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

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、电流 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。

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.