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

OXTR 甲基化作为人类鼻内 OT 影响的潜在调节剂

• 批准号: 8769006
• 负责人: JAMES K RILLING
• 金额: $ 19.5万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-16 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769006
• 关键词: Affect; Amygdaloid structure; Area; Arousal; Behavioral; Brain; Clinical effectiveness; Cognitive deficits; Computers; Cooperative Behavior; Corpus striatum structure; DNA Methylation; Data; Effectiveness; Functional Magnetic Resonance Imaging; Gene Expression; Genes; Hippocampus (Brain); Human; Individual; Insula of Reil; Measures; Memory; Mental disorders; Methylation; Oxytocin; Oxytocin Receptor; Placebos; Play; Receptor Gene; Relative (related person); Research; Rewards; Sampling; Scanning; Social Interaction; Variant; Woman; autism spectrum disorder; basal forebrain; density; human subject; interest; men; public health relevance; relating to nervous system; response; social; social attachment

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.

描述（由申请人提供）：对使用鼻内催产素（OT）作为对各种精神疾病的潜在治疗的兴趣越来越大，包括自闭症谱系障碍（ASD），并且初步研究表明，鼻腔内OT确实可以减轻在ASD个人中发现的某些社会认知缺陷。最终，鼻内OT在治疗ASD和其他精神疾病中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，因此可以调节对鼻内OT治疗的神经和行为反应性以及其潜在的临床有效性。该项目有两个具体的目标。目的1是确定OXTR的DNA甲基化是否会影响沉浸在真正的社会互动中的人类受试者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，我们从中收集了与人类和计算机合作伙伴一起玩社交，互动游戏，从中收集了行为和fMRI数据。我们假设甲基化将与合作行为的度量以及对合作和非合作社会互动的fMRI反应有关。 AIM 2将确定OXTR的DNA甲基化是否会调节鼻内OT对浸入真正社会相互作用的人类受试者中合作行为和相关的大脑活动的影响。在玩社交，互动游戏时，在接受fMRI扫描之前，先对100名受试者进行了治疗。另外100名受试者已通过鼻内安慰剂进行了预处理。我们假设甲基化水平将与鼻内OT（相对于安慰剂）的影响有关 合作行为以及鼻内OT对fMRI对合作和非合作社会互动的反应的影响。最终，这项研究可能会帮助我们确定最有可能从诸如OT之类的治疗中受益的人。