Neuroanatomical Subtypes of Callous-Unemotional Traits in a Community Sample of Youth.

Importance: Callous Unemotional (CU) traits are associated with significant clinical and neurophysiological heterogeneity that may affect treatment effectiveness. Objective: To uncover neuroanatomical subtypes of CU traits using weakly-supervised machine learning and assess whether emerging subtypes differ on relevant clinical, temperamental, and environmental constructs. Design Setting and Participants: Imaging data was from the longitudinal Adolescent, Brain, Cognitive Development (ABCD) Study. Participants were 9-10 years old at baseline (M=9.925, 69.9% male) and included 222 children with CU traits and 234 typically developing controls matched on age, sex and income. Main Outcomes and Measures: The weakly-supervised heterogeneity through discriminative analysis (HYDRA) model was trained on grey matter (GM) volumes from 84 regions of interest (ROIs) and tested for reproducibility using cross-validation and permutation testing. Derived subtypes were compared cross-sectionally and prospectively on relevant clinical, temperamental, and environmental measures and subsequent GM volume at 2-year follow up. Results: HYDRA revealed an optimal 2-subtype solution within children with CU traits. Subtypes showed comparable levels of aggression that were significantly higher than typically developing controls. At the same time, subtype 1 had larger GM volume, fewer internalizing symptoms, and less adversity exposure, while subtype 2 was characterized by smaller GM volume, more internalizing symptoms, and more adversity exposure. Conclusions and Relevance: This study provides evidence of neuroanatomically distinct subtypes of CU traits characterized by different clinical and etiological profiles, with implications for diagnosis and treatment.