title: IFN-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C.
abstract: Interferon (IFN)-alpha has been used to investigate pathways by which innate immune cytokines influence the brain and behaviour. 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 approximately 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 Multidimensional 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 was in turn correlated with increased symptoms of depression and fatigue (R=0.47, p<0.05 and R=0.48, p<0.05, 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.
authors.affiliation: Department of Psychiatry and Behavioural Sciences, Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Road, Atlanta, GA 30322, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Majer
authors.forename: Leonie A M
authors.initials: LA
authors.lastname: Welberg
authors.forename: Lucile
authors.initials: L
authors.lastname: Capuron
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pagnoni
authors.forename: Charles L
authors.initials: CL
authors.lastname: Raison
authors.forename: Andrew H
authors.initials: AH
authors.lastname: Miller
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use; D001479:Basal Ganglia / Q000187:drug effects / Q000503:physiopathology; D003863:Depression / Q000139:chemically induced* / Q000503:physiopathology; D005221:Fatigue / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D005500:Follow-Up Studies; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D011446:Prospective Studies; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data; D011930:Reaction Time / Q000187:drug effects; D012044:Regression Analysis; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012254:Ribavirin