Project Details
Description
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.
Status | Active |
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Effective start/end date | 9/10/20 → 8/31/24 |
Funding
- NATIONAL INSTITUTE OF MENTAL HEALTH: $609,917.00
- NATIONAL INSTITUTE OF MENTAL HEALTH: $598,024.00
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