Fidler, Deborah J PHD

Narrative This aim of this Administrative Supplement project is to evaluate the utility of sleep and brain activity data to advance the early detection of autism spectrum disorder (ASD) in young children with Down syndrome (DS). We will leverage ASD-related phenotyping data collected in R01HD110542 and collect sleep actigraphy and fNIRS data concurrently with ASD assessment visits. Evaluating the feasibility of collecting usable data from these measures, and the subsequent use of these measures when feasible, may advance the early detection of co- occurring DS and ASD, identify potential mechanisms that contribute to the onset of ASD in DS, and potentially contribute to the development of novel interventions.

People with Down syndrome, the genetic condition caused by trisomy 21, display a unique clinical profile across the lifespan, including much elevated rates of diverse co-occurring conditions. Research efforts investigating the mechanisms by which trisomy 21 causes the hallmarks of Down syndrome, as well as the factors that modify these effects, will accelerate discoveries to improve health outcomes in this population. This project aims to develop a network of Down syndrome research sites in the USA and Latin America to increase the racial, ethnic, and socio-cultural diversity of investigations of the population with Down syndrome.

This project aims to refine and evaluate EXPO (EXecutive function Play Opportunities), a new caregiver- mediated intervention designed to support the development of executive function in children with Down syndrome. In this R61/33, we will continue the intervention development process by transforming EXPO into an adaptive intervention, with modifications for children who show greater degrees of developmental delay and who may respond more slowly to EXPO. We will then test the restructured EXPO adaptive intervention with a two- arm, Singly Randomized Trial that will evaluate the effectiveness of EXPO pathways.

Attention Deficit and Hyperactivity Disorder (ADHD) is a major health concern for individuals with Down Syndrome (DS), but there is currently no scientific foundation for the early detection and treatment of this comorbidity. In this project, we will link ADHD symptom profiles in 4-5- year-old children with Down syndrome to infant cognitive presentations from a prior wave of data collection, and examine the influence of biomedical risk factors in this longitudinal relationship. Identifying the early cognitive and biomedical risk factors associated with ADHD in DS will directly address the NIH INCLUDE Project objective of “defining the presentation and course of co-occurring conditions in individuals with Down syndrome” to inform future treatment innovations and improve adaptation in this population.

This project aims to identify developmental and biomedical markers of risk for autism spectrum disorder (ASD) in young children with Down syndrome to advance early screening procedures. This project will focus on two areas of potential ASD risk: (1) developmental presentation during early childhood and (2) co-occurring biomedical conditions. Results will inform revised recommendations regarding early ASD screening in children with Down syndrome ages 18 to 45 months, which will be disseminated to medical providers, interventionists, and researchers aiming to advance treatment for ASD and other co- occurring conditions associated with Down syndrome.

This Supplement project aims to identify molecular markers of risk for autism spectrum disorder (ASD) in young children with Down syndrome (DS) to advance early screening procedures. We will leverage the ASD-related phenotyping data collected in project #R01HD110542 and collect blood samples concurrently with ASD assessment visits. The addition of biospecimen collection to parent project data collection could facilitate the discovery of molecular indicators of ASD in DS and advance early detection of DS+ASD. It could also identify potential mechanisms that contribute to the onset of DS+ASD and contribute to a new scientific foundation for early intervention and future treatments in this population.

This project aims to identify early developmental, biomedical, and molecular indicators of risk for severe or profound intellectual disability in young children with Down syndrome (DS). Young children with DS will be assessed at three time points and cognitive outcomes will be analyzed in relation to behavioral, biomedical, and molecular risk factors. Results of this work will promote greater inclusivity in DS research and may facilitate innovations in both biomedical and behavioral intervention.