Case Studies in Psychiatry for Updating the DSM

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Case Studies in Psychiatry for Updating the DSM

Tuesday, February 8, 2011

The New York Academy of Sciences

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The Diagnostic and Statistical Manual of Mental Disorders (DSM) is the benchmark by which psychiatric and mental health disorders are defined, diagnosed, and classified. A major revision of the DSM is currently underway, and the forthcoming DSM-5 will include sweeping changes to the way mental disorders are categorized and diagnosed. One prominent area of debate revolves around whether the time has come for insights from basic neuroscience, behavioral and cognitive science, and molecular genetics to be incorporated into the diagnostic criteria. This meeting will examine the current relationship between basic research and psychiatric diagnosis and the issues that need to be addressed for these two perspectives to more effectively inform one another. Speakers will focus on three disorders that stand at the forefront of this transition: attention-deficit/hyperactivity disorder, bipolar disorders, and major depressive disorder.

Networking reception to follow.

Agenda

*Presentation times are subject to change.


1:00 PM

Opening Remarks
Sonya Dougal, PhD, The New York Academy of Sciences

1:10 PM

Keynote Address
Toward a Scientific Psychiatry: The Bad and Good News
John H. Krystal, MD, Yale University School of Medicine

1:40 PM

Will Neuroimaging Have a Role in Updating DSM-6 Attention-Deficit/Hyperactivity Disorder (ADHD)?
F. Xavier Castellanos, MD, New York University Child Study Center

2:00 PM

Genetics of ADHD and Associated Comorbid Disorders
Maximilian Muenke, MD, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health

2:20 PM

The Brain in Bipolar Disorder: A Developmental View from Neuroimaging Research
Hilary Blumberg, MD, Yale School of Medicine

2:40 PM

Bipolar Disorder: Disorders of Synaptic and Neural Plasticity
Husseini K. Manji, MD, Johnson & Johnson

3:00 PM

Coffee Break

3:30 PM

Neurobiology of Mood Disorders: Implications for a Diagnostic Classification
J. John Mann, MD, Columbia University Medical Center

3:50 PM

Ketamine  - A Breakthrough Treatment for Therapy Resistant Depression
Dennis Charney, MD, Mount Sinai School of Medicine

4:10 PM

Panel Discussion
Moderator: Kevin Lee, PhD, Ellison Medical Foundation

5:00 PM

Closing Address
Darrel A. Regier, MD, MPH, American Psychiatric Association

5:30 PM

Networking Reception

Speakers

Organizers

Kevin Lee, PhD

The Ellison Medical Foundation

Kevin Lee, PhD, is the Deputy Executive Director of the Ellison Medical Foundation, a philanthropic organization supporting biomedical research in the fundamental mechanisms of Aging and Neuroscience. The Ellison Medical Foundation was established by Lawrence Ellison, founder and CEO of Oracle Corporation.

Dr. Lee is a graduate of the University of Michigan and received his Ph.D. in biology from the Massachusetts Institute of Technology. He brings over 20 years of research experience in molecular genetics and neurobiology in biotechnology and academic research settings to his position as Deputy Executive Director. Prior to joining the Ellison Medical Foundation, Dr. Lee served as Executive Vice President-Research of Sentigen Biosciences. He was responsible for the start-up and development of this New York City-based biotechnology company leading to its acquisition by Invitrogen Corporation in 2006. He has served as a member of the Scientific Review Board for the Simons Foundation Autism Research Initiative in New York.

Dr. Lee’s long-term scientific interest has been in using genetics to learn how neurons in the brain are “wired up” during development to make functional circuits that relay sensory information and control behavior. Prior to Sentigen, he worked with Dr. Thomas Jessell in the Center for Neurobiology and Behavior at Columbia University, where he studied the specification, axonal projection, and functional connectivity of sensory interneurons in the spinal cord. He has been a National Merit Scholar, a National Science Foundation Pre-Doctoral Fellow, and an HHMI Fellow of the Life Sciences Research Foundation. He is the recipient of biotechnology patents and is the author of numerous research publications.

Sonya Dougal, PhD

The New York Academy of Sciences

Keynote Speaker

John H. Krystal, MD

Yale University School of Medicine

John H. Krystal, M.D. Is Robert L. McNeil, Jr. Professor of Translational Research and Chair of the Department of Psychiatry of the Yale University School of Medicine. He is principal investigator of the NIAAA Center for the Translational Neuroscience of Alcoholism, the VA Alcohol Research Center, and the Clinical Neuroscience Division of the VA National Center for PTSD. His clinical research program combines multiple approaches (psychopharmacology, neuroimaging, genetics) to develop and test mechanistic hypotheses related to the treatment of alcoholism, schizophrenia, PTSD, and depression. He has been editor of Biological Psychiatry since 2006 and he is president-elect of the American College of Neuropsychopharmacology.

