In this RO3 application, the investigators propose to collect crucial pilot data on never-medicated schizophrenic patients treated sequentially with haloperidol and olanzapine. As yet, there are no combined functional/structural imaging studies which evaluate in a longitudinal design effects of typical and atypical antipsychotics in first episode schizophrenia. Moreover, published imaging studies have included mixed groups of--in varying proportions--acute/chronic, young-old, medicated/unmedicated, and previously medicated/drug-naive patients, making findings difficult to interpret. Thus, although some promising predictors of treatment response and propensity to develop side effects have emerged from the imaging literature, a prospective study of a more uniform sample of young, never-medicated patients is sorely needed. Toward this end, our proposed two-year project will obtain high-resolution co-registered PET/MRI measures in 20 drug-naive patients at three time points: (1) before treatment; (2) after 6 months of treatment with haloperidol; and after 6 months of treatment with olanzapine. Side effects will be monitored at regular intervals. Previous research has found that treatment with typical antipsychotics such as haloperidol leads to increases in both striatal size and metabolism, whereas striatal changes after atypical agents such as clozapine and sertindole are either less marked or entirely absent. Preliminary MRI reports suggest that striatal size increases after typical antipsychotics may be reversible after treatment with clozapine. The investigators will examine whether PET/MRI patterns associated with the newer atypical agent olanzapine are comparable to those reported for clozapine. The investigators will further correlate clinical improvement and measures of movement disorder with baseline metabolic rate and structure size. This proposal, if funded, will provide pilot data for a larger proposal which will examine the relationship between typical and atypical antipsychotics and movement disorders thus greatly impacting the quality of car delivered to the chronically mentally ill.
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