Article

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

Department of Psychiatry and Behavioural Sciences, Winship Cancer Institute, Emory University School of Medicine, 1365-C Clifton Road, Atlanta, GA 30322, USA.
Brain Behavior and Immunity (Impact Factor: 5.89). 08/2008; 22(6):870-80. DOI: 10.1016/j.bbi.2007.12.009
Source: PubMed

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.

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    • "Vitamin C also acts as a cofactor for the biosynthesis of the neurotransmitters norepinephrine, dopamine and serotonin [16] , as well as neuropeptide hormones, such as mood enhancing oxytocin [17] . Depression is often associated with fatigue and is common in Hepatitis C patients receiving interferon-alpha treatment [7] . Interestingly, depression is an early symptom of vitamin C depletion [18] and although our patient did not exhibit overt signs of depression, we and others have observed decreased depression in hypovitaminosis C individuals following supplementation with vitamin C [18] [19] . "

    Full-text · Article · Dec 2015
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    • "We therefore explored effects of aging on the glutamate response to IFN-alpha in patients with hepatitis C virus (HCV) and determined whether these effects were associated with alterations in inflammatory markers and behaviors previously shown to be altered in IFN-alpha-treated patients including tumor necrosis factor (TNF) and its soluble receptor sTNFR2, motivation, and motor activity (Capuron et al., 2012; Majer et al., 2008; Raison et al., 2010). "

    Full-text · Article · Oct 2015 · Brain Behavior and Immunity
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    • "We therefore explored effects of aging on the glutamate response to IFN-alpha in patients with hepatitis C virus (HCV) and determined whether these effects were associated with alterations in inflammatory markers and behaviors previously shown to be altered in IFN-alpha-treated patients including tumor necrosis factor (TNF) and its soluble receptor sTNFR2, motivation, and motor activity (Capuron et al., 2012; Majer et al., 2008; Raison et al., 2010). "
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    ABSTRACT: Inflammation-induced alterations in central nervous system (CNS) metabolism have focused on glutamate. At excessive concentrations, glutamate is toxic to glia and neurons, and inflammatory cytokines have been shown to influence glutamate metabolism by blocking glutamate reuptake and increasing glutamate release. Increased glutamate has also been found in depression, a disorder associated with increased inflammation. Data by our group have shown increased glutamate as measured by magnetic resonance spectroscopy (MRS) in basal ganglia and dorsal anterior cingulate cortex of patients administered the inflammatory cytokine interferon (IFN)-alpha. Given data that increasing age is associated with an exaggerated CNS inflammatory response, we examined whether older age (>55 years) would be associated with a greater IFN-alpha-induced increase in CNS glutamate. Using a longitudinal design, 31 patients with hepatitis C virus (HCV) underwent MRS, blood sampling for inflammatory markers, and behavioral assessments before (Visit1) and after four weeks (Visit 2) of either IFN-alpha (n=17) or no treatment (n=14). Older patients treated with IFN-alpha exhibited a significantly increased glutamate from Visit 1 to Visit 2 as reflected by the glutamate/creatine ratio (Glu/Cr) in left basal ganglia compared to older controls and younger IFN-alpha-treated and untreated subjects. In addition, increased Glu/Cr in older but not younger IFN-alpha-treated and untreated patients was associated with increased tumor necrosis factor, reduced motivation as measured by the Multidimensional Fatigue Inventory and increased choice movement time on the Cambridge Neuropsychological Test Automated Battery. Taken together, these preliminary data support the notion that older age may interact with inflammation to exaggerate the effects of inflammatory stimuli on CNS glutamate and behavior. Copyright © 2014. Published by Elsevier Inc.
    Full-text · Article · Dec 2014 · Brain Behavior and Immunity
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