Darrel A. Regier, MD, MPH

American Psychiatric Association

Dr. Regier has served for the past ten years as Executive Director of the American Psychiatric Institute for Research and Education (APIRE), as well as Director, Division of Research at the American Psychiatric Association (APA). A principle responsibility has been to coordinate the maintenance and revision plans for the APA’s Diagnostic and Statistical Manual. In 2006, he was named Vice-Chair of the DSM-V Revision Task Force to work jointly with the Task Force Chair, Dr. David Kupfer. Prior to taking this position, Dr. Regier completed 25 years at the National Institute of Mental Health (NIMH), during which time he directed three research divisions in the areas of epidemiology, prevention, clinical research, and health services research. He initiated the development of several areas of research including national surveys of prevalence of mental disorders, mental health service use in primary care and specialty settings, the organization and financing of such services, and international programs on the classification of mental disorders with the World Health Organization. He served as the Scientific Coordinator/Director for four National Advisory Mental Health Council reports to Congress on mental health insurance parity, and was a section editor of the Surgeon’s General’s Report on Mental Health. In the international arena, Dr. Regier served as the mental health coordinator for the Health Committee of the U.S./Russian Commission on Science and Technology and remains as a consultant to the World Health Organization’s mental health initiatives. He is currently the American Editor for the journal, Social Psychiatry and Psychiatric Epidemiology. He has also published over 200 articles, book chapters, and monographs. He received his medical degree from the Indiana University School of Medicine and completed his medical internship at Montefiore Hospital in the Bronx. After a psychiatry residency at the Massachusetts General Hospital (MGH)/Harvard Medical School, he completed his research training at the Harvard School of Public Health and a fellowship at MGH. At the completion of his NIMH service, Dr. Regier retired as a Rear Admiral and Assistant Surgeon General in the Commissioned Corps of the United States Public Health Service.

Speakers

Hilary Blumberg, MD

Yale School of Medicine

Dr. Hilary Patricia Blumberg is Associate Professor of Psychiatry, Diagnostic Radiology and in the Child Study Center, and Director of the Mood Disorders Research Program, at the Yale School of Medicine. She graduated summa cum laude from Harvard University and then completed her medical degree, psychiatry residency training and postdoctoral training in neuroimaging at Cornell University Medical College. She joined the faculty of the Yale School of Medicine in 1998. She has employed magnetic resonance imaging methods to identify brain circuitry differences in bipolar disorder, and utilized integrated genetic and developmental approaches to investigate mechanisms underlying the development of the disorder. She is the recipient of numerous awards, including the Klerman Award for Outstanding Clinical Research from the National Alliance for Research in Schizophrenia and Depression.

F. Xavier Castellanos, MD

New York University Child Study Center

F. Xavier Castellanos, MD is Neidich Professor of Child and Adolescent Psychiatry, Radiology, Physiology and Neuroscience, director of the Phyllis Green and Randolph Cowen Institute for Pediatric Neuroscience and vice-chair for research at the NYU Child Study Center in New York, NY. He also directs the Child and Adolescent Division at the Nathan Kline Institute for Psychiatric Research, Orangeburg, NY. Dr. Castellanos is an expert on the emerging neuroscience of Attention-Deficit/Hyperactivity Disorder (ADHD) and collaborates internationally on the neurobiology (imaging and genetics), and cognitive neuroscience of ADHD and autism spectrum disorders. Dr. Castellanos co-chairs the American Psychiatric Association DSM-5 Workgroup on ADHD and Disruptive Behavior Disorders and serves on the DSM-5 Task Force.

Dennis Charney, MD

Mount Sinai School of Medicine

Dr. Charney's arrival at Mount Sinai in 2004 signaled a new era of innovation in research, education, and clinical care. Since joining the faculty, he has established a culture of excellence that has elevated Mount Sinai School of Medicine — an institution founded in 1968 — to among the top medical schools in the nation. With an emphasis on translational research, Dr. Charney has accelerated the pace of change at Mount Sinai, streamlined collaboration across disciplines, and facilitated the integration of research, clinical care, and educational innovation. Dr. Charney led the creation of the School of Medicine’s Strategic Plan, an organizational restructuring that included the creation of 15 interdisciplinary research institutes. These institutes—chosen in the areas where Mount Sinai can truly excel—embody the institution’s mission as a leader in basic and clinical research.


