The Combined Health Information Database The Combined Health Information Database (CHID) is a bibliographic database produced by health-related agencies of the U.S. federal government (mostly from the National Institutes of Health) that can offer concise information for a targeted search. The CHID database is updated four times a year at the end of January, April, July, and October. Check the titles, summaries, and availability of CAM-related information by using the “Simple Search” option at the following Web site: http://chid.nih.gov/simple/simple.html. In the drop box at the top, select “Complementary and Alternative Medicine.” Then type “mood disorders” (or synonyms) in the second search box. We recommend that you select 100 “documents per page” and to check the “whole records” options. The following was extracted using this technique: •
Discussing Complementary Therapies With Cancer Patients: What Should We Be Talking About? (Editorial) Source: Journal of Clinical Oncology. 18(3): 2501-2504. July 2000. Summary: This editorial discusses the use of complementary and alternative medicine (CAM) by cancer patients and the implications for oncologists. The author highlights findings from two recent studies of CAM use among cancer patients. In the study by M.A. Richardson and colleagues (see AMJA02604), 83 percent of patients across a spectrum of malignancies and disease stages reported using CAM, including 69 percent who used some modality other than spirituality or psychotherapy. In the study by H. Boon and colleagues (see AMJA02603), the prevalence rate for CAM use among breast cancer patients was 67 percent. In both studies, cancer patients used a large number of CAM therapies and did so to improve quality of life, feel hopeful, gain control, and
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obtain relief from symptoms or side effects of conventional treatment. However, the available data suggest that patients are using CAM in conjunction with, not instead of, standard oncologic care. The author concludes that oncologists should directly ask patients if they are using CAM and what they expect from the CAM therapy. Oncologists also need to better address patients' needs for management of pain, anxiety or mood disorders, sleep disturbance, and other symptoms, and to offer patients greater empowerment and choice by encouraging them to participate more directly in the clinical decision-making process. The article has 19 references.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to mood disorders and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “mood disorders” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to mood disorders: •
“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:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441784&dopt=Abstract
•
Dopamine receptor D3 gene and response to lithium prophylaxis in mood disorders. Author(s): Serretti A, Lilli R, Lorenzi C, Franchini L, Smeraldi E. Source: The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (Cinp). 1998 December; 1(2): 125-129. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11281956&dopt=Abstract
•
Mood disorders: diagnosis, treatment, and support from a patient perspective. Author(s): Lewis L. Source: Psychopharmacology Bulletin. 2001 Autumn; 35(4): 186-96. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12397865&dopt=Abstract
•
Novel treatments of mood disorders based on brain circuitry (ECT, MST, TMS, VNS, DBS). Author(s): George MS, Nahas Z, Li X, Kozel FA, Anderson B, Yamanaka K, Chae JH, Foust MJ. Source: Semin Clin Neuropsychiatry. 2002 October; 7(4): 293-304. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12382211&dopt=Abstract
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•
Online empathy for mood disorders: patients turn to internet support groups. Author(s): Lamberg L. Source: Jama : the Journal of the American Medical Association. 2003 June 18; 289(23): 3073-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12813097&dopt=Abstract
•
Pharmacogenetics of lithium prophylaxis in mood disorders: analysis of COMT, MAO-A, and Gbeta3 variants. Author(s): Serretti A, Lorenzi C, Lilli R, Mandelli L, Pirovano A, Smeraldi E. Source: American Journal of Medical Genetics. 2002 May 8; 114(4): 370-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992559&dopt=Abstract
•
Predictors of psychosocial outcomes for patients with mood disorders: the effects of self-help group participation. Author(s): Powell TJ, Yeaton W, Hill EM, Silk KR. Source: Psychiatric Rehabilitation Journal. 2001 Summer; 25(1): 3-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11529450&dopt=Abstract
•
Transcranial magnetic stimulation in the treatment of mood disorder: a review and comparison with electroconvulsive therapy. Author(s): Hasey G. Source: Canadian Journal of Psychiatry. Revue Canadienne De Psychiatrie. 2001 October; 46(8): 720-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692974&dopt=Abstract
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 mood disorders; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Anorexia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Bipolar Disorder Source: Healthnotes, Inc.; www.healthnotes.com Bulimia Nervosa Source: Integrative Medicine Communications; www.drkoop.com Depression Source: Integrative Medicine Communications; www.drkoop.com High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com
•
Alternative Therapy Color Therapy Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,683,00.html
•
Herbs and Supplements Celecoxib Source: Healthnotes, Inc.; www.healthnotes.com Citalopram Source: Healthnotes, Inc.; www.healthnotes.com Diclofenac Source: Healthnotes, Inc.; www.healthnotes.com Etodolac Source: Healthnotes, Inc.; www.healthnotes.com
Alternative Medicine 121
Flurbiprofen Source: Healthnotes, Inc.; www.healthnotes.com Glimepiride Source: Healthnotes, Inc.; www.healthnotes.com Hypericum Perforatum Source: Integrative Medicine Communications; www.drkoop.com Ibuprofen Source: Healthnotes, Inc.; www.healthnotes.com Indapamide Source: Healthnotes, Inc.; www.healthnotes.com Indomethacin Source: Healthnotes, Inc.; www.healthnotes.com Ketoprofen Source: Healthnotes, Inc.; www.healthnotes.com Ketorolac Source: Healthnotes, Inc.; www.healthnotes.com Klamathweed Alternative names: St. John's Wort Source: Integrative Medicine Communications; www.drkoop.com L-tyrosine Source: Healthnotes, Inc.; www.healthnotes.com Mixed Amphetamines Source: Healthnotes, Inc.; www.healthnotes.com Moexipril Source: Healthnotes, Inc.; www.healthnotes.com Nabumetone Source: Healthnotes, Inc.; www.healthnotes.com Non-Steroidal Anti-Inflammatory Drugs Source: Healthnotes, Inc.; www.healthnotes.com Oxaprozin Source: Healthnotes, Inc.; www.healthnotes.com Perphenazine Source: Healthnotes, Inc.; www.healthnotes.com Piroxicam Source: Healthnotes, Inc.; www.healthnotes.com
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Prochlorperazine Source: Healthnotes, Inc.; www.healthnotes.com Rofecoxib Source: Healthnotes, Inc.; www.healthnotes.com Salsalate Source: Healthnotes, Inc.; www.healthnotes.com St. John's Wort Alternative names: Hypericum perforatum, Klamathweed Source: Integrative Medicine Communications; www.drkoop.com Sulindac Source: Healthnotes, Inc.; www.healthnotes.com Thioridazine Source: Healthnotes, Inc.; www.healthnotes.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. DISSERTATIONS ON MOOD DISORDERS Overview In this chapter, we will give you a bibliography on recent dissertations relating to mood disorders. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “mood disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on mood disorders, we have not necessarily excluded non-medical dissertations in this bibliography.
Dissertations on Mood Disorders ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to mood disorders. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •
Creativity and Temperament in Mood Disorders by Strong, Connie Moore; PhD from Pacific Graduate School of Psychology, 2002, 222 pages http://wwwlib.umi.com/dissertations/fullcit/3062672
•
Familial Coaggregation of Mood Disorders with Other Psychiatric and Medical Disorders by Hudson, James Irvin, III; SD from Harvard University, 2002 http://wwwlib.umi.com/dissertations/fullcit/f840833
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Gender, Lifestyle and Social Adjustment: Differences in Mood Disorders by Douglass, Karen Yvette; PsyD from Adler School of Professional Psychology, 2002, 113 pages http://wwwlib.umi.com/dissertations/fullcit/3056608
•
The Paradox of High Academic Scores in Teenagers with Mood Disorders by Stuart, Sylvia; PhD from Loyola University of Chicago, 2002, 86 pages http://wwwlib.umi.com/dissertations/fullcit/3077511
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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. CLINICAL TRIALS AND MOOD DISORDERS Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning mood disorders.
Recent Trials on Mood Disorders The following is a list of recent trials dedicated to mood disorders.8 Further information on a trial is available at the Web site indicated. •
Adolescence, Puberty, and Emotion Regulation Condition(s): Mood Disorder; Neurobehavioral Manifestation; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to compare how the brains of adolescents and adults are activated during tasks that involve emotional responses. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00016731
•
Clinical Trial of Fluoxetine in Anxiety and Depression in Children, and Associated Brain Changes Condition(s): Depression; Mood Disorder; Anxiety Disorder; Healthy Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will determine if fluoxetine (Prozac(r) (Registered Trademark)) is effective for treating anxiety or depression in children and adolescents.
8
These are listed at www.ClinicalTrials.gov.
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The study will also use functional magnetic resonance imaging (fMRI) to learn more about how the brain functions in children/adolescents taking this medication for anxiety or depression. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00018057 •
Clinical Trial of Leuprolide Acetate for the Treatment of PMS Condition(s): Depressive Disorder; Mood Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to examine the influence of estrogen and progesterone on mood and behavior in women with premenstrual syndrome. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001259
•
Clinical trials of three non-drug treatments for winter depression (SAD). Condition(s): Seasonal Affective Disorder; Mood Disorders; Depressive Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: We are offering non-pharmacologic therapy for alleviation of symptoms associated with depressed mood that recurs annually in fall or winter. The treatments are self-administered at home by the patient, with close clinical supervision. Our trials use specially designed devices that replenish two different environmental elements, naturally occurring light and negative ions in the air. Both factors may be reduced in winter, bringing on depression. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006517
•
Combined Hormone Replacement in Menstraully-Related Mood Disorders Condition(s): Premenstrual Syndrome Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to investigate the role of the hormones estrogen and progesterone in women with premenstrual syndrome (PMS). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00005011
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•
Effect of Acetylcholine on Thinking and Emotion in Individuals with Mood Disorders Condition(s): Mood Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to examine the role of a neurotransmitter system in regulating brain activity and cognitive performance in individuals with mood disorders. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00055575
•
Evaluation of Repetitive Transcranial Magnetic Stimulation (rTMS) in the Treatment of Mood Disorders Condition(s): Bipolar Disorder; Mood Disorder; Unipolar Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study is designed to evaluate repetitive transcranial magnetic stimulation (rTMS) as a potential treatment for depression. In rTMS, a rapidly changing magnetic field passes through your scalp and skull and generates a small electrical pulses in your brain. rTMS at lower intensities has helped some people with depression but we do not know what the results will be in your case using higher intensities, or whether you will be randomized to 3 weeks of high frequency (20 cycles er second), low frequency (1 cycle per second), or inactive (sham)rTMS. You will be assigned to receive one of these types of rTMS over the left front art of your brain five times per week for the three weeks. Each rTMS treatment session should take between 20-30 minutes of actual stimulation, but weekly ratings, memory testing, and blood sampling may require several hours per week. We will also ask you to have brain imaging procedures to see if these will predict response to high vs. low frequency rTMS. If you are randomized to the 3 weeks of sham rTMS, you will have the opportunity to receive one of the active stimulation frequencies for an additional 3 weeks. Responders to any phase will be offered an additional month of rTMS prior to study termination and recommendations of alternative treatments. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001545
•
Evaluation of the Genetics of Bipolar Disorder Condition(s): Anxiety Schizophrenia
Disorder;
Bipolar
Disorder;
Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH)
Healthy;
Mood
Disorder;
128 Mood Disorders
Purpose - Excerpt: The purpose of this study is to identify genes that may affect a person's chances of developing bipolar (BP) disorder and related conditions. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001174 •
Examination of Brain Serotonin Receptors in Patients with Mood Disorders Condition(s): Mood Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the function of certain brain chemicals and receptors in patients with mood disorders. This study will also examine how the stress hormone cortisol affects brain function. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00026832
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Family Psychoeducation for Children with Mood Disorders Condition(s): Mood Disorders Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to evaluate the effectiveness of a Multifamily Psychoeducation Group (MFPG) for the families of children with mood disorders. Phase(s): Phase I Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00050557
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Magnetic Resonance Imaging (MRI) of Neuropsychiatric Patients and Healthy Volunteers Condition(s): Bipolar Disorder; Healthy; Mood Disorder; Parkinson's Disease; Schizophrenia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to compare differences in brain structure, chemistry, and functioning in individuals with brain and mental disorders compared to healthy volunteers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00004571
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•
Neuropsychological Evaluation of Psychiatric and Neurological Patients Condition(s): Anxiety Disorder; Head Injury; Mood Disorder; Schizophrenia; Seizures Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will allow researchers to use various types of tests to evaluate cognitive and sensory functions. These tests, referred to as "batteries" will evaluate attention, executive functions, general intellectual functioning, language, memory, motor functions, orientation, personality, selected sensory and perceptual functions, vigilance (alertness), and visual-spatial functions. Children and adult patient will receive different test batteries. The goals of this research study are to; 1. Create descriptions based on the performance of each patient on the test batteries. Then use this information to relate patient behavior to their neurophysiological, neuroradiological, and biochemical descriptions. 2. Define subgroups of patients based on their neurobehavior in order to decrease the variability of psychiatric diagnoses, treatments, and prognoses. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001192
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Severe Mood and Behavioral Dysregulation in Children: Pathophysiology and Treatment with Lithium Condition(s): Mood Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study seeks to characterize symptoms of severe mood and behavioral dysregulation (SMBD) in children and adolescents. The study will also evaluate the effectiveness of lithium as a treatment for this condition while subjects participate in day-treatment or inpatient care. Phase(s): Phase IV Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00025935
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Study of Menstrually-Regulated Mood and Behavioral Disorder Condition(s): Mental Disorder; Mood Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to identify and describe the symptoms of premenstrual syndrome (PMS). Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001177
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Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Condition(s): Mood Disorders; Affective Disorders, Psychotic; Bipolar Disorder; Cyclothymic Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: STEP-BD is the largest treatment study ever conducted for bipolar disorder. It is a long-term outpatient study (5 years) that aims to find out which treatments, or combinations of treatments, are most effective for treating episodes of depression and mania and for preventing recurrent episodes. In addition, the study will evaluate treatment effectiveness in terms of quality of life, adherence to treatment, ability to work, social functioning, and treatment cost-effectiveness. While many treatments are used currently for bipolar disorder, including medications and psychotherapies, doctors are uncertain which of these treatments or combination of treatments actually work best. Findings from STEP-BD will help improve the treatment standards used by doctors in everyday clinical practice. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00012558
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The Effects of Hormones in Postpartum Mood Disorders Condition(s): Depressive Disorder; Mood Disorder; Postpartum Depression Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to determine how women who have experienced a postpartum mood disorder respond to estrogen and progesterone in comparison to women who have had an episode of major depression not related to PPD, and in comparison with women who have not experienced mood disorders. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001481
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The Psychobiology of Childhood Temperament Condition(s): Mood Disorders; Anxiety Disorders; Adolescents Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to use brain imaging technology to examine brain changes that occur in children when they are exposed to various kinds of emotional tasks and to determine if these changes are related to the child's temperament. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00060775
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Therapy for Depression with Co-occurring Panic or Anxiety Symptoms Condition(s): Depression; Mood Disorder; Anxiety Disorder; Panic Disorder; Major Depressive Disorder Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The purpose of this study is to develop and test a new therapy designed to treat depressed patients with co-occurring symptoms of panic or anxiety. Phase(s): Phase I; Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00051207
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Study of the Psychological Development of Children of Parents with and without Affective Disorders Condition(s): Bipolar Disorder; Involutional Depression; Mood Disorder Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This research study is the continuation of a study started more than 20 years ago. The study was designed to explore the effect that depressed parents have on their children and to better understand the factors that contribute to depression development and maintenance. The study will continue to investigate if children have certain characteristics in early and middle childhood that predict the later development of psychological disorders. In addition, the study will continue looking at the processes responsible for the development of children of parents with and without affective (mood) disorders. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001170
