The neural bases of placebo effects and their relation to regulatory processes

与不治疗相比，安慰剂治疗可以在临床上产生显著的益处 对照，跨越各种障碍。但安慰剂治疗本身就是药理上的。 和身体惰性：它们的好处来自活跃的大脑和心理反应 治疗环境。神经科学研究已经证实，安慰剂治疗会影响 与预期相关的皮质-皮质下大脑通路和神经化学系统， 对个人和社会意义的评估，以及价值驱动的学习。这些系统还 与精神健康障碍和其他几种神经学疾病的症状进展有关 和物质使用障碍。理解安慰剂的大脑和心理机制 效果将有助于改善心理和神经(例如，基于神经调节的) 各种疾病的治疗方法。 R01续订为一个正在进行的研究计划提供资金，该计划已经做出了根本性的贡献 对这部文学作品。它还发现了几个显著的差距，这些差距对 将安慰剂研究与心理健康联系起来。其中一个差距是我们对大脑的理解 安慰剂效应的潜在机制几乎完全来自于对疼痛的研究。建议数 研究扩展了先前的工作，以研究焦虑中安慰剂效应的大脑通路 和社交拒绝、消极情感过程与多重心理健康直接相关 精神错乱。模式识别(机器学习)分析识别与症状最相关的 途径，以及安慰剂和其他背景干预对这些途径的测试效果。在AIM 1(实验1-3)，我们建立了跨越多种情感症状的模型，分析了情感 进入特定症状的途径和跨多个 症状和结果。我们还讨论了内源性阿片类药物的作用，这与 安慰剂止痛，在其他负面情感体验中。另一个差距是最早的 对驱动强烈的安慰剂效应的背景变量的研究--包括社会影响， 治疗史--在大脑层面还没有广泛的研究。在目标2中，我们研究了 几种有希望的情境干预措施背后的大脑通路，这些干预措施增强了 安慰剂效应，包括成功或不成功的治疗反应的社会模型， 治疗成功或失败的初步经验，以及安慰剂建议之间的匹配 以及一个人接受它们的倾向。

Placebo treatments can induce clinically significant benefits, compared with no-treatment controls, across a variety of disorders. But placebo treatments themselves are pharmacologically and physically inert: Their benefits result from active brain and psychological responses to the treatment context. Neuroscientific studies have established that placebo treatments influence cortical-subcortical brain pathways and neurochemical systems relevant for expectation, appraisals of personal and social meaning, and value-driven learning. These systems are also related to symptom progression across mental health disorders and several other neurological and substance use disorders. Understanding the brain and psychological mechanisms of placebo effects will help improve psychological and neurological (e.g., neuromodulation-based) treatments across disorders. This R01 renewal funds an ongoing program of research that has made fundamental contributions to this literature. It has also identified several significant gaps that are particularly important for connecting placebo research to mental health. One gap is that our understanding of the brain mechanisms underlying placebo effects comes almost purely from studies of pain. The proposed studies extend previous work to study the brain pathways underlying placebo effects in anxiety and social rejection, negative affective processes directly relevant for multiple mental health disorders. Pattern-recognition (machine learning) analyses identify the most symptom-relevant pathways, and test effects of placebo and other context interventions on these pathways. In Aim 1 (Experiments 1-3), we develop models across multiple affective symptoms, parsing affective pathways into those that are symptom-specific and those that generalize across multiple symptoms and outcomes. We also address the role of endogenous opioids, strongly linked to placebo analgesia, in other negative affective experiences. Another gap is that most previous studies of the context variables that drive strong placebo effects—including social influences, treatment history—have not been studied extensively at the brain level. In Aim 2, we study the brain pathways underlying several promising context interventions that enhance the strength of placebo effects, including social modeling of successful or unsuccessful treatment response, initial experiences of treatment success or failure, and the match between placebo suggestions and a person’s predisposition to be receptive to them.