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）的特点是社交沟通方面存在显着损害，但这些损害的严重程度存在巨大的异质性。对于这种异质性的遗传、神经生物学和环境预测因素仍然知之甚少。新兴研究表明，所有这三个因素分别与自闭症谱系障碍的社会发展有关，但缺乏综合研究，导致许多问题没有得到解答，即自闭症谱系障碍儿童如何以及为何在发展过程和社交技能质量方面存在如此大的差异。更好地了解这些预测因素如何相互作用对于以下方面至关重要：1) 了解自闭症谱系障碍儿童社会性发展中的风险和保护因素； 2）确定患有自闭症谱系障碍（ASD）幼儿的预后； 3）根据个体特点选择最佳治疗方案； 4) 制定早期干预措施以改善社会发展。拟议的研究采用跨学科方法来研究遗传风险和早期养育如何相互作用，以预测自闭症儿童随后的大脑异质性和社会功能的行为标记。参与者将包括 25 名患有自闭症谱系障碍 (ASD) 的儿童和 25 名年龄和智商匹配的 7-9 岁典型发育 (TD) 对照儿童。所有儿童都曾在 12 个月、18 个月和 24 个月大时参加过一项高危婴儿研究，并同意返回加州大学洛杉矶分校大脑测绘中心进行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注意力和母亲同步性轨迹的群体差异，以及这些轨迹如何预测学龄期的社会功能。此外，该研究还将测试 1）社交奖励学习和 2）静息状态期间社交大脑网络中的大脑连接是否介导早期社交互动和后期社交功能之间的关系。最后，本研究将检查早期社交互动作为遗传风险（催产素受体基因 OXTR 的存在）风险等位基因与社交大脑网络连通性降低之间关系的中介因素。这项工作将通过促进对自闭症谱系障碍社会异质性的性质和发展的跨学科理解来对该领域做出贡献，并对改进早期预测和干预具有影响。这些目标与国家心理健康研究所的战略计划是一致的，该战略计划将基因研究与大脑和行为发展联系起来，以了解作为交易发展过程的非典型功能。