Common and Disorders-Specific Cortical Thickness Alterations in Internalizing, Externalizing and Thought Disorders in the Preadolescents of the ABCD Study

Overlap of brain changes across mental disorders has reinforced transdiagnostic models. However, the developmental basis for this overlap is unclear as are neural differences among internalizing, externalizing and thought disorders. These issues are critical to inform the theoretical framework for hierarchical transdiagnostic psychiatric taxonomy. We examined cortical thickness (CT) difference between healthy controls (n=4041) and patients with externalizing (n=1182), internalizing (n=1959) and thought (n=347) disorders in preadolescents (9-10 years) from the Adolescent Brain and Cognitive Development Study using linear mixed models. Genome-wide association analysis and cell type specificity analysis were performed on regional CT across 4,716 unrelated European youth. We found that youth with externalizing or internalizing disorders, but not thought disorders, exhibited significantly thicker cortex than controls. Externalizing and internalizing disorders shared thicker CT in left pars opercularis and caudal middle frontal gyrus related to lower cognitive performance. Somatosensory and primary auditory cortex were uniquely affected in externalizing disorders; primary motor cortex and higher-order visual association areas were uniquely affected in internalizing disorders. Only group of externalizing disorders demonstrated significant CT increase than controls at 2-year follow-up and decelerated cortical thinning from 10 to 12 years old. At genetic level, genes associated with CT in common and disorders-specific regions were also implicated in related diagnostic families. Microglia were the cell-type associated with CT for both externalizing/internalizing while dopaminergic/glutamatergic/GABAergic cells related only to externalizing-specific regions. These results showed that distinct anatomical trajectories relevant to internalizing/externalizing phenotypes may result from unique genetic and cell-type changes, but these occur in the background of significantly shared morphological variance.