Dopaminergic Genetic Variation and Trait Impulsivity: The Role of COMT rs4680 in Mixed Behavioral and Substance Addictions

<b>Background</b>: Impulsivity is a multidimensional trait associated with the development and maintenance of behavioral and substance addictions. Genetic polymorphisms, particularly within the dopaminergic system, are thought to modulate individual differences in impulsivity. The <i>COMT</i> rs4680 (Val158Met) polymorphism influences enzymatic activity of catechol-O-methyltransferase and may alter dopaminergic tone in the prefrontal cortex. This study investigated whether <i>COMT</i> rs4680 genotype interacts with addiction status (behavioral and substance addictions) to influence trait impulsivity. <b>Methods</b>: The study included 309 Polish men: 128 with mixed behavioral and substance addictions and 181 healthy controls. All participants completed the Barratt Impulsiveness Scale (BIS-11) and were genotyped for <i>COMT</i> rs4680. A two-way ANOVA was used to assess main and interaction effects of genotype and group on total and subscale BIS-11 scores. <b>Results</b>: Individuals with mixed addictions scored significantly higher on all BIS-11 subscales (<i>p</i> < 0.01). A significant interaction effect was observed for the Non-Planning (F_2,303 = 4.40, <i>p</i> = 0.0131, η² = 0.028) and Total BIS-11 scale (F_2,303 = 5.77, <i>p</i> = 0.0035, η² = 0.037), with the A/A genotype associated with increased impulsivity, especially among the clinical group. <b>Conclusions</b>: These findings support a gene-by-environment interaction in impulsivity, where <i>COMT</i> rs4680 Met/Met homozygotes may be more susceptible to heightened impulsivity in addiction contexts. The results highlight the potential utility of <i>COMT</i> genotyping in personalizing therapeutic strategies for impulse-related disorders such as addictive disorders. This study extends evidence on dopaminergic modulation of impulsivity to behavioral and substance addictions.