Homocysteine, MTHFR and schizophrenia studied AND meta-analysed

"Our study suggests that increased plasma total homocysteine levels may be associated with an increased risk of schizophrenia". Further: "The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia".

MTHFR (again!) @ Paul Whiteley

So said the results of the study and meta-analysis carried out by Akira Nishi and colleagues [1] (open-access) looking at the 'big H' alongside everyone's genetic Scrabble favourite MTHFR (methylenetetrahydrofolate reductase (NAD(P)H)).

The Nishi paper represents pretty good scientific value for money given that authors not only looked at plasma levels of total homocysteine in nearly 400 participants diagnosed with schizophrenia compared with nearly 1000 controls, they also genotyped for the MTHFR C677T polymorphism [2] (describing an amino acid substitution which reduces the activity of the enzyme methylenetetrahydrofolate reductase and results in elevated homocysteine levels) in a further 1700 participants with schizophrenia compared against over 3000 asymptomatic controls. For good measure, the authors then carried out a meta-analysis of the scientific literature looking at homocysteine and schizophrenia as a function of gender. Phew.

As per the opening paragraph, authors reported "significantly elevated plasma total homocysteine levels in patients with schizophrenia compared with controls, in both male and female subjects". The results of their meta-analysis confirmed such elevations in homocysteine "although antipsychotic medication might influence this outcome". Combined with the association made between a diagnosis of schizophrenia and the MTHFR SNP studied, all adds up to "disrupted 1-carbon metabolism [having] an important role in the pathophysiology of schizophrenia".

I don't mind saying that the Nishi results are really rather interesting to me. The links between schizophrenia and homocysteine have been talked about previously on this blog (see here) including the potential usefulness of folic acid and vitamin B12 for some cases of schizophrenia (see here). Nishi et al also talk about another potentially important part of their results with some mention of DNA methylation, something which also crosses over into other areas of research interest too (see here).

And so the evidence continues to stack up for the big H and MTHFR in some cases of schizophrenia...

Music then. The Pixies and Debaser.

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[1] Nishi A. et al. Meta-analyses of Blood Homocysteine Levels for Gender and Genetic Association
Studies of the MTHFR C677T Polymorphism in Schizophrenia. Schizophrenia Bulletin. 2014; 40: 1154-1163.

[2] Gilbody S. et al. Methylenetetrahydrofolate reductase (MTHFR) genetic polymorphisms and psychiatric disorders: a HuGE review. Am J Epidemiol. 2007 Jan 1;165(1):1-13.

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Nishi A, Numata S, Tajima A, Kinoshita M, Kikuchi K, Shimodera S, Tomotake M, Ohi K, Hashimoto R, Imoto I, Takeda M, & Ohmori T (2014). Meta-analyses of Blood Homocysteine Levels for Gender and Genetic Association Studies of the MTHFR C677T Polymorphism in Schizophrenia. Schizophrenia bulletin PMID: 24535549