Ventral Striatal Activation During Reward Processing in Psychosis: A Neurofunctional Meta-Analysis.

Abstract

Abnormal reward processing is suggested to underlie the formation of psychotic symptoms, likely driven by elevated ventral striatal (VS) dopamine levels. Functional magnetic resonance imaging studies reveal alterations of VS activity during reward processing in patients with chronic psychosis and first episode of psychosis, as well as individuals at high risk for psychosis, but findings are inconclusive, conflicting, and difficult to subject to meta-analysis without introducing bias because several studies reported that findings were not statistically significant but did not report statistics. To assess the differences between patients with schizophrenia spectrum disorders and healthy controls in VS activation during reward processing. Web of Knowledge database (incorporating Web of Science and MEDLINE) until July 2015, including references of eligible articles and reviews. Functional magnetic resonance imaging studies comparing VS activity during monetary reward processing between patients with schizophrenia spectrum disorders or clinical or genetic high-risk state for psychosis and healthy controls. Statistics and thresholds related to the main outcome measures and potential moderators were independently retrieved by 2 investigators. Effect sizes were analyzed using MetaNSUE, a random-effects method that enables the unbiased inclusion of nonstatistically significant unreported effects. Effect size of the group differences in VS activity, and correlation between VS activity and negative and positive symptom scores in patients. The meta-analysis included 23 studies (917 patients) for reward anticipation, 9 studies (358 patients) for reward feedback, and 8 studies (314 patients) for reward prediction error. We found significant bilateral VS hypoactivation during reward anticipation (23 studies, n = 917) in patients compared with healthy controls (left/right Cohen d, -0.50/-0.70; P < .001). Left VS abnormality was more severe in patients with high scores of negative symptoms during reward anticipation (r = -0.41; P < .001). Patients also showed hypoactivation during reward feedback (left/right d, -0.57/-0.56; P < .001). Simulations showed that exclusion of studies with nonstatistically significant unreported effects was associated with a strong bias (d bias = 0.22), whereas estimations using MetaNSUE were unbiased even when statistics were seldom reported (d bias < 0.001). This meta-analysis provides evidence that patients with psychosis demonstrate VS hypoactivation during reward anticipation. The assessment of VS prediction errors seems to be promising, but more studies are needed to draw valid conclusions.