Review
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatr. Jul 19, 2021; 11(7): 297-315
Published online Jul 19, 2021. doi: 10.5498/wjp.v11.i7.297
Glutamate and depression: Reflecting a deepening knowledge of the gut and brain effects of a ubiquitous molecule
Adejoke Yetunde Onaolapo, Olakunle James Onaolapo
Adejoke Yetunde Onaolapo, Behavioural Neuroscience Unit, Neurobiology Subdivision, Department of Anatomy, Ladoke Akintola University of Technology, Oyo State 234, Nigeria
Olakunle James Onaolapo, Behavioural Neuroscience Unit, Neuropharmacology Subdivision, Department of Pharmacology, Ladoke Akintola University of Technology, Oyo State 234, Nigeria
Author contributions: Both authors contributed equally to the writing of this manuscript.
Conflict-of-interest statement: Authors have nothing to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Olakunle James Onaolapo, MBBS, MSc, PhD, Senior Lecturer, Behavioural Neuroscience Unit, Neuropharmacology Subdivision, Department of Pharmacology, Ladoke Akintola University of Technology, P.M.B 4000, Oyo State 234, Nigeria. olakunleonaolapo@yahoo.co.uk
Received: March 7, 2021
Peer-review started: March 7, 2021
First decision: March 30, 2021
Revised: April 13, 2021
Accepted: May 10, 2021
Article in press: May 10, 2021
Published online: July 19, 2021
Abstract

The versatility of glutamate as the brain’s foremost excitatory neurotransmitter and modulator of neurotransmission and function is considered common knowledge. Years of research have continued to uncover glutamate’s effects and roles in several neurological and neuropsychiatric disorders, including depression. It had been considered that a deeper understanding of the roles of glutamate in depression might open a new door to understanding the pathological basis of the disorder, improve the approach to patient management, and lead to the development of newer drugs that may benefit more patients. This review examines our current understanding of the roles of endogenous and exogenous sources of glutamate and the glutamatergic system in the aetiology, progression and management of depression. It also examines the relationships that link the gut-brain axis, glutamate and depression; as it emphasizes how the gut-brain axis could impact depression pathogenesis and management via changes in glutamate homeostasis. Finally, we consider what the likely future of glutamate-based therapies and glutamate-based therapeutic manipulations in depression are, and if with them, we are now on the final chapter of understanding the neurochemical milieu of depressive disorders.

Keywords: Brain, Gut microbiome, Mental health, Mood disorders, Neurotransmitters

Core Tip: The versatility of glutamate as the brain’s foremost excitatory neurotransmitter, and modulator of intermediary metabolism in the gastrointestinal tract is considered common knowledge. Years of research suggest glutamate has a role to play in depression. Also, there is increasing evidence of a possible relationship between glutamate and the pathophysiology and/or treatment of depression. The complexity of depression suggests dysregulation of glutamate in sites such as the gastrointestinal tract and brain. The communication link involving dietary glutamate, the gut, endogenous glutamate, and the brain is a multidirectional pathway; the understanding of which is necessary to fully account for glutamate’s role in depression.