title: Insights from interferon-α-related depression for the pathogenesis of depression associated with inflammation.
abstract: Interferon-α (IFN-α) is a pleiotropic cytokine that is administered as a therapeutic in highly prevalent medical conditions such as chronic hepatitis C and B virus infection, melanoma and lymphoma. IFN-α induces, to a clinically relevant degree, concentration, memory, drive and mood disturbances in almost half of all patients. For this reason, IFN-α is increasingly being replaced by more specifically acting drugs. In the past decades, IFN-α has offered a valuable insight into the pathogenesis of major depression, particularly in settings associated with inflammation. IFN-α triggers immune responses, hypothalamo-pituitary-adrenal axis abnormalities and disturbances of brain metabolism resembling those in other depression states. IFN-α stimulates indoleamine-2,3 dioxygenase-1, activating the kynurenine pathway with reduced formation of the neurotransmitters serotonin and dopamine, excessive formation of the NMDA agonist quinolinic acid, and reduced formation of the NMDA antagonist kynurenic acid. In addition, IFN-α disturbs neurotrophic signaling and impedes neurite outgrowth, synaptic plasticity, endogenous neurogenesis and neuronal survival. Consequently, IFN-α-related depression may represent a model for the neurodegenerative changes that are noticed in late-life major depression. Indeed, the observation that brain responses in IFN-α-related depression resemble idiopathic depression is supported by the existence of common genetic signatures, among which of note, a number of neuronal survival and plasticity genes have been identified. In view of the high incidence of depressive symptoms, IFN-α-related depression is an attractive model for studying links between neuronal plasticity, neurodegeneration and depression. We predict that in the latter areas new targets for anti-depressant therapies could be identified, which may deepen our understanding of idiopathic major depression.
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Germany.
authors: Carolina
authors: C
authors: Hoyo-Becerra
authors: Department of Gastroenterology and Hepatology, University Hospital Essen, Germany.
authors: Joerg F
authors: JF
authors: Schlaak
authors: Department of Neurology, University Hospital Essen, Germany. Electronic address: dirk.hermann@uk-essen.de.
authors: Dirk M
authors: DM
authors: Hermann
mesh_terms: D016207:Cytokines / Q000276:immunology; D003866:Depressive Disorder / Q000139:chemically induced / Q000209:etiology* / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000150:complications* / Q000276:immunology; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D016898:Interferon-alpha
keywords: Cytokine; Dopamine; Glutamate; Neurogenesis; Neuronal degeneration; Neuronal plasticity; Serotonin