MTHFR and depressive disorder: Family, adoption, and monozygotic- and dizygotic-twin studies have supported that both genetic and environmental factors and their interconnection contribute to MDD, and the heritability of MDD was about 37% (2, 3) Previous multiple meta-analyses have shown that 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T confers a predisposition to depression (4–7).