Exploratory analysis of symptom-specific efficacy of transcranial magnetic stimulation in adolescent depression

doi:10.5498/wjp.v15.i12.111580

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World Journal of Psychiatry

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2220-3206

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Psychiatry. Dec 19, 2025; 15(12): 111580
Published online Dec 19, 2025. doi: 10.5498/wjp.v15.i12.111580

Exploratory analysis of symptom-specific efficacy of transcranial magnetic stimulation in adolescent depression

Wen-Juan Liu, Wan-Lin Chen, Hai-Si Chen

Wen-Juan Liu, Hai-Si Chen, Department of Psychosomatic Medicine, Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou 310013, Zhejiang Province, China

Wan-Lin Chen, School of Medicine, Hangzhou City University, Hangzhou 310015, Zhejiang Province, China

Co-first authors: Wen-Juan Liu and Wan-Lin Chen.

Author contributions: Liu WJ and Chen WL contributed equally to this article, they are the co-first authors of this manuscript; Chen HS revised the manuscript and provided expert consultation on the design of the study; Liu WJ, Chen WL, and Chen HS conceptualized the study and funding proposal, drafted the manuscript, and analyzed the data; and all authors critically reviewed the manuscript and approved of it in its final form.

Supported by the Hangzhou Medical and Health Science and Technology General Project, No. A20240472 and No. A20210156; the Plan Projects of Zhejiang Provincial Department of Science and Technology, No. 2025C01103; and the Major projects of Hangzhou Municipal Health Commission, No. Z20250275.

Institutional review board statement: This study was approved by the Medical Ethics Committee of Hangzhou Seventh People’s Hospital, approval No. 2025-005.

Informed consent statement: Written informed consent was obtained from parents, and written assent was obtained from all adolescent participants.

Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.

Data sharing statement: The data supporting this study’s findings are available from the corresponding author upon reasonable request.

Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/

Corresponding author: Hai-Si Chen, Department of Psychosomatic Medicine, Affiliated Mental Health Center and Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, No. 305 Tianmushan Road, Xihu District, Hangzhou 310013, Zhejiang Province, China. 834446096@qq.com

Received: July 7, 2025
Revised: August 26, 2025
Accepted: October 10, 2025
Published online: December 19, 2025
Processing time: 146 Days and 7.2 Hours

Abstract

BACKGROUND

Adolescent depression manifests through diverse, interconnected symptoms, yet the clinical profile in patients treated with repetitive transcranial magnetic stimulation (rTMS) remains inadequately characterized. While rTMS shows therapeutic potential, its efficacy may be overestimated due to limited research and symptom heterogeneity. Identifying key symptom clusters and evaluating their predictive value for treatment response is crucial for optimizing rTMS outcomes in this population.

AIM

To identify adolescent depression symptom clusters and assess their differential responses to rTMS treatment.

METHODS

One hundred adolescent patients with first-episode major depressive disorder were randomized into control and study groups. Both groups received sertraline treatment, while the study group additionally underwent 10 sessions of adjunctive rTMS. Depressive symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline, week 2, and week 4.

RESULTS

Hierarchical clustering revealed four distinct symptom clusters: Subjective mood, impaired activity, somatic concerns, and anxiety/insomnia. The main effect of treatment visit showed significant decreases in symptom severity across all clusters. In the study group, the effect size between baseline and week 4 was largest for the subjective mood cluster (Cohen’s d = 2.41) and smallest for somatic concerns (Cohen’s d = 0.59). In the control group, the largest effect size was observed in the anxiety/insomnia cluster (Cohen’s d = 1.20), with the smallest effect in impaired activity (Cohen’s d = 0.47).

CONCLUSION

This study identified four distinct symptom clusters with differential responses to rTMS treatment. The findings demonstrate that rTMS shows greatest efficacy for improving subjective mood symptoms, guiding targeted therapeutic approaches.

Keywords: Repetitive transcranial magnetic stimulation; Adolescent depression; Hierarchical clustering; Symptom clusters; Treatment response

Core Tip: This study reveals that adolescent depression consists of four distinct symptom clusters (subjective mood, impaired activity, somatic concerns, and anxiety/insomnia) which respond differentially to repetitive transcranial magnetic stimulation (rTMS). The most significant improvement was observed in the subjective mood cluster, suggesting that rTMS may be most effective for core emotional symptoms. These findings are critical for moving beyond a one-size-fits-all approach and optimizing personalized, symptom-targeted rTMS treatment strategies for adolescents.