Meta-analysis of MTHFR gene variants in schizophrenia, bipolar disorder and unipolar depressive disorder: Evidence for a common genetic vulnerability?

ACMG Practice Guideline: lack of evidence for MTHFR polymorphism testing

“…20 The potential associations between MTHFR genotype status and a number of medical complications have been evaluated using methodologies such as case-control, cohort, Mendelian randomization, and meta-analysis. A modest positive association has been found between the MTHFR "thermolabile" polymorphism and many different medical complications, including, but not limited to, thromboembolic disease (in non-North-American populations only), 21,22 stroke, [23][24][25][26][27] aneurysm, 28 peripheral artery disease, 29 migraine, 30 hypertension, 31,32 recurrent pregnancy loss, 33,34 male infertility, 35,36 risk for offspring with neural tube defects, 37,38 certain cancers, [39][40][41] neuropsychiatric disease, 42 and chemotherapy toxicity. 43,44 …”

Analysis of genetic polymorphisms of brain-derived neurotrophic factor and methylenetetrahydrofolate reductase in depressed patients in a Slovak (Caucasian) population

“…Later meta-analyses of genetic studies associated with major depressive disorder (Gilbody et al 2007;Lewis et al 2006;Zintzaras 2006;Lopez-Leon et al 2008;Gaysina et al 2008;Peerbooms et al 2011) also reported the MTHFR 677T (OR = 1.20) polymorphism as one of the six positively associated polymorphisms with MDD.…”

“…Later studies on Caucasian population showed also various results (Hernandez et al 2009;Huang et al 2010). While Huang et al (2010) Peerbooms et al (2011) have examined the association between MTHFR and multiple psychiatric disorders (such as schizophrenia, bipolar disorder, and depression together) using a cross-disorder design, not separately for particular disorders and found no decisive results. However, till now, no study was done in the Slovak population of depressed patients in association with MTHFR C677T polymorphism.…”

Severe Mood Lability and Depression in an Adolescent Girl with a Methylenetetrahydrofolate Reductase Gene Mutation

“…The C677T polymorphism has likewise had a complex and conflicting evidence base: a 2004 Chinese study narrowly missed finding a statistically significant association between C677T and mood pathology (Tan 2004), and ten years later a western study of several genetic variants believed to be associated with bipolar disorder failed to find any association between Complicating this picture are other meta-analyses, each one attempting to reconcile the contradictory results of the previously literature into one cohesive conclusion, that find either a small but statistically robust association between C677T and bipolar disorder (Rai 2011), or a broader association between both MTHFR polymorphisms and mood dysregulation and psychosis more generally (Peerbooms 2011). One meta-analysis concludes that C677T is associated with schizophrenia, bipolar disorder, and unipolar depression, while A1298C was associated with bipolar disorder only (Peerbooms 2011). …”