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Treatment of Mid-Life-Related Mood Disorders Condition(s): Depressive Disorder; Mood Disorder Study Status: This study is no longer recruiting patients. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Dehydroepiandrosterone (DHEA) is a hormone produced by the adrenal gland. As humans grow older the levels of DHEA naturally decrease. Low levels of DHEA have been associated with a variety of harmful effects, including increased heart disease, decreased immune system function, decreased bone density (osteoporosis), high cholesterol, and increased fat to muscle ratio. Blood levels of DHEA and its sulfate form, DHEA-S, begin dropping when humans are in their 20's. By the time humans are in their 40's and 50's, levels of DHEA and DHEA-S levels are at 50% of their peak. Previous studies have shown that levels of these hormones are associated with feelings of "well-being" and enjoyment of "leisure" activities. In this study researchers are interested in the effects on mood and behavior of DHEA in men and women with mid-life related mood disorders. Specifically, researchers would like to find
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out if increasing levels of DHEA will lessen the symptoms associated with these disorders. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001487 •
Clinical trials of two non-drug treatments for chronic depression Condition(s): Mood Disorders; Depressive Disorders; Depression; Chronic depression; Nonseasonal depression Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study investigates the potential efficacy of two nonpharmacologic treatments for nonseasonal depression, bright light exposure or highdensity negative air ion exposure. Treatments are self-administered at home by the patient under close clinical supervision. Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00006172
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Effects of Drugs on Cerebral Blood Flow in Patients with Mood Disorders Condition(s): Healthy; Mood Disorders Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Positron Emission Tomography (PET) is a technique used to investigate the functional activity of the brain. The PET technique allows doctors to study the normal biochemical and metabolic processes of the central nervous system of normal individuals and patients with neurologic illnesses without physical / structural damage to the brain. When a region of the brain is active, it uses more fuel in the form of oxygen and sugar (glucose). As the brain uses more fuel it produces more waste products, carbon dioxide and water. Blood carries fuel to the brain and waste products away from the brain. As brain activity increases blood flow to and from the area of activity increases also. Knowing these facts, researchers can use radioactive chemicals (H215O) and PET scans to observe what areas of the brain are receiving more blood flow. Patients diagnosed with mood disorders and healthy volunteers will receive positron emission tomographic (PET) scans with H215O while doing simple tasks. Patients will continue to receive scans while in different mood states and while taking different medications. Patients eligible for this study will be participating in other research studies measuring other clinical and biochemical parameters (mood and anxiety ratings, medication responses, and psychological test results). Information gathered from H215O PET scans measuring blood flow to specific brain areas will be compared to the data gathered from other studies. Objectives of this study are; 1. To determine differences in blood flow to the brain of patients with mood disorders compared to healthy volunteers. 2. To determine differences in blood flow to the brain of patients with subtype mood disorders (such as unipolar versus bipolar) compared to healthy volunteers. 2. To determine changes in blood flow to the brain of patients with
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mood disorders who experience spontaneous changes in symptoms 3. To determine changes in blood flow to the brain of patients with mood disorders who receive various kinds of therapy (medication, transcranial magnetic stimulation, etc.) 4. To determine if blood flow to specific areas of the brain can be used to predict how patients will respond to certain types of therapy 5. To compare blood flow changes with various other clinical and biochemical parameters. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001478 •
Neuroimaging of St. John's Wort-Induced Changes of Serotonin Metabolism in Normal Subjects Condition(s): Healthy; Mood Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: St. John's Wort is a popular dietary supplement that many people take to elevate mood or relieve stress. This study will test in normal volunteers whether this preparation may alter mood and if so, by what means. Animal studies suggest that St. John's Wort may work similarly to some antidepressants that affect levels of the chemical serotonin in the brain. Participants in this study must also be enrolled in NIMH protocol #98-M-0094 (SPECT Imaging of Dopamine and Serotonin Transporters in Neuropsychiatric Patients and Normal Volunteers) and protocol #91-M-014 (MRI Imaging of Neuropsychiatric Patients and Controls). Separate consent forms are required for each study. Candidates will undergo medical and psychiatric evaluations that may include blood and urine tests, electroencephalogram and electrocardiogram. Normal volunteers will have a mood assessment at the beginning of the study. They will then be randomly assigned to take either placebo (a pill with no active ingredient) or St. John's Wort 3 times a day for 2 weeks, and will be told what they are taking. After an 11week hiatus, they will again start treatment on the same schedule, but will not be told which preparation they are receiving. Each evening during the 2-week treatment periods, subjects will complete a brief self-rating mood assessment questionnaire. At the end of each treatment period, they will undergo SPECT brain imaging (a type of CT scan) to determine dopamine and serotonin distribution and density in the brain. For this procedure, study subjects take three drops of potassium iodide solution within 24 hours before the scan and two drops nightly for 3 days following the procedure. About 10 ml (less than two teaspoons) of blood are drawn before a radioactive tracer is injected. SPECT imaging is done the next day. After about 1 hour of imaging, subjects are given either a placebo or St. John's Wort, and then imaging continues for another 2 hours. During the procedure, up to five blood samples of 6 ml each may be drawn. At some point during the study, a MRI scan of the brain will be done. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001919
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New Drugs in the Treatment of Mood Disorders Condition(s): Anxiety Disorder; Mood Disorder; Psychotic Disorder Study Status: This study is completed.
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Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This clinical study compares the effectiveness of two anticonvulsants Lamotrigine (Lamictal) Monotherapy and Gabapentin (Neurontin) in patients with treatment resistant affective disorders. We initially have found that the response rate to lamotrigine (51%) exceeded that of gabapentin (28%) or placebo (21%). In this study the placebo phase has been dropped so that we examine possible clinical and biological factors predictors of response. The drugs will be given in a randomized order for six weeks each and you will not know when you are on a given one. There will be a 2-4 week "washout" period between treatments. If you respond well to one of these treatments, a longer open continuation period will be offered at the end of this study. This would involve one or both drugs in combination. A variety of rating scales and brain imaging procedures will also be offered before and during each drug evaluation. Both lamotrigine and gabapentin are generally well tolerated. A serious potentially life threatening rash occurs in about 1/500 patients treated with lamotrigine, however. Common side effects are rash, dizziness, unsteadiness, double vision, blurred vision, nausea, vomiting, insomnia, sedation, and headache. These side effects are usually mild, and resolve with continued time on the drug or a decrease in dosage. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001482 •
Omega-3 Fatty Acids in the Treatment of Bipolar Disorder: A Double-Blind, PlaceboControlled Trial Condition(s): Bipolar Disorder; Involutional Depression; Mood Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: This study will examine the effectiveness of omega-3 fatty acids, compounds found in plants and fish, in treating bipolar disorder. Some studies have indicated that omega-3 fatty acids may be effective in treating mood disorders. For example, one investigator has shown a correlation between the prevalence of major depression and the amount of fish consumed per capita worldwide. Others have found decreased amounts of EPA (one of the active ingredients in omega-3 fatty acids) in the red blood cells of patients with major depression. And a recent small study of patients with bipolar illness indicated that omega-3 fatty acids prevented relapses, especially of depression, in patients. Patients with bipolar disorder who are not benefiting satisfactorily on their current medications are eligible to participate in this study. Candidates will be screened with a psychiatric evaluation, routine blood tests, a urine test and other tests needed to monitor medications. Participants will be randomly assigned to one of two groups: one group will receive 6 grams of omega-3 fatty acid every day for 16 weeks; the second will receive a placebo (inactive capsule). In addition, patients in both groups will continue to take their previous medications. Every 2 weeks, all patients will have their vital signs checked and be evaluated for side effects and mood changes. At the end of the 16-week study period, all patients will be given the opportunity to continue in the study for another 8 months and receive active drug (omega-3 fatty acid). Patients who continue will be evaluated once a month and will have blood drawn on the last visit for routine tests. Phase(s): Phase II
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Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001146 •
Progestin (progesterone-like hormones) induced dysphoria (depressed mood, irritability, anxiety) Condition(s): Depressive Disorder; Mood Disorder; Psychomotor Agitation Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Often women are prescribed hormone replacement therapy (HRT) during the perimenopause or menopause. Hormone replacement therapy includes both estrogen and progesterone. The estrogen component of HRT helps to relieve the symptoms and has a beneficial effect on the heart and bones, but estrogen also increases the risk of uterine cancer. The progesterone component of the HRT (progestin) works to prevent the increased risk of uterine cancer. There is evidence that some women experience unpleasant mood symptoms (such as irritability, depressed mood and anxiety) while receiving hormone replacement therapy (HRT) while taking the progestin / progesterone component of the HRT. This study is designed to evaluate the ability of progestins to produce negative mood symptoms in women. Researchers intend on doing this by comparing the effects of medroxyprogesterone acetate (Provera) and a placebo inactive sugar pill. Patient's moods will be monitered based on their response to questionnaires answered in the outpatient clinic and at home. This research will attempt to answer the following questions: 1. Are progestins associated with changes in mood during hormone replacement therapy? 2. If progestins are associated with mood disturbance, is it because they are blocking the beneficial effects of estrogen? Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001770
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Study of the Hypothalmic-Pituitary-Adrenal (HPA) Axis and its Role in Major Depression Condition(s): Fatigue Syndrome, Chronic; Healthy; Mood Disorders Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: Major depression represents a major public health problem worldwide and in the U.S. Fifteen percent of the U.S. population has depression at some point in life (40 million individuals). The condition is more common in women, occurring at a female to male ratio of 5:2. Presently, 6-8% of all outpatients in primary care meet the diagnostic criteria for major depression. Fifteen percent of untreated patients with depression will commit suicide. Most of the people committing suicide are depressed. Researchers believe that by the year 2020 suicide will be the 10th most common cause of death in the U.S. In addition to mortality due to suicide, depression is also associated with other severe health conditions. Areas of the brain (hippocampus) begin to deteriorate, heart disease, and decreased bone mineral density (osteoporosis) are all associated with major depression. Researchers have believed for years that hormones controlled by the hypothalmus, pituitary gland, and adrenal gland
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(commonly referred to as the HPA axis or system) are in some way associated with psychiatric illnesses like depression. According to previous studies, researchers have theorized that increased activity of the HPA axis is associated with depressed patients with typical melancholic features. Melancholia refers to the feelings of anhedonia (absence of pleasure from activites that would normally be thought of as pleasurable), insomnia (inability to sleep), guilt, and psychomotor changes. On the other hand a decrease in activity of the HPA axis may be associated with the atypical features of depression. This study has already developed and refined studies that have improved the understanding of the HPA axis in healthy humans and depressed patients. Researchers have already identified and plan to continue identifying distinct subtypes of depressive disorders based on the activity of the HPA axis. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001479 •
The Effect of GnRH on Pitutitary Hormones in Menstrual-Cycle Mood Related Disorders Condition(s): Depressive Disorder; Healthy; Mental Disorders; Mood Disorders Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The normal menstrual cycle is produced by a series of hormonal signals that starts with the release of gonadotropin-releasing hormone (GnRH) from the hypothalamus. The hypothalamus is located in the brain and is often referred to as the master gland. GnRH then acts on the pituitary gland and causes it to release two hormones, follicle stimulating hormone (FSH) and lutenizng hormone (LH). LH and FSH act on the ovary and cause it to release the hormones directly involved in menstruation, estrogen and progesterone. The purpose of this research study is to evaluate the hypothalamic-pituitary-gonadal axis activity as measured by pituitary hormones, FSH and LH in response to intravenous doses of gonadotropin releasing hormone (GnRH) in menstrual cycle-related hormones. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001232
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The Effects of Sex Hormones on Cognition and Mood in Older Adults Condition(s): Cognition Disorders; Mood Disorders Study Status: This study is terminated. Sponsor(s): National Institute on Aging (NIA) Purpose - Excerpt: This study is investigating the effects of hormone replacement therapy on memory, mental abilities and mood in older adults aged 65-90. During the nine month long study, men will take testosterone for three months and women will take estrogen for three months. At four points during the study (once every three months), participants will complete a test battery and have blood drawn. Study Type: Interventional Contact(s): see Web site below
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Web Site: http://clinicaltrials.gov/ct/show/NCT00000175 •
The Role of Emotion in the Development of Psychopathology Condition(s): Mood Disorder Study Status: This study is completed. Sponsor(s): National Institute of Mental Health (NIMH) Purpose - Excerpt: The dysregulated experience and expression of emotion is implicated in psychiatric disorders associated both with externalizing problems (aggressive, antisocial behaviors) and internalizing problems (anxiety, depression). Adolescence is a critical juncture in the development of these disorders because of the increased incidence and differentiation of clinical problems during this time period. This is a biobehavioral, longitudinal investigation of the role of emotion in the development of psychopathology in adolescence. The focus is on socialization experiences and biological processes that contribute to emotion dysregulation and disorder in male and female youths between 11 and 16 years of age. Groups studied include (1) comorbid externalizers and internalizers, (2) externalizers only, (3) internalizers only, and (4) asymptomatic youth. The adolescents are assessed again two years later, with instruments and paradigms similar to those used at Time 1. One theme pertains to the integration and disconnection of emotions across systems (e.g., physiological and selfreport of experience), and how different patterns of emotion relate to psychopathology. A second theme pertains to development changes in how disorders are manifested (e.g., increased differentiation along gender specific pathways). The anticipated number of patient days per year is 240 for adolescents and mothers, and 120 days for fathers. Study Type: Observational Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00001654
Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “mood disorders” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •
For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/
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For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html
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For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/
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For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm
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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm
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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm
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For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp
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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm
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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/
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For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm
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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm
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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm
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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm
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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm
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For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials
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CHAPTER 6. PATENTS ON MOOD DISORDERS Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.9 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 “mood disorders” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on mood disorders, we have not necessarily excluded nonmedical patents in this bibliography.
