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

J Psychopharmacol. 2004 Dec;18(4):567-71. doi: 10.1177/0269881104047285.


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 B(12) 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 B(12) did not differ significantly between groups. A MTHFR C677T genotype is associated with increased risk of depressive episodes in this homogenous patient population.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Cohort Studies
  • Depressive Disorder / epidemiology
  • Depressive Disorder / genetics*
  • Depressive Disorder / psychology*
  • Female
  • Folic Acid / blood
  • Gene Frequency
  • Genotype
  • Homocystine / blood
  • Humans
  • Ireland / epidemiology
  • Male
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Vitamin B 12 / blood


  • Homocystine
  • Folic Acid
  • Methylenetetrahydrofolate Reductase (NADPH2)
  • Vitamin B 12