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

Although previous studies have found that ADHD is characterized by a delay in cortical maturation, it is not clear whether this phenomenon was secondary to developmental trajectories in subcortical regions (caudate, putamen, pallidum, thalamus, hippocampus and amygdala). Using the ADHD-200 dataset, we estimated subcortical volumes in 339 individuals with ADHD and 568 typically developing controls. We defined the growth trajectory of each subcortical structure, delineating a phase of childhood increase followed by an adolescent decrease in subcortical volumes using a quadratic growth model. From these trajectories, the age of attaining peak subcortical volumes was derived and used as an index of subcortical maturation. We found that subcortical structures (caudate, putamen, pallidum, thalamus, hippocampus and amygdala) followed curvilinear trajectories similar to those reported in previous studies. The volumes of these subcortical structures in ADHD were also delayed in the developmental trajectory, which suggested that ADHD may be characterized by a delay in subcortical maturation. This delay may lead to a shift in which individuals with ADHD go through the process of pruning the nerve connections that is part of the normal maturation process during adolescence. Further, we also found that the asymmetric development of subcortical structures was abnormal in ADHD, which resulted from the imbalance of the maturation delay of bilateral subcortical structures. The subcortical maturation delay may play an important role in the pathophysiology of ADHD. Our findings provide new potential targets to investigate the pathophysiology of ADHD.