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

描述(申请人提供)：鼻内催产素(OT)作为治疗包括自闭症谱系障碍(ASD)在内的各种精神疾病的潜在治疗方法的兴趣日益增长，初步研究表明，鼻内催产素确实可以缓解ASD患者的一些社会认知缺陷。最终，鼻腔催产素治疗ASD和其他精神障碍的有效性将取决于它在大脑中建立的催产素水平，以及脑组织催产素受体的密度和分布。OXTR基因的DNA甲基化有助于调节其表达，因此可能调节神经和行为对鼻腔催产素治疗的反应性及其潜在的临床疗效。这个项目有两个具体目标。第一个目标是确定OXTRDNA甲基化是否影响沉浸在真正社会互动中的人类受试者的合作行为和相关的大脑活动。我们收集了300名受试者的行为和功能磁共振数据，在他们与人类和计算机合作伙伴玩社交互动游戏时，我们将在现有的300名受试者样本中评估OXTR的甲基化状态。我们假设甲基化将与合作行为的测量以及对合作和非合作社会互动的功能磁共振反应相关联。目的2将确定OXTR的DNA甲基化是否调节鼻腔OT对沉浸在真正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。在玩社交互动游戏时，100名受试者在接受功能磁共振扫描之前，接受了鼻腔内OT的预治疗。另有100名受试者接受了鼻腔安慰剂的预治疗。我们假设甲基化水平将与鼻内催产素(相对于安慰剂)对测量的影响有关 以及鼻腔催产素对合作性和非合作性社会互动功能磁共振反应的影响。最终，这项研究可能有助于我们确定最有可能从鼻腔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.