Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics
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Clinical studies in patients with schizophrenia suggest that atypical neuroleptics are more effective than typical neuroleptics in reducing negative symptoms including apathy and anhedonia. Dysfunction of the dopaminergic reward system may contribute to negative symptoms in schizophrenia.
We used functional magnetic resonance imaging to assess the blood oxygen level dependency response in the ventral striatum of medicated schizophrenics and healthy control subjects during reward anticipation.
Twenty schizophrenics [ten medicated with typical (e.g., haloperidol) and ten with atypical (e.g., olanzapine and risperidone) neuroleptics] and ten age-matched healthy volunteers participated in an incentive monetary delay task in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or no consequence.
Healthy volunteers and schizophrenics treated with atypical neuroleptics showed ventral striatal activation in response to reward-indicating cues, but schizophrenics treated with typical neuroleptics did not. In patients treated with typical neuroleptics, decrease in activation of the left ventral striatum was correlated with the severity of negative symptoms.
Failure to activate the ventral striatum during reward anticipation was previously associated with the severity of negative symptoms in schizophrenia and was also found in schizophrenics treated with typical neuroleptics in this study. Significant blunting of ventral striatal activation was not observed in patients treated with atypical neuroleptics, which may reflect the improved efficacy of these drugs in treating negative symptoms.
KeywordsAccumbens Basal ganglia Reward Schizophrenia Motivation Functional magnetic resonance imaging Antipsychotic agents
This study was supported by the German Research Foundation (Deutsche Forschungs-gemeinschaft, HE 2597/4-2) and by investigator-initiated trials funded by Janssen-Cilag Germany and Lilly Germany. We declare that the experiments comply with the current laws of the country in which they were performed. Georg Juckel and Florian Schlagenhauf contributed equally to this work.
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