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American Journal of Epidemiology Advance Access originally published online on October 30, 2006
American Journal of Epidemiology 2007 165(1):1-13; doi:10.1093/aje/kwj347
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.

Methylenetetrahydrofolate Reductase (MTHFR) Genetic Polymorphisms and Psychiatric Disorders: A HuGE Review

Simon Gilbody1, Sarah Lewis2 and Tracy Lightfoot1

1 Department of Health Sciences, Alcuin College, University of York, York, United Kingdom
2 Department of Social Medicine, Faculty of Medicine, University of Bristol, Bristol, United Kingdom

Correspondence to Dr. Simon Gilbody, Department of Health Sciences, Alcuin College, University of York, York YO10 5DD, United Kingdom (e-mail: sg519{at}york.ac.uk).

The authors performed a meta-analysis of studies examining the association between polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, including MTHFR C677T and A1298C, and common psychiatric disorders, including unipolar depression, anxiety disorders, bipolar disorder, and schizophrenia. The primary comparison was between homozygote variants and the wild type for MTHFR C677T and A1298C. For unipolar depression and the MTHFR C677T polymorphism, the fixed-effects odds ratio for homozygote variants (TT) versus the wild type (CC) was 1.36 (95% confidence interval (CI): 1.11, 1.67), with no residual between-study heterogeneity (I2 = 0%)—based on 1,280 cases and 10,429 controls. For schizophrenia and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.44 (95% CI: 1.21, 1.70), with low heterogeneity (I2 = 42%)—based on 2,762 cases and 3,363 controls. For bipolar disorder and MTHFR C677T, the fixed-effects odds ratio for TT versus CC was 1.82 (95% CI: 1.22, 2.70), with low heterogeneity (I2 = 42%)—based on 550 cases and 1,098 controls. These results were robust to various sensitively analyses. This meta-analysis demonstrates an association between the MTHFR C677T variant and depression, schizophrenia, and bipolar disorder, raising the possibility of the use of folate in treatment and prevention.

anxiety; bipolar disorder; depression; folic acid; genetics; methylenetetrahydrofolate reductase (NADPH2); MTHFR; schizophrenia

Abbreviations: CI, confidence interval; HuGE, Human Genome Epidemiology; MTHFR, methylenetetrahydrofolate reductase; OR, odds ratio

Editor's note: This article also appears on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/).


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