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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.

摘要电休克疗法(ECT)是最有效的抗抑郁剂非侵入性脑刺激之一。针对患有严重抑郁症的成年人的治疗。然而，尽管进行了充分的试验，但仍有一些患者没有反应，虽然ECT在临床上是有益的，但它也会产生负面的认知影响，包括健忘、执行功能障碍和语言不流畅。以前的单部位和多部位ECT成像研究都很有限由于样本量不足和/或方法不规范。因此，在回答NIMH战略目标3.2“制定调整现有干预措施的策略，以优化结果”，我们的调查团队已经进行了临床研究，以开发急性ECT疗程管理的标准化方法，表型的抗抑郁和认知措施，最佳神经成像方案和E-field建模，和复杂的分析模型来整合和解释抗抑郁剂反应和认知- 损伤生物标志物。在这项前瞻性研究中，我们提出了整合多个单位的第一项调查分析包括临床和认知表型、全脑神经成像、EEG和E-field建模，以建立ECT诱导的抗抑郁反应(反应生物标记物)和认知不良影响(安全生物标志物)，以及寻找最佳ECT剂量的“甜蜜点” 抗抑郁剂的益处和认知安全性。患有严重抑郁障碍的成年患者(n=230)将接受标准化的急性ECT疗程，完成临床和认知测量，并接受结构性和三个时间点(基线、ECT#6和治疗完成后)和一个月的功能MRI 自然主义后续行动。所有核磁共振数据将在中央成像核心进行相同的处理和协调，以确保一致性。我们有三个主要目标：1)确定电场强度、发作时间之间的关系功率和生物标志物；2)确定电场强度、生物标志物和抗抑郁剂之间的关系结果；以及3)确定电场强度、生物标记物和认知结果之间的关系。一个探索性目标将对比研究中确定的抗抑郁反应和认知障碍生物标记物目前建议采用磁疗癫痫和健康对照受试者。最重要的假设这项研究的主要结论是，电磁场的变异性将解释抗抑郁药物和认知结果。公共卫生意义：该项目的成功完成将验证ECT的最佳剂量右侧海马区112V/m的电位点“)，这可以提供ECT的精确度和个体化信息波幅与“电场知晓ECT”。用于电场建模的标准化算法可以推广到广泛传播。这一提议将导致ECT的范式转变，不再是“试错”的方法参数选择，以个性化，精确的剂量，以改善患者的结果。