The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; Influence of antidepressant use and depressive state?
Background An important biological factor suggested in the pathophysiology of (recurrent) Major Depressive Disorder (MDD) concerns a polymorphism in a gene encoding for the MTHFR-enzyme of the one-carbon (1-C)-metabolism. Integratively investigating key 1-C-components (folate, homocysteine, vitamin B6 and B12), including the possible effects of antidepressant medication and depressive state, could provide more insight in the possible association between the MTHFR-polymorphism and recurrent MDD. Methods We compared the MTHFR C677T-polymorphism together with the key 1-C-components in clinically ascertained patients with recurrent MDD (n=137) to age- and gender-matched healthy controls (n=73). Results First, patients had lower folate (t=2.25; p=.025) as compared to controls; a difference that resolved after correction for demographics (t=1.22; p=.223). Second, patients that were depressed during sampling had lower vitamin B6 (t=-2.070; p=.038) and higher homocysteine (t=2.404; p=.016) compared to those in remission. Finally, current use of antidepressants had no influence on the 1-C-components. Conclusions Despite investigation of a specific recurrently depressed patient population, we found no clear associations with the 1-C-cycle, except for higher homocysteine and lower vitamin B6 during the depressed state. This suggests that 1-C-cycle alterations in MDD are state-associated, possibly resulting from high levels of acute (psychological) stress, and may provide a treatment target to reduce cardiovascular risk in this population.
|Keywords||Depressive disorder, Folate, Homocysteine, Methylenetetrahydrofolate Reductase (NADPH2)/genetics, Vitamin B6|
|Persistent URL||dx.doi.org/10.1016/j.jad.2014.04.048, hdl.handle.net/1765/63177|
|Journal||Journal of Affective Disorders|
Lok, A, Mocking, L.P.C.M, Assies, J, Koëter, M, Bockting, C.L.H, de Vries, G.J, … Schene, A.H. (2014). The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; Influence of antidepressant use and depressive state?. Journal of Affective Disorders, 166, 115–123. doi:10.1016/j.jad.2014.04.048