Observational Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Sep 19, 2025; 15(9): 109858
Published online Sep 19, 2025. doi: 10.5498/wjp.v15.i9.109858
Disease duration-stratified associations of thyroid hormone levels with psychopathology in hospitalized patients with schizophrenia: A cross-sectional study
Xiu-Ping Lei, De-Xin Liao, Guo-Ying Wu, Dan Shuai, Hong-Li Zhang, Bin-You Wang, Yi-Lin Wang
Xiu-Ping Lei, De-Xin Liao, Guo-Ying Wu, Dan Shuai, Hong-Li Zhang, Department of Psychiatry, Zigong Mental Health Center, Zigong 643020, Sichuan Province, China
Bin-You Wang, Yi-Lin Wang, Zigong Institute of Brain Science, Zigong Mental Health Center, Zigong 643020, Sichuan Province, China
Co-first authors: Xiu-Ping Lei and De-Xin Liao.
Co-corresponding authors: Bin-You Wang and Yi-Lin Wang.
Author contributions: Lei XP and Liao DX designed the study, analyzed data, wrote the manuscript, they contributed equally to this article, they are the co-first authors of this manuscript; Wu GY and Shuai D collected and verified data; Zhang HL edited the drafts; Wang BY and Wang YL conceived and designed the study, interpretation and revised the manuscript, conducted and directed all steps of the study, they contributed equally to this article, they are the co-corresponding authors of this manuscript; and all authors have approved the final version of this paper.
Supported by the Zigong Key Science and Technology Plan (Collaborative Innovation Project of Zigong Institute of Brain Sciences), No. 2023-NKY-02-04, No. 2023-NKY-02-07, No. 2023-NKY-03-03, and No. 2024-NKY-02-07.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Zigong Mental Health Center, approval No. 2023024.
Informed consent statement: All study participants and their legal guardians provided written informed consent before participating in the study.
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 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: Yi-Lin Wang, MD, Senior Research Fellow, Zigong Institute of Brain Science, Zigong Mental Health Center, No. 666 Gongshu Road, Gongjing District, Zigong 643020, Sichuan Province, China. wangyilinzg0321@163.com
Received: May 26, 2025
Revised: June 20, 2025
Accepted: July 14, 2025
Published online: September 19, 2025
Processing time: 95 Days and 0.7 Hours
Abstract
BACKGROUND

Neuroendocrine dysfunction, especially involving the hypothalamic-pituitary-thyroid axis, plays a critical role in the onset and progression of schizophrenia. Alterations in thyroid stimulating hormone (TSH), triiodothyronine (T3), free T3 (FT3), thyroxine (T4), and free T4 have been implicated in this process. Although previous studies have established an association between thyroid function and psychiatric symptoms, how thyroid hormone levels vary with disease duration remains underexplored.

AIM

To investigate duration stage-specific associations between thyroid hormones and psychotic symptoms among inpatients with stable schizophrenia.

METHODS

This cross-sectional study was conducted at Zigong Mental Health Center, China, and included 237 hospitalized patients with stable schizophrenia. Participants were stratified into three groups based on disease duration: 0-10 years, 10.1-20 years, and over 20 years. Peripheral blood samples were collected to measure serum thyroid hormone levels. Psychotic symptoms were assessed using the Positive and Negative Syndrome Scale. Covariate-adjusted linear regression analyses were performed to assess the relationships between thyroid hormone levels and Positive and Negative Syndrome Scale sub-scale scores.

RESULTS

The relationship between thyroid hormones and psychotic symptoms varied by disease duration. In patients with a disease course of 0-10 years, T4 [β = -0.848; 95% confidence interval (CI): -1.564 to -0.133; P = 0.021] and FT3 (β = -2.483; 95%CI: -4.693 to -0.273; P = 0.028) levels were significantly inversely associated with general psychopathology scores. Among those with 10.1-20 years of disease, only TSH showed a significant negative correlation with general psychopathology (β = -1.429; 95%CI: -2.348 to -0.509; P = 0.003). No significant correlations were found in the > 20 years group.

CONCLUSION

The associations between thyroid hormones and psychotic symptoms vary according to the duration of schizophrenia (T4/FT3 early; TSH mid), enabling the development of stage-adapted models and management.

Keywords: Thyroid hormones; Schizophrenia; Symptom; Disease duration; Positive and Negative Syndrome Scale

Core Tip: Although associations between thyroid function and psychopathology have been demonstrated, the link with disease stage remains unclear. This study explored the relationships between thyroid function and psychiatric symptoms in different stages of the disease to elucidate stage-specific interactions, aiming to expand the understanding of neuroendocrine pathways and enable personalized management for schizophrenia.