The purpose of the proposed project is to develop a research program on the application of genetic strategies to neuroimaging and neuropsychological studies of schizophrenia. Two subprojects are proposed: a genetic family study and a study of identical twins discordant for schizophrenia. In the family study, family history information on the psychiatric status of first degree relatives will be collected for schizophrenic and control index cases who are participants in ongoing studies of regional brain metabolism and dopamine receptors in schizophrenia. Siblings of index cases will be interviewed directly, and psychiatric status in parents and children will be determined from Family History Research Diagnostic Criteria (FH-RDC) interviews obtained from multiple informants. The family history information will be used: 1. To examine the relation between abnormalities in brain function and structure and the familial risk for schizophrenia and schizophrenia spectrum disorders. 2. To identify from these families multiplex sibships with at least one affected sibling. Regional brain function and structure will be studied in 10 of these sibships, including affected and unaffected family members, and 10 normal sibling pairs. Brain function will be assessed behaviorally with neuropsychological testing and neurophysiologically with positron emission tomography (PET) to measure regional cerebral glucose metabolism. Magnetic Resonance Imaging (MRI) will be used to assess regional brain structure. The second subproject, the twin study, will involve a collaboration with Dr. Fuller Torrey at the NIMH. Identical twins discordant for schizophrenia will be brought to the University of Pennsylvania for PET studies of regional cerebral glucose metabolism and D2 dopamine receptor distribution. These studies of discordant sibling pairs and discordant identical twins will help clarify the extent to which abnormalities in regional brain structure and function reflect a genetic predisposition to schizophrenia or factors associated with the disease process. In addition, the identification of """"""""loaded"""""""" families will provide a sample for future neuroimaging and genetic studies.
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