Sex-Based Dissociation of White Matter Microstructure in Children With Attention-Deficit/Hyperactivity Disorder

Abstract

Objective: Sexual dimorphism is evident in attention-deficit/hyperactivity disorder (ADHD), including subtype prevalence, adverse outcomes, and neural phenotype. Neurobiological studies of ADHD suggest that boys show more abnormalities in motor and premotor structure and function, whereas girls differ from typically developing (TD) peers in prefrontal circuitry. We applied diffusion tensor imaging (DTI) to identify ADHD-related sex-specific differences in motor/premotor and prefrontal white matter (WM) microstructure in children.

Method: DTI estimated differences in WM microstructure among 120 children 8 to 12 years of age, 60 with ADHD (30 boys and 30 girls) and 60 controls (30 boys and 30 girls), matched on age, IQ, and handedness. Effects of diagnosis and sex on fractional anisotropy (FA) were assessed in motor/premotor and prefrontal regions. Group differences in FA and associations with response control (e.g., reaction time variability [CVRT] and commission error rate) were examined separately within sex.

Results: Sex-by-diagnosis interactions were observed for FA in primary motor (M1) and medial orbitofrontal (MOFC) cortex. Post hoc tests revealed that boys with ADHD showed bilateral reductions in FA within M1, compared with TD peers; in contrast, girls with ADHD showed higher FA bilaterally within MOFC. Decreased M1 FA was associated with higher CVRT in boys and higher commission error rates in girls. For MOFC, lower FA was associated with greater CVRT and commission error rates across all participants with ADHD.

Conclusion: ADHD affects the white matter of boys and girls differently; boys appear to be more affected in regions responsible for control of basic actions, whereas girls show more abnormalities in regions responsible for higher-level, top-down control.

Keywords: attention; diffusion tensor imaging; intrasubject variability; response control; sex differences.