School of Biomedical Sciences, Faculty of Health and Medicine, University of Newcastle, Callaghan, Australia.; Centre for Translational Neuroscience and Mental Health, Hunter Medical Research Institute, Newcastle, New South Wales, Australia.
School of Biomedical Sciences, Faculty of Health and Medicine, University of Newcastle, Callaghan, Australia.; Schizophrenia Research Institute, Sydney, Australia.; Centre for Translational Neuroscience and Mental Health, Hunter Medical Research Institute, Newcastle, New South Wales, Australia..
Biol Psychiatry. 2015 Aug 15;78(4):231-9. doi: 10.1016/j.biopsych.2014.12.009. Epub 2014 Dec 18.
Psychiatric syndromes, including schizophrenia, mood disorders, and autism spectrum disorders, are characterized by a complex range of symptoms, including psychosis, depression, mania, and cognitive deficits. Although the mechanisms driving pathophysiology are complex and remain largely unknown, advances in the understanding of gene association and gene networks are providing significant clues to their etiology. In recent years, small noncoding RNA molecules known as microRNA (miRNA) have emerged as potential players in the pathophysiology of mental illness. These small RNAs regulate hundreds of target transcripts by modifying their stability and translation on a broad scale, influencing entire gene networks in the process. There is evidence to suggest that numerous miRNAs are dysregulated in postmortem neuropathology of neuropsychiatric disorders, and there is strong genetic support for association of miRNA genes and their targets with these conditions. This review presents the accumulated evidence linking miRNA dysregulation and dysfunction with schizophrenia, bipolar disorder, major depressive disorder, and autism spectrum disorders and the potential of miRNAs as biomarkers or therapeutics for these disorders. We further assess the functional roles of some outstanding miRNAs associated with these conditions and how they may be influencing the development of psychiatric symptoms.
精神疾病包括精神分裂症、情绪障碍和自闭症谱系障碍等，其特征是一系列复杂的症状，包括精神病、抑郁、躁狂和认知缺陷。尽管导致病理生理学的机制很复杂，目前仍知之甚少，但对基因关联和基因网络的理解的进步为其病因提供了重要线索。近年来，一种被称为 microRNA（miRNA）的小型非编码 RNA 分子已成为精神疾病病理生理学的潜在参与者。这些小 RNA 通过广泛地调节其稳定性和翻译来调节数百个靶转录本，从而影响整个基因网络。有证据表明，许多 miRNA 在神经精神疾病的死后神经病理学中失调，并且 miRNA 基因及其靶基因与这些疾病的关联具有很强的遗传支持。这篇综述介绍了 miRNA 失调和功能障碍与精神分裂症、双相情感障碍、重度抑郁症和自闭症谱系障碍的关联的累积证据，以及 miRNA 作为这些疾病的生物标志物或治疗靶点的潜力。我们进一步评估了与这些疾病相关的一些突出 miRNA 的功能作用，以及它们如何影响精神症状的发展。
