The COMT V158M polymorphism genetic test analyzes a specific variation in the COMT gene, which encodes catechol-O-methyltransferase (COMT), an enzyme responsible for metabolizing catecholamines, including dopamine, epinephrine, and norepinephrine. This test detects a single-nucleotide polymorphism (SNP) in the COMT gene, where a guanine (G) is replaced by an adenine (A). This change results in the substitution of valine (Val) with methionine (Met) at position 158 in the COMT enzyme, thereby affecting its activity and the metabolism of dopamine. Since COMT plays a key role in regulating dopamine levels in the prefrontal cortex, variations in COMT influence cognitive function, stress response, emotional regulation, and susceptibility to neuropsychiatric disorders such as anxiety, schizophrenia, and attention-deficit/hyperactivity disorder (ADHD).
COMT catalyzes the methylation of catecholamines, a process essential for neurotransmitter inactivation and removal from synapses. The COMT V158M polymorphism creates two enzyme variants with different functions: the high-activity Val (158V) allele and the low-activity Met (158M) allele. Studies show that individuals carrying the Met allele have reduced COMT enzymatic activity, resulting in higher dopamine levels in the prefrontal cortex, which are linked to improved cognitive flexibility, better working memory, and heightened emotional sensitivity. However, excessive dopamine buildup can lead to increased stress reactivity, higher anxiety, and a greater risk of mood disorders. Conversely, the Val allele is associated with faster dopamine breakdown, leading to lower dopamine levels in the prefrontal cortex, which may impair cognitive performance but also provide greater resilience to stress and emotional shifts.
The presence of the Met allele has been associated with increased vulnerability to anxiety-related disorders because decreased COMT activity prolongs dopamine signaling in brain regions that regulate emotions. Studies show that individuals with the Met/Met genotype may be more prone to stress-induced anxiety, panic disorders, and heightened emotional reactivity. Conversely, the Val/Val genotype tends to produce a more consistent stress response but may be associated with reduced cognitive flexibility and an increased risk of executive function problems. This polymorphism's influence on dopamine balance also affects psychiatric conditions such as schizophrenia, bipolar disorder, and depression, where changes in COMT activity impact neural circuits, reward processing, and impulse control.
The COMT V158M polymorphism has also been studied concerning attention-deficit/hyperactivity disorder (ADHD), with evidence suggesting that dopamine regulation affects attentional control and impulse regulation. The Met allele is linked to increased distractibility and emotional instability, while the Val allele is associated with a higher risk of cognitive impulsivity and hyperactivity. Variations in COMT activity may influence individual responses to stimulant medications like methylphenidate, highlighting a potential pharmacogenetic role of this polymorphism in ADHD treatment.
Besides neuropsychiatric disorders, this polymorphism has been studied for its role in pain perception, cardiovascular health, and hormone metabolism. The Met allele has been linked to heightened pain sensitivity due to prolonged catecholamine signaling in pain pathways, while the Val allele is associated with a higher pain threshold. The impact of COMT on estrogen metabolism has also been explored, as COMT activity influences the breakdown of catechol estrogens, with possible implications for hormone-related conditions such as breast cancer and endometriosis.
Genetic testing for the COMT V158M polymorphism provides insights into an individual’s genetic predisposition to dopamine-related cognitive and emotional traits, psychiatric conditions, pain sensitivity, and stress reactivity. Detecting this variant enables the assessment of neurotransmitter metabolism, cognitive flexibility, and emotional regulation, thereby improving our understanding of how genetics influences mental health, cognitive abilities, and personalized treatment responses.
The genetic testing of the COMT gene, V158M polymorphism, is also included in the tests:
- Methylation Genetic Testing, MethylGenomiX® Basic Panel
- Methylation Genetic Testing, MethylGenomiX® Comprehensive Panel
Last updated: 29/06/2025
