Characterization of the Attentional Profile in Women and Girls with a Fragile X Premutation Allele - PROJECT SUMMARY/ABSTRACT The current study will examine attention and the respective involved attentional subsystems among children and adult female carriers of the fragile X premutation allele (PM). The goals are to: 1) provide information about attentional subsystems and its presentation in this population; 2) examine whether there are age-related changes; and 3) investigate biological contributions to attention. In the US, approximately 1.5 million people carry a PM, defined as 55-200 expanded CGG repeats in the X-linked FMR1 gene. PM carriers do not have fragile X syndrome but they are at increased risk for fragile X-associated disorders in adulthood. Women with a PM are at risk for Fragile X-Associated Primary Ovarian Insufficiency, higher rates of mental health disorders and reported attention problems, and a late-life progressive neurodegenerative disorder, Fragile X Tremor/Ataxia Syndrome. No detailed examination of attentional subsystems exists in this population, but the possibility that underlying subtle changes in attention may reflect an etiology-specific phenotype and/or later cognitive and behavioral presentations is intriguing. To date, findings reported on performance-based measures of attention are inconclusive in PM women and lacking in PM girls. Via cross-sectional analysis of two cohorts, PM women and PM girls, each with an age-matched control group, the study will investigate whether mild, yet discernable, attention deficits are present in these cohorts using the Attention Network Test (ANT) and behavioral questionnaires. The ANT is a well-established, sensitive, cognitive task designed to measure the three attention networks of alerting, orienting and executive control. Intrasubject variability of reaction time on the ANT will also be calculated as a predictor of real-life outcomes. Preliminary studies led by the applicant with neurotypical children and PM women indicated that intrasubject variability is associated with reported attention and executive function problems while reaction time is not, supporting the utility of intrasubject variability to potentially bridge discrepancies between performance and reports. Behavioral characteristics of attention will be measured with self-reports for women and girls, and additional parent-reports for girls. This project will determine whether 1) women with a PM and 2) girls with a PM have an increased risk of attention problems compared to controls as determined with the ANT and standardized questionnaires; 3) whether cross sectional evaluation of attention problems shows evidence of worsening from childhood to adulthood in females with a PM; and 4) whether PM-related biological factors are associated with attentional outcomes in female PM carriers. Results will provide a rigorous assessment of the attentional profile in female children and adults with a PM. Facilitating detection of attention deficits in childhood and determining how these deficits manifest in adulthood may offer insight into a subtle underlying cognitive profile associated with a PM, allow for examination for potential age-related cognitive changes that might be associated with possible later risk, and provide a foundation for targeted and preventative interventions to enhance quality of life.
