Genetic and personality interactions shape impulse control disorders in Parkinson's disease

Background In Parkinson's disease (PD), predictive factors of Impulse Control Disorders (ICDs) remain insufficiently understood. Personality and polygenic risk scores (PRS) have both been independently associated with ICDs. Objectives Our objective was to study the interaction effects between personality dimensions and PRS on the odds of developing ICDs. Methods This case-control study included PD patients with and without ICDs (n = 250 patients). Personality was assessed using the Temperament and Character Inventory-Revised, and PRS were computed from genotyping data across 18 traits linked to psychiatric/behavioral phenotypes. Logistic regression models were used to evaluate main and interaction effects between personality dimensions and PRS on ICD odds. Results Higher scores in Self-Directedness, attention deficit hyperactivity disorder (ADHD)-PRS, and major depressive disorder (MDD)-PRS were associated with increased odds of ICD (odds ratios (ORs) between 1.31 and 1.54). Several personality*PRS interactions also significantly modulated the odds of developing ICDs. Notably, Novelty Seeking*MDD PRS and Harm Avoidance*MDD PRS interactions amplified the odds of ICD (ORs = 1.34 and 1.30, respectively), while the Harm Avoidance*ADHD PRS interaction attenuated it (OR = 0.74). Self-Directedness interactions showed both odds amplification (with PD-PRS [OR = 1.34] and MDD-PRS [OR = 1.43]) and slight attenuation (with ADHD-PRS [OR = 0.73]). Conclusions This study provides novel evidence that the odds of having ICD are modulated by cumulative and interactive effects of personality and genes in PD. Self-Directedness, ADHD and MDD PRS were individually associated with ICDs, and their combinations yielded complex, non-additive effects—either amplifying or attenuating odds. These findings highlight the importance of integrating both psychological and genetic profiles in personalized risk assessment for ICDs.