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World J Psychiatry. Apr 19, 2023; 13(4): 141-148
Published online Apr 19, 2023. doi: 10.5498/wjp.v13.i4.141
Kynurenine pathway of tryptophan metabolism in pathophysiology and therapy of major depressive disorder
Abdulla A-B Badawy, Shazia Dawood, Samina Bano
Abdulla A-B Badawy, Formerly School of Health Sciences, Cardiff Metropolitan University, Cardiff CF5 2YB, United Kingdom
Shazia Dawood, Pharmacy and Allied Health Sciences, Iqra University, Karachi 7580, Pakistan
Samina Bano, Biochemistry, Karachi University, Karachi 75270, Pakistan
Author contributions: Badawy AAB wrote the first draft; Dawood S and Bano S reviewed it and all three authors approved the final version.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abdulla A-B Badawy, BPharm, PhD, Professor Emerita, Formerly School of Health Sciences, Cardiff Metropolitan University, Western Avenue, Cardiff CF5 2YB, United Kingdom. badawyabdulla@yahoo.com
Received: November 25, 2022
Peer-review started: November 25, 2022
First decision: December 12, 2022
Revised: January 19, 2023
Accepted: March 21, 2023
Article in press: March 21, 2023
Published online: April 19, 2023
Core Tip

Core Tip: Antidepressant drugs inhibit the activity of liver tryptophan 2,3-dioxygenase (TDO) and bind specifically to the enzyme, but not to indoleamine 2,3-dioxygenase (IDO). IDO induction is not a major event in the pathophysiology of major depressive disorder (MDD), but may be masked and overridden by upregulation of kynurenine monooxygenase (KMO), the gateway to production of modulators of immune and neuronal functions. The pathophysiology of MDD may be underpinned by both the serotonin deficiency and glutamatergic activation mediated respectively by TDO induction and N-methyl-D-aspartate receptor activation. Inhibition of TDO and KMO should be the focus of MDD pharmacotherapy.