Brain morphological pattern is associated with the presence, severity and transition of transdiagnostic psychiatric disorders in preadolescents

Abstract

Cognitive function, psychological processes, mental states and behaviors are key dimensions of mental disorders across diagnostic categories, but whether they are linked to common or distinct brain morphological patterns underlying risk or resilience remains unclear. The current study is a longitudinal investigation of 8,672 youths from the Adolescent Brain Cognitive Development (ABCD) study aged 9–10 years at baseline (4,412 male; 4,260 female). A machine learning approach based on canonical correlation analysis was used to identify latent dimensional associations of cortical morphology (surface area, cortical and subcortical volume, cortical thickness and sulcal/gyral depth) with multidomain behavioral assessments, including cognitive scores and psychological measures indexing motivation, impulse control, mental states and behaviors across a continuum from healthy to pathological. We identified a robust latent brain structural variate across morphological measures that correlated positively with cognitive performance and negatively with psychological measures indexing greater psychopathology. Higher scores on this brain variate reflected larger cortical surface area and cortical volume, especially in the temporal gyri, together with a posterior–anterior gradient in cortical thickness, showing greater thickness in occipital, parietal and temporal cortices and lower thickness in cingulate and frontal regions. This brain variate and the related cognitive–psychological–behavioral variate remained stable and showed a dose-dependent relationship with cumulative psychiatric diagnoses assessed concurrently and at the 2-year follow-up, with lower brain variate scores associated with higher numbers of comorbid diagnoses. Brain scores were also associated with longitudinal transitions between healthy and diagnosed states: lower baseline scores associated with persistent psychiatric diagnoses and higher baseline scores associated with persistent healthy states, suggesting a vulnerability–resilience continuum for psychopathology. These findings advance the neurodevelopmental understanding of psychiatric disorders and highlight the potential utility of morphology-informed approaches for early screening and intervention in youth. This study investigates the relationship of brain morphology with cognitive and psychological dimensions in 8,672 youths, using machine learning to reveal significant correlations between cortical metrics and behavioral assessments, indicating a continuum of vulnerability and resilience for psychiatric disorders.