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What are COMT gene mutations?
A COMT gene mutation is a genetic mutation that affects the production of your COMT enzyme, the COMT enzyme activity affects cognitive function. COMT enzyme disruption can affect dopamine levels in those who have COMT gene mutations which can have serious health consequences especially for mental health, cognitive function and dopamine levels associated with the prefrontal cortex of the brain.
Prefrontal cortex
A COMT gene mutation is highly associated with chronic stress and or stress response affecting dopamine norepinephrine and epinephrine via the fight and or flight stress response that we all have. The COMT gene plays a powerful role in influencing our behaviour via manipulating your prefrontal cortex cognitive function causing stress reactivity or often unwanted stress responses such a anxiety, increased stress levels and cognitive deficits such as reduced ability to cope with life.
COMT Enzyme activity
COMT (catechol-O-methyltransferase) helps break down certain neurotransmitters and catecholamines, these include dopamine, epinephrine, and norepinephrine.
Catechol-O-methyltransferase (COMT) or COMT enzyme activity is important to the areas of the pre-frontal cortex, this area of the brain is involved with personality, inhibition of behaviours, short-term memory, planning, abstract thinking, and emotion/s.
COMT mutation is also involved with metabolizing estrogens. COMT catalyses the transfer of the methyl-group from SAM to catecholamine substrates, like L-DOPA, dopamine, epinephrine and norepinephrine.
COMT individuals can usually break down these neurotransmitters efficiently. But some COMT individuals may have trouble breaking these chemicals down from impaired function of the COMT enzyme because of the gene mutation.
With a positive COMT status (low comt enzyme), we have observed those people may have trouble with methyl donors.
This can lead to irritability, hyperactivity, or abnormal behaviour, these people may also be more sensitive to pain. COMT mutations slow the activity of the COMT enzyme which slows dopamine causing dopamine excess imbalances.
COMT genotype
COMT is also important in the detoxification of xenobiotics and the metabolism of catechol drugs. COMTV158 is associated with a 3-4 x reduction or increase in activity.
COMT V158M + H62H heterozygous is associated with low or high catecholamines.
COMT V158M + H62H homozygous is associated with high catecholamines and excess estrogen.
COMT Problems / Symptoms
- Anxiety
- Social anxiety
- Alcoholism
- Bipolar disorder (psychiatric disorders)
- Irritability
- Hyperactivity
- Abnormal behaviour (behavioral consequences)
- Psychosis
- Suicidal thoughts
- Negative self-thoughts
- Thyroid abnormalities
- Depression
- Fibromyalgia
- Panic attacks (Panic disorder)
- Poor libido
- Poor memory
- Hot flushes
- Toxicity (liver detoxification)
- Schizophrenia
- Fatigue (Stress hormones, adrenal fatigue syndrome)
- P.T.S.D (Post-traumatic stress disorder)
- Allergies (immune system)
- More sensitive to pain
- Infertility
- Autism
- Hormonal imbalances (estrogen imbalances, estrogen metabolites, catechol estrogens & harmful estrogen metabolites)
- Development disorders
- Cancer (Hormone-related)
- Neurological disorders
- Menopausal symptoms
- Andropausal symptoms (male menopause)
*Mental health symptoms in bold.
Reduced tolerance for methyl donors such as:
- 5-MTHF
- Methyl B12
- Caffeine
- SAMe (S-Adenosyl methionine)
- MSM (Methylsulfonylmethane)
- DMG (Dimethylglycine)
- TMG (Trimethylglycine) or Betaine
- CoQ10
- Melatonin
- Quercetin
- Carnitine
- Theanine
- Curcumin
- Green powders/smoothies
Dopamine disruption from COMT gene mutations
Because COMT can interfere with dopamine regulation this causes imbalances such as high dopamine or low dopamine. Dopamine levels are important
High dopamine
- Aggression
- Schizophrenia
- Impulsive
- Reckless
- Driven to create situations that stimulate them mentally and physically
- This may lead to violent, destructive or illegal behaviour if left unchecked
- Dr’s use antipsychotic medications to reduce a patient’s dopamine levels
Low dopamine
- Addictive tendencies
- Tremors / restless legs
- Low libido
- Lack motivation
- Depression
- Mental exhaustion
- Dull, boring dreams
- Risk of developing alcohol abuse or dependence
Problems with COMTV158
- Associated with violent behaviour
- Significantly associated with schizophrenia
- Increased susceptibility to psychosis
- Better performance tests of prefrontal cortex function and working memory
- This means increased tyrosine hydroxylase expression and increased dopamine levels
- COMT V158 – more susceptible to pain
- Affects cognitive function/cognitive deficits observed
COMT allele gene variants & COMT genotype
Alleles (An allele is a variant form of a gen or in this case a COMT gene variation).
rs4680(A) = Worrier. Met, more exploratory, lower COMT enzymatic activity, therefore higher dopamine levels, and lower pain. Threshold, enhanced vulnerability to stress, yet also more efficient at processing information under most conditions.
rs4680(G) = Warrior. Val, less exploratory, higher COMT enzymatic activity, therefore lower dopamine levels and higher pain threshold. But better stress resiliency, albeit with a modest reduction in executive cognition performance under most conditions.
