Given that IL-6 levels are increased in major depression (Maes et al. 1995a; Słuzewska et al. 1995; Frommberger et al. 1997; Liu et al. 2012), the findings on increased sIL-6R levels in melancholia may suggest that this phenotype is accompanied by increased IL-6 trans-signaling (Maes et al. 2014). Here, IL6R is linked to major depressive disorder.