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©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
Metabolic pathway modulation by olanzapine: Multitarget approach for treating violent aggression in patients with schizophrenia
Yan-Ning Song, Shuang Xia, Zhi Sun, Yong-Chao Chen, Lu Jiao, Wen-Hua Wan, Hong-Wei Zhang, Xiao Guo, Hua Guo, Shou-Feng Jia, Xiao-Xin Li, Shi-Xian Cao, Li-Bin Fu, Meng-Meng Liu, Tian Zhou, Lv-Feng Zhang, Qing-Quan Jia
Yan-Ning Song, Shuang Xia, Lu Jiao, Wen-Hua Wan, Xiao-Xin Li, Shi-Xian Cao, Li-Bin Fu, Department of Pharmacy, The Affiliated Encephalopathy Hospital of Zhengzhou University (Zhumadian Second People's Hospital), Zhumadian 463000, Henan Province, China
Zhi Sun, Qing-Quan Jia, Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Yong-Chao Chen, Department of Pharmacy, Zhumadian First People's Hospital, Zhumadian 463000, Henan Province, China
Hong-Wei Zhang, Scientific Education Section, The Affiliated Encephalopathy Hospital of Zhengzhou University (Zhumadian Second People's Hospital), Zhumadian 463000, Henan Province, China
Xiao Guo, Hua Guo, Shou-Feng Jia, Lv-Feng Zhang, Department of Psychiatry, The Affiliated Encephalopathy Hospital of Zhengzhou University (Zhumadian Second People's Hospital), Zhumadian 463000, Henan Province, China
Meng-Meng Liu, Clinical Laboratory, The Affiliated Encephalopathy Hospital of Zhengzhou University (Zhumadian Second People's Hospital), Zhumadian 463000, Henan Province, China
Tian Zhou, Publicity Division, The Affiliated Encephalopathy Hospital of Zhengzhou University (Zhumadian Second People's Hospital), Zhumadian 463000, Henan Province, China
Co-first authors: Yan-Ning Song and Shuang Xia.
Author contributions: Song YN and Xia S contributed equally to this work; Song YN contributed to conceptualization, investigation, data curation, methodology, visualization, writing; Xia S, Jiao L and Liu MM contributed to data curation, investigation; Sun Z performed methodology, reviewing, editing, supervision, data curation; Chen YC contributed to methodology, reviewing, editing; Wan WH contributed to investigation, formal analysis; Zhang HW was involved in formal analysis, follow-up, funding acquisition; Guo X, Guo H and Jia SF involved in formal analysis, supervision; Li XX performed supervision, resources; Cao SX performed validation, software; Fu LB performed investigation, follow-up; Zhou T and Zhang LF contributed to data curation; Jia QQ contributed to methodology, software, data extraction; All authors contributed to the interpretation of the study and approved the final version to be published.
Supported by Henan Provincial Science and Technology Research Project, No. 242102310203.
Institutional review board statement: This study was approved by the Medical Ethics Committee of Zhumadian Second People's Hospital (Approval No. Keshen-2023-001-01).
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: Technical appendix, statistical code, and dataset available from the corresponding author at
1017351438@qq.com. Participants gave informed consent for data sharing.
STROBE statement: The authors have read the STROBE Statement—checklist of items, and the manuscript was prepared and revised according to the STROBE Statement—checklist of items.
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: Zhi Sun, PhD, Professor, Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou 450052, Henan Province, China.
sunzhi2013@163.com
Received: September 22, 2024
Revised: November 5, 2024
Accepted: December 5, 2024
Published online: January 19, 2025
Processing time: 86 Days and 21.6 Hours
BACKGROUND
The use of network pharmacology and blood metabolomics to study the pathogenesis of violent aggression in patients with schizophrenia and the related drug mechanisms of action provides new directions for reducing the risk of violent aggression and optimizing treatment plans.
AIM
To explore the metabolic regulatory mechanism of olanzapine in treating patients with schizophrenia with a moderate to high risk of violent aggression.
METHODS
Metabolomic technology was used to screen differentially abundant metabolites in patients with schizophrenia with a moderate to high risk of violent aggression before and after olanzapine treatment, and the related metabolic pathways were identified. Network pharmacology was used to establish protein-protein interaction networks of the core targets of olanzapine. Gene Ontology functional analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were subsequently performed.
RESULTS
Compared with the healthy group, the patients with schizophrenia group presented significant changes in the levels of 24 metabolites related to the disruption of 9 metabolic pathways, among which the key pathways were the alanine, aspartate and glutamate metabolism and arginine biosynthesis pathways. After treatment with olanzapine, the levels of 10 differentially abundant metabolites were significantly reversed in patients with schizophrenia. Olanzapine effectively regulated six metabolic pathways, among which the key pathways were alanine, aspartate and glutamate metabolism and arginine biosynthesis pathways. Ten core targets of olanzapine were involved in several key pathways.
CONCLUSION
The metabolic pathways of alanine, aspartate, and glutamate metabolism and arginine biosynthesis are the key pathways involved in olanzapine treatment for aggressive schizophrenia.
Core Tip: Violent aggression is an important symptom of schizophrenia that causes serious harm to society and public health. This study integrated network pharmacology with blood metabolomics to explore the pathogenesis of violent aggression in patients with schizophrenia and the metabolic regulatory mechanism of olanzapine, establishing theoretical basis for fundamental research and clinical application of olanzapine in the treatment of violent aggression in patients with schizophrenia.
