Altered serum MMP-9, TIMP-1, and IGFBP-1 concentrations in chronic male schizophrenia patients: associations with illness duration and cognitive impairments

Background Dysregulation of neuroplasticity contributes to the pathogenesis of schizophrenia. Matrix metalloproteinases (MMPs) and endogenous tissue MMP inhibitors (TIMPs) are key regulators of extracellular matrix (ECM) remodeling essential for neuroplasticity, while insulin-like growth factor binding protein-1 (IGFBP-1) modulates ECM dynamics through integrin receptor signaling and MMP-mediated proteolysis. The current study investigated potential abnormalities in serum MMP-9, TIMP-1, and IGFBP-1 concentrations as biomarkers of ECM dysfunction among long-term hospitalized male schizophrenia patients and assessed associations with clinical characteristics. Methods Serum MMP-2, MMP-9, TIMP-1, and IGFBP-1 concentrations were compared between 80 male schizophrenia patients hospitalized for ≥5 years and 59 age-matched healthy male controls. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS) and cognitive functions using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Correlations between serum measurements and scores on the PANSS and RBANS were assessed while controlling for multiple covariates. Results Serum TIMP-1 concentration was significantly lower in the patient group ( Z =-2.547, P  = 0.012). Conversely, patients exhibited significantly elevated serum MMP-9 ( Z =-2.067, P  = 0.039), MMP-9/TIMP-1 ratio ( Z =-2.195, P  = 0.028), and IGFBP-1 ( Z =-5.994, P < 0.001). Serum IGFBP-1 concentration negatively correlated with RBANS immediate memory subscore ( r =-0.240, P  = 0.024), and elevated IGFBP-1 was identified as an independent risk factor for long-term hospitalization ( RR  = 2.257, P  < 0.001, 95%CI:1.571–3.243). Serum TIMP-1 concentration also positively correlated with illness duration ( r  = 0.376, P  = 0.001). Conclusions Long-term hospitalized male schizophrenia patients exhibit an ECM remodeling imbalance associated with memory impairment and predictive of chronic disease status. Therefore, molecules regulating ECM dynamics may be effective therapeutic targets for schizophrenia.