Genotype and corticosteroid treatment are distinctively associated with gray matter characteristics in patients with Duchenne muscular dystrophy

This study investigated if structural variation in specific gray matter areas is associated with corticosteroid treatment or genotype, and if cerebral morphological variations are related to neuropsychological and behavioral outcomes. The CAT12 toolbox in SPM was used for MRI segmentations, assessing subcortical structures, cortical thickness, gyrification, and sulci depths for DMD patients (n = 40; 9–18 years) and age-matched controls (n = 40). Comparisons were made between DMD vs. controls, daily vs. intermittent corticosteroid treatment (n = 20 each), and Dp140⁺ vs. Dp140^- gene mutations (n = 15 vs. 25). MANCOVA, CAT12 3D statistics and Pearson correlations were conducted. DMD patients showed differences in volumes of distinct subcortical structures, left hemisphere cortical thickness, and gyrification in multiple brain areas compared with healthy controls. The daily treated DMD group exhibited differences in subcortical volumes and different patterns of cortical thickness, sulci depth, and gyrification compared to the intermittent treated DMD group. DMD Dp140⁺ patients displayed altered gyrification and sulci depth compared to DMD Dp140^- patients. Finally, we found correlations between neurobehavioral outcomes and brain areas that showed differences in cortical morphology associated with corticosteroid treatment. Both genotype and corticosteroid treatment are associated with variations in subcortical volumes and cortical morphology, albeit in different ways. Corticosteroid treatment appears to have a more profound association with differences in gray matter characteristics of brain regions that are associated with functional outcomes.