Elsevier

Biological Psychiatry

Volume 65, Issue 12, 15 June 2009, Pages 1032-1039
Biological Psychiatry

Archival Report
Reward Feedback Alterations in Unmedicated Schizophrenia Patients: Relevance for Delusions

https://doi.org/10.1016/j.biopsych.2008.12.016Get rights and content

Background

Increased attribution of incentive salience to neutral or aversive stimuli might be associated with dysfunction of neuronal processing of positive and negative reinforcement and contribute to the formation of delusions in schizophrenia.

Methods

Fifteen unmedicated patients with schizophrenia (8 drug-naive and 7 drug-free for at least 3 months) and 15 age- and gender-matched healthy control participants underwent functional magnetic resonance imaging to investigate neural responses to feedback of (successful vs. unsuccessful) monetary gain or avoidance of loss. Functional connectivity was assessed between the medial prefrontal cortex (MPFC) and ventral striatum (VS), brain areas known to be activated by feedback of reward and loss.

Results

Responses to negative outcome in reward trials (omission of expected reward) were exaggerated in the MPFC of patients with schizophrenia. In contrast, schizophrenia patients showed reduced neural responses to successful versus unsuccessful avoidance of loss in the VS. Increased severity of delusions in schizophrenia patients was associated with a decrease in MPFC activation elicited by successful versus unsuccessful avoidance of loss. Functional connectivity between the MPFC and the VS was reduced in patients with schizophrenia compared with healthy control subjects.

Conclusions

These findings demonstrate a differential impairment of—and reduced connectivity between—VS and MPFC during processing of reward and loss-avoidance in drug-free patients with schizophrenia. Moreover, our results provide a link between the formation of delusions and the neural processing of aversive outcomes.

Section snippets

Subjects and Instruments

Thirty subjects were included (15 unmedicated schizophrenia patients and 15 healthy volunteers matched for age, gender, and handedness). The schizophrenia patients (12 men; mean age: 30.1 ± 8.1 years) fulfilled DSM-IV and ICD-10 criteria for schizophrenia and had no other psychiatric axis I disorder (Structured Clinical Interview for DSM-IV [SCID]) (19) and no current drug abuse or past history of drug dependence (SCID interview and random urine drug testing). Eight patients were drug-naïve,

Behavioral Performance

There was a significant effect of cue type (reward, loss-avoidance, or neutral) on reaction times (F = 9.870; p = .001) but no significant main effect for group (F = 1.559; p = .223) nor a group × cue interaction (F = .349; p = .709). Post hoc t tests revealed faster responses in reward (healthy control subjects: t = 2.471, p = .028, and schizophrenia patients: t = 2.046, p = .060) and loss-avoidance trials (healthy control subjects: t = 3.250, p = .006, and schizophrenia patients: t = 2.526, p

Discussion

In the present study, we observed dysfunctional neural processing of reward feedback and reduced altered fronto-striatal connectivity in unmedicated patients with schizophrenia. Neural responses to reward feedback were differentially altered in two core regions of the reward system, the MPFC and the VS: in the MPFC, healthy control subjects showed reduction of brain activation during feedback of unsuccessful reward trials, which was reversed in schizophrenia patients (i.e., schizophrenia

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    Authors FS and PS contributed equally to this work.

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