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Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism

BACKGROUND: The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growth leading to normalized brain volume in late childhood and beyond. While there...

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Autores principales: Yankowitz, Lisa D., Herrington, John D., Yerys, Benjamin E., Pereira, Joseph A., Pandey, Juhi, Schultz, Robert T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301552/
https://www.ncbi.nlm.nih.gov/pubmed/32552879
http://dx.doi.org/10.1186/s13229-020-00353-2
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author Yankowitz, Lisa D.
Herrington, John D.
Yerys, Benjamin E.
Pereira, Joseph A.
Pandey, Juhi
Schultz, Robert T.
author_facet Yankowitz, Lisa D.
Herrington, John D.
Yerys, Benjamin E.
Pereira, Joseph A.
Pandey, Juhi
Schultz, Robert T.
author_sort Yankowitz, Lisa D.
collection PubMed
description BACKGROUND: The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growth leading to normalized brain volume in late childhood and beyond. While there is consistent evidence for early brain overgrowth, there is mixed evidence for normalization of brain volume by middle childhood. The outcome of this debate is important to understanding the etiology and neurodevelopmental trajectories of ASD. METHODS: Brain volume was examined in two very large single-site samples of children, adolescents, and adults. The primary sample comprised 456 6–25-year-olds (ASD n = 240, typically developing controls (TDC) n = 216), including a large number of females (n = 102) and spanning a wide IQ range (47–158). The replication sample included 175 males. High-resolution T1-weighted anatomical MRI images were examined for group differences in total brain, cerebellar, ventricular, gray, and white matter volumes. RESULTS: The ASD group had significantly larger total brain, cerebellar, gray matter, white matter, and lateral ventricular volumes in both samples, indicating that brain volume remains enlarged through young adulthood, rather than normalizing. There were no significant age or sex interactions with diagnosis in these measures. However, a significant diagnosis-by-IQ interaction was detected in the larger sample, such that increased brain volume was related to higher IQ in the TDCs, but not in the ASD group. Regions-of-significance analysis indicated that total brain volume was larger in ASD than TDC for individuals with IQ less than 115, providing a potential explanation for prior inconsistent brain size results. No relationships were found between brain volume and measures of autism symptom severity within the ASD group. LIMITATIONS: Our cross-sectional sample may not reflect individual changes over time in brain volume and cannot quantify potential changes in volume prior to age 6. CONCLUSIONS: These findings challenge the “normalization” prediction of the brain overgrowth hypothesis by demonstrating that brain enlargement persists across childhood into early adulthood. The findings raise questions about the clinical implications of brain enlargement, since we find that it neither confers cognitive benefits nor predicts increased symptom severity in ASD.
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spelling pubmed-73015522020-06-18 Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism Yankowitz, Lisa D. Herrington, John D. Yerys, Benjamin E. Pereira, Joseph A. Pandey, Juhi Schultz, Robert T. Mol Autism Research BACKGROUND: The frequently cited Early Overgrowth Hypothesis of autism spectrum disorder (ASD) postulates that there is overgrowth of the brain in the first 2 years of life, which is followed by a period of arrested growth leading to normalized brain volume in late childhood and beyond. While there is consistent evidence for early brain overgrowth, there is mixed evidence for normalization of brain volume by middle childhood. The outcome of this debate is important to understanding the etiology and neurodevelopmental trajectories of ASD. METHODS: Brain volume was examined in two very large single-site samples of children, adolescents, and adults. The primary sample comprised 456 6–25-year-olds (ASD n = 240, typically developing controls (TDC) n = 216), including a large number of females (n = 102) and spanning a wide IQ range (47–158). The replication sample included 175 males. High-resolution T1-weighted anatomical MRI images were examined for group differences in total brain, cerebellar, ventricular, gray, and white matter volumes. RESULTS: The ASD group had significantly larger total brain, cerebellar, gray matter, white matter, and lateral ventricular volumes in both samples, indicating that brain volume remains enlarged through young adulthood, rather than normalizing. There were no significant age or sex interactions with diagnosis in these measures. However, a significant diagnosis-by-IQ interaction was detected in the larger sample, such that increased brain volume was related to higher IQ in the TDCs, but not in the ASD group. Regions-of-significance analysis indicated that total brain volume was larger in ASD than TDC for individuals with IQ less than 115, providing a potential explanation for prior inconsistent brain size results. No relationships were found between brain volume and measures of autism symptom severity within the ASD group. LIMITATIONS: Our cross-sectional sample may not reflect individual changes over time in brain volume and cannot quantify potential changes in volume prior to age 6. CONCLUSIONS: These findings challenge the “normalization” prediction of the brain overgrowth hypothesis by demonstrating that brain enlargement persists across childhood into early adulthood. The findings raise questions about the clinical implications of brain enlargement, since we find that it neither confers cognitive benefits nor predicts increased symptom severity in ASD. BioMed Central 2020-06-18 /pmc/articles/PMC7301552/ /pubmed/32552879 http://dx.doi.org/10.1186/s13229-020-00353-2 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Yankowitz, Lisa D.
Herrington, John D.
Yerys, Benjamin E.
Pereira, Joseph A.
Pandey, Juhi
Schultz, Robert T.
Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
title Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
title_full Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
title_fullStr Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
title_full_unstemmed Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
title_short Evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
title_sort evidence against the “normalization” prediction of the early brain overgrowth hypothesis of autism
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301552/
https://www.ncbi.nlm.nih.gov/pubmed/32552879
http://dx.doi.org/10.1186/s13229-020-00353-2
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