Attention, Memory, and Executive Function in Fragile X

尽管相当多的研究已经检查了脆性X综合征（FXS）的一般智力功能和适应行为，但只有少数研究检查了神经认知功能的特定领域，特别是在男性中。现有的研究受到横断面设计、缺乏比较组、样本年龄范围广以及评估方法不一致的限制。拟议中的项目将通过对注意力、记忆和执行功能进行更详细、系统和广泛的评估，大大增加我们对FXS神经认知功能的了解。该项目建立在现有的FXS儿童样本的基础上，这些儿童参加了一项前瞻性的纵向研究，他们即将进入青春期。我们将详细描述青春期早期认知功能和发展的本质，并将功能和发展与其他临床、遗传、神经心理学、生物学和社会人口学变量联系起来，以便更准确地描述FXS表型并了解该人群中的变异性。该研究将纳入68名8至13岁之间患有FXS的儿童样本。由68名心理年龄匹配的正常发育儿童组成的对照组将提供有关FXS与自身心理年龄相关的相对认知优势和劣势的见解。每个孩子每年都会接受一次综合评估，包括注意力、记忆力和执行功能。另外还将收集FMRP、青春期状况、社会经济状况、气质、自闭症行为、语言发展、视觉加工技能和行为问题等指标。这些额外的评估将测试蛋白质表达与神经认知功能之间的关系，确定发育模式的变化作为青春期的功能，为环境在影响结果中的作用提供一些见解，并通过提供一系列可能与FXS相关的特征的全面描述来增加FXS表型的特异性。一系列的分析程序，包括层次线性建模，将用于回答与确定神经认知概况，与对照组比较概况，检查随时间的变化，以及测试神经认知功能与其他感兴趣的变量之间的关系有关的四个具体目标。

Although considerable research has examined general intellectual functioning and adaptive behavior in fragile X syndrome (FXS), only a few studies have examined specific domains of neurocognitive functioning, especially in males. Existing research has been limited by cross-sectional designs, lack of comparison groups, a wide age range in the samples, and inconsistencies in assessment methodologies. The proposed project would add substantially to our knowledge about neurocognitive function in FXS by conducting more detailed, systematic, and expansive assessments of attention, memory, and executive function. The project builds on an existing sample of children with FXS participating in a prospective, longitudinal study who are about to enter puberty. We will describe in detail the nature of cognitive function and development over time during early adolescence, and relate function and development to other clinical, genetic, neuropsychological, biological, and sociodemographic variables in order to describe more precisely the FXS phenotype and understand the variability within this population. The study will incorporate a sample of 68 children with FXS between the ages of 8 and 13 years. A comparison group of 68 mental-age-matched typically developing children will provide insights into relative cognitive strengths and weaknesses in FXS in relation to their own mental age. Each child will be assessed annually using a comprehensive battery of attention, memory, and executive function measures. Additional measures will be collected of FMRP, pubertal status, socioeconomics status, temperament, autistic behavior, language development, visual processing skills, and behavior problems. These additional assessments will test the relationship between protein expression and neurocognitive function, identify changes in patterns of development as a function of puberty, provide some insights into the role of environment in affecting outcomes, and increase the specificity of the FXS phenotype by providing a comprehensive description of a range of features likely to be associated with FXS. A range of analytic procedures, including hierarchical linear modeling, will be used to answer four specific aims related to determining neurocognitive profiles, comparing profiles with the comparison group, examining change over time, and testing the relationship between neurocognitive function and other variables of interest.