Developmental Dynamics of Phenotypic Architecture in ASD

Abstract

The behavioral features of autism spectrum disorders (ASD) span multiple domains, yet how behavioral dimensions shape and contribute to ASD phenotypes remains unknown. Here, using large-scale phenotypic data from SPARK, I identified a reproducible architecture linking sensory-repetitive, motor, and social-communication features with broader clinical variation and show broad associations with psychopathology. This organization is recovered across independent SPARK subsets and independently replicated in the Simons Simplex Collection, where sensory-repetitive features again form the highest-ranking hubs. Anxiety-related symptoms contribute to but not fully account for this organization. Age-stratified analyses in SPARK revealed a marked reorganization of phenotypic architecture with sensory-repetitive features dominating the hub hierarchy in childhood and motor features rising to the highest relative positions in adolescence and adulthood. Together, these findings suggest that autism-related heterogeneity is not simply multidimensional but organized around a reproducible sensory-repetitive-centered architecture whose developmental expression varies across cohorts.