Social-Affective Bases of Word Learning in Fragile X Syndrome and Autism

描述（由申请人提供）：尽管脆性X综合征（FXS）是一种与特征性行为表型相关的单基因（即FMR1）疾病，但在影响的严重程度、神经认知障碍的概况和所显示的共病条件方面存在相当大的综合征内变异性。大约25-30%的FXS患者也符合自闭症的诊断标准（AUT），其余的人表现出低于诊断阈值的自闭症样行为。在这个项目中，我们专注于了解与FXS男孩的AUT状态相关的语言发展的综合征内变异性。我们建议使用一个成熟的范式（即新单词学习）来研究FXS儿童（有或没有AUT）使用社会情感线索学习新单词的方式（具体目标1）；这种学习过程如何影响后来的语言成绩（具体目标2）；以及AUT状态、症状和焦虑以及环境和FMR1基因的差异如何导致这些过程中的综合征内变异（Specific Aim 3）。四组男孩将参与其中，各组根据非语言心理年龄进行匹配：仅FXS；FXS和AUT合并症；特发性AUT;典型的发展中国家。在时间1，每个男孩将参加三个单词学习研究，每个研究都侧重于使用不同类型的社会情感线索。还将对AUT症状、焦虑、认知和语言进行评估。母体同步性，一种支持语言发展的二元互动策略，以及FMRP水平也将被测量。1.5年后，每个男孩的语言能力将再次被评估。采用方差分析、多元线性回归和路径分析来比较各组在单词学习任务中的表现，检验时间1单词学习与后期语言之间的关系，以及单词学习与自闭症症状域、焦虑、母亲同步性和FMR1变异之间的并发关系。该项目将在威斯康辛州的怀斯曼中心和麻省理工学院（CA）进行。该项目的独特之处在于它包含了这三个非典型群体，并关注语言问题背后的过程。

DESCRIPTION (provided by applicant): Although fragile X syndrome (FXS) is a single-gene (i.e., FMR1) disorder associated with a characteristic behavioral phenotype, there is considerable within-syndrome variability in the severity of affectedness and the profile of neurocognitive impairments and co-morbid conditions displayed. About 25-30% of people with FXS also meet diagnostic criteria for autism (AUT), with the remainder displaying autistic-like behavior below the diagnostic threshold. In this project, we focus on understanding within-syndrome variability in language development in relation to AUT status among boys with FXS. We propose to use a well-established paradigm (i.e., novel word learning) to study the ways in which children with FXS (with and without AUT) use social- affective cues to learn new words (Specific Aim 1); how such learning processes impact later language outcomes (Specific Aim 2); and how differences in AUT status and symptoms and anxiety, as well as in the environment and the FMR1 gene, contribute to within-syndrome variation in these processes (Specific Aim 3). Four groups of boys will participate, with the groups matched on nonverbal mental age: FXS only; co-morbid FXS and AUT; idiopathic AUT; and typically developing. At Time 1, each boy will participate in three word- learning studies, each focused on the use of a different type of social-affective cue. Assessments of AUT symptoms, anxiety, cognition, and language will also be conducted. Maternal synchrony, a dyadic interaction strategy known to support language development, and FMRP levels will also be measured. 1.5 years later, each boy's language will again be assessed. ANOVA, multiple linear regression, and path analysis will be used to compare the performance of the groups in the word learning tasks, to examine the relationship between Time 1 word learning and later language, and to examine the concurrent relationships among word learning, autism symptom domains, anxiety, maternal synchrony, and FMR1 variation. The project will be conducted at the Waisman Center (Wisconsin) and the M.I.N.D. Institute (CA). The project is unique in its inclusion of these three atypical groups and its focus on the processes underlying language problems.