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

Callous Unemotional (CU) traits are associated with significant clinical and neurophysiological heterogeneity that may affect treatment effectiveness.

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.

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.

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.

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.

This study provides evidence of neuroanatomically distinct subtypes of CU traits characterized by different clinical and etiological profiles, with implications for diagnosis and treatment.