Khan MM, Khan ZA, Khan MA. Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration. World J Psychiatry 2024; 14(6): 767-783 [PMID: 38984346 DOI: 10.5498/wjp.v14.i6.767]
Corresponding Author of This Article
Mohammad M Khan, PhD, Professor, Laboratory of Translational Neurology and Molecular Psychiatry, Department of Biotechnology, Era’s Lucknow Medical College and Hospital, Faculty of Science, Era University, Sarfarazganj, Hardoi Road, Lucknow 226003, India. mmkhan0@gmail.com
Research Domain of This Article
Psychiatry
Article-Type of This Article
Review
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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/
World J Psychiatry. Jun 19, 2024; 14(6): 767-783 Published online Jun 19, 2024. doi: 10.5498/wjp.v14.i6.767
Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration
Mohammad M Khan, Zaw Ali Khan, Mohsin Ali Khan
Mohammad M Khan, Laboratory of Translational Neurology and Molecular Psychiatry, Department of Biotechnology, Era’s Lucknow Medical College and Hospital, and Faculty of Science, Era University, Lucknow 226003, India
Zaw Ali Khan, Mohsin Ali Khan, Era’s Lucknow Medical College and Hospital, Era University, Lucknow 226003, India
Author contributions: Khan MM conceptualised the idea and wrote the manuscript; Khan ZA and Khan MA provided the resources.
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: Mohammad M Khan, PhD, Professor, Laboratory of Translational Neurology and Molecular Psychiatry, Department of Biotechnology, Era’s Lucknow Medical College and Hospital, Faculty of Science, Era University, Sarfarazganj, Hardoi Road, Lucknow 226003, India. mmkhan0@gmail.com
Received: January 6, 2024 Revised: May 5, 2024 Accepted: May 23, 2024 Published online: June 19, 2024 Processing time: 165 Days and 11.9 Hours
Abstract
Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.
Core Tip: Psychotropic medications are the first line of treatment for psychiatric disorders; however, their long-term use has been shown to induce various metabolic abnormalities including diabetes, obesity, and fatty liver disease. Although mechanism(s) underlying these metabolic abnormalities is not clear, lipid/fatty acid accumulation caused by enhanced de novo lipogenesis (DNL) could be the primary mediator. In this regard, various anti-inflammatory drugs that are used in combination therapy, have been shown to reduce DNL and the aforementioned metabolic abnormalities in laboratory animals. This suggests that DNL could be a potential pathological and therapeutic target, and a new avenue for translational research in psychiatric disorders.
