Are you a worrier or a warrior? There’s a definite genetic component to how you respond to stress – in this article I’m looking at the COMT gene polymorphism. Each variant has both positive and negative aspects, so if you know your genetics and understand what they mean, you’ll be better able to deal with stress in a way that suits. If you’ve had your DNA analysed, this is an opportunity for you to review your results and how you’re working with them, and if you haven’t had the test done, you could either talk to me about getting it done or have a guess as to which variant you are.
Let’s first of all take a look at the neurotransmitters dopamine and noradrenaline, their effects on your body, and foods and nutrients that support or affect their production.
Dopamine is a neurotransmitter involved in motivation and reward – pleasure, learning and a natural desire to satisfy bodily needs. The pleasure of good food, sex and playing games increases dopamine release. The greatest source of dopamine is in an area of the brain called the basal ganglia, located at the base of the forebrain. It is proposed that the basal ganglia are involved in ‘action selection’ – choosing the best action from a choice of possible behaviours. When an action is followed by an increase in dopamine activity (reward signal), that particular circuit is strengthened.
Dopamine in the right amounts causes improved alertness, memory, attention and endurance, and an increase in pleasure produced by rewarding events e.g. enjoying food. High levels of dopamine can cause agitation, anxiety, increased heart rate, body temperature and sweating, even loss of contact with reality (delusion, psychosis). Low levels of dopamine can cause poor concentration, forgetfulness, and behaviours caused by poor inhibitory control. ADHD (attention deficient hyperactivity disorder) is associated with low dopamine levels, and Parkinson’s disease is caused by a loss of dopamine secreting cells in a certain part of the brain.
Caffeine has stimulating effects on dopamine release, as does nicotine and other psychoactive drugs – cocaine, methamphetamine, and MDMA (ecstacy), which causes them to be addictive. Video gaming and gambling addictions are also associated with a dopamine imbalance. Anorexia, aggression, and alcoholism are also associated with low dopamine levels.
Noradrenaline (NA) is produced in the locus coeruleus in the pons (part of the brain stem), and as a neurotransmitter by the sympathetic nerves and adrenal glands. The general function of NA is to mobilise the brain and body for action, reaching peak levels during situations of stress, danger, or when presented with unpleasant stimuli such as pain, difficulty breathing, excess heat or cold.
In the fight-or flight response, caused by perceived threat of danger, the locus coeruleus activates the brain for action, while the sympathetic nervous system activates the body. Effects of NA include:
- Increased heart rate and elevated blood pressure
- Release of glucose from energy stores
- Increased blood flow to large muscles
- Reduced blood flow to gastrointestinal system
- Inhibition of ladder emptying
- Inhibition of gastrointestinal motility
In the brain, NA increases arousal, alertness, readiness for action, promotes vigilance, enhances formation and retrieval of memories, and focusses attention. NA enhances the ability of the brain to respond to incoming signals by changing the activity pattern in the pre-frontal cortex and other areas.
Adrenaline is structurally similar to NA, with an additional methyl group attached. Adrenaline is secreted by the adrenal medulla when triggered by the sympathetic nervous system due to stress or danger, and it has effects on almost every organ and system of the body.
Stress and Sympathetic Hyperactivation
Stress is any situation that is perceived as a threat, which activates the HPA axis and the NA system to stimulate the body and brain into action to deal with the danger. When this system is constantly being triggered, sympathetic hyperactivation can occur in which the following symptoms may become apparent:
- Aches and pains
- Rapid heartbeat and/or heart palpitations
- Elevated blood pressure
- Excess sweating
Chronic stress over time is detrimental to overall health and wellbeing due to resources being pulled away from the parasympathetic functions of detoxification, repair and general maintenance of the body. Symptoms of chronic stress include insomnia, loss of libido, gastrointestinal problems, impaired disease resistance and poor immunity, reduced rates of healing, depression, and increased vulnerability to addiction.
