I got the information after doing my gene test with 23andme. I ran the raw data through another software called promethease and that was among the results. I've seen this discussed a few times but it hasn't gotten a lot of attention.
I have a MET158VAL polymorphism in the COMT gene with the genotype VAL/VAL. That means the enzyme catechol-o-methyl transferase is highly active in my body and brain. This enzyme methylates many compounds, rendering them inactive.
Among these, are the catecholamines Dopamine, norepinephrine, epinephrine and others like caffeine and estrogens. Incidentally, I did a hormone panel a few years ago and my estrogen levels were radically low. My doctor didn't make anything of this and I could never figure out why. I think the low estrogen is the culprit behind my chronic joint pain. In support of this, aromatase inhibitors cause joint pain as a side effect because it lowers estrogens. Even supplements with small aromatase inhibition function like resveratrol and mangosteen, worsen this pain for me.
The lower dopamine levels specially in the prefrontal cortex can explain all the dopamine related issues I've had over the years such as lack of motivation, ADD and even the social phobia. Patients with high COMT activity are reported to be less motivated and more prone to ADD symptoms.
The concept of Warrior vs. worrier is directly related to the levels of COMT activity. The val/val genotype makes one a warrior while a met/met a worrier. Each has advantages and disadvantages mediated by low and high dopamine levels, respectively. The warrior tends to have low dopamine levels until said person is under stress. In this case, prefrontal dopamine levels increase (temporarily) improving focus and motivation. In my case, stress is not enough. I need to be angry. It is this anger that's helping me write this post (along with green tea) that I've been putting off for weeks. I've known for a long time that I became more focused and motivated when I was angry and I exploited this reaction to my advantage. I just never knew why.
Val158 alleles may be associated with an advantage in the processing of aversive stimuli (warrior strategy), while Met158 alleles may be associated with an advantage in memory and attention tasks (worrier strategy). Under conditions of increased dopamine release (eg, stress), individuals with Val158 alleles may have improved dopaminergic transmission and better performance, while individuals with Met158 alleles may have less efficient neurotransmission and worse performance.
I'm not implying that this is the only cause of social phobia but it's definitely one that can be diagnosed and even treated. There are certain compounds that inhibit the COMT enzyme and improve some of these issues. The most effective ones seem to be:
- Rhodiola Rosea
- Vitamin C
You've probably tried many of these supplements only to find they worsen anxiety. That's the effect of COMT inhibition. If you can find a way to mitigate the anxiety they provokes, you can probably benefit from the effect of increased dopamine.
Some ideas on how to do this:
- Combine with a cholinergic agent to enhance parasympathetic activity
- Magnesium and Lysine to keep cortisol low. Cortisol stimulates PNMT.
- Inhibit the enzyme dopamine beta hydroxylase to inhibit conversion of Dopamine to Norepinephrine.
- Inhibit the enzyme PNMT which converts Norepinephrine to epinephrine.
The COMT enzyme uses magnesium and SAMe as co-factors which could explains low levels or a high demand for these substances. SAMe is also a cofactor for the PNMT enzyme so it increases epinephrine production and worsen anxiety for some. I get anxiety from SAMe every single time.