SERPINE1 and depressive disorder: Depression is known to be associated with alteration of PAI-1 protein, blood coagulation, and fibrinolysis.33 Tsai et al. concluded that since PAI-1 dysregulation might be a biomarker for MDD, drugs that could decrease PAI-1 levels might help treat depression.27 Furthermore, PAI-1 may be a mediator in which MDD could precipitate CVD development via BDNF metabolism, adiposity, sleep dysregulation, and alteration of the hypothalamic-pituitary-adrenal (HPA)-axis.34