SIRT1 and major depressive disorder: Another study showed that FTO expression was also downregulated in the hippocampus of MDD patients and in three mouse models of depression, including that induced with CRS, which may regulate adrenoceptor β2 (ADRB2, regulating synaptic plasticity and depressive behaviors) and activate downstream c-MYC/SIRT1 to reverse depression-like behaviors [69].