1CHU Nantes, Addictology and Psychiatry Department, Nantes, France.
2Nantes Université, Univ Tours, CHU Nantes, CHU Tours, INSERM, MethodS in Patients centered outcomes and HEalth ResEarch, SPHERE, F-44000 Nantes, France.
J Behav Addict. 2022 Aug 11;11(3):766-777. doi: 10.1556/2006.2022.00051. Print 2022 Sep 26.
Parkinson's disease (PD) is one of the most prevalent neurodegenerative diseases. First-line medications consist of drugs that act by counteracting dopamine deficiency in the basal ganglia. Unfortunately, iatrogenic impulsive-compulsive behaviors (ICBs) can occur in up to 20% of PD patients over the course of their illness. ICBs must be considered multifactorial disorders that reflect the interactions of the medication with an individual's vulnerability and the underlying neurobiology of PD. We aimed to explore the predictive genetic, psychopathological and neurological factors involved in the development of ICBs in PD patients by building a complete model of individual vulnerability.
The PARKADD study was a case/non-case study. A total of 225 patients were enrolled ("ICB" group, N = 75; "no ICB" group, N = 150), and 163 agreed to provide saliva samples for genetic analysis. Sociodemographic, neurological and psychiatric characteristics were assessed, and genotyping for the characterization of polymorphisms related to dopaminergic and opioid systems was performed.
Factors associated with "ICBs" were younger age of PD onset, personal history of ICB prior to PD onset and higher scores on the urgency and sensation seeking facets of impulsivity. No gene variant was significantly associated, but the association with the opioid receptor mu 1 (OPRM1) rs1799971 polymorphism was close to significance.
The influence of gene-environment interactions probably exists, and additional studies are needed to decipher the possible role of the opioid system in the development of ICBs in PD patients.
帕金森病(PD)是最常见的神经退行性疾病之一。一线药物包括通过对抗基底神经节中多巴胺缺乏而起作用的药物。不幸的是,在疾病过程中,多达 20%的 PD 患者会出现医源性冲动-强迫行为(ICBs)。ICBs 必须被认为是反映药物与个体易感性和 PD 潜在神经生物学相互作用的多因素疾病。我们旨在通过构建个体易感性的完整模型,探讨与 PD 患者 ICBs 发展相关的预测遗传、心理病理和神经因素。
PARKADD 研究是一项病例对照研究。共纳入 225 名患者(“ICB”组,N=75;“无 ICB”组,N=150),其中 163 名同意提供唾液样本进行基因分析。评估了社会人口统计学、神经和精神特征,并对与多巴胺和阿片系统相关的多态性进行了基因分型。
与“ICBs”相关的因素包括 PD 发病年龄较小、PD 发病前有 ICB 个人史以及冲动的紧迫性和感觉寻求方面的评分较高。没有基因变异与“ICBs”显著相关,但与阿片受体 mu 1(OPRM1)rs1799971 多态性的关联接近显著。
基因-环境相互作用的影响可能存在,需要进一步研究来阐明阿片系统在 PD 患者 ICBs 发展中的可能作用。