Brain morphological changes across behaviour spectrums in attention-deficit/hyperactivity disorder

Background Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder with behavioural symptoms and grey matter volume (GMV) changes. However, previous studies have not fully elucidated the progressive and causal GMV changes associated with behavioural symptoms in ADHD.Aims This study aimed to explore the causal relationship between GMV alterations and behavioural symptoms in children and adolescents with ADHD using behaviour-causal structural covariance network (BCaSCN) analysis.Methods Structural magnetic resonance imaging (sMRI) data from 135 children and adolescents with ADHD and 182 neurotypical controls (NCs) were analysed. ADHD subtypes were identified based on GMV using a clustering algorithm to address the neuroanatomical heterogeneity. To investigate the causal relationships of GMV changes related to behavioural symptoms, sMRI data were sequentially ordered by ADHD index, inattentive index and hyperactive/impulsive index values to generate pseudo-time series data. These data were then analysed using region-of-interest-based BCaSCN analysis to explore potential progressive patterns of GMV change.Results Neuroanatomical subtyping revealed two ADHD subtypes with distinct GMV patterns compared with NCs. BCaSCN analysis showed that ADHD subtype 1 was closely associated with inattentiveness, involving prominent nodes in the frontal regions and cerebellum. In contrast, ADHD subtype 2 was more strongly linked to overall disease severity, with the cerebellum and hippocampus as primary hubs.Conclusions ADHD is associated with heterogeneous changes in GMV corresponding to distinct behavioural domains, highlighting the need for subtype-specific diagnostic and therapeutic strategies.