OXTR Methylation as a Potential Modulator of Intranasal OT Influences in Humans

描述（由申请人提供）：对使用鼻内催产素（OT）作为多种精神障碍（包括自闭症谱系障碍（ASD））的潜在治疗的兴趣日益增长，初步研究表明，鼻内OT确实可以减轻ASD个体中发现的一些社会认知缺陷。最终，鼻内OT治疗ASD和其他精神障碍的有效性将取决于它在大脑中建立的OT水平以及大脑OT受体的密度和分布。OXTR基因的DNA甲基化有助于调节其表达，因此可能调节对鼻内OT治疗的神经和行为反应及其潜在的临床有效性。该项目有两个具体目标。目的1是确定OXTR的DNA甲基化是否影响人类受试者在真正的社会互动中的合作行为和相关的大脑活动。OXTR的甲基化状态将在我们现有的300名受试者样本中进行评估，我们从这些受试者中收集了行为和fMRI数据，因为他们与人类和计算机合作伙伴进行社交互动游戏。我们假设甲基化将与合作行为的测量相关，以及与合作和非合作社会互动的功能磁共振成像反应相关。目的2将确定OXTR的DNA甲基化是否调节鼻内OT对沉浸在真正的社会互动中的人类受试者的合作行为和相关脑活动的影响。100名受试者在玩社交互动游戏时接受fMRI扫描之前接受鼻内OT预治疗。另外100例受试者接受鼻内安慰剂预治疗。我们假设甲基化水平与鼻内OT（相对于安慰剂）对测量的影响有关。 合作行为，以及鼻内OT对合作和非合作社会互动的fMRI反应的影响。最终，这项研究可能有助于我们确定最有可能从鼻内OT等治疗中受益的个体。

DESCRIPTION (provided by applicant): There is growing interest in the use of intranasal oxytocin (OT) as a potential treatment for a variety of psychiatric disorders, including autism spectrum disorders (ASD), and preliminary studies show that intranasal OT can indeed alleviate some social cognitive deficits found in ASD individuals. Ultimately, the effectiveness of intranasal OT in treating ASD and other mental disorders will depend upon both the levels of OT it establishes in the brain, as well as the density and distribution of brain OT receptors. DNA methylation of the OXTR gene helps to regulate its expression and may therefore modulate the neural and behavioral responsiveness to intranasal OT treatment as well as its potential clinical effectiveness. This project has two specific aims. Aim 1 is to determine if DNA methylation of OXTR influences cooperative behavior and associated brain activity in humans subjects immersed in genuine social interactions. Methylation status of OXTR will be assessed in our existing sample of 300 subjects from whom we have collected behavioral and fMRI data as they play a social, interactive game with human and computer partners. We hypothesize that methylation will associate with measures of cooperative behavior, as well as to fMRI responses to cooperative and non- cooperative social interactions. Aim 2 will determine if DNA methylation of OXTR modulates the effect of intranasal OT on cooperative behavior and associated brain activity in humans subjects immersed in genuine social interactions. 100 subjects were pre-treated with intranasal OT prior to receiving an fMRI scan while playing a social, interactive game. Another 100 subjects were pre-treated with an intranasal placebo. We hypothesize that methylation levels will be related to the effect of intranasal OT (relative to placebo) on measures of cooperative behavior, as well as to the effects of intranasal OT on fMRI responses to cooperative and non-cooperative social interactions. Ultimately, this research may help us to identify individuals who are most likely to benefit from a treatment like intranasal OT.