Patents on Mood Disorders By performing a patent search focusing on mood disorders, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 9Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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example of the type of information that you can expect to obtain from a patent search on mood disorders: •
.DELTA.9 Tetrahydrocannabinol (.DELTA.9 THC) solution metered dose inhaler Inventor(s): Byron; Peter R. (Richmond, VA), Lichtman; Aron H. (Richmond, VA), Martin; Billy R. (Richmond, VA), Peart; Joanne (Richmond, VA) Assignee(s): Virginia Commonwealth University (Richmond, VA) Patent Number: 6,509,005 Date filed: March 22, 1999 Abstract: The present invention provides therapeutic formulations for solutions of.DELTA.sup.9 -tetrahydrocannabinol (.DELTA.sup.9 THC) to be delivered by metered dose inhalers. The formulations, which utilize non-CFC propellants, provide a stable aerosol-deliverable source of.DELTA.sup.9 THC for the treatment of various medical conditions, such as: nausea and vomiting associated with chemotherapy; muscle spasticity; pain; anorexia associated with AIDS wasting syndrome; epilepsy; glaucoma; bronchial asthma; and mood disorders. Excerpt(s): The invention is generally related to the therapeutic use of.DELTA.sup.9 Tetrahydrocannabinol (.DELTA.sup.9 THC). In particular, the invention provides a metered dose inhaler (MDI) for the aerosol administration of.DELTA.sup.9 THC to patients suffering from nausea and vomiting associated with cancer chemotherapy, muscle spasticity, pain, anorexia associated with AIDS wasting syndrome, epilepsy, glaucoma, bronchial asthma, mood disorders, and the like. When marijuana is used illegally as a recreational psychoactive drug, the active ingredient.DELTA.sup.9 THC is usually delivered to the lungs as an impure non-pharmaceutical aerosol in the form of marijuana smoke. Aerosolized.DELTA.sup.9 THC in the inhaled smoke is absorbed within seconds and delivered to the brain efficiently. Table 2 and references 19-20 describe the pharmacokinetics of the administration of.DELTA.sup.9 THC. As can be seen, inhalation is the preferred route of delivery for.DELTA.sup.9 THC. When compared to oral delivery, inhalation provides a more rapid onset of pharmacological action and peak plasma levels. The effects achieved via inhalation are comparable to those achieved when the drug is administered intravenously, but inhalation is a much less invasive technique. Currently, the sources of.DELTA.sup.9 THC for patients who could benefit from the drug are very limited. An oral form of.DELTA.sup.9 THC (MARINOL) is marketed as a treatment for nausea and vomiting related to cancer chemotherapy, and as an appetite stimulant in patients suffering from AIDS wasting syndrome. In MARINOL, pharmaceutical grade.DELTA.sup.9 THC is dissolved in sesame oil, encapsulated in gelatin capsules and delivered orally. However, when the drug is taken orally, the absorption is slower and more variable than when inhaled, with an onset of action between 30 minutes and 2 hours (Table 2). Alternatively, some cancer patients do manage to obtain and smoke marijuana in order to alleviate such conditions as nausea and vomiting due to chemotherapy. This is, however, technically illegal and is thus obviously a less than ideal treatment protocol. There is no currently available pharmaceutically acceptable aerosol form of.DELTA.sup.9 THC. Web site: http://www.delphion.com/details?pn=US06509005__
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Cerebral-activating extract Inventor(s): Bormann; Joachim (Gottingen, DE), Demisch; Lothar (Frankfurt am Main, DE), Gurtelmeyer; Roman (Muhltal, DE), Koch; Rudinger (Frankfurt am Main, DE), Schatton; Wolfgang (Eschborn, DE) Assignee(s): Merz & Co. GmbH & Co. (Frankfurt am Main, DE) Patent Number: 5,262,162 Date filed: September 6, 1991 Abstract: The use of an effective monoamine oxidase-inhibitory amount or portion of black currant juice (Ribes nigrum L.) or concentrate or dry extract thereof to activate the brain and central nervous system, in a living animal, especially a human being, in need thereof, and thereby to increase the general cerebral performance, especially in healthy and elderly people, and for the prevention, treatment, and alleviation of neurodegenerative diseases associated with reduced cerebral performance, such as Parkinson's disease, dementia, and mood disorders, and compositions thereof for such purpose, are disclosed. Excerpt(s): The use of black currant juice (Ribes nigrum L.) or black currant juice concentrate or dry extract thereof, to inhibit monoamine oxidase and to activate the brain and central nervous system, in a living animal, especially a human being, in need thereof, and thereby to increase the general cerebral performance, especially in healthy and elderly people, and for the prevention, treatment, and alleviation of neurodegenerative diseases associated with reduced cerebral performance, such as Parkinson's disease, dementia, and mood disorders, and compositions thereof for such purpose. The neurotransmitter dopamine is one of the most essential cerebral neurotransmitters responsible for the modulation of cerebral performance. Reduced dopamine concentrations, which are often present in elderly people and specific neurodegenerative diseases, are always associated with reduced cerebral function. Web site: http://www.delphion.com/details?pn=US05262162__
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Certain aryl-aliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases Inventor(s): Jonsson; Mattias (Uppsala, SE), Nilsson; Bjorn (Uppsala, SE), Nilsson; Jonas (Uppsala, SE), Pelcman; Benjamin (Stockholm, SE), Ringberg; Erik (Uppsala, SE), Tejbrant; Jan (Enskede, SE), Thor; Markus (Knivsta, SE) Assignee(s): Biovitrum AB (Stockholm, SE) Patent Number: 6,465,467 Date filed: June 8, 2000 Abstract: Compounds of the general formula (I):wherein the variables are as defined in the specification are useful for the prophylaxis or treatment of serotonin-related, especially 5-HT.sub.2 receptor-related, diseases in human beings or animals, particularly diseases related to the 5-HT2.sub.c receptor, especially diseases such as eating disorders, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctionions, and urinary disorders. Excerpt(s): The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament which particularly acts
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on the central nervous system. Many diseases of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin has been implicated in a number of diseases and conditions which originate in the central nervous system. A number of pharmacological and genetic experiments involving receptors for serotonin strongly implicate the 5HT.sub.2c receptor subtype in the regulation of food intake (Obes. Res. 1995, 3, Suppl. 4, 449S-462S). The 5-HT.sub.2c receptor subtype is transcribed and expressed in hypothalamic structures associated with appetite regulation. It has been demonstrated that the non-specific 5-HT.sub.2c receptor agonist m-chlorophenylpiperazine (mCPP), which has some preference for the 5-HT.sub.2c receptor, causes weight loss in mice that express the normal 5-HT.sub.2c receptor while the compound lacks activity in mice expressing the mutated inactive form of the 5-HT.sub.2c receptor (Nature 1995, 374, 542546). In a recent clinical study, a slight but sustained reduction in body weight was obtained after 2 weeks of treatment with mCPP in obese subjects (Psychopharmacology 1997, 133, 309-312). Weight reduction has also been reported from clinical studies with other "serotonergic" agents (see e.g. IDrugs 1998, 1, 456-470). For example, the 5-HT reuptake inhibitor fluoxetine and the 5-HT releasing agent/reuptake inhibitor dexfenfluramine have exhibited weight reduction in controlled studies. However, currently available drugs that increase serotonergic transmission appear to have only a moderate and, in some cases, transient effects on the body weight. The 5-HT.sub.2c receptor subtype has also been suggested to be involved in CNS disorders such as depression and anxiety (Exp. Opin. Invest. Drugs 1998, 7, 1587-1599; IDrugs, 1999, 2, 109-120). Web site: http://www.delphion.com/details?pn=US06465467__ •
Composition and methods employing it for the treatment of 5-HT-mediated disorders Inventor(s): Evenden; John (Wellesley, MA), Thorberg; Seth-Olov (Strangnas, SE) Assignee(s): Astra Aktiebolag (Sodertalje, SE) Patent Number: 6,169,098 Date filed: July 9, 1999 Abstract: The invention relates to a composition comprising a first component (a) which is (R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1-benzopyran-5-carboxa mide hydrogen (2R,3R)-tartrate monohydrate and a second component (b) which is paroxetine, in the form of its free base, or a pharmaceutically acceptable salt and/or solvate thereof The invention is further directed to the preparation of the composition, pharmaceutical formulations containing said composition, and a method of treatment of affective disorders such as mood disorders and anxiety disorders with said composition, as well as a kit containing said composition. Excerpt(s): The present invention relates to a composition which comprises a first component (a) which is (R)-3-N,N-dicyclobutylamino-8-fluoro-3,4-dihydro-2H-1benzopyran-5-carboxa mide hydrogen (2R,3R)-tartrate monohydrate and a second component (b) which is paroxetine, or a pharmaceutically acceptable salt and/or solvate thereof The present invention also relates to a process for the preparation of the inventive composition, pharmaceutical formulations containing said composition and to the use of said composition either by concomitant administration or by separate administration as an improvement of the treatment of affective disorders such as depression, anxiety, obsessive compulsive disorder (OCD), etc. Today, it is generally considered that antidepressants take 2-4 weeks to reach full clinical effect. In contrast,
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the side effects occur immediately. Thus, slow onset of action of antidepressants leads to a vulnerable period for patients in which they experience the side effects, but not the therapeutic effects of drugs. There is often a heavy burden on the treating physician to persuade the patient to continue with the treatment during this period. Furthermore, in suicidal patients, as the onset of action is gradual, initiative may be regained without the experiencing of full reversal of symptoms, leaving a window of risk for suicide and a frequent requirement for hospitalization. An antidepressant with fast onset of action would not only be beneficial due to the faster symptom reduction, but would also be more acceptable to patients and physicians and reduce the need for, and duration of, hospitalization. The same long period to reach full clinical effect has been shown in the treatment of other affective disorders such as anxiety and OCD. In WO 96/33710 is disclosed that the compound (R)-5-carbamoyl-8-fluoro-3-N,N-dicyclobutylamino-3,4dihydro-2H-1-benzopyr an, which has high affinity to 5-HT receptors and antagonizes 5-HT.sub.IA -mediated responses, induces a rapid improvement of depressed patients treated with serotonin reuptake inhibitors. Web site: http://www.delphion.com/details?pn=US06169098__ •
Composition for controlling mood disorders in healthy individuals Inventor(s): Cavazza; Claudio (Rome, IT) Assignee(s): Sigma-Tau HealthScience S.p.A. (Pomezia, IT) Patent Number: 6,335,021 Date filed: December 20, 1999 Abstract: The use of acetyl L-carnitine and its pharmacologically acceptable salts is disclosed for producing a composition suitable for controlling mood disorders mainly in young individuals who are not affected by permanent pathological CNS disturbances. Excerpt(s): The present invention relates to the use of acetyl L-carnitine and its pharmacologically accetable salts for producing a composition suitable for controlling mood disorders in individuals not presenting permanent pathological alterations of the central nervous system (CNS) by restoring the normal balance of neurotransmitter levels. For the purposes of the present invention what is meant by "mood disorders" are those disorders which present as behavioural alterations of a depressive or manic type and, in particular, those disorders that present as oscillations between depressive and manic states alternating in the same individual. According to the present invention, these disorders also include the so-called premenstrual syndrome and states of bulimia. Normal variations in mood (melancholy, mildly depressed states, anguish or joy and moderate excitement) constitute habitual aspects of daily life and must be distinguished from the pathological fluctuations of affective disorders. Web site: http://www.delphion.com/details?pn=US06335021__
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Compositions containing sertraline and a 5-HT.sub.1D receptor agonist or antagonist Inventor(s): Chenard; Bertrand L. (New York, NY), Howard; Harry R. (New York, NY), Macor; John E. (New York, NY), Schulz; David W. (New York, NY), Sprouse; Jeffrey S. (New York, NY) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 5,597,826 Date filed: September 14, 1994 Abstract: The present invention relates to novel compositions containing the serotonin selective re-uptake inhibitor (SSRI), preferably (1S-cis)-4-(3,4-dichlorophenyl)-1,2,3,4tetrahydro-N-methyl-1-naphthalenam ine, and an agonist or antagonist of the serotonin 1 (5-HT.sub.1) receptor and to the use of such compositions for treating or preventing a condition selected from mood disorders, including depression, seasonal affective disorders and dysthmia, anxiety disorders including generalized anxiety disorder and panic disorder; agoraphobia, avoidant personality disorder; social phobia; obsessive compulsive disorder; post-traumatic stress disorder; memory disorders including dementia, amnestic disorders and age-associated memory impairment; disorders of eating behavior, including anorexia nervosa and bulimia nervosa; obesity; cluster headache; migraine; pain; Alzheimer's disease; chronic paroxysmal hemicrania; headache associated with vascular disorders; Parkinson's disease, including dementia in Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesias; endocrine disorders such as hyperprolactinaemia; vasospasm (particularly in the cerebral vasculature); hypertension; disorders in the gastrointestinal tract where changes in motility and secretion are involved; sexual dysfunction, including premature ejaculation; and chemical dependencies. Excerpt(s): The present invention relates to novel compositions containing the serotonin selective re-uptake inhibitor (SSRI) (1S-cis)-4-(3,4- dichlorophenyl)-1,2,3,4-tetrahydro-Nmethyl-1-naphthalenemine (hereinafter sertraline) and an agonist or antagonist of the serotonin 1 (5-HT.sub.1) receptor and to the use of such compositions for treating or preventing a condition selected from mood disorders, including depression, seasonal effective disorders and dysthmia, anxiety disorders including generalized anxiety disorder and panic disorder; agoraphobia, avoidant personality disorder; social phobia; obsessive compulsive disorder; post-traumatic stress disorder; memory disorders including dementia, amnestic disorders and age-associated memory impairment; disorders of eating behavior, including anorexia nervosa and bulimia nervosa; obesity; cluster headache; migraine; pain; Alzheimer's disease; chronic paroxysmal hemicrania; headache associated with vascular disorders; Parkinson's disease, including dementia in Parkinson's disease, neuroleptic-induced parkinsonism and tardive dyskinesias; endocrine disorders such as hyperprolactinaemia; vasospasm (particularly in the cerebral vasculature); hypertension; disorders in the gastrointestinal tract where changes in motility and secretion are involved; sexual dysfunction, including premature ejaculation; and chemical dependencies. U.S. Pat. No. 4,536,518 issued Aug. 20, 1985 refers to sertraline and derivatives thereof and states that these compounds are useful as antidepressant agents. U.S. Pat. No. 4,940,731 issued Jul. 10, 1990 refers to a method of treating premature ejaculation using sertraline. Web site: http://www.delphion.com/details?pn=US05597826__
