Association between MTHFR C677T polymorphism and depression: An updated meta-analysis of 26 studies
Yile Wu, Xiuxiu Ding, Yehuan Sun, Huiyun Yang, Jian Chen, Xue Yan Zhao, Yuhong Jiang, Xiaoling Lv, Zhenqiang Wu
Progress in Neuro-Psychopharmacology and Biological Psychiatry2013
Summary (paraphrased)
Prior studies of the MTHFR C677T polymorphism and depression had given inconclusive results, so the authors pooled 26 studies comprising 4,992 depression cases and 17,082 controls. The T allele was associated with increased depression risk overall (TT vs CC odds ratio 1.42, 95% CI 1.16-1.75). Subgroup analysis showed a stronger signal in Asian populations (TT vs CC OR 1.88) and only a marginal association in White populations, with no association in the elderly. The authors conclude the C677T variant contributes to depression susceptibility, most clearly in Asian samples.
Why it’s in the systems review
MTHFR is Powers-named and one-carbon metabolism is his recurring explanatory thread for persistent neuropsychiatric symptoms; this meta-analysis supplies the human association data — modest but real — that a susceptibility model needs. It also motivates the treatment-candidate side of the search: if impaired folate-pathway function raises depression risk, then folate-pathway interventions (e.g., the L-methylfolate augmentation RCT of Papakostas et al. 2012) become testable candidates rather than speculation.
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