HES5 and major depressive disorder: Several studies have investigated DNA methylation of some critical genes modulating depressive symptoms, including PTPRN2 (correlated with mood state disturbances), HES5 (associated with MDD and suicide), GATA2 (related to depressive behavior in rats), DGKA (differed significantly between MDDs and controls), NIPA2 (increased risk of MDD), PRDM7 (important in aging and Alzheimer), KCNIP1 (regulate neuronal membrane excitability), GRIK2 (related to mood disorders and depressive symptoms) (Wang et al., 2021).