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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. 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
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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__ •
HLDAT86 polynucleotides Inventor(s): Barnes; Michael R (Bishop's Stortford, GB) Assignee(s): SmithKline Beecham P.L.C. (Brentford, GB) Patent Number: 6,165,751 Date filed: April 28, 1998 Abstract: HLDAT86 (Wnt-4) polypeptides and polynucleotides and methods for producing such polypeptides by recombinant techniques are disclosed. Also disclosed are methods for utilizing HLDAT86 (Wnt-4) polypeptides and polynucleotides in the design of protocols for the treatment of kidney disorders, cancer, cardiac and vascular disease, inflammatory disorders, Alzheimers disease, schizophrenia and mood disorders., among others, and diagnostic assays for such conditions. Excerpt(s): This invention relates to newly identified polynucleotides, polypeptides encoded by them and to the use of such polynucleotides and polypeptides, and to their production. More particularly, the polynucleotides and polypeptides of the present invention relate to the Wnt signalling molecule family, hereinafter referred to as HLDAT86 (Wnt-4). The invention also relates to inhibiting or activating the action of such polynucleotides and polypeptides. This protein is likely to serve as a transducer molecule for developmental processes, during Wnt signal transduction. This is essential for normal morphogenesis and/or differentiated function in diverse tissues. A close orthologue of this gene, Wnt-4, has been described in the mouse (Gavin, et al, 1990. Genes. Dev. 4:2319-2332). Kidney defects were observed in Wnt-4 knockout mice, indicating a likely involvement of Wnt-4 in kidney development and morphogenesis. Expression of the mouse orthologue has also been observed across a number of other tissues in the mouse, some of which are of significant therapeutic target regions. Clearly there is a need for identification and characterization of further members of Wnt signalling molecule family which can play a role in preventing, ameliorating or correcting dysfunctions or diseases, including, but not limited to, kidney disorders, cancer, cardiac and vascular disease, inflammatory disorders, Alzheimers disease, schizophrenia and mood disorders. In one aspect, the invention relates to HLDAT86 (Wnt-4) polypeptides and recombinant materials and methods for their production. Another aspect of the invention relates to methods for using such HLDAT86 (Wnt-4) polypeptides and polynucleotides. Such uses include the treatment of kidney disorders, cancer, cardiac and vascular disease, inflammatory disorders, Alzheimers disease, schizophrenia and mood disorders., among others. In still another aspect, the invention relates to methods to identify agonists and antagonists using the materials provided by the invention, and treating conditions associated with HLDAT86 (Wnt-4) imbalance with the identified compounds. Yet another aspect of the invention relates to diagnostic assays for detecting diseases associated with inappropriate HLDAT86 (Wnt-4) activity or levels. Web site: http://www.delphion.com/details?pn=US06165751__
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Illumination devices and methods for treating light deficiency and mood disorders Inventor(s): Dial; Daniel Christoper (SE. 141 Mill Creek Rd., Shelton, WA 98584) Assignee(s): none reported Patent Number: 5,824,024 Date filed: May 3, 1996 Abstract: Illumination fixtures for use in treating light deficiency and mood disorders, as well as color therapy, are disclosed. The fixtures employ an illumination gas having a high neon gas content. Fixtures in which the glass tubing is bent and convoluted in a three dimensional arrangement provide a high level of illumination in a compact device and substantially reduce glare. Fixtures employing multiple color tubing, dimmer(s) and/or timer(s) may be used to simulate natural lighting conditions, such as sunrise, neon illumination sources may also be used in combination with an as a source for fiber optic cables. Excerpt(s): The present invention relates to illumination devices for use in treating conditions by exposure to a light source, such as light deficiency and mood disorders, as well as for color therapy and other types of light therapy. The illumination source of the present invention is especially useful for treating seasonal affective disorder. The invention furthermore relates to improved methods for treating various conditions using specified illumination sources. The psychological and physical effects of light deficiency and mood disorders are well established. Various forms of light therapy may be useful treatment for depression, sexual dysfunction, visual disorders, pre-menstrual syndrome ("PMS"), stress, learning disabilities and immune system deficiencies. Winter depression, or seasonal affective disorder ("SAD"), for example, may affect up to 20% of the population in certain geographical areas and is associated with reduced exposure to natural light during the winter season. The most common symptoms are depression, fatigue, withdrawal and changes in appetite and sleep patterns. Light therapy, in which patients are exposed to bright light, is the conventional treatment and has proved to be an effective treatment for many SAD sufferers. In light therapy, artificial light is used to simulate sunlight, which is generally from about 10 to about 200 times as bright as "normal" indoor light. Web site: http://www.delphion.com/details?pn=US05824024__
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Method and apparatus for diagnosis of a mood disorder or predisposition therefor Inventor(s): Miller; Steven Mark (Queensland, AU), Pettigrew; John Douglas (Queensland, AU) Assignee(s): The University of Queensland (Queensland, AU) Patent Number: 6,629,935 Date filed: March 19, 2001 Abstract: A method for diagnosis of a mood disorder or predisposition therefor in a test subject is disclosed. The method includes the steps of determining an interhemispheric switch rate of the test subject, and comparing the switch rate with a corresponding reference switch rate to diagnose presence or absence of the mood disorder or predisposition therefor. In a preferred embodiment, the interhemispheric switch rate is determined by measuring the rate of binocular rivalry in the test subject. Also disclosed is an apparatus for diagnosis of a mood disorder or predisposition therefor, use of the
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diagnostic method in genetic linkage studies for the identification of the molecular defect(s) underlying these disorders, and for the identification of compounds which may alleviate such disorders. Excerpt(s): A variety of mood disorders exist which compromise to varying degrees the social integration and quality of life of affected individuals. The major forms of mood disorder include bipolar disorder (manic depression) and unipolar disorders (major depression and unipolar mania). Other mood disorders include dysthymic disorder, cyclothymic disorder, seasonal affective disorder and substance-induced mood disorder. Bipolar disorder is a common condition with a lifetime prevalence of 1.2% to 1.6% (Weissman et al. 1988, Psych. Med. 18:141-153; Kessler et al. 1994, Arch. Gen. Psych. 51:8-19). It is characterised by recurrent episodes of mania and depression with symptomatic recovery between episodes. The pathophysiology of bipolar disorder remains poorly understood despite considerable research (Goodwin et al. 1998, Arch. Gen. Psych. 55:23-25). Although it is strongly heritable, the genetics are complex, with less than full concordance in monozygotic twins (Mitchell et al. 1993, Aust. & New Zeal. J. Psych. 27:560-580). At least four different susceptibility loci have been identified (Adams et al. 1998, Am. J. Hum. Genet. 62:10841091). A trait-dependent biological marker would assist genetic linkage studies (which are dependent upon the identification of the clinical phenotype) and would potentially lead to an understanding of the underlying molecular defect in bipolar disorder. Web site: http://www.delphion.com/details?pn=US06629935__ •
Method and compounds for use in the treatment of steroid induced states of the central nervous system Inventor(s): Backstrom; Torbjorn (Sofiehemsvagen 73 A, S-907 38, Umea, SE), Wang; Ming-De (KarnVagen 123, S-906 27, Umea, SE) Assignee(s): none reported Patent Number: 6,455,516 Date filed: March 11, 1999 Abstract: The use of epiallopregnanolone (3.beta.-hydroxy-5.alpha.-pregnan-20-one) for the treatment of steroid induced mood disorders and CNS disorders is disclosed. Further, the use of epiallopregnanolone for the manufacture of pharmaceuticals is disclosed, together with an list of symptoms suitable for treatment with epiallopregnanolone. Excerpt(s): The present invention concerns the treatment of steroid induced mood disorders and disorders of the central nervous system (CNS) and in particular new pharmaceuticals for this purpose. The progesterone metabolites known as pregnanolones have been the subject of various studies, at least partially elucidating their role in the neurological signal system in mammals. The nomenclature differs somewhat in the field, but the pregnanolone group is generally considered to encompass the following compounds: 3alpha-hydroxy-5alpha-pregnan-20one(allopregnanolone), 3alpha-hydroxy-5beta-pregnan-20-one (pregnanolone), 3betahydroxy-5alpha-pregnan-20-one (epiallopregnanolone), and 3beta-hydroxy-5-betapregnan-20-one (epipregnanolone). 3alpha-hydroxy-5alpha-pregnan-20-one is an important specific GABA-A {.gamma.-aminobutyric acid (A)} receptor enhancer. It has a specific binding site located on the alpha- and/or beta-unit of the GABA-A receptor. It acts by enhancing the effect of GABA on the opening frequency of the GABA-A receptor
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and the opening duration. It has an effect similar both to benzodiazepines and barbiturates but has a binding site separate from both these compounds. The effect is specific on the GABA-A receptor and can be blocked by the GABA-antagonist picrotoxin. 3alpha-hydroxy-5alpha-prenan-20-one has a CNS-depressing effect and it is possible to induce anaesthesia with a high pharmacological dose. It can also be used as anti-epileptic substance, sleeping-pill and as anti-migraine effect. It has also shown anxiolytic effects in animal experiments. All this in high concentrations and in high doses. Web site: http://www.delphion.com/details?pn=US06455516__ •
Method of determining and treating affective illness Inventor(s): Leuschner; Janet (4614 Fifth Ave., Apartment 407, Pittsburgh, PA 15213) Assignee(s): none reported Patent Number: 4,375,466 Date filed: April 14, 1980 Abstract: A method of determining affective illness (i.e. mood disorders) involves serological testing. The serotonin uptake of the patient's blood platelets is determined and compared with a standard blood platelet serotonin uptake characteristic of a particular type of affective illness to determine the patient's type of affective illness. A method of treating a patient having a particular affective illness is provided which includes treating the patient with an effective amount of at least one drug which is effective in treating persons having the same blood platelet serotonin uptake as the patient. Excerpt(s): This invention relates to the determination and treatment of affective illness. When an affectively ill patient is first voluntarily admitted to a psychiatric hospital or first seeks psychiatric or psychological treatment, he is normally in a depressed condition. This is because persons who are experiencing normal moods and those experiencing hypomania are quite satisfied with their psychological state. Thus, the most prevalent symptom when first examined, i.e. general behavior, is characteristic of both bipolar and unipolar disorders. The treating physician must accurately determine from which type of mood disorder the patient is suffering in order to prescribe the appropriate drug to alleviate the psychiatric condition, i.e. depression. Typically, a series of psychological tests are performed upon the patient which are a series of questions and answers and may include the response to certain stimuli which aid in determining whether a patient is unipolar or bipolar. Typical tests are the RDC (Research Diagnostic Criteria) and the SADS. Once having performed these psychological tests the physician selects the appropriate drug, depending on whether the patient is diagnosed as unipolar or bipolar. If the external manifestations of the patient during the testing process indicate that the patient is bipolar when, in fact, the patient is unipolar, the prescribed drug will not be effective in alleviating the symptoms and vice versa. For example, it has been found that tranylcypromine in the sulfate form (2-tranylcypromine sulfate) and other monoamine oxidase inhibitors are helpful in alleviating the depression in bipolar patients, whereas the same drug type is undesirable and may be ineffective or harmful in treating unipolar patients. In unipolar patients it has been found that amitriptyline in the hydrochloride form (10,11-dihydro-N,N-dimethyl-5H-dibenzo [.alpha.,.alpha.]cycloheptene-.sup.DELTA.5y -propylamine hydrochloride) and other tricyclopropylamine derivatives, including dibenzocycloheptadine derivatives, are useful in alleviating depression.
