Research Article

Depressive symptoms following interferon-α therapy: mediated by immune-induced reductions in brain-derived neurotrophic factor?

Gunter Kenis^a1a2a7, Jos Prickaerts^a2a7, Jim van Os^a1a7, Ger H. Koek^a3, Geert Robaeys^a4a5a6, Harry W. M. Steinbusch^a2a7 and Marieke Wichers^a1a7 c1

^a1 Department of Psychiatry and Neuropsychology, South Limburg Mental Health Research and Teaching Network, EURON, Maastricht University, Maastricht, The Netherlands

^a2 Department of Psychiatry and Neuropsychology, Section Cellular Neuroscience, Brain and Behaviour Institute, EURON, Maastricht University, Maastricht, The Netherlands

^a3 Department of Internal Medicine, Division of Gastroenterology and Hepatology, Academic Hospital Maastricht, Maastricht, The Netherlands

^a4 Department of Gastroenterology & Hepatology, Ziekenhuis Oost-Limburg, Genk, Belgium

^a5 Department of Hepatology, UZ Leuven, Belgium

^a6 Faculty of Medicine, Hasselt University, Belgium

^a7 European Graduate School of Neuroscience, Maastricht, The Netherlands

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.

(Received February 04 2010)

(Reviewed May 18 2010)

(Accepted June 22 2010)

(Online publication July 29 2010)

Key Words:

• Brain-derived neurotrophic factor;
• cytokine;
• hepatitis C, interferon-α;
• major depressive disorder

Correspondence:

^c1 Address for correspondence: Dr M. Wichers, Department of Psychiatry and Neuropsychology, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands. Tel.: +31-43-3688669 Fax: +31-43-3688689 Email: m.wichers@sp.unimaas.nl