A leading investigator on neurobiology and the treatment of mood and anxiety disorders, Dr. Charney has made fundamental contributions to the understanding of human anxiety, fear, mood, and resilience to stress. In addition, his research team has made major contributions to the discovery of novel and more effective treatments for mood and anxiety disorders. A prolific author, Dr. Charney has written more than 700 publications. He has authored or edited a dozen books, including Neurobiology of Mental Illness (Oxford University Press, USA, Third Edition, 2009); The Peace of Mind Prescription: An Authoritative Guide to Finding the Most Effective Treatment for Anxiety and Depression (Houghton Mifflin Harcourt, 2004); and The Physicians Guide to Depression and Bipolar Disorders (McGraw-Hill Professional, 2006). In 2011, Dr. Charney plans to publish his 13th book, which addresses emotional resilience.

Husseini K. Manji, MD

Johnson & Johnson

Husseini K. Manji, MD, FRCPC is the Global Therapeutic Area Head for Neuroscience for the Johnson & Johnson Pharmaceuticals Group. He was previously Chief, Laboratory of Molecular Pathophysiology & Experimental Therapeutics, NIH, and director of the NIH Mood and Anxiety Disorders Program, the largest program of its kind in the world. The major focus of his research has been the investigation of disease- and treatment-induced changes in gene and protein networks that regulate synaptic and neural plasticity in neuropsychiatric disorders. His work has helped to conceptualize these illnesses as genetically-influenced disorders of synaptic and neural plasticity, and has led to the investigation of novel therapeutics for refractory patients. He has also been actively involved in the development of biomarkers to help refine these multifactoral diseases into mechanism-based subcategories to develop targeted therapeutics. Dr. Manji is a previous recipient of numerous research awards, including the NIMH Director's Career Award for Significant Scientific Achievement, the A. E. Bennett Award for Neuropsychiatric Research, the NARSAD Mood Disorders Prize and the DBSA Klerman Senior Distinguished Researcher Award. Dr. Manji has been inducted into the National Academy of Sciences’ Institute of Medicine (IOM), has served as a Councilor of both the ACNP and Society of Biological Psychiatry, co-chairs the NIH Biomarkers Neuroscience Steering Committee, chaired the ACNP’s Task Force on New Medication Development, and is past president of the Society of Biological Psychiatry.

J. John Mann, MD

Columbia University Medical Center

Dr. J. John Mann is trained in Psychiatry and Internal Medicine and has a doctorate in Neurochemistry. He is Chief of the Molecular Imaging & Neuropathology Division and is The Paul Janssen Professor of Translational Neuroscience, Department of Psychiatry at Columbia University. His research employs functional brain imaging, neurochemistry and molecular genetics to probe the causes of depression and suicide. He has published 522 papers and edited 10 books on the subjects of the biology and treatment of mood disorders, suicidal behavior and other psychiatric disorders.

Maximilian Muenke, MD

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health

Dr. Muenke received his M.D. degree from the Free University of Berlin in 1979 where he graduated with a medical thesis in human genetics. After a medical internship at the Free University of Berlin, an award for postdoctoral training from the German Research Society, and a pediatrics residency at the Christian-Albrechts School of Medicine in Kiel, Dr. Muenke completed a postdoctoral fellowship in the Department of Human Genetics at Yale University where he worked on mapping human and murine genes with Uta Francke. He then moved to the Children's Hospital of Philadelphia/University of Pennsylvania School of Medicine where, after a clinical genetics fellowship under the direction of Elaine Zackai, he joined the faculty of the Departments of Pediatrics and Genetics. In 1997, Dr. Muenke joined the NHGRI as Chief of the Human Development Section within the Medical Genetics Branch, and in 2000 he was appointed Chief of the Medical Genetics Branch. His laboratory studies the genetics of normal and abnormal brain development.

Abstracts

Toward a Scientific Psychiatry: The Bad and Good News

John H. Krystal, MD, Yale University School of Medicine

Presentation will highlight critical limitations in our understanding of the neurobiology and genetics of psychiatric disorders that constrain the progress of our field in the realms of diagnosis, prognosis, treatment, and prevention. It will then highlight a number of areas where advances may contribute to shifts in our conceptualization of diagnosis and treatment.

Will Neuroimaging Have a Role in Updating DSM-6 Attention-Deficit/Hyperactivity Disorder (ADHD)?

F. Xavier Castellanos, MD, NYU Langone Medical Center and Nathan Kline Institute for Psychiatric Research

Attention-Deficit/Hyperactivity Disorder (ADHD), like all psychiatric disorders, is highly heterogeneous and will remain syndromically diagnosed in DSM-5. Multimodal imaging approaches, specially combined with emerging genetic findings, are beginning to provide the bases for a future neurobiologically grounded nosology. Recent key findings will be highlighted, along with a collaborative data-sharing initiative that is poised to accelerate the rate of discovery science relating to ADHD.

