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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：
Jon-Kar Zubieta
金额：
$ 56.3万
依托单位：
UNIVERSITY OF UTAH
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：
https://reporter.nih.gov/project-details/9341382
关键词：
Acute Affect Affective Amygdaloid structure Anterior Antidepressive Agents Area Back Behavioral Biological Biological Markers Brain Chronic Clinical Clinical Medicine Clinical Trials Cognitive Conduct Clinical Trials Cues Data Development Diagnosis Dopamine Double-Blind Method Double-blind trial Drug Targeting Ego Emotional Expectancy Genetic Polymorphism Genetic Variation Hydrocortisone Individual Intervention Learning Link Maintenance Major Depressive Disorder Measurement Measures Medial Mediating Moods Neurobiology Neurotic Disorders Neurotics Neurotransmitters Noise Nucleus Accumbens Opioid Receptor Patients Peripheral Personality Traits Personality inventories Pharmaceutical Preparations Placebo Effect Placebos Predictive Value Process Psychophysics Randomized Controlled Trials Recovery Regulation Reporting Rewards Science Selective Serotonin Reuptake Inhibitor Source Stimulus Stress Structure Symptoms System Testing Thalamic structure Therapeutic Therapeutic Agents Therapeutic Effect Therapeutic Intervention Transcend Treatment outcome Variant active method antidepressant effect arm biomarker discovery comparative effectiveness design effectiveness trial emotion regulation endogenous opioids expectation experience inflammatory marker inter-individual variation neurochemistry neurotransmission novel novel strategies open label predictive of treatment response public health relevance randomized placebo controlled trial relating to nervous system resilience response screening symptomatic improvement theories trait treatment 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.