Analysis of global gene expression at seven brain regions of patients with schizophrenia

Previous transcriptome analyses of brain samples provided several insights into the pathophysiology of schizophrenia. In this study, we aimed to re-investigate gene expression datasets from seven brain regions of patients with schizophrenia and healthy controls by adopting a unified approach. After adjustment for confounding factors, we detected gene expression changes in 2 out of 7 brain regions - the dorsolateral prefrontal cortex (DLPFC) and parietal cortex (PC). We found relatively small effect sizes, not exceeding absolute log fold changes of 1. Gene-set enrichment analysis revealed the following alterations: 1) down-regulation of GABAergic signaling (in DLPFC and PC); 2) up-regulation of interleukin-23 signaling together with up-regulation of transcription mediated by RUNX1 and RUNX3 as well as down-regulation of RUNX2 signaling (in DLPFC) and 3) up-regulation of genes associated with responses to metal ions and RUNX1 signaling (PC). The number of neurons was significantly lower and the number of astrocytes was significantly higher at both brain regions. In turn, the index of microglia was increased in DLPFC and decreased in PC. Finally, our unsupervised analysis demonstrated that cellular composition of the samples was a major confounding factor in the analysis of gene expression across all datasets. In conclusion, our analysis provides further evidence that small but significant changes in the expression of genes related to GABAergic signaling, brain development, neuroinflammation and responses to metal ions might be involved in the pathophysiology of schizophrenia. Cell sorting techniques need to be used by future studies to dissect the effect of cellular content.