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.

中文翻译：

---

催产素受体基因的表观遗传修饰：对自闭症症状严重程度和大脑功能连接的影响。

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。一些研究报告了催产素治疗自闭症谱系障碍 (ASD) 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方面的混合结果。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）、社会反应测量、和涉及社会认知和奖励处理的区域之间的静息状态功能连接（rsFC）（在 ASD 的一个子集中，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以及心理理论中涉及的皮质 - 皮质区域之间的低连接性有关。外显子 1 区 CpG 位点的甲基化与 ASD 中的社会反应缺陷以及纹状体和皮质脑区之间的超连接呈正相关。总之，这些发现为内含子区域的 OXTR 高甲基化提供了初步证据，作为 ASD 成人的潜在生物标志物，其发育沟通缺陷较轻，但在心智和自我意识理论方面存在障碍。还，