Inflammatory mechanisms in major depressive disorder

Curr Opin Psychiatry. 2011 Nov;24(6):519-25. doi: 10.1097/YCO.0b013e32834b9db6.


Purpose of review: As the 'monoamine hypothesis of depression' fails to explain all aspects of major depression, additional causes are being investigated. Several observations suggest that inflammatory mechanisms pay a role in the cause of major depressive disorder (MDD). This article reviews their role in major depression.

Recent findings: Recent studies support the concept that inflammatory mechanisms play a crucial role in the pathomechanisms of major depression. Major depression shares similarities with 'sickness behavior', a normal response to inflammatory cytokines. Elevations in proinflammatory cytokines and other inflammation-related proteins in major depression were found in plasma and cerebrospinal fluid (CSF) as well as in postmortem studies. Elevated levels of proinflammatory cytokines persist after clinical symptoms of depression are in remission and can also predict the onset of a depressive episode. Antidepressant treatment can lead to a normalization of elevated cytokine levels in major depression. Finally, we understand how inflammatory mechanisms affect the metabolism of tryptophan and how nonsteroidal antiinflammatory drugs (NSAIDs) can interfere with the effects of antidepressants.

Summary: Further studies are needed to fully understand the role of inflammatory mechanisms in major depression and the potential treatment implications.

Publication types

  • Review

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Cytokines / metabolism*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / immunology
  • Depressive Disorder, Major / metabolism*
  • Humans
  • Inflammation / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antidepressive Agents
  • Cytokines