The Genetics of Perfectionism

By Jessica Pizano, Fit to You LLC

Drive. It is so necessary. Without it we do not have the motivation to accomplish our goals and aspirations. Yet, for many, it can get way out of control. Often referred to as a Type “A” personality, this type of person is often quite successful. They are executives, doctors, lawyers, researchers, and other highly driven, successful individuals. And yet, this drive may also take a toll on their health. It may become a compulsion. It can lead to anxiety, repetitive thoughts, and sleep problems.
For many years there have been questions as to why we are the way that we are. Is it the way we are brought up by our parents, or is it more closely related to our nature? While the jury may still be out how much either may contribute, our genetics do hold some level of responsibility. The enzyme catechol-o-methyltransferase (COMT) is highly polymorphic. This means that many individuals have mutations in the gene, reflecting a change from the normal, wild type.
Why would this happen, you might ask? My guess is that it is likely a reflection of our society’s values. In this country, we push hard. Hard work and achievement are highly valued. The ability to take a step back, relax and enjoy time off is not often considered a priority. Consequently, when looking for a partner, we will often look for someone that will be a hard worker. This process is how we successfully change (evolve) our genetics over time. Someone without a COMT mutation may choose a spouse that has these characteristics. This gives their children a greater chance of possessing this characteristic and the gene. This would result in a child that either does not have the mutation or is perhaps heterozygous (one positive allele from dad and one negative allele from mom). Or perhaps one driven individual is attracted to another individual. In this case, if both were heterozygous, a child could be born with a wild type, heterozygous or even homozygous status (both alleles contain the mutation).

The Function of COMT
The primary purpose of the enzyme COMT is to breakdown neurotransmitters (the brain’s chemical messengers) including dopamine, norepinephrine and epinephrine. Dopamine plays a major role in reward-motivated behavior. Low levels are associated with addiction. In addiction individuals are looking for a way to increase their dopamine levels using their drug of choice. Destruction of the part of the brain (substantia nigra) that creates dopamine results in Parkinson’s disease and will result in a complete absence of this neurotransmitter. Dopamine may also be converted to another neurotransmitter called norepinephrine. Norepinephrine is responsible for allowing us to concentrate and to be vigilant. It plays a role in our sympathetic nervous system. This system is our “fight or flight” system. It can elevate heart rate, increase blood pressure, and increase the amount of glucose in the blood. The body can then convert norepinephrine into epinephrine. Epinephrine also functions within the sympathetic nervous system. It is responsible for increased energy and excitement that is associated with the “fight or flight” state.
Having active mutations in COMT will cause increased levels of these neurotransmitters as they require COMT for proper breakdown. This means it is common for individuals to have too much of these neurotransmitters in their system. This can lead to changes in behavior and increased levels of the stress hormone cortisol. While we certainly require each of these neurotransmitters for proper function, elevated levels may also be problematic. On the one side, the COMT mutation is associated with very good “executive function” and those with this gene are often well organized. However, this mutation is also highly correlated to obsessive compulsive disorder, though most people with will only have slight tendencies rather than the full blown disorder. COMT mutations can increase both anxiety and anger from the increased norepinephrine. Repetitive thoughts or actions can cause sleep issues and make it difficult to relax in general.

COMT Is Just One Enzyme
When looking at genetics, it is very important to realize that looking at any one gene in isolation is not very helpful. The vast majority of genes that we look at are enzymes. Enzymes work to speed up reactions within a pathway. Pathways consist of lots of different reactions that work together using various enzymes. We can influence these items through diet and supplementation (called nutrigenomics) because they require help from cofactors to make them work appropriately. Cofactors are usually vitamins and minerals, though they can also be other compounds made in the body. In the case of COMT, the cofactors are magnesium and S-adenosylmethionine (SAMe).
While initially, it might make sense to simply dose up the cofactors, it is not that simple. You have to look at the rest of the pathway to see if there are other mutations that could be negatively (or positively) impacted by this. Many practitioners talk about genetics in relation to the methylation cycle and the amino acid homocysteine. When homocysteine levels rise they increase one’s risk for heart disease, blood clots, miscarriage, and other health problems. To decrease homocysteine you need the vitamins folate, vitamin B6, and vitamin B12.
Folate and vitamin B12 come in several forms and may be either methylated or unmethylated. Methylation simply refers to the addition of a single carbon group bonded to three hydrogens (CH3). Methylation is important for proper gene regulation, neurotransmitter production and metabolism, detoxification, breakdown of certain hormones, building immune cells (T cells and NK cells), DNA and histone synthesis, energy production, creation of the myelin sheath on nerve cells, and building and maintaining cell membranes. How many methyl donors (compounds containing methyl groups) one tolerates has a lot to do with genetics. Those with COMT mutations generally will tolerate fewer methyl groups. This is because with increased methylation comes increased production of neurotransmitters including dopamine, norepinephrine and epinephrine which must then be broken down by COMT. This leads to elevated levels of these three neurotransmitters which overwhelm a mutated COMT enzyme. Overmethylation symptoms include: irritability, anxiety, headache, nausea, insomnia, sore muscles, achy joints, acne, rash, palpitations, and migraines. Methyl groups may be found in supplements including methylcobalamin (methyl B12), L-methylfolate, trimethylglycine (TMG), dimethylglycine (DMG), and SAM.
It is possible to work with someone who practices nutrigenomics to help improve methylation even if you do have COMT mutations. This often can help decrease anxiety, anger and OCD symptoms associated with this mutation. Appropriate and careful dosing of specific vitamins and minerals can be used in conjunction with genetic testing through and other lab tests to confirm whether the mutation is active or not. It is so important to remember that while you may have a particular mutation, that it requires an environmental influence (called epigenetics) to activate it. Activation may be temporary or permanent depending on how strong the epigenetic influence was.

