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

Objective: 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. Methods: This study involved 11,878 preadolescents (9-10 years) with baseline and 2-year follow-up data (n=6571) from the Adolescent Brain and Cognitive Development Study release 3.0. Linear mixed models were implemented in comparative and association analyses. Genome-wide association analysis, gene set enrichment analysis and cell type specificity analysis were performed on regional cortical thickness (CT) across 4,716 unrelated European youth. Results: 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, which 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 (fusiform and inferior temporal gyrus) were uniquely affected in internalizing disorders. Baseline CT in one externalizing-specific region (left isthmus of cingulate cortex) related to externalizing behaviors at both baseline and 2-year follow-up. 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. Conclusions: 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.