By Andrew M. Seaman
New York (Reuters Health) - Possessing one or another version of a gene key to metabolizing the B vitamin folate may make a big difference in who responds to vitamin supplements intended to treat negative symptoms of schizophrenia, according to a new study.
Researchers tracked 140 people with schizophrenia for 16 weeks and found that those with the so-called high-functioning FOLH1 gene variant had a greater response to folic acid and B12 supplements, compared to those with the low-functioning FOLH1 variant.
"That's a gene that actually controls the digestion of folate (or folic acid) into the bloodstream," said Dr. Joshua Roffman, the study's lead author from Massachusetts General Hospital in Charlestown.
Folate, one of the B vitamins, is used in the manufacturing of neurotransmitters, which send signals throughout the brain and body, and it's found in leafy vegetables, citrus fruits, beans and fortified grain products.
Since the 1960s, Roffman told Reuters Health, folate deficiencies have been tied to the development of schizophrenia, and researchers have observed spikes in cases of the mental disorder after famines in China and the Netherlands, for example.
But this new study, he said, is the first to look at the effects of folate supplements in a large population of people with the condition - at several medical centers in Massachusetts, New York and Michigan.
The researchers, who published their findings in JAMA Psychiatry, were targeting so-called negative symptoms in schizophrenia patients, which include apathy, withdrawal and an inability to display emotion.
Those are less severe than the more well-know symptoms of schizophrenia - including hallucinations, delusions and paranoia - but still lead to significant impairment, because they are unaffected by traditional antipsychotic drugs, experts said.
"There's nothing that's widely accepted that's demonstrated to help. So there is a big need for this kind of work," said Dr. Scott Stroup, a professor of psychiatry at New York's Columbia University who was not involved with the research.
For the new study, the researchers recruited 140 schizophrenia patients and randomly assigned them into two groups. One group received 2 milligrams of folic acid and 400 micrograms of vitamin B12, which increases folic acid's effect, per day for 16 weeks. The other group took placebo pills for comparison, but all patients also continued their normal medications.
At the beginning, each group scored in the mid-30s on a scale that measures the severity of their negative symptoms from 0 to 100 - with higher scores being more severe. Roffman said the participants all had moderate to severe symptoms.
Overall, those taking the supplements improved on the scale after the 16 weeks, but it wasn't until the researchers looked at each person's FOLH1 gene type that they identified who benefited the most.
Specifically, those with the high-functioning version of the FOLH1gene seemed to be able to process the supplements best, and saw their negative symptom score drop by about 5 points, compared to no significant change in the placebo group members with high-functioning FOLH1 genes.
"The level of symptom change we saw in this study would be detectable… but it's definitely a modest change," Roffman said.
He added that participants with high-functioning FOLH1 also had higher folate levels in their blood at the start of the study, compared to the participants with low-functioning FOLH1.
Folate levels in people with the low-functioning variant who took the supplements eventually caught up to those with the high-functioning variant, according to Roffman. And those participants might have improved on the symptom scale if the study had gone longer than 16 weeks.
Stroup told Reuters Health he doesn't think enough is known to use folic acid and B12 supplements to treat people with schizophrenia, but it's good that researchers are looking into it.
"I think the impact on negative symptoms was pretty small, but the paper itself is important," he said.
SOURCE: http://bit.ly/VP5E87 JAMA Psychiatry, online March 6, 2013.