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）的特征是社会沟通的显著障碍，但这些障碍的严重程度存在巨大的异质性。关于这种异质性的遗传、神经生物学和环境预测因子仍然知之甚少。新兴的研究表明，所有这三个因素分别与ASD的社会发展，但缺乏综合研究留下了许多问题没有回答，如何以及为什么ASD儿童在发展过程和社会技能的质量上有如此大的差异。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ASD儿童社会发展中的风险和保护因素; 2）确定ASD幼儿的预后; 3）根据个体特征选择最佳治疗方法; 4）制定早期干预措施以改善社会发展。这项研究采用跨学科的方法来研究遗传风险和早期养育如何相互作用，以预测ASD儿童大脑和社会功能行为标志物的后期异质性。参与者将是25名ASD儿童和25名年龄和智商匹配的典型发育（TD）对照，年龄7-9岁。所有儿童之前都参加了一项高风险婴儿研究，年龄分别为12，18和24个月，并同意返回加州大学洛杉矶分校脑成像中心进行持续的成像研究。拟议的研究将研究在早期亲子互动过程中儿童社会注意力和母亲同步轨迹的群体差异，以及这些轨迹如何预测学龄期的社会功能。此外，该研究还将测试在1）社会奖励学习和2）静息状态下社交脑网络中的大脑连接是否介导了早期社会互动和后期社会功能之间的关系。最后，本研究将研究早期的社会互动作为遗传风险（催产素受体基因OXTR的存在）风险等位基因和社会大脑网络连接减少之间关系的中介。这项工作将有助于该领域的促进跨学科的理解的性质和发展的社会异质性在ASD的影响，改善早期预测和干预。这些目标与美国国家心理健康研究所的战略计划相一致，该计划将基因研究与大脑和行为发展联系起来，以了解非典型功能作为一个交易性发展过程。

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.