Sex differences in brain development in fetuses and infants who are at low or high likelihood for autism

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Villa, L. M., Hampton, S., Aydin, E., Tait, R., Leming, M. J., Tsompanidis, A., Patterson, I., Allison, C. T., Austin, T., Suckling, J., Baron-Cohen, S., & Holt, R. J. (2021). Sex differences in brain development in fetuses and infants who are at low or high likelihood for autism [Preprint]. openRxiv. https://doi.org/10.1101/2021.03.08.21251862

Publication date: 11 Mar 2021 Added to AutiHub: 30 Sep 2026 Type: Preprint Article language: English
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12
Publication authors identified as autistic
1 / 12 (8.3%)
  1. L. M. Villa
  2. S. Hampton *
  3. E. Aydin
  4. R. Tait
  1. M. J. Leming
  2. A. Tsompanidis
  3. I. Patterson
  4. Carrie T. Allison
  1. T. Austin
  2. J. Suckling
  3. Simon Baron-Cohen
  4. R. J. Holt

Abstract

Abstract Background It is unknown whether the neural underpinnings of autism are present in utero. In addition, it is unclear whether typical neural sexual differentiation, which is associated with the development of autism, is evident in utero. We longitudinally investigated fetal and infant sex differences in brain structure and function, and differences in brain development in those at low and high likelihood for autism. Here, we use the term ‘typical’ interchangeably with the term ‘low-autism likelihood’. Methods Participants were longitudinally studied in utero first at 30-33 weeks of gestation, and then as infants 8-12 weeks after birth. We compared total brain volumes and resting-state functional connectivity between 15 female and 15 male low-autism likelihood fetuses (defined as having no first degree autistic relative). We also compared the brain structure and function of these 30 fetuses to a rare group of 11 fetuses (5 females and 6 males) who had an autistic mother or sibling, and therefore a higher likelihood of developing autism. Although a small sample, the high-autism likelihood group are reported as they are challenging to recruit. Additionally, we correlated sex differences in functional connectivity with autism likelihood group differences across the fetal and infant brains. Results There was a group-by-sex interaction in fetal total brain volume. Typical males, on average, showed faster total brain volume growth in the perinatal period than typical females. The high-autism likelihood group showed lower resting-state functional connectivity at both time-points compared to the typical group, and regions indicating sex differences overlapped with those associated with high-autism likelihood group differences in functional connectivity. Conclusions In utero sexual differentiation of brain structure was more pronounced in fetuses with a high likelihood for autism. Moreover, sexual differentiation of the fetal and infant brain may overlap with the neural development of autism.

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Cited references
73
With a DOI
72
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0
0 / 73 (0.0%) cited references include at least one author identified as autistic.
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0 / 73 (0.0%)
References with detected author names
73 / 73 (100.0%)
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0
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0
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1
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Author names detected in the cited bibliography
638
From DOI or external metadata
638
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0
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0
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0
107 / 638 (16.8%) names are linked to an author already present in AutiHub. 531 / 638 (83.2%) names are not yet linked.
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0 / 638 (0.0%)
Calculated across all author names detected in the cited bibliography. Among names linked to an author already present in AutiHub: 0 / 107 (0.0%). Distinct people identified as autistic: 0 / 425 (0.0%).
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