Dysfunction of ventral striatal reward prediction in schizophrenic patients treated with typical, not atypical, neuroleptics
- 922 Downloads
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.
- Bertolino A, Caforio G, Blasi G, De CM, Latorre V, Petruzzella V, Altamura M, Nappi G, Papa S, Callicott JH, Mattay VS, Bellomo A, Scarabino T, Weinberger DR, Nardini M (2004) Interaction of COMT (Val(108/158)Met) genotype and olanzapine treatment on prefrontal cortical function in patients with schizophrenia. Am J Psychiatry 161:1798–1805CrossRefPubMedGoogle Scholar
- Farde L, Nordstrom AL, Wiesel FA, Pauli S, Halldin C, Sedvall G (1992) Positron emission tomographic analysis of central D1 and D2 dopamine receptor occupancy in patients treated with classical neuroleptics and clozapine. Relation to extrapyramidal side effects. Arch Gen Psychiatry 49:538–544PubMedGoogle Scholar
- First MB, Spitzer RL, Gibbon M, Williams J (2001) Structured Clinical Interview for DSM-IV-TR axis I disorders, research version, patient edition with Psychotic Screen (SCID-I/P W/ PSY SCREEN). New York State Psychiatric Institute, New YorkGoogle Scholar
- Honey GD, Bullmore ET, Soni W, Varatheesan M, Williams SC, Sharma T (1999) Differences in frontal cortical activation by a working memory task after substitution of risperidone for typical antipsychotic drugs in patients with schizophrenia. Proc Natl Acad Sci U S A 96:13432–13437CrossRefPubMedGoogle Scholar
- Nielsen FA, Hansen LA (2002) Automatic anatomical labeling of Talairach coordinates and generation of volumes of interest via the BrainMap database. Neuroimage 16(2)Google Scholar