帕金森病中多巴胺能功能与动机的双向相关性。
Bidirectional Correlations Between Dopaminergic Function and Motivation in Parkinson's Disease.
机构信息
Medical Scientist Training Program, 1500Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Neurology, 1500Johns Hopkins University School of Medicine, Baltimore, MD, USA.
出版信息
J Geriatr Psychiatry Neurol. 2022 May;35(3):353-362. doi: 10.1177/0891988721996802. Epub 2021 Feb 24.
OBJECTIVE
To test the hypothesis that striatal dopamine function influences motivational alterations in Parkinson disease (PD), we compared vesicular monoamine transporter 2 (VMAT2) and dopamine transporter (DaT) imaging data in PD patients with impulse control disorders (ICDs), apathy, or neither.
METHODS
We extracted striatal binding ratios (SBR) from VMAT2 PET imaging (F-AV133) and DaTscans from the Parkinson's Progression Markers Initiative (PPMI) multicenter observational study. Apathy and ICDs were assessed using the Movement Disorders Society-revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP), respectively. We used analysis of variance (ANOVA) and log-linear mixed-effects (LME) regression to model SBRs with neurobehavioral metrics.
RESULTS
Among 23 participants (mean age 62.7 years, mean disease duration 1.8 years) with VMAT2 imaging data, 5 had apathy, 5 had an ICD, and 13 had neither. ANOVA indicated strong groupwise differences in VMAT2 binding in right anterior putamen [F(2,20) = 16.2, p < 0.0001), right posterior putamen [F(2,20) = 16.9, p < 0.0001), and right caudate [F(2,20) = 6.8, p = 0.006)]. Post-hoc tests and repeated-measures analysis with LME regression also supported right striatal VMAT2 elevation in the ICD group and reduction in the apathy group relative to the group with neither ICD nor apathy. DaT did not exhibit similar correlations, but normalizing VMAT2 with DaT SBR strengthened bidirectional correlations with ICD (high VMAT2/DaT) and apathy (low VMAT2/DaT) in all striatal regions bilaterally.
CONCLUSIONS
Our findings constitute preliminary evidence that striatal presynaptic dopaminergic function helps describe the neurobiological basis of motivational dysregulation in PD, from high in ICDs to low in apathy.
目的
为了验证纹状体多巴胺功能是否会影响帕金森病（PD）患者的动机改变这一假说，我们对比了伴有冲动控制障碍（ICD）、淡漠或两者皆无的 PD 患者的囊泡单胺转运体 2（VMAT2）和多巴胺转运体（DaT）成像数据。
方法
我们从帕金森进展标志物倡议（PPMI）多中心观察性研究中的 VMAT2 PET 成像（F-AV133）和 DaT 扫描中提取纹状体结合比（SBR）。使用运动障碍协会修订的统一帕金森病评定量表（MDS-UPDRS）和帕金森病冲动-强迫问卷（QUIP）分别评估淡漠和 ICD。我们使用方差分析（ANOVA）和对数线性混合效应（LME）回归来对 SBR 与神经行为学指标进行建模。
结果
在 23 名接受 VMAT2 成像数据的参与者（平均年龄 62.7 岁，平均病程 1.8 年）中，5 名患有淡漠，5 名患有 ICD，13 名两者皆无。ANOVA 表明，右侧前壳核[F(2,20) = 16.2，p < 0.0001]、右侧后壳核[F(2,20) = 16.9，p < 0.0001]和右侧尾状核[F(2,20) = 6.8，p = 0.006]的 VMAT2 结合存在强烈的组间差异。事后检验和 LME 回归的重复测量分析也支持 ICD 组右侧纹状体 VMAT2 升高，淡漠组 VMAT2 降低，与既无 ICD 也无淡漠的组相比。DaT 则没有表现出类似的相关性，但将 VMAT2 与 DaT SBR 进行归一化，可增强双侧所有纹状体区域与 ICD（高 VMAT2/DaT）和淡漠（低 VMAT2/DaT）之间的双向相关性。
结论
我们的发现初步证明了纹状体前突触多巴胺功能有助于描述 PD 中动机失调的神经生物学基础，从 ICD 中的高到淡漠中的低。
Zotero 插件