Trajectories of cerebral cortical development in childhood and adolescence and adult attention-deficit/hyperactivity disorder

Abstract

Background: Childhood attention-deficit/hyperactivity disorder (ADHD) persists into adulthood in around half of those affected, constituting a major public health challenge. No known demographic, clinical, or neuropsychological factors robustly explain the clinical course, directing our focus to the brain. Herein, we link the trajectories of cerebral cortical development during childhood and adolescence with the severity of adult ADHD.

Methods: Using a longitudinal study design, 92 participants with ADHD had childhood (mean 10.7 years, SD 3.3) and adult clinical assessments (mean 23.8 years, SD 4.3) with repeated neuroanatomic magnetic resonance imaging. Contrast was made against 184 matched typically developing volunteers.

Results: Attention-deficit/hyperactivity disorder persisted in 37 (40%) subjects and adult symptom severity was linked to cortical trajectories. Specifically, as the number of adult symptoms increased, particularly inattentive symptoms, so did the rate of cortical thinning in the medial and dorsolateral prefrontal cortex. For each increase of one symptom of adult ADHD, the rate of cortical thinning increased by .0018 mm (SE = .0004, t = 4.2, p < .0001), representing a 5.6% change over the mean rate of thinning for the entire group. These differing trajectories resulted in a convergence toward typical dimensions among those who remitted and a fixed, nonprogressive deficit in persistent ADHD. Notably, cortical thickening or minimal thinning (greater than -.007 mm/year) was found exclusively among individuals who remitted.

Conclusions: Adult ADHD status is linked with the developmental trajectories of cortical components of networks supporting attention, cognitive control, and the default mode network. This informs our understanding of the developmental pathways to adult ADHD.

Keywords: Attention; cerebral cortex; cognition; development; neuroimaging; recovery.

Figure 1

Distributions of the number of inattentive and hyperactive-impulsive symptoms in adulthood.

Figure 2

The top panel shows regions where the total number of ADHD symptoms in adulthood are significantly associated (p<0.05, adjusted for multiple comparisons) with the cortical trajectories from childhood into adulthood. The association is stronger for inattentive (B) than hyperactive-impulsive symptoms (C).

Figure 3

Scatterplot of individual slope estimates for the medial prefrontal/cingulate regions where the primary mixed model analysis showed trajectories to be associated with adult outcome.

Figure 4

Cortical thickness in regions linked to adult ADHD status for the right (A) and left (B) hemispheres. The trajectories differed significantly between the typically developing controls and remitted ADHD group (all p<0.001), but not between the typically developing and persistent ADHD groups (p>0.1). The two ADHD groups also had significantly different trajectories (p<0.001).