Format

Send to

Choose Destination
J Affect Disord. 2014 Sep;166:115-23. doi: 10.1016/j.jad.2014.04.048. Epub 2014 Apr 30.

The one-carbon-cycle and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in recurrent major depressive disorder; influence of antidepressant use and depressive state?

Author information

1
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands. Electronic address: a.lok@amc.uva.nl.
2
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands.
3
Department of Clinical Psychology, University of Groningen, Groningen, The Netherlands.
4
Department of Forensic Molecular Biology, Erasmus MC University Medical Center Rotterdam, Rotterdam, The Netherlands.
5
Department of Psychiatry, Academic Medical Center, University of Amsterdam, Meibergdreef 5, Amsterdam 1105 AZ, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University Nijmegen, Nijmegen, The Netherlands.

Abstract

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

PMID:
25012419
DOI:
10.1016/j.jad.2014.04.048
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center