What is the COMT gene and impacts on mood, hormone levels, and overall health?

• What is COMT?
• What does the COMT gene do?
• How can the COMT gene differ in individuals?
• Why do we respond to stress differently?
• The COMT pathway
• COMT personalities and traits
• Are you a 'Worrier' or a 'Warrior'?
• Interesting traits of 'Worriers' and 'Warriors'
• The Worrier - Lower COMT, higher dopamine
• The Warrior - Higher COMT, lower dopamine
• Genetic testing - COMT gene testing in Australia
• How Functional Medicine can help you

COMT gene

Catechol-O-methyltransferase (COMT) is one of a number of enzymes that process neurotransmitters such as dopamine, epinephrine, and norepinephrine.  As we know, not everyone in Australia or anywhere in the world responds to stress in the same way. Life experience influences our perception of stress, but certain genes make us more or less sensitive to stress. 

At Advanced Functional Medicine, we look to COMT gene testing for answers as part of the puzzle – its role in our mood and personality is pivotal and can lead us to treat mental health conditions with successful outcomes.  

Tendencies toward drug addiction, adrenalin seeking activities, and depression are often apparent in those with a genetically fast COMT enzyme.  Those with a slow COMT pathway may experience increased anxiety, inability to handle stress well, unable to wind down or sleep properly, and problems with the clearance of Estrogens, causing PMS and other related menstrual symptoms.

What does the COMT gene do?

It is currently thought that 80% of the population has a genetic variant on their COMT gene. This alone is reason enough for this gene to be one of the most well researched.

The COMT gene controls how the brain reacts to stress. It is involved in the metabolism and detoxification of stress hormones, influencing the level of estrogen, dopamine, norepinephrine, and epinephrine in the body.

The COMT pathway is vital for our mental and emotional health. 

How can the COMT gene differ in individuals?

The COMT gene comes in two varieties:

One breaks down dopamine and other neurotransmitters quickly while the other removes it slowly. 

So, what does this look like in real-life terms?

When stress levels are low, the slow variety of COMT keeps dopamine levels high.

When under stress, the brain is flooded with dopamine and other neurotransmitters. The fast variety (warriors) can remove the excess dopamine quickly and their performance is enhanced, while the slow variety (worriers) tend to become overwhelmed by the flood of dopamine. This leads to a shutdown of the executive control centre in the prefrontal cortex. 1

Why do we respond to stress differently? 

One big reason why stress affects each of us differently has to do with how well our bodies can detoxify catecholamines, the chemicals of stress. Plus, the methylation cycle has a huge influence on how well we both create and detoxify catecholamines. 

When people experience stress, some rally to the cause and increase their performance, while others seem to melt and fall apart under the same type of pressure.

How can people undergoing the same type of stress have such different experiences?

The answer lies in understanding how the COMT system influences the brain. 

More about the COMT pathway

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase. Two versions of this enzyme are made from the gene. The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain. Other tissues, including the liver, kidneys, and blood, produce a shorter form of the enzyme called soluble catechol-O-methyltransferase (S-COMT). This form of the enzyme helps control the levels of certain hormones.

In the brain, catechol-O-methyltransferase helps break down certain chemical messengers called neurotransmitters. These chemicals conduct signals from one nerve cell to another. Catechol-O-methyltransferase is particularly important in an area at the front of the brain called the prefrontal cortex, which organizes and coordinates information from other parts of the brain. This region is involved with personality, planning, inhibition of behaviours, abstract thinking, emotion, and working (short-term) memory. To function efficiently, the prefrontal cortex requires signaling by neurotransmitters such as dopamine and norepinephrine. Catechol-O-methyltransferase helps maintain the appropriate levels of these neurotransmitters in this part of the brain. 2

COMT personalities and traits

If your COMT Slow is balanced, you’re focused and alert; a Type A driven person, with good skin, great mood and are great at learning things. You will be able to focus, very detail-oriented with a good memory, as long as the system isn’t overstressed. However, if your body becomes overstressed from gut inflammation, food allergies, physical exhaustion, too much exercise, vitamin and mineral deficiencies, chronic infections, and the like, you have a recipe for being a stress mess! (Rostenburg, 2018)

With low COMT activity, you’re better at focusing, but tend to ruminate on things rather than letting them go; with high COMT activity, you rarely get stuck in a rut, but you just as rarely sit down to focus on one single thing. 3

If your COMT Slow is too slow, you’re having issues with calming down when stressed, have anxiety with school tests or public speaking, do not handle stressful situations well, you cannot fall asleep, and may have higher amounts of estrogen contributing to high estrogen issues such as PMS or fibroids. 4

If you have more of the COMT enzyme and are more efficient breaking down stress chemicals, then you naturally have fewer catecholamines floating around your body on a daily basis – and that includes dopamine, the ‘pleasure chemical’. Likewise, if you have less of the COMT enzyme, you have more of those chemicals – and more dopamine can have a positive effect on your sense of wellbeing. Dopamine changes the firing rate of your brain’s neurons, speeding up the brain like a turbocharger for an automobile engine.

