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Folate, vitamin B12 help schizophrenia symptoms

Monday March 11, 2013
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Adding folate and vitamin B12 to treatment with antipsychotic medication improved a core symptom component of schizophrenia in a study of more than 100 patients.

The study focused on negative symptoms of schizophrenia, including apathy, social withdrawal and a lack of emotional expressiveness. While the level of improvement across all participants was modest, results were more significant in individuals carrying specific variants in genes involved with folate metabolism.

"The symptoms of schizophrenia are complex, and antipsychotic medications provide no relief for some of the most disabling parts of the illness," corresponding author Joshua Roffman, MD, MMSc, of the Department of Psychiatry at Massachusetts General Hospital, said in a news release. "These include negative symptoms, which can be particularly devastating.

"Our finding that folate plus vitamin B12 supplementation can improve negative symptoms opens a new potential avenue for treatment of schizophrenia. Because treatment effects differed based on which genetic variants were present in each participant, the results also support a personalized medical approach to treating schizophrenia."

Previous studies have suggested that folate deficiency during pregnancy significantly increases the risk of schizophrenia among offspring. Earlier research by members of the MGH-based team associated low blood folate levels with more severe negative symptoms among patients with schizophrenia.

The current study, which appeared March 6 on the website of JAMA Psychiatry (formerly the Archives of General Psychiatry), was designed to investigate whether supplementation with folate and B12, which can magnify the effects of folate, reduced negative symptoms of schizophrenia. A 2011 pilot study found symptom improvement only among patients carrying a variant in a folate-pathway gene called MTHFR that reduced the gene’s activity.

To get a clearer picture of folate’s effect on negative symptoms, the researchers enrolled 140 patients with schizophrenia at community mental health centers in Boston, Rochester, N.Y., and Grand Rapids, Mich.

Participants were all taking antipsychotic medications — which have been shown to alleviate positive symptoms, such as hallucinations and delusions, but not negative symptoms — and were randomized to receive daily doses of either folate and vitamin B12 or a placebo for 16 weeks. Their medical and psychiatric status was evaluated every two weeks using standard symptom assessment tools and measurements of blood levels of folate and homocysteine, an amino acid that tends to rise when folate levels drop. Nutritional information was compiled to account for differences in dietary intake of the nutrients. Participants’ blood samples were analyzed to determine the variants they carried of MTHFR and three other folate-pathway genes previously associated with the severity of negative symptoms of schizophrenia.

Among all 140 participants in the study protocol, those receiving folate and vitamin B12 showed improvement in negative symptoms, but the degree of improvement was not statistically significant compared with the placebo group. But when the analysis accounted for the variants in the genes of interest, intake of the two nutrients did provide significant improvement in negative symptoms, chiefly reflecting the effects of specific variants in MTHFR and in a gene called FOLH1. Variants in the two other genes studied did not appear to have an effect on treatment outcome.

The full study is available at http://archpsyc.jamanetwork.com/article.aspx?articleid=1660588.


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