Ziegler David A, Ashourian Paymon, Wonderlick Julien S, Sarokhan Alison K, Prelec Drazen, Scherzer Clemens R, Corkin Suzanne
Department of Neurology and the Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA, USA; Department of Brain & Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA.
Scand J Psychol. 2014 Jun;55(3):278-86. doi: 10.1111/sjop.12113. Epub 2014 Apr 21.
Parkinson disease (PD) is an age-related degenerative disease of the brain, characterized by motor, cognitive, and psychiatric symptoms. Neurologists and neuroscientists now understand that several symptoms of the disease, including hallucinations and impulse control behaviors, stem from the dopaminergic medications used to control the motor aspects of PD. Converging evidence from animals and humans suggests that individual differences in the genes that affect the dopamine system influence the response of PD patients to dopaminergic medication. In this study, we tested the hypothesis that patients taking dopamine replacement therapy who carry candidate alleles that increase dopamine signaling, exhibit greater amounts of motor impulsivity. We examined the relation between inhibitory ability (measured by the Stop Signal Task) and polymorphisms of COMT Val158Met and DRD2 C957T in patients with idiopathic PD. On the Stop Signal Task, carriers of COMT Val/Met and Met/Met genotypes were more impulsive than Val/Val carriers, but we did not find a link between DRD2 polymorphisms and inhibitory ability. These results support the hypothesis that the Met allele of COMT confers an increased risk for behavioral impulsivity in PD patients, whereas DRD2 polymorphisms appear to be less important in determining whether PD patients exhibit a dopamine overdose in the form of motor impulsivity.
帕金森病（PD）是一种与年龄相关的脑部退行性疾病，其特征为运动、认知和精神症状。神经科医生和神经科学家现在明白，该疾病的一些症状，包括幻觉和冲动控制行为，源于用于控制帕金森病运动方面的多巴胺能药物。来自动物和人类的越来越多的证据表明，影响多巴胺系统的基因中的个体差异会影响帕金森病患者对多巴胺能药物的反应。在这项研究中，我们检验了这样一个假设：接受多巴胺替代疗法且携带增加多巴胺信号传导的候选等位基因的患者，表现出更多的运动冲动性。我们研究了特发性帕金森病患者的抑制能力（通过停止信号任务测量）与儿茶酚-O-甲基转移酶（COMT）Val158Met和多巴胺D2受体（DRD2）C957T基因多态性之间的关系。在停止信号任务中，COMT Val/Met和Met/Met基因型的携带者比Val/Val携带者更冲动，但我们未发现DRD2基因多态性与抑制能力之间存在关联。这些结果支持了这样的假设：COMT的Met等位基因会增加帕金森病患者出现行为冲动的风险，而DRD2基因多态性在确定帕金森病患者是否以运动冲动的形式出现多巴胺过量方面似乎不太重要。
