Document Detail


Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.
MedLine Citation:
PMID:  23026954     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Lucile Capuron; Giuseppe Pagnoni; Daniel F Drake; Bobbi J Woolwine; James R Spivey; Ronald J Crowe; John R Votaw; Mark M Goodman; Andrew H Miller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Archives of general psychiatry     Volume:  69     ISSN:  1538-3636     ISO Abbreviation:  Arch. Gen. Psychiatry     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-02     Completed Date:  2012-12-13     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  0372435     Medline TA:  Arch Gen Psychiatry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1044-53     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Nutrition and Integrative Neurobiology, National Institute for Agricultural Research 1286 - University Victor Segalen Bordeaux, Bordeaux, France.
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MeSH Terms
Descriptor/Qualifier:
Adult
Corpus Striatum / drug effects,  physiopathology*
Dihydroxyphenylalanine / analogs & derivatives,  diagnostic use
Dopamine / metabolism*
Female
Hepatitis C, Chronic / drug therapy
Humans
Interferon-alpha / administration & dosage,  adverse effects*,  pharmacology
Magnetic Resonance Imaging / instrumentation,  methods*
Male
Mental Disorders / chemically induced,  pathology,  physiopathology
Middle Aged
Neuropsychological Tests
Positron-Emission Tomography / instrumentation,  methods*
Reward*
Grant Support
ID/Acronym/Agency:
M01 RR0039/RR/NCRR NIH HHS; MH067990/MH/NIMH NIH HHS; R01 MH083746/MH/NIMH NIH HHS; R01 MH087604/MH/NIMH NIH HHS; UL1 RR025008/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Interferon-alpha; 2C598205QX/fluorodopa F 18; 63-84-3/Dihydroxyphenylalanine
Comments/Corrections

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