Hall Alison, Weaver Samuel R, Compton Lindsey J, Byblow Winston D, Jenkinson Ned, MacDonald Hayley J
School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham, Birmingham, UK.
Centre for Human Brain Health, University of Birmingham, Birmingham, UK.
Clin Park Relat Disord. 2021 Oct 29;5:100113. doi: 10.1016/j.prdoa.2021.100113. eCollection 2021.
Up to 40% of Parkinson's disease patients taking dopamine agonist medication develop impulse control behaviors which can have severe negative consequences. The current study aimed to utilize dopamine genetics to identify patients most at risk of developing these behaviors.
Demographic, clinical, and genetic data were obtained from the Parkinson's Progression Markers Initiative for de novo patients (n = 327), patients taking dopamine agonists (n = 146), and healthy controls (n = 160). Impulsive behaviors were identified using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease. 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. A higher score reflected higher central dopamine neurotransmission.
Patients on agonists with a low dopamine genetic risk score were over 18 times more likely to have an impulsive behavior compared to higher scores (p = 0.04). The 38% of patients taking agonists who had at least one impulsive behavior were more likely to be male and report higher Unified Parkinson's Disease Rating Scale I&II scores. With increasing time on dopamine agonists (range 92-2283 days, mean 798 ± 565 standard deviation), only patients with a high dopamine genetic risk score showed an increase in number of impulsive behaviors (p = 0.033). Predictive effects of the gene score were not present in de novo or healthy control.
A dopamine genetic risk score can identify patients most at risk of developing impulsive behaviors on dopamine agonist medication and predict how these behaviors may worsen over time.
高达40%服用多巴胺激动剂药物的帕金森病患者会出现冲动控制行为，这可能会产生严重的负面后果。当前的研究旨在利用多巴胺遗传学来识别最易出现这些行为的患者。
从帕金森病进展标志物倡议项目中获取了初发患者（n = 327）、服用多巴胺激动剂的患者（n = 146）以及健康对照者（n = 160）的人口统计学、临床和遗传数据。使用帕金森病冲动控制障碍问卷来识别冲动行为。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，为每位患者计算多巴胺遗传风险评分。较高的评分反映较高的中枢多巴胺神经传递。
多巴胺遗传风险评分低的服用激动剂的患者出现冲动行为的可能性是评分高的患者的18倍多（p = 0.04）。服用激动剂且至少有一种冲动行为的患者中，38%更可能为男性，且统一帕金森病评定量表I&II评分更高。随着服用多巴胺激动剂时间的增加（范围92 - 2283天，平均798 ± 565标准差），只有多巴胺遗传风险评分高的患者的冲动行为数量增加（p = 0.033）。基因评分在初发患者或健康对照者中不存在预测作用。
多巴胺遗传风险评分可以识别在服用多巴胺激动剂药物时最易出现冲动行为的患者，并预测这些行为如何随时间恶化。
