In our experiments, SAMe was reduced to a lower level in the MDD patients’ plasma and depression animal models (Fig. 8), it increased m6A RNA methylation levels, produced antidepressant-like behaviors in FST and CSDS (Fig. 8) and, notably, SAMe reversed the depressive-like behaviors of astrocytic OE-Alkbh5 mice. This evidence concerns the gene ALKBH5 and depressive disorder.