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Impact of folic acid on postpartum depression may be genetically determined

Published on

05 August 2011

According to a new study from UK, a protective effect of folic acid against depression outside pregnancy is particularly observed at women with the MTHFR C677T TT genotype.

The authors analyzed the data from more than 13,000 women during and after pregnancy. These women participated in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based population prospective study investigating factors that affect the health and development of children and their parents (1). The researchers examined the association between folic acid supplementation in pregnancy and MTHFR C677T genotype. They measured changes in depression scores assessed by the Edinburgh Postnatal Depression Scale (EPDS) between 18 and 32 weeks antenatally, and between 32 pregnancy weeks and 8 weeks postpartum, and between 8 and 21 months post partum. A questionnaire was used to determine the use of folic acid supplements.

The study was based on previous trials that showed low folate levels to be associated with depression in the general population. Folate participation in DNA methylation, an essential process for gene regulation, is one of the biological mechanisms that may provide an explanation to the question: how does folate affect central nervous system pathways that regulate the mood? The enzyme methyltetrahydrofolate reductase (MTHFR) metabolizes folate and plays a role in synthesis of methionine from homocysteine. MTHFR activity and circulating homocysteine levels is associated with a MTHFR gene in which a C677T polymorphism has been identified. Many women take folate acid supplements before conception and in the first 3 months of or even throughout pregnancy to reduce the risk of neural tube defects (NTDs).

The authors found no strong evidence for an association between folic acid supplementation, which could increase circulating folate levels and decrease homocysteine levels substantially, with changes in depression scores during pregnancy or up to 8 months postpartum. Irrespective of this, they “did find evidence to suggest that folic acid supplementation in pregnancy may protect against an increase in depressive symptoms between 8 and 21 months postpartum”. This effect was most pronounced among those individuals with the MTHFR C667T TT genotype for which the biggest impact of folic acid supplementation on circulation folate and homocysteine levels has been shown. According to the study’s findings the folic acid supplements “had the most beneficial impact on EPDS scores at 21 month postpartum among women with the TT genotype”.


  1. Lewis S.J. et al. Folic acid supplementation during pregnancy may protect against depression 21 months after pregnancy, an effect modified by MTHFR C677T genotype. European Journal of Clinical Nutrition 2011.

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