Folate supplementation in schizophrenia: A possible role for MTHFR genotype

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• 作者：Michele Hill^a ; ^b ; ^{michelehill1@gmail.com} ; Kelsey Shannahan^a ; ^b ; Sarah Jasinski^a ; ^b ; Eric A. Macklin^b ; ^c ; Lisa Raeke^a ; ^b ; Joshua L. Roffman^a ; ^b ; Donald C. Goff^a ; ^b
• 关键词：Folate ; Schizophrenia ; Negative symptoms ; MTHFR
• 刊名：Schizophrenia Research
• 出版年：2011
• 出版时间：April 2011
• 年：2011
• 卷：127
• 期：1-3
• 页码：41-45
• 全文大小：342 K

文摘

Background

Folate deficiency and the methylenetetrahydrofolate reductase (MTHFR) 677C > T polymorphism have been linked to negative symptoms in schizophrenia both independently and synergistically. This study examined the effect of folate supplementation on negative symptoms overall and in relation to MTHFR 677C > T genotype.

Method

Forty-six stable adult schizophrenia outpatients were enrolled and 32 were randomised, double-blind, in a parallel-group, twelve week add-on trial of folate 2 mg/d or matching placebo. The primary outcome measure was change from baseline to week 12 on the modified SANS total score using a mixed-model analysis. In addition, we measured the effect of MTHFR genotype on treatment effects and on changes in serum folate by grouping participants with T/T genotype together with C/T genotype and comparing their interactions to patients with C/C genotype.

Results

Twenty-eight participants completed the trial. Folate supplementation did not significantly affect negative symptoms compared to placebo across the entire cohort. However, there was a significant genotype × treatment effect on negative symptoms (F = 7.13, df = 1,39, p = 0.01). In addition, MTHFR status significantly moderated the relationship between change in serum folate and change in negative symptoms: among participants with at least one copy of the T allele negative symptoms were more likely to improve with increased serum folate (p = 0.03).

Conclusion

We did not detect a therapeutic benefit of folate supplementation in a sample of patients with residual negative symptoms. However, a possible association between genotypes associated with reduced MTHFR activity and benefit from folate supplementation should be investigated further.