Effects of the Co-Occurrence of Anxiety and Attention-Deficit/Hyperactivity Disorder on Intrinsic Functional Network Centrality Among Children with Autism Spectrum Disorder

Background: Children with autism spectrum disorder (ASD) present with a high co-occurrence of anxiety and attention-deficit/hyperactivity disorder (ADHD). However, it remains unclear whether the co-occurrence of anxiety and ADHD in children with ASD alters whole-brain functional networks.

Objectives: Here, we aimed to examine anxiety- and ADHD-related brain network centrality in children with ASD separately and their relationships with ASD symptoms.

Methods: We assessed clinical anxiety and ADHD levels in children with ASD, aged 6 to 13 years old. Participants were categorized into four groups: ASD only, ASD+anxiety, ASD+ADHD, and ASD+both anxiety and ADHD. Autism Diagnostic Interview-Revised (ADI-R) was used to measure ASD symptoms in four specific domains: social, verbal, nonverbal, and restricted repetitive behaviors (RRB). Subsequently, we compared voxel-wise network degree centrality (DC) among the four groups.

Results: We found seven significant clusters in the main effect test and they were centered on the left middle temporal gyrus (MTG), the right lingual gyrus (LG), the left occipital lobe (OL)/cuneus, the left middle occipital gyrus (MOG), the right sub-gyral/extra-nuclear/carcarine, the right precuneus, and the left superior frontal gyrus (SFG). Least significant difference (LSD) post hoc comparisons revealed that, compared with ASD only, ASD+ADHD and ASD+both showed higher DC level in the right calcarine, and ASD+anxiety showed no significant difference. Moreover, a similar pattern was observed in the left superior frontal gyrus (SFG). The DC level of the right calcarine was positively correlated with ADI-R nonverbal scores, while the left SFG was negatively correlated with ADI-R social scores.

Conclusions: Our findings suggest that the right calcarine and left SFG act as important nodes in the co-occurrence of anxiety and ADHD among children with ASD. Our works shed light on the brain mechanisms underlying behavioral changes related to the co-occurrence of anxiety and ADHD in children with ASD.