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名女性在脆弱的X心理迟缓-1（FMR1）基因上具有首要等位基因（Seltzer，Baker等，2012），该研究强调了FMR1 Premoty的临床表型的研究。新兴的证据表明，具有FMR1预言的人在语言语言中表现出缺陷或语言的社会使用（Aziz等，2003； Losh，Klusek等，2012）。务实的语言技能对于效果沟通至关重要，这一领域的缺陷可能导致社会交流和难以管理社会关系的困难（Bates，1976）。该提案旨在进一步描述具有FMR1预赛的女性的务实语言表型，包括实用主义和焦虑症之间的可能接口，这在具有FMR1 Premuntion的个体中以升高的速度（Bailey等人，2008年； Roberts等人，2009年）。将包括一个自闭症谱系障碍儿童（ASD）的母亲的比较组，以便为​​跨表型的分离提供信息，并阐明可能归因于FMR1的生化作用的务实特征范围。具体而言，这项研究的目的是：（1）确定母亲的特定方面具有FMR1首演的务实语言形象，这些方面与患有ASD的儿童的母亲的特征共享或不同，并与对照组相比，（2）评估语言语言缺陷对个人和家人的焦虑之间的关系以及（3）的关系，以及（3）确定如何与他人之间的关系，以及（3）。预先享用ASD的孩子的母亲和对照母亲的母亲。通过整合神经科学的科学进步，以采用联合行为（标准化和实验性）和生物标志物方法，该建议旨在阐明FMR1 Premuntion中实用损害的性质，潜在的机制和功能后果。这项研究将为可能与FMR1的生化效应特别相关的特征范围介绍，并对潜在的预防和治疗工作产生影响。这项研究将在专家跨学科的背景下在南卡罗来纳大学的出色培训环境中实施 具有成功合作历史的指导团队。拟议的培训计划的重点是：（1）对焦虑对语言功能的影响进行全面了解，（2）在使用压力的生理和神经内分泌标记方面获得专业知识，（3）培训以使用眼分配方法来使用索引语言和相关过程，（4）培训技巧和培训技能，例如培训专业技能，以及（5）授予诸如5）师范的技能，以及（5）5），以及（5）培训技能，以及（5）培训技能，以及（5）5）具有开发计划研究的必要技能的研究员，重点是识别与ASD和FMR1相关条件下的沟通障碍的概况和预测指标。