Grammatical Development in Boys with Fragile X Syndrome and Autism

描述(申请人提供)：脆性X综合征是导致智力残疾的主要遗传原因，大多数男性(95%)的智商低于70。大多数患有脆性X的男性表现出类似自闭症的行为，25%-30%的人符合DSM-IV自闭症共同诊断标准。患有脆性X基因和自闭症的男性通常被报道在认知和接受性/表达语言方面有更严重的全面障碍。然而，只有脆性X和共病的脆性X和自闭症的语言表型在不同的个体中是非常不同的。此外，自闭症对脆性X的语言表型的影响尚不清楚。拟议项目的目的是确定FXS和自闭症是否存在语法缺陷，同时研究自闭症对脆性X语言的影响。迄今为止，关于发展障碍语言发展的研究一直是描述性的，而不是理论驱动的。然而，关于语言障碍儿童的语法发展，有一系列丰富的理论驱动的研究。扩展的可选不定式解释(EOI)认为，有特定语言障碍的儿童似乎陷入了一个可选的不定式阶段，在这个阶段，他们将某些语法语素的使用视为可选的，尽管它们在成人语法中处于强制性地位。初步证据表明，患有脆性X的儿童和患有自闭症的儿童可能在语法发展的至少一个方面表现出缺陷(例如，限定标记；过去时：他走了)，而不依赖于非语言智商。本项目将通过检查所有限定标记(BE/DO)以及非限定语法语素(即复数-S，所有格-S，现在进行时-ing)来推进前期工作。这项调查将告诉我们，患有脆性X的男孩是否表现出类似SLI的语法特征，或者他们的语言是否具有所有语法语素的全局困难的特征。此外，还将通过比较患有和不患有自闭症的脆性X男孩和患有特发性自闭症的男孩，来检验共病自闭症对语法发展的影响。此外，这项拟议的研究还将检验评估FXS男孩和自闭症男孩语法的最有效方法。63名年龄在9-16岁之间的男孩将参与这项研究：仅患有FXS的男孩，患有FXS和自闭症的男孩，以及患有特发性自闭症的男孩。参与者将完成标准化测试、语言样本、自闭症诊断措施和句子模仿任务。这些结果将为脆性X和自闭症的表型提供信息，并为不同病因条件下语言障碍的变异性提供见解。这些拟议研究的信息将为(1)关于神经对语言发展的限制的假说以及(2)临床评估和干预程序提供信息。这项研究为今后评估语言系统的其他方面所需的研究奠定了基础。 公共卫生相关性：这项拟议的研究与公共卫生相关，因为它有助于一个研究项目，该项目的重点是显著提高包括脆性X和自闭症在内的智力残疾儿童的沟通能力。拟议的项目旨在了解评估智障儿童语言的最佳方法，这与NIDCD改善沟通障碍个人生活的使命相关。此外，通过研究自闭症对脆性X的影响，拟议的项目将提出关于语言发展的神经限制的假设，这与NIDCD和NIH的整体使命有关。

DESCRIPTION (provided by applicant): Fragile X syndrome is the leading inherited cause of intellectual disability, with the majority of males (95%) having IQs below 70. Most males with fragile X display autistic-like behaviors, and 25-30% meet the DSM-IV criteria for an autism co-diagnosis. Males with comorbid fragile X and autism are typically reported to have more severe overall impairments in cognition and receptive/expressive language. However, the language phenotype within fragile X only and comorbid fragile X and autism is extremely variable across individuals. Moreover, the impact of autism on the language phenotype of fragile X is not clear. The purpose of the proposed project is to determine if there is a grammatical deficit in FXS and in autism, while examining the consequences of comorbid autism on language in fragile X. Research on language development in developmental disabilities to date has been descriptive in nature, as opposed to theory-driven. There is however, a rich theory-driven line of research on grammatical development in children with language impairments. The extended optional infinitive account (EOI) posits that children with specific language impairment seem to get "stuck" in an optional infinitive stage in which they treat the use of certain grammatical morphemes as optional, despite their obligatory status in the adult grammar. Preliminary evidence suggests that children with fragile X and children with autism may demonstrate a deficit in at least one aspect of grammatical development (i.e., finiteness marking; past tense: he walked) independent of nonverbal IQ. This project will advance preliminary work by examining all finiteness markers (BE/DO), as well as non-finiteness grammatical morphemes (i.e., plural -s, possessive -s, present progressive -ing). This investigation will inform whether boys with fragile X show a grammatical profile similar to SLI, or if their language is characterized by global difficulty with all grammatical morphemes. In addition, the impact of co-morbid autism on grammatical development will be examined by comparing boys with fragile X with and without autism and boys with idiopathic autism. Additionally, the proposed study will examine the most effective method of assessing grammar in boys with FXS and boys with autism. Sixty-three boys between the ages of 9-16 years will participate in this study: boys with FXS only, boys with FXS and autism, and boys with idiopathic autism. Participants will complete standardized tests, a language sample, autism diagnostic measures, and a sentence imitation task. These results will inform the phenotypes of fragile X and autism and provide insights into the nature of variability in language impairments across different etiological conditions. The information from the proposed studies will inform (1) hypotheses regarding neural constraints on language development as well as (2) clinical assessment and intervention procedures. This study lays the groundwork for future studies needed to assess additional aspects of the linguistic system. PUBLIC HEALTH RELEVANCE: The proposed research is relevant to public health given that it contributes to a program of research focused on significantly improving the communication abilities of children with intellectual disabilities, including fragile X and autism. The proposed project seeks to understand the best method of assessment of language in children with intellectual disabilities, which is relevant to NIDCD's mission to improve the lives of individuals with communication disorders. Additionally, by examining the impact of autism on fragile X, the proposed project will suggest hypotheses about neural constraints on language development, which is relevant to the mission of NIDCD and the NIH as a whole.