Associations between early trajectories of amygdala development and later school-age anxiety in two longitudinal samples

Catherine A Burrows¹, Carolyn Lasch², Julia Gross³, Jessica B Girault³, Joshua Rutsohn⁴, Jason J Wolff⁵, Meghan R Swanson⁶, Chimei M Lee⁷, Stephen R Dager⁸, Emil Cornea⁹, Rebecca Stephens¹⁰, Martin Styner¹⁰, Tanya St John¹¹, Juhi Pandey⁹, Meera Deva¹⁰, Kelly N Botteron¹², Annette M Estes¹³, Heather C Hazlett³, John R Pruett Jr¹², Robert T Schultz⁹, Lonnie Zwaigenbaum¹⁴, John H Gilmore¹⁰, Mark D Shen¹⁵, Joseph Piven³, Jed T Elison¹⁶; IBIS Network

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: cburrows@umn.edu.
² Institute of Child Development, University of Minnesota, Minneapolis, MN, USA.
³ Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Educational Psychology, University of Minnesota, Minneapolis, MN, USA.
⁶ School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁷ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁸ Deptartment of Radiology, University of Washington Medical Center, Seattle, WA, USA.
⁹ Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁰ Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
¹¹ University of Washington Autism Center, University of Washington, Seattle, WA, USA.
¹² Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹³ University of Washington Autism Center, University of Washington, Seattle, WA, USA; Deptartment of Speech and Hearing Science, University of Washington, Seattle, WA, USA.
¹⁴ Deptartment of Pediatrics, University of Alberta, Edmonton, AB, Canada.
¹⁵ Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
¹⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, University of Minnesota, Minneapolis, MN, USA.

PMID: 38154378
PMCID: PMC10792190
DOI: 10.1016/j.dcn.2023.101333

Associations between early trajectories of amygdala development and later school-age anxiety in two longitudinal samples

Catherine A Burrows et al. Dev Cogn Neurosci. 2024 Feb.

. 2024 Feb:65:101333.

doi: 10.1016/j.dcn.2023.101333. Epub 2023 Dec 22.

Authors

Affiliations

¹ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA. Electronic address: cburrows@umn.edu.
² Institute of Child Development, University of Minnesota, Minneapolis, MN, USA.
³ Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
⁴ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁵ Department of Educational Psychology, University of Minnesota, Minneapolis, MN, USA.
⁶ School of Behavioral and Brain Sciences, University of Texas at Dallas, Dallas, TX, USA.
⁷ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.
⁸ Deptartment of Radiology, University of Washington Medical Center, Seattle, WA, USA.
⁹ Center for Autism Research, Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
¹⁰ Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
¹¹ University of Washington Autism Center, University of Washington, Seattle, WA, USA.
¹² Department of Psychiatry, Washington University School of Medicine in St. Louis, St. Louis, MO, USA.
¹³ University of Washington Autism Center, University of Washington, Seattle, WA, USA; Deptartment of Speech and Hearing Science, University of Washington, Seattle, WA, USA.
¹⁴ Deptartment of Pediatrics, University of Alberta, Edmonton, AB, Canada.
¹⁵ Carolina Institute for Developmental Disabilities and Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA; Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC, USA.
¹⁶ Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA; Institute of Child Development, University of Minnesota, Minneapolis, MN, USA.

PMID: 38154378
PMCID: PMC10792190
DOI: 10.1016/j.dcn.2023.101333

Abstract

Amygdala function is implicated in the pathogenesis of autism spectrum disorder (ASD) and anxiety. We investigated associations between early trajectories of amygdala growth and anxiety and ASD outcomes at school age in two longitudinal studies: high- and low-familial likelihood for ASD, Infant Brain Imaging Study (IBIS, n = 257) and typically developing (TD) community sample, Early Brain Development Study (EBDS, n = 158). Infants underwent MRI scanning at up to 3 timepoints from neonate to 24 months. Anxiety was assessed at 6-12 years. Linear multilevel modeling tested whether amygdala volume growth was associated with anxiety symptoms at school age. In the IBIS sample, children with higher anxiety showed accelerated amygdala growth from 6 to 24 months. ASD diagnosis and ASD familial likelihood were not significant predictors. In the EBDS sample, amygdala growth from birth to 24 months was associated with anxiety. More anxious children had smaller amygdala volume and slower rates of amygdala growth. We explore reasons for the contrasting results between high-familial likelihood for ASD and TD samples, grounding results in the broader literature of variable associations between early amygdala volume and later anxiety. Results have the potential to identify mechanisms linking early amygdala growth to later anxiety in certain groups.

Keywords: Amygdala; Anxiety; Autism spectrum disorder (ASD); Magnetic resonance imaging (MRI); Reproducibility.

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Conflict of interest statement

Declaration of Competing Interest The authors report no financial or personal relationships that influenced their work.

Figures

**Fig. 1**
Representative processed longitudinal MRIs from a single subject from the (A) IBIS and (B) EBDS samples. Volumetric segmentations are overlayed of the bilateral hippocampus (cyan) and amygdala (red); 3D renderings (coronal and axial views) are shown for the earliest age from each dataset (IBIS = 6 m, EBDS = Neonate). All IBIS images selected for visualization are T1-weighted; for EBDS the neonatal image is T2-weighted and 1- and 2-year images are T1-weighted.

**Fig. 2**
CBCL Anxiety Problems at school age are associated with altered amygdala trajectories from 6–24 months in the IBIS sample. A) Differences in total raw amygdala volume between participants with Anxiety Problem T-scores in a range of borderline or clinical concern (T-scores of 65 and above) and those with t-scores in the normal (nonclinical) range. B) Difference between these groups in residual total amygdala volume, after controlling for total cerebrum volume.

**Fig. 3**
BASC Anxiety at school age are associated with altered amygdala trajectories from neonate to 24 months in the EBDS sample. A) Differences in total raw amygdala volume between participants with Anxiety T-scores in a range of borderline or clinical concern (T-scores of 65 and above) and those with T-scores in the normal (nonclinical) range. B) Difference between these groups in residual total amygdala volume, after controlling for total cerebrum volume.

See this image and copyright information in PMC

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Associations between early trajectories of amygdala development and later school-age anxiety in two longitudinal samples

Affiliations

Associations between early trajectories of amygdala development and later school-age anxiety in two longitudinal samples

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical