SNP Highlight - COMT & Stress

One of the most fascinating SNPs we have come across in creating our Health Action Plans (HAPs) is catecholamine O-methyl transferase, or COMT. This enzyme is found all over the body, but the role the enzyme plays in the brain is the most interesting.  

Let’s take a step into a typical person’s life. At a certain point, they realize that they are running late, they forgot to send off a critical email, they have an argument with a loved one, and the list goes on. Each one of these stressors are our form of modern day tigers. When our body is “threatened,” it goes into fight or flight mode through the activation of our sympathetic nervous system. This is essentially the body telling the cells: “All systems are a go; everyone at their stations; we are about to hit warp drive.”

Three key hormones help our bodies and minds hit warp drive: dopamine, epinephrine and norepinephrine. Other hormones also get activated during this time, but we will focus on these 3 hormones. When we are running away from our “tigers,” our body increases the production of dopamine, norepinephrine and epinephrine to help us accomplish our task quickly and get away from that “scary tiger.”

Phew! That was close!  Now that the scary part is over, the brain has to break down the excess amounts of dopamine, epinephrine and norepinephrine. That is where COMT comes into play. COMT’s job is to clean up the mess. Think of it like a vacuum hose that goes around the synapse of brain cells and vacuums up the extra molecules. Perfect!

Well not quite so fast.

It turns out there are different variants in the COMT genes which lead to different vacuuming abilities. One variant is the parent: efficient, quickly zipping around the house vacuuming up all the dirt in a matter of minutes. The other variant is the child: lazy, taking forever to pull the vacuum cleaner out, getting overwhelmed by all the toys on the floor, and finally after multiple reminders finishing the job 2 hours after they started. Last is the 3rd variant, the “unmarried professional:” busy, staying on top of vacuuming mostly, but going through moments of not caring if the carpet is vacuumed and through periods of having a messy carpet.

This is what it looks like from your genetic reports:

Adult: AA AKA Val/Val, warrior ~20% of the population

Child: GG AKA Met/Met, worrier ~30% of the population

Professional: AG ~ 50% of the population

What does this mean for these different people under times of stress?

The “adult” COMT enzyme breaks down dopamine, epinephrine and norepinephrine quickly, which is great in times of stress. These individuals usually live in a more dopamine deficient state because their COMT enzyme is too efficient at breaking down these neurotransmitters. In times of stress, the levels of dopamine rise, bringing them up to a more middle of the road level. However, because these individuals tend to live in a more dopamine depleted state, they are more prone to participating in activities that will elicit a dopamine rush: extreme sports, fulfilling cravings, nursing addictions, anger and lack of impulse control. Since dopamine plays an important role in brain function, these individuals may struggle to stay focused on a task and may be prone to procrastination.

In contrast to the “adult,” the “child” breaks down dopamine, epinephrine and norepinephrine very slowly (think 3-4x slower than the “adult”), which becomes problematic during stressful times. These individuals usually live in a more dopamine excess state because their COMT enzyme is too lazy to break down these neurotransmitters. In times of stress, their levels of dopamine rise even higher causing feelings of overwhelm, even more stress, worry, paranoia, and anxiety. These individuals often feel pain much more acutely versus the “adult” and can have symptoms of chronic pain. In contrast to the “adult,” the stress-free child form of COMT tends to have very good concentration, is quick to learn and has an excellent memory because of the excess dopamine in the frontal lobe.

The “professional” is the equivalent of Goldilocks of the COMT world as they tend to have balanced dopamine levels. We say tend because these individuals can have episodes where they act more like a “child” or an “adult” depending on what is going on their life. In general, the “professional” handles stress relatively well. They do break down dopamine slower, but not as slowly as a child. They can usually tolerate a fair amount of stress, but at a certain point, their COMT enzyme can’t keep up with all the extra dopamine, and they flip into having more of the “child” like COMT enzyme.

In conclusion, knowing your COMT status can be tremendously helpful for understanding how you respond to stress, what are some possible results of having a particular COMT enzyme. We at TBG, have been able to use our understanding of some of our family member’s COMT status to help us understand why they might feel overwhelmed in certain situations, how we were unwittingly causing increased stress and just how unique we are in our response to various environmental or personal stressors.

Side note: While this was about COMT as a lone gene, it actually has a number of sidekicks that also play a role in dopamine production and transport. These sidekicks include: MAO-A, MTHFR and DRD2.

References:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2671786/

https://www.ncbi.nlm.nih.gov/pubmed/21543598

https://www.ncbi.nlm.nih.gov/pubmed/25466290

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065662

https://www.ncbi.nlm.nih.gov/pubmed/27359131

https://www.ncbi.nlm.nih.gov/pubmed/27138112

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0065662