Efficacy of real versus sham DLPFC-NAc rTMS for depressed adolescents with anhedonia using resting-state functional magnetic resonance imaging (fMRI): a study protocol for a randomized placebo-controlled trial

Abstract

Abstract Introduction Anhedonia is considered one of the core symptoms of major depressive disorder (MDD), which predicts adverse outcomes among adolescents, including illness severity, antidepressant refractoriness, recurrence of MDD and suicide. Patients who suffer from anhedonia have a faint response to selective serotonin reuptake inhibitors (SSRIs) and cognitive behavioral therapy (CBT). Previous research has indicated associations between anhedonia and abnormalities within the reward circuitry, highlighting the potential of the nucleus accumbens (NAc) as a viable target. Considering deep location of the NAc, repetitive transcranial magnetic stimulation (rTMS) has potential to modulate this specific region. Recent methodological advances suggest that treatment technology has significant potential in precisely targeting the left dorsolateral prefrontal cortex (DLPFC) and modulating the functional connectivity (FC) between DLPFC and NAc for adolescent patients with anhedonia. We will conduct a study to explore the safety and effectiveness of using resting-state fcMRI-guided rTMS for treating anhedonia in adolescents diagnosed with MDD. Methods and analysis This article presents a study protocol for a randomized, double-blind, placebo-controlled, parallel-group experiment. A quantity of 88 patients will be recruited and randomly assigned to receive either active rTMS or sham rTMS. The primary outcome is to determine the percentage change in the severity of anhedonia, as assessed through the Snaith-Hamilton Pleasure Scale (SHAPS), from the beginning to the end of the follow-up period (from baseline to 8 weeks after treatment). Secondary outcome measures will include fMRI measurements, Hamilton rating scale for depression (HAMD-17), Montgomery Asberg depression rating scale (MADRS), Chinese version of temporal experience of pleasure scale (CV-TEPS), Chinese version of Beck scale for suicide ideation (BSI-CV), clinical global impression (CGI) and monitoring adverse events. Assessments will be conducted at baseline, as well as at 1, 2, 4, and 8 weeks. Ethics and dissemination The study protocol received approval from the ethics committee of Xijing Hospital in September 2022 (Protocol ID: KY20222165-F-1). The study findings will be published in peer-reviewed journals. Trial registration number ClinicalTrials.gov, NCT05544071