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

TY - JOUR

T1 - The role of circulatory systemic environment in predicting interferon-alpha–induced depression

T2 - The neurogenic process as a potential mechanism

AU - Borsini, Alessandra

AU - Pariante, Carmine M.

AU - Zunszain, Patricia A.

AU - Hepgul, Nilay

AU - Russell, Alice

AU - Zajkowska, Zuzanna

AU - Mondelli, Valeria

AU - Thuret, Sandrine

PY - 2019/10

Y1 - 2019/10

N2 - Interferon (IFN)-α 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-α; and after four weeks of IFN-α), 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-α, were predictive of later development of IFN-α–induced depression (odds ratio=1.26, p=0.06, and =0.80, p=0.01, respectively). While serum after IFN-α 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.

AB - Interferon (IFN)-α 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-α; and after four weeks of IFN-α), 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-α, were predictive of later development of IFN-α–induced depression (odds ratio=1.26, p=0.06, and =0.80, p=0.01, respectively). While serum after IFN-α 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.

KW - Apoptosis

KW - Depression

KW - Hippocampal progenitor cells

KW - Inflammation

KW - Interferon-alpha

KW - Neurogenesis

KW - Serum

UR - https://www.scopus.com/pages/publications/85067552367

U2 - 10.1016/j.bbi.2019.06.018

DO - 10.1016/j.bbi.2019.06.018

M3 - Article

VL - 81

SP - 220

EP - 227

JO - Brain Behaviour and Immunity

JF - Brain Behaviour and Immunity

ER -