ELSEVIER Schizophrenia Research20 (1996) 29 32 SCHIZOPHRENIA RESEARCH D-amphetamine challenge effects on Wisconsin Card Sort Test. Performance in schizotypal personality disorder I Benjamin V. Siegel, Jr., Robert L. Trestman, S6amus O'Flaithbheartaigh, Vivian Mitropoulou, Farooq Amin, Richelle Kirrane, Jeremy Silverman, James Schmeidler, Richard S.E. Keefe, Larry J. Siever * Departments of Psychiatry, Mount Sinai School of Medicine and Bronx Veteran's Affairs Medical Center, New York, NY, USA Received 18 September 1995; accepted 30 December 1995 Abstract The authors assessed the effects on Wisconsin Card Sort (WCST) performance and psychiatric symptoms of 30 mg d-amphetamine, a dopamine and norepinephrine agonist, vs placebo in nine patients with schizotypal personality disorder (SPD). Patients, particularly those who made more perseverative errors, demonstrated amphetamine- associated improvement on WCST performance. The data in this preliminary study suggest that some of the cognitive dysfunction present in SPD may improve with amphetamine challenge. Keywords: Amphetamine; Schizotypal personality disorder; Schizophrenia; Wisconsin Card Sort Test 1. Introduction Schizophrenic patients (Goldberg et al., 1987), schizotypal personality disorder (SPD) patients (Trestman et al., 1995) and schizotypal relatives of schizophrenic patients (Nuechterlein, 1983; Mirsky et al., 1992; Keefe et al., 1994) show impairment on neuropsychological tasks sensitive to, but not limited to, prefrontal damage such as the Wisconsin Card Sort and Continuous *Corresponding author. Present address: Department of Psychiatry, Rte 116A,Bronx VeteransAdministration Medical Center, 130 WestKingsbridge Road, Bronx, NY 10468, USA. Tel: + 1 718-584-9000 ext. 5229. 1Presented at the Societyof BiologicalPsychiatry50th Annual Meeting, Miami, FL, May 17-21, 1995. Performance Task, suggesting that cognitive dys- function is a phenotypic marker of the genetic diathesis for schizophrenic illness. This cognitive dysfunction may be associated with reduced corti- cal dopamine activity. Low CSF levels of HVA correlate with deficits in performance of the WCST in schizophrenic patients (Kahn et al., 1994) and in clinically diagnosed SPD patients (Siever et al., 1993). These findings raise the possibility that dopa- mine enhancement may be effective in reversing cognitive impairment in schizophrenia-related dis- orders. Indeed, some schizophrenic patients given catecholamine agonists, such as amphetamine, show an improvement of their negative symptoms (Mathew and Wilson, 1989); in one study, schizo- phrenic patients' WCST performance (i.e. correct S0920-9964/96/$15.00 © 1996ElsevierScienceB.V.All rights reserved PII S0920-9964(95) 00002-3