The neuroprotective and neuroplastic potential of glutamatergic therapeutic drugs in bipolar disorder.
R Guglielmo, G Hasler
Neuroscience & Biobehavioral Reviews November 2022 DOI: 10.1016/j.neubiorev.2022.104906 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Interventions | Mood stabilizers Ketamine Psychedelics |
| Topics | Ketamine Neuroplasticity |
| Keywords | Bipolar disorder Glutamate Mood stabilizers Neuroprotection Psychedelics |
| Key findings | Argues that evidence from animal, post-mortem, imaging, pharmacological, and genome-wide association studies increasingly implicates the glutamate system in the pathophysiology of mood disorders, and that bipolar disorder has been re-conceptualized as a synaptic plasticity-related disorder. The authors contend that a paradigm shift from the monoamine hypothesis to a glutamate-focused neuroplasticity hypothesis may advance the search for new drugs and therapies, and they discuss glutamatergic mechanisms proposed to underlie the neuroprotective and neuroplastic effects of classic mood stabilizers, ketamine, and psychedelics. |
Abstract
The monoamine hypothesis has dominated research on the pathophysiology of mood disorders as well as the development of therapeutic drugs by over half a century. Nowadays a change of perspective is taking place. The glutamate system is increasingly implicated in the pathophysiology of mood disorders. The evidence spans from animal, post-mortem, imaging, pharmacological and genome-wide association studies. Bipolar disorder has been recently re-conceptualized as a synaptic plasticity-related disorder rather than simply as a result of deficits or excesses in individual neurotransmitters. A paradigm shift from a monoamine hypothesis to a neuroplasticity hypothesis focused on glutamate may represent a substantial advancement in the research for new drugs and therapies. In this review we summarize data from clinical and pre-clinical studies that have addressed glutamatergic alterations in bipolar disorder. Along with an in-depth discussion of glutamatergic alterations in bipolar disorder, we also report available data on the neuroprotective and neuroplastic potential of the classic mood stabilizers, ketamine, and psychedelics. The glutamatergic mechanisms underlying the efficacy of these drugs are described and discussed.
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
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- A Randomized Add-on Trial of an N-methyl-D-aspartate Antagonist in Treatment-Resistant Bipolar Depression Archives of General Psychiatry August 1, 2010
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Ketamine and Rapid-Acting Antidepressants: A Window into a New Neurobiology for Mood Disorder Therapeutics Annual Review of Medicine October 23, 2014
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
and 27 more in the library