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REVIEW

The neurobiological mechanism underlying ketamine’s rapid-acting antidepressant effect

Yingying Yin1,2* ,  Yonggui Yuan1,2*
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1 Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Jiangsu Provincial Key Laboratory of Brain Science and Medicine, Southeast University, Nanjing, China
2 Institute of Psychosomatics, Medical School of Southeast University, Nanjing, Jiangsu Province, China
JCBP 2024, 2(3), 2596 https://doi.org/10.36922/jcbp.2596
Submitted: 31 December 2023 | Accepted: 24 May 2024 | Published: 15 July 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Depression is one of the most common disabling mental disorders. However, first-line treatments for depression are typically slow-acting. Ketamine, a glutamatergic modulator with rapid antidepressant effects, has proven effective in treating both refractory depression and suicidal tendencies. The neurobiological mechanisms underlying the effects of antidepressants have become a research hotspot; yet, the exact processes remain unclear. Brain imaging studies have provided important evidence from macroscopic perspectives, such as brain structure and function, while biochemical studies have made significant discoveries from microscopic perspectives, including proteomics and genomics. Previous reviews have summarized a broad range of biomarkers related to the ketamine response, encompassing studies in imaging, electrophysiology, metabolism, immunology, genetics, and neurotrophy. In this review, we systematically summarize a number of potential biomarkers for predicting and modulating the efficacy of ketamine, from both macroperspectives (such as neuroimaging and neuroelectrophysiological markers) and microperspectives (such as neurobiochemical and genetic markers). Although research in this area is still in its infancy, these biomarkers can help clinicians identify whether ketamine intervention is needed for treatment-resistant depression, thereby reducing the burden on patients and society. However, the majority of biomarkers are still in the preclinical exploratory stage, and existing findings are limited. To realize the clinical application of these biomarkers, future studies should combine biomarkers of different types to investigate the relationships and interactions between them. This approach aims to optimize clinical outcomes by enhancing the involvement of biological targets in new models.

Keywords
Depression
Ketamine
Rapid-acting
Biomarker
Funding
This work was supported by the National Natural Science Foundation of China (grant number: 81971570 awarded to Yonggui Yuan; 81801349 awarded to Yingying Yin) for literature search, and the Natural Science Foundation of Jiangsu Province (grant number: BK20180373 awarded to Yingying Yin) for the analysis and interpretation of data for the paper’s publication.
Conflict of interest
The authors declare that they have no competing interests.
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Journal of Clinical and Basic Psychosomatics, Electronic ISSN: 2972-4414 Print ISSN: 3060-8562, Published by AccScience Publishing
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