A Randomized Controlled Trial of Sequential Bilateral Accelerated Theta Burst Stimulation in Adolescents with Suicidal Ideation Associated with Major Depressive Disorder

项目摘要/摘要 自杀是全世界青少年死亡的主要原因，也是世界上一个重大的公共卫生问题。 美国。尽管做出了以前的努力，但与青少年自杀有关的结果在过去几年中并没有改善。 好几年了。标准的临床和研究方法包括预防努力、风险评估、危机 干预和心理治疗技术。此前很少有研究集中于开发基于大脑的 抑郁症青少年主动自杀意念的治疗和生物标记物。从概念上讲， 前额叶皮质γ-氨基丁酸(GABA)抑制功能失调可能导致功能减退 青少年抑郁症患者自杀念头和行为的控制。经颅磁刺激 (TMS)前额叶皮质的治疗方案调节GABA抑制功能，突触 可塑性和抑郁症的临床症状。提供Theta Burst刺激的加速TMS方案 (TBS)给药诱导突触可塑性快速改变，调节GABA功能，具有快速作用临床 效果，并克服了标准TMS的许多实际限制。先前的研究与生物标记物 被称为长间隔皮质抑制(LICI)的GABA活性显示出临床应用的潜力 评估自杀风险并指导TMS的治疗干预。LICI患者的肌电检测 很容易收集，并在青少年中进行了广泛的研究。LICI的措施与 脑电(EEG)可以提供更精确和更复杂的GABA抑制措施 功能。然而，使用脑电进行LICI测量存在方法学上的挑战，而且没有先前的数据 在患有抑郁症的青少年中。本研究为随机、双盲、假对照序贯试验。 双侧加速TBS(ATBS)治疗重度抑郁障碍(MDD)青少年的自杀意念。全 受试者(双臂)将同时接受标准护理治疗。三个TBS会议将是 每日给药10天(每周5天)，共30次。在每个TBS会话期间， 连续TBS首先被传递到右侧背外侧前额叶皮质，然后间歇性TBS被 传递到左侧背侧前额叶皮质。建议的TBS参数是从以前的工作中采用的 在青少年中。对照组每天接受3次双侧假TBS治疗，共10次 几天。本研究将检验序贯双侧ATBS的安全性、可行性和临床效果。这个 主要的临床结果将在10天的治疗和第二年的哥伦比亚大学评估 自杀严重程度评定量表意念严重程度分量表。研究小组将收集事前和事后的 治疗LICI通过肌电测量来评估自杀风险并指导TBS方案的治疗。并发 使用脑电的LICI措施将解决进一步开发和完善LICI生物标记物的探索性目标。 现有的基础设施和协作将促进顺序双边的快速临床实施 ATBS和皮质抑制生物标志物。

PROJECT SUMMARY/ABSTRACT Suicide is a leading cause of death in adolescents worldwide and a substantial public health problem in the United States. Despite prior efforts, outcomes related to suicide in adolescents are not improving over the years. Standard clinical and research approaches involve prevention efforts, risk assessment, crisis intervention, and psychotherapeutic techniques. Few prior studies have focused on developing brain-based treatments and biomarkers for active suicidal ideation in adolescents with depression. Conceptually, dysregulations in prefrontal cortex gamma-aminobutyric acid (GABA) inhibitory function could lead to reduced control of suicidal thoughts and behaviors in adolescents with depression. Transcranial magnetic stimulation (TMS) treatment protocols delivered to the prefrontal cortex modulate GABA inhibitory function, synaptic plasticity, and clinical symptoms of depression. Accelerated TMS protocols that deliver theta burst stimulation (TBS) dosing induce synaptic plasticity changes rapidly, modulate GABA function, have rapid-acting clinical effects, and overcome the many practical limitations of standard TMS. Prior research with a biomarker of GABA activity called long-interval cortical inhibition (LICI) demonstrates potential for clinical implementation to assess suicide risk and guide treatment interventions with TMS. Electromyography (EMG) measures of LICI are easily collected and have been studied extensively in adolescents. Measures of LICI with electroencephalography (EEG) may provide more precise and sophisticated measures of GABA inhibitory function. However, there are methodologic challenges with the use of EEG for LICI measures and no prior data in adolescents with depression. This study is a randomized, double-blind, sham-controlled trial of sequential bilateral accelerated TBS (aTBS) for suicidal ideation in adolescents with major depressive disorder (MDD). All subjects (in both arms) will concurrently receive standard of care treatment. Three TBS sessions will be administered daily for 10 days (5 days per week) for a total of 30 sessions. During each TBS session, continuous TBS is first delivered to the right dorsolateral prefrontal cortex and then intermittent TBS is delivered to the left dorsolateral prefrontal cortex. The proposed TBS parameters were adopted from prior work in adolescents. The comparison group will receive 3 daily sessions of bilateral sham TBS treatment for 10 days. This study will examine the safety, feasibility, and clinical effects of sequential bilateral aTBS. The primary clinical outcome will be assessed over 10 days of treatment and the following year with the Columbia Suicide Severity Rating Scale severity of ideation subscale. The research team will collect pre- and post- treatment LICI measures with EMG to assess suicide risk and guide treatment with TBS protocols. Concurrent LICI measures with EEG will address an exploratory aim to further develop and refine LICI biomarkers. Existing infrastructure and collaborations will foster the rapid clinical implementation of sequential bilateral aTBS and cortical inhibition biomarkers.