Inflammation, stress and depression: An exploration of ketamine's therapeutic profile. Issue 4 (April 2023)

• Record Type: Journal Article
• Authors: Johnston, Jenessa N.; Greenwald, Maximillian S.; Henter, Ioline D.; Kraus, Christoph; Mkrtchian, Anahit; Clark, Neil G.; Park, Lawrence T.; Gold, Philip; Zarate, Carlos A.; Kadriu, Bashkim
• Is Part Of: Drug discovery today. Volume 28:Issue 4(2023)
• Publication Date: 2023-04
• Subjects: Ketamine -- depression -- stress -- inflammation -- treatment-resistant depression -- anhedonia; Drugs -- Design -- Periodicals; Drugs -- Research -- Periodicals; 615.1
• DOI: 10.1016/j.drudis.2023.103518
• Languages: English
• ISSNs: 1359-6446

Abstract

Highlights: Chronic stress, depression and inflammation have been consistently linked. Stress-induced inflammatory states can contribute to treatment resistance. Ketamine could be uniquely placed to target inflammation. Ketamine's effects can be mediated through the HPA axis or kynurenine pathway. Anti-inflammatory antidepressant therapies could improve treatment resistance. Abstract : Well-established animal models of depression have described a proximal relationship between stress and central nervous system (CNS) inflammation – a relationship mirrored in the peripheral inflammatory biomarkers of individuals with depression. Evidence also suggests that stress-induced proinflammatory states can contribute to the neurobiology of treatment-resistant depression. Interestingly, ketamine, a rapid-acting antidepressant, can partially exert its therapeutic effects via anti-inflammatory actions on the hypothalamic–pituitary adrenal (HPA) axis, the kynurenine pathway or by cytokine suppression. Further investigations into the relationship between ketamine, inflammation and stress could provide insight into ketamine's unique therapeutic mechanisms and stimulate efforts to develop rapid-acting, anti-inflammatory-based antidepressants.