Cystatins are associated with neuronal degeneration and nervous system healing. Cystatin C (Cys C) has recently been linked to brain injury and immunological inflammation. This study aimed to determine the relationship between serum Cys C levels and depression following intracranial hemorrhage (ICH). Between September 2020 and December 2022, 337 patients with ICH were sequentially recruited and followed up for three months. The post-stroke depression (PSD) and non-PSD groups were separated based on the 17-item Hamilton Depression Rating Scale (HAMD). The PSD diagnosis was established based on the DSM-IV criteria. Cys-C levels were documented within twenty-four hours of admission. Three months after ICH, 93 (27.6%) of 337 enrolled patients were diagnosed with depression. The Cys C levels were significantly higher in depressed patients than in nondepressed patients after ICH (1.32 vs 1.01; p<0.001). After adjusting for potential confounding variables, depression after ICH was associated with the highest quartile of Cys C levels (odds ratio (OR) = 3.195, 95% CI: 1.562-6.536; p=0.001). The receiver operating characteristic curve (ROC) curve predicted that the ideal cut-off for CysC levels as a predictor of depression after ICH would be 0.730, resulting in 84.5% sensitivity and 88.4% specificity, with an area under curve (AUC) of 0.880 (95% CI: 0.843-0.917; p< 0.0001). Increased CysC concentrations were independently related to depression three months after ICH, highlighting that CysC levels at admission may be a potential biomarker for predicting the onset of depression following ICH.
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