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Method of preparing a forskohlin composition from forskohlin extract and use of forskohlin for promoting lean body mass and treating mood disorders Inventor(s): Badmaey; Viadimir (Piscataway, NJ), Majeed; Muhammed (Piscataway, NJ), Rajendran; R. (Bangalora, IN) Assignee(s): Sabinsa Corporation (Piscataway, NJ) Patent Number: 5,804,596 Date filed: February 27, 1997 Abstract: A method of promoting lean body mass in an individual is disclosed, comprising administering to the individual a lean body mass promoting effective amount of forskohlin. A method of treating a mood disorder is also disclosed, comprising administering to a patient in need thereof a mood disorder treating effective amount of forskohlin. Compositions suitable for promoting lean body mass and/or treating a mood disorder are also disclosed, the composition comprising about 1 to about 40% forskohlin in combination with at least one physiologically acceptable carrier or excipient. A method of preparing a forskohlin composition from a forskohlin extract of Coleus Forskoli plant is further disclosed, as well as a forskohlin composition prepared by the method. Excerpt(s): Most weight loss pharmaceutical compositions and nutraceutical aids are designed to decrease the amount of body fat in an individual by decreasing the individual's appetite for food, decreasing the amount of food absorption in the individual, slowing down the rate of fatty acid synthesis within the body, or increasing the rate of catabolism of fatty acids. The following are some examples of weight loss products and their mechanisms. Dexfenfluramine increases the brain levels of serotonin, a neurotransmitter and neurohormone that quells the appetite. Sibutramine also increases the levels of serotonin, as well as noradrenaline, and works to quell the appetite. Neuropeptide Y inhibitors curb the appetite, as well as stimulating the body to burn more sugars and less fat. Bromeriptine mimics the neurotransmitter dopamine, and may reduce blood sugar and fat production by the liver. Leptin, a hormone generated by adipocytes, affects the hypothalamus. Cholecystokinin, a hormone and neurotransmitter, acts to reduce appetite. Butabindide blocks an enzyme that inactivates cholecystokinin. Orlistat interferes with pancreatic lipase, which results in poor absorption of dietary fat. Insulinotropin is a glucagon-like hormone which prevents obesity by slowing down the emptying of the stomach. Bta-243 stimulates betaadrenergic receptors on adipocytes, with a resulting increase in the burning of fatty acids. Troglitazone is a synthetic hormone which signals muscle cells to utilize fat for energy, rather than sugars. Cytokine regulators change the activity of hormone-like cytokines and alter the communication among cells, resulting in weight loss. Hydroxycitric acid acts as an inhibitor of enzyme citrate lyase, which subsequently slows down the synthesis of fatty acids and increases the rate at which fatty acids are burned. The average amount of body fat in the American male is 22 to 25%, and in the American female, the average amount of fat is 33 to 35%. These values are far above optimal values, which are 15 to 19% for 20-29 year old males and 19 to 23% for 20-29 year old females. Corresponding values for 40-49 year olds are 17 to 21% and 21 to 25%, respectively; and for 60 year olds, the corresponding values are 19 to 23% and 23 to 27%, respectively. In highly overweight individuals, fat tissue can constitute up to 70% of body weight. The remaining percentage of body composition corresponds to the lean
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body mass. Lean body mass is composed of muscle, vital organs, bone, connective and other non-fatty tissues in the body, and most of the body water. The body's metabolic rate is in direct proportion to the amount of lean body mass. Therefore, considering the lean body mass is important for any weight loss strategy. Web site: http://www.delphion.com/details?pn=US05804596__ •
Method, compositions, and compounds for allosteric modulation of the gaba receptor by members of the androstane and pregnane series Inventor(s): Hogenkamp; Derk (Carlsbad, CA), Upasani; Ravindra B. (Foothill Ranch, CA), Xia; Haiji (Foothill Ranch, CA) Assignee(s): CoCensys, Inc. (Irvine, CA) Patent Number: 5,939,545 Date filed: July 2, 1997 Abstract: Methods, compositions, and compounds for modulating the GABA.sub.A receptor-chloride ionophore complex to alleviate stress, anxiety, seizures, mood disorders, PMS and PND and to induce anesthesia. Excerpt(s): The present invention is directed to methods, compositions, and compounds for modulating animal (and human) brain excitability via the gamma-aminobutyric acid A (GABA.sub.A) receptor-chloride ionophore complex (GRC). Specifically, the present invention is directed to methods, compositions, and compounds for modulating brain excitability through binding to the neurosteroid receptor site on the GRC. Brain excitability is defined as the level of arousal of an animal, a continuum that ranges from coma to convulsions, and is regulated by various neurotransmitters. In general, neurotransmitters are responsible for regulating the conductance of ions across neuronal membranes. At rest, the neuronal membrane possesses a potential (or membrane voltage) of approximately -80 mV, the cell interior being negative with respect to the cell exterior. The potential (voltage) is the result of ion (K.sup.+, Na.sup.+, Cl.sup.-, organic anions) balance across the neuronal semipermeable membrane. Neurotransmitters are stored in presynaptic vesicles and are released under the influence of neuronal action potentials. When released into the synaptic cleft, an excitatory chemical transmitter such as acetylcholine will cause membrane depolarization (change of potential from -80 mV to -50 mV). This effect is mediated by postsynaptic nicotinic receptors which are stimulated by acetylcholine to increase membrane permeability to Na.sup.+ ions. The reduced membrane potential stimulates neuronal excitability in the form of a postsynaptic action potential. In the case of the GRC, the effect on brain excitability is mediated by GABA, a neurotransmitter. GABA has a profound influence on overall brain excitability because up to 40% of the neurons in the brain utilize GABA as a neurotransmitter. GABA regulates the excitability of individual neurons by regulating the conductance of chloride ions across the neuronal membrane. GABA interacts with its recognition site on the GRC to facilitate the flow of chloride ions down an electrochemical gradient of the GRC into the cell. An intracellular increase in the levels of this anion causes hyperpolarization of the transmembrane potential, rendering the neuron less susceptible to excitatory inputs (i.e., reduced neuron excitability). In other words, the higher the chloride ion concentration in the neuron, the lower the brain excitability (the level of arousal). Web site: http://www.delphion.com/details?pn=US05939545__
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Methods and materials for treating depression and mood disorder Inventor(s): Cho; Suk H. (Idaho Falls, ID), Perkes; Lynn (Rexburg, ID) Assignee(s): Melaleuca, Incorporated (Idaho Falls, ID) Patent Number: 6,068,846 Date filed: August 5, 1999 Abstract: The present invention provides methods and materials for the treatment of depression or mood disorder. Specifically, the invention involves the use of 5-HTP and an extract to treat depression or mood disorders when administered orally. In addition, the invention provides less expensive, naturally derived dietary supplements to treat mild to moderate depression or mood disorder. Excerpt(s): The present invention relates to methods and materials for the treatment of depression or mood disorder. More particularly, the invention relates to the treatment of mild to moderate depression or mood disorder by a novel composition of Hypericum perforalum, Griffonia Simplicifolia, and/or specific vitamins. The present invention relates to tablets, capsules, tinctures, or syrup containing a specific amount of Hypericum perforalum, Griffonia Simplicifolia, and/or specific vitamins for internal use. Depression is the most common mood disorder in the modern world. There are a variety of types and levels of depression. The spectrum of depression can range from a condition that is temporary, lasting a few days, to clinical depression that can be a much more serious disorder. This medical disorder can be characterized by persistent severe feelings of worthlessness, guilt, sadness, helplessness, and hopelessness. Common symptoms can include inactivity, difficulty thinking or concentrating, appetite changes, sleep disturbances, and suicidal tendencies. There are several theories that postulate why depression exists. Stressful life style, diet, chemical imbalances, and traumatic events are all thought to cause depression. Although the mechanisms of depression are not completely understood, therapies are available to treat this disorder. Treatments typically involve using antidepressant drugs in combination with counseling. Approximately seventeen million Americans suffer from clinical depression and over twenty-eight million Americans take antidepressant drugs. Modern drugs focus on manipulating neurotransmitter levels in the brain. The most commonly used drugs are Prozac, Zoloft, and Paxil, which predominately work by increasing serotonin levels either by inhibiting the reuptake of serotonin or preventing serotonin breakdown. Most prescriptions can be expensive and patients can experience unwanted side effects from these medications. In addition, some of these medications can become ineffective after prolonged use. Web site: http://www.delphion.com/details?pn=US06068846__
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Methods for treating bipolar mood disorder associated with markers on chromosome 18q Inventor(s): Escamilla; Michael (San Francisco, CA), Freimer; Nelson B. (San Francisco, CA), Leon; Pedro (San Jose, CR), McInnes; Lynne Allison (San Francisco, CA), Reus; Victor I. (San Francisco, CA), Sandkuijl; Lodewijk (Delft, NL) Assignee(s): The Regents of the University of California (Oakland, CA), The University of Costa Rica (San Jose, CR) Patent Number: 6,136,532 Date filed: November 24, 1997
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Abstract: The present invention is directed to methods of detecting the presence of a bipolar mood disorder susceptibility locus in an individual, comprising analyzing a sample of DNA for the presence of a DNA polymorphism on the long arm of chromosome 18 between markers D18S469 and D18S554, wherein the DNA polymorphism is associated with a form of bipolar mood disorder. The invention for the first time provides strong evidence of a susceptibility gene for bipolar mood disorder that is located in the 18q22-q23 region of the long arm of chromosome 18. The disclosure describes the use of linkage analysis and genetic markers in this 18q22-q23 region to fine map the region and the use of genetic markers to genetically diagnose (genotype) bipolar mood disorder in individuals, to confirm phenotypic diagnoses of bipolar mood disorder, to determine appropriate treatments for patients with particular genotypic subtypes. Isolated polynucleotides useful for genetic linkage analysis of BP-I and methods for obtaining such isolated polynucleotides are also described. Excerpt(s): Manic-depressive illness, or bipolar mood disorder (BP), is characterized by episodes of elevated mood (mania) and depression and is among the most prevalent and potentially devastating of psychiatric syndromes. The most severe and clinically distinctive forms of BP are BP-I (severe bipolar mood disorder) and SAD-M (schizoaffective disorder manic type), and are characterized by at least one full episode of mania, with or without episodes of major depression (defined by lowered mood, or depression, with associated disturbances in rhythmic behaviors such as sleeping, eating, and sexual activity). A milder form of BP is BP-II, bipolar mood disorder with hypomania and major depression. BP-I often co-segregates in families with more etiologically heterogeneous syndromes, such as unipolar major depressive disorder (MDD), which is a more broadly defined phenotype. See McInnes, L. A. and Freimer, N. B., Mapping genes for psychiatric disorders and behavioral traits, Curr. Opin. in Genet. and Develop., 5:376-381 (1995). An estimated 2-3 million people in the United States are affected by BP-I. Currently, individuals are typically evaluated for bipolar mood disorder using the clinical criteria set forth in the most current version of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM). Many drugs have been used to treat individuals diagnosed with bipolar mood disorder, including lithium salts, carbamazepine and valproic acid. However, none of the currently available drugs is able to treat every individual diagnosed with severe BP-I (termed BP-I) and drug treatments are effective in only approximately 60-70% of individuals diagnosed with BP-I. Moreover, it is currently impossible to predict which drug treatments will be effective in particular BP-I affected individuals. Commonly, upon diagnosis affected individuals are prescribed one drug after another until one is found to be effective. Early prescription of an effective drug treatment is critical for several reasons, including the avoidance of extremely dangerous manic episodes and the risk of progressive deterioration if effective treatments are not found. Also, appropriate treatment may prevent depressive episodes in BP-I individuals; these episodes are also dangerous and are characterized by a high suicide rate. The high prevalence of the disorder, together with frequent occurrence of hospitalizations, psychosocial impairment, suicide and substance abuse, has made BP-I a major public health concern. Mapping genes for common diseases believed to be caused by multiple genes, such as BP-I, may be complicated by the typically imprecise definition of phenotypes, by etiologic heterogeneity, and by uncertainty about the mode of genetic transmission of the disease trait. With psychiatric disorders there is even greater ambiguity in distinguishing between individuals who likely carry an affected genotype from those who are genetically unaffected. For example, one can define an affected phenotype for BP by including one or more of the broad grouping of diagnostic classifications that constitute the mood disorders: BP-I, SAD-M, MDD, and BP-II.
