Although the use of recombinant human IFN-α2b in establishing a murine model of IFN-α-induced depression remains controversial [59, 60], we found that the administration of high-dose recombinant human IFN-α2b over a long period did induce depressive-like behaviors and led to distinct neuroinflammatory changes in some emotion-related regions of the brain. Here, IFNA1 is linked to major depressive disorder.