273 | id == 273
273 | category_id == 7
273 | category_order == 5
273 | category_name == Mood
273 | category_color == #C47AC0
273 | slug == COMT-mood
273 | title == Can This Gene Influence Your Risk of Mood Disorders (COMT)?
273 | meta_description == The COMT gene breaks down neurotransmitters and is associated with mood disorders. Learn more here!
273 | summary == <p style="text-align:justify"><strong>The COMT gene encodes a protein that breaks down the neurotransmitters dopamine, epinephrine, and norepinephrine. Certain variants have been associated with mood disorders such as major depression and bipolar disorder. Read on to learn where your COMT gene stands!</strong></p>
273 | overall_score_text == Your Mood Disorder Risk Score (based on COMT Gene)
273 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/COMT--Mood-Disorders.jpg
273 | author_id == 12
273 | author_name == Carlos Tello
273 | author_title == PhD
273 | author_order == 55
273 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
273 | author_intro == <p><strong>Carlos received his PhD and MS from the Universidad de Sevilla.</strong></p>    <p>Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.</p>
273 | author_social_media_name == linkedin
273 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
273 | author_social_order == 1
273 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
273 | reviewer_id == 14
273 | reviewer_name == Shany Lahan
273 | reviewer_title == MS (Neuroscience)
273 | medical_reviewer_id == 11
273 | medical_reviewer_name == Puya Yazdi
273 | medical_reviewer_title == MD
273 | publish_date == 2020
273 | publish_date == 8
273 | publish_date == 14
273 | avg_rating == 5.0
273 | tags_id == 617
273 | tags_name == Bipolar Disorder
273 | tags_id == 65
273 | tags_name == COMT Gene
273 | tags_id == 51
273 | tags_name == Dopamine
273 | tags_id == 53
273 | tags_name == Epinephrine
273 | tags_id == 618
273 | tags_name == Major Depression
273 | tags_id == 12
273 | tags_name == Mood
273 | tags_id == 52
273 | tags_name == Norepinephrine
273 | permissions_favorite == False
273 | permissions_rate == False
273 | content_article == <p><em><span style="font-weight: 400;">The information in this post is presented for educational purposes only, and should not be used to replace standard medical care. If you or your loved ones have symptoms of mood disorders, you should immediately report to a physician.</span></em></p> <h2><strong>What Is the <em>COMT </em>Gene?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/comt/"><em><span style="font-weight: 400;">COMT</span></em></a> <span style="font-weight: 400;">gene codes for an enzyme called </span><em><span style="font-weight: 400;">catechol-o-methyltransferase</span></em><span style="font-weight: 400;"> (also called COMT). As its name implies, COMT transfers a methyl group to catechol-containing compounds. COMT uses </span><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">SAM-e</span></a><span style="font-weight: 400;"> as its methyl donor. Therefore, having either too little SAM-e, or too much S-adenosylhomocysteine (SAH) &mdash; which is formed when SAM-e loses its methyl group &mdash; results in inhibition of COMT [</span><a href="https://pubmed.ncbi.nlm.nih.gov/8576124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/12371153/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The main function of COMT is to help break down </span><em><span style="font-weight: 400;">catecholamines</span></em><span style="font-weight: 400;">, a family of neurotransmitters that includes </span><a href="https://selfhacked.com/blog/dopamine/"><span style="font-weight: 400;">dopamine</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">norepinephrine</span></a><span style="font-weight: 400;"> (also known as </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">noradrenaline</span></a><span style="font-weight: 400;">), and epinephrine (also known as adrenaline) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16878403/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">COMT is widely distributed in organs such as the brain, adrenal glands, liver, kidneys, lungs, intestines, and mammary glands [</span><a href="https://pubmed.ncbi.nlm.nih.gov/8027527/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/8055944/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The <em>COMT </em>gene encodes an enzyme of the nervous system that breaks down the neurotransmitters dopamine, norepinephrine, and adrenaline by transferring a methyl group to them, from SAM-e.</span></p> <h3><strong>Dopamine Transmission and Inactivation by COMT</strong></h3> <p><span style="font-weight: 400;">Dopamine is a neurotransmitter involved in multiple cognitive and behavioral processes such as executive function, </span><a href="http://selfhacked.com/blog/21-drugs-increase-motivation/"><span style="font-weight: 400;">motivation</span></a><span style="font-weight: 400;">, reward, and movement control. Outside the brain, it helps relax the blood vessels, increase urine output, reduce gastrointestinal motility and </span><a href="https://selfhacked.com/blog/insulin-101/"><span style="font-weight: 400;">insulin</span></a><span style="font-weight: 400;"> production, and regulate immune cell activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/15152198/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30446950/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Importantly, dopamine must be quickly inactivated to terminate the signal. Failing to do so is associated with many mental disorders such as schizophrenia and addictive behaviors. In most parts of the brain, this is achieved through dopamine transporters that promote its removal. </span><strong>In the prefrontal cortex, where dopamine transporters are much less abundant, dopamine breakdown by COMT accounts for over 60% of dopamine inactivation</strong><span style="font-weight: 400;"> [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6793120/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6672678/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Dopamine is a neurotransmitter involved in multiple cognitive, behavioral, and physiological processes. COMT inactivates dopamine to terminate its transmission.