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Impact of autism genetic risk on brain connectivity: a mechanism for the female protective effect.
Lawrence, Katherine E; Hernandez, Leanna M; Fuster, Emily; Padgaonkar, Namita T; Patterson, Genevieve; Jung, Jiwon; Okada, Nana J; Lowe, Jennifer K; Hoekstra, Jackson N; Jack, Allison; Aylward, Elizabeth; Gaab, Nadine; Van Horn, John D; Bernier, Raphael A; McPartland, James C; Webb, Sara J; Pelphrey, Kevin A; Green, Shulamite A; Bookheimer, Susan Y; Geschwind, Daniel H; Dapretto, Mirella.
Afiliação
  • Lawrence KE; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Hernandez LM; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Fuster E; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Padgaonkar NT; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Patterson G; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Jung J; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Okada NJ; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Lowe JK; Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Hoekstra JN; Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Jack A; Department of Psychology, George Mason University, Fairfax, VA 22030, USA.
  • Aylward E; Center for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA 98101, USA.
  • Gaab N; Harvard Graduate School of Education, Cambridge, MA 02138, USA.
  • Van Horn JD; Department of Psychology and School of Data Science, University of Virginia, Charlottesville, VA 22904, USA.
  • Bernier RA; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA.
  • McPartland JC; Child Study Center, Yale School of Medicine, New Haven, CT 06510, USA.
  • Webb SJ; Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA 98195, USA.
  • Pelphrey KA; Center on Child Health, Behavior, and Development, Seattle Children's Research Institute, Seattle, WA 98101, USA.
  • Green SA; Department of Neurology, University of Virginia, Charlottesville, VA 22904, USA.
  • Bookheimer SY; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Geschwind DH; Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, Los Angeles, CA 90095, USA.
  • Dapretto M; Department of Neurology, University of California Los Angeles, Los Angeles, CA 90095, USA.
Brain ; 145(1): 378-387, 2022 03 29.
Article em En | MEDLINE | ID: mdl-34050743
ABSTRACT
The biological mechanisms underlying the greater prevalence of autism spectrum disorder in males than females remain poorly understood. One hypothesis posits that this female protective effect arises from genetic load for autism spectrum disorder differentially impacting male and female brains. To test this hypothesis, we investigated the impact of cumulative genetic risk for autism spectrum disorder on functional brain connectivity in a balanced sample of boys and girls with autism spectrum disorder and typically developing boys and girls (127 youth, ages 8-17). Brain connectivity analyses focused on the salience network, a core intrinsic functional connectivity network which has previously been implicated in autism spectrum disorder. The effects of polygenic risk on salience network functional connectivity were significantly modulated by participant sex, with genetic load for autism spectrum disorder influencing functional connectivity in boys with and without autism spectrum disorder but not girls. These findings support the hypothesis that autism spectrum disorder risk genes interact with sex differential processes, thereby contributing to the male bias in autism prevalence and proposing an underlying neurobiological mechanism for the female protective effect.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Transtorno do Espectro Autista Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Transtorno Autístico / Transtorno do Espectro Autista Idioma: En Ano de publicação: 2022 Tipo de documento: Article