COMT Gene

The COMT gene is responsible for producing an enzyme called catechol-O-methyltransferase. This enzyme helps in the breakdown of catecholamines, thereby inactivating them. Catecholamines, termed as fight or flight hormones, include dopamine, epinephrine, and norepinephrine. They are produced in response to stress. They are responsible for increasing heart rate, blood pressure, breathing rate, muscle strength, and alertness. They also play a role in increasing blood flow to major organs like the brain, heart, and kidneys.

COMT is one of the enzymes involved in the breakdown of dopamine in the brain. This occurs in the prefrontal cortex of the brain. This part of the brain is involved in cognitive function and decision making. 

The COMT Variants

COMT gene comes in two main variants - one that breaks down dopamine quickly and the other one that breaks it down slowly. 

What does this mean?

One variant produces high levels of the enzyme, which breaks down dopamine faster, leading to its lower levels in the brain.

The other variant produces lower levels of the enzyme, which results in slower breakdown of dopamine, resulting in its higher levels in the brain.

rs4680 SNP

The COMT gene variants are influenced by the allele present at rs4680. 

rs4680, also called Val158Met, is a well studied SNP in the COMT  gene.

The G allele here is associated with higher COMT enzymatic levels compared to the A allele. 

The presence of two A alleles at rs4680 results in lower enzyme activity. This leads to dopamine build-up in the brain. People with the AA type are more susceptible to stress, anxiety, and pain and are called “worriers.”

The presence of two G alleles at rs4680 leads to elevated enzymatic levels. This results in faster breakdown of dopamine. People with the GG type clear dopamine quickly at times of stress and can fight it out better. They are referred to as the “warrior.”

There’s also a third and much less discussed variant. Here, there’s one copy of the A allele and one copy of the G allele at rs4680. People with the AG type have higher dopamine levels than the AA type and lower levels than the GG type.

They are assigned a status that’s between a worrier and a warrior. The outcome of AG genotype can be as follows:

A higher likelihood of warrior personality (compared to AA type);

A higher likelihood of worrier personality (compared to GG type)

GenotypeImplication
AAHigher levels of dopamine
AGIntermediate levels of dopamine (lower than AA genotype and higher than GG genotype) 
GGLow levels of dopamine
COMT gene allele variations

Despite the negative connotation to the word “worriers,” these people are at certain advantages as well. They are known to be: 

- more creative 

- have higher IQ

- better motor skills

- better verbal memory and reading comprehension

- a more positive outlook towards life

Boosting Dopamine Levels Naturally

Dopamine promotes the feeling of pleasure and reward, which can help with better attention and memory. Some ways of boosting dopamine levels include:

- Increasing protein intake

- Consuming probiotics

- Exercising

- Enough sunlight exposure

- Getting adequate sleep

Counteracting Excess Dopamine

Higher dopamine levels have been associated with addiction and mental disorders like ADHD, obsessive-compulsive disorder, and schizophrenia. The “reward” feeling elicited by dopamine makes you want ‘more of something.’ When the levels of dopamine are higher than normal, this behavior can result in addiction. 

- Inhaling lemon essential oil speeds up the breakdown of dopamine and contributes to anti-anxiety and antidepressant effects.

- Tryptophan and 5-HTP are two amino acids that deplete excess dopamine. They are available as supplements. However, it is important to consult a qualified medical practitioner before getting started on any supplements.  

- Licorice root, a common ingredient in candies, is being studied for its antidotal properties for cocaine addiction, as it blocks dopamine production. However, the US FDA mentions that licorice containing food must be consumed in moderation. 

- Vitamin B6 is a cofactor required for dopamine synthesis. Dopamine toxicity has been managed in animals by vitamin B6 administration

Summary 

1. COMT gene encodes the enzyme catechol-O-methyltransferase that is involved in the metabolism of catecholamines like dopamine, epinephrine, and norepinephrine. 

2. COMT gene has two variants - one that breaks down dopamine quickly, and the other that breaks it down slowly.

3. rs4680, also known as Val158Met, is an SNP in the COMT gene. The G allele of this SNP is associated with higher enzymatic levels compared to the A allele. 

