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


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] . "
    12/2015; 2(2). DOI:10.5430/crcp.v2n2p57
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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.
    Brain Behavior and Immunity 12/2014; 46. DOI:10.1016/j.bbi.2014.12.004 · 5.89 Impact Factor
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    • "reated HCV patients , Hilsabeck , Hassanein , Perry ( 2005 ) found that depression in association with poor social functioning , poor physical functioning and female gender , accounted for 68 % of the variance for fatigue . This symptom triad of depression , physical symptoms and fatigue are further exacerbated by HCV treatment with IFNa therapy ( Majer et al . , 2008 ; Raison et al . , 2009 ) . Several studies have demonstrated a relationship between pro - inflammatory cytokines activation and resulting phenomenon of ' ' sick - ness behavior ' ' , which includes symptoms of depression , lethargy , anorexia , hypersomnia , muscle and joint aches ( Dantzer , 2009 ; Naess et al . , 2012 ; Wichers et al"
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    ABSTRACT: Patients infected with chronic hepatitis C virus (HCV) commonly suffer from the triad of depression, pain and fatigue. This symptom triad in HCV is likely influenced by additional psychological and interpersonal factors, although the relationship is not clearly understood. This retrospective study aimed to characterize the relationship between attachment style and depressive and physical symptoms in the HCV-infected population. Over 18 months, 99 consecutively referred HCV infected patients were assessed with the Hamilton Depression Rating Scale (HDRS), Fatigue Severity Scale, Patient Health Questionnaire-15 for physical symptoms and the Relationship Questionnaire for attachment style. An ANOVA was used to identify differences between attachment styles and Pearson correlations were used to evaluate the association between depression, fatigue and physical symptoms. Approximately 15 % of patients in the sample had a fearful attachment style. Patients with fearful attachment style had significantly higher depressive symptoms compared to a secure attachment style (p = .025). No differences in physical and fatigue symptoms were observed between attachment styles. Further, HDRS scores were significantly associated with fatigue scores (p < .001) and physical symptoms (p < .001), reinforcing the relationship between these symptom domains in HCV-infected patients. Although depressive, physical and fatigue symptoms are inter-related in HCV-infected patients, our study results suggest that only depressive symptoms were influenced by the extremes of attachment style. Screening of relationship styles may identify at-risk HCV-infected individuals for depression who may have difficulty engaging in care and managing physical symptoms.
    Journal of Clinical Psychology in Medical Settings 10/2012; 20(2). DOI:10.1007/s10880-012-9335-y · 1.49 Impact Factor
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