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The prenatal sex steroid theory of autism

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Autism affects males more often than females. This is likely to be true even after taking into account under-diagnosis of females with Asperger Syndrome. One candidate biological mechanism for this is prenatal sex steroid hormones, that shape brain development, which themselves are under genetic control and have epigenetic properties. In this lecture I summarize work from our lab from 4 lines of evidence: (1) Testing if one sex steroid hormone, testosterone, measured in the womb is associated with individual differences in typical children’s language and social development, attention to detail and narrow interests, autistic traits, and brain structure and function. (2) Testing if elevated prenatal sex steroid levels are associated with autism itself. (3) Testing if proxies of prenatal sex steroid levels in people with autism are also atypical. (4) Testing if post-natal sex steroid hormones in autism are elevated. These studies implicate a specific biological pathway (the Δ4 sex steroid pathway) as one important factor in the aetiology of autism. A recent animal model testing this theory is discussed, and the ethics of translating these findings is considered.

Key Books Baron-Cohen, S, (2003) The Essential Difference: men, women and the extreme male brain. Penguin/Basic Books. Baron-Cohen, S, et al (2005) Prenatal testosterone in mind: Studies of amniotic fluid. MIT Press/Bradford Books.

Links: www.autismresearchcentre.com

Key Journal Articles Baron-Cohen, S, et al (2005) Sex differences in the brain: implications for explaining autism. Science, 310, 819-823. Baron-Cohen, S, et al (2011) Why are Autism Spectrum Conditions more prevalent in males? Public Library of Science Biology, 9, 1-10; and Supplementary Material. Baron-Cohen, S, et al (2014). Attenuation of typical sex difference in 800 adults with autism vs. 3,900 controls. PLoS ONE , 9, e102251. Baron-Cohen, S, et al (2015) ‘The “Reading the Mind in the Eyes” Test: Complete absence of typical sex difference in ~400 men and women with autism’. PLoS ONE , DOI:10.1371/journal.pone.0136521 August 27, 2015 Baron-Cohen, S, et al (2015) Elevated fetal steroidogenic activity in autism. Molecular Psychiatry, 1-8. and Supplementary Material. Chakrabarti, B, et al (2009) Genes related to sex-steroids, neural growth and social-emotional behaviour are associated with autistic traits, empathy and Asperger Syndrome. Autism Research, 2, 157-177. Lai, et al (2013) Biological sex affects the neurobiology of autism. Brain, 136, 2799-2815. Lombardo, et al (2012) Fetal testosterone influences sexually dimorphic gray matter in the human brain. Journal of Neuroscience. 32(2): 674-80. Pohl, et al (2014) Uncovering steroidopathy in women with autism: a latent class analysis. Molecular Autism, 5, 27. Ruigrok, et al (2014) A meta-analysis of sex differences in human brain structure. Neuroscience and Biobehavioral Reviews, 39: 34-50. Ruta, L, et al (2011) Increased serum androstenedione in adults with Autism Spectrum Conditions. Psychoneuroendocrinology. 36(8), 1154-63. Schwarz, E, et al (2010) Sex-specific serum biomarker patterns in adults with Asperger’s Syndrome. Molecular Psychiatry. 16 (12): 1213-20.

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