Collectively, here we hypothesize that increased Oxtr methylation may contribute to the maintenance of early life stress-induced depression susceptibility in adult mice, and that LPM570065, a novel and potent 5-HT/NE/DA triple reuptake inhibitor, may exert its antidepressant effects by reducing Oxtr methylation to reverse depression susceptibility. This evidence concerns the gene OXTR and major depressive disorder.