A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood

Derek Sayre Andrews; Joshua K. Lee; Danielle Jenine Harvey; Einat Waizbard-Bartov; Marjorie Solomon; Sally J. Rogers; Christine Wu Nordahl; David G. Amaral

doi:10.1016/j.biopsych.2020.10.013

A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood

Derek Sayre Andrews
, Joshua K. Lee
, Danielle Jenine Harvey
, Einat Waizbard-Bartov
, Marjorie Solomon
, Sally J. Rogers
, Christine Wu Nordahl
, David G. Amaral

University of California at Davis

Research output: Contribution to journal › Article › peer-review

65 Scopus citations

Abstract

Background: Cross-sectional diffusion-weighted magnetic resonance imaging studies suggest that young autistic children have alterations in white matter structure that differ from older autistic individuals. However, it is unclear whether these differences result from atypical neurodevelopment or sampling differences between young and older cohorts. Furthermore, the relationship between altered white matter development and longitudinal changes in autism symptoms is unknown. Methods: Using longitudinal diffusion-weighted magnetic resonance imaging acquired over 2 to 3 time points between the ages of approximately 2.5 to 7.0 years in 125 autistic children and 69 typically developing control participants, we directly tested the hypothesis that autistic individuals have atypical white matter development across childhood. Additionally, we sought to determine whether changes in white matter diffusion parameters were associated with longitudinal changes in autism severity. Results: Autistic children were found to have slower development of fractional anisotropy in the cingulum bundle, superior longitudinal fasciculus, internal capsule, and splenium of the corpus callosum. Furthermore, in the sagittal stratum, autistic individuals who increased in autism severity over time had a slower developmental trajectory of fractional anisotropy compared with individuals whose autism decreased in severity. In the uncinate fasciculus, autistic individuals who decreased in autism symptom severity also had greater increases in fractional anisotropy with age. Conclusions: These longitudinal findings indicate that previously reported differences in diffusion-weighted magnetic resonance imaging measures between younger and older autism cohorts are attributable to an atypical developmental trajectory of white matter. Differences in white matter development between individuals whose autism severity increased, remained stable, or decreased suggest that these functional differences are associated with fiber development in the autistic brain.

Original language	English
Pages (from-to)	424-432
Number of pages	9
Journal	Biological Psychiatry
Volume	89
Issue number	5
DOIs	https://doi.org/10.1016/j.biopsych.2020.10.013
State	Published - 1 Mar 2021
Externally published	Yes

Bibliographical note

Publisher Copyright:
© 2020 Society of Biological Psychiatry

Funding

The research reported in this article was supported by the National Institute of Mental Health (Grant No. R01MH104438 [to CWN], R01MH103284 [to MS], R01MH103371 [to DGA]), and the MIND Institute Autism Research Training Program (Grant No. T32MH073124 [to DSA]), as well as the UC Davis Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and the National Institute of Child Health and Human Development, MIND Institute Intellectual and Developmental Disabilities Research Center (Grant No. U54HD079125 [DJH; principal investigator, Leonard Abbeduto). We thank the families and children who participated in the APP and GAIN studies and all members of the research study staff. DGA is on the scientific advisory board for Stemina Biomarker Discovery and Axial Biotherapeutics. All other authors report no biomedical financial interests or potential conflicts of interest. The research reported in this article was supported by the National Institute of Mental Health (Grant No. R01MH104438 [to CWN], R01MH103284 [to MS], R01MH103371 [to DGA]), and the MIND Institute Autism Research Training Program (Grant No. T32MH073124 [to DSA]), as well as the UC Davis Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and the National Institute of Child Health and Human Development, MIND Institute Intellectual and Developmental Disabilities Research Center (Grant No. U54HD079125 [DJH; principal investigator, Leonard Abbeduto ).

Funders	Funder number
MIND Institute Autism Research Training Program
MIND Institute Intellectual and Developmental Disabilities Research Center	U54HD079125
National Institute of Mental Health	R01MH103371, R01MH104438, T32MH073124, R01MH103284
National Institute of Child Health and Human Development
University of California, Davis
Intellectual and Developmental Disabilities Research Center

Keywords

Autism
Development
Diffusion
Imaging
Longitudinal
White Matter

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10.1016/j.biopsych.2020.10.013

Cite this

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title = "A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood",

abstract = "Background: Cross-sectional diffusion-weighted magnetic resonance imaging studies suggest that young autistic children have alterations in white matter structure that differ from older autistic individuals. However, it is unclear whether these differences result from atypical neurodevelopment or sampling differences between young and older cohorts. Furthermore, the relationship between altered white matter development and longitudinal changes in autism symptoms is unknown. Methods: Using longitudinal diffusion-weighted magnetic resonance imaging acquired over 2 to 3 time points between the ages of approximately 2.5 to 7.0 years in 125 autistic children and 69 typically developing control participants, we directly tested the hypothesis that autistic individuals have atypical white matter development across childhood. Additionally, we sought to determine whether changes in white matter diffusion parameters were associated with longitudinal changes in autism severity. Results: Autistic children were found to have slower development of fractional anisotropy in the cingulum bundle, superior longitudinal fasciculus, internal capsule, and splenium of the corpus callosum. Furthermore, in the sagittal stratum, autistic individuals who increased in autism severity over time had a slower developmental trajectory of fractional anisotropy compared with individuals whose autism decreased in severity. In the uncinate fasciculus, autistic individuals who decreased in autism symptom severity also had greater increases in fractional anisotropy with age. Conclusions: These longitudinal findings indicate that previously reported differences in diffusion-weighted magnetic resonance imaging measures between younger and older autism cohorts are attributable to an atypical developmental trajectory of white matter. Differences in white matter development between individuals whose autism severity increased, remained stable, or decreased suggest that these functional differences are associated with fiber development in the autistic brain.",

keywords = "Autism, Development, Diffusion, Imaging, Longitudinal, White Matter",

author = "Andrews, \{Derek Sayre\} and Lee, \{Joshua K.\} and Harvey, \{Danielle Jenine\} and Einat Waizbard-Bartov and Marjorie Solomon and Rogers, \{Sally J.\} and Nordahl, \{Christine Wu\} and Amaral, \{David G.\}",

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AU - Solomon, Marjorie

AU - Rogers, Sally J.

AU - Nordahl, Christine Wu

AU - Amaral, David G.

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A Longitudinal Study of White Matter Development in Relation to Changes in Autism Severity Across Early Childhood

Abstract

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Keywords

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