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A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder
Open accessAbstract
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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“However, the proinflammatory cytokines IL-1, IL-6, TNF-α, and IFN-γ have been implicated in neuronal development, neuroplasticity, synaptogenesis, and tissue repair[15].”
From Neuroinflammation and cytokine abnormality in major depression: cause or consequence in that illness? (2016) · cites this paper as [15]
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Cites
A synaptic model of memory: long-term potentiation in the hippocampus
Bliss, T. V. P., & Collingridge, G. L. (1993) · Nature · doi:10.1038/361031a0 · Cited by 11,566
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
(2015) · American Journal Of Pathology · doi:10.2353/ajpath · Cited by 4,961
Cytokines sing the blues: inflammation and the pathogenesis of depression
Raison, C. L., Capuron, L., & Miller, A. H. (2006) · Trends in Immunology · doi:10.1016/j.it.2005.11.006 · Cited by 3,009
Signalling pathways of the TNF superfamily: a double-edged sword
Aggarwal, B. B. (2003) · Nature Reviews Immunology · doi:10.1038/nri1184 · Cited by 2,793
Squire, L. R., Stark, C. E. L., & Clark, R. E. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.27.070203.144130 · Cited by 2,680
Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway
HEINRICH, P. C., BEHRMANN, I., MÜLLER-NEWEN, G., SCHAPER, F., & GRAEVE, L. (1998) · Biochemical Journal · doi:10.1042/bj3340297 · Cited by 2,130
Synaptic scaling mediated by glial TNF-α
Stellwagen, D., & Malenka, R. C. (2006) · Nature · doi:10.1038/nature04671 · Cited by 1,715
The stressed hippocampus, synaptic plasticity and lost memories
Kim, J. J., & Diamond, D. M. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn849 · Cited by 1,543
Glial reduction in the subgenual prefrontal cortex in mood disorders
Öngür, D., Drevets, W. C., & Price, J. L. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.22.13290 · Cited by 1,525
Research works printed but not linked: 8
- Manji, 2001, Psychopharmacology Bulletin, 35, 5
- Zakzanis, 1998, Neuropsychiatry, Neuropsychology, and Behavioral Neurology, 11, 111
- Bielau, 2005, European Archives of Psychiatry and Neurological Sciences, 255, 401
- 10.1002/(sici)1098-2396(200002)35:23.0.co;2-p · DOI
- 10.1210/en.132.4.1569 · DOI
- 10.1002/(sici)1097-4547(19970515)48:43.0.co;2-7 · DOI
- Li, 2007, Cellular & Molecular Immunology, 4, 407
- Kubera, 2000, Polish Journal of Pharmacology, 52, 237
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Yoo, S. S., Gu, S. M., Nam, K. T., Choi, J. S., Lee, Y. S., Yeo, I. J., Yu, J. E., Kim, S., Lee, D. W., Ham, H. J., et al. (2026) · Biomolecules & Therapeutics · doi:10.4062/biomolther.2025.246
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Kalidasan, Y., Venkatesan, V., Kantipudi, S. J., & Ramachandran, I. (2026) · Pharmacogenetics and Genomics · doi:10.1097/fpc.0000000000000609
Li, A., Han, L., Guo, J., Zhang, N., Liu, R., Zhang, J., Li, X., Yuan, Z., & Cheng, J. (2026) · Neuroscience Bulletin · doi:10.1007/s12264-026-01660-z
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Metadata
- 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
- Publisher
- Oxford University Press (OUP)
- Published
- 2009-02-19
- Volume
- 12
- Issue
- 04
- Pages
- 561
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC2771334
- OpenAlex
- W2164978865
- Cited by
- 350
- References
- 212
- 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
- bronze
- doi.org
- 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 (medical) › 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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