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

电休克疗法是目前最有效的抗抑郁非侵入性脑刺激疗法之一 治疗成人重度抑郁症。然而，尽管进行了充分的试验，许多患者仍没有反应， 虽然在临床上是有益的，但ECT可能会产生负面的认知影响，包括健忘症，执行力下降， 功能障碍和言语不流利。之前的单中心和多中心ECT成像研究受到限制 样本量不足和/或方法不标准。因此，在回答NIMH战略 目标3.2“制定战略，调整现有干预措施，以优化成果”，我们的调查 团队已经进行了临床研究，以开发急性ECT过程管理的标准化方法， 用于表型分析的抗抑郁药和认知测量，最佳神经成像方案和电场建模， 和复杂的分析模型，以整合和解释抗抑郁反应和认知， 损伤生物标志物。在这项前瞻性研究中，我们提出了第一个调查整合多个单位， 分析包括临床和认知表型、全脑神经成像、EEG和电场建模， 建立ECT诱导的抗抑郁反应的潜在机制（反应生物标志物）， 认知不良反应（安全性生物标志物），以及找到ECT剂量的“最佳点”， 抗抑郁益处和认知安全性。成年重度抑郁症患者（n = 230）将接受 标准化的急性ECT疗程，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后和治疗完成后）和一个月时的功能MRI 自然主义的后续行动。所有MRI数据将在中央成像中心进行相同的处理和协调， 确保一致性。我们有三个主要目的：1）确定电场强度，发作时间和发作次数之间的关系 功率和生物标志物; 2）确定电场强度，生物标志物和抗抑郁药之间的关系 结果;和3）确定电场强度、生物标志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志物 目前建议与磁惊厥治疗和健康对照组。总体假设 电场变异性将解释抗抑郁药和认知结果。 公共卫生意义：该项目的成功完成将验证最佳ECT剂量（“甜蜜”）。 在右侧海马内的112 V/m的“点”），然后可以告知ECT的精确性和个体化 “电场通知ECT”的振幅。用于电场建模的标准化算法可以被推广， 广泛传播。这一建议将导致从“试错”的ECT方法的范式转变 参数选择到个体化、精确给药，以改善患者结局。

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.