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Old 05-21-2012, 10:20 AM   #1 (permalink)
 
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Default Figured out why I have low Dopamine - High COMT enzyme activity

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.

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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
  • EGCG
  • Oleuropein
  • Quercetin
  • 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.
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Old 05-21-2012, 10:32 AM   #2 (permalink)
 
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You can read more about the Warrior vs worrier idea here:

http://www.cnsspectrums.com/aspx/art...?articleid=642
http://www.snpedia.com/index.php/Rs4680
http://www.selfgrowth.com/articles/W...e_Are_You.html
http://www.ncbi.nlm.nih.gov/pubmed/17008817

There are some studies that show an association between a COMT polymorphism and social phobias:

http://www.ncbi.nlm.nih.gov/pubmed/15337664

There are also other genes that are linked to anxiety disorders such as MAO-A and 5-HTT, SLC6A4, BDNF.

To give you an idea, Manganese is a potent MAO inhibitor and it can explain why I reacted so well to it.
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Old 05-21-2012, 04:47 PM   #3 (permalink)
 
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in general genotype VAL/VAL (higher COMT-activity) is associated with low neuroticsm, low anxiety and high extraversion. so in your case it would not make sense..
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Old 05-21-2012, 09:42 PM   #4 (permalink)
 
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great post and interesting info on COMT and choline. cortisol gives me a feeling of GAD instead of SAD. SAD i believe to be buried deep within the psyche.

i also find when i harness anger i can get motivated. sometimes i'll start ****ing throwing around the ****ing f word every other ****ing word and it seems like people respect me more. perhaps they're entertained by the perceived spiral out of control. in the end anger cannot be an answer for me. it is a negative mental condition.

im still working it out but i believe the real answer to social anxiety is complete honesty, faith and selflessness. with these traits there can be no shame. obviously you have neural pathways to rewrite and as we know ours are dug deep.
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Old 05-21-2012, 11:23 PM   #5 (permalink)
 
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Quote:
Originally Posted by misread View Post
in general genotype VAL/VAL (higher COMT-activity) is associated with low neuroticsm, low anxiety and high extraversion. so in your case it would not make sense..
As ironic as it sounds, I used to be a very outgoing friendly guy. This SA problems only kicked in in my early 20's. That aspect of me is still there. The anxiety issues (non-phobic) have a lot to do with my upbringing and with family problems I've had. However, having the VAL/VAL polymorphism IS associated with social phobia. You can see that in some of the studies I posted above and there were more that I found. It's all about the dopamine and having a high COMT activity predisposes one to low dopamine resulting in not only different degrees of social phobia, but also ADD, lack of movitation, depression and other problems.

Maybe as a whole, Val/val has less anxiety and less neuroticism but it's not completely absent. Keep in mind though, that most people are not VAL/VAL or MET/MET. We are the minority. The majority of people are VAL/MET and are as normal as anyone can be.

I took this information and checked other people I suspected had similar traits. (within my family). Ran their gene tests and alas, VAL/VAL was the result everytime. In one particular case, I thought someone was MET/MET because they had the high trait anxiety and neuroticism but was able to focus well when it came to academic tasks. I was surprised to find this person was VAL/VAL but brilliant. All the genes that are linked to intelligence supported this. So the COMT gene alone, doesn't account for academic performance and success. Where in my case, I'm dumb and slow and when you add ADD and lack of motivation, geez..

However, I'm a warrior in every way the articles describes it. I finally put a name to the type of personality I have. I always welcome challenges, hence why I've picked the hardest things, the road less traveled by. I took all AP classes in high school and always chose the tough courses in college. I even went to Medical school. Ofcourse, I struggled given some of my limitations but I was able to graduate in very good standing. I never let problems get the best of me, I always focus on trying to solve them. Hence, why most of my posts are in the supplements forum, not anyone of the many "I hate having SA" subforums.

I found an old post here where someone looked at the COMT idea and was actually trying to RAISE the enzyme. NONONO! You want MORE dopamine, not less. Don't get stuck in the anxiety and neuroticism characteristics because it's only part of the problem and one that wasn't clearly defined.

