与抗精神病药物治疗相关的DNA甲基化和基因素修饰:系统性审查
Diogo Marques1,2,3,4, Nazanin Vaziri1,2,3,4, Steven C Greenway2,4,5,6,7
1Department of Medical Genetics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Molecular psychiatry
|September 3, 2024
概括
抗精神病药物会以不同的方式影响表观基因组变化,如DNA甲基化和基因素修饰. 了解这些表观基因组效应,如克洛扎促进低甲基化,是个性化精神医学的关键.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学 是一个
背景情况:
- 抗精神病药物对于精神分裂症谱系障碍至关重要,但它们的有效性和副作用在个体之间有很大差异.
- 治疗反应的个体间差异部分归因于仍然不完全理解的表观遗传学过程.
研究的目的:
- 系统地审查和评估关于抗精神病药物对表观基因组修饰的影响现有研究.
- 综合各种抗精神病药物诱导的DNA甲基化和基因素修饰的发现.
主要方法:
- 系统的文献搜索和65项研究的评估.
- 基于表观基因组变化的研究分类:全球甲基化,全基因组甲基化,候选基因甲基化和基因组修饰.
- 分析特定的抗精神病药物,包括哈洛佩里多尔,克洛扎平,瑞斯佩里和奎平.
主要成果:
- 利一贯显示全球超甲基化增加,由全基因组分析支持.
- 克洛扎似乎促进了整个表观基因组的低甲基化,对基因组甲基化 (例如,H3K4me3在Gad1) 和乙化产生了特定的影响.
- 候选基因甲基化研究显示出不同的结果,其中一些基因经历过高甲基化 (Glra1,Drd2) 和其他基因经历过低甲基化 (SLC6A4,DUSP6,DTNBP1).
- 里斯佩里和奎蒂阿平在不同大脑区域和不同细胞类型的组织蛋白标记上表现出不同的影响.
结论:
- 抗精神病药物对表观基因组修饰产生选择性和复杂的影响,包括DNA甲基化和基因素标记.
- 解读这些药物诱导的表观遗传变化对于在精神病学中推进个性化医学至关重要.
- 需要进一步的研究,以充分阐明抗精神病药物和表观遗传学之间的动态,以改善治疗策略.
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