Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype.
As low folate status has been implicated in depression, high folate intake, in the form of supplements, during pregnancy might offer protection against depression during pregnancy and postpartum. We examined the association between change in self-reported depressive symptoms (Edinburgh Postnatal Depression Scale) at different timepoints during and following pregnancy and self-reported folic acid supplementation during pregnancy in a prospective cohort of 6809 pregnant women. We also tested whether there was a main effect of methylenetetrahydrofolate reductase (MTHFR) C677T genotype (which influences folate metabolism and intracellular levels of folate metabolites and homocysteine) on change in depression scores, and carried out our analysis of folic acid supplementation and depression stratifying by genotype. We found no strong evidence that folic acid supplementation reduced the risk of depression during pregnancy and up to 8 months after pregnancy. However, we did find evidence to suggest that folic acid supplements during pregnancy protected against depression 21 months postpartum, and that this effect was more pronounced in those with the MTHFR C677T TT genotype (change in depression score from 8 months to 21 months postpartum among TT individuals was 0.66 (95% CI=0.31-1.01) among those not taking supplements, compared with -1.02 (95% CI=-2.22-0.18) among those taking supplements at 18 weeks pregnancy, P(difference)=0.01). Low folate is unlikely to be an important risk factor for depression during pregnancy and for postpartum depression, but may be a risk factor for depression outside of pregnancy, especially among women with the MTHFR C677T TT genotype.