</span></p> <h3><strong>Dopamine in Mood Disorders</strong></h3> <p><span style="font-weight: 400;">Dopamine plays a key role in </span><a href="https://selfhacked.com/blog/natural-treatments-depression/"><strong>depression</strong></a> <span style="font-weight: 400;">through its control of cognitive functions, such as motivation, reward, attention, and decision-making. Drugs that activate dopamine receptors or prevent dopamine removal via transporters act as antidepressants, while those that block dopamine&rsquo;s action or decrease its availability reduce motivation and worsen mood [</span><a href="https://pubmed.ncbi.nlm.nih.gov/23792050/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong>Bipolar disorder</strong><span style="font-weight: 400;"> is another mood disorder that alternates depression with episodes of hyperactivity and euphoria (manic phases). Dopamine and </span><a href="https://selfhacked.com/blog/glutamate/"><span style="font-weight: 400;">glutamate</span></a><span style="font-weight: 400;"> transmission is overactivated during the manic phase. Over time, this reduces sensitivity to these neurotransmitters and ultimately results in depression [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3000635/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Altered dopamine transmission is associated with both major depression and bipolar disorder.</span></p> <h2><strong>Your COMT Results for Mood Disorders</strong></h2> <p>*9391514211443632*</p> <p>&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP: </strong><strong><em>COMT </em></strong><strong>rs4680</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased risk of depression in White people</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Increased risk of mood disorders in Asians.</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">41% of the world population has genotype &lsquo;GG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In people with European ancestry, both alleles are equally frequent</span></li> </ul> <p><strong>Other Important SNPs&nbsp;</strong></p> <p><strong><em>COMT </em></strong><strong>rs737865</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Normal risk of mood disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with depression and suicidal behavior&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">60% of the world population has genotype &lsquo;AA&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; variant is slightly more common in European descendents</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs165599&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Increased risk of bipolar disorder and better response to antidepressants</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Normal risk of mood disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; allele is slightly more frequent than &lsquo;A&rsquo; in the global population</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In European descendants, &lsquo;A&rsquo; is the most common allele</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs2020917&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal risk of mood disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Associated with female depression</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar to that of rs737865 for all ethnicities</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs165774&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal risk of mood disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Associated with reduced rates of female depression</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only 5% of the world population has genotype &lsquo;AA&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Allele &lsquo;A&rsquo; is slightly more common in people of European ancestry (10% of &lsquo;AA&rsquo;)</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs2239393&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Normal risk of mood disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with early-onset depression</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Only 14% of the world population has genotype &lsquo;GG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; variant is slightly more common in people with a European background</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs5993883&nbsp;</strong></p> <ul> <li style="list-style-type: none;"> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Normal risk of mood disorders</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Associated with increased severity of bipolar disorder</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Approximately 1 out of 2 people worldwide has genotype &lsquo;TG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In European descendants, &lsquo;G&rsquo; is the most common allele</span></li> </ul> </li> </ul> <p>&nbsp;</p> <p>*4091146377194217*</p> <p>&nbsp;</p> <h2><strong>Influence of <em>COMT </em>Variants on Mood Disorders</strong></h2> <h3><strong>Rs4680</strong></h3> <p><span style="font-weight: 400;">By far, </span><a href="../../../snp/rs4680/"><span style="font-weight: 400;">rs4680</span></a><span style="font-weight: 400;"> is the most widely-studied COMT gene variant. Its minor &lsquo;A&rsquo; allele encodes a less-stable protein that results in reduced COMT levels and activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/7703232/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10581325/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In White people, the major &lsquo;G&rsquo; allele has been associated with major depression. However, the effects of this polymorphism on mood disorders seem to largely depend on ethnicity. In Asian people, the &lsquo;A&rsquo; variant has been associated with both major depression and bipolar disorder [</span><a href="https://pubmed.ncbi.nlm.nih.gov/26803486/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19578924/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">A widely-investigated <em>COMT </em>underactive variant is associated with increased rates of mood disorders in White people. However, it has the opposite effect in Asian people.