TY  - JOUR
T1  - DOpaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration
AU  - Capuron L, Pagnoni G, Drake DF, et al
Y1  - 2012/10/01
N1  - 10.1001/archgenpsychiatry.2011.2094
JO  - Archives of General Psychiatry
SP  - 1044
EP  - 1053
VL  - 69
IS  - 10
N2  - 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 (18F-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 18F-dopa uptake and decreased 18F-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 18F-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.
SN  - 0003-990X
M3  - doi: 10.1001/archgenpsychiatry.2011.2094
UR  - http://dx.doi.org/10.1001/archgenpsychiatry.2011.2094
ER  -