Inflammation and Its Discontents: The Role of Cytokines in the Pathophysiology of Major Depression

Andrew H. Miller, Vladimir Maletic, Charles L Raison

Research output: Contribution to journalArticle

1810 Citations (Scopus)

Abstract

Recognition that inflammation may represent a common mechanism of disease has been extended to include neuropsychiatric disorders including major depression. Patients with major depression have been found to exhibit increased peripheral blood inflammatory biomarkers, including inflammatory cytokines, which have been shown to access the brain and interact with virtually every pathophysiologic domain known to be involved in depression, including neurotransmitter metabolism, neuroendocrine function, and neural plasticity. Indeed, activation of inflammatory pathways within the brain is believed to contribute to a confluence of decreased neurotrophic support and altered glutamate release/reuptake, as well as oxidative stress, leading to excitotoxicity and loss of glial elements, consistent with neuropathologic findings that characterize depressive disorders. Further instantiating the link between inflammation and depression are data demonstrating that psychosocial stress, a well-known precipitant of mood disorders, is capable of stimulating inflammatory signaling molecules, including nuclear factor kappa B, in part, through activation of sympathetic nervous system outflow pathways. Interestingly, depressed patients with increased inflammatory biomarkers have been found to be more likely to exhibit treatment resistance, and in several studies, antidepressant therapy has been associated with decreased inflammatory responses. Finally, preliminary data from patients with inflammatory disorders, as well as medically healthy depressed patients, suggest that inhibiting proinflammatory cytokines or their signaling pathways may improve depressed mood and increase treatment response to conventional antidepressant medication. Translational implications of these findings include the unique opportunity to identify relevant patient populations, apply immune-targeted therapies, and monitor therapeutic efficacy at the level of the immune system in addition to behavior.

Original languageEnglish (US)
Pages (from-to)732-741
Number of pages10
JournalBiological Psychiatry
Volume65
Issue number9
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

Depression
Cytokines
Inflammation
Antidepressive Agents
Biomarkers
Therapeutics
Neuronal Plasticity
NF-kappa B
Sympathetic Nervous System
Brain
Depressive Disorder
Mood Disorders
Neuroglia
Neurotransmitter Agents
Glutamic Acid
Immune System
Oxidative Stress
Population

Keywords

  • Cytokines
  • depression
  • excitotoxicity
  • hypothalamic-pituitary-adrenal axis
  • inflammation
  • monoamines
  • stress

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

Inflammation and Its Discontents : The Role of Cytokines in the Pathophysiology of Major Depression. / Miller, Andrew H.; Maletic, Vladimir; Raison, Charles L.

In: Biological Psychiatry, Vol. 65, No. 9, 01.05.2009, p. 732-741.

Research output: Contribution to journalArticle

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