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Folate and vitamin B12 reduce disabling schizophrenia symptoms in some patients
Date:3/6/2013

associated with more severe negative symptoms in previous research, in this study it was the high-functioning FOLH1 variant that predicted a better treatment outcome. Measurement of participants' blood folate levels throughout the study provided an explanation for this unexpected finding. Those with the low-functioning FOLH1 variant started the trial with substantially lower folate levels, suggesting a problem with folate absorption. Although supplementation enabled their blood folate levels to eventually catch up with those of participants with the high-functioning variant, it was probably too late to produce symptom improvement during the 16-week trial period.

"For participants who did show a benefit, it took the full 16 weeks of treatment for that benefit to appear," Roffman explains. "While we don't know why this is the case, changes in gene expression which take time are a likely explanation. Folate plays a critical role in DNA methylation, which regulates gene expression, so it's plausible that its effects on negative symptoms act through gene expression changes. Participants with the low-functioning FOLH1 variant might eventually show a benefit of folate supplementation if treated for a longer period of time, but that needs to be investigated in future studies."

He adds that, while the benefits of supplementation for the overall group were modest, the lack of effective treatment for negative symptoms and the safety of folate and vitamin B12 supplementation support the need for larger-scale trials. In addition, the impact of genotype on this study's results suggests the need to investigate the role of folate pathway variants in conditions such as dementia and cardiovascular disease, in which low folate appears to increase risk but supplementation trials have had inconclusive results.

"We are now conducting a clinical trial of 1-methylfolate, which bypasses some of these folate-pathway enzymes and might have greater efficiency a
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Contact: Kristen Stanton
kstanton3@partners.org
617-643-3907
Massachusetts General Hospital
Source:Eurekalert

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