Neuroplasticity and the next wave of antidepressant strategies
Shawn P. Hayley, Darcy Litteljohn
Frontiers in Cellular Neuroscience 2013 DOI: 10.3389/fncel.2013.00218 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Ketamine Erythropoietin (EPO) |
| Topics | Neuroplasticity |
| Citations | 92 |
| Key findings | The authors posit that depression arises when psychological and immune stressors interact with a vulnerable genetic background to disturb BDNF and neuroplastic processes, producing reduced hippocampal neurogenesis and cortical synaptogenesis. They argue that the chronic, relapsing nature of depression stems from "faulty wiring" of emotional circuits, and that antidepressant treatments, including ketamine and potentially erythropoietin (EPO), work at least partly by modulating neuroplasticity. |
Abstract
Depression is a common chronic psychiatric disorder that is also often co-morbid with numerous neurological and immune diseases. Accumulating evidence indicates that disturbances of neuroplasticity occur with depression, including reductions of hippocampal neurogenesis and cortical synaptogenesis. Improper trophic support stemming from stressor-induced reductions of growth factors, most notably brain derived neurotrophic factor (BDNF), likely drives such aberrant neuroplasticity. We posit that psychological and immune stressors can interact upon a vulnerable genetic background to promote depression by disturbing BDNF and neuroplastic processes. Furthermore, the chronic and commonly relapsing nature of depression is suggested to stem from "faulty wiring" of emotional circuits driven by neuroplastic aberrations. The present review considers depression in such terms and attempts to integrate the available evidence indicating that the efficacy of current and "next wave" antidepressant treatments, whether used alone or in combination, is at least partially tied to their ability to modulate neuroplasticity. We particularly focus on the N-methyl-D-aspartate (NMDA) antagonist, ketamine, which already has well documented rapid antidepressant effects, and the trophic cytokine, erythropoietin (EPO), which we propose as a potential adjunctive antidepressant agent.
Comparable studies
Other narrative reviews on neuroplasticity, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| A neurotrophic hypothesis of depression: role of synaptogenesis in the actions of NMDA receptor antagonists | 2012 | Review | |
| Towards an understanding of psychedelic-induced neuroplasticity. Review of preclinical and clinical studies | 2023 | Review | |
| Buddha's Brain: Neuroplasticity and Meditation [In the Spotlight] | 2008 | Review | |
| Neuroplasticity as a convergent mechanism of ketamine and classical psychedelics | 2021 | Review | |
| Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms | 2020 | Review |
Citations in the library
Cited by 9
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review Current Neuropharmacology November 12, 2014
- Therapeutic mechanisms of psilocybin: Changes in amygdala and prefrontal functional connectivity during emotional processing after psilocybin for treatment-resistant depression Journal of Psychopharmacology January 16, 2020
- The Past and Future of Psychedelic Science: An Introduction to This Issue Journal of Psychoactive Drugs March 15, 2019
- The Effects of Daytime Psilocybin Administration on Sleep: Implications for Antidepressant Action Frontiers in Pharmacology December 3, 2020
and 4 more in the library
Cites 25
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- A Randomized Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Major Depression Archives of General Psychiatry August 1, 2006
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Ketamine Pharmacology: An Update (Pharmacodynamics and Molecular Aspects, Recent Findings) CNS Neuroscience & Therapeutics April 10, 2013
- Rapid Resolution of Suicidal Ideation After a Single Infusion of anN-Methyl-D-Aspartate Antagonist in Patients With Treatment-Resistant Major Depressive Disorder The Journal of Clinical Psychiatry July 13, 2010
and 20 more in the library