Multimodal neural correlates of childhood psychopathology

Complex structural and functional changes occurring in typical and atypical development necessitate multidimensional approaches to better understand the risk of developing psychopathology. Here, we simultaneously examined structural and functional brain network patterns in relation to dimensions of psychopathology in the Adolescent Brain Cognitive Development (ABCD) dataset. Several components were identified, recapitulating the psychopathology hierarchy, with the general psychopathology (p) factor explaining most covariance with multimodal imaging features, while the internalizing, externalizing, and neurodevelopmental dimensions were each associated with distinct morphological and functional connectivity signatures. Connectivity signatures associated with the p factor and neurodevelopmental dimensions followed the sensory-to-transmodal axis of cortical organization, which is related to the emergence of complex cognition and risk for psychopathology. Results were consistent in two separate data subsamples and robust to variations in analytical parameters. Although model parameters yielded statistically significant brain-behavior associations in unseen data, generalizability of the model was rather limited for all three latent components (r change from within- to out-of-sample statistics: LC1_within = 0.36, LC1_out = 0.03; LC2_within = 0.34, LC2_out = 0.05; LC3_within = 0.35, LC3_out = 0.07). Our findings help in better understanding biological mechanisms underpinning dimensions of psychopathology, and could provide brain-based vulnerability markers.