Epigenetic modification is a production of gene‐environment cross‐talk, epigenetic mechanism is a critical cause of major depressive disorder and chronic stress exposure.[33, 34] As a DNA hydroxymethylase, Tet2 has been reported to be involved in the pathogenesis of various neurological diseases, such as ischemic stroke,[35] multiple sclerosis,[36] Alzheimer's disease,[37] and Parkinson's disease.[38] Our team focuses on the role of the TET enzymes, particularly Tet2, in the mechanism of depression. The gene discussed is TET2; the disease is early-onset autosomal dominant Alzheimer disease.