Schizophrenia Research Group

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The Duke Schizophrenia Research Group (SRG) is a group of basic and clinical scientists dedicated to the causes of schizophrenia and its treatment. One of the prime directions of our work is understanding the mechanisms of cognitive deficits in patients with schizophrenia and their treatment. In proof-of-concept trials, we will not only provide the same expertise that we normally provide for industry-supported and NIMH-supported clinical trials, but also a variety of tools that will help to enhance the detection of a cognitive signal, such as functional and structural imaging, pharmacogenetics, cognitive neuroscience tasks, and metabolomics. Further, our faculty include basic scientists whose work is devoted to translational research on the pharmacology of cognition and its relation to cognitive disorders in humans. Our group thus provides a unique convergence of expertise for understanding the mechanisms of cognitive impairment and treatment in schizophrenia. We have schizophrenia patient populations available across the Duke and University of North Carolina Health Systems, and the Singapore Institute of Mental Health, the largest provider of mental health care in Singapore.

Faculty

Members of the SRG include:

Richard Keefe, PhD, is Professor in the Department of Psychiatry and Behavioral Sciences. Dr. Keefe has been the organizer of the Schizophrenia Research Group and administrative coordinator of its activities. His areas of expertise include cognition and the treatment of cognitive deficits in schizophrenia and related disorders. He is the Director of the Chief Neuropsychologists for the TURNS and TENET Projects, which use a network established by NIMH to implement trials assessing the cognitive efficacy of new compounds for schizophrenia. He and his lab have supported the development and implementation of over 25 multi-site clinical trials on cognitive efficacy in schizophrenia and other disorders, including pharmaceutical industry trials, TURNS, and the CATIE schizophrenia and dementia trials.

R. Alison Adcock, MD, PhD, is Assistant Professor in the Department of Psychiatry and Behavioral Sciences and Core Faculty in the Center for Cognitive Neuroscience. Dr. Adcock’s laboratory seeks to understand the neuromodulatory systems that allow anticipatory states (e.g., motivation and prediction) to shape memory (e.g., Adcock et al., Neuron, 2006). The laboratory uses mainly fMRI, behavioral testing, and psychophysics to study inter-related questions such as How do anticipatory affective states (e.g., motivation, excitement) affect storage of memories? Does modulation of memory facilitate prediction of future events? What specific effects do neuromodulators like dopamine have on memory formation? On prediction? Dr. Adcock is currently investigating how learning and memory deficits in schizophrenia relate to dysfunction in predictive, neuromodulatory brain mechanisms.

Marc G. Caron, PhD, James B. Duke Department of Professor of Cell Biology, Medicine and Neurobiology. Dr Caron’s laboratory interests and approaches involve the use of genetic and molecular biology techniques coupled with the use of animal (mouse) models to understand the function of various neurotransmitters that mediate their actions through G protein coupled receptors (GPCR). We have several mouse models in which the genes for neurotransmitter transporters, GPCRs, GPCR kinases, arrestin proteins as well as signal transduction kinases have been inactivated. These animal models provide a wealth of opportunities to examine the role neurotransmitters such as dopamine, norepinephrine and serotonin play in normal and aberrant physiological conditions. For example, animals lacking the dopamine transporter gene behave as animals treated chronically with psychostimulants, which recapitulates manifestations of not only psychotic behaviors but also individual treated with anorexic agents. Mice in which loss-of-function mutations in the human tryptophan hydroxylase gene are being engineered should recapitulate conditions akin to depression and produce a marked influence on feeding behaviors. Studies in the Caron laboratory are funded in large part by grants from the NIH, with some projects involving collaborations with the pharmaceutical industry.

Avshalom Caspi, PhD, grew up in Israel and received his professional education in the United States (PhD; Cornell University). His research spans the fields of psychology, epidemiology, and genetics. His current work is concerned with three broad questions. (1) How do childhood experiences shape the course health inequalities across the life span? (2) How do genetic differences between people shape the way they respond to their environments? (3) What are the best ways to assess and measure personality differences between people? For his research on human development and mental health, he has received awards from the American Psychological Association, the Society for Research in Adolescence, the American Public Health Association, and the International Society for the Study of Behavioral Development, as well as the Mortimer D. Sackler MD Prize for Distinguished Achievement in Developmental Psychobiology. He has served on the Executive Council of the International Society for the Study of Behavioral Development, and is involved in international teaching and training initiatives in developmental psychopathology. He works at Duke University in the USA, at the Institute of Psychiatry, King's College London in the UK, and at the Dunedin School of Medicine, in New Zealand.

