Attention-deficit/hyperactivity disorder is characterized by a delay in cortical maturation

Abstract

There is controversy over the nature of the disturbance in brain development that underpins attention-deficit/hyperactivity disorder (ADHD). In particular, it is unclear whether the disorder results from a delay in brain maturation or whether it represents a complete deviation from the template of typical development. Using computational neuroanatomic techniques, we estimated cortical thickness at >40,000 cerebral points from 824 magnetic resonance scans acquired prospectively on 223 children with ADHD and 223 typically developing controls. With this sample size, we could define the growth trajectory of each cortical point, delineating a phase of childhood increase followed by adolescent decrease in cortical thickness (a quadratic growth model). From these trajectories, the age of attaining peak cortical thickness was derived and used as an index of cortical maturation. We found maturation to progress in a similar manner regionally in both children with and without ADHD, with primary sensory areas attaining peak cortical thickness before polymodal, high-order association areas. However, there was a marked delay in ADHD in attaining peak thickness throughout most of the cerebrum: the median age by which 50% of the cortical points attained peak thickness for this group was 10.5 years (SE 0.01), which was significantly later than the median age of 7.5 years (SE 0.02) for typically developing controls (log rank test chi(1)(2) = 5,609, P < 1.0 x 10(-20)). The delay was most prominent in prefrontal regions important for control of cognitive processes including attention and motor planning. Neuroanatomic documentation of a delay in regional cortical maturation in ADHD has not been previously reported.

Fig. 1.

The age of attaining peak cortical thickness in children with ADHD compared with typically developing children. (A) dorsal view of the cortical regions where peak thickness was attained at each age (shown, ages 7–12) in ADHD (Upper) and typically developing controls (Lower). The darker colors indicate regions where a quadratic model was not appropriate (and thus a peak age could not be calculated), or the peak age was estimated to lie outside the age range covered. Both groups showed a similar sequence of the regions that attained peak thickness, but the ADHD group showed considerable delay in reaching this developmental marker. (B) Right lateral view of the cortical regions where peak thickness was attained at each age (shown, ages 7–13) in ADHD (Upper) and typically developing controls (Lower). Again, the delay in ADHD group in attaining peak cortical thickness is apparent.

Fig. 2.

Regions where the ADHD group had delayed cortical maturation, as indicated by an older age of attaining peak cortical thickness.

Fig. 3.

Kaplan–Meier curves illustrating the proportion of cortical points that had attained peak thickness at each age for all cerebral cortical points (Left) and the prefrontal cortex (Right). The median age by which 50% of cortical points had attained their peak differed significantly between the groups (all P < 1.0 × 10⁻²⁰)

Fig. 4.

Regions where the ADHD group had early cortical maturation, as indicated by a younger age of attaining peak cortical thickness.