Neurobiology of non-specific and specific treatment responses in Major Depression
重度抑郁症非特异性和特异性治疗反应的神经生物学
基本信息
- 批准号:9341382
- 负责人:
- 金额:$ 56.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-09-01 至 2021-05-31
- 项目状态:已结题
- 来源:
- 关键词:AcuteAffectAffectiveAmygdaloid structureAnteriorAntidepressive AgentsAreaBackBehavioralBiologicalBiological MarkersBrainChronicClinicalClinical MedicineClinical TrialsCognitiveConduct Clinical TrialsCuesDataDevelopmentDiagnosisDopamineDouble-Blind MethodDouble-blind trialDrug TargetingEgoEmotionalExpectancyGenetic PolymorphismGenetic VariationHydrocortisoneIndividualInterventionLearningLinkMaintenanceMajor Depressive DisorderMeasurementMeasuresMedialMediatingMoodsNeurobiologyNeurotic DisordersNeuroticsNeurotransmittersNoiseNucleus AccumbensOpioid ReceptorPatientsPeripheralPersonality TraitsPersonality inventoriesPharmaceutical PreparationsPlacebo EffectPlacebosPredictive ValueProcessPsychophysicsRandomized Controlled TrialsRecoveryRegulationReportingRewardsScienceSelective Serotonin Reuptake InhibitorSourceStimulusStressStructureSymptomsSystemTestingThalamic structureTherapeuticTherapeutic AgentsTherapeutic EffectTherapeutic InterventionTranscendTreatment outcomeVariantactive methodantidepressant effectarmbiomarker discoverycomparative effectivenessdesigneffectiveness trialemotion regulationendogenous opioidsexpectationexperienceinflammatory markerinter-individual variationneurochemistryneurotransmissionnovelnovel strategiesopen labelpredictive of treatment responsepublic health relevancerandomized placebo controlled trialrelating to nervous systemresilienceresponsescreeningsymptomatic improvementtheoriestraittreatment response
项目摘要
DESCRIPTION (provided by applicant): In science, profound changes in paradigm have emerged when previously unexplained phenomena, typically disregarded as noise or measurement error, are explained by a new theoretical structure. If a comparable phenomenon could be found in clinical medicine, an unexplained source of variance, it would be the so-called "placebo effect". It should be noted that placebo effects have a different meaning for clinical trials and for neurobiologists. In the former case, they are considered "non-specific", and contributing to the variability, "noise", in treatment responses. This effect is particularly prominent in Major Depressive Disorder (MDD), a chronic and disabling illness that nevertheless presents with ≈ 30-50% responses attributable to placebo. For the neurobiologists, however, there is now uncontroversial evidence that the cognitive-emotional integrative processes that take place in the context of positive expectations associated with a potential therapeutic intervention, induce changes in brain function and neurochemistry that are associated with symptom improvement and illness recovery. In that context, "true" neurobiological placebo responses represent potential mechanisms of resiliency and treatment response, as well as new treatment target opportunities, as will be described in this application and backed by convincing preliminary data. This application proposes to examine "non-specific" and "specific" neurobiological contributions to treatment response, objectively explaining variance by studying the function of a neurotransmitter system linked with the regulation of stress, affect and mood, but also placebo responses, the endogenous opioid system and µ-opioid receptors. We are to determine interindividual variations in the function of µ-opioid receptor-mediated neurotransmission in patients diagnosed with moderate-severe MDD and the effect of placebo and active antidepressant administrations on these mechanisms. The data acquired will determine neurobiological factors that are associated with symptom improvement across "non-specific" and "drug-specific" conditions. Contributing variables that would explain variability in these mechanisms, specifically genetic variation, biomarkers and personality trait variation will be examined and pooled to develop markers of treatment response and orient novel approaches to the conduct of clinical trials. Some of these markers, specifically those linked to functional genetic polymorphisms would also direct the examination of novel treatment approaches not currently contemplated in drug target screening.
