Objective: To assess the interplay of polygenic dopamine risk scores and psychiatric symptoms in the development of impulse control disorders (ICDs) in de novo patients with Parkinson’s disease (PD).

Background: Up to 45% of patients with PD experience ICDs, which are characterized by a loss of voluntary control over impulses, drives, or temptations regarding excessive hedonic behavior. While several risk factors for ICD development have been identified, these are often studied in isolation. We aimed to investigate whether previously identified genetic and psychiatric risk factors interact towards the prediction of ICDs in PD.

Method: We selected 278 ICD-free de novo PD patients from the Parkinson’s Progression Markers Initiative database (www.ppmi-info.org). ICD presence at baseline and follow-up assessments during a four-year period was evaluated via the Questionnaire for Impulsive-Compulsive Disorders in Parkinson’s Disease (QUIP). Symptoms of anxiety and depression at baseline were measured via the State-Trait-Anxiety Inventory (STAI-Y) and Geriatric Depression Scale (GDS-15), respectively. Furthermore, a dopamine genetic risk score was calculated for each patient 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).

Results: In total, 146 participants (47.5%) developed an ICD and the average onset time was 36 months (range 3-96) from baseline. Results of a Cox proportional hazard model showed that individuals with both higher baseline STAI-Y scores (reflecting more trait anxiety) and higher dopamine risk scores were at increased risk of ICD development (HR=1.03, p=.025). This interaction effect remained significant after controlling for age, gender, and UPDRS motor scores.

Conclusion: Our findings suggest that genetic and psychiatric predictors of ICD development in PD interact and jointly result in increased ICD risk during the course of the disorder. This implies that early screening of anxiety symptoms in combination with genotyping can be used to predict ICD risk.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genetic-and-psychiatric-risk-factors-for-impulse-control-disorders-in-de-novo-parkinsons-disease/