This will be a study of candidate gene probes in multiplex families of schizophrenia. Five families with a schizophrenic proband and at least one affected first-degree relative, totaling an estimated 75 persons will be evaluated clinically and genetically. Clinical evaluations will include interviews (CASH, SANS, SAPS), a battery of neuropsychological tests for organic dysfunction, MRI Scans, continuous performance task testing, and smooth pursuit eye movement examinations. Three levels of """"""""affected"""""""" will be defined based on these evaluations: 1) schitophrenic vs non- schizophrenic, 2) schizophrenic or schizotypal vs all others, and 3) schizophrenia or schizotypal or abnormal CPT or SPEM vs all others. DNA will be extracted from buffy coat preparations from blood samples and used for Southern blotting and analysis with DNA probes. Candidate gene probes are cloned human genes which are relevant to brain function and therefore, human behavior. For example, we presently have clones for pro-opiomelanocortin, Nerve Growth Factor, and somatostatin. Polymorphic probes will be studied in the multiplex schizophrenia families to determine whether these gene segregates with the disease, suggesting that it may play a role in causing the illness. Conversely, if two or more affected individuals in the same family do not share an allele for the gene, it can be excluded as a cause of the disease. In this manner, we will study all of the currently available candidate gene probes of relevance to schizophrenia to determine whether any appear to be linked to the disease and whether any can be excluded as a cause of the disease.
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