The Prenatal Sex Steroid Theory of Autism
Presenting Author(s): Prof. Sir Simon Baron-Cohen
Date and time: 22 Mar 2024 from 10:20 to 11:20
Location: Wildrose Salon C (Virtual)
Learning Objectives
1. To introduce this theory;
2. To summarise the evidence relevant to the theory; and
3. To understand the causes of autism.
Literature References
Books
1. Baron-Cohen, S, (2003) The Essential Difference: men, women and the extreme male brain. Penguin/Basic Books.
2. Baron-Cohen, S, et al (2005) Prenatal testosterone in mind: Studies of amniotic fluid. MIT Press/Bradford Books.
3. Baron-Cohen, S, (2011) Zero Degrees of Empathy. Penguin/Basic Books
4. Baron-Cohen, S, (2020) The Pattern Seekers. Penguin/Basic Books.
Links
Key Journal Articles
1. Baron-Cohen, S, et al (2005) Sex differences in the brain: implications for explaining autism. Science, 310, 819-823.
2. 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.
3. Baron-Cohen, S, et al (2015) Elevated fetal steroidogenic activity in autism. Molecular Psychiatry, 1-8. and Supplementary Material.
4. Baron-Cohen, S, et al (2019) Foetal estrogens and autism. Molecular Psychiatry. 25, 2970-2978.
5. Floris, D, et al (2023) The link between autism and sex-specific neuroanatomy, and associated cognition and gene expression. American Journal of Psychiatry, 1, 50-64.
6. Greenberg, D, M, et al (2018) Testing the Empathizing-Systemizing theory of sex differences and the Extreme Male Brain theory of autism in half a million people. PNAS, 115, 12152-7.
7. Lai, et al (2013) Biological sex affects the neurobiology of autism. Brain, 136, 2799-2815.
8. Lombardo, et al (2012) Fetal testosterone influences sexually dimorphic gray matter in the human brain. Journal of Neuroscience. 32(2): 674-80.
9. Pohl, et al (2014) Uncovering steroidopathy in women with autism: a latent class analysis. Molecular Autism, 5, 27.
10. Ruta, L, et al (2011) Increased serum androstenedione in adults with Autism Spectrum Conditions. Psychoneuroendocrinology. 36(8), 1154-63.
11. Schwarz, E, et al (2010) Sex-specific serum biomarker patterns in adults with Asperger's Syndrome. Molecular Psychiatry. 16 (12): 1213-20.
12. Warrier, V, et al (2018) Genome-wide meta-analysis of cognitive empathy: heritability, and correlates with sex, neuropsychiatric conditions and cognition. Molecular Psychiatry, 23, 1402–1409.
13. Warrier, V, et al (2018) Genome-wide analyses of self-reported empathy: correlations with autism, schizophrenia, and anorexia nervosa. Translational Psychiatry, 8, 8-10.
Abstract
In the general population, females on average show higher levels of empathy and males on average show a stronger drive to systemize. Empathy involves both a cognitive element (recognizing another person’s mental state) and an affective element (responding to another person’s mental state with an appropriate emotion). Systemizing is the drive to analyse or build systems (whether these are mechanical, mathematical, musical, natural, abstract, motoric, or collectible). Systems are anything that follows if-and-then rules. I present evidence that autistic people score below average on different measures of cognitive empathy and that they are intact and even sometimes superior on measures of systemizing. If one takes the difference (D scores) between one’s scores on empathy and on systemizing then autism can be viewed as an extreme of the typical male brain. Autism is strongly genetic and is diagnosed more often in males than females. This appears to be true even after taking into account under-diagnosis of females. One candidate biological epigenetic mechanism that might influence typical sex differences and may play a role in ‘masculinizing’ the autistic brain is prenatal sex steroid hormones, that shape brain development via epigenetic and apoptotic mechanisms. I summarize work from our lab showing how levels of prenatal sex steroid hormones such as testosterone and estrogen are associated with typical sex differences in empathy and systemizing and autistic traits, and are elevated in autistic people.