Japanese researchers have demonstrated that both men and women with schizophrenia have significantly higher plasma homocysteine levels than healthy controls.
The findings arise from a series of analyses investigating the effects of gender and methylenetetrahydrofolate reductase (MTHFR) C677T genotype on blood homocysteine levels in Japanese patients with schizophrenia.
Shusuke Numata (The University of Tokushima Graduate School) and colleagues initially showed that men with schizophrenia (n=225, mean age 58 years) had significantly higher levels of plasma homocysteine than mentally healthy male controls (n=331, mean age 38 years) regardless of MTHFR C677T genotype. Plasma homocysteine was also significantly higher in women with schizophrenia (n=156, mean age 59 years) for each genotype compared with mentally healthy female controls (n=667, mean age 43 years).
These findings were confirmed in meta-analyses of 12 association studies containing data on men (1079 patients with schizophrenia and 1559 controls) and 10 association studies containing data on women (615 patients with schizophrenia and 1461 controls). The results showed that plasma homocysteine levels were significantly higher in patients with schizophrenia than in controls, with standardized mean differences of 0.76 and 0.50 in men and women, respectively.
The authors note, however, that there was significant heterogeneity among the studies that may have been caused by genetic variations, clinical factors such as medication or environmental factors such as folic, vitamin B6, vitamin B12, obesity, smoking status and caffeine consumption. These factors were not taken into consideration in the analyses.
Numata and team also conducted a meta-analysis of six studies assessing the association between the MTHFR C677T polymorphism and schizophrenia in Japanese populations (4316 schizophrenia cases and 6062 controls). They found that carriers of the CC genotype had a 16% increased risk of schizophrenia compared with carriers of the TT genotype. There was no significant heterogeneity among the studies.
When the researchers used Mendelian randomisation to combine the results of the genetic association meta-analysis with those of the gene–homocysteine association study, they found that each standard deviation increase in plasma homocysteine level was associated with a 14% increased risk of schizophrenia.
Writing in Schizophrenia Bulletin, Numata and co-authors conclude that their study suggests that “increased plasma total homocysteine levels may be associated with an increased risk of developing schizophrenia”.
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