Food and Behaviour Research

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Inflammatory cytokine-associated depression

Lotrich FE (2015) Brain Res. 2015 Aug 18 1617 113-125  doi: 10.1016/j.brainres.2014.06.032. Epub 2014 Jul 5.

Web URL: View this and related abstract via PubMed here. Free full text is available online.


Inflammatory cytokines can sometimes trigger depression in humans, are often associated with depression, and can elicit some behaviors in animals that are homologous to major depression. Moreover, these cytokines can affect monoaminergic and glutamatergic systems, supporting an overlapping pathoetiology with major depression.

This suggests that there could be a specific major depression subtype, inflammatory cytokine-associated depression (ICAD), which may require different therapeutic approaches. However, most people do not develop depression, even when exposed to sustained elevations in inflammatory cytokines. Thus several vulnerabilities and sources of resilience to inflammation-associated depression have been identified. These range from genetic differences in neurotrophic and serotonergic systems to sleep quality and omega-3 fatty acid levels.

Replicating these sources of resilience as treatments could be one approach for preventing "ICAD". This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease.

  • Stress, obesity, gut flora, diet, and genetics can increase inflammation.
  • Vulnerability to inflammation can result from decreased neurotrophic support.
  • Other vulnerabilities include sleep quality, fatty acids, and genetics.
  • In vulnerable people, this leads to effects on monoamines and glutamatergic systems.
  • This can potentially result in inflammatory-cytokine associated major depression.


This review summarises the current evidence that inflammation can be a cause of depression in some individuals, exploring how this vulnerable subgroup might be identified, and outlining the implications of the latest research in this area for developing more effective treatments.

Some of the vulnerability factors and treatments for 'inflammatory depression' identified to date involve nutrition, as existing evidence shows that 
(1) low omega-3 fatty acid status can increase the risk of depression and other mood states following use of the drug interferon (which increases inflammatory cytokines)
(2) supplementation with long-chain omega-3 fatty acids can prevent interferon-induced depression in at least some individuals, as shown by clinical trials.

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