Examining the role of neuroinflammation in major depression

Psychiatry Res. 2015 Sep 30;229(1-2):27-36. doi: 10.1016/j.psychres.2015.06.009. Epub 2015 Jun 21.


Recent findings have established a connection between inflammation and major depression and specifically the role of the hypothalamic-pituitary-adrenal (HPA) axis in depression. This article reviews clinical and experimental studies examining the role of the HPA axis, HPA hyperactivity (resulting in increased cortisol levels), as well as the proinflammatory cytokines tumor necrosis factor, C-reactive protein, and the interleukins, in depressed patients. Similarly this paper will review data supporting increased cytokine levels in depression and specifically differential effects in treatment-resistant patients, as well as potentially distinguishing in particular depression subtypes. Understanding the role of the immune system and inflammation in patients with major depression is essential in order to develop efficacious treatments potentially targeting inflammation in relation to the depression in order to reduce patient symptomatology and comorbidities.

Keywords: Hypothalamic pituitary adrenal axis; Inflammation; Interleukin; Major depression; Tumor necrosis factor.

Publication types

  • Review

MeSH terms

  • C-Reactive Protein / metabolism
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / immunology*
  • Early Diagnosis
  • Humans
  • Hypothalamo-Hypophyseal System / physiopathology
  • Inflammation Mediators / blood*
  • Interleukin-6 / blood
  • Pituitary-Adrenal System / physiopathology
  • Statistics as Topic
  • Tumor Necrosis Factor-alpha / blood


  • Inflammation Mediators
  • Interleukin-6
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein