The simple truth about the genetic complexity of schizophrenia

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• Dr. Danny Weinberger, National Institutes of Health, USA
• Tuesday 29 September 2009, 09:15-10:00
• West Road Concert Hall.

If you have a question about this talk, please contact Hannah Critchlow.

This talk is part of the Cambridge Clinical Neuroscience and Mental Health Symposium, 29th – 30th September 2009 at West Road Concert Hall. This event is free to attend for cambridge neuroscientists although registration is required. To register, and for further information, rlease visit: http://www.neuroscience.cam.ac.uk/cnmhs/

Abstract: Over the past six years, genes putatively related to the etiology of schizophrenia and related conditions have been identified. There is considerable controversy about whether any of the genetic evidence so far is valid. This controversy resides largely in questions about the strength of statistical evidence, though it is generally agreed that the end game in gene identification of complex disorders such as mental illnesses cannot be based on statistics. The end game is a biological one, based on demonstrating that variation in a candidate gene impacts on the biology of the gene so that it biases towards expression of the biology of the illness. Ultimately, the genes tell us what schizophrenia is at a basic cellular level. This talk will address the biological clues that have emerged so far about the genetic origins of schizophrenia and some of the likely explanations for the current controversies. The findings that will be reviewed converge on the conclusion that there are many genetic and molecular pathways to schizophrenia and related phenotypes, that Interactions of variations within genes, between genes, and with the environment confound simple models of genetic association in psychiatry but show biologically lawful effects on brain-related intermediate phenotypes. Thus, simple models of genetic association do not work, and solutions will require new approaches and new thinking.

References: Huffaker SJ, Chen J, Nicodemus KK, et al: A primate-specific, brain isoform of KCNH2 affects cortical physiology, cognition, neuronal repolarization and risk of schizophrenia. Nature Medicine 15: 509-518, 2009.

Tan HY, Nicodemus KK, Chen Q, et al: Genetic variation in AKT1 is linked to dopamine-associated prefrontal cortical structure and function in humans. J Clin Investigation 18:2200-2208, 2008.

Nicodemus KK, Marenco S, Batten AJ, et al: Serious obstetric complications interact with hypoxia-regulated/vascular-expression genes to influence schizophrenia risk. Mol Psychiatry 13:873-877, 2008.

Biosketch: Daniel Weinberger is Director of the Genes, Cognition, and Psychosis Program of the Intramural Research Program, National Institute of Mental Health, National Institutes of Health in Bethesda, Maryland. He attended college at the Johns Hopkins University and medical school at the University of Pennsylvanian and did residencies in psychiatry at Harvard Medical School and in neurology at George Washington University. He is board certified in both psychiatry and neurology.

Daniel’s research at the NIMH has focused on brain mechanisms involved in the pathogenesis and treatment of neuropsychiatric disorders, especially schizophrenia. His work has defined dysfunctional neural systems in the brain that appear to underlie many of the clinical symptoms of the illness. He was instrumental in focusing research on the role of abnormal brain development as a risk factor for schizophrenia. His lab has identified the first specific genetic mechanism of risk for schizophrenia, and the first genetic effects that account for variation in specific human cognitive functions and in human temperament. In addition, he and his colleagues developed the first high fidelity animal model of schizophrenia. In 2003, Science magazine highlighted the genetic research of his lab as the second biggest scientific breakthrough of the year, second to the origins of the cosmos.

He is the recipient of many honors and awards, including the NIH Directors Award, The William K. Warren Medical Research Institute Award, the Adolf Meyer Prize of the American Psychiatric Association, the Research Prize of the World Federation of Societies of Biological Psychiatry, the Gold Medal Award of the Society of Biological Psychiatry, the Foundation’s Fund Prize from the American Psychiatric Association, and the Lieber Prize of the National Alliance for Research on Schizophrenia and Affective Disorders. He is past president of the Society of Biological Psychiatry, past President of the American College of Neuropsychopharmacology and has been elected to the Institute of Medicine of the National Academy of Sciences. He sits on the editorial boards of sixteen scientific journals. He has published over four hundred scientific articles and has authored or edited six books.

This talk is part of the Clinical Neuroscience and Mental Health Symposium series.

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