Abstract
Up to 45% of patients with Parkinson's disease (PD) experience impulse control disorders (ICDs), characterized by a loss of voluntary control over impulses, drives or temptations. This study aimed to investigate whether previously identified genetic and psychiatric risk factors interact towards the development of ICDs in PD. A total of 278 de novo PD patients (ICD-free at enrollment) were selected from the Parkinson's Progression Markers Initiative database. ICD presence at baseline and yearly follow-up assessments were evaluated via the Questionnaire for Impulsive-Compulsive Disorders. Symptoms of anxiety and depression at baseline were measured via the State-Trait-Anxiety Inventory and Geriatric Depression Scale, respectively. Furthermore, an individual dopamine genetic risk score was calculated according to polymorphisms in genes coding for dopamine (D1, D2 and D3 receptors and catechol-O-methyltransferase), with higher scores reflecting higher central dopamine neurotransmission. In total, 146 participants (47.5%) developed an ICD with an average onset time of 36 months (range 3-96) from baseline. Results from a Cox proportional hazards model showed a trait anxiety × genetics interaction, suggesting that individuals with both higher baseline trait anxiety scores and higher dopamine genetic risk scores were at increased risk of ICD development. This interaction remained significant after controlling for age, sex and motor symptom severity. Our findings suggest that genetic and psychiatric predictors of impulsivity in PD interact and jointly yield increased ICD risk during the course of the disorder. This implies that early screening of anxiety symptoms in combination with genotyping can be useful to identify those at risk for ICD.