Aging Language Trajectories in Premutation Carrier Mothers

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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.