Aging Language Trajectories in Premutation Carrier Mothers

早突变携带者母亲的衰老语言轨迹

基本信息

批准号：
9892021
负责人：
Jessica Klusek
金额：
$ 7.45万
依托单位：
UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-04-01 至 2022-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9892021
关键词：
Adopted Adult Advocate Age Aging Caring Child Child Rearing Clinical Clinical Management Cognitive Cognitive deficits Cohort Effect Communication Competence Data Development Disabled Children Environmental Risk Factor Exhibits FMR1 Fragile X Syndrome Genes Genetic Predisposition to Disease Glean Growth Individual Intervention Investigation Knowledge Language Language Disorders Life Light Linguistics Long-Term Effects Mental Health Molecular Abnormality Mothers Mutate Perception Phenotype Premature aging syndrome Prevention Production Publishing Quality of life Research Risk Sampling Selection Bias Severities Social Interaction Stress Symptoms Techniques Time United States Woman Work age related base clinical effect density disability experience healthy aging indexing innovation interest longitudinal design middle age physical conditioning population based premature primary caregiver screening skills social therapy development

项目摘要

PROJECT SUMMARY/ABSTRACT About 1 in 151 women in the US are carriers of a genetic abnormality called the FMR1 premutation. Mothers who carry the FMR1 premutation are at risk for passing the mutated gene to their children, which may result in fragile X syndrome. The FMR1 premutation is also associated with its own clinical symptoms, which appear to worsen with age. New, emerging evidence suggests that premutation carrier mothers may experience premature age-related decline in language production skills that may begin as early as the third or fourth decade of life. Language production deficits impede effective communication, reduce perceptions of competence, and negatively impact social interaction. Premutation carrier mothers are particularly vulnerable to the negative consequences of language deficits, as they are the primary caregivers for their children with fragile X and effective communication skills are necessary to care and advocate for their disabled children. Yet, a major obstacle in the field is that all existing evidence has been gleaned from cross-sectional data. Longitudinal research is needed to confirm the presence of age-related linguistic decline across early-to-middle adulthood. There is also a need to better understand how environmental factors, such as elevated parenting stress associated with caring for a child with a disability, contribute to the expression of premutation symptoms over time. Poor understanding of the aging premutation phenotype and its mechanisms represents a substantial barrier to effective clinical management of premutation carriers, as we lack the data needed to understand the long-term effects of this genetic abnormality over time. The present study will represent one of the first longitudinal investigations of premutation carriers. We will delineate age-related changes in language skills across early-to-mid adulthood (Aim 1) and determine the effect of elevated parenting stress on aging trajectories (Aim 2). We are uniquely poised to pursue this work given our access to a rare corpus of previously-collected longitudinal language samples from premutation carrier mothers. We will use well-established language sample analytic techniques to extract new language variables from these existing samples: propositional density, grammatical complexity, and dysfluency. Adopting an innovative statistical approach—an accelerated longitudinal design-- we will track age-related change in these features across early-to-mid adulthood (30-62 years). This work will contribute significantly to current understanding of the aging premutation phenotype, inform critical age periods for intervention, and shed light on parenting stress as a potential intervention target for ameliorating premutation symptoms.

项目概要/摘要在美国，大约每 151 名女性就有 1 名是 FMR1 前突变基因异常的携带者。携带 FMR1 前突变的母亲有将突变基因传给孩子的风险，这可能导致脆性 X 综合征的 FMR1 前突变也与其自身的临床症状相关。新的、不断出现的证据表明，前突变携带者母亲的情况可能会随着年龄的增长而恶化。经历与年龄过早相关的语言表达能力下降，最早可能从三岁或三岁开始语言能力的缺陷阻碍了有效的沟通，降低了对生活的看法。能力和社交互动的负面影响前突变携带者母亲特别容易受到影响。语言缺陷的负面后果，因为他们是脆弱儿童的主要照顾者 X 和有效的沟通技巧是照顾和倡导残疾儿童所必需的。该领域的障碍是所有现有证据都是从横截面数据中收集的。需要进行研究来证实在成年早期到中期是否存在与年龄相关的语言衰退。还需要更好地了解环境因素（例如养育压力增加）如何影响与照顾残疾儿童有关，有助于表达突变前症状对衰老前突变表型及其机制的了解不足是一个重大问题。前突变携带者的有效临床管理的障碍，因为我们缺乏了解所需的数据随着时间的推移，这种遗传异常的长期影响。本研究将是对前突变携带者的首次纵向研究之一。描绘成年早期到中期语言技能与年龄相关的变化（目标 1）并确定养育压力增加对衰老轨迹的影响（目标 2）。鉴于我们可以访问先前从前突变中收集的纵向语言样本的罕见语料库我们将使用成熟的语言样本分析技术来提取新的语言。这些现有样本中的变量：命题密度、语法复杂性和采用不流畅。创新的统计方法——加速的纵向设计——我们将跟踪与年龄相关的变化这项工作将为当前的成年早期到中期（30-62 岁）的这些特征做出重大贡献。了解衰老前突变表型，告知干预的关键年龄期，并阐明养育压力作为改善突变前症状的潜在干预目标。