IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C

• Type of Material: Article
• Authors: Matthias Majer, Emory University; Leonie AM Welberg, Macmillan Publishers Limited; Lucile Capuron, Emory University; Giuseppe Pagnoni, Emory University; Charles L Raison, Emory University; Andrew H Miller, Emory University
• Language: English
• Date: 2008-08
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2008 Elsevier
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bbi.2007.12.009
• Title of Journal or Parent Work: Brain, Behavior, and Immunity
• ISSN: 0889-1591
• Volume: 22
• Issue: 6
• Start Page: 870
• End Page: 880
• Grant/Funding Information: This work was supported in part by funding from the National Institute of Mental Health (K05-MH069124, R01-HL073921, and R01-MH067990) and the Emory General Clinical Research Center (MO1-RR00039).
• Keywords: motor slowing; hepatitis C; interferon-alpha; basal ganglia; neuropsychological tests; depression; dopamine; fatigue
• Research Categories: Psychology, Behavioral; Health Sciences, Mental Health

Abstract

Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behavior. Previous studies suggest that altered basal ganglia function may contribute to IFN-alpha-induced neuropsychological and behavioural changes. To further examine IFN-alpha effects on neuropsychological functions related to basal ganglia (as well as other brain regions), and explore the relationship between altered neuropsychological function and IFN-alpha-induced depression and fatigue, a selected subset of the Cambridge Neuropsychological Test Automated Battery was administered to 32 hepatitis C patients at baseline (Visit 1) and following ~12 weeks (Visit 2) of either no treatment (n=12) or treatment with IFN-alpha plus ribavirin (n=20). Symptoms of depression and fatigue were assessed using the Montgomery-Asberg Depression Rating Scale and the Multi-Dimensional Fatigue Inventory. Compared to control subjects, patients treated with IFN-alpha/ribavirin exhibited significant decreases in motor speed as measured in the simple and five-choice movement segments of the CANTAB reaction time task and slower response times in the rapid visual information processing task, a task of sustained attention. Decreased motor speed on the five-choice movement segments of the reaction time task were in turn correlated with increased symptoms of depression and fatigue (R=0.47, p<.05 and R=0.48, p<.05, respectively). IFN-alpha/ribavirin treatment had no effects on executive function, decision time in the reaction time task, or target detection accuracy in the sustained attention task. Motor slowing and its correlation with psychiatric symptoms suggest that altered basal ganglia function may contribute to the pathogenesis of IFN-alpha-induced behavioural changes.