</span></p> <h3><strong>Other Variants</strong></h3> <p><span style="font-weight: 400;">The minor &lsquo;G&rsquo; variant of </span><a href="../../../snp/rs737865/"><span style="font-weight: 400;">rs737865</span></a><span style="font-weight: 400;"> has been associated with earlier onset of major depression and increased susceptibility to mood disorders (major depression, postpartum depression, and bipolar disorder) in women. In major depression patients not responding to medication, this variant was associated with suicidal behavior. Studies failed to link this polymorphism to changes in COMT expression, protein levels, and enzyme activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/21600957/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23351565/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30692067/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21940152/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30218069/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;A&rsquo; allele of </span><a href="../../../snp/rs165599/"><span style="font-weight: 400;">rs165599</span></a><span style="font-weight: 400;"> reduces </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression. The major variant at this polymorphism has been associated with increased rates of bipolar disorder and worse verbal memory, but better cognitive performance (executive function, memory, verbal fluency, and intelligence) during manic episodes. In people with major depression, this variant predicted better response to antidepressants [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180576/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21595525/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17547583/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22713126/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19095219/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;T&rsquo; allele of </span><a href="../../../snp/rs2020917/"><span style="font-weight: 400;">rs2020917</span></a><span style="font-weight: 400;"> increases </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression and, possibly, activity. This variant has been associated with increased rates of female depression (including postpartum) [<a href="https://pubmed.ncbi.nlm.nih.gov/23351565/">R</a>,&nbsp;<a href="https://pubmed.ncbi.nlm.nih.gov/30692067/">R</a></span><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;A&rsquo; allele of </span><a href="../../../snp/rs165774/"><span style="font-weight: 400;">rs165774</span></a><span style="font-weight: 400;"> increases </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">gene expression, but encodes a COMT protein with reduced activity. This variant has been associated with reduced depression rates in women [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748386/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27347613/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;G&rsquo; allele of </span><a href="../../../snp/rs2239393/"><span style="font-weight: 400;">rs2239393</span></a><span style="font-weight: 400;"> was associated with early development of depression in a Finnish study [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3191433/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;G&rsquo; allele of </span><a href="../../../snp/rs5993883/"><span style="font-weight: 400;">rs5993883</span></a><span style="font-weight: 400;"> is associated with cognitive symptoms during manic periods in people with bipolar disorder, and lower performance in verbal learning, memory, and cognitive control after treatment for this condition. The effect of this polymorphism on COMT activity hasn&rsquo;t been investigated, but it could alter gene expression [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3702534/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4818866/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Several <em>COMT </em>variants have been associated with increased incidence and severity of major depression and bipolar disorder.</span></p> <h2><strong>Recommendations to Reduce Mood Disorders</strong></h2> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*3577892694467390*</p> <p>&nbsp;</p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Cognitive-Behavioral Therapy</strong></h4> <p><span style="font-weight: 400;">One of the most common forms of therapy used by mental health professionals is cognitive-behavioral therapy (CBT). The main idea behind the use of CBT in depression is to help patients change their patterns of thinking and make behavioral changes to improve coping and reduce distress [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933381/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/9635215/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">CBT is widely used to improve both mood and anxiety disorders, with strong clinical evidence of its effectiveness. Neurobiological evidence suggests that CBT works by reducing the activity of brain regions involved in emotional processing (such as the amygdala and hippocampus) and cognitive processing (such as the prefrontal and anterior cingulate cortex) [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933381/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25932596/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20655801/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a clinical trial on over 150 people with IBS and symptoms of depression, those with the &lsquo;AA&rsquo; genotype benefited the least from CBT in terms of mood improvement and pain relief [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334775/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">CBT is widely used as a standard treatment for mood disorders. Your <em>COMT </em>variant may determine your rate of success.</span></p> <h4><strong>Exercise</strong></h4> <p><span style="font-weight: 400;">People who engage in regular </span><a href="https://selfhacked.com/blog/top-14-proven-health-benefits-exercise-references-mechanisms/"><span style="font-weight: 400;">physical activity</span></a><span style="font-weight: 400;"> experience fewer depressive and anxious symptoms. Both aerobic (e.g swimming) and anaerobic (e.g. weight training) exercise effectively lower depression and enhance mood [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16639173/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22786489/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/11148895/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a small trial on 14 women with depression, an aerobic exercise program (45-50 min/session 3x/week for 16 weeks) reduced COMT activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/26773917/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Regular physical exercise reduces depressive symptoms. Its effects on COMT activity may contribute to this benefit.