A normative modelling approach reveals age-atypical cortical thickness in a subgroup of males with autism spectrum disorder

Understanding heterogeneity is an important goal on the path to precision medicine for autism spectrum disorders (ASD). We examined how cortical thickness (CT) in ASD can be parameterized as an individualized metric of atypicality relative to typically-developing (TD) age-related norms. Across a large sample (n = 870 per group) and wide age range (5–40 years), we applied normative modelling resulting in individualized whole-brain maps of age-related CT atypicality in ASD and isolating a small subgroup with highly age-atypical CT. Age-normed CT scores also highlights on-average differentiation, and associations with behavioural symptomatology that is separate from insights gleaned from traditional case-control approaches. This work showcases an individualized approach for understanding ASD heterogeneity that could potentially further prioritize work on a subset of individuals with cortical pathophysiology represented in age-related CT atypicality. Only a small subset of ASD individuals are actually highly atypical relative to age-norms. driving small on-average case-control differences.