Interaction of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and folic acid levels in recurrent depression

Introduction Low folate status and depression has been found in many studies of depressive patients. The evidence of folate being a factor in depression is strengthened by an emerging association of depression with a common polymorphism of a gene involved in the metabolism of folate: methylene tetrahydrofolate reductase (MTHFR). A thermolabile variant (677C > T) of the enzyme 5,10-methylenetetrahydrofolate reductase is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with recurrent depression. We measured the prevalence of MTHFR in relation to plasma levels of folate, vitamin B6 and B12 and homocysteine in recurrent Major Depressive Disorder (MDD-R) patients compared to a matched control group. Methods The present study was part of the Dutch DELTA study in remitted depressed (rMDD) patients with at least two depressive episodes in the past. MTHFR C677T genotype frequencies of rMDD patients (mean age 46.5 ± 9.6 years) with recurrent depressive disorder (n = 137) were compared with age- and sex-matched controls (HC; n = 70). Serum levels of folate, homocysteine and vitamin B6 and B12 were compared between groups. Results We found no difference in prevalences of CC, CT and TT genotypes between both groups. Serum levels of folate, homocysteine and vitamins B6 and B12 were not significantly different between groups. In patients with the wild type (CC) was associated with lower folic acid levels compared to matched controls (p = .04), while folate levels were not significantly different between MDD and HC for other genotypes. Discussion In contrast to healthy controls the CC genotype of the MTHFR C677T polymorphism mimics low folate status in rMDD-patients. This interaction is important as folic acid may have an antidepressant effect in itself, or as an adjunct to antidepressant drugs. The present study strengthens the accumulating evidence for the need 1) to control folic acid status in MDD and 2) to further analyse the impact of genotypes on folic acid metabolism in recurrent depression.