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Web site: http://www.delphion.com/details?pn=US06136532__ •
Methods of treating anxiety and mood disorders with oleamide Inventor(s): Geracioti, Jr.; Thomas D. (254 Greendale Ave., Cincinnati, OH 45220), Kasckow; John W. (9202 Sheralce La., Cincinnati, OH 45231) Assignee(s): none reported Patent Number: 6,359,010 Date filed: November 22, 2000 Abstract: A method of treating conditions characterized by anxiety and/or depression, by the administration of oleamide or related compounds is disclosed. Excerpt(s): The mood and anxiety disorders in their various permutations constitute a major source of personal suffering and impaired ability to engage in productive work and interpersonal relationships. Between 5 and 9% of women and between 2 and 3% of men meet the diagnostic criteria for major depression at any time; 10-25% of all women suffer major depression sometime in their lives, while 5-10% of men will develop major depressive disorder (American Psychiatric Association, 1994). The anxiety disorders obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), panic disorder, and generalized anxiety disorder (GAD) show lifetime prevalence rates of approximately 2.5%, 7%, 2.5%, and 5% respectively. Between 3 and 13% of individuals in community samples are regarded to meet the diagnostic criteria for social phobia. Mood and anxiety disorders are common comorbidities (American Psychiatric Association, 1994) and the most common antidepressant medications--including the serotonin reuptake inhibitors, the mixed serotonin-catecholamine reuptake inhibitors, the tricyclic antidepressants, and the monoamine oxidase inhibitors--are all effective treatments for anxiety and panic attacks. Affective disorders, while characterized by depressed mood of varying degrees, exist in various forms. Thus, melancholic depression is characterized by continuously-depressed mood and pervasive hopelessness, insomnia with early-morning awakening (with the inability to return to sleep), loss of appetite and weight loss, and excessive feelings of guilt (American Psychiatric Association, 1994). In contrast, so-called "atypical" depression is characterized by hypersomnia (oversleeping), hyperphagia and weight gain, and--often-mood reactivity. In general--regardless of whether or not the depressive syndrome is melancholic, atypical, or some admixture of the two--a diagnosis of major depression is given when depressed mood is present, or loss of interest or pleasure in all activities is present, for at least two weeks (American Psychiatric Association 1994). If less severe or incapacitating, depressed mood is considered dysthymia. Depressed mood can occur in the form of a cycling mood abnormality such as bipolar mood disorder, cyclothymia, or menstrual-related mood disorder. Mood disorders are commonly seen in general medical practice and some general medical disorders resemble depression in important respects. In particular, both fibromyalgia and chronic fatigue syndrome are medical disorders that have clinical and pathophysiologic features in common with atypical depression. Web site: http://www.delphion.com/details?pn=US06359010__
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Osanetant in the treatment of depression and depressive disorders Inventor(s): Emonds-Alt; Xavier (Combaillaux, FR), Soubrie; Philippe (Valflaunes, FR), Steinberg; Regis (Prades le Lez, FR) Assignee(s): Sanofi-Synthelabo (Paris, FR) Patent Number: 6,420,388 Date filed: October 5, 2001 Abstract: The invention relates to a method for the treatment of mood disorders utilizing osanetant or a pharmaceutically acceptable salt thereof. Excerpt(s): The subject of the present invention is a novel use of osanetant. This compound and its pharmaceutically acceptable salts are described in European Patent Application EP 673 928. These compounds are described as being selective antagonists of the human NK.sub.3 receptor which are useful for the treatment of disorders associated with dysfunction of the dopaminergic and noradrenergic systems. Web site: http://www.delphion.com/details?pn=US06420388__
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Treatment of mood disorders with functional antagonists of the glycine/NMDA receptor complex Inventor(s): Skolnick; Phil (Potomac, MD), Trullas; Ramon (Bethesda, MD) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 5,086,072 Date filed: June 18, 1990 Abstract: A method is disclosed for the treatment of mood disorders, including major depression, by administering an effective mood disorder treating amount of a compound possessing functional antagonist properties for the N-methyl-D-aspartate receptor complex. Excerpt(s): The present invention is concerned with the treatment of mood disorders in patients. More specifically, the present invention is concerned with the treatment of mood disorders, including major depressions, utilizing a class of compounds which possess functional antagonist properties at the N-methyl-D-aspartate (NMDA) receptor complex. The N-methyl-D-aspartate (NMDA) subtype of glutamate receptor and its associated cation channel are allosterically coupled to a strychnine-insensitive glycine receptor, forming a "supramolecular complex" (1). Excessive activation of this "supramolecular complex" has been linked to various neuropsychopharmacological disorders including seizure disorders, ischemic brain damage, and other neuropathologies. Both structural requirements for ligand binding to strychnineinsensitive glycine receptors on this "supramolecular complex" and their regional distribution in the central nervous system have been reported to differ remarkably from strychnine-sensitive glycine receptors. It has also been reported that there is an absolute requirement that there be present glycine for activation of NMDA receptor complexes as expressed in Xenopus oocytes (19). Skolnick et al, in copending U.S. patent application Ser. No. 07/390,745, filed on Aug. 8, 1989, discloses a method of treating neuropharmacological disorders which result from excessive activation of the NMDAreceptor complex, by administering to a patient an effective neuropsychopharmacological disorder-treating amount of a compound possessing
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partial agonist properties for the strychnine-insensitive glycine modulatory site of the NMDA-receptor complex. Suitable partial agonists of the NMDA-receptor complex, disclosed by Skolnick et al, include 1-aminocyclopropanecarboxylic acid, and derivatives thereof. Copending U.S. patent application Ser. No. 07/390,745, filed on Aug. 8, 1989, is incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US05086072__ •
Treatment of posttraumatic stress disorder, obsessive-compulsive disorder and related neuropsychiatric disorders Inventor(s): Fogel; Barry S. (Waban, MA) Assignee(s): Synchroneuron, LLC (Waban, MA) Patent Number: 6,391,922 Date filed: March 19, 1999 Abstract: The present invention describes a novel treatment for neuropsychiatric disorders, including anxiety disorders, mood disorders, psychotic disorders, somatoform disorders, and neuropsychiatric symptoms resulting from movement disorders. The treatment of the present invention utilizes any agent that simultaneously act as NMDA-type glutamate receptor antagonists and GABA-A receptor agonists. Preferably these two activities are characteristic of a single agent, for example acamprosate (calcium N-acetylhomotaurinate). Alternatively, separate agents having these activities can be combined as a compound or mixture and thereby administered together. The invention also provides for a third agent that acts as a non-competitive NMDA-receptor blocking agent or ion channel blocker, that augments the effect of the primary treatment. A particularly preferred ion channel blocking agent is magnesium. Excerpt(s): The present invention relates to novel drug treatments for neuropsychiatric disorders, for example anxiety disorders, psychotic disorders, mood disorders and somatoform disorders. These treatments relieve symptoms of disorders characterized by repetitive, stereotyped, an unwanted, intrusive, or involuntary thoughts, perceptions, or behaviors. These include posttraumatic stress disorder, obsessive-compulsive disorder, somatization disorder, hypochondriasis, and body dysmorphic disorder. Contemporary drug therapy for these conditions is limited in efficacy, with many patients continuing to have symptoms despite treatment. Antidepressants, mood stabilizers, anti-anxiety drugs, and antipsychotic drugs all have been used to treat them. Even when they provide some relief, persistent intrusive, repetitive mental phenomena may remain as a distressing symptom. Thus, when a person with posttraumatic stress disorder is treated with an antidepressant, mood may improve while "flashbacks" of the traumatic event continue. Clearly, there is a need for additional medications efficacious for the treatment of these disorders, and especially for medications that suppress or eliminate the recurrent unwanted, intrusive, or involuntary thoughts, perceptions and behaviors characteristic of those disorders. Such medications might also be used to reduce such symptoms when they occur as part of another psychiatric syndrome, such as depression or schizophrenia, or when they are incidental to a neurological disorder such as Tourette's syndrome or Huntington's disease. "re-experiencing the trauma, psychic numbing or avoidance of stimuli associated with the trauma, and increased arousal. Reexperiencing phenomena include intrusive memories, flashbacks, nightmares, and psychological or physiological distress in response to trauma reminders. Intrusive memories are spontaneous, unwanted, distressing recollections of the traumatic event. Repeated nightmares contain themes of the trauma or a highly accurate and detailed re-
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creation of the actual event(s). Flashbacks are dissociative states in which components of the event are relived, and the person feels as if he or she is experiencing the event for a few seconds for as long as days. Reactivity to trauma-related stimuli can involve intense emotional distress or physical symptoms similar to those of a panic attack, when the patient is exposed to sights, sounds, smells or events that were present during the traumatic event. Avoidance may include thoughts, feelings, situations or activities that are reminders of the trauma. Numbing may occur through amnesia, emotional detachment, restricted affect, or loss of interest in activities. Increased arousal may include insomnia, irritability, hypervigilance, increased startle response, or impaired concentration. This disorder can have pervasive effects on an individual's interpersonal behavior and all spheres of his or her life." (Charney D S et al.: Neurobiological mechanisms of human anxiety. In Fogel B S, Schiffer R B, Rao S M: Neuropsychiatry. Baltimore: Williams & Wilkins, 1996, pp. 257-286). Web site: http://www.delphion.com/details?pn=US06391922__ •
Uses of.alpha.-conotoxin peptides Inventor(s): Cartier; G. Edward (Salt Lake City, UT), Luo; Siqin (Salt Lake City, UT), McIntosh; J. Michael (Salt Lake City, UT), Olivera; Baldomero M. (Salt Lake City, UT), Yoshikami; Doju (Salt Lake City, UT) Assignee(s): University of Utah Research Foundation (Salt Lake City, UT) Patent Number: 6,265,541 Date filed: December 23, 1998 Abstract: The present invention relates to the use of.alpha.-conotoxin peptides having the general formulaXaa.sub.1 -Xaa.sub.2 -Cys-Cys-Xaa.sub.3 -Xaa.sub.4 -Pro-Xaa.sub.5 Cys-Xaa.sub.6 -Cys (SEQ ID NO: 1)for treating disorders regulated at neuronal nicotinic acetylcholine receptors. Such disorders include, but are not limited to, cardiovascular disorders, gastric motility disorders, urinary incontinence, nicotine addiction, mood disorders (such as bipolar disorder, unipolar depression, dysthymia and seasonal effective disorder) and small cell lung carcinoma, as well as the localization of small cell lung carcinoma. In this formula, Xaa.sub.1 is des-Xaa.sub.1, Tyr, mono-iodo-Tyr or diiodo-Tyr, Xaa.sub.2 is any amino acid, Xaa.sub.3 is any amino acid, Xaa.sub.4 is any amino acid, Xaa.sub.5 is any amino acid and Xaa.sub.6 represents a peptide of 3-7 amino acids. Disulfide linkages exist between the first and third cysteines and the second and fourth cysteines. Pro may be replaced with hydroxy-Pro. The C-terminus may contain a hydroxyl or an amide group, preferably an amide group. Excerpt(s): This invention relates to uses of relatively short peptides about 14-17 residues in length, which are naturally available in minute amounts in the venom of the cone snails or analogs to the naturally available peptides, and which include two cyclizing disulfide linkages. The publications and other materials used herein to illuminate the background of the invention, and in particular, cases to provide additional details respecting the practice, are incorporated by reference, and for convenience are referenced in the following text by author and date and are listed alphabetically by author in the appended bibliography. Mollusks of the genus Conus produce a venom that enables them to carry out their unique predatory lifestyle. Prey are immobilized by the venom that is injected by means of a highly specialized venom apparatus, a disposable hollow tooth that functions both in the manner of a harpoon and a hypodermic needle.
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Web site: http://www.delphion.com/details?pn=US06265541__
Patent Applications on Mood Disorders As of December 2000, U.S. patent applications are open to public viewing.10 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 mood disorders: •
Bisarylamines as potassium channel openers Inventor(s): Andrew McNaughton-Smith, Grant; (Morrisville, NC), Salvatore Amato, George; (Cary, NC) Correspondence: Townsend And Townsend And Crew, Llp; Two Embarcadero Center; Eighth Floor; San Francisco; CA; 94111-3834; US Patent Application Number: 20020193597 Date filed: March 11, 2002 Abstract: Compounds, compositions and methods are provided which are useful in the treatment of diseases through the modulation of potassium ion flux through voltagedependent potassium channels. More particularly, the invention provides bisarylamines, compositions and methods that are useful in the treatment of central or peripheral nervous system disorders (e.g., migraine, ataxia, Parkinson's disease, bipolar disorders, trigeminal neuralgia, spasticity, mood disorders, brain tumors, psychotic disorders, myokymia, seizures, epilepsy, hearing and vision loss, Alzheimer's disease, age-related memory loss, learning deficiencies, anxiety and motor neuron diseases) and as neuroprotective agents (e.g., to prevent stroke and the like) by opening potassium channels associated with the onset or recurrence of the indicated conditions. Excerpt(s): The present application claims priority to U.S. Provisional Patent Application Serial No. 60/277,329, filed on Mar. 19, 2001, the disclosure of which is incorporated herein by reference in its entirety for all purposes. This invention relates to the use of certain bisarylamines as potassium channel openers and to the treatment of diseases modulated by potassium channel opening. Additionally, this invention relates to novel compounds that are useful as potassium channel openers. Ion channels are cellular proteins that regulate the flow of ions, including calcium, potassium, sodium and chloride, into and out of cells. These channels are present in all human cells and affect such processes as nerve transmission, muscle contraction and cellular secretion. Among the ion channels, potassium channels are the most ubiquitous and diverse, being found in a variety of animal cells such as nervous, muscular, glandular, immune, reproductive, and epithelial tissue. These channels allow the flow of potassium in and/or out of the cell under certain conditions. For example, the outward flow of potassium ions upon opening of these channels makes the interior of the cell more negative, counteracting depolarizing voltages applied to the cell. These channels are regulated, e.g., by calcium sensitivity, voltage-gating, second messengers, extracellular ligands, and ATPsensitivity. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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This has been a common practice outside the United States prior to December 2000.
