Martini Alice, Dal Lago Denise, Edelstyn Nicola M J, Salgarello Matteo, Lugoboni Fabio, Tamburin Stefano
School of Psychology, Keele University, Newcastle-under-Lyme, United Kingdom.
Department of Nuclear Medicine, Ospedale Sacro Cuore Don Calabria, Verona, Italy.
Front Neurol. 2018 Dec 4;9:1018. doi: 10.3389/fneur.2018.01018. eCollection 2018.
Around 30% Parkinson's disease (PD) patients develop impulse control disorders (ICDs) to D dopamine agonists and, to a lesser extent, levodopa. We aim to investigate striatal dopaminergic function in PD patients with and without ICD. PubMed, Science Direct, EBSCO, and ISI Web of Science databases were searched (from inception to March 7, 2018) to identify PET or SPECT studies reporting striatal dopaminergic function in PD patients with ICD (ICD+) compared to those without ICD (ICD-). Studies which included drug naïve patients, explored non-pharmacological procedures (e.g., deep brain stimulation), and those using brain blood perfusion or non-dopaminergic markers were excluded. Standardized mean difference (SDM) was used and random-effect models were applied. Separate meta-analyses were performed for dopamine transporter level, dopamine release, and dopamine receptors availability in the putamen, caudate, dorsal, and ventral striatum. A total of 238 studies were title and abstract screened, of which 19 full-texts were assessed. Nine studies (ICD+: = 117; ICD-: = 175 patients) were included in the analysis. ICD+ showed a significant reduction of dopamine transporter binding in the putamen (SDM = -0.46; 95% CI: -0.80, -0.11; = 2.61; = 0.009), caudate (SDM = -0.38; 95% CI: -0.73, -0.04; = 2.18; = 0.03) and dorsal striatum (SDM = -0.45; 95% CI: -0.77, -0.13; = 2.76; = 0.006), and increased dopamine release to reward-related stimuli/gambling tasks in the ventral striatum (SDM = -1.04; 95% CI: -1.73, -0.35; = 2.95; = 0.003). Dopamine receptors availability did not differ between groups. Heterogeneity was low for dopamine transporter in the dorsal striatum ( = 0%), putamen ( = 0%) and caudate ( = 0%), and pre-synaptic dopamine release in the dorsal ( = 0%) and ventral striatum ( = 0%); heterogeneity was high for dopamine transporter levels in the ventral striatum ( = 80%), and for dopamine receptors availability in the ventral ( = 89%) and dorsal ( = 86%) striatum, putamen ( = 93%), and caudate ( = 71%). ICD+ patients show lower dopaminergic transporter levels in the dorsal striatum and increased dopamine release in the ventral striatum when engaged in reward-related stimuli/gambling tasks. This dopaminergic imbalance might represent a biological substrate for ICD in PD. Adequately powered longitudinal studies with drug naïve patients are needed to understand whether these changes may represent biomarkers of premorbid vulnerability to ICD.
约30%的帕金森病（PD）患者会对多巴胺激动剂产生冲动控制障碍（ICD），在较小程度上也会对左旋多巴产生冲动控制障碍。我们旨在研究有无ICD的PD患者的纹状体多巴胺能功能。检索了PubMed、Science Direct、EBSCO和ISI Web of Science数据库（从数据库建立至2018年3月7日），以确定正电子发射断层扫描（PET）或单光子发射计算机断层扫描（SPECT）研究，这些研究报告了有ICD的PD患者（ICD+）与无ICD的PD患者（ICD-）的纹状体多巴胺能功能。排除了纳入未用过药物治疗患者的研究、探索非药物治疗方法（如深部脑刺激）的研究，以及使用脑血流灌注或非多巴胺能标记物的研究。使用标准化均数差（SDM）并应用随机效应模型。对壳核、尾状核、背侧和腹侧纹状体中的多巴胺转运体水平、多巴胺释放及多巴胺受体可用性进行了单独的荟萃分析。共筛选了238项研究的标题和摘要，其中19篇全文进行了评估。9项研究（ICD+组：n = 117；ICD-组：n = 175例患者）纳入分析。ICD+组在壳核（SDM = -0.46；95%置信区间：-0.80，-0.11；Z = 2.61；P = 0.009）、尾状核（SDM = -0.38；95%置信区间：-0.73，-0.04；Z = 2.18；P = 0.03）和背侧纹状体（SDM = -0.45；95%置信区间：-0.77，-0.13；Z = 2.76；P = 0.006）中多巴胺转运体结合显著降低，在腹侧纹状体中对奖励相关刺激/赌博任务的多巴胺释放增加（SDM = -1.04；95%置信区间：-1.73，-0.35；Z = 2.95；P = 0.003）。两组间多巴胺受体可用性无差异。背侧纹状体（I² = 0%）、壳核（I² = 0%）和尾状核（I² = 0%）中的多巴胺转运体以及背侧（I² = 0%）和腹侧纹状体（I² = 0%）中的突触前多巴胺释放的异质性较低；腹侧纹状体中多巴胺转运体水平（I² = 80%）以及腹侧（I² = 89%）和背侧（I² = 86%）纹状体、壳核（I² = 93%）和尾状核（I² = 71%）中多巴胺受体可用性的异质性较高。ICD+患者在背侧纹状体中多巴胺能转运体水平较低，在参与奖励相关刺激/赌博任务时腹侧纹状体中多巴胺释放增加。这种多巴胺能失衡可能是PD中ICD的生物学基础。需要对未用过药物治疗的患者进行足够样本量的纵向研究，以了解这些变化是否可能代表病前对ICD易感性的生物标志物。
