Whooley Emma, Koppelmans Vincent, MacDonald Hayley J, Hall Alison, Ruitenberg Marit F L
Department of Health, Medical and Neuropsychology, Leiden University, Leiden, The Netherlands.
Department of Psychiatry, University of Utah, Salt Lake City, Utah, USA.
J Neuropsychol. 2025 Jan 28. doi: 10.1111/jnp.12415.
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.
高达45%的帕金森病（PD）患者会出现冲动控制障碍（ICD），其特征是对冲动、驱力或诱惑失去自主控制能力。本研究旨在调查先前确定的遗传和精神风险因素是否相互作用，影响PD患者ICD的发生。从帕金森病进展标志物倡议数据库中选取了278例新发PD患者（入组时无ICD）。通过冲动控制障碍问卷评估基线及每年随访时ICD的存在情况。分别通过状态-特质焦虑量表和老年抑郁量表测量基线时的焦虑和抑郁症状。此外，根据多巴胺（D1、D2和D3受体以及儿茶酚-O-甲基转移酶）编码基因的多态性计算个体多巴胺遗传风险评分，评分越高反映中枢多巴胺神经传递越高。共有146名参与者（47.5%）出现了ICD，从基线开始的平均发病时间为36个月（范围3 - 96个月）。Cox比例风险模型的结果显示特质焦虑×基因相互作用，表明基线特质焦虑评分较高且多巴胺遗传风险评分较高的个体发生ICD的风险增加。在控制年龄、性别和运动症状严重程度后，这种相互作用仍然显著。我们的研究结果表明，PD中冲动性的遗传和精神预测因素相互作用，并在疾病过程中共同导致ICD风险增加。这意味着早期筛查焦虑症状并结合基因分型有助于识别有ICD风险的个体。
