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，每151名妇女中就有1人在脆性X智力低下-1(FMR1)基因上有前突变等位基因(Seltzer，Baker等人，2012年)，这突出了对FMR1前突变的临床表型的研究是一个重要的公共卫生优先事项。新出现的证据表明，携带FMR1预突变的个体在语用语言或语言的社会使用方面存在缺陷(Aziz等人，2003；Losh，Klusek等人，2012)。语用语言技能对于有效的交际至关重要，而这方面的不足可能会导致无效的社会交流和难以管理社会关系(Bates，1976)。这一建议旨在进一步描述携带FMR1预突变的女性的语用语言表型，包括语用学和焦虑症之间的可能接口，在携带FMR1预突变的个体中，这两种疾病的发生率较高(Bailey等人，2008年；Roberts等人，2009年)。将包括一组患有自闭症谱系障碍(ASD)儿童的母亲，以告知不同表型之间的分离，并阐明可能归因于FMR1生化效应的一系列语用特征。具体地说，本研究的目的是：(1)找出FMR1基因突变母亲的语用语言特征与ASD儿童母亲相同或不同的特征，并与对照组进行比较；(2)评价语用语言缺陷对个体和家庭结果的功能影响；(3)确定语用语言与焦虑的关系，以及它在FMR1基因突变母亲、ASD儿童母亲和对照母亲中的差异。通过整合神经科学的科学进展，应用行为(标准化和实验)和生物标记物相结合的方法，该建议旨在阐明FMR1前突变中语用障碍的性质、潜在机制和功能后果。这项研究将提供可能与FMR1的生化效应具体相关的一系列特征，并对潜在的预防和治疗努力具有意义。这项研究将在南卡罗来纳大学优秀的培训环境中进行，在专家、跨学科的背景下进行 拥有成功合作历史的导师团队。拟议的培训计划集中于：(1)全面了解焦虑对语言功能的影响，(2)获得使用应激的生理和神经内分泌标记物的专业知识，(3)培训使用眼球追踪方法来索引语言和相关过程，(4)磨练语用语言评估和理论方面的技能，以及(5)磨练专业技能，如补助金撰写、研究伦理等。拟议的研究和培训经验将为研究员提供必要的技能，以制定一系列研究计划，侧重于确定ASD和FMR1相关疾病的沟通障碍的特征和预测因素。