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Interesting NY Times Article - slightly OT


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Thanks for the link! Just before I read this, I was trying to work through a math strategy with my 2nd grader (who is a worrier to the max). She was a wreak, fearing that she was the only one who didn't "get it" and that she'd "get in trouble" for not being able to meet timed math test goals (for which she has a 504 but that's a different post).

 

So I read her the part that says stress before a test is a good thing. She scrunched up her face like I was crazy, so I showed her the sentence to prove I wasn't making this stuff up and she thought about it. Then her face lit up like a storm had just passed and she said "you're right! it does help me focus!" Now maybe she won't be so hard on herself and can come to see performance anxiety as something less than paralyzing failure.

 

Interestingly, COMT is one of the genes Yasko and 23andMe looks at.

COMT degrades dopamine, in the process using up methyl groups. Individuals who are COMT (+/+) degrade dopamine slowly, and as such have a lot of methyl groups floating around. If we supplement a COMT (+/+) individuals with methyl-B12 (or any other methyl donor for that matter) we can “OD” them with free methyl groups, too much of a good thing, and this leads to mood swings related to fluctuations in neurotransmitter levels. Individuals who are COMT (-/-) have normal COMT function; they break down dopamine rapidly, using up methyl groups in the process. COMT (-/-) individuals need and tolerate methyl donors quite well. So if you are (+) for the MTR up regulation and/or (+) for the MTRR down regulation, and you are also COMT (-/-), all we need to do is to give you methyl-B12. We are giving you the methyl-B12 that you need, and any extra methyl groups left over can be put to good use. Conversely, if you are COMT (+/+), we know that you have an excess of methyl groups floating around. We will give you hydroxy-B12, expecting it to combine with the methyl groups available to form the methyl-B12 you need (without ODing you with too many free methyl groups). This is all very confusing, and it gets worse when we consider the individual who is (+/-) for COMT, and when we factor in how one’s VDR gene status interacts with their COMT status. I will give you specific recommendations, whether you need methyl-B12, hydroxy-B12, or both in combination, in my analysis of your Methyl Cycle genotype.

 

COMT degrades dopamine, norepinephrine, and to a somewhat lesser extent other neurotransmitter substances, by tacking on to them a free methyl group that COMT obtains from SAMe. The V158M and H62H alleles of COMT are down mutations. Individuals (+/+) or (+/-) for these genes will degrade dopamine only slowly. Now, while COMT (+) status is not the norm, from our perspective it is not necessarily a bad thing. We need dopamine to defend against microbes and heavy metals; here being (+) for COMT is actually in our favor. BH4 deficiency is the consequence of CBS, BHMT, and the “backward” MTHFR A1298C defects. We need BH4 to carry out multiple physiologic steps, including the generation of dopamine. If our COMT (+) status keeps us from breaking down dopamine, we do not need to “spend” BH4 to make dopamine, leaving more BH4 available for other critical functions. The downside of being COMT (+) is that you will have a lot of free methyl groups floating around, as you are not using them up breaking down dopamine. Thus if we need to give you other Methyl Cycle intermediates (such as methyl-B12 if you have MTR/MTRR issues), we risk ODing you with methyl groups. Too many methyl groups can lead to mood swings. Panic attacks and bi-polar mood disorder are seen with greater frequency in COMT (+) individuals; this makes sense. COMT (-) individuals, on the other hand, need and tolerate methyl groups. A third, and less frequently encountered COMT abnormality, COMT 61, is a down regulation defect. Individuals (+) for COMT 61 breakdown dopamine quite rapidly and are at greatest need for methyl donors.

 

The bipolar mood swings are a classic problem for DD. So when I get our 23andMe results, I'm betting she'll be COMT+

 

(sorry - I didn't mean to make everything about methylation - it's just so cool how it all fits together).

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