</span></p> <h4><strong>Light Therapy</strong></h4> <p><span style="font-weight: 400;">&ldquo;Light therapy&rdquo; typically involves placing a &ldquo;light box&rdquo; (usually with a brightness of about 10,000 lux) nearby for 30 minutes each morning shortly after waking up. Light therapy has been reported to be especially effective for seasonal affective disorder (&ldquo;SAD&rdquo;), as the bright artificial light offsets the lack of </span><a href="https://selfhacked.com/blog/avoiding-sun-will-kill-14-proven-science-based-health-benefits-sun/"><span style="font-weight: 400;">sunlight</span></a><span style="font-weight: 400;"> that people often experience during the winter months [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16041296/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">For instance, bright light therapy reduced the symptoms of winter seasonal depression in a clinical trial on 99 people. This therapy may also help with non-seasonal depression, as seen in another trial on 122 people [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17151164/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26580307/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a clinical trial on 87 people with bipolar disorder in their depressive phase, light therapy (combined with </span><a href="https://selfhacked.com/blog/health-benefits-sleep/"><span style="font-weight: 400;">sleep</span></a><span style="font-weight: 400;"> deprivation) was less effective at improving mood in those with the &lsquo;GG&rsquo; genotype at rs4680 [</span><a href="https://pubmed.ncbi.nlm.nih.gov/19520435/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Light therapy is especially effective for seasonal affective disorder. The effectiveness of this therapy may depend on your <em>COMT </em>genotype.</span></p> <h3><strong>Diet</strong></h3> <h4><strong>Sufficient Folate Intake</strong></h4> <p><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">Folate</span></a><span style="font-weight: 400;"> (</span><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">vitamin B9</span></a><span style="font-weight: 400;">) is an antioxidant vitamin with key roles in cellular metabolism, blood cell production, immune response, brain development and function, and fertility [</span><a href="https://pubmed.ncbi.nlm.nih.gov/29889360/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/17209196/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/1887065/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10746355/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This vitamin restores SAM-e levels by producing its precursor </span><a href="http://selfhacked.com/blog/methionine-good-bad-surprising-truth-methionine-restriction/"><span style="font-weight: 400;">methionine</span></a><span style="font-weight: 400;"> from the amino acid </span><a href="https://selfhacked.com/blog/optimal-homocysteine-levels-increase-decrease/"><span style="font-weight: 400;">homocysteine</span></a><span style="font-weight: 400;">. </span><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">Folate</span></a><span style="font-weight: 400;"> is also involved in the synthesis of </span><a href="https://www.selfhacked.com/blog/how-to-increase-serotonin"><span style="font-weight: 400;">serotonin</span></a><span style="font-weight: 400;"> and dopamine. An imbalance in these neurotransmitters can lead to the development of depression and anxiety disorders [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17030196/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18950248/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">According to one meta-analysis, depressed patients have lower folate levels and lower dietary intake of this vitamin. In four trials of over 590 patients with depression, </span><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">folic acid</span></a><span style="font-weight: 400;"> had a stimulatory effect on serotonin receptors in the brain and improved responsiveness to antidepressants [</span><a href="https://pubmed.ncbi.nlm.nih.gov/28759846/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23212058/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036555/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10967371/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Increasing folate levels in 22 people with eating disorders led to significant improvements in depressive symptoms [</span><a href="https://pubmed.ncbi.nlm.nih.gov/23848107/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Food sources of this vitamin include green leafy vegetables, citrus fruits, and legumes [</span><a href="https://www.ncbi.nlm.nih.gov/books/NBK114318"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Folate is an antioxidant vitamin with key roles in cellular metabolism, immune response, brain function, and fertility. Abundant evidence associates deficiencies in this vitamin with depression.</span></p> <h4><strong>Extra Virgin Olive Oil</strong></h4> <p><a href="https://selfhacked.com/blog/olive-oil/"><span style="font-weight: 400;">Olive oil</span></a><span style="font-weight: 400;"> consumption is associated with reduced depression rates. In a study on over 1300 healthy volunteers, peole eating a Mediterranean diet with olive oil had lower depression scores [</span><a href="https://pubmed.ncbi.nlm.nih.gov/26402520/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6132244/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Extra virgin olive oil is rich in phenolic compounds. One of them, oleacein, is a catechol-containing compound with the potential to inhibit COMT [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30935952/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Olive oil consumption is associated with reduced depression rates. Its phenolic compound oleacein inhibited COMT in test tubes.