The inflammation hypothesis in geriatric depression

Int J Geriatr Psychiatry. 2011 Nov;26(11):1109-18. doi: 10.1002/gps.2672. Epub 2011 Mar 2.


Background: A large body of research has focused on "mediating mechanisms" and predisposing brain abnormalities to geriatric depression, but little is known about its etiology. This paper examines whether age-related and comorbid disease-related immune deregulation is an etiologic contributor to geriatric depression.

Methods: This article reviews findings on neuroinflammation during the aging process and depression as well as studies of anti-inflammatory actions of classical antidepressants and antidepressant actions of anti-inflammatory agents.

Results: Aging results in increased peripheral immune responses, impaired peripheral-CNS immune communication, and a shift of the CNS into a pro-inflammatory state. These exaggerated and prolonged immune responses may lead to changes in the function of emotional and cognitive networks pertinent to geriatric depression and to behavioral changes reminiscent of the depressive and cognitive symptoms of geriatric depression. Some antidepressants may reduce the expression of inflammation markers. Limited data suggest that some anti-inflammatory agents may have antidepressant properties.

Conclusions: A synthesis of available findings suggests that aging-related and comorbid disease-related inflammatory processes may promote changes in the neural systems predisposing to geriatric depression or facilitating metabolic changes that mediate depressive syndromes. The "inflammation hypothesis" in geriatric depression cannot be tested in its entirety, but it can lead to testable hypotheses and data on mechanisms by which inflammatory processes promote geriatric depression. The significance of such an effort is that it may lead to a novel treatment development model bringing to bear recent advances of anti-inflammatory pharmacology to the treatment of depressed elderly patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aged
  • Aging / immunology
  • Aging / physiology
  • Anti-Inflammatory Agents / therapeutic use
  • Antidepressive Agents / therapeutic use
  • Brain / metabolism
  • Central Nervous System / immunology
  • Central Nervous System / physiology*
  • Depressive Disorder / drug therapy
  • Depressive Disorder / immunology*
  • Depressive Disorder / pathology
  • Encephalitis / immunology*
  • Encephalitis / psychology
  • Humans
  • Inflammation Mediators / metabolism


  • Anti-Inflammatory Agents
  • Antidepressive Agents
  • Inflammation Mediators