ArticleArchives of general psychiatry2012
Dopaminergic mechanisms of reduced basal ganglia responses to hedonic reward during interferon alfa administration.
Article in Archives of general psychiatry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07161245 (A Randomized Clinical Trial on the Improvement of Fatigue in Patients With Primary Biliary Cholangitis by Implementation of a Multimodal Rehabilitation Program and Study of Its Pathophysiological Mechanisms), which is not on this map. Cited by 242 papers, 4 of them syntheses that pooled it.
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The trial behind it
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A Randomized Clinical Trial on the Improvement of Fatigue in Patients With Primary Biliary Cholangitis by Implementation of a Multimodal Rehabilitation Program and Study of Its Pathophysiological Mechanisms
Who cites it
242 citing papers in PubMed, 4 syntheses or guidelines pooled it, 375 citations in OpenAlex.
- Psychiatric medication and physical performance parameters - Are there implications for treatment?Frontiers in psychiatry · 2022Pooled it
- Sickness and the Social Brain: Love in the Time of COVID.Frontiers in psychiatry · 2021Pooled it
- HMGB1 involved in stress-induced depression and its neuroinflammatory priming role: a systematic review.General psychiatry · 2019Pooled it
- Functional neuroanatomy of peripheral inflammatory physiology: A meta-analysis of human neuroimaging studies.Neuroscience and biobehavioral reviews · 2018Pooled it
- Effects of Dopaminergic Therapy with Levodopa (L-DOPA) on Fear and Anxiety-Related Circuits and Symptoms in Patients with Depression and Higher Inflammation.Brain, behavior, and immunity · 2026Trial
- Low-dose naltrexone as an adjunctive treatment for major depressive disorder: findings from a randomized, double-blind, placebo-controlled hybrid parallel-arm study.Frontiers in pharmacology · 2026Trial
- Inflammation-induced depressed mood and reward responsivity as a function of age in female adults: a randomized controlled trial of endotoxin.Translational psychiatry · 2025Trial
- A randomized proof-of-mechanism trial of TNF antagonism for motivational deficits and related corticostriatal circuitry in depressed patients with high inflammation.Molecular psychiatry · 2025Trial
- Sustained effects of repeated levodopa (L-DOPA) administration on reward circuitry, effort-based motivation, and anhedonia in depressed patients with higher inflammation.Brain, behavior, and immunity · 2025Trial
- Systemic inflammation enhances stimulant-induced striatal dopamine elevation in tobacco smokers.Brain, behavior, and immunity · 2022Trial
- Functional connectivity in reward circuitry and symptoms of anhedonia as therapeutic targets in depression with high inflammation: evidence from a dopamine challenge study.Molecular psychiatry · 2022Trial
- Ketamine modulates fronto-striatal circuitry in depressed and healthy individuals.Molecular psychiatry · 2021Trial
- Effects of stress-induced inflammation on reward processing in healthy young women.Brain, behavior, and immunity · 2020Trial
- Sex Differences in the Relationship Between Inflammation and Reward Sensitivity: A Randomized Controlled Trial of Endotoxin.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2019Trial
- Interferon-beta-induced changes in neuroimaging phenotypes of appetitive motivation and reactivity to emotional salience.NeuroImage. Clinical · 2019Trial
- Systemic inflammation enhances stimulant-induced striatal dopamine elevation.Translational psychiatry · 2017Trial
- Lipopolysaccharide Alters Motivated Behavior in a Monetary Reward Task: a Randomized Trial.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2017Trial
- Monocyte abundance and glycolytic reprogramming associate with motivational impairment in depression.Brain, behavior, and immunity · 2026Article
- Major Depressive Disorder and Serum Inflammatory Biomarkers as Predictors of Reward-Processing Dysfunction in an American Indian Sample.Biological psychiatry. Cognitive neuroscience and neuroimaging · 2026Article
- tVNS and obesity-related inflammation: a prospective sham-controlled randomized crossover study protocol.BMC psychology · 2026Article
182 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
contextInflammatory 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.
objectivesTo 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.
designCross-sectional and longitudinal studies.
settingOutpatient 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 measuresNeural 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.
resultsPatients 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.
conclusionsThese 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.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.