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INF-alpha-induced motor slowing is associated with increased depression and fatigue in patients with chronic hepatitis C
Majer M, Welberg LAM, Capuron L, Pagnoni G, Raison CL, Miller AH
Brain Behavior and Immunity 2008;22:870-880.
Summary
This is a report from one of the 'modeling' studies conducted by the CDC CFS collaborative research group. Modeling studies conducted collaboratively with research group investigators from Emory University measure immune and neuroendocrine parameters and sleep, metabolism, mood, and cognitive responses to interferon (IFN)-α therapy for hepatitis C virus (HCV). IFN-α is a powerful immune modulator, and patients who receive IFN-α develop a CFS-like illness. Insights gained from studies of IFN-α have helped us to interpret results from field studies of CFS. In this study, we found that patients receiving IFN-α develop significant decreases in motor speed associated with a several cognitive tasks. These changes are virtually identical to what we see in persons with CFS. The findings suggest that the cognitive deficits seen in persons with CFS and those receiving IFN-α reflect altered basal ganglia function.
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 behavioral 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 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 behavioral changes.
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