Sex, Gender, and Camouflage in Autism Spectrum Disorder: A Multimodal, Accelerated Longitudinal Design

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PROJECT SUMMARY Autism spectrum disorder (ASD) is 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 distinguishing features between autistic males and females. It has also been hypothesized that these differences serve as potential mechanisms that underlie autistic camouflage. Also critical to the study of sex differences in ASD is the study of gender and gender diversity. A number of international studies have identified higher rates of gender diversity in autistic adolescents and adults, with potentially higher rates in autistic females. No study has charted the trajectories of these interwoven characteristics (sex, gender, camouflaging) together or in early childhood. Representative, longitudinal studies are required to elucidate the developmental and etiological significance of previously observed sex differences and to characterize gender diversity and camouflaging in early 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 biological sex (Harrop, Parish-Morris) and gender (Strang, Harrop) impact the trajectories of young autistic children 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 two aims: Aim One: Evaluate the impact of biological sex on developmental trajectories of young autistic children. We will probe phenotypic and mechanistic sex differences overtime, focusing on SM and RRBs. We will also chart the emergence of behavioral markers of camouflage. Aim Two: Characterize trajectories of congruence/incongruence between biological sex and gender in young autistic children. We will identify early signs of gender diversity in young autistic and NT children through parent and self-report. We will also examine the role of gender in predicting SM and RRBs and common phenotypic variables to understand how biological sex at birth (Aim One) and gender (Aim Two) differentially predict trajectories in autistic youth. This R01 project will chart the dynamic interplay between emergent ASD symptomology, biological sex, and gender in early childhood. This work will inform sex-sensitive screening protocols and provide evidence for sex- and gender-sensitive interventions to better address the needs of autistic females.