The Limbic System in Children and Adolescents With Attention-Deficit/Hyperactivity Disorder: A Longitudinal Structural Magnetic Resonance Imaging Analysis.

ABSTRACT

Background: During childhood and adolescence, attention-deficit/hyperactivity disorder (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. Methods: Structural magnetic resonance imaging data (380 scans), emotional regulation (Affective Reactivity Index), and ADHD symptom severity (Conners 3 ADHD Index) were measured at up to 3 time points between 9 and 14 years of age in a sample of children and adolescents with ADHD (n = 57) and control children (n = 109). Results: Compared with the control group, the ADHD group had lower volume of the amygdala (left ß standardized [ß_std] = -0.38; right ß_std = -0.34), hippocampus (left ß_std = -0.44; right ß_std = -0.34), cingulate gyrus (left ß_std = -0.42; right ß_std = -0.32), and orbitofrontal cortex (right ß_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 Conners 3 ADHD Index-by-age interaction effect on the volume of the left mammillary body (ß_std = 0.17) in the ADHD group across the 3 study time points. Conclusions: 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.