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Cited by 2,136Tryptophan and brain disordersStress Responses and CortisolTreatment of Major Depression

The Bidirectional Relationship of Depression and Inflammation: Double Trouble

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Beurel, Eléonore, Toups, Marisa, Nemeroff, Charles B.·2020·Neuron
DOI 10.1016/j.neuron.2020.06.002PMC PMC7381373
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Abstract

Depression represents the number one cause of disability worldwide and is often fatal. Inflammatory processes have been implicated in the pathophysiology of depression. It is now well established that dysregulation of both the innate and adaptive immune systems occur in depressed patients and hinder favorable prognosis, including antidepressant responses. In this review, we describe how the immune system regulates mood and the potential causes of the dysregulated inflammatory responses in depressed patients. However, the proportion of never-treated major depressive disorder (MDD) patients who exhibit inflammation remains to be clarified, as the heterogeneity in inflammation findings may stem in part from examining MDD patients with varied interventions. Inflammation is likely a critical disease modifier, promoting susceptibility to depression. Controlling inflammation might provide an overall therapeutic benefit, regardless of whether it is secondary to early life trauma, a more acute stress response, microbiome alterations, a genetic diathesis, or a combination of these and other factors.

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  • The sustained up-regulation of the IL-17 pathway and Lcn2 in chronic stress mirrors clinical observations in patients with anxiety or depression.

    “The sustained up-regulation of the IL-17 pathway and Lcn2 in chronic stress mirrors clinical observations in patients with anxiety or depression”

    From Comparative Analysis of HPA-Axis Dysregulation and Dynamic Molecular Mechanisms in Acute Versus Chronic Social Defeat Stress (2025) · cites this paper as [60]

    In “Immune Cells > Th Cell Differentiation” (page unavailable), the review reports elevated Th17 cells in patients with major depressive disorder, elevated IL-17A in some but not all such patients, and increased IL-17A after stress in rodents. This supports an IL-17-related parallel, but our copy does not establish sustained up-regulation or a matching clinical observation for Lcn2. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Beurel, E., Toups, M., & Nemeroff, C. B.
Affiliations
  • University of Miami (US)
  • The University of Texas at Austin (US)
Corresponding author
Nemeroff, Charles B.
ORCID
Venue
Neuron
Publisher
Elsevier BV
Published
2020-07
Volume
107
Issue
2
Pages
234-256
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2020.06.002
PMC
PMC7381373
OpenAlex
W3036454441
Cited by
2,136
References
67
Citations by year
2026: 313 · 2025: 547 · 2024: 460 · 2023: 395 · 2022: 285 · 2021: 128 · 2020: 6 · 2013: 1
FWCI
13.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institutes of Health
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
depression, inflammation, major depressive disorder, immune dysregulation, innate immunity, adaptive immunity, antidepressant response, early trauma, stress response, gut microbiota, genetic susceptibility, mood regulation, disease susceptibility
MeSH terms
Affect, Antidepressive Agents, Depression, Major Depressive Disorder, Depressive Disorder, Major, Humans, Immune System, Inflammation

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