Sex Differences in Autism Spectrum Disorder: a Review

Abstract

Purpose of Review

Neurodevelopmental disorders disproportionately affect males. The mechanisms underlying male vulnerability or female protection are not known and remain understudied. Determining the processes involved is crucial to understanding the etiology and advancing treatment of neurodevelopmental disorders. Here, we review current findings and theories that contribute to male preponderance of neurodevelopmental disorders, with a focus on autism.

Recent Findings

Recent work on the biological basis of the male preponderance of autism and other neurodevelopmental disorders includes discussion of a higher genetic burden in females and sex-specific gene mutations or epigenetic changes that differentially confer risk to males or protection to females. Other mechanisms discussed are sex chromosome and sex hormone involvement. Specifically, fetal testosterone is involved in many aspects of development and may interact with neurotransmitter, neuropeptide, or immune pathways to contribute to male vulnerability. Finally, the possibilities of female underdiagnosis and a multi-hit hypothesis are discussed.

Summary

This review highlights current theories of male bias in developmental disorders. Topics include environmental, genetic, and epigenetic mechanisms; theories of sex chromosomes, hormones, neuroendocrine, and immune function; underdiagnosis of females; and a multi-hit hypothesis.

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Acknowledgements

This work was supported by NIMH grant R34MH104407 (Brodkin, PI), the Asperger Syndrome Program of Excellence at University of Pennsylvania (Brodkin, co-Director), and Simons Foundation (SFARI) grant 345034 (Abel, PI). We would like to thank Joseph F. Lynch III for his help editing the manuscript.

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Correspondence to Edward S. Brodkin.

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Sarah L. Ferri, Ted Abel, and Edward S. Brodkin declare no conflict of interest.

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This article is part of the Topical Collection on Sex and Gender Issues in Behavioral Health

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Ferri, S.L., Abel, T. & Brodkin, E.S. Sex Differences in Autism Spectrum Disorder: a Review. Curr Psychiatry Rep 20, 9 (2018). https://doi.org/10.1007/s11920-018-0874-2

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Keywords

  • Neurodevelopmental disorders
  • Autism
  • Sex differences
  • Female protective effect
  • Extreme male brain theory
  • Fetal testosterone