Yıldırım Sariye Aybüke, Dal Irmak, Özkan-Kotiloğlu Selin, Baskak Bora, Kaya-Akyüzlü Dilek
Department of Forensic Biology, Institute of Forensic Sciences, Ankara University, Ankara 06590, Türkiye.
Department of Molecular Biology and Genetics, Faculty of Science and Art, Kırşehir Ahi Evran University, Kırşehir 34400, Türkiye.
World J Psychiatry. 2025 Jul 19;15(7):107597. doi: 10.5498/wjp.v15.i7.107597.
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.
由于包括遗传和表观遗传机制在内的多种生物学以及社会心理因素，精神分裂症治疗反应中的个体差异给该疾病的管理带来了重大挑战。药物表观遗传学研究表观遗传机制如何影响治疗效果的变异性和不良副作用。氯氮平（非典型）和氟哌啶醇（典型）等抗精神病药物通过改变DNA甲基转移酶和组蛋白乙酰转移酶直接诱导表观遗传变化，同时间接影响神经炎症和应激反应途径。使用表观遗传标记（DNA甲基化、包括微小RNA和长链非编码RNA在内的非编码RNA）的个性化医疗在改善抗精神病治疗的药物反应和减少副作用方面具有巨大潜力。这些进展可能通过解决治疗反应中涉及的复杂性来彻底改变精神分裂症的治疗。然而，在临床实践中实施基于表观遗传调控的策略所面临的伦理和技术障碍是该领域需要谨慎应对的基本挑战。本综述探讨了抗精神病药物疗效中涉及的表观遗传机制。
