Spatial working memory and problem solving in schizophrenia: The effect of symptom stabilization with atypical antipsychotic medication Peter J. Snyder a,b , Colleen E. Jackson a , Danijela Piskulic c , James Olver c , Trevor Norman c , Paul Maruff d,e, ⁎ a Department of Psychology, University of Connecticut, Storrs, CT, USA b Child Study Center, Yale University School of Medicine, New Haven, CT, USA c Department of Psychiatry, University of Melbourne, Melbourne, Victoria, Australia d CogState Ltd., Melbourne, Victoria, Australia e School of Psychological Science, LaTrobe University, Melbourne, Victoria, Australia Received 26 April 2006; received in revised form 10 April 2007; accepted 14 July 2007 Abstract Reasoning and problem solving in the spatial domain are important aspects of executive function that are reliably impaired in schizophrenia, and the Groton Maze Learning Test© (GMLT) provides a valid measure of spatial working memory. In the current study, 34 patients with first-episode schizophrenia and 20 matched controls were assessed for baseline spatial working memory abilities using this hidden maze learning test. Approximately one month after baseline assessment, allowing for symptoms to stabilize in response to treatment with therapeutic doses of atypical antipsychotic medications for individuals with schizophrenia, all participants were again assessed with the GMLT. Prior to pharmacologic intervention, patients with schizophrenia showed significant impairments in performance of all aspects of the GMLT, including measures of learning efficiency and error monitoring. One month of treatment was associated with a reliable improvement in these domains, although impairments in accuracy and error monitoring on this spatial working memory test persisted despite symptomatic improvement. These results indicate that impairments in spatial working memory are present at the earliest stages of the illness, and that such deficits in performance remain present, albeit ameliorated, after treatment with atypical antipsychotic medication. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: First-episode schizophrenia; Symptom stabilization; Neuropsychology; Cognition 1. Introduction Significant cognitive impairment remains an impor- tant barrier to social and occupational achievement for individuals with schizophrenia. While atypical antipsy- chiotics are successful in reducing positive and negative symptoms, substantial cognitive impairment remains resistant to meaningful improvement with current pharmacotherapy (Heinrichs and Zakzanis, 1998). As such, the measurement and tracking of disease-related cognitive dysfunction, in clinical research and pharma- ceutical trials, continues to be an important focus of current research efforts (e.g., the NIH-funded MATRICS Available online at www.sciencedirect.com Psychiatry Research 160 (2008) 316 – 326 www.elsevier.com/locate/psychres ⁎ Corresponding author. CogState, Ltd., Level 7, 21 Victoria Street, Melbourne, 3000, Victoria, Australia. Tel.: +61 3 9349 1300; fax: +61 3 9348 2689. E-mail address: pmaruff@cogstate.com (P. Maruff). 0165-1781/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2007.07.011