Genetics of ADHD and Associated Comorbid Disorders

Maximilian Muenke, MD, Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health

Attention-Deficit /Hyperactivity Disorder (ADHD), the most common behavioral disorder of childhood, is a complex genetic disorder with a heritability of at least 70%. To better understand the underlying causes we have studied large multigenerational families segregating ADHD. We have now identified genes that individually or in combination with other genes contribute to ADHD and comorbid disorders, such as oppositional defiant disorder (ODD), conduct disorder (CD), substance use disorder (SUD). Understanding the genetic basis of ADHD, ODD, CD, and SUD specific for each individual is a first step towards personalized medicine of these disorders.

The Brain in Bipolar Disorder: A Developmental View from Neuroimaging Research

Hilary Blumberg, MD, Yale School of Medicine

Adolescence is increasingly recognized as a critical period in the development of bipolar disorder. Dr. Blumberg will present neuroimaging research demonstrating differences in bipolar disorder in the brain circuitry that subserves emotional regulation, as well as the progression of brain differences during adolescence. She will discuss a neurodevelopmental model of bipolar disorder and its implications for the expression of the disorder in youths, as well as preliminary evidence for genetic mechanisms involved.

Bipolar Disorder: Disorders of Synaptic and Neural Plasticity

Husseini K. Manji, MD, Johnson & Johnson

Bipolar Disorder (BPD) is a multifactorial disorder resulting from interconnected genetic vulnerability and environmental stressors, and characterized by dysfunction in diverse biological systems that include an intricate network of limbic, striatal, and fronto-cortical circuits mediating mood state, cognition, self-awareness, insight, and many other functions. There is growing interest in BPD endophenotypes, in part because genes predisposing to BPD may be transmitted without expression of the clinical phenotype and because they may help resolve key questions regarding the molecular/genetic basis of this disorder. While much work remains to be done in evaluating candidate endophenotypes, this research avenue has enormous potential for unraveling the etiology and pathophysiology of BPD. Despite many formidable obstacles, there has also been progress in our understanding of the underlying molecular and cellular basis of BPD. In particular, recent evidence demonstrating that impaired signaling pathways may play a role in the pathophysiology of BPD, and that mood stabilizers exert major effects on signaling pathways that regulate neural and synaptic plasticity, have generated considerable excitement in the clinical neuroscience community, and are reshaping views about the neurobiological underpinnings of this disorder. Abnormalities in cellular plasticity cascades likely also represent the underpinnings of the impaired structural plasticity seen in morphometric studies of BPD. Many of these pathways play critical roles not only in "here and now" synaptic plasticity, but also in long-term cellular resilience. These observations serve to explain the regional atrophic, and perhaps degenerative, aspect of the illness in some patients, as well as the presence of signs normally associated with ischemic/hypoxic insults, such as white matter hyperintensities. The growing body of preclinical/clinical data also suggests that for many patients, optimal treatment may be attained by providing trophic support as well as targeting synaptic plasticity. Ongoing research may lead to a reconceptualization of our diagnostic classification and, ultimately, to treatment approaches tailored to illness stage and patient subpopulations.

Neurobiology of Mood Disorders: Implications for a Diagnostic Classification

J. John Mann, MD, Columbia University/ New York State Psychiatric Institute

Structural and functional brain imaging studies have identified similarities and differences in bipolar disorder and major depressive disorder that suggest that mood specific classification system is better than the current clinical categories for understanding the underlying pathophysiology. The identification of trait biological abnormalities is consistent with genetic and early life experiences molding the brain to create the neurological substrate of mood disorders in adulthood. Future directions include use of biomarkers to guide treatment selection and identify new treatment targets.

Ketamine - A Breakthrough Treatment for Therapy Resistant Depression

Dennis Charney, MD, Mount Sinai School of Medicine

The pace of therapeutic discovery for depression has lagged significantly behind other areas of medicine and current treatments are limited in efficacy and demonstrate a reliably slow time to onset of therapeutic benefit. However, reports of a rapid-onset antidepressant effect of the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine, even in patients with treatment-resistant depression (TRD), have engendered a new wave of clinical and basic science research examining the glutamate system and the NMDA receptor complex in depression pathophysiology and treatment. Recent observations link NMDA receptor blockade by ketamine with rapid up-regulation of synapse-related proteins and enhancement of neurotrophic effects. New research strategies hold significant potential to identify novel and urgently needed treatments with improved efficacy and a more rapid onset of therapeutic action.

DSM-5 Conceptual Development and Developmental Status

Darrel A. Regier, MD, MPH, American Psychiatric Association

This presentation will review the developmental evolution of psychiatric classification and the current developmental process for DSM-5. Approaches for modifying the overall structure of the classification to consider underlying vulnerabilities, as well as the inclusion of developmental, dimensional, disability, and gender/culture features of mental disorders will be mentioned. The objectives of the field trials will include clinical utility, feasibility, reliability, and limited validity assessments in both academic and routine practice settings.

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