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Journal of Clinical and

Basic Psychosomatics

REVIEW ARTICLE
The neurobiological mechanism underlying

ketamine’s rapid-acting antidepressant effect

1,2
1,2
Yingying Yin * and Yonggui Yuan *
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

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
*Corresponding authors: review, we systematically summarize a number of potential biomarkers for predicting
Yingying Yin
(yinyy@seu.edu.cn) and modulating the efficacy of ketamine, from both macroperspectives (such as
Yonggui Yuan neuroimaging and neuroelectrophysiological markers) and microperspectives (such
(101011406@seu.edu.cn) as neurobiochemical and genetic markers). Although research in this area is still in its
Citation: Yin Y, Yuan Y. The infancy, these biomarkers can help clinicians identify whether ketamine intervention
neurobiological mechanism is needed for treatment-resistant depression, thereby reducing the burden on
underlying ketamine’s rapid-acting patients and society. However, the majority of biomarkers are still in the preclinical
antidepressant effect. J Clin Basic
Psychosom. 2024;2(3):2596. exploratory stage, and existing findings are limited. To realize the clinical application
doi: 10.36922/jcbp.2596 of these biomarkers, future studies should combine biomarkers of different types
Received: December 31, 2023 to investigate the relationships and interactions between them. This approach aims
to optimize clinical outcomes by enhancing the involvement of biological targets in
Accepted: May 24, 2024
new models.
Published Online: July 15, 2024
Copyright: © 2024 Author(s). Keywords: Depression; Ketamine; Rapid-acting; Biomarker
This is an Open-Access article
distributed under the terms of the
Creative Commons Attribution
License, permitting distribution,
and reproduction in any medium, 1. Introduction
provided the original work is
properly cited. Depression is the most common disabling mental disorder. At present, the first-
Publisher’s Note: AccScience line treatment for depression is selective serotonin reuptake inhibitors, which have
Publishing remains neutral with shortcomings such as slow onset, low cure rate, and significant side effects. Therefore,
regard to jurisdictional claims in
published maps and institutional the development of new antidepressants has become a major challenge in the field of
affiliations. psychiatry. In this context, ketamine has been used.

Volume 2 Issue 3 (2024) 1 doi: 10.36922/jcbp.2596