Switching schizophrenia patients from typical neuroleptics to olanzapine: Effects on BOLD response during attention and working memory

Abstract

Dysfunctional activation of the dorsolateral prefrontal cortex (DLPFC) during working memory (WM) in schizophrenia patients has repeatedly been observed, however little is known about specific medication effects on the modulation of DLPFC activation. We measured activation of DLPFC during a WM task in a longitudinal fMRI study in ten schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to olanzapine (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. We analyzed the fMRI data with SPM5 in a 2 x 2 x 2 design (group x session x task). Schizophrenia patients showed fewer correct responses compared to healthy controls at both time points. The fMRI data revealed a significant group by task interaction in the bilateral DLPFC and the right parietal cortex, indicating a reduced BOLD response in the patient group. After switching to olanzapine, schizophrenia patients displayed a significant increase in the BOLD response during the 0-back condition in the DLPFC. This study showed that switching patients from conventional neuroleptics to olanzapine did not significantly alter the frontal or parietal BOLD response during working memory task. However, medication status had influences on the activation during attentional task (0-back), emphasizing the importance of baseline selection in pharmacological fMRI studies. (C) 2008 Elsevier B.V. and ECNP. All rights reserved.