Glutamate and GABA Systems in the Pathophysiology of Major Depression and Antidepressant Response to Ketamine
Marc S. Lener, Mark J. Niciu, E. Ballard, Minkyung Park, Lawrence T. Park, Allison C. Nugent, Carlos A. Zarate
Biological Psychiatry May 12, 2016 DOI: 10.1016/j.biopsych.2016.05.005 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Intervention | Ketamine |
| Dose | subanesthetic dose |
| Topics | Depression Esketamine Ketamine |
| Key findings | The authors propose that depression involves disrupted excitatory and inhibitory neurotransmission and neuronal plasticity, with altered glutamate and GABA linked to network dysfunction, and that ketamine's antidepressant response occurs partly by reversing these neurochemical and physiological disturbances. They argue future research should combine neuroimaging approaches to identify biologically homogeneous subgroups and treatment-response biomarkers of glutamatergic modulation. |
Abstract
In patients with major depressive disorder (MDD) or bipolar disorder (BD), abnormalities in excitatory and/or inhibitory neurotransmission and neuronal plasticity may lead to aberrant functional connectivity patterns within large brain networks. Network dysfunction in association with altered brain levels of glutamate (Glu) and gamma-aminobutyric acid (GABA) have been identified in both animal and human studies of depression. In addition, evidence of an antidepressant response to subanesthetic dose ketamine has led to a collection of studies that have examined neurochemical (e.g. glutamatergic and GABA-ergic) and functional imaging correlates associated with such an effect. Results from these studies suggest that an antidepressant response in association with ketamine occurs, in part, by reversing these neurochemical/physiological disturbances. Future studies in depression will require a combination of neuroimaging approaches from which more biologically homogeneous subgroups can be identified, particularly with respect to treatment response biomarkers of glutamatergic modulation.
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 55
- Ketamine: A tale of two enantiomers Journal of Psychopharmacology November 6, 2020
- Ketamine and depression: a narrative review Drug Design, Development and Therapy August 1, 2019
- Fast-acting antidepressant activity of ketamine: highlights on brain serotonin, glutamate, and GABA neurotransmission in preclinical studies. Pharmacology & Therapeutics July 1, 2019
- Glutamatergic Neurotransmission: Pathway to Developing Novel Rapid-Acting Antidepressant Treatments The International Journal of Neuropsychopharmacology November 14, 2018
- Ketamine treatment for depression: a review Discover Mental Health April 15, 2022
and 50 more in the library
Cites 26
- 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
- Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial American Journal of Psychiatry August 28, 2013
- Ketamine Anesthesia & Analgesia November 1, 1998
- Ketamine and Other NMDA Antagonists: Early Clinical Trials and Possible Mechanisms in Depression American Journal of Psychiatry October 1, 2015
and 21 more in the library