Genetic mechanisms underlying gray matter volume changes in patients with drug-naive first-episode schizophrenia

Abstract Brain structural damage is a typical feature of schizophrenia. Investigating such disease phenotype in patients with drug-naive first-episode schizophrenia (DFSZ) may exclude the confounds of antipsychotics and illness chronicity. However, small sample sizes and marked clinical heterogeneity have precluded definitive identification of gray matter volume (GMV) changes in DFSZ as well as their underlying genetic mechanisms. Here, GMV changes in DFSZ were assessed using a neuroimaging meta-analysis of 19 original studies, including 605 patients and 637 controls. Gene expression data were derived from the Allen Human Brain Atlas and processed with a newly proposed standardized pipeline. Then, we used transcriptome–neuroimaging spatial correlations to identify genes associated with GMV changes in DFSZ, followed by a set of gene functional feature analyses. Meta-analysis revealed consistent GMV reduction in the right superior temporal gyrus, right insula and left inferior temporal gyrus in DFSZ. Moreover, we found that these GMV changes were spatially correlated with expression levels of 1,201 genes, which exhibited a wide range of functional features. Our findings may provide important insights into the genetic mechanisms underlying brain morphological abnormality in schizophrenia.