Precision phenotyping to uncover the latent structure and genetic correlates of impulsivity

Background: Impulsivity is a multidimensional transdiagnostic construct that is a key feature of many forms of psychopathology, but its underlying latent architecture and genetic correlates remain unclear. Methods: We comprehensively measured impulsivity-related constructs with 105 self-report questionnaire items across 16 scales and subscales in 859 non-clinical adult participants. We used exploratory structural equation modeling and item response theory to measure the target impulsivity traits with high precision. We also calculated polygenic risk scores for impulsivity traits and attention deficit hyperactivity disorder (ADHD) based on genome-wide association studies of independent discovery samples.Results: A hypothesized three-factor model of impulsivity, comprising Disinhibition – affect-free lack of premeditation; Urgency – emotion-based rash action; and Reward Sensitivity – sensation-, novelty-, and excitement-seeking; provided a better fit to the data compared to one- and two-factor models. Disinhibition was associated with impulsivity polygenic risk scores reflecting lack of perseverance (r2 = .017, p = .252 x 10-3) and with ADHD polygenic risk scores (r2 = .014, p =. 826 x 10-3). Reward sensitivity was also associated with ADHD polygenic risk scores (r2 = .018, p = .193 x 10-3). Conclusions: The pattern of observed genetic correlations was consistent with the proposed three-factor model of impulsivity and suggest that disinhibition and reward sensitivity represent independent risk pathways for ADHD, consistent with a dual pathways model. We propose that Disinhibition, Urgency, and Reward Sensitivity represent candidate phenotypes for better understanding the multidimensional nature of Impulsivity.