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What is the COMT Gene and Enzyme?
The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase. This enzyme is involved in the breakdown of certain neurotransmitters, such as dopamine, epinephrine, and norepinephrine. The COMT enzyme plays a crucial role in regulating dopamine signaling in the prefrontal cortex, where dopamine transporters are relatively sparse. Dopamine levels in the prefrontal cortex are critical for memory, attention, judgment, and other executive functions. When the COMT enzyme functions properly, it helps maintain a balance of these neurotransmitters, supporting optimal cognitive function and emotional regulation.
What are COMT gene mutations?
A COMT gene mutation, specifically COMT gene polymorphisms, 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 gene variants influence the enzyme’s ability to metabolize neurotransmitters, affecting the efficacy of medications and nutritional supplements, as well as their involvement in estrogen metabolism and implications for individual health outcomes. 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 genetic variants, such as COMT V158M + H62H heterozygous, are associated with different levels of catecholamines, leading to either 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)
Genetic polymorphisms, including those in the COMT gene, can lead to a variety of symptoms and conditions.
*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 certain COMT genetic variants can interfere with dopamine regulation, this causes imbalances such as high dopamine or low dopamine. Dopamine levels are important
High dopamine
Aggression
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.
Studies on postmortem human brain tissues have provided insights into how COMT allele gene variants affect cognitive functions.
(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.
Looking for genetic testing, COMT gene testing and or COMT gene mutation treatments, contact us here.
Clinical Significance of COMT Gene Mutations
Clinical studies have shown that the COMT Val/Val genotype may have significant behavioral consequences regarding cognitive function, memory, attention, motivation, and judgment. In individuals with the Val/Val genotype, dopaminergic agents have been shown to improve executive function and working memory to a greater degree in both animal and human studies. However, these agents may produce a deleterious effect on cognition in individuals with the Met/Met genotype. The COMT gene mutations can affect cognitive function and dopamine levels in the brain, leading to various health consequences, especially for mental health and cognitive function. Understanding your COMT genotype can help tailor treatments to improve cognitive and emotional outcomes.
COMT Pharmacogenomics
Genomind’s pharmacogenetic testing focuses on COMT as it relates to dopamine in the prefrontal cortex (PFC) because there is a relative lack of dopamine transporter proteins in the PFC. The activity of these transporters can be up or down-regulated to balance the activity of enzymes. The relative lack of dopamine transporters in the PFC means that dopamine levels in the PFC are largely determined by the activity of the COMT enzyme. The COMT gene plays a powerful role in influencing behavior and cognitive function, and genetic testing can help identify individuals who may benefit from personalized treatment strategies. By understanding your COMT genotype, healthcare providers can develop more effective, individualized treatment plans.
Testing for COMT Gene Mutations
Genetic testing for COMT gene mutations can help identify individuals who may be at risk for certain health conditions, such as anxiety, depression, and cognitive deficits. The test can also help determine the best course of treatment for individuals with COMT gene mutations. Genomind offers free educational content and resources on pharmacogenetics and the COMT gene to help healthcare professionals learn more about the clinical utility of pharmacogenetic testing and how it can be used to improve patient outcomes. By identifying your COMT genotype, you can take proactive steps to manage your health and well-being more effectively.
Supplements and Cofactors
Magnesium is a cofactor that is needed for the COMT enzyme to work properly. One study found positive effects for liver COMT levels along with better heart health from supplementing with magnesium. A high-quality magnesium supplement may be worth considering if you aren’t getting enough magnesium from food sources. Vitamin D has previously been shown to influence midbrain dopaminergic neuron function and can increase the rate-limiting synthetic enzyme for dopamine. Other supplements and cofactors, such as folate, vitamin B6, and SAM, may also be beneficial for individuals with COMT gene mutations. However, it’s essential to consult with a healthcare professional before starting any new supplements or medications. Proper supplementation can support the COMT enzyme and help maintain balanced dopamine levels, contributing to better cognitive and emotional health.
