However, these studies have not proven the roles of endogenous HMGB1 in depression-related behaviors, as they only showed pro-depressive actions of exogenously applied HMGB1 and anti-depressive actions of non-selective inhibitors for HMGB1, such as glycyrrhizin, which binds to and inhibits not only HMGB1 but also other metabolic enzymes [14,15]. Here, HMGB1 is linked to major depressive disorder.