Effects of Expectation on Placebo-Induced Dopamine Release in Parkinson Disease
Effects of Expectation on Placebo-Induced Dopamine Release in Parkinson Disease
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DOI：
10.1001/archgenpsychiatry.2010.88
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发表时间：
2010-08-01
影响因子：
--
通讯作者：
Stoessl, A. Jon
中科院分区：
文献类型：
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作者：
Lidstone, Sarah C.;Schulzer, Michael;Stoessl, A. Jon
背景：期望在安慰剂效应的机制中起着核心作用。在帕金森病（PD）中，安慰剂效应与黑质纹状体和中脑投射中内源性多巴胺的释放有关，但控制这种多巴胺释放的因素尚未确定。目的：确定对临床改善的预期强度如何影响中度PD患者对安慰剂的纹状体多巴胺释放程度。设计：随机、重复测量研究，以感知期望作为独立的受试者间变量。设置：加拿大不列颠哥伦比亚省温哥华市的不列颠哥伦比亚省大学医院。患者：35例接受左旋多巴治疗的轻度至中度PD患者。干预：语言操作被用来调节病人的期望值，病人被告知他们有一个特定的概率（25%、50%、75%或100%）的患者实际上接受的是安慰剂。使用[C-11]雷氯必利正电子发射断层扫描测量对安慰剂的多巴胺能反应。临床反应也进行了测量（统一帕金森病评定量表）和主观反应，确定使用患者自我report.Results：显着的多巴胺释放时，宣布接受活性药物的概率为75%，但不是在其他概率。安慰剂诱导的纹状体所有区域的多巴胺释放也与活性药物开放给药的多巴胺能反应高度相关。而先前的药物治疗的反应是主要的决定因素，安慰剂诱导的多巴胺释放在运动纹状体，预期的临床改善，另外需要驱动多巴胺释放在腹侧striatum.Conclusions：改善的信念的强度可以直接调节多巴胺释放在PD患者。我们的研究结果表明，不确定性和/或显着性的重要性和以上患者的先前治疗反应，在调节安慰剂效应，并有重要的意义，临床试验的解释和设计。
Context: Expectations play a central role in the mechanism of the placebo effect. In Parkinson disease (PD), the placebo effect is associated with release of endogenous dopamine in both nigrostriatal and mesoaccumbens projections, yet the factors that control this dopamine release are undetermined.Objective: To determine how the strength of expectation of clinical improvement influences the degree of striatal dopamine release in response to placebo in patients with moderate PD.Design: Randomized, repeated-measures study with perceived expectation as the independent between-subjects variable.Setting: University of British Columbia Hospital, Vancouver, British Columbia, Canada.Patients: Thirty-five patients with mild to moderate PD undergoing levodopa treatment.Intervention: Verbal manipulation was used to modulate the expectations of patients, who were told that they had a particular probability (25%, 50%, 75%, or 100%) of receiving active medication when they in fact received placebo.Main Outcome Measures: The dopaminergic response to placebo was measured using [C-11] raclopride positron emission tomography. The clinical response was also measured (Unified Parkinson Disease Rating Scale) and subjective responses were ascertained using patient self-report.Results: Significant dopamine release occurred when the declared probability of receiving active medication was 75%, but not at other probabilities. Placebo-induced dopamine release in all regions of the striatum was also highly correlated with the dopaminergic response to open administration of active medication. Whereas response to prior medication was the major determinant of placebo-induced dopamine release in the motor striatum, expectation of clinical improvement was additionally required to drive dopamine release in the ventral striatum.Conclusions: The strength of belief of improvement can directly modulate dopamine release in patients with PD. Our findings demonstrate the importance of uncertainty and/or salience over and above a patient's prior treatment response in regulating the placebo effect and have important implications for the interpretation and design of clinical trials.