Charting Sex-Specific Developmental Trajectories in Autistic Children: A Multimodal, Accelerated Longitudinal Design

Autism spectrum disorder (ASD) has historically been diagnosed at a rate of four males to one female. Autistic females are diagnosed later than males and present with a nuanced profile of strengths and weaknesses that vary by developmental stage. In early childhood, our team, and others, have identified social motivation (SM) and restricted and repetitive behaviors (RRBs) as features that distinguish autistic males and females, with females showing greater SM and different patterns of RRBs. These relative strengths have been hypothesized to be potential mechanisms underlying autistic camouflage. However, camouflaging is also associated with detrimental outcomes, including poorer mental health. No study has charted sex-specific developmental trajectories in autism during early childhood. As such, representative, longitudinal studies are required to elucidate the developmental and etiological significance of previously observed sex differences (social motivation, RRBs, adaptive behavior, executive functioning, mental health) and to characterize early markers of camouflaging in childhood. We will conduct an Accelerated Longitudinal Design (ALD) across two sites (UNC and CHOP) in a sample of 140 neurotypical (NT) and 140 autistic children, equally split by sex, aged 4 to 8, recruited in 5 cohorts and studied over four timepoints. ALDs have been identified as a promising methodology to study development in ASD and recruit hard-to-reach groups. This multi-site effort will enable us to recruit sufficient autistic females to examine age- and sex-linked developmental trajectories. Our team is uniquely positioned to study how sex impacts the trajectories of young autistic children across domains (SM, RRBs, executive functioning, adaptive behavior, mental health) through multimodal measures (parent-report, direct observation, eye tracking) that can probe the mechanisms that underlie cross–sectionally observed sex differences in ASD. Our study has three aims designed to evaluate the impact of biological sex on developmental trajectories of young autistic children and NT controls. In Aim 1, we will probe phenotypic and mechanistic sex differences over time, focusing on SM and RRBs using across measurement modalities. In Aim 2, we will examine potential early sex differences in key areas of adaptive behavior, executive functioning, and mental health. In Aim 3 (exploratory), we will analyze the emergence of behavioral markers of camouflage (linguistic, gestures, smiling). This R01 project will chart the dynamic interplay between emergent ASD symptomology, sex, and development across early childhood. Our findings will inform sex-sensitive screening protocols and provide evidence for targeted supports to better address the needs of young autistic females.