Sex Differences in the Amygdala Resting-State Connectome of Children With Autism Spectrum Disorder

Research output: Contribution to journalArticle

Abstract

Background: Multifactorial liability models predict greater dissimilarity in the neural phenotype of autism spectrum disorder (ASD) in female individuals than in male individuals, while gender incoherence and extreme male brain models predict attenuated sex differences in ASD. The amygdala is an informative target to explore these models because it is implicated in both the neurobiology of ASD and sex differences in typical development. Methods: This study investigated amygdala resting-state functional connectivity in a cohort of 116 children with ASD (36 female) and 58 typically developing children (27 female) 2 to 7 years of age during natural sleep. First, multivariate distance matrix regression assessed global sex and diagnostic differences across the amygdala connectome. Second, univariate general linear models identified regions with mean connectivity differences. Results: Multivariate distance matrix regression revealed greater differences between typically developing children and those with ASD in females than in males, consistent with multifactorial liability models, and attenuated sex differences in the left amygdala connectome of children with ASD in a pattern consistent with the gender incoherence model. Univariate analysis identified similar sex differences in dorsomedial and ventral prefrontal cortices, lingual gyrus, and posterior cingulate cortex, but also noted that lower amygdala connectivity with superior temporal sulcus is observed across sexes. Conclusions: This study provides evidence that compared with sex-matched control subjects, ASD manifests differently in the brain at the time of diagnosis and prior to the influence of compensatory mechanisms in male and female children, consistent with multifactorial liability models, and that ASD is associated with reduced sex differences in a pattern consistent with gender incoherence models.

Original languageEnglish (US)
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
DOIs
StateAccepted/In press - Jan 1 2019

Fingerprint

Connectome
Amygdala
Sex Characteristics
Occipital Lobe
Neurobiology
Autism Spectrum Disorder
Gyrus Cinguli
Brain
Temporal Lobe
Prefrontal Cortex
Linear Models
Sleep
Phenotype

Keywords

  • Amygdala
  • Autism
  • Connectome
  • Gender
  • Imaging
  • Sex

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cognitive Neuroscience
  • Clinical Neurology
  • Biological Psychiatry

Cite this

@article{6bffbeb2579f46e9b8d69f81af0b54a4,
title = "Sex Differences in the Amygdala Resting-State Connectome of Children With Autism Spectrum Disorder",
abstract = "Background: Multifactorial liability models predict greater dissimilarity in the neural phenotype of autism spectrum disorder (ASD) in female individuals than in male individuals, while gender incoherence and extreme male brain models predict attenuated sex differences in ASD. The amygdala is an informative target to explore these models because it is implicated in both the neurobiology of ASD and sex differences in typical development. Methods: This study investigated amygdala resting-state functional connectivity in a cohort of 116 children with ASD (36 female) and 58 typically developing children (27 female) 2 to 7 years of age during natural sleep. First, multivariate distance matrix regression assessed global sex and diagnostic differences across the amygdala connectome. Second, univariate general linear models identified regions with mean connectivity differences. Results: Multivariate distance matrix regression revealed greater differences between typically developing children and those with ASD in females than in males, consistent with multifactorial liability models, and attenuated sex differences in the left amygdala connectome of children with ASD in a pattern consistent with the gender incoherence model. Univariate analysis identified similar sex differences in dorsomedial and ventral prefrontal cortices, lingual gyrus, and posterior cingulate cortex, but also noted that lower amygdala connectivity with superior temporal sulcus is observed across sexes. Conclusions: This study provides evidence that compared with sex-matched control subjects, ASD manifests differently in the brain at the time of diagnosis and prior to the influence of compensatory mechanisms in male and female children, consistent with multifactorial liability models, and that ASD is associated with reduced sex differences in a pattern consistent with gender incoherence models.",
keywords = "Amygdala, Autism, Connectome, Gender, Imaging, Sex",
author = "Lee, {Joshua K.} and Amaral, {David G.} and Marjorie Solomon and Rogers, {Sally J.} and Sally Ozonoff and Nordahl, {Christine Wu}",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.bpsc.2019.08.004",
language = "English (US)",
journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",
issn = "2451-9022",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Sex Differences in the Amygdala Resting-State Connectome of Children With Autism Spectrum Disorder

AU - Lee, Joshua K.

AU - Amaral, David G.

AU - Solomon, Marjorie

AU - Rogers, Sally J.

AU - Ozonoff, Sally

AU - Nordahl, Christine Wu

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Background: Multifactorial liability models predict greater dissimilarity in the neural phenotype of autism spectrum disorder (ASD) in female individuals than in male individuals, while gender incoherence and extreme male brain models predict attenuated sex differences in ASD. The amygdala is an informative target to explore these models because it is implicated in both the neurobiology of ASD and sex differences in typical development. Methods: This study investigated amygdala resting-state functional connectivity in a cohort of 116 children with ASD (36 female) and 58 typically developing children (27 female) 2 to 7 years of age during natural sleep. First, multivariate distance matrix regression assessed global sex and diagnostic differences across the amygdala connectome. Second, univariate general linear models identified regions with mean connectivity differences. Results: Multivariate distance matrix regression revealed greater differences between typically developing children and those with ASD in females than in males, consistent with multifactorial liability models, and attenuated sex differences in the left amygdala connectome of children with ASD in a pattern consistent with the gender incoherence model. Univariate analysis identified similar sex differences in dorsomedial and ventral prefrontal cortices, lingual gyrus, and posterior cingulate cortex, but also noted that lower amygdala connectivity with superior temporal sulcus is observed across sexes. Conclusions: This study provides evidence that compared with sex-matched control subjects, ASD manifests differently in the brain at the time of diagnosis and prior to the influence of compensatory mechanisms in male and female children, consistent with multifactorial liability models, and that ASD is associated with reduced sex differences in a pattern consistent with gender incoherence models.

AB - Background: Multifactorial liability models predict greater dissimilarity in the neural phenotype of autism spectrum disorder (ASD) in female individuals than in male individuals, while gender incoherence and extreme male brain models predict attenuated sex differences in ASD. The amygdala is an informative target to explore these models because it is implicated in both the neurobiology of ASD and sex differences in typical development. Methods: This study investigated amygdala resting-state functional connectivity in a cohort of 116 children with ASD (36 female) and 58 typically developing children (27 female) 2 to 7 years of age during natural sleep. First, multivariate distance matrix regression assessed global sex and diagnostic differences across the amygdala connectome. Second, univariate general linear models identified regions with mean connectivity differences. Results: Multivariate distance matrix regression revealed greater differences between typically developing children and those with ASD in females than in males, consistent with multifactorial liability models, and attenuated sex differences in the left amygdala connectome of children with ASD in a pattern consistent with the gender incoherence model. Univariate analysis identified similar sex differences in dorsomedial and ventral prefrontal cortices, lingual gyrus, and posterior cingulate cortex, but also noted that lower amygdala connectivity with superior temporal sulcus is observed across sexes. Conclusions: This study provides evidence that compared with sex-matched control subjects, ASD manifests differently in the brain at the time of diagnosis and prior to the influence of compensatory mechanisms in male and female children, consistent with multifactorial liability models, and that ASD is associated with reduced sex differences in a pattern consistent with gender incoherence models.

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KW - Imaging

KW - Sex

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