title: Depressive symptoms following interferon-α therapy: mediated by immune-induced reductions in brain-derived neurotrophic factor?
abstract: Interferon-α (IFN-α) therapy for the treatment of hepatitis C is known to induce depressive symptoms and major depression in a substantial proportion of patients. While immune activation and disturbances in peripheral tryptophan catabolism have been implicated, the exact underlying mechanism remains unknown. A role for brain-derived neurotrophic factor (BDNF) in the pathophysiology of mood disorders has recently emerged. This study examined whether depressive symptoms over time are associated with changes in serum BDNF concentration in hepatitis C patients treated with IFN-α, and whether BDNF mediates the effects of IFN-α-induced immune activation on depressive symptoms. For this purpose, 17 hepatitis C patients received IFN-α treatment with ribavirin. Patients were assessed before and at 1, 2, 4, 8, 12 and 24 wk after start of treatment. Depressive symptoms were assessed using the Montgomery-Asberg Depression Rating Scale (MADRS). In addition, cytokine concentrations and serum BDNF levels were measured at all time-points. Serum levels of BDNF decreased during the course of treatment, and were significantly and inversely associated with total MADRS score. Furthermore, pro-inflammatory cytokine levels predicted lower subsequent BDNF levels, whereas low BDNF levels, as well as increased cytokine levels, were independently associated with the development of depressive symptoms during IFN-α treatment. These findings suggest that the effect of IFN-α-induced immune activation on depression may be explained in part by alterations in neuroprotective capacity, reflected by decreases in serum BDNF following IFN-α treatment.
authors.affiliation: Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands.
authors.forename: Gunter
authors.initials: G
authors.lastname: Kenis
authors.forename: Jos
authors.initials: J
authors.lastname: Prickaerts
authors.forename: Jim
authors.initials: J
authors.lastname: van Os
authors.forename: Ger H
authors.initials: GH
authors.lastname: Koek
authors.forename: Geert
authors.initials: G
authors.lastname: Robaeys
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Marieke
authors.initials: M
authors.lastname: Wichers
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003863:Depression / Q000139:chemically induced / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007155:Immunologic Factors / Q000009:adverse effects* / Q000627:therapeutic use; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D011569:Psychiatric Status Rating Scales; D012254:Ribavirin / Q000627:therapeutic use; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D019208:Brain-Derived Neurotrophic Factor; D016207:Cytokines; D007155:Immunologic Factors; D016898:Interferon-alpha; D012254:Ribavirin; D006854:Hydrocortisone