I hope other people will try to find out if they are affected by this. I'm easy to figure out and not impossible to treat. One thing is knowing that low dopamine causes SA, another is knowing WHY you have low dopamine.
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Old 05-22-2012, 05:48 PM   #6 (permalink)
 
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Hey Beggiatoa,Interesting stuff!How's treating the overactive comt enzyme working out for you?What approach are you using i.e egec,rhodiola,quercetin?Also I'm a little confused about the magnesium bit.You claimed that the comt enzyme was reliant on magnesium but also suggested to use magnesium for the resultant anxiety of inhibiting comt enzyme.Anyway thanks for the post and previous posts.If everyone was as dedicated as you are we would of figured this **** out years ago!
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Old 05-22-2012, 08:14 PM   #7 (permalink)
 
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Quote:
Originally Posted by Beggiatoa View Post
I even went to Medical school. Ofcourse, I struggled given some of my limitations but I was able to graduate in very good standing.
So you are a doctor?

I agree with another post that it can be difficult to follow what you are saying. Some of the jargon e.g. VAL\VAL I do not understand.
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Old 05-24-2012, 12:47 PM   #8 (permalink)
 
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I don't fully understand what this mean and the magnesium part is a bit of speculation on my part. Magnesium and SAMe are cofactors for the enzyme and anxiety tends to deplete magnesium from your body faster than non-anxious people so it would make sense to keep some at hand. What is clear, however, is the association between high COMT activity/low dopamine and social anxiety. My contribution to this is how there are ways to partly inhibit the enzyme to allow a higher pre-frontal dopamine concentration. This should alleviate some of the low Dop. related problems.

I'm trying to figure out the best way (for me) to do this. There are medications that inhibit COMT but they are all liver toxic. I think I'll try a combination of Rhodiola and white tea and see how that goes.

Again, this is only one cause of social phobia like behavior but not the only one. If you want to understand more, read the links in the first post.
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Old 05-24-2012, 02:45 PM   #9 (permalink)
 
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Have you tried not fapping? Worked wonders for me.
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Old 05-24-2012, 05:52 PM   #10 (permalink)
 
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Quote:
Originally Posted by Define Me View Post
Have you tried not fapping? Worked wonders for me.
What is fapping?
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Old 05-24-2012, 07:14 PM   #11 (permalink)
 
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Quote:
Originally Posted by hoddesdon View Post
What is fapping?
A disease.

That we've all got to fight against to prevent SA.
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Old 05-25-2012, 09:16 AM   #12 (permalink)
 
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Quote:
Originally Posted by hoddesdon View Post
What is fapping?
Masturbating.
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Old 05-25-2012, 09:18 AM   #13 (permalink)
 
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^ this is disgusting.
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Old 05-26-2012, 12:33 PM   #14 (permalink)
 
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Quote:
Originally Posted by Define Me View Post
Have you tried not fapping? Worked wonders for me.
Actually, I have. It does works wonders
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Old 05-27-2012, 08:32 AM   #15 (permalink)
 
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Beggiatoa, I just want to say you are the damn man. You describe my in detail. ADD, lack of motivation and those other problems happen as well.

Rhodiola Rosea, Manganese, Magnesium, Vitamin C do wonders for me. I'm going to order some supplements again Better than Xanax I guess.
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Old 05-27-2012, 09:40 AM   #16 (permalink)
 
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You need to check out the CILTEP stack discovered at another forum:
http://www.longecity.org/forum/topic...80#entry516708
It worked to decrease my SA big time. It is basically quercetin and forskolin taken once or twice a day with some sort of stimulant.
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Old 05-28-2012, 03:59 PM   #17 (permalink)
 
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Thanks for the link Owtsgmi. I write on that forum as well. My nick there is Lufega. I'll have to give that thread a read again. I was interesting in inducing LTP before. I got great effects from carnosine.
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Old 05-29-2012, 01:32 AM   #18 (permalink)
 
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Quote:
Originally Posted by Beggiatoa View Post
Thanks for the link Owtsgmi. I write on that forum as well. My nick there is Lufega. I'll have to give that thread a read again. I was interesting in inducing LTP before. I got great effects from carnosine.
Ha..just read your post over "there" and had a feeling Lufega was the same poster. Your posts offer great insight... I appreciate the well thought out research. Plus, it's nice to get some cross talk among the forums to share ideas. I'll look into carnosine...that's one I haven't tried yet. What does it do for you?
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Old 05-29-2012, 06:09 AM   #19 (permalink)
 
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It helped in terms of retaining information when I studied. Like I wrote there, i can't remember what else I was using it with but I reacted very well. I have some left I'll pick again soon. I'm trying to go through the bin of retired supplements. Might as well, since I paid for them all :P
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Old 05-31-2012, 06:22 PM   #20 (permalink)
 
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pyridoxal-5'-phosphate is also a comt inhibitor. Very cool !
PMID:3004168
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