Wawrzczak-Bargieła Agnieszka, Bilecki Wiktor, Maćkowiak Marzena
Department of Pharmacology, Laboratory of Pharmacology and Brain Biostructure, Maj Institute of Pharmacology, Polish Academy of Sciences, Smętna 12, 31-343 Kraków, Poland.
Brain Sci. 2023 Mar 1;13(3):426. doi: 10.3390/brainsci13030426.
Schizophrenia is regarded as a neurodevelopmental disorder with its course progressing throughout life. However, the aetiology and development of schizophrenia are still under investigation. Several data suggest that the dysfunction of epigenetic mechanisms is known to be involved in the pathomechanism of this mental disorder. The present article revised the epigenetic background of schizophrenia based on the data available in online databases (PubMed, Scopus). This paper focused on the role of epigenetic regulation, such as DNA methylation, histone modifications, and interference of non-coding RNAs, in schizophrenia development. The article also reviewed the available data related to epigenetic regulation that may modify the severity of the disease as a possible target for schizophrenia pharmacotherapy. Moreover, the effects of antipsychotics on epigenetic malfunction in schizophrenia are discussed based on preclinical and clinical results. The obtainable data suggest alterations of epigenetic regulation in schizophrenia. Moreover, they also showed the important role of epigenetic modifications in antipsychotic action. There is a need for more data to establish the role of epigenetic mechanisms in schizophrenia therapy. It would be of special interest to find and develop new targets for schizophrenia therapy because patients with schizophrenia could show little or no response to current pharmacotherapy and have treatment-resistant schizophrenia.
精神分裂症被视为一种神经发育障碍,其病程贯穿一生。然而,精神分裂症的病因和发展仍在研究中。多项数据表明,表观遗传机制功能障碍已知参与了这种精神障碍的发病机制。本文基于在线数据库(PubMed、Scopus)中的现有数据,对精神分裂症的表观遗传背景进行了综述。本文重点关注表观遗传调控,如DNA甲基化、组蛋白修饰和非编码RNA干扰,在精神分裂症发展中的作用。文章还回顾了与表观遗传调控相关的现有数据,这些数据可能作为精神分裂症药物治疗的潜在靶点来改变疾病的严重程度。此外,基于临床前和临床结果,讨论了抗精神病药物对精神分裂症表观遗传功能障碍的影响。现有数据表明精神分裂症中表观遗传调控发生了改变。此外,这些数据还显示了表观遗传修饰在抗精神病作用中的重要作用。需要更多数据来确定表观遗传机制在精神分裂症治疗中的作用。寻找和开发精神分裂症治疗的新靶点将具有特别重要的意义,因为精神分裂症患者对当前药物治疗可能反应甚微或无反应,存在难治性精神分裂症。