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神经精神疾病分期中的表观遗传学和生物标志物。

Epigenetics and biomarkers in the staging of neuropsychiatric disorders.

机构信息

Department of Psychology, University of Gothenburg, Box 500, 405 30, Gothenburg, Sweden.

出版信息

Neurotox Res. 2010 Nov;18(3-4):347-66. doi: 10.1007/s12640-010-9163-5. Epub 2010 Mar 17.

Abstract

Epigenetics, or alterations in the phenotype or gene expression due to mechanisms other than changes in the underlying DNA sequence, reflects the sensitivity and responsiveness of human and animal brains in constantly varying circumstances regulating gene expression profiles that define the biomarkers and present the ultimate phenotypical outcomes, such as cognition and emotion. Epigenetics is associated with functionally relevant alterations to the genome in such a fashion that under the particular conditions of early, adolescent, and adult life, environmental signals may activate intracellular pathways that remodel the "epigenome," triggering changes in gene expression and neural function. Thus, genetic influences in neuropsychiatric disorders that are subject to clinical staging, epigenetics in schizophrenia, epigenetic considerations in the expression of sensorimotor gating resulting from disease conditions, biomarkers of drug use and addiction, current notions on the role of dopamine in schizophrenia spectrum disorders, and the discrete interactions of biomarkers in persistent memory were to greater or lesser extents reflected upon. The relative contributions of endophenotypes and epistasis for mediating epigenetic phenomena and the outcomes as observed in the analysis of biomarkers appear to offer a multitude of interactive combinations to further complicate the labyrinthine machinations of diagnosis, intervention, and prognosis.

摘要

表观遗传学,或由于除了基础 DNA 序列变化之外的机制导致的表型或基因表达的改变,反映了人类和动物大脑在不断变化的环境中的敏感性和反应性,调节着决定生物标志物和最终表型结果的基因表达谱,如认知和情绪。表观遗传学与基因组中功能相关的改变有关,以至于在早期、青少年和成年生活的特定条件下,环境信号可以激活细胞内途径,重塑“表观基因组”,引发基因表达和神经功能的变化。因此,受临床分期影响的神经精神障碍中的遗传影响、精神分裂症中的表观遗传学考虑因素、疾病状态下感觉运动门控表达中的表观遗传学考虑因素、药物使用和成瘾的生物标志物、目前关于多巴胺在精神分裂症谱系障碍中的作用的概念,以及持久记忆中生物标志物的离散相互作用都在不同程度上得到了反映。中介表观遗传现象和生物标志物分析中观察到的结果的内表型和上位性的相对贡献似乎提供了多种相互作用的组合,使诊断、干预和预后的复杂机制更加复杂。

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