Despite affecting 1 in 68 United States children, the mechanisms and early course of autism spectrum disorder (ASD) are largely unknown, delaying initiation of interventions known to alter the course of behavioral and neural development. Current studies of ASD emergence largely focus on infant siblings of children with ASD (ASIBs) who exhibit 20 times higher ASD risk than children without a family history. As a complement to this approach, studying the emergence of ASD in high-risk neurogenetic syndromes informs: (1) the generalizability of behav- ioral ASD ?red flags? to non-ASIBs, given the majority of children with ASD do not have positive sibling histories, and (2) genetic and biological pathways subserving ASD features, facilitating mechanistically-sensitive treat- ments. However, syndromic ASD studies are rarely attempted in infants due to the high costs, travel demands, and logistical challenges of assessing low-incidence groups. Furthermore, existing telehealth methods that could circumvent these challenges are not compatible with experimental, laboratory-based methods (e.g. visual atten- tion tasks, psychophysiology) sensitive to ASD risk. This Mentored Patient-Oriented Research Career Develop- ment Award (K23) will prepare Dr. Tonnsen, a clinically trained psychologist with expertise in ASD emergence in syndromic infants, to address these barriers by establishing a novel, telehealth-based assessment framework for prodromal ASD surveillance. This project leverages the candidate?s current expertise in biobehavioral pre- dictors of ASD through additional mentored training in (1) new ASD risk domains outside of her current expertise (e.g. social communication, motor skills), (2) telehealth-based clinical research, (3) mechanisms and pathways of syndromic ASD, (4) psychometrics and measurement, and (5) program management, academic writing, and ethics. Primary mentors are experts in the measurement of developmental psychopathology (Don Lynam, Ph.D.), syndromic ASD and telehealth (Leonard Abbeduto, Ph.D.), and social communication development in infants (Amanda Seidl, Ph.D.). Additional training is provided by a national team of experts across both patient-oriented (e.g. clinical profiles, treatment trials, healthcare engineering) and basic (e.g. genetics, mouse models) domains. With the support of her mentorship team, Dr. Tonnsen will develop and validate a telehealth assessment battery of prodromal ASD risk in local infants with syndromic intellectual disability (Aim 1). She will then remotely apply the battery to a national longitudinal sample of infants with Angelman syndrome (50% ASD risk) and fragile X syndrome (25-60% ASD risk;
Aim 2) to generate preliminary data and hypotheses for a subsequent R01. The proposed research is innovative because it represents a substantial departure from current methodological frameworks and participant samples for prospective ASD studies, laying the foundation for higher-powered, lower-cost, and wider-reaching studies of ASD emergence. Furthermore, the protected time, training, and data afforded by this project will crystallize Dr. Tonnsen?s path to independence as an interdisciplinary expert in re- mote surveillance of syndromic ASD in infants.
Autism spectrum disorder (ASD) affects 1 in 68 children, yet no reliable risk factors have been established in infants. Using a novel telehealth-based assessment framework, this study will examine ASD risk factors in infants with ASD-associated genetic syndromes to better understand the genetic and developmental mechanisms of ASD and potential treatment pathways. Characterizing infant risk profiles associated with ASD is important for early identification, which facilitates targeted treatments that are proven to improve individual outcomes and reduce public health costs associated with ASD. .