Reward system activation in schizophrenic patients switched from typical neuroleptics to olanzapine
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High blockade of dopamine D2 receptors in the ventral striatum including the nucleus accumbens may interfere with reward anticipation and cause secondary negative symptoms such as apathy or anhedonia. This may not be the case with newer neuroleptics such as olanzapine, which show less dopamine D2 receptor blockade and a faster off-rate from the receptor.
We used functional magnetic resonance imaging to assess the blood oxygenation level dependent response in the ventral striatum of schizophrenics medicated with typical neuroleptics (T1) and after switching them to olanzapine (T2) and of healthy control subjects at corresponding time points during reward anticipation.
Materials and methods
Ten schizophrenics, while medicated with typical neuroleptics (T1) and after having been switched to olanzapine (T2), and ten matched healthy volunteers participated in a monetary incentive delay task, in which visual cues predicted that a rapid response to a subsequent target stimulus would either result in monetary gain or have no consequence.
During reward anticipation, healthy volunteers showed significantly higher ventral striatal activation compared to schizophrenic patients treated with typical neuroleptics but not olanzapine, which was reflected in a significant interaction between group and session. In patients treated with typical neuroleptics, but not with olanzapine, decreased left ventral striatal activation was correlated with negative symptoms.
Failure to activate the ventral striatum during reward anticipation was pharmacologically state-dependent and observed only in patients treated with typical neuroleptics but not with olanzapine, which may indicate that this drug did not induce secondary negative symptoms via interference with reward anticipation.
KeywordsAccumbens Basal ganglia Reward Schizophrenia Motivation Functional magnetic resonance imaging Antipsychotic agents
This study was supported by the German Research Foundation (Deutsche Forschungsgemeinschaft; HE 2597/4-2) and by investigator-initiated trails funded by Lilly Germany and by the Bernstein Center for Computational Neuroscience Berlin (BMBF grant 01GQ0411).
Dr. Schlagenhauf, Mr. Koslowski, Mr. Kahnt, Mrs. Dembler, Dr. Knutson, Dr. Kienast and Dr. Wrase reported no biomedical financial interests or potential conflicts of interest. Dr. Juckel reports having received research funding from Lilly (IIT) and consultant fees from Janssen-Cilag, AstraZenics, Lilly, GSK and Bristol Myers Squibb. Dr. Gallinat disclosed research support from AstraZeneca and fees as consultant from Bristol Myers Squibb. Dr. Heinz has received research funding from the German Research Foundation and the Bernstein Center for Computational Neuroscience Berlin (German Federal Ministry of Education and Research), Eli Lilly & Company, Janssen-Cilag, and Bristol-Myers Squibb. Dr. Heinz has received Speaker Honoraria from Janssen-Cilag, Johnson & Johnson, Lilly, Pfizer, and Servier.
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