Shorter Kimberly R, Miller Brooke H
McKnight Brain Institute and Departments of Psychiatry and Medicine, University of Florida College of Medicine, Gainesville, FL 32607, USA.
McKnight Brain Institute and Departments of Psychiatry and Medicine, University of Florida College of Medicine, Gainesville, FL 32607, USA.
Prog Biophys Mol Biol. 2015 Jul;118(1-2):1-7. doi: 10.1016/j.pbiomolbio.2015.04.008. Epub 2015 May 7.
Epigenetic modifications, including DNA methylation, histone modifications, and non-coding RNAs, have been implicated in a number of complex diseases. Schizophrenia and other major psychiatric and neurodevelopmental disorders are associated with abnormalities in multiple epigenetic mechanisms, resulting in altered gene expression during development and adulthood. Polymorphisms and copy number variants in schizophrenia risk genes contribute to the high heritability of the disease, but environmental factors that lead to epigenetic modifications may either reduce or exacerbate the expression of molecular and behavioral phenotypes associated with schizophrenia and related disorders. In the present paper, we will review the current understanding of molecular dysregulation in schizophrenia, including disruption of the dopamine, NMDA, and GABA signaling pathways, and discuss the role of epigenetic factors underlying disease pathology.
表观遗传修饰，包括DNA甲基化、组蛋白修饰和非编码RNA，已被认为与多种复杂疾病有关。精神分裂症以及其他主要的精神和神经发育障碍与多种表观遗传机制异常有关，导致发育过程和成年期基因表达改变。精神分裂症风险基因中的多态性和拷贝数变异导致了该疾病的高遗传性，但导致表观遗传修饰的环境因素可能会降低或加剧与精神分裂症及相关疾病相关的分子和行为表型的表达。在本文中，我们将综述目前对精神分裂症分子调节异常的理解，包括多巴胺、N-甲基-D-天冬氨酸（NMDA）和γ-氨基丁酸（GABA）信号通路的破坏，并讨论表观遗传因素在疾病病理中的作用。
