Tardive dyskinesia-depression association in Chinese patients with chronic schizophrenia: The mediating role of insomnia and gender differences

doi:10.5498/wjp.117824

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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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Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.

World J Psychiatry. Jul 19, 2026; 16(7): 117824
Published online Jul 19, 2026. doi: 10.5498/wjp.117824

Tardive dyskinesia-depression association in Chinese patients with chronic schizophrenia: The mediating role of insomnia and gender differences

San-Rong Xiao, Qiu-Yue Yin, Jing-Min Zhu, Yan Liu, Wen-Zhi Tan, Ting Wang, Xiang-Yang Zhang

San-Rong Xiao, Yan Liu, School of Public Policy and Administration, Nanchang University, Nanchang 330031, Jiangxi Province, China

Qiu-Yue Yin, Institute of Education Development, Nanchang University, Nanchang 330031, Jiangxi Province, China

Jing-Min Zhu, Ting Wang, Department of Humanities, Jiangxi University of Chinese Medicine, Nanchang 330004, Jiangxi Province, China

Wen-Zhi Tan, School of Education, University of Queensland, Brisbane 4072, Australia

Xiang-Yang Zhang, Institute of Psychology, CAS Key Laboratory of Mental Health, Chinese Academy of Sciences, Beijing 100101, China

Co-first authors: San-Rong Xiao and Qiu-Yue Yin.

Co-corresponding authors: Ting Wang and Xiang-Yang Zhang.

Author contributions: Xiao SR and Yin QY contributed equally to this manuscript and are co-first authors. Xiao SR was responsible for the methodology; Yin QY was responsible for writing the original draft; Yin QY and Liu Y were responsible for data curation; Yin QY and Zhu JM were responsible for the formal analysis; Xiao SR and Zhu JM were responsible for validation; Tan WZ and Wang T were responsible for reviewing and editing; Wang T and Zhang XY were responsible for conceptualization, resources, supervision, and project administration as the co-corresponding authors. All authors read and agreed to the published version of the manuscript.

AI contribution statement: ChatGPT or similar AI tools are only used for limited language polishing and grammar correction during the manuscript preparation process. The main text of the manuscript (including the abstract, introduction, and all review sections) is written and revised by the author. No part of the scientific content in the manuscript is generated by AI. The AI tools are only used for language editing and improving readability. They are not used for literature selection, data analysis, content generation or manuscript writing. The AI tools did not participate in the design of the review framework, literature interpretation or the formulation of scientific conclusions. Any images, charts or graphic materials included in the manuscript were not generated by AI. All authors are fully responsible for the originality, accuracy and completeness of the manuscript.

Institutional review board statement: This study was approved by the Institutional Ethical Review Board, Institute of Psychology, Chinese Academy of Sciences (No. H18031).

Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.

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 data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request.

Corresponding author: Xiang-Yang Zhang, PhD, Postdoc, Professor, Research Fellow, Institute of Psychology, CAS Key Laboratory of Mental Health, Chinese Academy of Sciences, No. 16 Lincui Road, Chaoyang District, Beijing 100101, China. zhangxy@psych.ac.cn

Received: December 23, 2025
Revised: February 23, 2026
Accepted: April 2, 2026
Published online: July 19, 2026
Processing time: 186 Days and 9 Hours

Abstract

BACKGROUND

There is growing evidence linking tardive dyskinesia (TD) - a prevalent iatrogenic movement disorder among chronic schizophrenia patients - to the development of depressive symptomatology. However, two critical gaps remain in the existing literature on Chinese individuals diagnosed with chronic schizophrenia: (1) The potential mediating role of insomnia in the association between TD and depression has not been systematically explored; and (2) Gender-specific differences in this relationship remain understudied.

AIM

To examine the association between TD and depressive severity in Chinese individuals diagnosed with chronic schizophrenia and to explore the mediating role of insomnia and gender differences.

METHODS

This study, conducted across two psychiatric hospitals in China, recruited 669 chronic schizophrenia inpatients (68% male) using a multicenter design: Guangzhou Huiai Hospital and Wuhan Mental Health Center. Demographic and clinical data were collected. Psychopathology and symptom severity were assessed using the Positive and Negative Syndrome Scale, Hamilton Depression Rating Scale (HAMD), Insomnia Severity Index, and Abnormal Involuntary Movement Scale.

RESULTS

The prevalence of TD in this cohort was 46.6%. Compared to patients without TD, those with TD had more severe insomnia (Insomnia Severity Index score: 2 vs 1; Z = 3.262, P = 0.001) and depression (HAMD total score: 7 vs 6; Z = 2.042, P = 0.041). Insomnia was found to partially mediate the TD-depression relationship in the subsequent mediation analysis: Total effect (TD-depression) = 0.480 (P < 0.001), direct effect = 0.298 (P < 0.001; 62%), and indirect effect (via insomnia) = 0.183 (P < 0.001; 38%), with 95% confidence intervals: 0.099, 0.276, excluding zero. Gender-stratified analyses revealed that: (1) Among males, TD patients differed from non-TD patients only in HAMD diurnal variation (Z = 3.259, P = 0.001); and (2) Among females, TD patients had higher HAMD total scores (10 vs 7; Z = 2.034, P = 0.042), greater diurnal variation (Z = 4.906, P < 0.001), and more severe psychomotor retardation (Z = 2.496, P = 0.013) compared with non-TD females.

CONCLUSION

TD is associated with greater depressive severity in Chinese patients with chronic schizophrenia. Notable gender differences were observed, with females exhibiting a broader and more severe depressive symptom profile. Routine screening for insomnia and depression in patients with TD, along with gender-tailored interventions, may improve clinical outcomes.

Keywords: Tardive dyskinesia; Depression; Chronic schizophrenia; Insomnia; Mediation effect; Gender differences

Core Tip: This study of 669 Chinese patients with chronic schizophrenia demonstrates that tardive dyskinesia (TD) is associated with increased depressive severity, with insomnia partially mediating this relationship (accounting for 38% of the total effect). Gender differences were identified: Female patients with TD exhibited more severe overall depression, greater diurnal variation, and increased psychomotor retardation, whereas male patients with TD differed from non-TD males only in diurnal variation. These findings point to the critical need for systematic evaluation of insomnia and depression in the TD patient population and highlight the need for gender-specific interventions to optimize care in this vulnerable population.