Neuroanatomical markers of genetic liability to psychosis and first episode psychosis: A voxelwise meta-analytical comparison

Objectives. To address at a meta-analytical level the neuroanatomical markers of genetic liability to psychosis and a of first episode of psychosis. Methods. Fifteen voxel-based morphometry (VBM) studies of antipsychotic-naive subjects at genetic high-risk (HR) for psychosis or with a first-episode psychosis (FEP) were included in a Signed Differential Mapping (SDM) meta-analysis. Publication bias was assessed with funnel plots and Egger's intercept. Heterogeneity was assessed with Q statistics and I ² index. Results. The database comprised 458 HR and 206 antipsychotic-naïve FEP subjects, matched with controls. Gray matter (GM) reductions as compared to controls, were observed in the left parahippocampal gyrus and in the bilateral anterior cingulate gyrus in the HR group, and in the right superior temporal gyrus, in the left insula and in the left cerebellum in the FEP group. Further GM decreases were observed in the FEP group as compared to the HR group in the left anterior cingulate, in the right precuneus, in the left cerebellum and in the right superior temporal gyrus. Limitations. The cross-sectional nature of the included studies prevented the comparison of high risk subjects who later did or did not develop a psychotic episode. Other caveats are based on the methodological heterogeneity across individual imaging studies. Conclusions. GM reductions in the anterior cingulate are markers of genetic liability to psychosis while reductions in the superior temporal gyrus and cerebellum can be interpreted as markers of a first onset of the illness.