</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>SAM-e</strong></h4> <p><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">SAM-e</span></a><span style="font-weight: 400;">, the primary &ldquo;methyl donor&rdquo; used to activate the COMT enzyme, is classified as a supplement in the US and a prescription drug in some European countries.</span></p> <p><span style="font-weight: 400;">SAM-e is one of the most studied complementary treatments for depression; extensive clinical reviews have documented its safety and efficacy. It acts faster than common antidepressants and yields similar results [</span><a href="https://pubmed.ncbi.nlm.nih.gov/12420702/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19909689/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26295824/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A large evidence-based database, Cochrane, reviewed eight clinical trials with over 900 depressed patients. They concluded that SAM-e works as well as antidepressant drugs and noted its excellent safety profile. However, neither of the treatment options was significantly better than placebo [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457972/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a recent study of 60 patients with mild-to-moderate depression, a combination of SAM-e and vitamin B complex improved symptoms while causing no side effects [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6247995/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">According to four studies with over 170 patients, SAM-e (800-1,600 mg daily) can even combat drug-resistant depression when added to standard treatment. It provided significant improvement in 35-60% of the patients [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20595412/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.sciencedirect.com/science/article/abs/pii/S2212958815000415"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3666233/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/15538131/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Importantly, the health authorities advise against combining SAM-e with antidepressants due to potential drug interactions [</span><a href="https://www.mayoclinic.org/drugs-supplements-same/art-20364924"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">SAM-e is the methyl donor required for COMT activity. As a supplement, it has been widely investigated as a complementary treatment for depression.</span></p> <h4><strong>St. John&rsquo;s Wort</strong></h4> <p><span style="font-weight: 400;">A systematic review of over 35 studies and almost 7000 patients found </span><a href="https://selfhacked.com/blog/saint-johns-wort/"><span style="font-weight: 400;">St. John&rsquo;s wort</span></a><span style="font-weight: 400;"> effective for the treatment of depression. The review also associated St. John&rsquo;s wort use with fewer adverse effects compared to conventional antidepressants (such as SSRIs) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/27589952/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Similarly, a review of 27 studies and over 3800 patients found St. John&rsquo;s wort to be as safe and effective as SSRIs for mild-to-moderate depression [</span><a href="https://pubmed.ncbi.nlm.nih.gov/28064110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Its extract and active compound hypericin inhibited COMT and another enzyme that also breaks down catecholamine neurotransmitters (MAO) in test tubes, possibly explaining the antidepressant effects of this herb [</span><a href="https://pubmed.ncbi.nlm.nih.gov/7857510/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">St. John&rsquo;s wort is a well-known herbal remedy for depression. Its ability to inhibit COMT may account for this effect.</span></p> <h4><strong>Passionflower</strong></h4> <p><a href="https://selfhacked.com/blog/passion-flower-benefits/"><span style="font-weight: 400;">Passionflower</span></a><span style="font-weight: 400;"> contains indole alkaloids, which can boost the levels of essential neurotransmitters in the brain, such as dopamine, serotonin, and noradrenaline. This feature makes them promising candidates for the development of new antidepressants [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328930/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22432466/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The species of passionflower that produces &ldquo;passion fruit&rdquo; (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">. </span><em><span style="font-weight: 400;">edulis</span></em><span style="font-weight: 400;">), relieved the symptoms of depression in mice by raising the levels of serotonin and dopamine [</span><a href="https://pubmed.ncbi.nlm.nih.gov/28893593/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23702036/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study in mice, the extract of another passionflower species (</span><em><span style="font-weight: 400;">P</span></em><span style="font-weight: 400;">. </span><em><span style="font-weight: 400;">incarnata</span></em><span style="font-weight: 400;">) also increased dopamine levels and inhibited COMT [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5542920/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Preliminary research in animals suggests that passionflower may help with depression, possibly by inhibiting COMT.</span></p>
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273 | content_learn_more_9391514211443632_text == Based on the variants we looked at, your COMT gene is associated with somewhat increased risk of mood disorders. Cognitive-behavioral therapy, physical exercise, light therapy, and dietary folate and olive oil can help. Keep scrolling to find out more.
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rsIDs = rs165774,rs165599,rs737865,rs2239393,rs2020917,rs5993883,rs4680
rsStatus = rs165774,COMT,chr22,19965038,G,A,,,34,17,HET
rsStatus = rs165599,ARVCF,chr22,19969258,G,A,C,,23,11,HET
rsStatus = rs737865,COMT,chr22,19942598,A,G,T,,17,12,HET
rsStatus = rs2239393,COMT,chr22,19962905,A,G,,,21,13,HET
rsStatus = rs2020917,COMT,chr22,19941361,C,T,,,24,16,HET
rsStatus = rs5993883,COMT,chr22,19950115,T,G,,,12,9,HET
rsStatus = rs4680,COMT,chr22,19963748,G,A,,,19,11,HET
