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.

电击疗法（ECT）是最有效的抗抑郁药之一的非侵入性脑刺激之一重度抑郁症的成年人的疗法。但是，许多患者未能对优选的适当试验做出反应，尽管在临床上有益，但ECT可以产生不良的认知影响，包括失忆症，执行功能障碍和言语失调。以前的单位和多站点ECT成像研究受到限制通过不足的样本量和/或方法的非标准化。因此，回答NIMH战略目标3.2“制定策略来调整现有干预措施以优化结果”，我们的调查团队已经进行了临床研究，以开发标准化的急性ECT课程的方法，表型，最佳神经影像协议和电子场建模的抗抑郁药和认知度量，以及复杂的分析模型，以整合和解释抗抑郁药反应和认知 - 损害生物标志物。在这项前瞻性研究中，我们提出了第一个整合多个单位的投资分析包括临床和认知表型，全脑神经影像学，脑电图和电子场建模建立ECT诱导的抗抑郁反应（反应生物标志物）和认知不良反应（安全生物标志物），并找到ECT剂量的“最佳点”以达到最佳抗抑郁药的益处和认知安全。大抑郁症患者（n = 230）将接受标准化的急性ECT课程，完整的临床和认知测量以及进行结构和三个时间点的功能性MRI（基线，ECT＃6之后以及治疗完成后）和一个月自然主义后续行动。所有MRI数据将在中央成像核心的处理和协调与确保统一。我们有三个主要目的：1）确定电子场强度，ICTAL之间的关系力量和生物标志物； 2）确定电子场强度，生物标志物和抗抑郁药之间的关系结果； 3）确定电子场强度，生物标志物和认知结果之间的关系。一个探索目的将对比抗抑郁药反应和认知障碍生物标志物。磁性癫痫疗法和健康比较对象的当前建议。总体假设这项投资的是，电子场的可变性将解释抗抑郁和认知结果。公共卫生的意义：成功完成该项目将验证最佳剂量（“甜蜜右海马内的112 V/m的点”，然后可以为ECT的精确和个性化提供信息带有“电子火场通知”的放大器。可以推广用于电子场建模的标准化算法，并且广泛传播。该建议将导致ECT的“反复试验”方法的范式转变参数选择为个性化的精确剂量，以改善患者的预后。