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Schizophr Res. 2010 May;118(1-3):189-200. doi: 10.1016/j.schres.2010.01.022. Epub 2010 Feb 26.

Switching schizophrenia patients from typical neuroleptics to aripiprazole: effects on working memory dependent functional activation.

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Department of Psychiatry, Charité-Universitaetsmedizin Berlin, Campus Mitte, Germany.



Deficits in working memory (WM) are a core symptom of schizophrenia patients and have been linked to dysfunctional prefrontal activation, which might be caused by a mesocortical hypodopaminergic state. Aripiprazole--a partial dopamine antagonist--is a novel antipsychotic, which increases frontal dopamine concentrations in preclinical studies. However, little is known about specific medication effects on the modulation of frontal activation during WM performance.


We measured BOLD-response during a WM task in a longitudinal fMRI-study in eleven schizophrenia patients first when they received conventional antipsychotics (T1) and a second time after they had been switched to aripiprazole (T2). A healthy control group matched for age, handedness and gender was investigated at two corresponding time points. Data was analyzed with SPM5 in a 2 x 2 x 2 design (groupxsessionxtask).


Schizophrenia patients showed fewer correct responses compared to healthy controls at T1 and a trend-wise normalization at T2. The task activated the fronto-parietal network during the contrast 2-back>0-back in all participants. At T1 patients revealed a hypoactivation in the dorsal anterior cingulate cortex (ACC), which normalized after switch to aripiprazole and correlated with improved task performance. This was due to a significant increase in the patients group while the control group did not change, as corroborated by a significant groupxtime interaction in this region.


This study showed for the first time that the partial dopamine antagonist aripiprazole increases BOLD-signal during a WM task in the cognitive part of the ACC in schizophrenia patients, which may reflect its beneficial effect on cognitive deficits.

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