Our present study demonstrated that decreased brain pH is a common feature in several preclinical animal models of depression (e.g. mice exposed to social defeat stress, corticosterone-treated mice, and Sert KO mice) and comorbid depression (DM mouse model induced by streptozotocin treatment and colitis mouse model induced by dextran sulfate sodium treatment). The gene discussed is SLC6A4; the disease is diabetes mellitus.