The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis.


Lewis, SJ; Lawlor, DA; Davey Smith, G; Araya, R; Timpson, N; Day, IN; Ebrahim, S; (2006) The thermolabile variant of MTHFR is associated with depression in the British Women's Heart and Health Study and a meta-analysis. Molecular psychiatry, 11 (4). pp. 352-60. ISSN 1359-4184 DOI: https://doi.org/10.1038/sj.mp.4001790

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Abstract

Low dietary folate intake has been implicated as a risk factor for depression. However, observational epidemiological studies are plagued by problems of confounding, reverse causality and measurement error. A common polymorphism (C677T) in MTHFR is associated with methyltetrahydrofolate reductase (MTHFR) activity and circulating folate and homocysteine levels and offers insights into whether the association between low folate and depression is causal. We genotyped this polymorphism in 3,478 women in the British Women's Heart and Health Study. In these women, we looked at the association between genotype and three indicators of depression; ever diagnosed as depressed, currently taking antidepressants and the EuroQol mood question. We also carried out a systematic review and meta-analysis of all published studies which have looked at the association between MTHFR C677T genotype and depression. In the British Women's Heart and Health Study, we found evidence of an increased risk of ever being diagnosed as depressed in MTHFR C677T TT individuals compared with CC individuals, odds ratio (OR) 1.35(95% CI: 1.01, 1.80). Furthermore, we identified eight other studies, which have examined the association between depression and MTHFR C677T. We were able to include all of these studies in our meta-analysis together with our results, obtaining an overall summary OR of 1.36 (95% CI: 1.11, 1.67, P=0.003). Since this genotype influences the functioning of the folate metabolic pathway, these findings suggest that folate or its derivatives may be causally related to risk of depression.

Item Type: Article
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Non-Communicable Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
PubMed ID: 16402130
Web of Science ID: 236339700005
URI: http://researchonline.lshtm.ac.uk/id/eprint/12059

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