Abstract

Individuals with autism spectrum disorder (ASD) display significant variation in clinical outcome. For instance, across age, some individuals’ adaptive skills naturally improve or remain stable, while others’ decrease. To pave the way for ‘precision-medicine’ approaches, it is crucial to identify the cross-sectional and, given the developmental nature of ASD, longitudinal neurobiological (including neuroanatomical and linked genetic) correlates of this variation. We conducted a longitudinal follow-up study of 333 individuals (161 with ASD and 172 neurotypicals, aged 6-30 years), with two assessment time points separated by ~12-24 months. We collected behavioural (Vineland Adaptive Behavior Scale-II, VABS-II) and neuroanatomical (structural magnetic resonance imaging) data. ASD participants were grouped into clinically meaningful “Increasers”, “No-changers”, and “Decreasers” in adaptive behaviour (based on VABS-II scores). We compared each clinical subgroup’s neuroanatomy (surface area and cortical thickness at T1, ∆T (intra-individual change) and T2) to that of the neurotypicals. Next, we explored the neuroanatomical differences’ potential genomic associates using the Allen Human Brain Atlas. Clinical subgroups had distinct neuroanatomical profiles in surface area and cortical thickness at baseline, neuroanatomical development, and follow-up. These profiles were enriched for genes previously associated with ASD and for genes previously linked to neurobiological pathways implicated in ASD (e.g., excitation-inhibition systems). Our findings suggest that distinct clinical outcomes (i.e., intra-individual change in clinical profiles) linked to ASD core symptoms are associated with atypical cross-sectional and longitudinal, i.e., developmental, neurobiological profiles. If validated, our findings may advance the development of interventions, e.g., targeting mechanisms linked to relatively poorer outcomes.