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.