Abnormalities of gray matter volume and structural covariance in children with attention-deficit/hyperactivity disorder subtypes: implications for clinical correlations

Abstract

Attention deficit and hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder characterized by attention deficits, hyperactivity, and impulsivity. This study investigated brain structural differences in children with ADHD compared to typically developing children. Our sample included 199 ADHD children (114 ADHD-predominantly inattentive; 85 ADHD-combined presentation subtypes) and 94 typically developing controls. All participants completed clinical assessments and MRI scans. We conducted whole-brain voxel-based morphometry (VBM) analysis, structural covariance analysis, and clinical correlation. We used Analysis of Covariance (ANCOVA) and Multivariate Analysis of Covariance (MANCOVA) to compare gray matter volume (GMV) and structural covariance between the ADHD subgroups and typically developing children. We also analyzed correlations between structural covariance and clinical symptoms. The results showed significant GMV differences, particularly in the frontal cortex and basal ganglia, among ADHD subtypes and typically developing children. Compared to controls, children with ADHD combined presentation (ADHD-C) exhibited significantly larger GMV in the right precentral gyrus, right inferior frontal gyrus, right superior frontal gyrus, and left cingulate gyrus, while children with ADHD-predominantly inattentive (ADHD-I) exhibited larger GMV in the right cingulate gyrus. Within the ADHD subtypes, ADHD-C children displayed larger GMV in the left caudate nucleus compared to ADHD-I children. Structural covariance analysis highlighted the altered connectivity patterns, involving the striatum and regions within the default mode network. Correlation analysis indicated associations between altered brain structures and symptoms, cognitive abilities, and social functioning. Our findings suggested that specific brain regions are implicated in ADHD pathology and associated with clinical symptoms, paving ways for developing diagnostic markers and future interventions.