Genotype plays role in schizophrenia

[LNN]

So some smart researchers at Mass General (home of Jenike and Geller) have discovered that a gene variant can help some people with schizophrenia improve by supplementing with....folate and B12. (dare I let myself think conventional science is catching on?)

 

Genotype plays role in schizophrenia response to folate

 

By: BIANCA NOGRADY, Clinical Psychiatry News Digital Network

 

Folate and vitamin B12 supplements may improve the negative symptoms of schizophrenia but only in patients with a genetic variant that influences folate metabolism, a study has shown.

 

"Although four such variants have previously been associated with negative symptom severity, the genotype that contributed most strongly to treatment response was FOLH1 484T>C," wrote Dr. Joshua L. Roffman, of the psychiatry department at Massachusetts General Hospital, Boston, and his colleagues.

 

© thinkstockphotos.com

 

 

 

Patients treated with folate plus vitamin B12 showed significant improvement on the Scale for the Assessment of Negative Symptoms (SANS), compared with placebo (group difference, –0.33 change in score per week; 95% confidence interval, –0.62 to –0.05), when genotype was taken into account.

 

Among patients homozygous for the 484T allele – a genetic variant in the folate hydrolase 1 (FOLH1) gene – the benefits of folate and vitamin B12 supplements were even greater (–0.59 change in SANS score per week; 95% CI, –0.99 to –0.18), according to results published in JAMA Psychiatry (formerly Archives of General Psychiatry) (2013 March 6 [doi: 10.1001/jamapsychiatry.2013.900]).

 

The double-blind, placebo-controlled study randomized 140 outpatients with schizophrenia, who had persistent symptoms despite treatment with antipsychotics, to 2 mg of folic acid and 400 mcg of vitamin B12 daily for 16 weeks or placebo. The patients were 18-68 years old, had been treated with an antipsychotic for at least 6 months, and were at a stable dose for at least 6 weeks. They also had to have scored at least 60 on the Positive and Negative Syndrome Scale.

 

The study found that only the high-functioning variant of FOLH1 (484T) was associated with a benefit from supplementation, while the effects of supplementation did not reach significance for either the low-functioning variant of FOLH1 (484C) or the MTHFR, MTR, or COMT genotypes.

 

While the treatment effects were modest, the researchers noted that even small effects could be clinically meaningful given the disability associated with negative symptoms, the paucity of available treatments for these symptoms, and the minimal side effects of vitamin supplements.

 

Folate deficiency is known to be a risk factor for schizophrenia, and all four genetic variants included in the study have been associated with increased severity of negative symptoms such as apathy, social withdrawal, and loss of emotional expressiveness.

 

"Thus, the finding that only patients homozygous for the T allele exhibited improvement in negative symptoms after 16 weeks of folate supplementation could reflect diminished folate absorption, and briefer exposure to higher folate levels, among C allele carriers," the researchers wrote.

 

The authors suggested that the findings could have implications for other health conditions associated with reduced folate and elevated homocysteine concentrations, such as stroke, cardiovascular disease, and dementia. "The current results suggest that individual differences in folate metabolism related to the presence of common functional genetic variants may have a bearing on treatment outcomes in these other disorders, as well as negative symptoms of schizophrenia," Dr. Roffman and his colleagues noted.

 

The research was funded by the National Institute of Mental Health and an award from the Howard Hughes Medical Institute, with support from Harvard Catalyst. The investigators disclosed receiving support and grants from a number of pharmaceutical companies and research organizations.

[ptcgirl]

Very Interesting! I'm trying to figure out how to find a good dr or info on LOW homocysteine and +mthfr c677t. Our llmd and pandas dr's don't know anything about them. I found an interesting article on it by Kara Fitzgerald http://www.drkendalstewart.com/wp-content/uploads/2011/09/Significance-of-Low-Plasma-Homocysteine.pdf and so I ordered Vital Detox Formula that has MSM, Glutathione, N-Acetylcysteine, and taurine in it. Does anyone have any info on this stuff? Feel like I'm trying to be a doctor here because I can't find a dr that knows anything about it. Ugh. My DD is doing pretty well right now (about 90%), I hate to mess anything up, but feel like if there is an imbalance it needs to be addressed. Thoughts? Advice?

[LNN]

Very Interesting! I'm trying to figure out how to find a good dr or info on LOW homocysteine and +mthfr c677t. Our llmd and pandas dr's don't know anything about them. I found an interesting article on it by Kara Fitzgerald http://www.drkendalstewart.com/wp-content/uploads/2011/09/Significance-of-Low-Plasma-Homocysteine.pdf and so I ordered Vital Detox Formula that has MSM, Glutathione, N-Acetylcysteine, and taurine in it. Does anyone have any info on this stuff? Feel like I'm trying to be a doctor here because I can't find a dr that knows anything about it. Ugh. My DD is doing pretty well right now (about 90%), I hate to mess anything up, but feel like if there is an imbalance it needs to be addressed. Thoughts? Advice?

 

When I was looking for our sweet spot on methylfolate dosing, my DD developed Low homocysteine with C677T because I was giving her way too much methylfolate (and not enough methylB12 either).

 

One note on what you ordered - MSM, Glutathione, NAC and Taurine are all sulfurs, which would be bad if your DD has a CBS mutation. Taurine helps balance glutamate and Gaba but should be avoided for those with CBS. I always figured my DD was negative for CBS because she tolerates Bactrim - a sulfur abx. Turns out she is heterozygous (+/-) for two CBS snps. So just be aware. If you see sudden mood swings, stop the supplement and read up on using CoQ10, carnitine and Yucca to counteract the negative response.

[ptcgirl]

Good info. Okay, I will wait to get the results back for 23andme (for the CBS results, etc) for my dd before giving any supplements. I just ordered the kit. What's another two months to wait?