Serum KNG and FVIII may serve as potential biomarkers for depression.

Background: The global burden of major depressive disorder (MDD) is rising, with current diagnostic methods hindered by significant subjectivity and low inter-rater reliability. Several studies have implied underlying link between coagulation-related proteins, such as kininogen (KNG) and coagulation factor VIII (FVIII), and depressive symptoms, offering new insights into the exploration of depression biomarkers. This study aims to elucidate the roles of KNG and FVIII in depression, potentially providing a foundational basis for biomarker research in this field.

Methods: A three-part experiment was conducted: (1) we measured serum levels of KNG and FVIII in the chronic unpredictable mild stress (CUMS) model; (2) KNG adeno-associated-virus overexpression (KNG-AAV-OE) model was constructed to further investigate the roles of KNG and FVIII. Meanwhile, quantity PCR, western blotting and immunofluorescence staining detected the KNG-FVIII pathway. (3) Peripheral blood samples were gathered from healthy control (HC, N = 21), as well as first-episode drug-naive patients with MDD (FEDN-MDD, N = 21), to further confirm the association between KNG, FVIII and depression.

Results: Firstly, serum KNG and FVIII levels were significantly elevated in the CUMS model. Then, the rats exhibited pronounced depressive-like behaviors in the KNG-AAV-OE model, with corresponding increases in serum KNG and FVIII. Lastly, clinical data showed increased KNG and FVIII levels in FEDN-MDD compared to HC. Furthermore, KNG and FVIII levels exhibited a strong positive correlation with the scores of the 24-item Hamilton Depression Scale and the 14-item Hamilton Anxiety Scale.

Conclusion: To sum up, this study highlights critical roles of serum KNG and FVIII in depression and the KNG-AAV-OE may lead the augment of FVIII in serum. Consequently, our research may offer new evidence and foundation for depression biomarkers research in the future.