4. People with AA type have higher levels of dopamine. They don’t perform well under stress and are called worriers. People with the GG type have lower dopamine levels. They perform better in stressful situations and are called warriors.

5. The third type, AG, is associated with intermediate dopamine levels. People with the AG type are assigned a status that is between a worrier and a warrior.

6. Levels of dopamine can be increased naturally by getting adequate sleep, exercising, sunlight exposure, consuming probiotics, and more protein.

7. Inhaling lemon essential oil, consumption of licorice root, and other supplements can help deal with high dopamine levels. 

References

1. https://www.snpedia.com/index.php/Rs4680

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3991696/

3. https://pubmed.ncbi.nlm.nih.gov/24782743/

4. https://pubmed.ncbi.nlm.nih.gov/24853458/

5. https://pubmed.ncbi.nlm.nih.gov/24225542/

6. http://www.haskins.yale.edu/Reprints/HL1712.pdf

7. https://pubmed.ncbi.nlm.nih.gov/17687265/

8. https://pubmed.ncbi.nlm.nih.gov/16780969/

9. https://www.sciencedaily.com/releases/2009/02/090218223504.htm

10. https://pubmed.ncbi.nlm.nih.gov/2035239/

A research study on the data from Adolescent Brain Cognitive Development (ABCD) Study suggests a relationship between certain regions in the brain and weight gain among children and adolescents. The study explored the relationship between “reward region” and food processing and suggests that this region may predict obesity in children. 

Childhood obesity is a serious problem in the United States, putting children and adolescents at risk for poor health. Overweight children are much more likely to become overweight adults unless they adopt and maintain healthier patterns of eating and exercise.

Previous research has identified a region in the brain associated with overeating or unhealthy eating behavior.

The Reward System Region In The Brain

Almost all our actions are driven by two things: Necessity and Reward. An activity can be considered a reward when it motivates us or gives us pleasure. Neurons, the brain's fundamental working unit, communicates this "reward" using dopamine, which is popularly known as the "happy hormone." 

Incidentally, food-reward is common in animal training routines. An animal is rewarded with a treat when it performs certain actions and this programming of food-reward is routinely used by animal trainers in zoos and entertainment venues and other animal training facilities.

Hedonic Hunger

Hedonic hunger describes eating for pleasure than hunger - to enjoy the taste rather than to meet the body's energy needs. This pleasure eating triggers the brain's reward system region, which can lead to overeating - a common cause of obesity.

The Study

"The ABCD study or the Adolescent Brain Cognitive Development Study is the largest long-term study of brain development and child health in the United States." The study was done on over 10,000 children from ages 9-10 and was followed up through early adulthood. 

Using the data from this study, the researchers attempted to investigate the relationship between the reward system region in the brain (called the nucleus accumbens) and eating behavior by examining 5300 research participants.

It was observed that when 2000 participants returned for a one year follow up, the waist circumference had increased by an average of 2.76 centimeters per participant.

The cell density (number of cells for a given area) in the reward region of the brain was examined using a noninvasive MRI technique. 

The MRI revealed changes in the cell density that reflected the increase observed in the waist circumference. 

The study speculates that the increase in this cell density can be because of an inflammation caused due to a diet rich in high-fat foods. 

The findings essentially tell us that a vicious cycle of pleasure eating leading to changes in brain, in turn leading to overeating and increasing the risk of obesity.

Not all children who carry a few extra pounds can be classified as obese. Weight fluctuations are commonly observed in the growing stage of children. Before you decide on dietary changes for your child based on any weight gain you see, it's best to consult a doctor. The doctor may use growth charts, calculate the BMI and, take a family history, and, if necessary, may order a few tests to outline the issue behind the weight gain. 

References

  1. https://www.sciencedaily.com/releases/2012/05/120503103446.htm
  2. https://en.wikipedia.org/wiki/Dopamine
  3. https://abcdstudy.org/about/
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