This research program will examine platelet monoamine oxidase (MAO) to determine if differences exist in the amount or structural properties of the enzyme between schizophrenics and normal controls. Patients will be classified according to the Research Diagnostic Criteria, and by means of the Schedule for Affective Disorders and Schizophrenia, which were developed for the objective diagnostic assessment of mental patients. Within the schizophrenic group, illness factors found in previous studies to correlate with MAO changes, i.e., prognosis, chronicity and paranoia, and various symptom clusters, drug therapy, hospitalization and demographic variables will be studied in relationship to MAO measures. If significant differences are found in MAO measures between schizophrenics or a subtype of schizophrenics and normals, non-schizophrenic psychiatric patients will be studied to determine if MAO differences are specific to schizophrenia. Further, MAO will be assessed longitudinally in a group of schizophrenics with respect to stability over time, clinical change and neuroleptic drug effects. In the biochemical studies, the purification of human platelet MAO, the study of its kinetic properties with different substrates and inhibitors, and an examination of its structure through electrophoretic and immunoassays with monospecific and monoclonal antibodies will provide new knowledge about this important enzyme. In the clinical studies, immunological assays of MAO concentrations in platelets, and electrophoretic and immunological techniques for analyzing structural differences between MAO variants will be used to compare normal and schizophrenic MAO. These biochemical methods include more sensitive and specific tests of MAO protein quantity and structure than have been available for previous studies of the problem. We expect to answer definitively whether MAO is defective in schizophrenia, and if a defect exists, to examine its source.
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