1. Dopaminergic Mechanisms of Reduced Basal Ganglia Responses to Hedonic Reward During Interferon Alfa Administration
- Author
-
Lucile Capuron, Giuseppe Pagnoni, James R. Spivey, Daniel Drake, Mark M. Goodman, John R. Votaw, Ronald J. Crowe, Bobbi J. Woolwine, Andrew H. Miller, Nutrition et Neurobiologie intégrée (NutriNeuro), Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Modena e Reggio Emilia (UNIMORE), Emory University [Atlanta, GA], National Institute of Mental Health [MH067990], DANA Foundation, Public Health Service grant from the Clinical and Translational Science Award program [UL1 RR025008], Public Health Service grant from the General Clinical Research Center program [M01 RR0039], General Clinical Research Center program, National Institutes of Health, and National Center for Research Resources
- Subjects
Male ,SYMPTOMS ,interferon-alpha ,Dopamine ,[SDV]Life Sciences [q-bio] ,TIME UPTAKE DATA ,Neuropsychological Tests ,GRAPHICAL EVALUATION ,0302 clinical medicine ,Interferon ,Basal ganglia ,hepatitis ,reward ,immune function ,0303 health sciences ,Mental Disorders ,Putamen ,fMRI ,Middle Aged ,DEPRESSION ,Magnetic Resonance Imaging ,Dihydroxyphenylalanine ,3. Good health ,Psychiatry and Mental health ,medicine.anatomical_structure ,EARLY PARKINSONS-DISEASE ,cytokines ,dopamine ,basal ganglia ,PET ,FDOPA ,inflammation ,depression ,fatigue ,Female ,medicine.symptom ,RHESUS-MONKEYS ,Psychology ,CHRONIC HEPATITIS-C ,medicine.drug ,Adult ,medicine.medical_specialty ,Alpha interferon ,Article ,03 medical and health sciences ,Reward ,Arts and Humanities (miscellaneous) ,Internal medicine ,medicine ,Humans ,Interferon alfa ,030304 developmental biology ,CYTOKINES ,Ventral striatum ,Interferon-alpha ,Anhedonia ,Hepatitis C, Chronic ,BRAIN TRANSFER CONSTANTS ,Corpus Striatum ,Endocrinology ,Positron-Emission Tomography ,IMMUNE STIMULATION ,030217 neurology & neurosurgery - Abstract
International audience; Context: Inflammatory cytokines or cytokine inducers can alter basal ganglia activity, including reducing responsiveness to rewarding stimuli that may be mediated by cytokine effects on dopamine function. Objectives: To determine whether long-term administration of the inflammatory cytokine interferon alfa reduces the basal ganglia response to reward and whether such changes are associated with decreased presynaptic striatal dopamine function and altered behavior. Design: Cross-sectional and longitudinal studies. Setting: Outpatient research unit and neuroimaging facilities at Emory University, Atlanta, Georgia. Patients: Medically stable adults with chronic hepatitis C virus (HCV) infection eligible for interferon alfa treatment. Main Outcome Measures: Neural activity in the ventral striatum during a hedonic reward task as measured by functional magnetic resonance imaging, uptake and turnover of radiolabeled fluorodopa F 18 (F-18-dopa) in caudate and putamen using positron emission tomography, and interferon alfa-induced depression, anhedonia, fatigue, and neurotoxicity. Results: Patients with HCV receiving interferon alfa for 4 to 6 weeks (n = 14) exhibited significantly reduced bilateral activation of the ventral striatum in the win vs lose condition of a gambling task compared with patients with HCV awaiting interferon alfa treatment (n = 14). Reduced activation of the ventral striatum was, in turn, significantly correlated with anhedonia, depression, and fatigue. In a separate longitudinal study, patients with HCV treated with interferon alfa for 4 to 6 weeks (n = 12) exhibited significantly increased F-18-dopa uptake and decreased F-18-dopa turnover in caudate and putamen and in the same ventral striatal regions identified in the functional magnetic resonance imaging study. Baseline and percentage change in F-18-dopa uptake and turnover were correlated with behavioral alterations, including depression, fatigue, and neurotoxicity, during interferon alfa administration. Conclusions: These data replicate and extend findings that inflammatory stimuli, including inflammatory cytokines, such as interferon alfa, alter basal ganglia activity and behavior in association with significant changes in presynaptic striatal dopamine function consistent with decreased dopamine synthesis or release. Arch Gen Psychiatry. 2012;69(10):1044-1053
- Published
- 2012
- Full Text
- View/download PDF