Michelle Diaz, PhD, is an Assistant Director in the Brain Imaging & Analysis Center at Duke University . Her primary research focus is on how the brain supports language. She has investigated this using electrophysiology and functional Magnetic Resonance Imaging (fMRI) in healthy young and older adults. Most recently she has been working on a project examining which areas of the brain are involved in semantic analysis. The focus of the project has been to separate task-related activation from semantic and orthographic analyses. She is also involved in the Bioinformatics Research Network (BIRN) research project, which focuses on task and calibration development for multi-site research projects.

David Goldstein, PhD, received his PhD in Biological Sciences from Stanford University in 1994, and from 1999-2005 was the Wolfson Professor of Genetics at University College London. In May 2005, became the Director of the Institute for Genome Science & Policy’s Center for Population Genomics & Pharmacogenetics at the Duke University Medical Center (www.genome.duke.edu). Goldstein’s work focuses on the genetics and pharmacogenetics of schizophrenia and other neuropsychiatric conditions.

Rima Kaddurah-Daouk, PhD, received her education in biochemistry at the American University of Beirut and subsequently trained in molecular biology at the Johns Hopkins Medical School where she worked with Nobel Laureate Dr . Hamilton Smith on mechanism of protein-DNA recognition. Subsequent training and research at the Harvard Medical School and the Massachusetts Institute of Technology enabled her to combine biochemical and biological approaches that led to the identification of genes and pathways possibly implicated in cancer Biology and neuronal cell survival. She has authored key papers around the concept of energy impairment in disease and has over forty patents and patent applications around her findings. These discoveries enabled the establishment of two biotechnology companies that moved the research from the bench to the clinic. Dr. Kaddurah-Daouk is one of the pioneers in the field of metabolomics and plays a leading role in its development. She established the Metabolomics Society and serves as its first president. She also co-founded one of the leading biotechnology companies in the field of metabolomics and is establishing a National Metabolomics Research Network. She recently joined the faculty at Duke University Medical Center Department of Psychiatry where she is building several programs that bridge genetic and biochemical metabolomics approaches to bring a deeper understanding of pathways implicated in disease and in drug response.

Allison Ashley-Koch, PhD, is an Assistant Research Professor in the Section of Medical Genetics, Department of Medicine. Her research focuses on the genetic epidemiology of Mendelian and complex genetic disorders. Dr. Ashley-Koch’s primary interest is the genetics of psychiatric disorders, including attention deficit hyperactivity disorder, autism, and trichotillomania. She is also performing studies to identify genes involved in and essential tremor, as well as genes that modify the clinical severity of sickle cell disease. Dr. Ashley-Koch served the Center for Human Genetics as a post-doctoral fellow and research associate from 1998 to 2000.

K. Ranga Rama Krishnan, MB ChB, is the Executive Vice Dean for the Duke-NUS Graduate Medical School Singapore (GMS). He is also Professor and previous served as Chairman of the Department of Psychiatry and Behavioral Sciences, Duke University Medical Center , Durham , North Carolina. Dr. Krishnan earned his medical degree and completed a rotating internship at Madras Medical College in Madras, India . He then completed his residency and held a fellowship in neurobiology at the Duke University Medical Center. Dr. Krishnan has created a translational research center for depression in the elderly, the only such center in the United States funded by the National Institutes of Health. He serves on the scientific boards of numerous biotech and pharmaceutical companies and has co-founded companies in the obesity and neuroscience arena. Dr. Krishnan serves or has served on many editorial boards of scientific journals and has received numerous awards. He has recently received the 2007 Distinguished Scientist Award from the American Association for Geriatric Psychiatry.

Ed Levin, PhD, is Professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center, with joint appointments in Psychology, Pharmacology and the School of the Environment. The primary research effort of his laboratory is to understand neurobehavioral interactions underlying cognitive function and to apply this knowledge to better understand cognitive dysfunction in schizophrenia and to develop novel therapeutic treatments. He has conducted a series of studies supported by NIMH concerning the interactions of antipsychotic drugs with nicotinic treatments to improve cognitive function. His principal research focus concerns nicotinic receptor systems and their interactions with other transmitter systems. He uses NMDA glutamate antagonist treatment and neonatal hippocampal lesion models of the cognitive impairment of schizophrenia to test the therapeutic treatments.

