1/4-Deciphering Mechanisms of ECT Outcomes and Adverse Effects (DECODE)

1/4-破译ECT结果和不良反应的机制（DECODE）

基本信息

批准号：
10671071
负责人：
Randall Espinoza
金额：
$ 57.18万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-01 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10671071
关键词：
Acute Address Adult Adverse effects Algorithms Amnesia Anatomy Antidepressive Agents Biological Markers Blood flow Brain Clinical Clinical Research Cognitive Collaborations Corpus striatum structure Data Disease remission Dissociation Dose Electroconvulsive Therapy Electroencephalography Ensure Executive Dysfunction Functional Magnetic Resonance Imaging Hippocampus Image Impaired cognition Individual Intervention Investigation Knowledge Magnetic Resonance Imaging Major Depressive Disorder Measures Medial Methodology Methods Modeling National Institute of Mental Health Neuronal Plasticity Outcome Patient-Focused Outcomes Patients Phenotype Prefrontal Cortex Process Prospective Studies Protocols documentation Public Health Research Infrastructure Safety Sample Size Seizures Site Spottings Standardization Structure System Testing Thalamic structure Time Weight biomarker identification cognitive benefits effective therapy electric field executive function follow-up imaging study improved magnetic resonance imaging/electroencephalography magnetic seizure therapy meter multiple data types neuroimaging noninvasive brain stimulation response response biomarker side effect therapy outcome verbal

项目摘要

Electroconvulsive therapy (ECT) is one of the most effective antidepressant non-invasive brain stimulation therapies for adults with major depression. However, a number of patients fail to respond despite adequate trials, and while clinically beneficial, ECT can produce adverse cognitive effects including amnesia, executive dysfunction, and verbal dysfluency. Previous single- and multi-site ECT-imaging investigations have been limited by insufficient sample size and/or non-standardization of methodology. Therefore, in answer to NIMH Strategic Objective 3.2 “Develop strategies for tailoring existing interventions to optimize outcomes,” our investigative teams have conducted clinical studies to develop standardized methods for acute ECT course administration, antidepressant and cognitive measures for phenotyping, optimal neuroimaging protocols and E-field modeling, and sophisticated analytic models to integrate and interpret the antidepressant-response and cognitive- impairment biomarkers. In this prospective study we propose the first investigation integrating multiple units of analysis including clinical and cognitive phenotyping, whole-brain neuroimaging, EEG, and E-field modeling to establish the mechanisms underlying ECT-induced antidepressant response (response biomarkers) and cognitive adverse effects (safety biomarkers), as well as to find the “sweet spot” of ECT dosing for optimal antidepressant benefit and cognitive safety. Adult patients with major depressive disorder (n = 230) will receive a standardized acute ECT course, complete clinical and cognitive measures and undergo structural and functional MRI at three time points (baseline, after ECT #6, and following treatment completion) and one-month naturalistic follow-up. All MRI data will be processed and harmonized identically at a central imaging core to ensure uniformity. We have three primary aims: 1) Determine the relationships between E-field strength, ictal power, and biomarkers; 2) Determine the relationships between E-field strength, biomarkers, and antidepressant outcomes; and 3) Determine the relationships between E-field strength, biomarkers, and cognitive outcomes. An exploratory aim will contrast antidepressant-response and cognitive-impairment biomarkers identified in the current proposal with magnetic seizure therapy and healthy comparison subjects. The overarching hypothesis of this investigation is that the E-field variability will explain antidepressant and cognitive outcomes. Public Health Significance: Successful completion of this project will verify the optimal ECT dose (the “sweet spot”) of 112 V/m within the right hippocampus which can then inform precision and individualization of ECT amplitude with “E-field informed ECT”. The standardized algorithms for E-field modeling can be generalized and widely disseminated. This proposal will result in a paradigm shift from “trial and error” approaches of ECT parameter selection to individualized, precision dosing to improve patient outcomes.

电休克疗法（ECT）是最有效的抗抑郁非侵入性脑刺激疗法之一然而，尽管进行了充分的试验，但仍有许多患者未能做出反应。虽然 ECT 在临床上有益，但它也会产生不良的认知影响，包括健忘症、执行力下降等。以前的单部位和多部位 ECT 成像研究受到限制。由于样本量不足和/或方法不标准化，因此，回答 NIMH 战略。目标 3.2 “制定调整现有干预措施以优化结果的策略”，我们的调查团队进行了临床研究，以开发急性 ECT 课程管理的标准化方法，用于表型分析的抗抑郁和认知措施、最佳神经影像方案和电场建模，和复杂的分析模型来整合和解释抗抑郁反应和认知反应在这项前瞻性研究中，我们提出了第一项整合多个单位的研究。分析包括临床和认知表型、全脑神经影像、脑电图和电场建模建立 ECT 诱导的抗抑郁反应的机制（反应生物标志物）和认知不良影响（安全生物标志物），以及找到 ECT 最佳剂量的“最佳点” 患有重度抑郁症的成年患者 (n = 230) 将获得抗抑郁益处和认知安全。标准化急性 ECT 课程、完整的临床和认知测量并接受结构和三个时间点（基线、ECT #6 后以及治疗完成后）和一个月的功能性 MRI 所有 MRI 数据都将在中央成像核心进行相同的处理和协调，以实现自然跟踪。确保一致性。我们有三个主要目标：1) 确定电场强度、发作期之间的关系。 2) 确定电场强度、生物标志物和抗抑郁药物之间的关系结果；3) 确定电场强度、生物标志物和认知结果之间的关系。探索性目标将对比在研究中确定的抗抑郁药反应和认知障碍生物标志物目前提出的磁癫痫治疗和健康比较受试者的总体假设。这项研究的重点是电场变异性将解释抗抑郁和认知结果。公共卫生意义：该项目的成功完成将验证最佳 ECT 剂量（“甜蜜右海马体内 112 V/m 的点”），然后可以告知 ECT 的精确性和个性化电场建模的标准化算法可以被推广和应用。该提案将导致 ECT 的“试错”方法发生范式转变。参数选择到个性化、精确剂量，以改善患者的治疗效果。