The Limbic System in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder: A Longitudinal Structural MRI Analysis

During childhood and adolescence, ADHD is associated with changes in symptoms and brain structures, but the link between brain structure and function remains unclear. The limbic system, often termed the “emotional network”, plays an important role in a number of neurodevelopmental disorders, yet this brain network remains largely unexplored in ADHD. Investigating the developmental trajectories of key limbic system structures during childhood and adolescence will provide novel insights into the neurobiological underpinnings of ADHD. Structural MRI data (379 scans), emotional regulation (affective reactivity index; ARI), and ADHD symptom severity (Connor’s 3 ADHD index; CAI) were measured at up to three time points between 9 and 14 years of age in a sample of ADHD (n=57) and controls (n=109). Relative to controls, the ADHD group had lower volume of the amygdala (left: β_std =-0.38; right: β_std =-0.34), hippocampus (left: β_std =-0.44; right: β_std =-0.34), cingulate gyrus (left: β_std =-0.42; right: β_std =-0.32), and orbitofrontal cortex (right: β_std =-0.33) across development (9-14 years). There were no significant group-by-age interactions in any of the limbic system structures. Exploratory analysis found a significant CAI-by-age interaction on the volume of the left mammillary body (β_std =0.17) in the ADHD group across the three study time points. Children and adolescents with ADHD displayed lower volume and atypical development in limbic system structures. Furthermore, atypical limbic system development was associated with increased symptom severity, highlighting a potential neurobiological correlate of ADHD severity.