Neuro-anatomic evidence for the maturational delay hypothesis of ADHD

Attention deficit hyperactivity disorder (ADHD) has been hypothesized to be related to a delay rather than a deviance of normal brain development before it was first defined by the DSM-III (1). The hypothesis was initially based on the behavioral observation that children with ADHD behave like younger children who are naturally more active, more impulsive, and have a shorter attention span than older children. This is well expressed in the definition of the disorder in the DSM-IV, where ADHD is characterized by an age-inappropriate display of inattention, hyperactivity, and impulsiveness. The behavioral observation is further supported by the cognitive profile of ADHD children: They show deficits in late developing higher cognitive functions of inhibitory self-control, attention, and temporal foresight (2, 3). The fact that ADHD symptoms tend to improve with age and up to 80% of children (depending on the follow-up length and definition of persistence) grow out of ADHD in adulthood (4) further supports the theory of a maturational lag that eventually normalizes in a considerable proportion of children. Indirect neurobiological support comes from cross-sectional structural imaging studies finding reduced size in cortico-striatal brain regions that are known to develop late in adolescence (5) and functional imaging studies showing reduced brain activation in ADHD compared with their age-matched peers in precisely those brain areas whose functions develop progressively with age between childhood and adulthood (6–10). Cross-sectional studies, however, are confounded by cohort effects; direct testing of the maturational delay hypothesis requires longitudinal imaging studies that map the developmental trajectories of brain maturation in healthy and ADHD children. In a recent issue of PNAS, Shaw et al. (11) study largely longitudinal data to provide direct neurobiological evidence for the maturational delay hypothesis of ADHD.