Childhood white matter morphology and longitudinal change in symptoms of attention-deficit/hyperactivity disorder.

Abstract

Aim: To identify features of childhood white matter morphology associated with longitudinal change in the symptoms of attention-deficit/hyperactivity disorder (ADHD) from childhood to adolescence and whether brain white matter microstructure in childhood predicts ADHD symptom progression into adolescence.

Method: This was a single-site, prospective, longitudinal study of children with ADHD (n = 99, 31 females) and typically developing controls (n = 73, 24 females) assessed in childhood (aged 8-12 years) and adolescence (aged 12-17 years). Parent ratings of ADHD symptom severity were obtained in childhood and adolescence. Diffusion-weighted imaging data were collected in childhood; we derived measures of fiber bundle cross-section (morphology) using fixel-based analysis, a fiber-specific analytical framework. Linear regression was used to examine symptom change and nonparametric permutation testing was conducted for brain-behavior associations. Clinical trajectories and white matter microstructure were also compared between females and males to inform our understanding of the brain basis for sex differences in the clinical presentation of ADHD.

Results: Females with ADHD showed greater improvement than males in inattention and similar reductions in hyperactivity and impulsivity from childhood to adolescence. Higher fiber cross-section in corticospinal and parieto-occipital pontine tracts in childhood was associated with greater improvement in the severity of ADHD hyperactivity and impulsivity symptoms into adolescence.

Interpretation: ADHD symptom trajectories from childhood to adolescence differed between males and females and were related to individual variation in structural brain connectivity in childhood.