Inflammation, stress and depression: an exploration of ketamine’s therapeutic profile
J. Johnston, Maximillian Greenwald, I. Henter, C. Kraus, A. Mkrtchian, Neil G Clark, Lawrence T. Park, P. Gold, C. Zarate, B. Kadriu
Drug Discovery Today February 1, 2023 DOI: 10.1016/j.drudis.2023.103518 via Semantic Scholar
Summary
Stress triggers inflammation in the brain, a pattern also seen in the blood of people with depression. This stress-induced inflammation may contribute to treatment-resistant depression. The rapid-acting antidepressant ketamine works partly by reducing inflammation through effects on the HPA axis, the kynurenine pathway, or by suppressing cytokines. Understanding the link between ketamine, inflammation, and stress could reveal how ketamine works and lead to new rapid-acting antidepressants that target inflammation.
Study at a glance
| Characteristics | Review Peer reviewed |
|---|---|
| Keywords | Medicine Psychology |
| Citations | 64 |
| Key finding | Ketamine's antidepressant effects may be partly due to its anti-inflammatory actions on the HPA axis, kynurenine pathway, or cytokine suppression, and stress-induced inflammation may contribute to treatment-resistant depression. |
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.