As businesses start to open and we find our new normal, for some, the lasting effects from isolation may take more time to heal. Feelings of anxiety, depression, and worry are more common for some. Genetic susceptibility combined with major life stressors can impact our mental health. In this article, I review how genetic testing can help you to understand your risk and strategies to intervene and manage your mood holistically.
Neurotransmitter pathways influence brain chemistry, affecting mood, personality, and mental health. While these pathways are complex, genetic variations in enzymes that influence the availability of neurotransmitters, such as dopamine, serotonin and adrenaline are linked to susceptibilities to anxiety and depression. Polymorphisms in the COMT gene impact dopamine metabolism and account for about 60% of the metabolic degradation of dopamine and neurotransmission.
The COMT gene, and specifically the rs4680 SNP, has two versions, noted as Val (G allele) and Met (A allele). Studies show varying effects of these SNPs on the tendency towards anxiety, depression, and response to treatment.
- Women with the less active Met/Met genotype are associated with increased tendency for “anticipatory worry” and “fear of uncertainty” according to the Temperament and Character Inventory (TCI)
- Those with the Met allele tend to score higher on depression scales (Beck Depression Inventory and Hamilton Depression Rating Scale) and have a higher BMI compared to those with the Val/Val genotype.
- The Met allele is associated with an increased activity in limbic areas and the prefrontal cortex in response to stress, which is seen in individuals who report higher levels of anxiety; however, these individuals are more likely to have a better response to antidepressant treatment.
- Individuals with panic disorder and the Met/Met genotype may benefit less from exposure-based CBT treatment methods as compared to patients carrying at least one Val-allele.
Genetics influences our response to stressful life event, however “our genes are not our destiny”. The brain is ‘neuroplastic’, meaning that we can change the actual structure of the brain and therefore behavioural response with certain strategies. By knowing a little about your brain chemistry through genetic testing you can determine your tendencies and the best treatment approach.
- Antypa N, Drago A, Serretti A. The role of COMT gene variants in depression: Bridging neuropsychological, behavioral and clinical phenotypes. Neuroscience & Biobehavioral Reviews. 2013 Sep 1;37(8):1597–610. 1.
- Bieliński M, Jaracz M, Lesiewska N, Tomaszewska M, Sikora M, Junik R, et al. Association between COMT Val158Met and DAT1 polymorphisms and depressive symptoms in the obese population. Neuropsychiatr Dis Treat. 2017;13:2221–9.
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- Haxhibeqiri V, Haxhibeqiri S, Topciu-Shufta V, Agani F, Goci Uka A, Hoxha B, et al. The Association of Catechol-O-Methyl-Transferase and Interleukin 6 Gene Polymorphisms with Posttraumatic Stress Disorder. Psychiatr Danub. 2019 Jun;31(2):241–8.
- Lonsdorf TB, Rück C, Bergström J, Andersson G, Öhman A, Lindefors N, et al. The COMTval158met polymorphism is associated with symptom relief during exposure-based cognitive-behavioral treatment in panic disorder. BMC Psychiatry. 2010 Nov 26;10:99.
- Stein DJ, Newman TK, Savitz J, Ramesar R. Warriors Versus Worriers: The Role of COMT Gene Variants. CNS spectr. 2006 Oct;11(10):745–8.
Dr. Robyn Murphy, ND
Scientific Advisory Board Member