Anxiety in children and youth with autism spectrum disorder and the association with amygdala subnuclei structure

Abstract

Autism spectrum disorder (ASD) is clinically characterized by social and communication difficulties as well as repetitive behaviors. Many children with ASD also suffer from anxiety, which has been associated with alterations in amygdala structure. In this work, the association between amygdala subnuclei volumes and anxiety was assessed in a cohort of 234 participants (mean age = 11.0 years, SD = 3.9, 95 children with ASD, 139 children were non-autistic). Children underwent magnetic resonance imaging. Amygdala subnuclei volumes were extracted automatically. Anxiety was assessed using the Screen for Child Anxiety Related Disorders, the Child Behavior Checklist, and the Strength and Difficulties Questionnaire. Children with ASD had higher anxiety scores relative to non-autistic children on all anxiety measures (all, p < 0.05). Anxiety levels were significantly predicted in children with ASD by right basal (right: B = 0.235, p = 0.002) and paralaminar (PL) (B = −0.99, p = 0.009) volumes. Basal nuclei receive multisensory information from cortical and subcortical areas and have extensive projections within the limbic system while the PL nuclei are involved in emotional processing. Alterations in basal and PL nuclei in children with ASD and the association with anxiety may reflect morphological changes related to in the neurocircuitry of anxiety in ASD. Lay abstract Autism spectrum disorder (ASD) is clinically characterized by social communication difficulties as well as restricted and repetitive patterns of behavior. In addition, children with ASD are more likely to experience anxiety compared with their peers who do not have ASD. Recent studies suggest that atypical amygdala structure, a brain region involved in emotions, may be related to anxiety in children with ASD. However, the amygdala is a complex structure composed of heterogeneous subnuclei, and few studies to date have focused on how amygdala subnuclei relate to in anxiety in this population. The current sample consisted of 95 children with ASD and 139 non-autistic children, who underwent magnetic resonance imaging (MRI) and assessments for anxiety. The amygdala volumes were automatically segmented. Results indicated that children with ASD had elevated anxiety scores relative to peers without ASD. Larger basal volumes predicted greater anxiety in children with ASD, and this association was not seen in non-autistic children. Findings converge with previous literature suggesting ASD children suffer from higher levels of anxiety than non-autistic children, which may have important implications in treatment and interventions. Our results suggest that volumetric estimation of amygdala’s subregions in MRI may reveal specific anxiety-related associations in children with ASD.