Parkinson Institute, Istituti Clinici di Perfezionamento, via Bignami 1, 20126 Milan, Italy.
Brain Struct Funct. 2011 Nov;216(4):289-99. doi: 10.1007/s00429-011-0314-0. Epub 2011 May 4.
The development of an impulse control disorder (ICD) is now recognized as a potential nonmotor adverse effect of dopamine replacement therapy in Parkinson's disease (PD). Here, recent epidemiological, neurophysiological and genetic advances are summarized to outline potential mechanisms involved. It is safe to say that dopaminergic drugs, particularly dopamine agonists, are able to induce ICDs only in a minority of patients, while the majority are somehow protected from this adverse effect. While it seems clear that men with early-onset PD are more vulnerable, other predisposing factors, such as various current or pre-PD personality traits, are a matter of debate. In terms of neurophysiological advances, one may find striking analogies to the addiction literature suggesting a causal chain beginning with certain predisposing conditions of striatal dopamine synapses, an "unnatural" increase of dopamine stimulation and a characteristic pattern of resulting functional changes in remote networks of appetitive drive and impulse control. Future prospects include potential add-on medications and the possible identification of genetic predispositions at a genome-wide scale. Functional imaging of pharmacogenetic interactions (imaging pharmacogenomics) may be an important tool on that road.
冲动控制障碍（ICD）的发展现已被认为是帕金森病（PD）中多巴胺替代疗法的一种潜在非运动性不良反应。在这里，总结了最近的流行病学、神经生理学和遗传学进展，以概述潜在的相关机制。可以肯定的是，多巴胺能药物，特别是多巴胺激动剂，仅能在少数患者中引发 ICD，而大多数患者在某种程度上对此种不良反应具有抵抗力。虽然似乎很清楚，早发性 PD 的男性更容易受到影响，但其他易患因素，如各种当前或 PD 前的人格特征，仍存在争议。就神经生理学进展而言，人们可能会发现与成瘾文献惊人的相似之处，表明存在从纹状体多巴胺突触的某些易患条件开始的因果链，即“非自然”增加多巴胺刺激以及导致远程食欲和冲动控制驱动网络产生特征性功能变化。未来的前景包括潜在的附加药物和全基因组范围内可能确定的遗传易感性。药物遗传学相互作用的功能成像（影像药物基因组学）可能是该领域的重要工具。
