A Family-Genetic Study of Language in Autism

项目摘要 语用差异（即，社交）语言是与自闭症最密切相关的语言缺陷 谱系障碍（ASD）和广泛自闭症表型（BAP），一组亚临床特征， 亲属在质量上与ASD的定义特征相似，并被认为反映了遗传易感性， 临床上未受影响的亲属）。从最初的奖励期间的调查结果表明，回顾性，纵向 儿童语言和父母认知发展的措施，以及我们的电池， 语用能力的心理语言学和计算语言学测量，可在ASD患者中测量 和他们的父母，是非常有希望的ASD内表型的标记物，可以在遗传学上靶向， 神经生物学和治疗研究。这种竞争性的更新主要建立在这些发现和我们的 相关的工作，在三个重要方面。首先，考虑到父母早期的语言水平和 儿童期的认知发育预测成年期的BAP，以及下一代的ASD严重程度（即，他们的 儿童），我们扩大我们的研究设计和方法显着，调查一个独特的，更广泛的 回顾性发展、认知、社会、行为和人格测量的档案数据库 从高中到年轻的ASD患者的祖父母和父母的队列中， 成年岁月这些丰富的资源，加上我们现有的纵向数据家长的小学测试 记录（我们将继续收集），将提供前所未有的发展概况， 儿童期和青年期（在有ASD孩子之前）可以预测ASD的遗传风险。我们也 通过分析，进一步探讨我们的候选语用语言内表型的生物学基础 听觉脑干反应与ASD家族中语用语言的扩展电池有关。最后， 我们研究了ASD患者家族中这些候选内表型的分子基础， 通过测量脆性X智力迟钝蛋白，这是FMR 1的蛋白产物， （涉及ASD神经病学），与听觉脑干有很强的联系， 数据显示可能与ASD患者家庭成员的语用语言特征有关。

Project Summary Differences in pragmatic (i.e., social) language are the language deficit most robustly associated with Autism Spectrum Disorder (ASD) and the Broad Autism Phenotype (BAP, a constellation of subclinical features in relatives that parallel in quality the defining characteristics of ASD and are believed to reflect genetic liability in clinically unaffected relatives). Findings from the initial award period indicate that retrospective, longitudinal measures of childhood language and cognitive development in parents, together with our battery of psycholinguistic and computational linguistic measures of pragmatic ability, measurable in individuals with ASD and their parents, are highly promising markers of ASD endophenotypes that can be targeted in genetic, neurobiological and treatment studies. This competing renewal builds significantly on these findings and our related work, in three important ways. First, given striking findings that parents' early rates of language and cognitive growth in childhood predict the BAP in adulthood, and ASD severity in the next generation (i.e., their children), we expand our study design and methods significantly, to investigate a unique and more expansive archival database of retrospective developmental, cognitive, social, behavior and personality measures available on a cohort of grandparents and parents of individuals with ASD, from high school through young adult years. These rich resources, together with our existing longitudinal data on parents' grade school testing records (which we will continue to collect), will afford an unprecedented look at developmental profiles through childhood and young adulthood (prior to having a child with ASD) that may predict genetic risk of ASD. We also further investigate the biological basis of our candidate pragmatic language endophenotypes through analysis of auditory brainstem response related to an expanded battery of pragmatic language in ASD families. Finally, we investigate the molecular basis of these candidate endophenotypes in families of individuals with ASD through measurement of the Fragile X Mental Retardation Protein, which is the protein product of FMR1 (implicated in ASD symptomatology), with strong connections to the auditory brainstem, and which preliminary data show may relate to pragmatic language features in family members of individuals with ASD.