BRAIN MORPHOLOGY, DOPAMINE, AND EYE-TRACKING ABNORMALITIES IN 1ST-EPISODE SCHIZOPHRENIA - PREVALENCE AND CLINICAL CORRELATES

Objective: To characterize the pathophysiology of schizophrenia and to identify biologic markers in first-episode patients with no or little prior treatment exposure. Design: Prospective study of an inception c ohort. Setting: Psychiatric division of an academic medical center wit h a suburban metropolitan catchment area. Patients: 70 patients in the ir first episode of schizophrenia (77%) or schizoaffective disorder (2 3%) with no (70%) or limited prior neuroleptic exposure (30%), and 50 healthy volunteer control subjects. Assessment Measures: Demographic a nd clinical evaluations of natural history and psychopathology; methyl phenidate hydrochloride and apomorphine hydrochloride stimulation test s as measures of central nervous system dopamine activity; brain magne tic resonance imaging; eye-tracking examinations. Results: Preliminary analyses demonstrate that pathobiologic features previously identifie d in heterogeneous and primarily chronically ill patients are also pre sent in subgroups during their first episode. These incude psychotogen ic response to methylphenidate (59%), abnormal growth hormone (GH) sec retion (50%), abnormal brain morphology (31%), and eye-tracking dysfun ction (51%). An association of pathobiologic variables with increased symptom severity and earlier age of onset was observed but not statist ically significant. The strongest associations among biologic variable s were for the following: GH secretion and psychotogenic response to m ethylphenidate, which may reflect increased dopamine agonist neural ac tivity; decreased GH response to apomorphine and third-ventricle enlar gement, which may represent a neuropathologic correlate of anterior pi tuitary abnormalities; and morphologic abnormalities of the medial tem poral lobe and third ventricle were associated with normal eye trackin g, suggesting that these pathobiologic features are mediated by distin ct processes. Conclusions: These phenomena appear to be a consequence of the disease rather than the effects of chronicity, drug treatment, or institutionalization. It remains to be determined if these biologic phenomena will remain stable over time or change with disease progres sion. A companion article examines the clinical significance of these findings.