Gene-brain-environment interactions: Predicting social skill heterogeneity in ASD

基因-大脑-环境相互作用：预测自闭症谱系障碍的社交技能异质性

• 批准号: 8784935
• 负责人: Shulamite Abra Green
• 金额: $ 4.99万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-28 至 2017-07-27
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8784935
• 关键词: Address; Age; Amygdaloid structure; Attention; Behavioral; Brain; Brain Mapping; Characteristics; Child; Complex; Data; Development; Developmental Delay Disorders; Developmental Disabilities; Developmental Process; Early Intervention; Environment; Functional Magnetic Resonance Imaging; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genotype; Health Benefit; Heterogeneity; Image; Impairment; Individual; Insula of Reil; Intervention; Lead; Learning; Link; Measures; Mediating; Mediator of activation protein; Methods; National Institute of Mental Health; Nature; Neurobiology; Outcome; Oxytocin; Oxytocin Receptor; Parent-Child Relations; Parenting behavior; Parents; Participant; Play; Prefrontal Cortex; Public Health; Receptor Gene; Reporting; Research; Rest; Rewards; Risk; Role; School-Age Population; Severities; Social Development; Social Functioning; Social Interaction; Social Network; Strategic Planning; Testing; Ventral Striatum; Work; autism spectrum disorder; base; cohort; early childhood; early experience; experience; high risk infant; improved; infancy; interdisciplinary approach; longitudinal design; outcome forecast; parental influence; public health relevance; response; risk variant; social; social communication; social skills

DESCRIPTION (provided by applicant): While autism spectrum disorders (ASDs) are characterized by significant impairments in social-communication, there is tremendous heterogeneity in the severity of these impairments. Very little is still known about the genetic, neurobiological, and environmental predictors of this heterogeneity. Emerging research suggests that all three of these factors relate separately to social development in ASD, but the lack of integrative research leaves many questions unanswered about how and why children with ASD differ so greatly in developmental course and quality of social skills. A better understanding of how these predictors interact is crucial to 1) understand risk and protective factors in the social development of children with ASD; 2) determine prognosis for young children with ASD; 3) select optimal treatments based on individual characteristics; and 4) develop early interventions to improve social development. The proposed study takes an interdisciplinary approach to examine how genetic risk and early parenting interact to predict later heterogeneity in brain and behavioral markers of social functioning in children with ASD. Participants will be 25 children with ASD and 25 age- and IQ-matched typically developing (TD) controls, ages 7-9 years. All children previously participated in a high-risk infant study at ages , 12, 18, and 24 months and have agreed to return for ongoing imaging studies at the UCLA Brain Mapping Center. The proposed study will examine group differences in trajectories of child social attention and maternal synchrony during early parent-child interactions, as well as how these trajectories predict social functioning in school-age. Additionally, the study will test whether brain connectivity in social brain networks during 1) social reward learning and 2) resting state mediates the relationship between early social interactions and later social functioning. Finally, this study will examine the early social interactions as mediators of the relationship between genetic risk (presence of oxytocin receptor gene OXTR) risk alleles and reduced connectivity in social brain networks. This work will contribute to the field by facilitatig an interdisciplinary understanding of the nature and development of social heterogeneity in ASD with implications for improvement of early prediction and intervention. These aims are consistent with the National Institute of Mental Health's strategic plan to link studies of genes with brain and behavioral development to understand atypical functioning as a transactional developmental process.

描述（由申请人提供）：虽然自闭症谱系障碍（ASD）的特征是社会通讯的重大障碍，但这些障碍的严重性存在很大的异质性。关于这种异质性的遗传，神经生物学和环境预测指标，仍然很少知道。新兴研究表明，这三个因素与ASD的社会发展分开有关，但是缺乏综合研究使许多关于如何以及为什么ASD儿童在发展过程和社交技能质量方面差异很大的问题。更好地理解这些预测因素如何相互作用对1）了解ASD儿童的社会发展中的风险和保护因素； 2）确定ASD幼儿的预后； 3）根据个人特征选择最佳治疗； 4）制定早期干预措施以改善社会发展。拟议的研究采用了跨学科的方法来研究遗传风险和早期育儿如何相互作用，以预测ASD儿童社会功能的大脑和行为标志物的后期异质性。参与者将是25名ASD和25岁和IQ匹配的儿童，通常是7-9岁的儿童（TD）对照。所有儿童以前都参加了12、18和24个月的高危婴儿研究，并同意返回UCLA脑映射中心正在进行的成像研究。拟议的研究将研究早期亲子互动期间儿童社会关注和孕产妇同步的轨迹的群体差异，以及这些轨迹如何预测学院时代的社会功能。此外，该研究将测试1）社交奖励学习期间社交大脑网络中的大脑连通性是否会介导早期社交互动与后期社会功能之间的关系。最后，这项研究将研究早期的社会互动，作为遗传风险（存在催产素受体基因OXTR）之间关系的介体风险等位基因和社交大脑网络中的连通性降低。这项工作将通过对ASD中社会异质性的性质和社会异质性的性质和发展的跨学科的理解来为该领域做出贡献，对改善早期预测和干预的影响。这些目标与美国国家心理健康研究所的战略计划一致，即将基因研究与大脑和行为发展联系起来，以将非典型功能理解为交易发展过程。