Dopamine is a key neurotransmitter related to our wellbeing. Higher levels of dopamine and other catecholamines can bring about greater satisfaction in life but too-high levels can make you less extroverted, more worrisome and anxious, contribute to OCD, and more neurotic. In fact, excessively high levels can lead to toxicity and psychosis. Lower levels of catecholamines mean you’re better equipped to handle stress but also at greater risk of depression, substance abuse, anger, and impulsivity.

In other words, these neurotransmitters can be a double-edged sword, and it can be difficult to weigh the benefits against the costs of having more or less of them in your system. 

Are you a ‘Worrier’ or a ‘Warrior’?

There are two variants of the COMT gene known as the ‘Worrier’ gene and the ‘Warrior’ gene. The ‘Worrier’ gene breaks down catecholamines slowly, while the ‘Warrior’ gene breaks down neurotransmitters more quickly. 

Interesting traits of ‘Worriers’ and ‘Warriors‘

The Worrier (Lower COMT, higher dopamine)

The Good

• Gets more pleasure out of life events
• More creative 
• Higher IQ 
• Better working memory
• Improved reading comprehension 
• Increased cognitive function when not under stress
• More exploratory 
• cognitive flexibility
• Increased verbal fluency for males (but decreased it for females)
• Better fine motor skills
• Better ability to aim
• Ability to focus more when they realize they have made an error
• Better absorption of tea polyphenols/EGCG
• Lower risk for alcoholism

The Bad

• Worse handling of stress or pain
• High anxiety, OCD, panic disorder, phobic anxiety
• Lower emotional resilience/more negative emotions/less able to handle negative events well
• More impulsive 
• More depression 
• Less cooperative, helpful and empathic 
• Less extroverted 
• More neurotic 
• Higher homocysteine 
• Higher risk of ADHD and ADHD severity 

The Warrior (Higher COMT, lower dopamine) 

The Good

• Better handling of stress and pain
• Better at learning languages
• More cooperative, helpful and empathic 
• Higher emotional resilience/able to handle negative events well
• Increased verbal fluency for females (also decreased for males)

The Bad

• Less pleasure out of life 
• Lower IQ 
• Worse executive function/processing information, but better under stress. 
• Worse fine motor skills 
• Less Exploratory 
• More childhood depressive symptoms 
• Increased risk for breast cancer
• Increased risk for endometrial cancer 5

Genetic testing – COMT gene testing in Australia

Dr. Ben Lynch talks about “dirty” genes that can cause lifelong, life-threatening, and chronic health problems, including cardiovascular disease, autoimmune disorders, anxiety, depression, digestive issues, obesity, cancer, and diabetes.

You can learn more about your own predispositions through genetic testing and start to take steps to mitigate the negatives. 

The below extract from a strategene genetic report shows a slow COMT profile.  This variant is associated with a 40% reduction in COMT activity and fits the worrier profile as dopamine levels may stay elevated as they cant clear as easily from the body.

A Warrior profile would look present like the image below.  This profile clears neurotransmitters quickly, more prone to depression,  substance abuse, adrenaline-seeking activities, etc.

A balanced profile has one variant in each of the below COMT genes, representing a more balanced stress profile.  

Remember, diet, lifestyle, and environment are key in managing your genes. These are greatly influenced by the interactions your genes have with your surroundings.  This includes what you eat, how much you exercise, are there nutrient imbalances, gut infections, viral load, etc.

At Advanced Functional Medicine, we often uncover a range of deficiencies in patients.  These often include low Vitamin D, low B12, low, B2 (Riboflavin), low B6 (pyridoxine), and low methylfolate. B vitamins are important cofactors needed to create our hormones and neurotransmitters. Deficiencies in B vitamins are associated with increased depression, anxiety, and fatigue. 

How Functional Medicine can help you take control of your COMT gene

Naturally, as humans, we blame ourselves when overwhelmed by stress. Identifying genetic mutations or disorders, such as through COMT gene testing, helps people understand how their life choices can impact their biochemistry in a way that either supports or undermines their health and happiness. 

Dopamine and the other catecholamines noradrenaline and adrenaline (also known as epinephrine and norepinephrine) determine how you ride the stress wave – but they also determine so much more than that as well including your personality traits, concentration and ability to learn, making genetic testing for the COMT gene critical in understanding how you can better serve your own mental health outcomes.

Understanding the nature of your COMT gene can assist in implementing a targeted and personalised plan that can provide key information and actions to assist your natural stress response throughout the rest of your life.  

Using natural remedies for depression and anxiety and other disorders may help you cope better with the stress in your life.  It is vital that you include healthy eating, good sleep, movement and avoid excessive environmental toxins.

A step by step guide is available on the Advanced Functional Medicine website to easily arrange your genome test.  This includes COMT gene testing as well as MTHFR, MTRR, CBS, SOD2, VDR, PEMT, and many more. 

We offer full appointments to discuss your genetic profile in depth and advise how your genetic profile may be influencing your health.

Have you had your genes tested? 

What COMT variation are you? 

Do you fit the warrior or worrier profile? 

Please leave a comment below or contact us for more information and advice on COMT gene testing and how we can help you.