Epigenetic modification of the oxytocin receptor gene: implications for autism symptom severity and brain functional connectivity
Epigenetic modification of the oxytocin receptor gene: implications for autism symptom severity and brain functional connectivity
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DOI：
10.1038/s41386-020-0610-6
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发表时间：
2020-01-13
影响因子：
7.6
通讯作者：
Young, Larry J.
中科院分区：
文献类型：
--
作者：
Andari, Elissar;Nishitani, Shota;Young, Larry J.
催产素在社会认知中的作用引起了社会神经科学和精神病学的极大兴趣。一些研究报告了自闭症谱系障碍（ASD）催产素治疗后社会症状的改善，而另一些研究则指出影响其效率的内源性因素以及长期临床益处的混合结果。ASD中催产素受体基因（OXTR）的表观遗传修饰可能是治疗效果的信息生物标志物。然而，关于ASD中OXTR甲基化、临床严重程度和脑功能之间的关系知之甚少。在这里，我们研究了OXTR甲基化，ASD诊断（在N = 35 ASD和N = 64神经典型组），社会反应性的措施，和静息状态功能连接（rsFC）之间的关系，涉及社会认知和奖励处理（在ASD的子集，N = 30）。与神经型受试者相比，患有ASD的成年人在内含子1区域显示出更高的OXTR甲基化水平。这种高甲基化与临床症状和涉及心理理论的皮质-皮质区域之间的连接不足有关。外显子1区域CpG位点的甲基化与ASD患者的社会反应缺陷以及纹状体和皮质脑区之间的超连通性呈正相关。总之，这些研究结果提供了内含子区域OXTR高甲基化的初步证据，作为ASD成人的潜在生物标志物，其发育沟通缺陷不太严重，但心理理论和自我意识受损。此外，外显子1区域的OXTR甲基化可能是对生活经历敏感的社交性的潜在生物标志物。
The role of oxytocin in social cognition has attracted tremendous interest in social neuroscience and psychiatry. Some studies have reported improvement in social symptoms following oxytocin treatment in autism spectrum disorders (ASD), while others point to endogenous factors influencing its efficiency and to mixed results in terms of long-term clinical benefits. Epigenetic modification to the oxytocin receptor gene (OXTR) in ASD could be an informative biomarker of treatment efficacy. Yet, little is known about the relationship between OXTR methylation, clinical severity, and brain function in ASD. Here, we investigated the relationship between OXTR methylation, ASD diagnosis (in N = 35 ASD and N = 64 neurotypical group), measures of social responsiveness, and resting-state functional connectivity (rsFC) between areas involved in social cognition and reward processing (in a subset of ASD, N = 30). Adults with ASD showed higher OXTR methylation levels in the intron 1 area compared with neurotypical subjects. This hypermethylation was related to clinical symptoms and to a hypoconnectivity between cortico-cortical areas involved in theory of mind. Methylation at a CpG site in the exon 1 area was positively related to social responsiveness deficits in ASD and to a hyperconnectivity between striatal and cortical brain areas. Taken together, these findings provide initial evidence for OXTR hypermethylation in the intron area as a potential biomarker for adults with ASD with less severe developmental communication deficits, but with impairments in theory of mind and self-awareness. Also, OXTR methylation in the exon 1 area could be a potential biomarker of sociability sensitive to life experiences.