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.

电休克治疗（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之一。 在医学上有效。尽管其明显的非局灶性作用导致全身性癫痫发作，但其治疗作用 益处是特定于一些临床综合征，包括重度抑郁症（MDD）和双相情感障碍。 抑郁症（BD）。这两种综合征在奖赏处理方面有着共同的核心缺陷（即快感缺失）。ECT 改善情绪障碍和综合症中的快感缺失，这意味着对功能的选择性影响 奖励网络的动力学和结构特性。 奖励相关功能代表了病理相关性的关键行为维度 神经精神障碍，并在RDoC矩阵中具有正效价结构的中心位置。那里 越来越多的人认识到，“快感缺失”并不代表一个单一的维度; 子类别，三个结构出现了明确的相关性行为和疾病：完善（喜欢）， 动机（欲望）和强化（学习）。定量行为测量存在于每一个这些 第三，临床有效性作为生物标志物和反应的预测因素。 奖赏网络的解剖结构是众所周知的，其核心在腹侧被盖区（VTA）， 伏隔核（NAc），以及通过中皮质边缘核向皮质和皮质下结的投射 路径及其分支。人类连接组计划（HCP）大大推进了 人类大脑连接成像技术，加速新兴领域的创新， 连接组学我们小组的初步数据描述了获得多模态MRI测量的可行性 奖励回路生物学（形态测量，纤维束成像，功能连接）在接受ECT的患者中， 提取临床上有意义的信息，以确定治疗目标，并开发生物标志物和预测因子。 在治疗研究由于缺乏明确的目标和有用的药物而停滞不前的时候， 生物标志物，了解我们最有效的治疗机制是我们领域的优先事项。在这 研究中，我们提出了一种新的翻译策略，利用高效率和快速反应的优势， ECT，并使用它来探测电路级的目标接合。通过系统神经科学框架， 根据NIMH的战略重点和RDoC计划，我们将重点关注奖励回路及其临床应用。 在两个临床综合征的维度，通常用ECT治疗：MDD和BD。我们将使用 HCP多模式MRI方案结合经验证的奖励结构行为测量，以评估 ECT之前、期间和之后的患者，以及将进行成像的匹配健康对照队列 两次这项研究是创新的建议，联合收割机ECT与多模态MRI作为一个框架，研究 快感缺乏的转诊断，与翻译的目的是（1）发现治疗目标，（2）开发 生物标志物和（3）识别响应的预测因子。