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MTHFR and Schizophrenia

Syd Barrett of Pink Floyd

I’ve always loved Pink Floyd, Syd Barrett was in the group initially and influenced the band as seen in the Dark Side of the Moon album. Shine On indeed.  MTHFR has been associated with many heartbreaking problems, one of them is Schizophrenia.  There are many genes associated with schizophrenia, and while this is only one, at least it’s one you can do something about.

This article talks about how schizophrenia was associated with a scandinavian population but couldn’t be expanded into the larger Nordic population. The study does not say there is no correlation between C677T and Schizophrenia, it just says that it didn’t impact the age at which schizophrenia was diagnosed.  In a Syrian study there was  a definite correlation between A1298C and schizophrenia, and a separate study showed the same for the Chinese.

This Cross function table shows more than one gene can be associated with Schizophrenia (and Bipolar) and MTHFR is definitely one of them along with MTR and NOS3 in the category of oxidative stress.  The primary association between these genes is the interaction of stimulation of the glutamate binding site of the NMDA receptor through homocysteine.

Pregnancy

One studies show an association with amount of gray matter in neonates and psychiatric risk.  There were several genes under consideration but COMT (rs4680), was found to have a strong association.

It seems one thing that can be done is to take choline during pregnancy. Recommended during the last two trimesters and early in life at amounts of 3.6g of PS in the morning and 2.7g in the evening, it has shown to reduce risk factors measured at day 33.  Deficient inhibition is typically found in schizophrenic patients, measured as the ability to react to he first clicking sound but to inhibit the reaction in a second click.  This was the test used on infants to see if there was a positive effect of the supplement and there seems to be!

It was also found that genes for schizophrenia and autism are switched on during rapid development, which interestingly is when neural tube defects also have issues (helped by folate supplementation).  In children and adolescents there was an association with MTHFR and mental illness only in cases of high homocysteine.

Link to Cancer and Cardiovascular Diseases

“Women with schizophrenia were 3.3 times more likely to die of cardiovascular disease and men 2.2 times more likely. Women with schizophrenia were 1.7 times more likely to die of cancer while men were 1.4 times more likely, compared with those without schizophrenia”.  We can see a correlation.  Is it not interesting that problems  folate metabolism can contribute to cardiovascular risk and cancer as well?   Since folate metabolism is related to cardiovascular risk and it maybe addressed with Methyl Folate, it’s certainly worth it to have a little insurance in case it is effective.  We don’t yet  have a recommended dose for this aspect but until we do, maybe create some sort of baseline.  Other studies also tentatively recommend folate supplementation, especially for C677T women.

The Brain

An association of both the major SNPs in MTHFR were shown to affect men but not women, while other studies were less specific about gender but found the same SNPs as significant, especially C677T.  In this study a combination of COMT Val158 and MTHFR together was found to affect cognition in schizophrenics, however it was found that the C677T  mutation of MTHFR actually attenuated COMT hyperfunction!.   This implies that there is some lower and upper level that must be targetted, and that MTHFR participates in it.  Is this why MTHFR is continued to be passed on, is this the evolutionary advantage of C677T?

C677T has been shown to increase preseveration (repeated thoughts about the same thing).  Other studies show that MTHFR and MTR,  folate regulation enzymes and COMT, and FOLH1 contribute to negative symptoms in schizophrenics as a group and even more so than C677T alone. Another example of MTHFR contributing but not being the only actor.

Based on he complexity found in terms of schizophrenia and other genes, why not take a little Methyl Folate?  If you have a 1st degree relative with schizophrenia, take a small dose.   It’s a step that is easy and accessible with very little negative impact.  Add choline if you are pregnant.  It seems that the problems with schizophrenia manifest during gestation and early infancy.  While it’s not clear whether it would help an adult with this condition, I would certainly be willing to try it.  Since no studies tell us how much to take, it  would seem prudent to err on the side of smaller doses.

UPDATE 3/26/2013:  A study referenced gave 2 mg of folate plus 400 µg of vitamin B12 per day or placebo for 4 months to schizophrenia patients.  The greatest improvement were seen with the FOLH1 gene, but:

“When they examined the effects of the individual polymorphisms, they found a slight, though not significant, benefit for folate use in the T allele carriers of MTHFR, and no effect for MTR and COMT variants.

But “Among patients receiving folate supplements, the greatest improvements were seen for those who had the lowest baseline levels of red blood cell folate (r = 0.43, P=0.04)”.

It’s possible that if there is an insufficiency in the blood, it may be even greater than the liver.  So large doses may be warranted to shore up the liver and until blood levels reach targeted values, and then dosages can be decreased. The study also used folic acid and not MethylFolate (grrr!)   Small improvements were seen, and if you have schizophrenia, small improvements simply from taking vitamins are welcome.

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