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. 2020 Sep;59(9):1069-1079.
doi: 10.1016/j.jaac.2019.08.008. Epub 2019 Aug 23.

Understanding Hippocampal Development in Young Children With Autism Spectrum Disorder

Vanessa P Reinhardt  1 , Ana-Maria Iosif  1 , Lauren Libero  1 , Brianna Heath  1 , Sally J Rogers  1 , Emilio Ferrer  1 , Christine Nordahl  2 , Simona Ghetti  1 , David Amaral  2 , Marjorie Solomon  3
Affiliations

Understanding Hippocampal Development in Young Children With Autism Spectrum Disorder

Vanessa P Reinhardt et al. J Am Acad Child Adolesc Psychiatry. 2020 Sep.

Abstract

Objective: We examined growth trajectories of hippocampal volume (HV) in early childhood in a longitudinal cohort of male and female participants with autism spectrum disorder (ASD) and typically developing (TD) individuals, and investigated HV in those with large brains. Relations between factors potentially associated with hippocampal size and growth were investigated.

Method: Participants received 1 to 3 structural magnetic resonance imaging scans between ages 25 and 80 months (unique participants: ASD, n =200; TD, n =110; total longitudinal scans, n = 593). HV growth during this period was examined using mixed-effects linear models. Associations between early HV and growth rates, and IQ and adaptive functioning, were evaluated.

Results: After accounting for cerebral hemisphere volume, male participants exhibited larger left and right HV than female participants. Hippocampal growth rates did not differ by sex. In children with larger hemisphere volumes, male and female participants with ASD had relatively larger HV than TD participants of similar hemisphere volume. This effect was present in a broader group than only those with disproportionate megalencephaly (male participants with large cerebral volumes relative to body size). Right hippocampi were larger than left hippocampi in both groups and sexes. Right versus left volume differences were greater for ASD. After adjusting for hemisphere volume, male participants with ASD showed a significant positive association between right hippocampal growth and adaptive behavior.

Conclusion: HV was relatively greater in ASD in analyses adjusting for hemisphere volume, whereas only subtle differences were observed in HV and growth between participants with ASD and TD participants in unadjusted analyses, suggesting that ASD involves atypical coupling between HV and brain size.

Keywords: IQ; adaptive functioning; hippocampus; longitudinal; neurogenesis.

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Conflict of interest statement

Disclosure: Dr. Amaral has served as a consultant for Stemina Biomarkers Discovery and Axial Therapeutics. Drs. Reinhardt, Iosif, Libero, Heath, Rogers, Ferrer, Nordahl, Ghetti, and Solomon have reported no biomedical financial interests or potential conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Left and Right Hippocampal Volume Trajectories in Boys (A, B) and Girls (C, D) With Autism Spectrum Disorder (ASD) and Those Typically Developing (TD) Note: Straight lines represent estimated volumes from the unadjusted models; highlighted areas along each line represent 95% CIs from the unadjusted models. TD-F = typically developing female. Please note color figures are available online.)
See this image and copyright information in PMC

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