A Transdiagnostic Assessment of Electroconvulsive Therapy Modulation of Anhedonia and Reward circuitry: Targets, Biomarkers and Predictors of Response

电惊厥治疗快感缺失和奖励回路调节的跨诊断评估：目标、生物标志物和反应预测因子

• 批准号: 9398707
• 负责人: Joan A Camprodon
• 金额: $ 75.1万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-05 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9398707
• 关键词: Amygdaloid structure; Anatomy; Anhedonia; Anisotropy; Anterior; Ants; Area; Behavior; Behavioral; Bilateral; Biological Markers; Biology; Bipolar Depression; Brain; Brain imaging; Clinical; Clinical Trials; Data; Diagnosis; Diffuse; Dimensions; Disease; Dorsal; Electroconvulsive Therapy; Generalized seizures; Goals; Hippocampus (Brain); Human; Image; Imaging technology; Inferior; Inferior frontal gyrus; Insula of Reil; Lead; Learning; Lobule; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Medicine; Methodology; Mood Disorders; Motivation; National Institute of Mental Health; Neurosciences; Nucleus Accumbens; Parietal; Pathologic; Pathway interactions; Patients; Positive Valence; Property; Protocols documentation; Psychiatry; Psychological reinforcement; Radial; Research Domain Criteria; Rewards; Severities; Structure of superior frontal gyrus; Subcategory; Symptoms; Syndrome; System; Therapeutic; Therapeutic Human Experimentation; Time; Unipolar Depression; Ventral Tegmental Area; base; behavior measurement; cingulate cortex; cohort; connectome; dentate gyrus; effective therapy; experience; improved; innovation; morphometry; multimodality; neuroimaging; neuropsychiatric disorder; neuroregulation; novel; pleasure; predicting response; putamen; response; reward circuitry; reward processing; stem; targeted biomarker; therapeutic target; tool; tractography; translational approach

Electroconvulsive Therapy (ECT) is the most effective treatment in psychiatry, and among the most effective in medicine. Despite its apparent non-focal effects leading to a generalized seizure, its therapeutic benefits are specific to a few clinical syndromes, including major depressive disorder (MDD) and bipolar depression (BD). These two syndromes share core deficits in reward processing (i.e. anhedonia). ECT improves anhedonia across mood disorders and syndromes, implying selective effects on the functional dynamics and structural properties of reward networks. Reward-related functions represent key behavioral dimensions of pathological relevance across neuropsychiatric disorders, and have a central place as positive valence constructs in the RDoC matrix. There has been a growing recognition that “anhedonia” does not represent a unitary dimension; among its subcategories, three constructs emerge with clear relevance to behavior and disease: consummation (liking), motivation (wanting) and reinforcement (learning). Quantitative behavioral measures exist for each of these three, with clinical validity as biomarkers and predictors of response. The anatomy of the reward network is well known, with a core in the ventral tegmental area (VTA) and the Nucleus Accumbens (NAc), and projections to cortical and subcortical nodes via the mesocorticolimbic pathway and its ramifications. The Human Connectome Project (HCP) has significantly advanced the technologies for imaging brain connections in humans, accelerating innovation in the emerging field of Connectomics. Preliminary data from our group describes the feasibility of obtaining multimodal MRI measures of reward circuit biology (morphometry, tractography, functional connectivity) in patients undergoing ECT, and extracting clinically meaningful information to identify treatment targets and develop biomarkers and predictors. At a time when therapeutic research is stalled due to the absence of clear targets and useful biomarkers, understanding the mechanisms of our most effective treatments is a priority for our field. In this study, we propose a novel translational strategy that takes advantage of the high efficacy and fast response of ECT, and uses it to probe target engagement at the circuit level. With a systems neuroscience framework, in line with NIMH strategic priorities and the RDoC Initiative, we will focus on reward circuitry and its clinical dimensions across two clinical syndromes that are commonly treated with ECT: MDD and BD. We will use HCP multimodal MRI protocols combined with validated behavioral measures of reward constructs to assess patients before, during and after ECT, in addition to a cohort of matched healthy controls that will be imaged twice. This study is innovative in its proposal to combine ECT with multimodal MRI as a framework to study anhedonia transdiagnostically, with the translational aims to (1) discover treatment targets, (2) develop biomarkers and (3) identify predictors of response.

电击疗法（ECT）是精神病学中最有效的治疗方法，也是最有效的治疗方法 在医学方面有效。尽管显而易见的非焦源作用导致了广义性癫痫发作，但其治疗 益处是一些临床综合症，包括重度抑郁症（MDD）和双极性 抑郁（BD）。这两种综合症共享核心的奖励处理（即Anhedonia）。 ect 改善跨情绪障碍和综合征的跨性别，这意味着对功能的选择性影响 奖励网络的动态和结构特性。 与奖励相关的功能代表了整个病理相关性的关键行为方面 神经精神疾病，在RDOC基质中具有正价构建体的中心位置。那里 人们越来越认识到“狂欢”并不代表统一的维度。其中 子类别，出现了三个结构，清楚地缓解了行为和疾病：消费（喜欢）， 动机（想要）和增强（学习）。每一个都存在定量行为措施 第三，具有临床有效性为生物标志物和反应的预测指标。 奖励网络的解剖结构是众所周知的，在腹侧对段区域（VTA）和 伏隔核（NAC），以及通过中皮质骨的皮质和皮质下淋巴结项目 途径及其后果。人类连接项目（HCP）已显着提高 用于成像人类大脑连接的技术，加速了新兴领域的创新 连接组学。我们小组的初步数据描述了获得多模式MRI测量的可行性 奖励电路生物学（形态计量学，拖拉术，功能连通性）的患者，并且 提取临床上有意义的信息以识别治疗目标并开发生物标志物和预测因子。 在由于没有明确的目标和有用的情况下，热研究停滞不前 生物标志物，了解我们最有效治疗的机制是我们领域的优先事项。在这个 研究，我们提出了一种新颖的翻译策略，利用了高效和快速响应的优势 ECT并使用它来探测电路级别的目标参与。使用系统神经科学框架 与NIMH的战略优先事项和RDOC倡议有关，我们将专注于奖励电路及其临床 两种临床综合征的尺寸通常用ECT治疗：MDD和BD。我们将使用 HCP多模式MRI方案与经过验证的奖励结构的行为度量相结合，以评估 ECT之前，之中和之后的患者除了将成像的一系列匹配的健康对照组 两次。这项研究具有将ECT与多模式MRI结合为研究的框架的提议中的创新性 经诊断性的Anhedonia经过转化的目的是（1）发现治疗靶标，（2）发展 生物标志物和（3）确定反应的预测指标。