Dopaminergic influences on executive function and impulsive behaviour in impulse control disorders in Parkinson's disease
Dopaminergic influences on executive function and impulsive behaviour in impulse control disorders in Parkinson's disease
复制标题
DOI：
10.1111/jnp.12026
复制
发表时间：
2013-09-01
影响因子：
2.2
通讯作者：
McDonald, Kathryn
中科院分区：
文献类型：
--
作者：
Leroi, Iracema;Barraclough, Michelle;McDonald, Kathryn
帕金森病（PD）患者的冲动控制障碍（ICDs）可能是认知障碍、冲动反应和多巴胺能状态相互作用的结果。多巴胺能状态可能受到药理学或基因型（儿茶酚- o -甲基转移酶；COMT）因素的影响。我们试图通过比较（n=35）和（n=55） icd在不同药理学条件下（开或关多巴胺能药物）的延迟折扣、反应抑制以及开状态下执行功能的各个方面来进一步研究这种相互作用。然后，当整个PD组被分为COMT的不同等位基因变体（val/val vs. met/met）时，我们对这些相同的任务进行了探索性的亚组分析。同时纳入健康对照组（HC, n=20）。我们发现，在PD和icd患者中，与没有icd的患者相比，在服药状态下的认知灵活性（设定移动、语言流畅性和注意力）没有受到损害。相比之下，与HC组相比，两个PD组的工作记忆或认知焦点任务在ON时受到损害。在延迟折扣任务中，有icd的PD组在开药状态下比无icd的PD组表现出更大的冲动选择，而在关药状态下没有。然而，当打开时，在反应抑制任务上没有组间差异。最后，met纯合子组与val纯合子组在执行功能测试中的表现不同。我们的结论是，执行功能和冲动决策不同领域的损伤水平差异区分了PD中ICD患者和非ICD患者，这可能部分受多巴胺能状态的影响。药物和基因型对ICD中多巴胺能状态的影响可能很重要。
The development of impulse control disorders (ICDs) in Parkinson's disease (PD) may arise from an interaction among cognitive impairment, impulsive responding and dopaminergic state. Dopaminergic state may be influenced by pharmacologic or genotypic (catechol-O-methyltransferase; COMT) factors. We sought to investigate this interaction further by comparing those with (n=35) and without (n=55) ICDs on delay-discounting in different pharmacologic conditions (ON or OFF dopaminergic medication) and on response inhibition as well as aspects of executive functioning in the ON state. We then undertook an exploratory sub-group analysis of these same tasks when the overall PD group was divided into different allelic variants of COMT (val/val vs. met/met). A healthy control group (HC; n=20) was also included. We found that in those with PD and ICDs, cognitive flexibility' (set shifting, verbal fluency, and attention) in the ON medication state was not impaired compared with those without ICDs. In contrast, our working memory, or cognitive focus', task was impaired in both PD groups compared with the HC group when ON. During the delay-discounting task, the PD with ICDs group expressed greater impulsive choice compared with the PD group without ICDs, when in the ON, but not the OFF, medication state. However, no group difference on the response inhibition task was seen when ON. Finally, the met homozygous group performed differently on tests of executive function compared with the val homozygous group. We concluded that the disparity in levels of impairment among different domains of executive function and impulsive decision-making distinguishes those with ICD in PD from those without ICD, and may in part be affected by dopaminergic status. Both pharmacologic and genotypic influences on dopaminergic state may be important in ICD.