Cited by 350Tryptophan and brain disordersTreatment of Major DepressionNeuroinflammation and Neurodegeneration Mechanisms

A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder

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Khairova, Rushaniya A., Machado-Vieira, Rodrigo, Du, Jing, Manji, Husseini K.·2009·The International Journal of Neuropsychopharmacology

Abstract

A growing body of data suggests that hyperactivation of the immune system has been implicated in the pathophysiology of major depressive disorder (MDD). Several pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 (IL-1) have been found to be significantly increased in patients with MDD. This review focuses on these two cytokines based on multiple lines of evidence from genetic, animal behaviour, and clinical studies showing that altered levels of serum TNF-alpha and IL-1 are associated with increased risk of depression, cognitive impairments, and reduced responsiveness to treatment. In addition, recent findings have shown that centrally expressed TNF-alpha and IL-1 play a dual role in the regulation of synaptic plasticity. In this paper, we review and critically appraise the mechanisms by which cytokines regulate synaptic and neural plasticity, and their implications for the pathophysiology and treatment of MDD. Finally, we discuss the therapeutic potential of anti-inflammatory-based approaches for treating patients with severe mood disorders. This is a promising field for increasing our understanding of the mechanistic interaction between the immune system, synaptic plasticity, and antidepressants, and for the ultimate development of novel and improved therapeutics for severe mood disorders.

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Authors
Khairova, R. A., Machado-Vieira, R., Du, J., & Manji, H. K.
Affiliations
National Institutes of Health (US)
Corresponding author
Manji, Husseini K.
Venue
The International Journal of Neuropsychopharmacology
Published
2009-02-19
Volume
12
Issue
04
Pages
561
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
OpenAlex
W2164978865
Cited by
350
References
209
Citations by year
2026: 14 · 2025: 16 · 2024: 22 · 2023: 25 · 2022: 18 · 2021: 29 · 2020: 22 · 2019: 23 · 2018: 17 · 2017: 20 · 2016: 20 · 2015: 19 · 2014: 27 · 2013: 14 · 2012: 23
FWCI
0.85
Type
journal article
Language
en
Open access
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • U.S. Department of Health and Human Services
  • National Institutes of Health
  • National Institute of Mental Health (Z01MH002835)
Topics
  • Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
major depressive disorder, inflammatory cytokines, synaptic plasticity, TNF-α, interleukin-1, neuroinflammation, cognitive impairment, treatment resistance, anti-inflammatory therapy, antidepressants
MeSH terms
Animals, Antidepressive Agents, Brain Chemistry, Depressive Disorder, Major, Major Depressive Disorder, Humans, Neuronal Plasticity, Cytokines, Mood Disorders

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