描述(由适用提供):在科学中,当以前无法解释的现象(通常被视为噪声或测量误差)时,出现了范式的深刻变化。如果在临床医学(一种意外的方差来源)中发现了可比的现象,那将是所谓的“安慰剂效应”。应该注意的是,安慰剂作用对于临床试验和神经生物学家具有不同的含义。在前一种情况下,它们被认为是“非特异性”,并在治疗反应中有助于变异性“噪声”。这种作用在重度抑郁症(MDD)中尤为突出,这是一种慢性和致残性疾病,尽管如此,却呈现出约30-50%的反应,归因于安慰剂。然而,对于神经生物学家而言,现在有毫无争议的证据表明,在与潜在理论干预相关的积极期望的背景下发生的认知情感综合过程,诱导与症状改善和疾病恢复有关的脑功能和神经化学的变化。在这种情况下,“真”神经生物学安慰剂反应代表了弹性和治疗反应的潜在机制,以及新的治疗目标机会,如本应用中所述,并得到令人信服的初步数据的支持。应用建议对治疗反应的“非特异性”和“特定”神经生物学贡献,通过研究与压力,情感和情绪的调节的神经递质系统的功能客观地解释差异,但也安慰剂反应,以及内源性阿片类药物系统和µ-Opioid受体。我们将确定在诊断患有中度重度MDD的患者中μ-阿片受体介导的神经传递功能的个体变化以及安慰剂和主动抗抑郁药对这些机制的影响。获取的数据将确定与“非特异性”和“药物特异性”疾病的症状改善相关的神经生物学因素。将检查和汇总的贡献变量,这些变量可以解释这些机制的变异性,特别是遗传变异,生物标志物和人格特质变异,以开发治疗反应的标记和对临床试验进行的新型新颖方法。这些标记中的一些,特别是与功能性遗传多态性相关的标记也将指导对药物靶筛选中目前未考虑的新型治疗方法的检查。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
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Jon-Kar Zubieta其他文献
Jon-Kar Zubieta的其他文献
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{{ truncateString('Jon-Kar Zubieta', 18)}}的其他基金
Neurobiology of non-specific and specific treatment responses in Major Depression
重度抑郁症非特异性和特异性治疗反应的神经生物学
- 批准号:
9003106 - 财政年份:2016
- 资助金额:
$ 56.3万 - 项目类别:
Neurobiology of Placebo Effects in Fibromyalgia
纤维肌痛安慰剂效应的神经生物学
- 批准号:
8893900 - 财政年份:2014
- 资助金额:
$ 56.3万 - 项目类别:
Neurobiology of Placebo Effects in Fibromyalgia
纤维肌痛安慰剂效应的神经生物学
- 批准号:
8667689 - 财政年份:2014
- 资助金额:
$ 56.3万 - 项目类别:
Neurobiology of Placebo Effects in Fibromyalgia
纤维肌痛安慰剂效应的神经生物学
- 批准号:
9352267 - 财政年份:2014
- 资助金额:
$ 56.3万 - 项目类别:
Interaction of Smoking and Chronic Pain at Neurochemical and Phenotypic Levels
吸烟与慢性疼痛在神经化学和表型水平上的相互作用
- 批准号:
8236910 - 财政年份:2009
- 资助金额:
$ 56.3万 - 项目类别:
Predicting Placebo Responses Across Disease States
预测不同疾病状态下的安慰剂反应
- 批准号:
8089448 - 财政年份:2009
- 资助金额:
$ 56.3万 - 项目类别:
Interaction of Smoking and Chronic Pain at Neurochemical and Phenotypic Levels
吸烟与慢性疼痛在神经化学和表型水平上的相互作用
- 批准号:
7935470 - 财政年份:2009
- 资助金额:
$ 56.3万 - 项目类别:
Predicting Placebo Responses Across Disease States
预测不同疾病状态下的安慰剂反应
- 批准号:
7932818 - 财政年份:2009
- 资助金额:
$ 56.3万 - 项目类别:
Interaction of Smoking and Chronic Pain at Neurochemical and Phenotypic Levels
吸烟与慢性疼痛在神经化学和表型水平上的相互作用
- 批准号:
8610270 - 财政年份:2009
- 资助金额:
$ 56.3万 - 项目类别:
Interaction of Smoking and Chronic Pain at Neurochemical and Phenotypic Levels
吸烟与慢性疼痛在神经化学和表型水平上的相互作用
- 批准号:
8423407 - 财政年份:2009
- 资助金额:
$ 56.3万 - 项目类别:
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