Researchers at McMaster University, Hamilton, ON, Canada performed a systematic review and meta-analysis of 15 studies of methylenetetrahydrofolate reductase gene (MTHFR C677T) and migraine in 447 patients selected from the Depression Case Control study (age 18 years or older). MTHFR C677T polymorphism was associated with migraine with aura (MA) (p=0.039), and the association remained significant after adjusting for age, sex and depression status. T allele homozygosity is significantly associated with MA and total migraine, but not migraine without aura. In studies of non-Caucasian population, the TT genotype was associated with total migraine, whereas in studies of Caucasians this variant was associated with MA only. 
COMMENT. This study adds to the evidence for the role of MTHFR C677T gene variant in migraine with aura and shows a significant association between this genetic variant and MA in Caucasian population and total migraine in non-Caucasian population. A common polymorphism from the MTHFR gene, the C677T, is reported to be associated with both migraine and depression independently.
A population-based longitudinal community study of major depression and migraine in patients age >12 years found respondents with migraine were 60% more likely to develop major depressive episodes (MDE) compared with those without migraine. Similarly, respondents with MDE were 40% more likely to develop migraine compared with those without MDE, but after adjustment for stress and childhood trauma, this association disappeared. Environmental factors such as childhood trauma and stress may shape the expression of this bidirectional relationship. (Modgill G et al. Headache Nov 15, 2011[Epub ahead of print]