Christine E. Marx MD, MA, is Associate Professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center and Durham VA Medical Center. Dr. Marx investigates the relevance of neurosteroids to the pathophysiology and therapeutics of neuropsychiatric disorders, including schizophrenia, post-traumatic stress disorder (PTSD), and Alzheimer's disease. Her laboratory quantifies neurosteroids with femtomolar sensitivity by gas chromatography/mass spectrometry, preceded by high performance liquid chromatography. Dr. Marx has determined that neurosteroids are altered in patients with schizophrenia and may be associated with specific symptom domains. She is particularly interested in translating these bench efforts to clinical investigations. Along these lines, Dr. Marx is currently directing two pilot randomized controlled clinical trials with neurosteroid augmentation strategies targeting cognitive symptoms in patients with schizophrenia and PTSD.

Terrie Moffitt, PhD, studies how genetic and environmental risks work together to shape the course of abnormal human behaviors and psychiatric disorders. Her particular interest is in antisocial and criminal behavior, but she also studies depression, psychosis, and addiction. She is a licensed clinical psychologist, who completed her clinical hospital training at the UCLA Neuropsychiatric Institute (1984). She is associate director of the Dunedin Longitudinal Study, which follows 1000 people born in 1972 in New Zealand. She has studied the cohort from birth to age 32 so far. She also directs the Environmental-Risk Longitudinal Twin Study, which follows 1100 British families with twins born in 1994-1995. She has studied the twins from birth to age 12 so far. For her research, she has received the American Psychological Association's Early Career Contribution Award (1993) and Distinguished Career Award in Clinical Child Psychology (2006). Moffitt was also awarded a Royal Society-Wolfson Merit Award (2002-2007), the Klaus-Grawe Prize (2009), and was co-recipient of the Stockholm Prize in Criminology (2007). She is a fellow of the Academy of Medical Sciences (1999), the American Society of Criminology (2003), the British Academy (2004), Academia Europaea (2005), and the American Academy of Political and Social Science (2008). She has served on investigative panels for institutions such as the Nuffield Council on Bioethics (ethics of behavioural genetics research) and the US National Academy of Sciences (research into firearms and violence). Currently, Moffitt is a member of the working party to draft diagnostic criteria for disruptive disorders and ADHD for the DSM-V, forthcoming from the American Psychiatric Association in 2012. She works at Duke University in the USA, at the Institute of Psychiatry, King's College London in the UK, and at the Dunedin School of Medicine, in New Zealand.

Ashwin Patkar, MD, is an Associate Professor of Psychiatry and Medical Director of Duke Addictions Program at Duke University Medical Center , Durham , NC . Dr Patkar earned his medical degree from G S Medical College in Bombay, India, his MRCPsych from the Royal College of Psychiatrists, England and Neuropharmacology degree from University of Nottingham, England. He completed his psychiatry residency at Thomas Jefferson University , Philadelphia and was the Director of Biological Psychiatry and Clinical Trials at Thomas Jefferson University . He is Board Certified with the American Board of Neurology and Psychiatry with subspecialty Certification in Addiction Psychiatry and American Society of Addiction Medicine (ASAM) Certification in Addiction Medicine. Dr. Patkar’s focus of research is translational research in addictions. He has been awarded NIH (NIDA) grants to investigate genetic and biological markers of substance abuse. He is the Co-Principal Investigator of the Data and Statistical Coordinating Center for NIDA supported Clinical Trials Network that aims to bring science based medicine into clinical practice and a Co-Investigator on a National Institute on Alcohol and Alcoholism grant to address rural underage drinking. Dr Patkar is involved in SAMHSA supported services and outcome research focusing on patients with co-occurring disorders, and HIV/hepatitis C. Dr. Patkar has published over 80 peer reviewed articles and book chapters and has given over 250 presentations and invited lectures at national and international meetings. He has received the American Academy of Addiction Psychiatry Research Award, the Lilly Biological Psychiatry Fellowship Award and has served on NIH review committee and Advisory Boards for Industry. He is a member of the American Psychiatry Association, American Society of Addiction Medicine, American Academy of Addiction Psychiatry, American Medical Association and World Psychiatric Association.

