Probing brain developmental patterns of myelination and associations with psychopathology in youth using gray/white matter contrast

Background: Cortical myeloarchitecture shows substantial development across childhood and adolescence, and aberrations in these trajectories are relevant for a range of mental disorders. The differential myelination of the cortex can be approximated using signal intensities in T1-weighted magnetic resonance images (MRI). Methods: To test the sensitivity of grey/white matter contrast (GWC) to age and individual differences in psychopathology and general cognitive ability in youth (8-23 years), we formed data-driven psychopathology and cognitive components using a large population-based sample, the Philadelphia Neurodevelopmental Cohort (PNC) (n=6487, 52% females). We then tested for associations with regional GWC defined by an independent component analysis (ICA) in a subsample with available MRI data (n=1467, 53% females). Results: The analysis revealed a global GWC component, which showed an age-related decrease from late childhood and across adolescence. In addition, we found regional anatomically meaningful components with differential age associations explaining variance beyond the global component. When accounting for age and sex, both higher symptom levels of anxiety or prodromal psychosis and lower cognitive ability were associated with higher GWC in insula and cingulate cortices and with lower GWC in pre- and postcentral cortices. We also found several independent regional associations with anxiety, prodromal psychosis and cognitive ability. Conclusion: Independent modes of GWC variation are sensitive to global and regional brain developmental processes, possibly related to ongoing intracortical myelination, and individual differences in regional GWC are associated with both mental health and general cognitive functioning.

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