Catecholamines dopamine, noradrenaline and adrenaline are converted from the amino acids tyrosine and phenylalanine in the following pathway:
Phenylalanine -> Tyrosine -> L-DOPA -> Dopamine -> NA -> Adrenaline
- Phenylalanine is an essential amino acid, and tyrosine is considered non-essential in that we can synthesize it from phenylalanine. These amino acids are found in protein foods such as meat, eggs, dairy products, nuts and legumes. Ensuring you have sufficient protein in your diet is essential for brain and nervous system health, and stress regulation.
- Tyrosine is converted to L-DOPA by the enzyme tyrosine hydroxylase and requires iron as a cofactor, therefore good iron levels are also important for effective brain and nervous system function.
- Conversion of dopamine to NA requires vitamin C (ascorbic acid) as a co-factor. It has long been known that stress depletes vitamin C, so pay particular attention to vitamin C in your diet if you have a tendency to become stressed.
- NA is converted to adrenaline by the enzyme phenylethanolamine N-methyl transferase (PNMT) with S-adenosyl-L-methionine (SAME) from the methylation cycle as a co-factor. Therefore ensure adequate B2, B6, B12, and folate for effective methylation, and depending on your MTHFR genetics, you may require specific nutrients or additional choline as well.
- Dopamine, NA and adrenaline and broken down by the enzymes MAO (monoamine oxidase) and COMT (catecholamine o-methyl transferase)
Coming back to the COMT enzyme polymorphism…
There are three variants of the COMT enzyme that breaks down catecholamines dopamine, noradrenaline, and adrenaline. The GG variant is the ‘wild type’ that functions at 100 % activity. Individuals with this variant are more of a ‘warrior’ temperament in that they’re able to break down stress hormones rapidly so their effects are short lived. This enables them to have a greater ability to handle stressful situations and would do well in emergency services. However, if they have low dopamine, they can become somewhat aggressive in their approach to dealing with stress.
The second variant AG is more of a balanced genotype with 35 – 40 % reduced activity. Individuals with this genotype will still have a slower breakdown of catecholamines and the tendency will be an increased vulnerability to the effects of stress. This is due to increased levels of dopamine and NA, which on one hand is beneficial because they increase alertness and the ability to focus and concentrate, but if the levels become too high can lead to anxiety.
The AA genotype has only 25% of the activity of the GG genotype, resulting in a significantly increased vulnerability to stress and anxiety due to elevated levels of catecholamines. For these individuals, being in a calm environment will enable them to stay focussed without becoming overly stressed.
Individuals with the AG or AA genotypes are more susceptible to the effects of substances that affect dopamine levels and can easily become addicted. For this reason, consciously moderating your caffeine, alcohol, and sugar intake – especially when stressed – is particularly important, and avoid smoking, psychoactive drugs, video gaming or gambling (or seek help if you have a problem). Because these individuals have a tendency to high dopamine and NA, if they consume substances that increase it further, they can become addicted to the high dopamine state, which eventually leads to a depletion resulting in a rebound depression – low energy, lack of motivation, and even aggression.
Warriors, the GG genotype, sometimes need a bit of stress to increase their adrenaline and dopamine levels to stimulate them into action, and a cup of coffee or two may help!
Other Genetics Factors
Tyrosine hydroxylase (TH) is the enzyme that converts the amino acid tyrosine into L-DOPA, the precursor to dopamine. The genetic polymorphism for this gene creates an enzyme that converts tyrosine into dopamine at a greater rate when triggered by stress, resulting in higher levels of dopamine and noradrenaline than the ‘wild type’. If the individual has a fast TH enzyme combined with the warrior COMT genotype, it’s not a big problem, however if the fast TH converter is a worrier COMT genotype, then the increased effects of dopamine and NA levels are even greater, the combination of which makes the individual much more vulnerable to stress and anxiety.
In conclusion, understanding your genetic predispositions and risk factors can help you to make better choices for your health and lifestyle. Before I had my DNA tested I knew that I could get stressed quite easily, and now I understand why. Up until recently I didn’t think that coffee was a problem for me, but even though I have the ability to metabolise caffeine effectively, the effects of caffeine on my dopamine and NA levels because of my COMT and TH genetics are probably not beneficial. I also have to make sure that I do practice my meditation, take herbs that are nervous system tonics, and exercise daily to keep my stress and anxiety levels low.