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Folate, Vitamin B₁₂, Homocysteine, and the MTHFR 677CT Polymorphism in Anxiety and Depression

The Hordaland Homocysteine Study

Ingvar Bjelland, MD; Grethe S. Tell, PhD, MPH; Stein Emil Vollset, MD, DrPH; Helga Refsum, MD; Per Magne Ueland, MD

Arch Gen Psychiatry. 2003;60:618-626.

Background  An association between depression and folate status has been demonstrated in clinical studies, whereas data are sparse on the relationship between depression and other components of 1-carbon metabolism such as vitamin B₁₂, homocysteine, and the methylenetetrahydrofolate reductase 677CT polymorphism. The relationship between anxiety and these components is less well known. This study examined the associations between folate, total homocysteine, vitamin B₁₂, and the methylenetetrahydrofolate reductase 677CT polymorphism, and anxiety and depression in a large population-based study.

Methods  Anxiety and depression, measured by the Hospital Anxiety and Depression Scale, were assessed in 5948 subjects aged 46 to 49 years (mean, 47.4 years) and 70 to 74 years (mean, 71.9 years) from the Hordaland Homocysteine Study cohort. By means of logistic regression models, anxiety and depression scores were examined in relation to the factors listed above.

Results  Overall, hyperhomocysteinemia (plasma total homocysteine level ≥15.0 µmol/L [≥2.02 mg/dL]) (odds ratio, 1.90; 95% confidence interval, 1.11-3.25) and T/T methylenetetrahydrofolate reductase genotype (odds ratio, 1.69; 95% confidence interval, 1.09-2.62), but not low plasma folate or vitamin B₁₂ levels, were significantly related to depression without comorbid anxiety disorder. Plasma folate level was inversely associated with depression only in the subgroup of middle-aged women. None of the investigated parameters showed a significant relationship to anxiety.

Conclusion  Our results provide further evidence of a role of impaired 1-carbon metabolism in depression.

From the Department of Public Health and Primary Health Care (Drs Bjelland, Tell, and Vollset), Locus for Homocysteine and Related Vitamins (Drs Bjelland, Tell, Vollset, and Ueland), and Department of Pharmacology (Drs Refsum and Ueland), University of Bergen, Bergen, Norway.

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