This study will build on our previous work concerning the phenomenology and classification of schizophrenia. Its basic and primary aim is to explore and develop new approaches to the classification of schizophrenia that unite neurobiological, phenomenological, longitudinal, and etiological aspects of the disorder. We postulate that the schizophrenic syndrome is heterogeneous and that it includes a spectrum of disorders. In this proposal, we will examine 60 first-episode patients drawn from the schizophrenia spectrum and 90 """"""""young chronic"""""""" patients (patients under 30 years of age who have been ill less than five years). These subjects will be drawn from the entire schizophrenia spectrum. They will be evaluated at baseline with a comprehensive clinical assessment, indicators of motor function (smooth pursuit eye movements and finger tapping), neuropsychological assessment, and magnetic resonance imaging. Thereafter they will be followed at six-month intervals in order to identify predictors of outcome and indicators of good vs. poor prognosis. We also propose to explore the heterogeneity of schizophrenia by examining at least fifteen multiplex families. We have identified approximately five such families in which at least two members suffer from schizophrenia. The assessment of these family members will include evaluation, including psychometric measures of schizotype in addition to clinical evaluation, magnetic resonance imaging, neuropsychological evaluation, and smooth pursuit eye movements. Detailed birth history will also be obtained. The study will permit us to evaluate the schizophrenia spectrum and to explore the possibility that this spectrum of disorders represents an additive accumulation of multiple risk factors that determine the clinical presentation of the disorder. A final aspects of the study involves instrument development. In addition to the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS), which are now widely used, we have developed a full interview for the assessment of schizophrenia and affective disorders, the Comprehensive Assessment of Symptoms and History (CASH). We propose extensive reliability and validity studies using this instrument.
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