Childhood white matter organization predicts adolescent internalizing problems among youth with and without ADHD.

This study investigated whether childhood white matter organization in those with and without ADHD predicted the emergence of internalizing problems in adolescence. Further, we aimed to determine whether (i) this longitudinal effect was mediated by motor skill level, and/or (ii) white matter organization in children with ADHD mediated the expected relationship between motor skill level and internalizing problems in adolescence. Participants were 40 children with ADHD and 36 typically developing (TD) controls aged between 8 and 13 years, who were followed-up during adolescence (12-18 years). All underwent diffusion MRI at Time 1, and assessment of motor competence using the Movement ABC-2 (MABC-2). At Time 2, internalizing problems (i.e., 'depression', 'anxiety', and 'somatization') were measured using the parent- and self-report Behavior Assessment System for Children (BASC). Following pre-processing of diffusion MRI scans, fixel based analysis was conducted and fibre cross-section (FC) extracted. TractSeg was then used to delineate the superior longitudinal fasciculus (SLF), inferior longitudinal fasciculus (ILF) and the uncinate fasciculus (UC). Results showed that childhood FC within the UF was a significant predictor of parent and child-rated depression scores in adolescence. Further, childhood FC of the bilaterial ILF was a significant predictor of parent report depression scores in adolescence. These effects were stable for those with and without ADHD, and no group differences in FC were observed in those white matter regions found to be associated with adolescent depressive symptoms. We failed to find evidence that motor ability mediated the relationship between white matter organization of the UF of ILF and depressive symptoms. When childhood motor ability was considered as a predictor of adolescent depressive scores (an effect that was significant for parent reported effects), this effect was mediated by childhood FC of the UF. This work suggests that low motor skill in children with and without ADHD may provide a developmental marker for emotional and behavioral dysregulation in adolescence, with this effect partly explained by childhood white matter organization within fronto-limbic circuitry.