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Original Investigation | Meta-analysis

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

Joaquim Radua, MD, BStat, PhD1,2; André Schmidt, PhD1,3; Stefan Borgwardt, MD, PhD1,3; Andreas Heinz, MD, PhD4,5; Florian Schlagenhauf, MD4,5; Philip McGuire, MD, PhD1; Paolo Fusar-Poli, MD, PhD1
[+] Author Affiliations
1Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, England
2Fundación para la Investigación y Docencia Maria Angustias Giménez Germanes Hospitalàries, Centro de Investigación Biomédica en Red de Salud Mental, Barcelona, Spain
3Department of Psychiatry, University of Basel, Basel, Switzerland
4Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité, Universitätsmedizin Berlin, Germany
5Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
JAMA Psychiatry. 2015;72(12):1243-1251. doi:10.1001/jamapsychiatry.2015.2196.
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Importance  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.

Objective  To assess the differences between patients with schizophrenia spectrum disorders and healthy controls in VS activation during reward processing.

Data Sources  Web of Knowledge database (incorporating Web of Science and MEDLINE) until July 2015, including references of eligible articles and reviews.

Study Selection  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.

Data Extraction and Synthesis  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.

Main Outcomes and Measures  Effect size of the group differences in VS activity, and correlation between VS activity and negative and positive symptom scores in patients.

Results  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).

Conclusions and Relevance  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.

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Forest Plots of the Ventral Striatum Response to Reward Anticipation in Psychosis

In studies with known measures, symbols show the mean, and error bars, the 95% confidence interval (CI). Studies with nonstatistically significant unreported effects are distinguished by the presence of a shaded bar around the mean showing the interval containing 95% of the imputed effect sizes; the central symbol shows the mean, and the error bars, the 95% CI. Size of the data marker corresponds to the relative weight assigned in the pooled analysis. FEP indicates first episode of psychosis; FGA, first-generation antipsychotic; HR, individuals at high risk for schizophrenia; and SGA, second-generation antipsychotic. The location of the ventral striatum is indicated for reference.

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