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Certain arylaliphatic and heteroaryl-aliphatic piperazinyl pyrazines and their use in the treatment of serotonin-related diseases Inventor(s): Jonsson, Mattias; (Uppsala, SE), Nilsson, Bjorn; (Uppsala, SE), Nilsson, Jonas; (Uppsala, SE), Pelcman, Benjamin; (Stockholm, SE), Ringberg, Erik; (Uppsala, SE), Tejbrant, Jan; (Enskede, SE), Thor, Markus; (Knivsta, SE) Correspondence: Jeffrey D. Hsi; Fish & Richardson P.C.; 225 Franklin Street; Boston; MA; 02110-2804; US Patent Application Number: 20030092694 Date filed: October 11, 2002 Abstract: The invention relates to compounds of the general formula (I): 1whereinAr is optionally substituted aryl or heteroaryl;A is (i) --O--, --S--, --SO.sub.2--, --NH--, (ii) a C.sub.1-4-alkyl- or C.sub.1-6-acyl-substituted nitrogen atom or (iii) a C.sub.1-8-alkylene chain or a heteroalkylene chain having 2 to 8 chain atoms, which optionally contains at least one unsaturation, and which may be substituted and/or contain a bridge to form a saturated or partially or fully unsaturated ring having 3-8 ring members;B is -C(R.sub.4)(R.sub.5)--, --OC(R.sub.4)(R.sub.5)--, --N(R.sub.6)C(R.sub.4)(R.sub.5)--, -N(R.sub.6)--, --O--, --S-- or --SO.sub.2--;R is optionally substituted C.sub.3-8-cycloalkyl, aryl or heteroaryl;R.sub.1 is (i) a saturated or unsaturated azacyclic or aminoazacyclic ring, or a saturated diazacyclic or aminodiazacyclic ring, which has 4 to 7 ring members, or a saturated aminoazabicyclic, azabicyclic or diazabicyclic ring which has 7 to 10 ring members, which rings optionally are substituted in one or more positions, or a group -[C(R.sub.4)(R.sub.5)].sub.xN(R.sub.2a)(R.sub.3a)];R.sub.2a, R.sub.3a, R.sub.4, R.sub.5, R.sub.6 and x are as defined in the claims, and n is 0 or 1; and pharmaceutically acceptable salts, hydrates and prodrug forms thereofThe compounds may be prepared by per se conventional methods and can be used for treating a human or animal subject suffering from a serotonin-related disorder, such as eating disorders, especially obesity, memory disorders, schizophrenia, mood disorders, anxiety disorders, pain, sexual dysfunctions, and urinary disorders The invention also relates to such use as well as to pharmaceutical compositions comprising a compound of formula (I) Excerpt(s): The present application is a continuation-in-part application of app. Ser. No. 09/5/73,348, "Novel Compounds, Their Use and Preparation", Attorney Docket No. 1614-233P, filed on May 19, 2000, which claims priority to provisional App. No. 60/137,527, filed on Jun. 3, 1999; the entire contents of which are hereby incorporated by reference. The present invention relates to novel compounds, to pharmaceutical compositions comprising the compounds, to processes for their preparation, as well as to the use of the compounds for the preparation of a medicament which particularly acts on the central nervous system. Many diseases of the central nervous system are influenced by the adrenergic, the dopaminergic, and the serotonergic neurotransmitter systems. For example, serotonin has been implicated in a number of diseases and conditions which originate in the central nervous system. A number of pharmacological and genetic experiments involving receptors for serotonin strongly implicate the 5HT.sub.2c receptor subtype in the regulation of food intake (Obes. Res. 1995, 3, Suppl. 4, 449S-462S). The 5-HT.sub.2c receptor subtype is transcribed and expressed in hypothalamic structures associated with appetite regulation. It has been demonstrated that the non-specific 5-HT.sub.2c receptor agonist m-chlorophenylpiperazine (mCPP), which has some preference for the 5-HT.sub.2c receptor, causes weight loss in mice that express the normal 5-HT2c receptor while the compound lacks activity in mice expressing the mutated inactive form of the 5-HT.sub.2c receptor (Nature 1995, 374, 542546). In a recent clinical study, a slight but sustained reduction in body weight was
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obtained after 2 weeks of treatment with mCPP in obese subjects (Psychopharmacology 1997, 133, 309-312). Weight reduction has also been reported from clinical studies with other "serotonergic" agents (see e.g. IDrugs 1998, 1, 456-470). For example, the 5-HT reuptake inhibitor fluoxetine and the 5-HT releasing agent/reuptake inhibitor dexfenfluramine have exhibited weight reduction in controlled studies. However, currently available drugs that increase serotonergic transmission appear to have only a moderate and, in some cases, transient effects on the body weight. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Composition comprising cocoa Inventor(s): Raggers, Rene John; (Amsterdam, NL), Ter Laak, Wies; (Amsterdam, NL), Verdegem, Peter Julien Edward; (Zetten, NL) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20020172732 Date filed: March 21, 2001 Abstract: The invention pertains to a composition and a method for the treatment of mood disorders, in particular of treating, preventing or alleviating depression, mood disorders or insufficient mood, obesity, overweight, premenstrual syndrome, craving, carbohydrate craving, chocolate craving, menopausal complaints, erectile dysfunction and/or reduced libido, The composition contains cocoa or one or more of its pharmacologically active components, and a dopamine D2 receptor agonist. Excerpt(s): The invention concerns nutritional and pharmaceutical compositions containing cocoa components for improving mood. Cocoa and chocolate comprise several advantageous pharmacologically active components, and have therefore, knowingly or unknowingly, been used to alleviate or treat certain disorders. There remains a vast interest for compositions which induce the pharmacological effects of cocoa or chocolate, however which do not have the adverse side effect induced by chocolate and/or cocoa or one or more of its pharmacological components. Products available within the art, which provide the advantageous effects of the pharmacological compounds within the cocoa/chocolate, appeared insufficient. Many cocoa-containing products have high fat or carbohydrate content, causing obesity and overweight. Alternatives to these products include diet and low fat products, such as low fat cocoa powder, cocoa extracts and the like. Pharmacological compounds within cocoa or chocolate have been used in products providing appetite suppression and mood improvement. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Delta9 tetrahydrocannabinol (Delta9 THC) solution metered dose inhalers and methods of use Inventor(s): Byron, Peter R.; (Richmond, VA), Lichtman, Aron H.; (Richmond, VA), Martin, Billy R.; (Richmond, VA), Peart, Joanne; (Richmond, VA) Correspondence: Mcguire Woods; Tysons Corner; Suite 1800; 1750 Tysons Boulevard; Mclean; VA; 22102-4215; US Patent Application Number: 20020031480 Date filed: September 4, 2001 Abstract: The present invention provides therapeutic formulations for solutions of.DELTA.sup.9-tetrahydrocannabinol (.DELTA.sup.9 THC) to be delivered by metered dose inhalers. The formulations, which use non-CFC propellants, provide a stable aerosol-deliverable source of.DELTA.sup.9 THC for the treatment of various medical conditions, such as: nausea and vomiting associated with chemotherapy--muscle spasticity; pain; anorexia associated with AIDS wasting syndrome, epilepsy; glaucoma; bronchial asthma; and mood disorders. Excerpt(s): This application is a continuation-in-part of pending U.S. Ser. No. 09/273,766 which claims priority of U.S. provisional application serial No. 60/105,850 filed Oct. 27, 1998, and the complete contents of those applications are incorporated herein by reference. The invention is generally related to the therapeutic use of.DELTA.sup.9 Tetrahydrocarnabinol (.DELTA.sup.9 THC). In particular, the invention provides a metered dose inhaler (MDI) for the aerosol administration of.DELTA.sup.9 THC to patients suffering from nausea and vomiting associated with cancer chemotherapy, muscle spasticity, pain, anorexia associated with AIDS wasting syndrome, epilepsy, glaucoma, bronchial asthma, mood disorders, and the like. In 1997, the National Institutes of Health (NIH) released a review of the scientific data concerning potential therapeutic uses for marijuana. In that review, the NIH found that marijuana may indeed have beneficial medicinal effects and recommended that researchers develop alternative dosage forms for the drug, such as a "smoke free" inhaled delivery system. Workshop on the medical utility of marijuana, National Institutes of Health, August 1997. Studies have documented therapeutically beneficial medicinal uses of the major active component of marijuana,.DELTA.sup.9 tetrahydrocannabinol (.DELTA.sup.9 THC). Beal, J. A., Olson, R., Lefkowitz, L., Laubenstein, L., Bellman, P., Yangco, B., Morales, J. O., Murphy, R., Powderly, W., Plasse, T. F., Mosdell, K. W. and Shepard, K. W., Long-term efficacy and safety of dronabinol for acquired immunodeficiency syndrome-associated anorexia, J Pain. Symptom Manage. 14:7-14 (1997); Beal, J. A., Olson, R., Laubenstein, L., Morales, J. O., Beliman, B., Yangco, B., Lefkowitz, L., Plasse, T. F. and Shepard, K. V. Dronabinol as a treatment for anorexia associated with weight loss in patients with AIDS, J Pain. Symptom Manage,. 10: 89-97 (1995); McCabe, M., Smith, F. P., MacDonald, J. S., Wooley, P. V., Goldberg, D. and Schein, P. S., Efficacy of tetrahydrocannabinol in patients refractory to standard antiemetic therapy, Invest. New Drugs 6:243-246 (1988); Lucas, V. S. and Laszlo, J.DELTA.sup.9-THC for refractory vomiting induced by cancer chemotherapy, JAMA 243:1241-1243 (1980); Sallan, S. E., Cronin, C., Zelen, M. and Zinberg, N. E., Antiemetics in patients receiving chemotherapy for cancer: a randomized comparison of.DELTA.sup.9 THC and prochlorperazine, N. Engl. J Med., 302:135-138 (1980); Frytak, S., Moertel, C. G., O'Fallon, J R., Rubin, J., Creagan, E. T., O'Connell, M. J., Schutt, A. J. and Schwartau, N. W., Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy: a comparison with prochlorperazine and a placebo, Ann. Inter. Med 91:825-830 (1979); Chang, A. E., Shiling, D. J., Stillman, R. C., Goldgerg, N. H., Seipp, C.
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A., Barofdky, I., Simon, R. M. and Rosenberg S A,.DELTA.sup.9 THC as an antiemitic in cancer patients receiving high-dose methotrexate. Ann. Internal Med. 91:819-824 (1979); Sallan, S. E., Zinberg, N. E. and Frei, I. E., Antiemetic effect of.DELTA.sup.9 THC in patients receiving cancer chemotherapy, New Engl. J Med. 293:795-797 (1975); Noyes, J R., Brunk, S. F., Baram, D. A. and Canter, A., The analgesic properties of.DELTA.sup.9 THC and codeine. J Clin. Pharmacol 15:139-143 (1975); Noyes, R., Jr., Brunk, S. F., Baram, D. A. and Canter, A., Analgesic effect of.DELTA.sup.9 tetrahydrocannabinol, Clin. Pharmacol & Ther 18:84-89 (1975); Brenneisen, R., Egli, A., Elosohlly, M. A., Henn, V. and Spiess, Y., The effect of orally and rectally administered.DELTA.sup.9 THC on spasticity: a pilot study with 2 patients, Int. J Clin. J Pharmocol Ther. 34:446-452 (1996); Ungerleider, J. T., Andyrsiak, T. F. L., Ellison, G. W. and Myers, L. W.,.DELTA.sup.9 THC in the treatment of spasticity associated with multiple sclerosis, Adv. Alcohol Subst. Abuse 7:39-50 (1987); Clifford, D. B., Tetra-hydrocannabinol for tremor in multiple sclerosis, Ann. Neurol 13:669-171 (1983); Petro, D. J. and Ellenberger, C., Treatment of human spasticity with delta 9-tetrahydrocannabinol, J Clin. Pharmacol 21:413S-416S (1981); Maurer, M., Henn, V., Dittrich, A. and Hofman, A., Delta 9tetrahydrocannabinol shows antispastic and analgesic effects in a single case doubleblind trial, Eur. Arch. Psychiatry Neurol Sci. 240:1-4 (1990); Merrift, J., Crawford, W., Alexander, P., Anduze, A. and Gelbart, S., Effects of marihuana on intra ocular and blood pressure in glaucoma, Opht. 87:222-228 (1980); Cooler, P. and Gregg, J. M., Effect of delta 9-.DELTA.sup.9 THC on intra ocular pressure in humans. South. Med J 70:951954 (1977). Table 1 summarizes the findings of these studies. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Felbamate derived compounds Inventor(s): MacDonald, Timothy L; (Charlottesville, VA) Correspondence: University OF Virginia Patent Foundation; 1224 West Main Street, Suite 1-110; Charlottesville; VA; 22903; US Patent Application Number: 20030166648 Date filed: November 1, 2002 Abstract: The invention relates to the use of certain felbamate derivatives to treat neuropathic pain, obesity, glaucoma, depression, and mood disorders, as well as other conditions. Excerpt(s): Felbamate (2-phenyl-1,3-propanediol dicarbamate) is a known pharmaceutical compound having been described in U.S. Pat. Nos. 2,884,444 and 4,868,327, the disclosures of which are expressly incorporated herein. Felbamate is a modulator of NMDA (N-methyl-D-aspartate) receptor function, and a glycine site antagonist but also has other reported mechanisms of actions. Felbamate has also been reported to interact at the AMPA/kainate receptor, facilitate the function of the GABA receptor, and modulate Na.sup.+ channel conductance. Felbamate has also been demonstrated to decrease delayed neuronal cell death after kainic acid induced status epilepticus in animals. Glycine or d-serine were able to functionally reverse the anticonvulsant and ischemic protective effect of felbamate. Felbamate has been proposed for use in treating various neurological disorders including the control of epileptic seizures. For example, U.S. Pat. No. 4,978,680 discloses the use of felbamate for the prevention and control of epileptic seizures; U.S. Pat. No. 5,082,861 relates to the use of felbamate for the prevention and control of epileptic seizures associated with complex partial seizures; and U.S. Pat. No. 5,292,772 relates to the use of felbamate for the
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prevention and control of epileptic seizures associated with Lennox-Gastaut syndrome. The disclosures of U.S. Pat. Nos. 4,978,680, 5,082,861 and 5,292,772 are expressly incorporated herein. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Involvement of the BDNF gene in mood disorders Inventor(s): Kennedy, James Lowery; (Toronto, CA), Macciardi, Fabio; (Toronto, CA) Correspondence: Bereskin And Parr; Scotia Plaza; 40 King Street West-suite 4000 Box 401; Toronto; ON; M5h 3y2; CA Patent Application Number: 20030064401 Date filed: August 30, 2002 Abstract: Methods and kits for determining susceptibility of a patient to mood disorders are described. The method involves analyzing a sample comprising nucleic acids from a patient for a polymorphism in the promoter region of the BDNF gene. Excerpt(s): This application claims the benefit under 35 USC.sctn.119(e) from U.S. provisional patent application Ser. No. 60/316,024, filed Aug. 31, 2001. The present invention relates to methods and kits for determining susceptibility of a patient to mood disorders. Bipolar Disorder (BP) is a severe psychiatric disease that afflicts about 1% of the general population worldwide (American Psychiatric Association, 1994). BP is characterized by recurrent episodes of mania and depression. Family, adoption and twin studies (Craddock and Jones, 1999) have shown that the disorder has a strong genetic component, and a non-mendelian mode of inheritance with more than one gene involved. (Gershon, 1990; McGuffin and Katz, 1989). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Kainate receptor subunit GLUR7 polymorphisms for diagnosing predisposition and for therapy of mood disorders Inventor(s): Heinemann, Stephen F.; (La Jolla, CA), Schiffer, Hans H.; (San Diego, CA) Correspondence: Barry S. Wilson; Foley & Lardner; 23rd Floor; 402 West Broadway; San Diego; CA; 92101-3542; US Patent Application Number: 20030033619 Date filed: May 11, 2001 Abstract: Provided are methods for determining the predisposition of a subject to a mood disorder by determining in a biological sample of a subject, the presence of a kainate receptor subunit GluR7 allelic genotype or allelic phenotype associated with predisposition to a mood disorder. The allelic genotype is homozygosity for a thymine containing nucleotide at position 928 (928T/T) or homozygosity for a guanine containing nucleotide position 928 (928G/G). In addition, a predominant expression of one GluR7 allele over the other allele in a heterozygous individuals also predicts predisposition to a mood disorder. The present invention also includes a method of treating or preventing a mood disorder and methods for identifying a compound useful for treatment. Transgenic non-human animals that express only a particular human GluR7 allele at nucleotide position 928 also are provided as a model of a human mood disorder.
