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 名女性中就有 1 名具有脆性 X 智力迟钝 - 1 (FMR1) 基因的前突变等位基因（Seltzer、Baker 等人，2012 年），这突出了关于FMR1 前突变的临床表型是一个重要的公共卫生优先事项。新出现的证据表明，FMR1 前突变的个体表现出语用语言或语言的社会使用方面的缺陷（Aziz 等人，2003 年；Losh、Klusek 等人，2012 年）。实用的语言技能对于有效的沟通至关重要，这方面的缺陷可能会导致无效的社会交流和难以管理社会关系（Bates，1976）。该提案旨在进一步描述具有 FMR1 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存在的界面，这种情况在具有 FMR1 前突变的个体中发生率较高（Bailey 等人，2008 年；Roberts 等人） .，2009）。将纳入一组患有自闭症谱系障碍 (ASD) 儿童的母亲，以了解不同表型之间的分离，并阐明可能归因于 FMR1 生化效应的一系列实用特征。具体来说，本研究旨在：(1) 确定 FMR1 前突变母亲的语用语言特征的具体方面与自闭症谱系障碍 (ASD) 儿童的母亲的特征相同或不同，并与对照组进行比较，(2) 评估功能性语言特征语用语言缺陷对个人和家庭结果的影响，以及（3）确定语用语言与焦虑之间的关系，以及 FMR1 前突变的母亲、自闭症谱系障碍儿童的母亲和对照之间的差异妈妈们。通过整合神经科学领域的科学进展，应用行为（标准化和实验）和生物标志物相结合的方法，该提案旨在阐明 FMR1 前突变中语用障碍的性质、潜在机制和功能后果。这项研究将揭示可能与 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工作产生影响。这项研究将在南卡罗来纳大学优秀的培训环境中、在专家、跨学科的背景下实施 拥有成功合作历史的导师团队。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记的专业知识，（3）培训使用眼动追踪方法来索引语言和相关过程，（4）磨练实用语言评估和理论技能，以及（5）提高专业技能，如资助写作、研究道德等。拟议的研究和培训经验将为研究员提供必要的技能，以发展重点研究计划线确定 ASD 和 FMR1 相关病症中沟通障碍的概况和预测因素。