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

临床和动物模型中催产素反应的（表观）遗传学特征

• 批准号: 9246676
• 负责人: SIMON G GREGORY
• 金额: $ 65.6万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-14 至 2022-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9246676
• 关键词: Amygdaloid structure; Animal Model; Area; Behavioral; Biological Models; Brain; Brain region; C58/J Mouse; Candidate Disease Gene; Child; Clinical; Clinical Trials; Communication; Cytosine; DNA; DNA Methylation; Data; Development; Disease; Dopamine; Drug usage; Epigenetic Process; Etiology; Eye; Funding; Gene Expression; Gene Targeting; Genes; Genetic; Genetic Predisposition to Disease; Genetic Variation; Genotype; Hippocampus (Brain); Hormones; Human; Impairment; Individual; Knockout Mice; Language Development; Lifestyle-related condition; Mediating; Mediator of activation protein; Methylation; Modification; Mouse Strains; Mus; Mutant Strains Mice; Neuromodulator; Neurotransmitters; Oxytocin; Oxytocin Receptor; Participant; Pathway interactions; Pattern; Phenotype; Play; Regulation; Research; Research Personnel; Research Support; Rewards; Role; Sampling; Signal Transduction; Single Nucleotide Polymorphism; Social Behavior; Social Interaction; Tissues; Translating; United States National Institutes of Health; Ventral Striatum; affiliative behavior; autism spectrum disorder; behavioral response; density; developmental disease; efficacy trial; epigenetic regulation; epigenome; functional status; genetic predictors; genetic profiling; improved; interest; methylome; mouse model; non-genetic; novel; promoter; psychosocial; repetitive behavior; response; social; transcriptome; transcriptomics; treatment duration; treatment response

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.

自闭症谱系障碍（ASDs）是一组异质性的发育障碍，具有特异性