Trajectories of Cerebral Cortical Development in Childhood and Adolescence and Adult Attention-Deficit/Hyperactivity Disorder

  • Philip Shaw
    Address correspondence to Philip Shaw, M.D., Ph.D., National Human Genome Research Institute, Social and Behavioral Research Branch, Section on Neurobehavioral Clinical Research, Building 31, B1 B37, Room 3N 202, Bethesda, MD 20892
    Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Maryland

    Intramural Program of the National Institute of Mental Health, Bethesda, Maryland
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  • Meaghan Malek
    Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Maryland
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  • Bethany Watson
    Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Maryland
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  • Deanna Greenstein
    Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Maryland
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  • Pietro de Rossi
    Section on Neurobehavioral Clinical Research, Social and Behavioral Research Branch, National Human Genome Research Institute, Bethesda, Maryland

    Neurosciences, Mental Health and Sensory Functions Department, School of Medicine and Psychology, Sapienza University, Sant’Andrea Hospital, Rome, Italy
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  • Wendy Sharp
    Intramural Program of the National Institute of Mental Health, Bethesda, Maryland
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      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.


      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.


      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.


      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.

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