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

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:
$60.0万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2018
资助国家:
美国
项目状态:
已结题
起止时间:
2018-04-15 至 2024-01-31
关键词:
AffectiveAnatomyAreaBehavioralBehavioral AssayBehavioral GeneticsBrainBrain DiseasesBrain StemCandidate Disease GeneCannabinoidsClinicClinicalClinical TreatmentClinical TrialsCognitiveColoradoCorpus striatum structureDataData SetDiseaseDizygotic TwinsDopamineEconomicsEpilepsyFoundationsFunctional Magnetic Resonance ImagingGeneticGenetic MarkersGenetic PolymorphismGenetic ResearchGenomeGoalsHealthHealth Care CostsHealth PersonnelHeritabilityHippocampus (Brain)HumanImageIndividualIndividual DifferencesInstitutesLaboratoriesLeadLinkMagnetic Resonance ImagingMeasurementMeasuresMechanicsMedicalMental DepressionMental HealthMeta-AnalysisMethodsMigraineModelingModernizationNeurobiologyNeurosciencesNucleus AccumbensOpioidOutcomePainParkinson DiseaseParticipantPersonalityPersonsPharmaceutical PreparationsPlacebo ControlPlacebo EffectPlacebosPlayPopulation HeterogeneityPredisposing FactorPredispositionProcessProtocols documentationPsychological ImpactPublic HealthRecording of previous eventsResearchResearch DesignSamplingSchizophreniaScienceSensitivity and SpecificitySerotoninSourceStructureSumSymptomsSystemTestingTwin Multiple BirthUniversitiesVisceralWagesWomen&aposs Healthautism spectrum disorderbasebrain behaviorbrain pathwaychronic paincostcost effectivedesignexperiencegenetic approachgenetic predictorsgenome wide association studygray matterhealingimaging geneticsinnovationinsightnervous system disorderneurochemistryneuroimagingneuropathologyneurophysiologynovel strategiesnovel therapeuticspain sensitivityplacebo analgesiapolygenic risk scorepredictive modelingpsychologicrecruitrelating to nervous systemresilienceresponsescreeningsuccesstooltreatment effect

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英文摘要
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.
期刊论文(14)
专著(0)
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会议论文
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
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
作者: []
通讯作者:
DOI: 10.1016/j.bpsgos.2022.07.002
发表时间: 2023-07
期刊: Biological psychiatry global open science
影响因子: --
作者: []
通讯作者:
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