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15-03-2011 | Mental health | Article

Folate may improve negative symptoms in some schizophrenia patients


Free abstract

MedWire News: Folate supplementation appears to improve negative symptoms in schizophrenia patients, but only among those with a genetic variant of a folate-metabolizing enzyme, study results show.

It follows an earlier study by the same group showing that schizophrenia patients with low serum folate levels who were also homozygous for the 677C>T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene had severe negative symptoms.

Nevertheless, Michele Hill (Massachusetts General Hospital, Boston, USA) and colleagues say "the significant pharmacogenetic effect must be interpreted with caution," adding that "larger studies of genotyped samples with wider ranges of baseline folate levels are needed."

Folate plays a key role in one-carbon metabolism and is essential for gene transcription, homocysteine metabolism, and the synthesis of several neurotransmitters. Indeed folate deficiency has been associated with several neuropsychiatric disorders including schizophrenia.

Meanwhile 677C>T of MTHFR has been linked to the overall risk for schizophrenia and, specifically, to negative symptoms, cognitive deficits, and related impairment in prefrontal function.

However, folate supplementation in schizophrenia is still matter of debate, with only two studies suggesting evidence of any benefit for negative symptoms.

The researchers recruited 46 stable adult schizophrenia outpatients, of whom 32 were randomized in a double-blind, parallel-group manner to a 12-week add-on trial of folate 2 mg/d or matching placebo. They also typed individuals for the 677C>T polymorphism at the MTHFR gene.

The primary outcome measure was change from baseline to week 12 on the modified Scale for Assessment of Negative Symptoms (SANS).

Hill and colleagues found that folate supplementation did not significantly affect negative symptoms compared to placebo across the entire cohort.

However, among participants with at least one copy of the MTHFR T allele (n=14; 56%), negative symptoms were more likely to improve with increased serum folate status compared with CC homozygotes.

Hill and colleagues comment: "It is unclear that a higher dose of folate would produce a greater therapeutic effect; nor is it clear whether a lower folate dose would be sufficient in patients with the MTHFR 677T allele."

The study results are published in the journal Schizophrenia Research.

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

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