Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs
Serotonergic and Dopaminergic Lesions Underlying Parkinsonian Neuropsychiatric Signs
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DOI：
10.1002/mds.28722
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发表时间：
2021-09-08
影响因子：
8.6
通讯作者：
Thobois, Stephane
中科院分区：
文献类型：
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作者：
Maillet, Audrey;Metereau, Elise;Thobois, Stephane
背景帕金森病（PD）的特征是与单胺能神经传递系统改变相关的异质性运动和非运动表现。然而，表征伴随多巴胺能和多巴胺能功能障碍后，不同的持续时间的帕金森氏病，以及他们各自参与的表达和严重程度的神经精神症状，得到了很少的关注到目前为止。方法为了填补这一空白，我们进行了一项横断面研究，结合临床和双示踪剂正电子发射断层扫描（PET）神经成像方法，使用放射性配体多巴胺（[C-11]-N-（3-碘丙-2E-烯基）-2-β-甲氧羰基-3-β-（4-甲基苯基）-去甲托烷）（[C-11] PE 2 I）和血清素（[C-11]-N，N-二甲基-2-（-2-氨基-4-氰基苯硫基）-苄胺）（[C-11]DASB）再摄取，在帕金森病的不同持续时间后（即，在短病程中，初治药物（n = 27，0-2年病程），患有冷漠（n = 14）或无冷漠（n = 13）;中度疾病持续时间（n = 15，4-7年持续时间）和长期疾病持续时间，非痴呆（n = 15，8-10年持续时间）患者）。还入组了15例年龄匹配的健康受试者。结果主要发现有三点：（1）帕金森病病程越长，多巴胺能和多巴胺能损害越严重，从中脑/皮层下向皮层扩散;（2）帕金森病发病时冷漠的存在与更严重的皮层和皮层下多巴胺能和多巴胺能损害有关，类似于病程中期患者的失神经支配模式;（3）帕金森病患者的冷漠、抑郁和特质焦虑的严重程度似乎主要与皮质纹状体边缘区的多巴胺能改变有关。总之，这些研究结果突出了帕金森病不同病程后发生的几种神经精神症状的表达中，多巴胺能变性的突出作用。(c)2021国际帕金森和运动障碍协会
Background Parkinson's disease (PD) is characterized by heterogeneous motor and nonmotor manifestations related to alterations in monoaminergic neurotransmission systems. Nevertheless, the characterization of concomitant dopaminergic and serotonergic dysfunction after different durations of Parkinson's disease, as well as their respective involvement in the expression and severity of neuropsychiatric signs, has gained little attention so far. Methods To fill this gap, we conducted a cross-sectional study combining clinical and dual-tracer positron emission tomography (PET) neuroimaging approaches, using radioligands of dopamine ([C-11]-N-(3-iodoprop-2E-enyl)-2-beta-carbomethoxy-3-beta-(4-methylphenyl)-nortropane) ([C-11]PE2I) and serotonin ([C-11]-N,N-dimethyl-2-(-2-amino-4-cyanophenylthio)-benzylamine) ([C-11]DASB) reuptake, after different durations of Parkinson's disease (ie, in short-disease duration drug-naive de novo (n = 27, 0-2 years-duration), suffering from apathy (n = 14) or not (n = 13); intermediate-disease duration (n = 15, 4-7 years-duration) and long-disease duration, non-demented (n = 15, 8-10 years-duration) patients). Fifteen age-matched healthy subjects were also enrolled. Results The main findings are threefold: (1) both dopaminergic and serotonergic lesions worsen with the duration of Parkinson's disease, spreading from midbrain/subcortical to cortical regions; (2) the presence of apathy at PD onset is associated with more severe cortical and subcortical serotonergic and dopaminergic disruption, similar to the denervation pattern observed in intermediate-disease duration patients; and (3) the severity of parkinsonian apathy, depression, and trait-anxiety appears primarily related to serotonergic alteration within corticostriatal limbic areas. Conclusions Altogether, these findings highlight the prominent role of serotonergic degeneration in the expression of several neuropsychiatric symptoms occurring after different durations of Parkinson's disease. (c) 2021 International Parkinson and Movement Disorder Society