Department of Psychiatry and Behavioural and Clinical Neurosciences Institute, University of Cambridge, Cambridge, UK; Cambridgeshire and Peterborough NHS Foundation Trust, Cambridge, UK.
Departments of Pharmacology and Psychiatry, Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL, USA.
Lancet Neurol. 2017 Mar;16(3):238-250. doi: 10.1016/S1474-4422(17)30004-2. Epub 2017 Feb 15.
Dopaminergic medications used in the treatment of patients with Parkinson's disease are associated with motor and non-motor behavioural side-effects, such as dyskinesias and impulse control disorders also known as behavioural addictions. Levodopa-induced dyskinesias occur in up to 80% of patients with Parkinson's after a few years of chronic treatment. Impulse control disorders, including gambling disorder, binge eating disorder, compulsive sexual behaviour, and compulsive shopping occur in about 17% of patients with Parkinson's disease on dopamine agonists. These behaviours reflect the interactions of the dopaminergic medications with the individual's susceptibility, and the underlying neurobiology of Parkinson's disease. Parkinsonian rodent models show enhanced reinforcing effects of chronic dopaminergic medication, and a potential role for individual susceptibility. In patients with Parkinson's disease and impulse control disorders, impairments are observed across subtypes of decisional impulsivity, possibly reflecting uncertainty and the relative balance of rewards and losses. Impairments appear to be more specific to decisional than motor impulsivity, which might reflect differences in ventral and dorsal striatal engagement. Emerging evidence suggests impulse control disorder subtypes have dissociable correlates, which indicate that individual susceptibility predisposes towards the expression of different behavioural subtypes and neurobiological substrates. Therapeutic interventions to treat patients with Parkinson's disease and impulse control disorders have shown efficacy in randomised controlled trials. Large-scale studies are warranted to identify individual risk factors and novel therapeutic targets for these diseases. Mechanisms underlying impulse control disorders and dyskinesias could provide crucial insights into other behavioural symptoms in Parkinson's disease and addictions in the general population.
用于治疗帕金森病患者的多巴胺能药物与运动和非运动行为副作用相关,例如运动障碍和冲动控制障碍,也称为行为成瘾。左旋多巴诱导的运动障碍在慢性治疗数年后发生在多达 80%的帕金森病患者中。冲动控制障碍,包括赌博障碍、暴食障碍、强迫性行为和强迫性购物,在接受多巴胺激动剂治疗的帕金森病患者中约占 17%。这些行为反映了多巴胺能药物与个体易感性以及帕金森病的潜在神经生物学之间的相互作用。帕金森病啮齿动物模型显示慢性多巴胺能药物的强化作用增强,以及个体易感性的潜在作用。在患有帕金森病和冲动控制障碍的患者中,在决策冲动的亚型中观察到损伤,可能反映了不确定性以及奖励和损失的相对平衡。损伤似乎比运动冲动更特定于决策,这可能反映了腹侧和背侧纹状体的参与差异。新出现的证据表明冲动控制障碍亚型具有可分离的相关性,这表明个体易感性促使不同行为亚型和神经生物学基础的表达。针对帕金森病和冲动控制障碍患者的治疗干预措施已在随机对照试验中显示出疗效。需要进行大规模研究以确定这些疾病的个体风险因素和新的治疗靶点。冲动控制障碍和运动障碍的潜在机制可以为帕金森病和一般人群中的其他行为症状以及成瘾提供重要的见解。