Transcriptomic analysis of the human prefrontal cortex (datasets GSE54567 and GSE54568) revealed mitochondrial deacetylase sirtuin 3 (SIRT3) as the most significantly suppressed gene in depression (p < 0.01), suggesting an impairment in Superoxide dismutase 2 (SOD2)-mediated antioxidant defense. Here, SIRT3 is linked to major depressive disorder.