Exploring the potential antidepressant mechanisms of TNFα antagonists

Kyle J. Brymer, Raquel Romay-Tallon, Josh Allen, Hector J. Caruncho, Lisa E. Kalynchuk

Research output: Contribution to journalReview ArticleResearchpeer-review

34 Citations (Scopus)


Human and animal studies suggest an intriguing relationship between the immune system and the development of depression. Some peripherally produced cytokines, such as TNF-α, can cross the blood brain barrier and result in activation of brain microglia which produces additional TNF-α and fosters a cascade of events including decreases in markers of synaptic plasticity and increases in neurodegenerative events. This is exemplified by preclinical studies, which show that peripheral administration of pro-inflammatory cytokines can elicit depression-like behavior. Importantly, this depression-like behavior can be ameliorated by anti-cytokine therapies. Work in our laboratory suggests that TNF-α is particularly important for the development of a depressive phenotype and that TNF-α antagonists might have promise as novel antidepressant drugs. Future research should examine rates of inflammation at baseline in depressed patients and whether anti-inflammatory agents could be included as part of the treatment regimen for depressive disorders.

Original languageEnglish
Article number98
Number of pages9
JournalFrontiers in Neuroscience
Issue number2
Publication statusPublished - 2019
Externally publishedYes


  • Antidepressant
  • Cytokines
  • Depression
  • Hippocampus
  • Inflammation
  • Rat
  • Stress
  • TNF-α

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