Identification of preventive biomarkers associated with circadian rhythms in traumatic brain injury-mediated depression: Expression of SERPINE1 protein and bioinformatics analysis.

Traumatic brain injury (TBI) represents the leading cause of trauma-related mortality, with depression being the most common psychiatric condition following TBI. Although disruptions in circadian rhythms and clock genes have been linked to both conditions, their precise regulatory mechanisms remain unclear. Identifying circadian rhythm-related genes is critical for the prevention and diagnosis of TBI and depression. This study employs Mendelian Randomization (MR) analysis to establish a positive correlation between TBI and depression. Using Weighted Gene Co-expression Network Analysis (WGCNA) on Gene Expression Omnibus (GEO) datasets derived from TBI and depression tissue samples, we identified 99 shared genes functionally linked to circadian rhythms. Furthermore, machine learning algorithms and Receiver Operating Characteristic (ROC) curve analysis identified SERPINE1 as a key diagnostic biomarker for both TBI and depression. In vivo and in vitro experiments further demonstrated that TBI often triggers the development of depression. Suppressing SERPINE1 expression reduced Claudin-1 and BDNF protein levels, alleviating TBI and depressive symptoms. Our findings indicate that SERPINE1 overexpression, which is positively correlated with neutrophil levels, may increase the risk of depression following TBI by disrupting circadian rhythms. This positions SERPINE1 as a critical predictive and diagnostic biomarker for TBI-mediated depression.