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World J Psychiatry. Jul 19, 2026; 16(7): 119439
Published online Jul 19, 2026. doi: 10.5498/wjp.119439
Published online Jul 19, 2026. doi: 10.5498/wjp.119439
Divergent lymphocyte associations with depression severity and case status in first-episode, drug-naive adolescents: A multicenter study
Xi-Wang Fan, Yi-Zhe Wang, Ming-Lin Gao, Hui Zhao, Clinical Research Center for Mental Disorders, Shanghai Pudong New Area Mental Health Center, School of Medicine, Tongji University, Shanghai 200124, China
Jia-Zhe Hou, Jing Yang, Li-Juan Zhang, Health Management Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, Shanghai 201613, China
Ying Shen, Psychosomatic Medicine, The Third People’s Hospital of Ganzhou, Ganzhou 341000, Jiangxi Province, China
Dai Jian, Department of Clinical Psychology, Jiangbin Hospital of Guangxi Zhuang Autono
Qin Zhou, The Affiliated Xuzhou Eastern Hospital of Xuzhou Medical University, Xuzhou Eastern People’s Hospital, Xuzhou 221004, Jiangsu Province, China
Co-first authors: Xi-Wang Fan and Jia-Zhe Hou.
Author contributions: Fan XW contributed to methodology, formal analysis; Fan XW, Hou JZ, Wang YZ, Gao ML, and Yang J contributed to manuscript writing - review and editing; Fan XW, Hou JZ, Wang YZ, Yang J, Zhao H, and Zhang LJ participated in manuscript writing - original draft; Hou JZ was involved in data sorting, analysis, visualization; Wang YZ participated in validation; Shen Y contributed to investigation and resources; Shen Y, Jian D, and Zhou Q contributed to data curation; Jian D and Zhou Q were involved in investigation; Zhao H contributed to and supervised the study; Zhang LJ contributed to study conceptualization, supervision, project administration, and funding acquisition; Fan XW and Hou JZ contributed equally to this manuscript and are co-first authors.
AI contribution statement: During manuscript preparation, relevant language-editing tools were used solely for English-language polishing and grammatical refinement. The scientific content of the manuscript, including the study conception and design, data collection and analysis, interpretation of results, and formulation of conclusions, was completed independently by the authors and was not generated by artificial intelligence. These tools were used only to improve linguistic accuracy, clarity, and readability. They were not used for data processing, statistical analysis, result generation, or the development of academic content. Artificial intelligence tools had no role in the conception or design of the study, interpretation of findings, or any scholarly decision-making. No figures, images, or other visual materials in this manuscript were generated by artificial intelligence. We would like to emphasize that all scientific aspects of the study were conducted independently by the authors, and artificial intelligence tools were used strictly for language refinement purposes.
Supported by National Natural Science Foundation of China, No. 81872720; and the Shanghai Municipal Health Commission, No. 2023ZZ02027; and the National Clinical Key Specialty Construction Project of China, No. Z155080000004.
Institutional review board statement: The study protocol was reviewed and approved by the Ethics Committee of the Shanghai Pudong New Area Mental Health Center, Approval No.[2022] Research Review No. 011. All research activities were conducted in strict accordance with the principles of the Declaration of Helsinki and complied with relevant national and local regulatory standards to ensure the ethical conduct of research involving human participants.
Informed consent statement: Written informed consent was obtained from all participants aged 18 years or above. For participants younger than 18 years, written informed consent was obtained from a parent or legal guardian, and a written agreement for study participation was obtained from the adolescent when applicable.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author upon reasonable request.
Corresponding author: Li-Juan Zhang, PhD, Health Management Center, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, Tongji University, No. 50 Chifeng Road, Yangpu District, Shanghai 201613, China.
Received: January 29, 2026
Revised: February 22, 2026
Accepted: March 24, 2026
Published online: July 19, 2026
Processing time: 148 Days and 18.6 Hours
Revised: February 22, 2026
Accepted: March 24, 2026
Published online: July 19, 2026
Processing time: 148 Days and 18.6 Hours
Core Tip
Core Tip: This two-stage multicenter study reveals a divergent immunopurified in first-episode, drug-naive adolescents with major depressive disorder. While patients exhibited significantly lower lymphocyte counts and lymphocyte-to-monocyte ratios than healthy controls, higher levels of these markers paradoxically correlated with greater disease severity, particularly in females. A composite model integrating these indices demonstrated robust diagnostic discrimination (area under the curve = 0.82). These findings support a stage-dependent immunopsychiatric paradigm, suggesting that routine peripheral immune metrics offer a practical, objective tool for identifying major depressive disorder and stratifying severity in youth.