Aripiprazole and sulpiride have differenzial effects on working memory performance and brain activity in patients with schizophrenia and healthy controls

The aim of this study was to investigate the effects of a single dose of aripiprazole as compared to placebo (and sulpiride) on working memory cognition and related brain activity in patients with schizophrenia and healthy controls. Twelve patients with chronic schizophrenia (diagnosed according to DSM-IV criteria) and twelve healthy volunteers matched for gender, age and verbal intelligence were tested on three occasions using a randomized, double-blind and double-dummy design with single oral doses of aripiprazole 15mg (at -3h), sulpiride 400mg (at -1.5h) or placebo. Domperidone co-medication was used to prevent nausea. Antipsychotic medication was discontinued for 1 day before each testing session. Imaging was performed at a 1.5T GE scanner using standard EPI sequences and a blocked working memory (n-back) task. Imaging data were analysed using CamBA (www-bmu.psychiatry.cam.ac.uk/software). There were significant n-back (2- vs. 0-back) and group (patient vs. controls) effects and significant drug x group, drug x n-back and drug x group x n-back interactions (all p<0.05) for working memory performance (hit rates). Aripiprazole had no effect on n-back working memory performance in the patients and impaired 2-back hit rates in healthy controls. Analysis of fMRI data revealed a typical fronto-parietal working memory network. Aripiprazole had differenzial effects on BOLD activity changes in a left prefrontal and sulpiride in a frontomedial working memory network.

This study was supported by Bristol-Myers Squibb, UK