Feasibility, safety, and preliminary clinical efficacy of resting-state functional connectivity MRI-guided rTMS for adolescents with major depressive disorder: Protocol for a randomized, double-blind, three-arm, sham-controlled pilot trial

by Hongyi Chen, Danyu Xu, Wenjing Wang, Xinyin Luo, Xiaocong Jiang, Ningyi Wan, Yuhuan Wei, Ting Wang, Li Zhang, Xuemei Li, Xinyu Zhou

Major depressive disorder (MDD) is highly prevalent in adolescents, and a substantial proportion of patients show inadequate response or limited tolerability to first-line treatments such as selective serotonin reuptake inhibitors and cognitive behavioral therapy, highlighting the need for additional treatment options. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in adults with depression, but evidence in adolescents remains limited. Resting-state functional connectivity MRI (rs-fcMRI) may provide a circuit-informed approach for individualizing rTMS target selection within the dorsolateral prefrontal cortex (DLPFC) based on its functional connectivity with the subgenual anterior cingulate cortex (sgACC).

This is a randomized, double-blind, three-arm, sham-controlled pilot trial. Forty-five adolescents with MDD will be assigned in a 1:1:1 ratio to conventional left DLPFC-targeted rTMS, rs-fcMRI-guided rTMS targeting the individualized DLPFC site showing the strongest negative connectivity with the sgACC, or sham stimulation. Treatment will be delivered over 4 weeks. Primary outcomes will include recruitment feasibility, intervention adherence, 6-month retention, preliminary clinical efficacy, and safety, assessed by enrollment, completion of 20 treatment sessions, completion of 6-month follow-up, CDRS-R-based response and remission, and adverse events/serious adverse events. Secondary outcomes will include depressive and anxiety symptoms, suicidality, sleep quality, global clinical status and improvement, rumination, and pediatric health-related quality of life.

This pilot trial will provide preliminary evidence regarding the feasibility, acceptability, safety, and early clinical efficacy signals of rs-fcMRI-guided rTMS in adolescents with MDD. By comparing individualized circuit-informed targeting with conventional left DLPFC stimulation and sham stimulation, the study may help clarify whether this imaging-guided neuromodulation approach is practicable and clinically informative in this population. The findings are expected to support refinement of study procedures, outcome selection, and trial design for a future fully powered randomized controlled trial.Trial registration: ClinicalTrials.gov NCT07185438.

Abnormal Time and Space Experiences Among Transitional‐Age Youth With a Major Depressive Disorder: A Phenomenological Qualitative Study

ABSTRACT

Aim

To explore the abnormal experiences of time and space among transitional-age youth with major depressive disorder.

Design

A descriptive phenomenological qualitative study.

Methods and Setting

The study was conducted at a psychiatric hospital in China. Purposive sampling was used to recruit transitional-age youth with major depressive disorder. Data were collected through semi-structured interviews and analysed using Colaizzi's method.

Findings

Seventeen participants were interviewed. The abnormal experiences of time and space among transitional-age youth with major depressive disorder were synthesised into five overarching themes: (1) Disturbance of Time Order; (2) Slackening of the Flow of Time; (3) Vital Inhibition; (4) Desynchronisation of Social Rhythms; and (5) Disturbance of Lived Space.

Conclusions

This study highlights that pervasive abnormalities in temporal and spatial experiences characterise transitional-age youth with major depressive disorder. These disturbances shape their sense of self, personal development, relationships and engagement with the world, underscoring the need for interventions that address these temporal and spatial disturbances within the context of developmental transition.

Impact

This study addresses a knowledge gap regarding the subjective experience of time and space among transitional-age youth with major depressive disorder. This study highlights that transitional-age youth with major depressive disorder experience desynchronisation across temporal, spatial, bodily and social domains. Moreover, the desynchronisation of social rhythms appears to be a unique and developmentally salient challenge for transitional-age youth with major depressive disorder. These insights expand phenomenological understandings of major depressive disorder and highlight the developmental vulnerabilities of major depressive disorder as it navigates this critical life phase.

Patient or Public Contribution

Five participants were involved in reviewing and providing feedback on the interview content and results. Their contributions included enhancing the authenticity and credibility of the findings.

Reporting Method

The study followed the Consolidated Criteria for Reporting Qualitative Research guidelines.