The role of circulatory systemic environment in predicting interferon-alpha-induced depression: The neurogenic process as a potential mechanism

Interferon (IFN)-alpha treatment for hepatitis C virus (HCV) is a well-recognized clinical model for inflammation-induced depression, but the brain cellular mechanisms underlying these effects are still not clear. Previous data reported an alteration in peripheral levels of inflammatory and neuroplasticity markers in the blood of depressed versus non-depressed patients. We investigated the in vitro effect of serum from depressed and non-depressed HCV patients (at baseline, before IFN-alpha; and after four weeks of IFN-alpha), on the apoptotic and neurogenic processes in a human hippocampal progenitor cells model. Results show that higher apoptosis during proliferation observed upon treatment of cells with baseline serum, and lower neuronal differentiation observed upon treatment with serum after 4 weeks of IFN-alpha, were predictive of later development of IFN-alpha induced depression (odds ratio = 1.26, p = 0.06, and = 0.80, p = 0.01, respectively). While serum after IFN-alpha increased neurogenesis compared with baseline serum, a lower increase in neurogenesis was also predictive of later development of depression (odds ratio = 0.86; p = 0.006). Our results provide evidence for the fundamental role of the systemic milieu (captured by serum samples) in the regulation of hippocampal neurogenesis by inflammation, a putative mechanism involved in the development of neuropsychiatric conditions.