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Excerpt(s): The present invention relates generally to the identification of cell receptors and encoding genes that are involved in neurological disease and the identification of receptors and encoding genes involved in mono and bipolar mood disorders. Mood disorders rank among the top ten causes of disability worldwide. Unipolar depressive disorder and bipolar disorder are mood disorders with high prevalence in the population and an enormous impact on the life of affected individuals and society (Oruc et al., (1998a) Med. Arch., 52:107-112; Craddock and Jones, (1999) Am. J. Psychiatry, 149443-454; Oruc et al., (1998b) Med. Arch, 52:167-173; Doris et al., (1999) Lancet, 354:1369-1375). Disability and suffering from a mood disorder even extends beyond the patient to their spouses, children, parents, siblings, and friends, who experience frustration, guilt, anger, financial hardship and, on occasion, physical abuse, all in their attempts to assuage or cope with the depressed person's suffering. A large portion of health care expenditures go to treating individuals having depression. Paradoxically, much of treatment does not address the mood disorder because individuals try to seek treatment for other problems in order to avoid the stigma associated with having a mood disorder diagnosis. Consequently, patients with depression undergo extensive and expensive diagnostic procedures of no benefit while their mood disorder goes undiagnosed. The genetics of mood disorders appears complex and it has been proposed that anticipation and/or genomic imprinting of candidate genes contribute to the observed mode of inheritance (Grigoroiu-Serbanescu (1992) Rom J Neural Psychiatry, 30,265-277. Grigoroiu-Serbanescu (1995) Acta Psychiatr Scand, 92, 365-370.; McMahon, et al. (1995) Am J Hum Genet, 56, 1277-1286; Kato, et al. (1996) Am J Med Genet, 67, 546-550; Grigoroiu-Serbanescu, et al.(1997) Br J Psychiatry, 170, 162-166). Researchers have identified genes generally involved in neurodegenerative disease such as genes of serotonergic, catecholaminergic or GABAergic neurotransmitter systems as well as the genes of the glutamate receptor system. Despite these intensive research efforts, the specific genes involved in mood disorder pathology remain to be identified. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method of treating depression with delta receptor agonist compounds Inventor(s): Chang, Kwen-Jen; (Chapel Hill, NC), Gengo, Peter J.; (Raleigh, NC), Pendergast, William; (Durham, NC) Correspondence: Intellectual Property / Technology Law; PO Box 14329; Research Triangle Park; NC; 27709; US Patent Application Number: 20030144299 Date filed: October 29, 2002 Abstract: Compositions and methods for treatment of depression or other affective mood disorders or pathological mental and/or emotional states, by administration to a subject suffering or susceptible to same, of therapeutically effective delta receptor agonist compound(s), optionally in combination with other mood disorder-combating agents. Excerpt(s): This application claims priority from U.S. Provisional Patent Application No. 60/340,084 filed on Oct. 29, 2001 and U.S. Provisional Patent Application No. 60/337,887 filed on Nov. 2, 2001. The present invention relates to compositions and methods of treatment of depression or other affective mood disorders or pathological mental and/or emotional states, by administration to a subject suffering or susceptible to same, of delta opioid receptor agonist compound(s), optionally in combination with other agents. Depression is a difficult mental disorder to treat. Patients having such a disorder
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are often reluctant to seek the medical attention necessary to diagnose the disorder. Such reluctance is often related to the patient's fear of the stigma associated with seeking psychiatric help or to the patient's feeling of worthlessness associated with depression. Moreover, once the patients seek competent psychiatric help, it is difficult to successfully treat the disorder through a psychoanalytic approach alone. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Novel heterocyclic urea derivatives and their use as dopamine D3 receptor ligands Inventor(s): Bordeau, Kenneth J.; (Kintnersville, PA), Brooks, Sarah; (Belmont, CA), Hemmerle, Horst; (Indianapolis, IN), Hendrix, James A.; (Hillsborough, NJ), Mueller, Paul J.; (Hoboken, NJ), Strupczewski, Joseph T.; (Flemington, NJ), Urmann, Matthias; (Eschborn, DE), Zhao, Xu-Yang; (Bridgewater, NJ) Correspondence: Ross J. Oehler; Aventis Pharmaceuticals INC.; Route 202-206, Mail Code: D-303a; Bridgewater; PA; 08807; US Patent Application Number: 20030229066 Date filed: February 19, 2002 Abstract: The invention relates to heterocyclic substituted urea derivatives that display selective binding to dopamine D.sub.3 receptors. In another aspect, the invention relates to a method for treating central nervous system disorders associated with the dopamine D.sub.3 receptor activity in a patient in need of such treatment comprising administering to the subject a therapeutically effective amount of said compounds for alleviation of such disorder. The central nervous system disorders that may be treated with these compounds include Psychotic Disorders, Substance Dependence, Substance Abuse, Dyskinetic Disorders (e.g. Parkinson's Disease, Parkinsonism, NeurolepticInduced Tardive Dyskinesia, Gilles de la Tourette Syndrome and Huntington's Disease), Dementia, Anxiety Disorders, Sleep Disorders, Circadian Rhythm Disorders and Mood Disorders. The subject invention is also directed towards processes for the preparation of the compounds described herein as well as methods for making and using the compounds as imaging agents for dopamine D.sub.3 receptors. Excerpt(s): 1) Psychoses (including schizophrenia)--See, for example, Biochem Pharmacol, 1992, 3(4), 659-66; Clin Neuropharmacol, 1993,16(4), 295-314; Neuropsychopharmacology, 1997, 16(6), 375-84; Am J Psychiatry, 1999,156(4), 610-616; Psychopharmacology (Berl), 1995, 120(1), 67-74. 2) Substance dependence and substance abuse--See, for example, Neuroreport, 1997, 8(9-10), 2373-2377; J Pharmacol Exp Ther, 1996, 278(3),1128-37; Brain Res Mol Brain Res, 1997, 45(2), 335-9. 3) Mood Disorders (including mania, depressive disorders and bipolar disorders)--See, for example, Clin Neuropharmacol, 1998, 21 (3),176-80; Am J Med Genet, 1998, 81 (2),192-4; J Clin Psychiatry, 1995, 56(11), 514-518; J Clin Psychiatry, 1995, 56(9), 423-429; Am J Med Genet,1995, 60(3), 234-237; Pharmacopsychiatry, 1999, 32(4), 127-135; J Affect Disord, 1999, 52(1-3), 275-290; Am J Psychiatry, 1999,156(4), 610-616. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Portable light delivery apparatus and methods Inventor(s): Savage, Henry C. JR.; (Orem, UT), Savage, Kent W.; (American Fork, UT) Correspondence: Trask Britt; P.O. Box 2550; Salt Lake City; UT; 84110; US Patent Application Number: 20030187486 Date filed: March 29, 2002 Abstract: A portable light delivery device for delivering light to the blood supply of a human body through a non-ocular area of skin on the body includes an attachment member, a portable light delivery unit connected to the attachment and a portable power supply. The portable light delivery provides one or more wavelengths of light within a specifically-determined range of intensity and a specifically determined angle of illumination. A portable control unit may be included on the light delivery device for selectively controlling the light delivery unit. A programming device associated with the control unit selectively changes the programming of the controller. The light delivery device is portably secured to a region of the body having a substantial amount of blood vessels near the surface thereof to deliver light to the blood supply of the body for treating mood disorders, seasonal affective disorder and disorders involving circadian rhythm and sleep. Excerpt(s): This invention relates to means for delivering light to the blood supply of a human body to treat mood disorders, sleep and body cycle problems in humans. More particularly, the present invention concerns a portable and wearable light source apparatus, and methods related thereto, for delivering light to the blood supply by exposing a non-ocular portion of the body to light in pre-selected wavelengths, for preselected periods of time at optimal times of the day. Seasonal affective disorder (SAD) is a form of recurrent depressive or bipolar disorder, that seems to occur at times in the year when the natural amount of light decreases, such as in the winter. Symptoms of SAD include hypersomnia, carbohydrate-craving and weight gain, as well as panic disorders and other ailments. In such cases, it has been found to be effective to apply light therapy, that is to introduce the body to artificial light of varying intensities and wavelengths and at different times of the day, in order to increase the amount of light provided to the body. See, e.g. "Winter Depression and Phototherapy," Gysin F; Gross F Acta Med Port (Portugal) December 1997, 10 (12) p 887-93. Other types of non-seasonal, major depressive disorders, such as bulimia, have also been found to respond favorably to the application of various types of artificial light to supplement the natural light to the body of the subject. See, e.g., "Light Therapy in Bulimia Nervosa" Blouin A G et al, Department of Psychiatry, Ottawa Civic Hospital, Ontario, Canada. Psychiatry Res (Ireland) Feb. 28, 1996, 60 (1) p 1-9. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Regulation of human glur5 -like receptor Inventor(s): Ramakrishnan, Shyam; (Brighton, MA) Correspondence: Banner & Witcoff; 1001 G Street N W; Suite 1100; Washington; DC; 20001; US Patent Application Number: 20030099982 Date filed: September 18, 2002
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Abstract: Reagents and methods for regulating the high affinity binding of GluR5-like receptor (GR5LR) to kainate are provided. Such reagents and methods can be used inter alia, to treat or prevent urinary incontinence, epilepsy, schizophrenia and other mood disorders, neurodegenerative diseases such as Huntington's disease and Alzheimer's disease, ischemia, and pain. Excerpt(s): The invention relates to the area of regulation of glutamate-gated ion channel receptors. More particularly, the invention relates to the regulation of human GluR5-like receptors to increase or decrease excitatory neurotransmission at synapses. L-glutamate is the major excitatory neurotransmitter in the vertebrate central nervous system (CNS). L-glutamate opens cation channels that mediate fast excitatory synaptic responses and establish and maintain synaptic plasticity underlying learning and memory. These cation channels also mediate cell death resulting from excessive glutamate release in the CNS due to acute injury or environmental excitotoxins. Thus, glutamate receptors are involved in the developmental plasticity processes and long term potentiation. Further, the continuous activation of glutamate receptors can contribute to the pathogenesis of diseases such as ischemia, pain, epilepsy, schizophrenia, Huntington's disease, Parkinson's disease and Alzheimer's disease. There are distinct ionotropic glutamate receptor subtypes: NMDA, AMPA-low affinity kainate, and high affinity kainate receptors. The AMPA-low affinity kainate and high affinity kainate receptors are referred to as non-NMDA receptors. GluR5 is a high affinity kainate glutamate receptor. GluR5 has a high affinity for domoate and kainate and is capable of forming homomeric channels that can be gated by domoate, kainate, L-glutamate, and AMPA. See Sommer et al., EMBO J. 11, 1651-1656, 1992; Bettler et al., Neuron. 5, 583-595, 1990. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
System and method for longitudinal analysis of mood disorders Inventor(s): Glenn, Tasha; (Fullerton, CA), Whybrow, Peter C.; (Plainfield, NH) Correspondence: Price And Gess; Suite 250; 2100 S.E. Main Street; Irvine; CA; 926146238; US Patent Application Number: 20020150872 Date filed: July 26, 2001 Abstract: In a computer system having a storage device, a method for gathering clinical data useful in the clinical analysis and treatment of mood disorders. The method includes such steps as displaying a main menu including a multiplicity of icons depicting inquiries to be answered by a patient; and, storing the patient's answers to the inquiries as clinical data generated on a regular basis by the patient. The method further includes selecting a point on a scale depicting the patient's current mood; selecting a sleep icon for updating sleep data; and, selecting a medication icon for updating type and amount of medication taken. The present invention is also capable of creating longitudinal charts and statistics based on selections made by a patient over a given period of time. Excerpt(s): This Application claims the benefit of U.S. Provisio
