Khan MM, Khan ZA, Khan MA, Pandey G. Childhood insulin resistance and neural stem cell dysfunction in psychiatric disorders: Role of de novo lipogenesis and treatment perspectives. World J Stem Cells 2025; 17(7): 106194 [DOI: 10.4252/wjsc.v17.i7.106194]
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, and Faculty of Science, Era University, Sarfarazganj, Hardoi Road, Lucknow 226003, Uttar Pradesh, India. mmkhan0@gmail.com
Research Domain of This Article
Psychiatry
Article-Type of This Article
Evidence 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 Stem Cells. Jul 26, 2025; 17(7): 106194 Published online Jul 26, 2025. doi: 10.4252/wjsc.v17.i7.106194
Childhood insulin resistance and neural stem cell dysfunction in psychiatric disorders: Role of de novo lipogenesis and treatment perspectives
Mohammad M Khan, Zaw Ali Khan, Mohsin Ali Khan, Gauri Pandey
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, Uttar Pradesh, India
Mohammad M Khan, Faculty of Pharmaceutical Sciences, UCSI University, Cheras 56000, Kuala Lumpur, Malaysia
Zaw Ali Khan, Mohsin Ali Khan, Era’s Lucknow Medical College and Hospital, Era University, Lucknow 226003, Uttar Pradesh, India
Gauri Pandey, Department of Biotechnology, Faculty of Science, Era University, Lucknow 226003, Uttar Pradesh, India
Author contributions: Khan MM conceptualized the idea and wrote the manuscript; Khan ZA and Khan MA reviewed the manuscript and provided the resources; Pandey G helped with the literature search and figure design.
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, and Faculty of Science, Era University, Sarfarazganj, Hardoi Road, Lucknow 226003, Uttar Pradesh, India. mmkhan0@gmail.com
Received: February 19, 2025 Revised: April 20, 2025 Accepted: June 25, 2025 Published online: July 26, 2025 Processing time: 156 Days and 2.1 Hours
Abstract
Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells (NSCs). However, insulin resistance (IR) is associated with impaired NSC proliferation and cognitive dysfunction, which are the hallmarks of psychiatric disorders (PDs). In addition to insulin, de novo lipogenesis (DNL) also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling. However, enhanced DNL is associated with lipid/fatty acid accumulation, IR, and impaired NSC proliferation. Intriguingly, data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs. Further, evidence suggests that patients with PDs may develop IR during childhood or before adolescence; therefore, DNL could be enhanced preceding the development of IR. Regarding treatment, while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL, various adjunctive drugs/therapies, including chemical, physical, and stem cell therapy, which have shown promising success in treating PDs, reduce DNL while enhancing insulin sensitivity, NSC proliferation, and cognitive function in laboratory animals. Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies, especially stem cell therapy in treating PDs including schizophrenia and depression, are discussed.
Core Tip: Childhood insulin resistance (IR) is a potential risk factor for developing psychiatric disorders (PDs). Although insulin regulates neural stem cell (NSC) proliferation and function, IR is associated with impaired NSC proliferation and cognitive dysfunction, which are prominent features of PDs. While the mechanisms underlying IR and NSC dysfunction in PDs remain unclear, intracellular lipids/fatty acids synthesized via de novo lipogenesis could be the primary mediators. Since psychotropic drugs further deteriorate IR and stimulate de novo lipogenesis, prospects of various adjunctive therapies, especially stem cell therapy, in treating IR in schizophrenia and depression are discussed.
