Investigating Neural and Psychotherapeutic Mediators of Placebo Response in MDD

研究 MDD 安慰剂反应的神经和心理治疗调节因素

• 批准号: 8455483
• 负责人: Christian Anthony Webb
• 金额: $ 4.71万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8455483
• 关键词: Accounting; Address; Adolescent; Adult; Anhedonia; Anterior; Antidepressive Agents; Area; Attention; Behavioral; Characteristics; Clinical Trials; Cognitive; Cognitive Therapy; Complement; Conduct Clinical Trials; Corpus striatum structure; Data; Depressed mood; Development; Disease; Dopamine; Dorsal; Educational process of instructing; Endogenous depression; Event-Related Potentials; Exhibits; Expectancy; Feedback; Fellowship; Functional disorder; Goals; Hypersensitivity; Individual; Intervention; Knowledge; Lead; Learning; Link; Literature; Major Depressive Disorder; Mediating; Mediator of activation protein; Mental Depression; Mentors; Mentorship; Meta-Analysis; Neurobiology; Outcome; Patients; Pharmaceutical Preparations; Placebo Effect; Placebos; Play; Process; Psychological reinforcement; Psychotherapeutic Processes; Psychotherapy; Recurrence; Relative (related person); Research; Research Support; Research Training; Rewards; Role; Spontaneous Remission; Symptoms; Techniques; Therapeutic; Training; Treatment outcome; United States National Institutes of Health; Work; Youth; base; cingulate cortex; density; depressive symptoms; expectation; experience; improved; indexing; interpersonal therapy; neuromechanism; patient expectation; programs; relating to nervous system; response; skills; young adult

DESCRIPTION (provided by applicant): The placebo effect has received increased attention in both the adult and youth Major Depressive Disorder (MDD) treatment literatures. Approximately 60% of the symptom improvement experienced by clinically depressed patients in studies of antidepressants or psychotherapy may be attributable to factors underlying the placebo effect (e.g., patients' expectations of symptom improvement). However, the mechanisms through which the placebo effect results in depressive symptom improvement remain poorly understood. Indeed, the National Institute of Health has called for increased research in this area (RFA-DA-12- 003, RFA-DA-12-004). A greater understanding of precisely how and why depressed patients improve in treatment could ultimately lead to the development of more effective and efficient treatments for this recurrent and highly debilitating disorder. An F32 postdoctoral fellowship would allow the applicant to investigate several promising neural and psychotherapeutic mediators of placebo response in psychotherapy for adolescent MDD. More specifically, given their role in reward mechanisms (including the expectation of reward), dopamine and the anterior cingulate cortex (ACC) may play important roles in mediating placebo response in MDD treatment. Indeed, the administration of a placebo may be conceptualized as eliciting the expectation of a particular type of reward (i.e., symptom improvement). Based on this framework, the current proposal focuses on the feedback-related negativity (FRN) and feedback-related positivity (FRP), two well-established electrophysiological indices of dopamine-mediated reinforcement learning processes, which are hypothesized to originate from dorsal ACC and striatal regions. Directly relevant to the proposed research, both FRN and FRP dysfunctions have emerged in MDD. Specifically, relative to controls, depressed adults have been characterized by larger FRN amplitude following negative feedback and blunted FRP amplitude in response to the expectation of a reward and reward outcome. Under the expert guidance of Dr. Diego Pizzagalli (primary mentor), a leader in the study of the neurobiological underpinnings of depression, the applicant will receive critical training in collecting, processing and analyzing high-density event-related potentials (ERP) data to assess these neural variables within the context of a clinical trial of MDD treatment. In addition, with regards to psychotherapeutic mechanisms that may underlie placebo response, the current study will investigate the mediating role of (1) the therapeutic alliance between therapists and patients, as well as (2) the extent to which patients acquire and utilize the central cognitive, behavioral and interpersonal skills encouraged in modern psychotherapy. Dr. John Weisz (secondary mentor) will provide key mentorship in the proper conduct of clinical trials of psychotherapy for MDD. Collectively, the proposed tailored research training plan will allow the applicant to acquire new skills and knowledge in neuroscientific approaches to depression, which will complement current expertise in psychotherapy research. PUBLIC HEALTH RELEVANCE: Despite the growing body of research supporting the efficacy of psychotherapy for the treatment of clinical depression in adolescents, very little is known regarding why and how psychotherapy works. The goal of the project is to investigate promising neurobiological and psychotherapeutic processes that may help explain why and how depressed adolescents improve in therapy. An understanding of the "active ingredients" and mechanisms of symptom improvement in depression treatment is critical, as it may ultimately lead to the development of more effective and efficient interventions for depression in youth.

描述（由申请人提供）：安慰剂效应在成人和青年主要抑郁症（MDD）治疗文献中都受到了越来越多的关注。临床上抑郁症患者在抗抑郁药或心理治疗研究中经历的症状改善的大约60％可能归因于安慰剂作用的基础因素（例如，患者对症状改善的预期）。然而，安慰剂作用导致抑郁症状改善的机制仍然鲜为人知。实际上，美国国家卫生研究院呼吁在该领域进行更多的研究（RFA-DA-12- 003，RFA-DA-12-004）。对确切的抑郁症患者的治疗方法的精确程度以及为什么最终会导致这种复发性且高度衰弱的疾病的更有效治疗的发展。 F32博士后奖学金将使申请人能够调查青少年MDD心理治疗中安慰剂反应的几个有希望的神经和心理治疗介质。更具体地说，鉴于它们在奖励机制中的作用（包括对奖励的期望），多巴胺和前扣带回皮层（ACC）可能在MDD治疗中介导安慰剂反应中起重要作用。实际上，安慰剂的给药可能被概念化为引起对特定类型奖励的期望（即症状改善）。基于此框架，当前的提案着重于与反馈相关的负效率（FRN）和与反馈相关的阳性（FRP），这是多巴胺介导的增强学习过程的两个完善的电生理指数，这些指标源自背部ACC和纹状体区域。与拟议的研究直接相关，MDD中出现了FRN和FRP功能障碍。具体而言，相对于对照组，抑郁症的成年人的特征是较大的FRN振幅在负反馈和钝化的FRP振幅后，响应了对奖励和奖励结果的期望。在研究神经生物学基础的领导者迭戈·比萨加利（Diego Pizzagalli）博士（主要导师）的专家指导下，申请人将在收集，加工和分析高密度事件相关电位（ERP）数据方面接受关键的培训，以评估MDD治疗临床试验的这些神经变量。此外，关于可能是安慰剂反应的心理治疗机制，当前的研究将调查（1）治疗师与患者之间的治疗联盟的中介作用，以及（2）患者在现代心理治疗中鼓励的中心认知，行为和人际关系的中心认知，行为和人际关系的程度。约翰·韦斯（John Weisz）博士（次要导师）将在适当的MDD心理治疗临床试验中提供关键指导。总的来说，拟议的量身定制的研究培训计划将使申请人获得抑郁症神经科学方法的新技能和知识，这将补充心理治疗研究中当前的专业知识。 公共卫生相关性：尽管越来越多的研究支持了心理治疗在青少年治疗临床抑郁症治疗临床抑郁症方面的功效，但关于为什么和心理治疗的工作原理，知之甚少。该项目的目的是调查有希望的神经生物学和心理治疗过程，这可能有助于解释青少年抑郁症的治疗方面以及如何改善治疗。对抑郁症治疗中“活跃成分”和症状改善的机制的理解至关重要，因为它最终可能导致对青年抑郁症的更有效和有效的干预措施发展。