Measuring gene-environment transactions to identify sensitive periods for infant social behavior & brain growth

项目摘要/摘要 这个项目建立在我们实验室最近的研究基础上，该研究首次表明基因直接塑造 孩子看世界的方式：孩子花时间看什么--以及她如何、何时、在哪里 外表--都受到遗传变异的强烈影响(Constantino等人，《自然》，2017)。同卵双胞胎，谁 分享相同的基因变异，有效地同步他们对社交内容的看法。此外，这些相同的 自闭症谱系障碍儿童的社交面貌指标显著且有差异地降低 (Χ2=64.03P&lt；0.0001)。在目前的项目中，我们将测量遗传和环境对 社会视觉参与和大脑从出生到蹒跚学步的成长，量化基因- 随时间推移的环境事务。我们将使用眼球跟踪来测量婴儿对社交世界的看法 和MRI测量受控遗传变异条件下大脑连通性的变化：相同和 异卵双胞胎从出生后第一周就开始了。我们将招收240对双胞胎(120对)，收集眼睛- 跟踪10个时间点的数据，5个时间点的神经成像数据，以及标准化的社交评估- 3个时间点的沟通能力。这个应用程序将检验这样的假设：一个接一个的基因- 生命最初几年的按年龄进行的环境交易是一种强有力的发展宣传 机制，能够为典型的社会发展提供必要的共享媒介的机制， 但同样有能力将不同的初始负债引导到非典型的社会发展中 导致一种称为自闭症谱系障碍的综合症社会残疾。通过量化发展的 基因-环境交易的时机及其对社会表型呈现的影响 行为和大脑发育，这个项目将提供对可修改的行为路径的洞察，这些路径提供了 最大的治疗潜力，以防止或先发制人出现非典型肺炎的有害后果 在ASD和其他神经发育障碍中发现的发育。

PROJECT SUMMARY/ABSTRACT This project builds on recent research in our laboratory that showed for the first time that genes directly shape the way a child sees the world: what a child spends time looking at—as well as how, when, and where she looks—are all strongly influenced by genetic variation (Constantino et al, Nature, 2017). Identical twins, who share the same genetic variation, effectively synchronize their looking to social content. Moreover, these same measures of social looking are markedly and differentially decreased in children with autism spectrum disorder (ASD) (Χ2= 64.03, P < 0.0001). In the current project, we will measure genetic and environmental influence on social visual engagement and brain growth from birth through toddlerhood, quantifying effects of gene- environment transactions over time. We will use eye-tracking to measure how infants look at the social world and MRI to measure changing brain connectivity under conditions of controlled genetic variation: identical & fraternal twins followed from the first week after birth. We will enroll 240 twins (120 pairs), collecting eye- tracking data at 10 time points, neuroimaging data at 5 time points, and standardized assessments of social- communicative competency at 3 time points. This application will test the hypothesis that gene-by- environment-by-age transactions in the first years of life serve as a powerful developmental canalizing mechanism, a mechanism capable of providing the necessary shared medium for typical social development, and yet equally capable of channeling diverse initial liabilities off-course, into atypical social development resulting in the syndromic social disability called autism spectrum disorder. By quantifying the developmental timing of gene-environment transactions, together with their impact on phenotypic presentation of social behavior and brain growth, this project will provide insights into modifiable behavioral pathways that offer the greatest therapeutic potential to prevent or preempt the emergence of deleterious consequences of atypical development as found in ASD and other neurodevelopmental disabilities.