(AA allele) = Low activity or higher dopamine which needs certain nutrients for support B6, SAM, magnesium, and FAD.
(G allele) = High activity or lower dopamine which need inhibitors such as quercetin, green tea, and Rhodiola.
Vitamin D & COMT
Vitamin D has previously been shown to influence midbrain dopaminergic neuron function. While increasing the rate-limiting synthetic enzyme for dopamine.
COMT Liver detox – Phase 2
- COMT gene /TXNRD2 A4251G
- COMT gene TXNRD2 T2439C
COMT Neurotransmitter Pathway: Serotonin & Dopamine
- COMT gene 61 P199P
- COMT gene A26166G
- COMT gene A309G
- COMT gene C27870T
- COMT gene C28914T
- COMT gene A7406G
- COMT gene C31430T
- COMT gene C30196T
- COMT gene G*522A
- COMT gene G28299A
- COMT gene T13376G
- COMT gene T13376G
- COMT gene H62H
- COMT gene T24075C
- COMT gene T26501G
- COMT gene V158M
COMT Activity
- COMT gene 61 P199P
- COMT gene A26166G
- COMT gene A1324G
- COMT gene C30196T
- COMT gene A309G
- COMT gene A7406G
- COMT gene C27870T
- COMT gene C28914T
- COMT gene T24075C
- COMT gene C31430T
- COMT gene G*522A
- COMT gene G28299A
- COMT gene H62H
- COMT gene T13376G
- COMT gene T26501G
- COMT gene V158M
About COMT gene mutation & lifestyle and environmental factors
COMT has many jobs, one major one being the control of dopamine levels, dopamine levels determine how you feel and therefore can control your mood, stress response, behaviour and can lead to mental health problems including many psychiatric disorders. The COMT enzyme activity is prefrontal cortex dominant and influences regulating dopamine signalling.
- Many people with COMT genetic variation have trouble with:
- Regulating dopamine signaling
- Stress reduction strategies/stress management/ controlling stress levels
- Managing MTHFR gene mutations
- Dopamine agonists
- High protein foods
- Experience early menopause symptoms
- Trouble detoxifying harmful substances
- Attention deficit hyperactivity disorder
- Strenuous exercise
- Antipsychotic treatment
- Cognitive functions
- Significant fight and or flight responses
- Balancing enzyme activity via dopaminergic agents
- Amino acid homeostasis
- Poor coping mechanisms or higher than normal coping mechanisms
How COMT functions & the COMT mutation
COMT controls dopamine release as a soluble catechol, COMT activity controls your body’s ability to activate dopamine transporters. A COMT mutation causes chemical messengers called neurotransmitters to dysregulate, this causes changes in COMT enzymes and nerve cells that go on to affect cognitive functions, for a COMT mutation to become problematic there is usually a set of factors such as toxicity, stress, viruses, environmental influences. A COMT mutation should never be ignored when there is symptoms because this can lead to more severe problems such as detoxification circuit dysfunction, bipolar disorder, debilitating anxiety and or depression.
Bipolar disorder is a good example, this is because when you have dopamine regulation imbalances you may have a slow COMT pathway combined with a fast COMT pathway, managing a situation like this means you can COMT inhibitors and or COMT promotors to essentially balance out the problem.
The prefrontal cortex requires signaling that the prefrontal cortex requires signaling by neurotransmitters such as dopamine and norepinephrine. Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain.
Single nucleotide polymorphisms or COMT gene mutation also significantly controls stress response and in many cases causes adrenal fatigue, this is because catechol o methyltransferase causes stress response reactions despite there being in many cases no reason for the reaction.
MTHFR genes & COMT gene mutation
Many people are now finding via genetic testing that they have MTHFR gene mutations and in many cases we find that these people blame their MTHFR genes for their COMT symptoms, the fact is that MTHFR works with methylation and thereby helps to provide the co-factors that support COMT genes to do their job. Using COMT inhibitors/dopaminergic agents is often not a good idea because COMT inhibitors can get in the way of or cover up a bigger problem that can be improved greatly when do the right way via proper natural treatment methods.
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