Aging Language Trajectories in Premutation Carrier Mothers

早突变携带者母亲的衰老语言轨迹

• 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
• 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

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.

项目总结/摘要 在美国，每151名女性中就有1名携带有一种称为FMR 1前突变的遗传异常。 携带FMR 1前突变的母亲有将突变基因遗传给孩子的风险，这可能会 导致脆性X综合征。FMR 1前突变也与其自身的临床症状有关， 似乎随着年龄的增长而恶化。新出现的证据表明，前突变携带者母亲可能 经历过早的与年龄相关的语言生产技能下降，可能早在第三或第四个月就开始开始。 人生的第四个十年语言产生缺陷阻碍有效沟通，减少对 能力，并对社会交往产生负面影响。前突变携带者的母亲特别容易受到 语言缺陷的负面影响，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必要的照顾和倡导他们的残疾儿童。然而，一个主要的 该领域的一个障碍是，所有现有的证据都是从横截面数据中收集的。纵向 需要进行研究，以确认在成年早期至中期存在与年龄有关的语言能力下降。 还需要更好地了解环境因素，如养育压力的增加， 与照顾残疾儿童有关，有助于表达突变前症状， 时间对衰老前突变表型及其机制的认识不足， 对前突变携带者进行有效临床管理的障碍，因为我们缺乏了解 这种遗传异常的长期影响。 本研究将代表一个第一次纵向调查的前突变携带者。我们将 描述与年龄相关的语言技能在成年早期到中期的变化（目标1），并确定 提高养育压力对衰老轨迹的影响（目标2）。我们是独一无二的准备从事这项工作 考虑到我们可以访问一个罕见的语料库，以前收集的纵向语言样本，从前突变 携带者母亲我们将使用成熟的语言样本分析技术来提取新的语言 这些现有样本的变量：命题密度，语法复杂性和不流利性。采用 一个创新的统计方法-加速纵向设计-我们将跟踪与年龄相关的变化， 这些特征在早期至中期成年（30-62岁）。这项工作将大大有助于目前 了解衰老前突变表型，告知干预的关键年龄段，并阐明 父母压力作为改善突变前症状的潜在干预目标。