Characterizing the (epi)genetics of oxytocin response in clinical and animal models

自闭症谱系障碍(ASD)是一组不同种类的发育障碍，具有特定的 核心特征，包括社交互动受损和不正常的重复行为。几项正在进行的研究， 包括我们自己在内，正在评估药物催产素的使用来改善患有以下疾病的人的社会缺陷 自闭症和其他心理社会障碍。我们假设对催产素治疗的行为反应是 由遗传和表观遗传因素介导，这些因素，特别是基因的表观遗传介体 表达，可能是基线反应的关键和/或可能在催产素暴露期间改变。这项建议 将探索表观基因组和遗传易感性在催产素治疗反应中的作用 作为正在进行的针对高功能和低功能儿童的临床试验的一部分而收集的样本 对于自闭症，我们将研究大脑和大脑区域的转录组和表观基因组(5mC和5hmC)。 已知对催产素治疗有阳性反应的ASD小鼠模型的外围；我们还将 研究催产素受体OXTR通过5-羟甲基胞嘧啶的新调节机制。数据 由这些目标产生的结果不仅有助于开发(Epi)催产素反应的遗传预测因子，而且它们 将为其他使用催产素治疗心理社会障碍的试验提供参考。

The autism spectrum disorders (ASDs) are a heterogeneous group of developmental disorders with specific core features, including impaired social interaction and abnormal repetitive behavior. Several ongoing studies, including our own, are assessing the use of the drug oxytocin to ameliorate social deficits in individuals with ASDs and other psychosocial disorders. We hypothesize that behavioral response to oxytocin treatment is mediated by genetic and epigenetic factors and that these factors, particularly epigenetic mediators of gene expression, may be pivotal to baseline response and/or may change during oxytocin exposure. This proposal will explore the role of the epigenome and genetic predisposition to oxytocin treatment response in longitudinal samples that have already been collected as part of an ongoing clinical trial in high and low functioning children with ASDs; we will investigate the transcriptome and epigenome (5mC and 5hmC) in regions of the brain and periphery of a mouse model of ASD known to have positive response to oxytocin treatment; we will also examine novel regulatory mechanisms of oxytocin's receptor OXTR via 5-hydroxy methyl cytosine. The data generated by these aims will not only serve to develop (epi)genetic predictors of oxytocin response, but they will inform other trials using oxytocin to treat psychosocial disorders.