School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
Centre for Brain and Mental Health Research, University of Newcastle and the Hunter Medical Research Institute, Newcastle, NSW 2308, Australia.
Cells. 2020 Aug 5;9(8):1837. doi: 10.3390/cells9081837.
Schizophrenia is a severe psychiatric disorder with a complex array of signs and symptoms that causes very significant disability in young people. While schizophrenia has a strong genetic component, with heritability around 80%, there is also a very significant range of environmental exposures and stressors that have been implicated in disease development and neuropathology, such as maternal immune infection, obstetric complications, childhood trauma and cannabis exposure. It is postulated that epigenetic factors, as well as regulatory non-coding RNAs, mediate the effects of these environmental stressors. In this review, we explore the most well-known epigenetic marks, including DNA methylation and histone modification, along with emerging RNA mediators of epigenomic state, including miRNAs and lncRNAs, and discuss their collective potential for involvement in the pathophysiology of schizophrenia implicated through the postmortem analysis of brain tissue. Given that peripheral tissues, such as blood, saliva, and olfactory epithelium have the same genetic composition and are exposed to many of the same environmental exposures, we also examine some studies supporting the application of peripheral tissues for epigenomic biomarker discovery in schizophrenia. Finally, we provide some perspective on how these biomarkers may be utilized to capture a signature of past events that informs future treatment.
精神分裂症是一种严重的精神疾病，其症状和体征复杂多样，会导致年轻人出现严重的残疾。虽然精神分裂症有很强的遗传成分，遗传率约为 80%，但也有大量的环境暴露和压力源与疾病发展和神经病理学有关，如母体免疫感染、产科并发症、儿童期创伤和大麻暴露。据推测，表观遗传因素以及调节性非编码 RNA 介导了这些环境压力源的作用。在这篇综述中，我们探讨了最著名的表观遗传标记，包括 DNA 甲基化和组蛋白修饰，以及新兴的 RNA 介导的表观基因组状态调节剂，包括 miRNA 和 lncRNA，并讨论了它们通过脑组织的死后分析共同参与精神分裂症病理生理学的潜在作用。鉴于外周组织（如血液、唾液和嗅上皮）具有相同的遗传组成，并暴露于许多相同的环境暴露，我们还检查了一些支持应用外周组织进行精神分裂症表观基因组生物标志物发现的研究。最后，我们提供了一些关于这些生物标志物如何被用来捕捉过去事件的特征，为未来的治疗提供信息的观点。
