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.
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