Social Communication Trajectories as Predictors of FXAND in Young Children with the FMR1 Premutation

University Of South Carolina At Columbia, Columbia SC

Investigators

Abstract

Project 1 Component Modified Project Summary/Abstract Section Approximately 50-93% of individuals with the fragile X premutation (FXpm) are affected by Fragile X-Associated Neuropsychiatric Disorders (FXAND), a cluster of neuropsychiatric symptoms that encompasses anxiety, autism spectrum disorder (ASD) and related symptoms. However, very little is known about the FXpm phenotype in early childhood when FXAND features likely begin to emerge and early intervention would be most effective. Thus, detailed characterization of the FXpm pediatric phenotype is critical to identify individual differences in clinical features, facilitate early identification, and inform timing and targets of treatment. Early emerging social communication deficits likely contribute to FXAND-related outcomes, but little is understood about the developmental trajectory or consequences of social communication in early childhood in FXpm. Furthermore, the mechanisms that contribute to early social communication deficits in FXpm remain unknown. The overarching objectives of Project 1 are to (a) identify the pediatric phenotype in children with FXpm focusing on social communication and its effects on anxiety and ASD symptom severity; and (b) determine how auditory processing and molecular-genetic variation contribute to phenotypic heterogeneity in young children with FXpm. We will achieve these objectives through the following specific aims: (1) Identify how social communication deficits emerge and change across preschool and their relationship to FXAND outcomes; (2) Determine the extent to which auditory processing is altered in preschoolers with FXpm and predicts social communication deficits across development in preschoolers with FXpm; and (3) Determine how molecular-genetic variation predicts social communication deficits across preschool in FXpm. This innovative project leverages completed and ongoing studies to address critical research gaps in preschoolers with FXpm (n=60) contrasted to sex- and age-matched NT controls (n=40) through prospective longitudinal assessment at 3, 4, and 5 years of age. A multi-trait, multi-method approach will be employed to include several measures of social communication, behavioral and neurophysiological indices of auditory processing, and several indices of FMR1-related molecular-genetic variation. What little is known about the FXpm pediatric phenotype applies primarily to clinically referred children from well-resourced families and is not generalizable to the broader population of children with FXpm in the US. Therefore, we will recruit an unbiased sample in order to answer critical questions about the FXpm pediatric phenotype and identify potential mechanisms of involvement that can be targeted by early intervention. This work will have tremendous impact by informing a greater mechanistic understanding of deficits and timing of symptom progression of FXAND in FXpm which will inform future studies aimed at improving long-term outcomes in persons diagnosed with FMR1 conditions.