Brain and Genetic Predictors of Individual Differences in Pain and Placebo Analgesia

疼痛和安慰剂镇痛个体差异的大脑和遗传预测因子

• 批准号: 10343749
• 负责人: Naomi P. Friedman
• 金额: $ 60万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-04-15 至 2024-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10343749
• 关键词: Affective; Anatomy; Area; Behavioral; Behavioral Assay; Behavioral Genetics; Brain; Brain Diseases; Brain Stem; Candidate Disease Gene; Cannabinoids; Clinic; Clinical; Clinical Treatment; Clinical Trials; Cognitive; Colorado; Corpus striatum structure; Data; Data Set; Disease; Dizygotic Twins; Dopamine; Economics; Epilepsy; Foundations; Functional Magnetic Resonance Imaging; Genetic; Genetic Markers; Genetic Polymorphism; Genetic Research; Genome; Goals; Health; Health Care Costs; Health Personnel; Heritability; Hippocampus (Brain); Human; Image; Individual; Individual Differences; Institutes; Laboratories; Lead; Link; Magnetic Resonance Imaging; Measurement; Measures; Mechanics; Medical; Mental Depression; Mental Health; Meta-Analysis; Methods; Migraine; Modeling; Modernization; Neurobiology; Neurosciences; Nucleus Accumbens; Opioid; Outcome; Pain; Parkinson Disease; Participant; Personality; Persons; Pharmaceutical Preparations; Placebo Control; Placebo Effect; Placebos; Play; Population Heterogeneity; Predisposing Factor; Predisposition; Process; Protocols documentation; Psychological Impact; Public Health; Recording of previous events; Research; Research Design; Sampling; Schizophrenia; Science; Sensitivity and Specificity; Serotonin; Source; Structure; Sum; Symptoms; System; Testing; Twin Multiple Birth; Universities; Visceral; Wages; Women' s Health; autism spectrum disorder; base; brain behavior; brain pathway; chronic pain; cost; cost effective; design; experience; genetic approach; genetic predictors; genome wide association study; gray matter; healing; imaging genetics; innovation; insight; nervous system disorder; neurochemistry; neuroimaging; neuropathology; neurophysiology; novel strategies; novel therapeutics; pain sensitivity; placebo analgesia; polygenic risk score; predictive modeling; psychologic; recruit; relating to nervous system; resilience; response; screening; success; tool; treatment effect

Project Summary Throughout history, placebo effects have been variously considered as tricks played upon the gullible by medical practitioners and powerful but mysterious healing forces. With the advent of direct measurements of human brain function, modern science has shown that placebo effects are neither of these. Rather, they reflect the principled impact of psychological and brain processes on diseases of the brain and body. Placebo effects represent an opportunity because they provide a window into internal brain processes that influence health, and a challenge because many clinical trials have now failed due to large and durable placebo responses, at great cost to health care providers and consumers. Definitive studies of the brain pathways involved in placebo responses—and the genetic, environmental, and neural factors that lead some individuals to respond more strongly than others—are critical to harnessing placebo effects, eliminating or controlling placebo responses in clinical trials, and understanding the psychological and brain factors that predispose one to successful treatment and “spontaneous” improvement. Placebo analgesia is the best-studied type of placebo effect, with well-developed paradigms and preliminary data on its brain mechanisms. This background provides a foundation for larger-scale, definitive studies. In this project, we propose the first such large-scale study of brain mechanisms of placebo analgesia, combining neuroimaging, behavioral, and genetic approaches. It builds on 15 years’ experience in PI Wager’s laboratory on fMRI and placebo analgesia and 40 years of genetics research at the Institute for Behavior Genetics (IBG) at the University of Colorado, Boulder. We will use fMRI to characterize the neural bases of placebo effects in 600 twins recruited from the Colorado Twin Sample and predict individual differences in placebo effects across two forms of pain. In Aim 1, we will develop models that predict the magnitude of individuals’ placebo effects in pain and pain neurophysiology based on a) fMRI activity, b) brain structure, and a combination of personality, behavioral, and cognitive measures that can be deployed clinically. In Aim 2, we conduct the first analyses of heritability of placebo effects and their neural predictors, and genetic correlations that can identify brain features whose relationships with placebo effects are genetic in origin. In Aim 3, we leverage the >50,000 person Enhancing Neuro-Imaging Genetics through Meta-analysis (ENIGMA) consortium to identify genome-wide associations with placebo-linked brain features and develop polygenic risk scores for placebo effects. The research products from this endeavor will include data and models useful for characterizing and screening participants in clinical trials, assessing interactions between placebo responses and other treatments, and assessing placebo effects across disorders.

