This application is for a Scientist Development Award for Clinicians (SDAC) to further the principal investigator's research training in human genetics and its application to the study of severe, chronic psychopathology in children and adolescents. Funding is requested to free time to pursue didactic instruction and collaborative research in this area. The preceptor will be Michael Boehnke, Ph.D., Associate Professor of Biostatistics at the University of Michigan. The scientific focus for SDAC activities will be obsessive-compulsive disorder (0CD). 0CD is a common psychiatric syndrome that often begins in childhood, persists into adulthood, and aggregates in families. It is relatively consistent in its clinical presentation across the lifespan. Recent family studies indicate that a form of 0CD is related genetically to Gilles de la Tourette syndrome. Family studies using current diagnostic procedures and analytic methods are necessary for investigating the possible modes of expression and transmission of 0CD in families. The general aim of the family case-control study described in this application is to systematically assess and compare the clinical characteristics and family psychiatric history of child, adolescent, and adult probands with 0CD. It is hypothesized that (1) early-onset 0CD is more frequent in males than in females, (2) the prevalence of 0CD is higher in the relatives of probands with early-onset 0CD than in the relatives of probands with late-onset 0CD, (3) the inheritance of 0CD is influenced by a single major locus, (4) chronic tic disorders are more frequent in male 0CD probands, and (5) the prevalence of chronic tic disorders is higher in the relatives of female 0CD probands than in the relatives of male 0CD probands. The data will be inspected for other findings, including comparisons with matched normal controls and their relatives. In summary, this study will advance our knowledge of the etiology of 0CD, and will provide a medium for the scientific development of the principal investigator.
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