Pharmacology of Cognition in Schizotypal Personality

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DESCRIPTION (provided by applicant): The proposed studies are designed to characterize the cognitive impairment associated with schizotypal personality disorder (SPD) using a cognitive battery including recently developed tests to evaluate the effect of a pharmacologic intervention with guanfacine on the cognitive function of SPD subjects. This proposal builds on findings that SPD patients demonstrate impaired performance on tests of vigilance/attention, encoding, working memory, and episodic memory, but not on generalized tests of intelligence as well as findings that guanfacine can improve cognitive function in Attention Deficit Disorder and schizophrenia. This study is designed to test the primary hypotheses that SPD patients will show substantial cognitive impairment compared to healthy and other personality disorder patient comparison groups on: 1) an auditory and visual Continuous Performance Task (CPT) as well as divided attention: the dual task CPT with both modes, 2) encoding: California Verbal Learning Test (CVLT) and Visual Object Learning Task (VOLT) - first trial, 3) episodic memory: CVLT and VOLT - delayed, and 4) working memory [N-back CPT, Paced Auditory Serial Addition Test (PASAT), DOT test], and interference (Flanker test). The modified A-X CPT with and without interference will also allow us to test a context model and a capacity model of cognitive impairment in schizophrenia. In addition, comparison measures are included in the baseline testing battery, which are hypothesized not to differ between groups as well as measures hypothesized to distinguish groups at baseline but not to respond to guanfacine. These tasks will be administered prior to pharmacologic intervention, and during a double-blind randomized placebo-controlled trials of guanfacine at regular intervals during the trial, with all patients receiving medication the last four weeks. It is hypothesized that there wilt be significant improvements in performance on these tasks, but not on the control tasks in the SPD group following active medication compared to placebo with a significant diagnosis by drug interaction in the SPD group compared to the OPD comparison group.