Profiles and Predictors of Pragmatic Language Impairments in the FMR1 Premutation

FMR1 前突变中语用语言障碍的概况和预测因素

• 批准号: 8716154
• 负责人: Jessica Klusek
• 金额: $ 5.31万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-01-24 至 2017-01-23
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8716154
• 关键词: Adopted; Affect; Affective; Alleles; Anxiety; Anxiety Disorders; Area; Autistic Disorder; Back; Behavioral; Biochemical; Biological Markers; Child; Clinical; Collaborations; Communication; Communication impairment; Development; Diagnosis; Disease susceptibility; Environment; FMR1 Gene; Family; Fragile X Syndrome; Friendships; Genes; Genetic; Genetic Predisposition to Disease; Grant; Health; High Prevalence; Impairment; Individual; Language; Language Disorders; Lead; Light; Link; Literature; Mental Health; Mentorship; Methods; Mood Disorders; Mothers; Mutate; Mutation; Nature; Neurosciences; Neurosecretory Systems; Outcome; Ovarian; Phenotype; Physiological; Population; Prevention; Process; Public Health; Quality of life; Recording of previous events; Relative (related person); Research; Research Ethics; Research Training; Risk; Scientific Advances and Accomplishments; Severities; Social Environment; Social support; South Carolina; Stress; Subgroup; Theoretical model; Training; Tremor/Ataxia Syndrome; Universities; Woman; Work; Writing; autism spectrum disorder; clinical phenotype; comparison group; disorder control; environmental stressor; experience; functional outcomes; hypothalamic-pituitary-adrenal axis; indexing; physical conditioning; population based; premature; public health priorities; public health relevance; research study; screening; skills; social; theories

DESCRIPTION (provided by applicant): New population-based screening indicates that 1 in 151 women have premutation alleles on the Fragile X Mental Retardation-1 (FMR1) gene (Seltzer, Baker, et al., 2012), which highlights research on the clinical phenotype of the FMR1 premutation as a significant public health priority. Emerging evidence suggests that individuals with the FMR1 premutation show deficits in pragmatic language, or the social use of language (Aziz et al., 2003; Losh, Klusek, et al., 2012). Pragmatic language skills are critical for effectie communication, and deficits in this area may lead to ineffective social interchange and difficulty managing social relationships (Bates, 1976). This proposal aims to further delineate the pragmatic language phenotype of women with the FMR1 premutation, including the possible interface between pragmatics and anxiety disorders, which are seen at elevated rates among individuals with the FMR1 premutation (Bailey et al., 2008; Roberts et al., 2009). A comparison group of mothers of children with autism spectrum disorder (ASD) will be included in order to inform disassociation across phenotypes and shed light on the range of pragmatic features that may be attributed to the biochemical effects of FMR1. Specifically, this study aims to: (1) identif specific aspects of the pragmatic language profile of mothers with the FMR1 premutation that are shared or distinct from the profile of mothers of children with ASD, and compared to controls, (2) evaluate the functional impact of pragmatic language deficits on individual and family outcomes, and (3) determine the relationship between pragmatic language and anxiety, and how it differs among mothers with the FMR1 premutation, mothers of children with ASD, and control mothers. By integrating scientific advances in neuroscience to apply a combined behavioral (both standardized and experimental) and biomarker approach, this proposal aims to clarify the nature, underlying mechanisms and functional consequences of pragmatic impairments in the FMR1 premutation. This research will inform the range of features that may be specifically linked to the biochemical effects of FMR1, and has implications for potential prevention and treatment efforts. This research will be implemented within the excellent training environment at the University of South Carolina, within the context of an expert, interdisciplinary mentorship team that has a proven history of successful collaboration. The proposed training plan focuses on: (1) developing a comprehensive understanding of the impact of anxiety on language function, (2) attaining expertise in the use of physiological and neuroendocrine markers of stress, (3) training to use eyetracking methods to index language and related processes, (4) honing skills in pragmatic language assessment and theory, and (5) sharpening professional skills such as grant writing, research ethics, etc. The proposed research and training experiences will provide the fellow with the necessary skills to develop a programmatic line of research focused on identifying profiles and predictors of communication impairments in ASD and FMR1-associated conditions.

描述（由申请人提供）：新的基于人群的筛查表明，151名妇女中有1名在脆性X智力迟钝-1（FMR 1）基因上具有前突变等位基因（Seltzer，Baker等人，2012），其强调了对FMR 1前突变的临床表型的研究作为重要的公共卫生优先事项。新出现的证据表明，具有FMR 1前突变的个体在语用语言或语言的社会使用方面表现出缺陷（Aziz et al.，2003; Losh，Klusek等人，2012年）。语用语言技能对于有效的交流至关重要，这方面的缺陷可能导致无效的社会交流和难以管理社会关系（贝茨，1976）。该建议旨在进一步描述具有FMR 1前突变的女性的语用语言表型，包括语用学和焦虑症之间可能的界面，其在具有FMR 1前突变的个体中以升高的比率出现（Bailey等人，2008; Roberts等人，2009年）。将包括自闭症谱系障碍（ASD）儿童的母亲的比较组，以告知表型之间的分离，并阐明可能归因于FMR 1的生化作用的实用特征的范围。具体而言，本研究旨在：（1）确定FMR 1前突变母亲的语用语言特征的特定方面，这些方面与ASD儿童的母亲的特征相同或不同，并与对照组进行比较，（2）评估语用语言缺陷对个人和家庭结果的功能影响，以及（3）确定语用语言和焦虑之间的关系，以及FMR 1前突变的母亲、ASD儿童的母亲和对照母亲之间的差异。通过整合神经科学的科学进展，应用组合的行为（标准化和实验）和生物标志物的方法，该提案的目的是澄清的性质，潜在的机制和功能后果的语用障碍FMR 1前突变。这项研究将揭示可能与FMR 1的生化作用有关的一系列特征，并对潜在的预防和治疗工作产生影响。这项研究将在南卡罗来纳州大学的优秀培训环境中实施，在专家，跨学科的背景下， 具有成功合作历史的指导团队。拟议的培训计划侧重于：（1）全面了解焦虑对语言功能的影响，（2）获得使用压力的生理和神经内分泌标志物的专业知识，（3）使用眼动追踪方法索引语言和相关过程的培训，（4）磨练实用语言评估和理论的技能，以及（5）锐化专业技能，如拨款写作，拟议的研究和培训经验将为研究员提供必要的技能，以开发一个专注于确定ASD和FMR 1相关条件中沟通障碍的概况和预测因素的研究方案。