VDAC genes down-regulation in brain samples of individuals with schizophrenia is revealed by a systematic meta-analysis

Abstract

Mitochondrial dysfunction was shown to be involved in schizophrenia pathophysiology. Abnormal energy states can lead to alterations in neural function and thereby to the cognitive and behavioral aberrations characteristics of schizophrenia. Voltage-dependent anion-selective channels (VDAC) are located in the outer mitochondrial membrane and are involved in mitochondrial energy production. Only few studies explored VDAC genes’ expression in schizophrenia, and their results were not consistent. We conducted a systematic meta-analysis of ten brain samples gene expression datasets (overall 368 samples, 179 schizophrenia, 189 controls). In addition, we conducted a meta-analysis of three blood samples datasets (overall 300 samples, 167 schizophrenia, 133 controls). Pairwise correlation analysis was conducted between the VDAC and proteasome subunit genes’ expression patterns. VDAC1, VDAC2 and VDAC3 showed significant down-regulation in brain samples of patients with schizophrenia. They also showed significant positive correlations with the proteasome subunit genes’ expression levels. Our findings suggest that VDAC genes might play a role in mitochondrial dysfunction in schizophrenia. VDAC1 was down-regulated also in blood samples, which suggests its potential role as a biomarker for schizophrenia. The correlation with proteasome subunits, which were previously shown to be down-regulated in a subgroup of the patients, suggests that our findings might characterize a subgroup of the patients. This direction has the potential to lead to patients’ stratification and more precisely-targeted therapy and necessitates further study.