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The MTHFR C677T polymorphism is associated with depressive episodes in patients from Northern Ireland

Department of Mental Health, Queen’s University Belfast, Belfast, UK, chriskelly{at}bch.n-i.nhs.uk

Anne P. McDonnell

Department of Mental Health, Queen’s University Belfast, Belfast, UK

Timothy G. Johnston

Department of Mental Health, Queen’s University Belfast, Belfast, UK

Ciaran Mulholland

Department of Mental Health, Queen’s University Belfast, Belfast, UK

Stephen J. Cooper

Department of Mental Health, Queen’s University Belfast, Belfast, UK

Dorothy McMaster

Department of Medicine, Queen’s University Belfast, Belfast, UK

Alun Evans

Department of Epidemiology and Public Health, Queen’s University Belfast, Belfast, UK

Alexander S. Whitehead

Department of Pharmacology and Centre for Pharmacogenetics, University of Pennsylvania, Philadelphia, PA, USA

Low plasma folate and its derivatives have been linked with depressive disorders in studies dating back over 30 years. A thermolabile variant (677C>T) of the enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is associated with low serum folate. The present study aimed to explore whether the thermolabile variant of MTHFR is associated with a vulnerability to depressive episodes. MTHFR C677T genotype frequencies in a cohort of patients (mean age 48 years) with depressive disorder (n = 100) were compared with those in age- and sex-matched controls. Serum levels of folate, homocysteine and vitamin B₁₂ were also compared between groups. The thermolabile variant of MTHFR was significantly more common in the group with a history of depressive disorder (P= 0.03). Serum levels of folate, homocysteine and vitamin B₁₂ did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.

Key Words: depression • folic acid • homocysteine • MTHFR • vitamin B12

Journal of Psychopharmacology, Vol. 18, No. 4, 567-571 (2004)
DOI: 10.1177/0269881104047285


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