Effects of season of birth and a common MTHFR gene variant on the risk of schizophrenia

Eur Neuropsychopharmacol. 2011 Apr;21(4):300-5. doi: 10.1016/j.euroneuro.2010.10.001. Epub 2010 Nov 19.


Season of birth - in particular winter birth - has been persistently related to increased schizophrenia risk. Variation in folate intake is among the explanations for this seasonal effect. Methylenetetrahydrofolate reductase (MTHFR) is an essential enzyme in the folate mediated methylation transfer reactions. Interestingly, the MTHFR gene has been related to schizophrenia risk in various studies. We investigated a possible interaction between MTHFR 677C>T polymorphism and winter birth in the development of schizophrenia in a group of 742 schizophrenia patients and 884 control subjects. All subjects were of Dutch ancestry. Winter birth (December up to and including February) was associated with a 20% increase in schizophrenia risk (odds ratio (OR) of 1.20 and 95% confidence interval (CI), 0.96-1.5; P=0.113). The MTHFR 677TT genotype was associated with an overall schizophrenia risk of 1.13 (95% CI, 0.82-1.57; P=0.454) compared with the MTHFR 677CC genotype. In the winter period the MTHFR 677TT genotype associated schizophrenia risk was 0.90 (95% CI, 0.47-1.70; P=0.744). In conclusion, neither winter birth nor MTHFR genotype were significantly associated with increased schizophrenia risk. There was no evidence for interaction between MTHFR 677TT genotype and winter birth in the development of schizophrenia.

MeSH terms

  • Adult
  • Case-Control Studies
  • Female
  • Folic Acid Deficiency / physiopathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Maternal Nutritional Physiological Phenomena
  • Methylenetetrahydrofolate Reductase (NADPH2) / genetics*
  • Middle Aged
  • Netherlands
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Schizophrenia / epidemiology*
  • Schizophrenia / etiology
  • Schizophrenia / genetics*
  • Seasons*


  • Methylenetetrahydrofolate Reductase (NADPH2)