Maternal MTHFR C677T Genotype & Depressed Mood during Pregnancy Affects SLC6A4 Methylation in Infants at Birth

Abstract

In utero and early postnatal exposure to depressed maternal mood may program childhood behaviour via epigenetic processes. Methylenetetrahydrofolate reductase (MTHFR) is an enzyme important for methyl metabolism. A common variant in the MTHFR gene, C677T, is associated with depression. We investigated the effect of maternal MTHFR C677T genotype on maternal mood (Edinburgh Postnatal Depression Scale, EPDS), during pregnancy (n=82 women, all receiving folate supplements) and on promoter methylation of two genes implicated in depression, brain derived neurotrophic factor, BDNF, and sodium‐dependent serotonin transporter, SLC6A4, in the women and their infants at birth. Women with the MTHFR 677TT genotype had greater (P<0.05) mid gestational depressed mood (mean age 24.98±0.51 weeks). Maternal MTHFR 677TT genotype was also associated with lower (P<0.05) maternal and infant SLC6A4 promoter methylation but not BDNF methylation. We also found a negative relationship (P<0.01) between maternal depressed mood (EPDS scores) and maternal SLC6A4 promoter methylation. These findings show that maternal MTHFR C677T genotype and mood influence maternal and infant SLC6A4 promoter methylation and suggests that disrupted maternal methyl metabolism and depression during pregnancy affects gene‐specific DNA methylation patterns, which may have long‐term consequences for childhood behaviour.Grant Funding SourceCIHR