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Cited by 302Tryptophan and brain disordersStress Responses and CortisolTreatment of Major Depression

Cytokines, stress and depressive illness: Brain-immune interactions.

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Anisman, Hymie, Merali, Zul·2003·Annals of Medicine
DOI 10.1080/07853890310004075
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Abstract

Cytokines, signaling molecules of the immune system, have been implicated as a contributing factor for mood disorders such as depression. Several lines of evidence supporting this contention are briefly reviewed and caveats are introduced. Essentially, a relationship between cytokines and depression is based on the findings that: 1) proinflammatory cytokines (interleukin-1, interleukin-6, tumor necrosis factor-alpha) and bacterial endotoxins elicit sickness behaviors (e.g., fatigue, soporific effects) and symptoms of anxiety/depression that may be attenuated by chronic antidepressant treatment, 2) cytokines induce neuroendocrine and central neurotransmitter changes reminiscent of those implicated in depression, and these effects are exacerbated by stressors, 3) severe depressive illness is accompanied by signs of immune activation and by elevations of cytokine production or levels, and 4) immunotherapy, using interleukin-2 or interferon-alpha, promotes depressive symptoms that are attenuated by antidepressant treatment. It is argued that cytokine synthesis and release, elicited upon activation of the inflammatory response system, provoke neuroendocrine and brain neurotransmitter changes that are interpreted by the brain as being stressors, and contribute to the development of depression. Furthermore, such effects are subject to a sensitization effect so that a history of stressful experiences or cytokine activation augment the response to later challenges and hence the evolution of depression

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  • Selected inflammatory markers include cytokines known to be sensitive in humans to negative and positive affect.

    “our selection of inflammatory markers included cytokines known to be sensitive in humans to negative and positive affect ( Anisman & Merali, 2003; Stellar et al., 2015)”

    From Stage 2 Registered Report: Refinement of tickling protocols to improve positive animal welfare in laboratory rats (2025) · cites this paper as Anisman & Merali, 2003

    The sections “Cytokine correlates of depression” and “Depressed mood associated with cytokine therapy” link cytokine levels or secretion with depression, anxiety, and mood changes in humans. They support sensitivity to negative affect, but do not establish sensitivity to positive affect. Page numbers were not available in our copy. (LLM, conf=0.87)

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Cited by

Sorted by citations

Authors
Anisman, H., & Merali, Z.
Affiliations
University of Ottawa (CA)
ORCID
Merali, Zul
Venue
Annals of Medicine
Publisher
Informa UK Limited
Published
2003-01
Volume
35
Issue
1
Pages
2-11
ISSN
  • 0785-3890 (ISSN-L)
  • 1365-2060
DOI
10.1080/07853890310004075
OpenAlex
W2057670077
Cited by
302
References
7
Citations by year
2026: 5 · 2025: 6 · 2024: 3 · 2023: 8 · 2022: 8 · 2021: 13 · 2020: 11 · 2019: 6 · 2018: 8 · 2017: 11 · 2016: 17 · 2015: 11 · 2014: 13 · 2013: 14 · 2012: 13
FWCI
1.56
Type
journal article
Language
en
Open access
Locations
  • Annals of Medicine (publishedVersion)
  • PubMed (publishedVersion)
  • eCommons - AKU (Aga Khan University) (submittedVersion)
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
cytokines, depression, neuroimmune interactions, inflammatory cytokines, interleukin-1, interleukin-6, TNF-α, endotoxin, sickness behavior, stress, neuroendocrine changes, neurotransmitters, immune activation, immunotherapy, interleukin-2, interferon-alpha, antidepressant treatment, sensitization, mood disorders
MeSH terms
Antidepressive Agents, Depressive Disorder, Female, Humans, Male, Prognosis, Stress, Psychological, Neuroimmunomodulation, Cytokines, Risk Assessment

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