Voxel-wise meta-analysis of fMRI studies in patients at clinical high risk for psychosis.

Background: Reliable neurofunctional markers of increased vulnerability to psychosis are needed to improve the predictive value of psychosis risk syndrome and inform preventive interventions. Methods: I performed a signed differential mapping (SDM) voxel-wisemeta-analysis of functional magnetic resonance imaging (fMRI) studies of patients at clinical high risk for psychosis. Results: Ten studies were included in the analysis. Compared with controls, high-risk patients showed reduced neural activation in the left inferior frontal gyrus (Brodmann area [BA] 9) and in a cluster spanning the bilateral medial frontal gyrus (BA 8,6), bilateral superior frontal gyrus (BA 8,6)and the left anterior cingulate (BA 32). There was no publication bias. Heterogeneity across studies was low. Sensitivity analysis confirmed the robustness of the findings. Limitations: The cross-sectional nature of the included studies prevented the comparison of high-risk patients who later experienced a psychotic episode with those who did not. Other caveats are reflected in methodologic heterogeneity across tasks employed by different individual imaging studies. Conclusion: Reduced neurofunctional activation in prefrontal regions may represent a neurophysiologic correlate of increased vulnerability to psychosis.