项目摘要 通过历史，安慰剂效果被各种被视为医学对雕像的技巧 从业者和强大但神秘的治疗力量。随着人类直接测量的进步 大脑功能，现代科学表明安慰剂作用既不是这些。相反，它们反映了 心理和大脑过程对大脑和身体疾病的主要影响。安慰剂效果 代表机会，因为它们为影响健康的内部大脑过程提供了一个窗口，并且 一个挑战，因为许多临床试验现在由于安慰剂的大量反应而失败， 卫生保健提供者和消费者的成本。 对安慰剂反应中涉及的大脑途径的确切研究以及遗传，环境和 导致某些人比其他人更强烈反应的神经因素 - 对利用安慰剂至关重要 在临床试验中的效果，消除或控制安慰剂反应，并了解心理和 大脑因素使人们易于成功治疗和“自发”改善。安慰剂镇痛 是最有研究的安慰剂效应，具有发达的范例和大脑的初步数据 机制。该背景为大规模，确定的研究奠定了基础。 在这个项目中，我们提出了第一个对安慰剂镇痛的大脑机制的大规模研究，结合了 神经影像，行为和遗传方法。它以Pi Wager的实验室的15年经验为基础 在fMRI和安慰剂镇痛以及行为遗传研究所（IBG）的40年遗传学研究上 科罗拉多大学博尔德大学。我们将使用fMRI来表征600的安慰剂效应的神经底座 从科罗拉多双胞胎样本中招募的双胞胎，并预测两个人的安慰剂效应中的个体差异 疼痛的形式。在AIM 1中，我们将开发模型，以预测个体的安慰剂在痛苦中的幅度 基于a）fMRI活性，b）大脑结构和人格结合的疼痛神经生理学， 行为和可以在临床上部署的认知措施。在AIM 2中，我们进行了首次分析 安慰剂作用的遗传力及其神经预测因子以及可以识别大脑特征的遗传相关性 其与安慰剂作用的关系是起源的遗传。在AIM 3中，我们利用> 50,000人 通过荟萃分析（Enigma）联盟增强神经成像遗传学，以鉴定全基因组 与安慰剂连接的大脑特征相关联并发展多基因风险评分以达到安慰剂效应。这 这项工作的研究产品将包括用于表征和筛选的数据和模型 参与临床试验的参与者，评估安慰剂反应与其他治疗之间的相互作用，以及 评估跨疾病的安慰剂作用。

项目成果

Effect sizes and test-retest reliability of the fMRI-based neurologic pain signature.

• DOI: 10.1016/j.neuroimage.2021.118844
• 发表时间: 2022-02-15
• 期刊: NeuroImage
• 影响因子: 5.7
• 作者: Han X;Ashar YK;Kragel P;Petre B;Schelkun V;Atlas LY;Chang LJ;Jepma M;Koban L;Losin EAR;Roy M;Woo CW;Wager TD
• 通讯作者: Wager TD

A New Look at Gray Matter Decreases in Chronic Pain.

对慢性疼痛灰质减少的新认识。

• DOI: 10.1016/j.biopsych.2023.12.009
• 发表时间: 2024
• 期刊: Biological psychiatry
• 影响因子: 10.6
• 作者: Wager,TorD;Zorina-Lichtenwalter,Katerina;Friedman,NaomiP
• 通讯作者: Friedman,NaomiP

The neural signature of the decision value of future pain.

• DOI: 10.1073/pnas.2119931119
• 发表时间: 2022-06-07
• 期刊: Proceedings of the National Academy of Sciences of the United States of America
• 影响因子: 11.1

Sleep Health at the Genomic Level: Six Distinct Factors and Their Relationships With Psychopathology.

• DOI: 10.1016/j.bpsgos.2022.07.002
• 发表时间: 2023-07
• 期刊: Biological psychiatry global open science

A human colliculus-pulvinar-amygdala pathway encodes negative emotion.

• DOI: 10.1016/j.neuron.2021.06.001
• 发表时间: 2021-08-04
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Kragel PA;Čeko M;Theriault J;Chen D;Satpute AB;Wald LW;Lindquist MA;Feldman Barrett L;Wager TD
• 通讯作者: Wager TD