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Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Psychiatry. Jul 19, 2025; 15(7): 107597
Published online Jul 19, 2025. doi: 10.5498/wjp.v15.i7.107597
Pharmacoepigenetics in schizophrenia: Predicting drug response
Sariye Aybüke Yıldırım, Irmak Dal, Selin Özkan-Kotiloğlu, Bora Baskak, Dilek Kaya-Akyüzlü
Sariye Aybüke Yıldırım, Irmak Dal, Selin Özkan-Kotiloğlu, Dilek Kaya-Akyüzlü, Department of Forensic Biology, Institute of Forensic Sciences, Ankara University, Ankara 06590, Türkiye
Selin Özkan-Kotiloğlu, Department of Molecular Biology and Genetics, Faculty of Science and Art, Kırşehir Ahi Evran University, Kırşehir 34400, Türkiye
Bora Baskak, Department of Psychiatry, Faculty of Medicine, Ankara University, Ankara 06590, Türkiye
Co-first authors: Sariye Aybüke Yıldırım and Irmak Dal.
Author contributions: Yıldırım SA and Dal I contributed equally to this work and as co-first authors of the manuscript; Yıldırım SA, Dal I, Özkan-Kotiloğlu S, Baskak B, and Kaya-Akyüzlü D designed the overall concept of the study and outlined the manuscript, conducted the literature review, prepared the draft of the manuscript, and approved the submitted version.
Conflict-of-interest statement: The authors have no conflicts of interest 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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Dilek Kaya-Akyüzlü, PhD, Professor, Department of Forensic Biology, Institute of Forensic Sciences, Ankara University, Mamak, Ankara 06590, Türkiye. kayadilek79@gmail.com
Received: March 27, 2025
Revised: April 9, 2025
Accepted: May 26, 2025
Published online: July 19, 2025
Processing time: 105 Days and 21 Hours
Abstract

Individual differences in treatment response in schizophrenia pose a significant challenge in the management of the disease, due to several biological as well as psychosocial factors, including genetic and epigenetic mechanisms. Pharmacoepigenetics investigates how epigenetic mechanisms affect the variability in effectiveness of treatments and adverse side effects. Antipsychotics such as clozapine (atypical) and haloperidol (typical) directly induce epigenetic changes by altering DNA methyltransferases and histone acetyltransferases, while indirectly affecting neuroinflammatory and stress response pathways. Personalized medicine using epigenetic markers (DNA methylation, non-coding RNAs including microRNAs and long non-coding RNAs) holds great promise for improving the drug response and reducing the side effects of antipsychotic treatment. These developments could revolutionize the treatment of schizophrenia by addressing the complexities involved in responding to treatment. However, ethical and technical barriers to implementing strategies based on epigenetic regulation in clinical practice are fundamental challenges that need to be carefully addressed in this field. This review examined the epigenetic mechanisms involved in the efficacy of antipsychotic drugs.

Keywords: Pharmacoepigenetics; Treatment failures; Personalized medicine; Antipsychotic drugs; Schizophrenia

Core Tip: Epigenetic mechanisms play a critical role in the pathogenesis of schizophrenia and contribute to variability in treatment response. Advances in personalized medicine and epigenetic studies offer promising avenues to improve schizophrenia treatment by tailoring therapeutic strategies to individual genetic and epigenetic profiles. However, further research is needed to develop more specific and effective epigenetic therapies to overcome challenges related to treatment efficacy and duration. Integrating epigenetic data into personalized medicine approaches will ultimately improve patient outcomes and revolutionize schizophrenia management.