The Estrogen Connection
For females with the COMT mutation, estrogen metabolism is another associated problem. While many associate COMT almost exclusively with the breakdown of neurotransmitters, it also works in the estrogen pathway to break down estrogen in combination with the enzyme Phosphatidylethanolamine N-Methyltransferase (PEMT). Mutations in one or both of these genes may cause estrogen dominance.
Estrogen dominance describes a state where there is increased estrogen usually because the body is unable to efficiently break it down. This can be caused by genetic mutations in COMT and PEMT, poor detoxification, or even chronic constipation. Often this develops as a woman enters her 30s or 40s and can cause symptoms including decreased sex drive, irregular or abnormal menstrual periods, water retention, breast swelling and tenderness, fibrocystic breasts, headaches (often premenstrual), mood swings, weight gain, cold hands and feet, hair loss, thyroid dysfunction, sluggish metabolism, brain fog, memory problems, fatigue, sleep issues, and PMS. Estrogen dominance may also lead to allergies, autoimmune disorders, breast cancer, uterine cancer, infertility, ovarian cysts, and increased blood clotting, and may even accelerate the aging process.
For those with COMT mutations, there will often be a worsening of anxiety, anger and OCD symptoms in the two weeks prior to menstruation (post ovulation). This is because in addition to the work the enzyme needs to do in breaking down neurotransmitters, it becomes extra taxed trying to eliminate estrogen. For those that also have PEMT mutations in combination with COMT, the mood-based symptoms may be even greater.

Despite the presence of genetic polymorphisms, it is possible to help correct these mood and estrogen metabolism problems using nutrigenomics and functional medicine. Certainly, supplementation with magnesium glycinate or malate may be helpful for those with COMT mutations, as will examining the function of the whole methylation pathway. This will allow appropriate supplementation with other needed cofactors in the pathway. Improving one’s diet to include less antibiotics and hormones by choosing organic grass fed meats and free range poultry; increased fiber through inclusion of vegetables, fruits, legumes and whole grains; increased antioxidant intake by consuming seven to 11 servings of fruits and vegetables per day; lean proteins found in fish, beans, nuts, seeds, eggs and poultry; and healthy fat consumption by including fish and fish oils, nuts, seeds, coconut products, and olive oil is also essential for improved mood and health.

Jessica Pizano
Jessica Pizano is the owner of Fit to You, LLC, which offers personalized training programs and nutrition/health counseling. Her concentrations include genetics and nutrigenomics, general health and fitness, weight loss, food allergies/sensitivities, autoimmune disease, post-rehabilitative work, training/nutrition for medical conditions, obesity intervention, pre- and post-natal exercise and nutrition, and Pilates. A certified personal trainer and a corrective exercise specialist through the National Academy of Sports Medicine, she is also certified in mat Pilates through PHI Pilates and earned her Clinical Exercise Specialist and Longevity Wellness Specialist through the American Council on Exercise. She completed her training to practice Health Coaching at the Institute for Integrative Nutrition and is certified as a holistic health practitioner through the American Association of Drugless Practitioners. She earned a master’s degree in human nutrition that emphasizes functional medicine at the University of Bridgeport. Currently, Jessica practices personal training, nutrition counseling, and nutrigenomics in her studio in Avon. She may be contacted at (860) 321-7234 or online at