Association of Amygdala Development With Different Forms of Anxiety in Autism Spectrum Disorder

Derek Sayre Andrews, Leon Aksman, Connor M. Kerns, Joshua K. Lee, Breanna M. Winder-Patel, Danielle Jenine Harvey, Einat Waizbard-Bartov, Brianna Heath, Marjorie Solomon, Sally J. Rogers, Andre Altmann, Christine Wu Nordahl, David G. Amaral

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 magnetic resonance imaging scans were acquired at up to four time points for 71 autistic and 55 typically developing (TD) children (∼2.5–12 years, 411 time points). 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) and 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 children. Results: Autistic children with DSM anxiety had significantly larger right amygdala volumes than TD children 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 than TD, autism–no anxiety, and autism–DSM anxiety groups and smaller right amygdala volumes at time 4 than 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, co-occurring conditions in autism.

Original languageEnglish
Pages (from-to)977-987
Number of pages11
JournalBiological Psychiatry
Volume91
Issue number11
DOIs
StatePublished - 1 Jun 2022
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2022 Society of Biological Psychiatry

Funding

This research was supported by an Autism Center of Excellence grant awarded by the National Institute of Child Health and Development (Grant No. P50 HD093079 [to DGA, CWN, MS, SJR] ), the National Institute of Mental Health (Grant Nos. R01MH104438 [to CWN], R01MH103284 [to MS], and R01MH103371 [to DGA]), the Medical Investigation of Neurodevelopmental Disorders (MIND) Institute Intellectual and Developmental Disabilities Research Center (Grant No. P50 HD103526 ), the MIND Institute Autism Research Training Program (Grant No. T32MH073124 [to DSA]), and a Medical Research Council eMedLab Medical Bioinformatics Career Development Fellowship (Grant No. MR/L016311/1 [to AA]).

FundersFunder number
MIND Institute Autism Research Training Program
Medical Research Council eMedLab Medical BioinformaticsMR/L016311/1
National Institute of Mental HealthR01MH103371, R01MH104438, T32MH073124, R01MH103284
National Institute of Child Health and Human DevelopmentP50 HD093079
Intellectual and Developmental Disabilities Research CenterP50 HD103526

    Keywords

    • Anxiety
    • Autism
    • Brain
    • Development
    • Longitudinal
    • MRI

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