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

描述(由申请人提供)：虽然自闭症谱系障碍(ASD)的特征是社交沟通方面的严重障碍，但这些障碍的严重程度存在巨大的异质性。目前对这种异质性的遗传、神经生物学和环境预测因子知之甚少。新出现的研究表明，这三个因素分别与自闭症儿童的社会发展有关，但缺乏综合研究留下了许多问题，即自闭症儿童的发展过程和社交技能质量如何以及为什么会有如此大的差异。更好地了解这些预测因素是如何相互作用的，对于1)了解自闭症儿童社会发展中的风险和保护因素；2)确定自闭症儿童的预后；3)根据个人特征选择最佳治疗方法；以及4)制定早期干预措施，以改善社会发展，是至关重要的。这项拟议的研究采用跨学科的方法，研究遗传风险和早期父母教养是如何相互作用，以预测自闭症儿童未来大脑和社会功能的行为标记物的异质性。参与者将是25名患有自闭症的儿童和25名年龄和智商匹配的典型发育中(TD)儿童，年龄在7-9岁之间。所有儿童在12个月、18个月和24个月的时候都参加了一项高风险婴儿研究，并同意返回加州大学洛杉矶分校脑成像中心进行成像研究。这项拟议的研究将考察早期亲子互动期间儿童社交注意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，这项研究还将测试在1)社交奖励学习和2)休息状态期间社交大脑网络中的大脑连接性是否在早期社交互动和后来的社交功能之间起中介作用。最后，这项研究将考察早期社会互动作为遗传风险(存在催产素受体基因OXTR)风险等位基因和社交大脑网络连接性降低之间关系的中介。这项工作将通过促进对ASD社会异质性的性质和发展的跨学科理解，以及对改进早期预测和干预的影响，为该领域做出贡献。这些目标与国家心理健康研究所的战略计划一致，该计划将基因研究与大脑和行为发育联系起来，以理解非典型功能是一个交易性发育过程。

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.