Marvin S. Swartz, MD, is Professor and Head, Division of Social and Community Psychiatry and Co-Director of the Services Effectiveness Research Program in the Department of Psychiatry and Behavioral Sciences, a large services research group focusing on the effectiveness of services for children and adults with serious mental illness. As Director of the Duke Area Health Education Center (AHEC) Program he is responsible for educating mental health and primary care clinicians and other stakeholders about evidence-based treatment for mental illness and substance abuse. He currently serves as Co-PI for the Duke Endowment funded North Carolina Evidence-based Practice Center which is disseminating these practices through-out North Carolina. He is also a Network Member in the MacArthur Foundation Research Network on Mandated Community Treatment and directs the MacArthur-funded National Ressource Center on Psychiatric Advance Directives . Dr. Swartz’ publications have focused on outcomes of care for individuals with serious mental illnesses and with legal issues in psychiatric care. He also serves as Co-PI of the NIMH funded Clinical Antipsychotics Trials of Intervention Effectiveness and has co-led measurement of clinical and functional outcomes, Co-PI of the NIMH-funded study Effectively Implementting Psychiatric Advance Directives and PI of the NY State of Office of Mental Health/ MacArthur Foundation Evaluation of Assisted Outpatient Treatment in NY.

Joseph P. McEvoy, MD, is Professor in the Department of Psychiatry and Behavioral Sciences at Duke University Medical Center. Dr. McEvoy is the Deputy Clinical Director of John Umstead Hospital. He is responsible for the recruitment of patients with schizophrenia for Duke research studies. He led the design team for the CATIE Schizophrenia trials, and recruited more patients for the CATIE study than any of the other 56 sites. He is an internationally recognized leader on the treatment of schizophrenia and on the pharmacological mechanisms of effective treatments of psychosis.

Diana Perkins, MD, MPH, is Professor of Psychiatry at UNC–Chapel Hill School of Medicine and Medical Director of "Outreach and Support Intervention Services (OASIS), an innovated treatment program for individuals at clinical high risk for schizophrenia or who are in the early stages of recovery from a first episode of schizophrenia. She is PI on a three-site NIMH-sponsored study on the prediction of conversion to psychosis in individuals at clinical high risk for psychotic disorders. She is also an investigator in the NIMH-sponsored "North American Prodrome Longitudinal Study (NAPLS)", which includes the results of eight NIMH funded studies of the psychosis prodrome pooled into a federated data base.

Jeff Swanson, PhD, is Professor in the Department of Psychiatry and Behavioral Sciences. Swanson is a medical sociologist (Ph.D. Yale, 1985) with postdoctoral training in adult psychiatric epidemiology and mental health services research at the University of North Carolina at Chapel Hill and Duke University Medical Center . Swanson has authored or coauthored over 130 research publications on topics including violence and severe mental illness, schizophrenia treatment effectiveness, involuntary outpatient commitment and other forms of leveraged community treatment, psychiatric advance directives, treatment decision-making for severely ill patients, and the impact of disability law and policy on redressing discrimination against persons with psychiatric and other disabilities. He was also the Duke-site principal investigator of the Schizophrenia Care and Assessment Program (SCAP), a 3-year observational study of schizophrenia treatment effectiveness among 2,400 patients in 6 U.S. sites. In 2004, Swanson received an Independent Research Scientist Career Award from the National Institute of Mental Health (K02-MH67864-01) to pursue a five-year program of research on violence risk management and psychiatric treatment.

William Wetsel, PhD, received his PhD degree at the Massachusetts Institute of Technology and had postdoctoral training at the Western Psychiatric Institute and Clinic at the University of Pittsburgh . He worked at the National Institute of Environmental Health Sciences for more than 10 years where he was Chief of the Laboratory of Molecular Endocrinology Workgroup. He has broad experience in many aspects of neuroscience that include molecular, biochemical, morphological, pharmacological, physiological, and behavioral analyses. As the Director of the Mouse Behavioral and Neuroendocrine Analysis Core Facility, his research has focused upon developing mouse genetic models of human neuroendocrine, neurological, and psychiatric dysfunction. Currently, there are more than 40 lines of mutant mice in the Core Facility that display endophenotypes similar to human patients diagnosed with attention deficit-hyperactivity disorder, schizophrenia, depression, drug abuse, anxiety, obsessive-compulsive disorder, post-traumatic stress disorder, Parkinson’s disease, and Huntington’s disease. To evaluate these phenotypes, more than 100 tests or assays have been developed to assess neuroendocrine, neurochemical (monoamines, acetylcholine), pharmacological, and behavioral responses. Presently, multi-electrode assemblies are being used to analyze brain region-specific and collective neural circuit responses in wild type and mutant mice to vehicle and various drug treatments. Morphology studies are being conducted with magnetic resonance imaging (MRI); fMRI experiments will become available in summer 2006. Metabolomic expertise is already available for studies in mice. Hence, with the animal models available in the Mouse Behavioral and Neuroendocrine Analysis Core Facility can be used to provide comprehensive assessments of preclinical drug effects for the pharmaceutical industry.