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Cited by 596Tryptophan and brain disordersStress Responses and CortisolTreatment of Major Depression

Inflammation-Induced Anhedonia: Endotoxin Reduces Ventral Striatum Responses to Reward

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Eisenberger, Naomi I., Berkman, Elliot T., Inagaki, Tristen K., Rameson, Lian T., Mashal, Nehjla M., Irwin, Michael R.·2010·Biological Psychiatry
DOI 10.1016/j.biopsych.2010.06.010PMC PMC3025604
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Abstract

Background Although inflammatory activity is known to play a role in depression, no work has examined whether experimentally induced systemic inflammation alters neural activity that is associated with anhedonia, a key diagnostic symptom of depression. To investigate this, we examined the effect of an experimental inflammatory challenge on the neural correlates of anhedonia-namely, reduced ventral striatum (VS) activity to reward cues. We also examined whether this altered neural activity related to inflammatory-induced increases in depressed mood.Methods Participants (n = 39) were randomly assigned to receive either placebo or low-dose endotoxin, which increases proinflammatory cytokine levels in a safe manner. Cytokine levels were repeatedly assessed through hourly blood draws; self-reported and observer-rated depressed mood were assessed regularly as well. Two hours after drug administration, neural activity was recorded as participants completed a task in which they anticipated monetary rewards.Results Results demonstrated that subjects exposed to endotoxin, compared with placebo, showed greater increases in self-reported and observer-rated depressed mood over time, as well as significant reductions in VS activity to monetary reward cues. Moreover, the relationship between exposure to inflammatory challenge and increases in observer-rated depressed mood was mediated by between-group differences in VS activity to anticipated reward.Conclusions The data reported here show, for the first time, that inflammation alters reward-related neural responding in humans and that these reward-related neural responses mediate the effects of inflammation on depressed mood. As such, these findings have implications for understanding risk of depression in persons with underlying inflammation.

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  • Bacterial endotoxin administration reduces neural activity in the ventral striatum.

    “bacterial endotoxin administration also reduces neural activity in the ventral striatum”

    From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Eisenberger, Berkman, et al., 2010

    The Results (Neural Responses to the MID Task) report less left ventral striatum activity in the endotoxin group than in the placebo group during reward anticipation. The claim omits that task condition and implies a general ventral striatum reduction, although the paper found no significant difference in the right ventral striatum. (LLM, conf=0.86)

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  • Cytokines decrease dopamine release in the basal ganglia, associated with decreased effort-based motivation and reduced activation of reward circuitry in the ventral striatum.

    “Dopamine has a fundamental role in motivation and motor activity, and cytokines have been shown to decrease the release of dopamine in the basal ganglia in association with decreased effort-based motivation as well as reduced activation of reward circuitry in the basal ganglia, in particular the ventral striatum89–91.”

    From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [90]

    The Results (Neural Responses to the MID Task; page not available in our copy) report reduced left ventral-striatum activity during reward anticipation after endotoxin, but no significant difference in the right ventral striatum. The Discussion says cytokine-producing agents can alter striatal monoamine levels; it does not establish decreased dopamine release or an association with decreased effort-based motivation. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Inflammatory stimuli are associated with reductions in reward responsiveness in the striatum across multiple neuroimaging platforms in otherwise non-depressed individuals given IFNα, endotoxin or typhoid vaccination.

    “Inflammatory stimuli have been associated with reductions in reward responsiveness in the striatum across many neuroimaging platforms, demonstrating the validity and reproducibility of these cytokine-mediated effects on the brain in otherwise non-depressed individuals peripherally administered IFNα, endotoxin or typhoid vaccination and imaged by PET, functional magnetic resonance imaging (fMRI), M”

    From The role of inflammation in depression: from evolutionary imperative to modern treatment target (2016) · cites this paper as [90]

    The Results report reduced ventral striatum responses to monetary reward cues after endotoxin versus placebo, and the Methods identify the imaging method as fMRI (page numbers unavailable in our copy). The paper supports the endotoxin/fMRI example, but not the broader claim of reproducibility across PET and other platforms or after IFNα or typhoid vaccination. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • Neural activity in the ventral striatum mediates the effects of endotoxin administration on increases in depressed mood, as rated by an independent observer.

    “neural activity in the ventral striatum mediated the effects of endotoxin administration on increases in depressed mood, as rated by an independent observer”

    From From stress to inflammation and major depressive disorder: A social signal transduction theory of depression. (2014) · cites this paper as Eisenberger, Berkman, et al., 2010

  • Stimulated increases in proinflammatory cytokines were associated with sickness behavior symptoms resembling affective-cognitive and somatic symptoms of depression.

    “Stimulated increases in proinflammatory cytokines were associated with symptoms such as fatigue, negative mood, anhedonia, cognitive impairment, social withdrawal, motor slowing – a variety of symptoms collectively referred to as sickness behavior and resembling those of affective-cognitive and somatic symptoms of depression (Dantzer et al., 2008; Eisenberger et al., 2010).”

    From The interplay between stress, inflammation, and emotional attention: relevance for depression (2019) · cites this paper as Eisenberger et al., 2010

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  1. [27]First MB Spitzer RL Gibbon M Williams JB 1996 Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition, Version 2.0 New York New York State Psychiatric Institute

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Authors
Eisenberger, N. I., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R.
Affiliations
  • University of California, Los Angeles (US)
  • University of Oregon (US)
  • Northwestern University (US)
Corresponding author
Eisenberger, Naomi I.
ORCID
Venue
Biological Psychiatry
Publisher
Elsevier BV
Published
2010-10
Volume
68
Issue
8
Pages
748-754
ISSN
0006-3223 (ISSN-L)
DOI
10.1016/j.biopsych.2010.06.010
PMC
PMC3025604
OpenAlex
W2053020615
Cited by
596
References
35
Citations by year
2026: 50 · 2025: 52 · 2024: 39 · 2023: 39 · 2022: 31 · 2021: 44 · 2020: 48 · 2019: 50 · 2018: 50 · 2017: 31 · 2016: 39 · 2015: 29 · 2014: 27 · 2013: 21 · 2012: 30
FWCI
7.60
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Biological Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Alliance for Research on Schizophrenia and Depression Young Investigator Award
  • Dana Foundation
  • University of California Los Angeles (UCLA)
  • postdoctoral research fellowship (T32-MH19925)
  • UCLA Integrative Study of Mood Disorders
  • UCLA Cousins Center at the Semel Institute for Neurosciences
  • UCLA Claude D. Pepper Older Americans Independence Center Inflammatory Biology Core
  • General Clinical Research Centers Program (M01-RR00865)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
inflammation, anhedonia, endotoxin, ventral striatum, reward processing, depression, inflammatory cytokines, depressive mood, mediation
MeSH terms
Adolescent, Adult, Basal Ganglia, Depression, Endotoxins, Female, Humans, Inflammation, Magnetic Resonance Imaging, Male, Placebos, Reward, Cytokines, Pleasure

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