Neuroinflammation through the vagus nerve-dependent gut-microbiota-brain axis in treatment-resistant depression.
Progress in Brain Research 2023 DOI: 10.1016/bs.pbr.2023.01.003 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Depression Ketamine Neuroplasticity |
| Keywords | Fecal microbiota transplantation Gut microbiota Vagus nerve stimulation |
| Key findings | The vagus nerve-dependent gut-microbiota-brain axis plays a key role in neuroinflammation and depression, and interventions like FMT, vagus nerve stimulation, and arketamine may treat TRD. |
Abstract
Neuroinflammation plays a key role in the pathogenesis of major depressive disorder (MDD), including treatment-resistant depression (TRD). Patients with TRD have higher levels of inflammatory biomarkers compared with responders to antidepressants. Multiple lines of evidence suggest that the gut-microbiota-brain axis via the vagus nerve plays a key role in neuroinflammation. Preclinical and clinical data suggest that fecal microbiota transplantation (FMT) from MDD patients or rodents with depression-like behaviors cause depression-like behaviors in rodents through systemic inflammation. Importantly, subdiaphragmatic vagotomy blocked these depression-like phenotypes and systemic inflammation in rodents after FMT of depression-related microbes. Subdiaphragmatic vagotomy also blocked the antidepressant-like effects of serotonergic antidepressants in rodents. Preclinical findings suggest that the new antidepressant, (R)-ketamine (or arketamine), may restore the altered composition of gut microbiota in rodents with depression-like behaviors, contributing to the beneficial effects of arketamine. In this chapter, the author reviews the role of the vagus nerve-dependent gut-microbiota-brain axis in depression (including TRD), and also discuss the potential of FMT, vagus nerve stimulation, and arketamine for the treatment of TRD.
Comparable studies
Other narrative reviews on ketamine for depression, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Synthesizing the Evidence for Ketamine and Esketamine in Treatment-Resistant Depression: An International Expert Opinion on the Available Evidence and Implementation Adults with treatment-resistant depression | 2021 | Review | |
| Ketamine: a paradigm shift for depression research and treatment | 2019 | Review | |
| Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective | 2019 | Review | |
| Ketamine: A tale of two enantiomers | 2020 | Review | |
| Molecular mechanisms underlying the antidepressant actions of arketamine: beyond the NMDA receptor | 2021 | Review |
Citations in the library
Cited by 15
- Are “mystical experiences” essential for antidepressant actions of ketamine and the classic psychedelics? European Archives of Psychiatry and Clinical Neuroscience February 27, 2024
- Ketamine and its two enantiomers in anesthesiology and psychiatry: A historical review and future directions Journal of Anesthesia and Translational Medicine July 11, 2024
- (R)-(-)-Ketamine: The Promise of a Novel Treatment for Psychiatric and Neurological Disorders. International Journal of Molecular Sciences June 20, 2024
- Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis. Neurobiology of Disease September 1, 2024
- A role of gut-brain axis on prophylactic actions of arketamine in male mice exposed to chronic restrain stress. Pharmacology, Biochemistry, and Behavior May 1, 2024
and 10 more in the library
Cites 25
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Translational Psychiatry September 1, 2015
- Double-Blind, Placebo-Controlled, Dose-Ranging Trial of Intravenous Ketamine as Adjunctive Therapy in Treatment-Resistant Depression (TRD) Molecular Psychiatry October 3, 2018
- Rapid‐acting antidepressant ketamine, its metabolites and other candidates: A historical overview and future perspective Psychiatry and Clinical Neurosciences June 19, 2019
- Intravenous arketamine for treatment-resistant depression: open-label pilot study European Archives of Psychiatry and Clinical Neuroscience February 20, 2020
and 20 more in the library