PHARMACOLOGY OF COGNITION IN SCHIZOTYPAL PERSONALITY

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DESCRIPTION (Adapted from applicant's abstract): The proposed studies aim to define the cognitive impairment associated with SPD and to evaluate the effect of an acute pharmacologic intervention with amphetamine on the cognitive function of SPD patients. SPD patients share important phenomenologic, genetic, and neurobiologic commonalities with chronic schizophrenia, particularly a core cognitive/attentional impairment. Their study, however, minimized the multiple confounding artifacts associated with the study of schizophrenic patients and offers an opportunity to potentially disentangle the multiple pathophysiologic mechanisms implicated in the schizophrenic disorders. Like schizophrenic patients, SPD patients demonstrate impaired performance on tests of visuospatial working memory, verbal learning, and sustained attention compared to other personality disorder patients and normal controls in the investigator's studies to date. Preliminary data suggests amphetamine can ameliorate these cognitive impairments in SPD patients. This study is designed to test the primary hypotheses that SPD patients will show cognitive impairment in both verbal and visuospatial domains respectively in three areas of cognitive function compared to other non-odd cluster personality disorder (OPD) patients and normal controls: 1) working memory (Paced Auditory Serial Addition Test (PASAT) and DOT tests) 2) learning and memory (serial word list learning and Wechsler Memory Scale Visual Reproduction (WMS-VR)) and 3) sustained attention (Continuous Performance Task (CPT-IP), digits and shapes. SPD patients will be evaluated on these cognitive tasks during placebo and amphetamine to test the hypothesis that 4) they will demonstrate significant improvement in performance in these three domains after administration of 30 mgs. of oral amphetamine and 5) there will be a significant diagnosis by drug interaction for the performance of these cognitive tasks with the SPD group demonstrating significantly improved performance compared to the OPD or the normal comparison group after amphetamine compared to placebo.