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

与不治疗相比，安慰剂治疗可诱导临床显著获益 控制，在各种疾病。但安慰剂治疗本身是不安全的， 和身体惰性：他们的好处来自活跃的大脑和心理反应， 治疗背景。神经科学研究已经证实，安慰剂治疗会影响 皮质-皮质下脑通路和与预期相关的神经化学系统， 对个人和社会意义的评价，以及价值驱动的学习。这些系统也 与精神健康障碍和其他几种神经系统疾病的症状进展相关 和物质使用障碍。了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） 治疗各种疾病。 R 01的更新资助了一项正在进行的研究计划，该计划做出了重要贡献 这些文学。它还查明了一些重大差距， 将安慰剂研究与心理健康联系起来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疼痛研究。拟议 研究扩展了先前的工作，研究焦虑中安慰剂效应的大脑通路。 社会排斥、负性情感过程与多重心理健康直接相关 紊乱模式识别（机器学习）分析确定最相关的 途径，并测试安慰剂和其他背景干预对这些途径的影响。在Aim中 1（实验1-3），我们开发了跨多种情感症状的模型，解析情感 这些途径分为特定于特定的途径和跨多个 症状和结果。我们还讨论了内源性阿片类药物的作用，与 安慰剂镇痛，在其他负面的情感体验。另一个差距是， 对驱动强烈安慰剂效应的背景变量的研究，包括社会影响， 治疗史-尚未在大脑水平上进行广泛研究。在目标2中，我们研究了 几种有前景的背景干预措施的大脑通路， 安慰剂效应，包括成功或不成功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 以及一个人接受这些的倾向。

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.