Abstract

Background:

Methods

Results

Conclusions

Introduction

Methods and Materials

Results

Discussion

References

Acknowledgements

Disclosures

Abstract

Background:
The amygdala is widely implicated in both anxiety and autism spectrum disorder. However, no studies have investigated the relationship between co-occurring anxiety and longitudinal amygdala development in autism. Here, the authors characterize amygdala development across childhood in autistic children with and without traditional DSM forms of anxiety and anxieties distinctly related to autism.

Methods:
Longitudinal MRI scans were acquired at up to four timepoints for 71 autistic and 55 typically developing (TD) children (~2.5-12 years, 411 timepoints). Traditional DSM anxiety and anxieties distinctly related to autism were assessed at study Time 4 (~8-12 years) using a diagnostic interview tailored to autism: The Anxiety Disorders Interview Schedule-IV with the Autism Spectrum Addendum. Mixed effects models were used to test group differences at study Time 1 (3.18 years), Time 4 (11.36 years), and developmental differences (age-by-group interactions) in right and left amygdala volume between autistic children with and without DSM or autism distinct anxieties, and TD.

Results:
Autistic children with DSM anxiety had significantly larger right amygdala volumes compared to TD at both study Time 1 (5.10% increase) and Time 4 (6.11% increase). Autistic children with autism distinct anxieties had significantly slower right amygdala growth compared to TD, autism-no anxiety, and autism-DSM anxiety groups and smaller right amygdala volumes at Time 4 compared to the autism-no anxiety (-8.13% decrease) and autism-DSM anxiety (-12.05% decrease) groups.

Conclusions:
Disparate amygdala volumes and developmental trajectories between DSM and autism distinct forms of anxiety suggest different biological underpinnings for these common, cooccurring conditions in autism.

Introduction

Symptoms of autism spectrum disorder (ASD or autism) include impaired social interaction and communication and restricted repetitive behaviors (1). It is estimated that 42-69% of autistic individuals also meet diagnostic criteria for a clinical anxiety disorder (2,3). Though the amygdala has been widely implicated in both anxiety and autism (4), only three studies have investigated associations between amygdala structure and anxiety within autism (5–۷). No studies of autism have investigated the development of the amygdala longitudinally in relation to anxiety, nor the associations between different forms of anxiety and the amygdala in autism.

Clinical anxiety can manifest in several forms, including generalized anxiety disorder (GAD), separation anxiety, specific phobia, and social phobia (henceforth ‘DSM anxiety’) (۱). However, distinguishing anxiety from ASD symptoms is challenging (2,8). Recently developed tools recognize classically defined symptoms of anxiety (e.g., anticipatory anxiety, fearful avoidance) that manifest within contexts that are somewhat unique to autism. These symptoms would not be captured by traditional assessments (9). Such autism-distinct anxieties (henceforth ‘distinct anxiety’) include fears related to social confusion (as opposed to fear of negative evaluation which is required for a DSM diagnosis of social phobia), uncommon phobias (e.g., specific sounds, facial features), excessive worry related to losing access to materials related to circumscribed interests, and fears of change (3).