A Dose-Finding, Biomarker Validation, and Effectiveness Study of Transcranial Magnetic Stimulation for Adolescents With Depression.

Charles P Lewis, Paul A Nakonezny, Ayse Irem Sonmez, Can Ozger, Juan F Garzon, Deniz Doruk Camsari, Deniz Yuruk, Magdalena Romanowicz, Julia Shekunov, Michael J Zaccariello, Jennifer L Vande Voort, Paul E Croarkin
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Abstract

Objective: Research and clinical application of transcranial magnetic stimulation (TMS) for adolescents with major depressive disorder (MDD) has advanced slowly. Significant gaps persist in our understanding of optimized, age-specific protocols and dosing strategies. This study aimed to compare the clinical effects of 1 Hz versus 10 Hz TMS regimens and examine a biomarker-informed treatment approach with glutamatergic intracortical facilitation (ICF).

Method: Participants with moderate-to-severe symptoms of MDD were randomized to 30 sessions of left prefrontal 1 Hz or 10 Hz TMS, stratified by baseline ICF measures. The primary clinical outcome measure was the Children's Depression Rating Scale, Revised (CDRS-R). The CDRS-R and ICF biomarker were collected weekly.

Results: Forty-one participants received either 1 Hz (n = 22) or 10 Hz (n = 19) TMS treatments. CDRS-R scores improved compared to baseline in both 1 Hz and 10 Hz groups. For participants with low ICF at baseline, the overall least squares means of CDRS-R scores over the 6-week trial showed that depressive symptom severity was lower for the group treated with 1 Hz TMS than for those who received 10 Hz TMS. There were no significant changes in weekly ICF measurements across the 6 weeks of TMS treatment.

Conclusion: Low ICF may reflect optimal glutamatergic N-methyl-d-aspartate (NMDA) receptor activity that facilitates the therapeutic effect of 1 Hz TMS through long-term depression-like mechanisms on synaptic plasticity. The stability of ICF suggests that it is a tonic, trait-like measure of NMDA receptor-mediated neurotransmission, with potential utility to inform parameter selection for therapeutic TMS in adolescents with MDD.

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经颅磁刺激治疗青少年抑郁症的剂量测定、生物标志物验证和有效性研究。
目的:针对青少年重度抑郁障碍(MDD)患者的经颅磁刺激(TMS)研究和临床应用进展缓慢。我们对优化的、针对特定年龄的方案和剂量策略的理解仍存在很大差距。本研究旨在比较1赫兹与10赫兹TMS治疗方案的临床效果,并研究谷氨酸能皮质内促进(ICF)的生物标志物治疗方法:中重度MDD症状参与者被随机分配到30个疗程的左前额叶1赫兹或10赫兹TMS治疗中,并根据基线ICF测量进行分层。主要临床结果指标是儿童抑郁量表修订版(CDRS-R)。每周收集 CDRS-R 和 ICF 生物标志物:41名参与者接受了1赫兹(22人)或10赫兹(19人)TMS治疗。与基线相比,1 赫兹和 10 赫兹组的 CDRS-R 评分均有所提高。对于基线 ICF 较低的参与者,6 周试验中 CDRS-R 评分的最小二乘法均值显示,接受 1 赫兹 TMS 治疗组的抑郁症状严重程度低于接受 10 赫兹 TMS 治疗组。在6周的TMS治疗中,每周的ICF测量值没有明显变化:低ICF可能反映了最佳的谷氨酸能N-甲基-d-天冬氨酸(NMDA)受体活性,通过对突触可塑性的长期抑郁样机制,促进了1 Hz TMS的治疗效果。ICF的稳定性表明,它是NMDA受体介导的神经递质的一种强直性、特征性测量方法,具有潜在的实用性,可为青少年多发性抑郁症患者的TMS治疗参数选择提供参考。
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来源期刊
CiteScore
21.00
自引率
1.50%
发文量
1383
审稿时长
53 days
期刊介绍: The Journal of the American Academy of Child & Adolescent Psychiatry (JAACAP) is dedicated to advancing the field of child and adolescent psychiatry through the publication of original research and papers of theoretical, scientific, and clinical significance. Our primary focus is on the mental health of children, adolescents, and families. We welcome unpublished manuscripts that explore various perspectives, ranging from genetic, epidemiological, neurobiological, and psychopathological research, to cognitive, behavioral, psychodynamic, and other psychotherapeutic investigations. We also encourage submissions that delve into parent-child, interpersonal, and family research, as well as clinical and empirical studies conducted in inpatient, outpatient, consultation-liaison, and school-based settings. In addition to publishing research, we aim to promote the well-being of children and families by featuring scholarly papers on topics such as health policy, legislation, advocacy, culture, society, and service provision in relation to mental health. At JAACAP, we strive to foster collaboration and dialogue among researchers, clinicians, and policy-makers in order to enhance our understanding and approach to child and adolescent mental health.
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