Heterogeneity has been consistent problem in the research and treatment of schizophrenia. Despite marked variation in the onset, phenomenology, treatment response and outcome of schizophrenics, our ability to identify subtypes is remarkably limited. A major problem in schizophrenia research has been the use of cross-sectional study designs and heterogeneous patient samples previously exposed to neuroleptics which have potentially confounding effects on the disease. This study proposes to identify biologic correlates of the phenomenology and course of schizophrenia by using a prospective, longitudinal, repeated measures design assessing biologic and clinical parameters in patients, from the onset of their illness. Preliminary results reveal significant abnormalities in brain morphology, growth hormone secretion and psychotogenic response to dopamine agonists in first episode treatment naive patients which are correlated with treatment response and outcome. Analyses further suggests the existence of distinct pathophysiologic processes, i.e. neurodevelopmental and neurodegenerative, and the presence of two subtypes of schizophrenia. This application is to continue the study for four years to complete patient entry, follow-up and data analysis. Upon completion approximately 120 first episode patients will have entered the study. They will be followed prospectively for at least three years and assessed at specific time intervals with measures of psychopathology, side effects and social adjustment to examine clinical variables of treatment response, illness course and outcome; measures of CNS DA activity and brain morphology. During the first of each subsequent episode we plan to treat all patients within a standardized treatment protocol to be able to characterize patients' treatment responsivity. Outpatient management will minimize drug exposure and, where clinically indicated attempt to withdraw patients from medication.
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