Is there an association between prenatal testosterone and autistic traits in adolescents?

Niamh Dooley,Amber Ruigrok,Rosemary Holt,Carrie Allison,Alexandros Tsompanidis,Jack Waldman,Bonnie Auyeung,Michael V Lombardo,Simon Baron-Cohen

doi:10.1016/j.psyneuen.2021.105623

Abstract

Prenatal testosterone (pT) is a crucial component in physiological masculinization in humans. In line with the Prenatal Sex Steroid Theory of autism, some studies have found a positive correlation between pT and autistic traits in childhood. However, effects in adolescence have not been explored. Hormonal and environmental changes occurring during puberty may alter the strength or the nature of prenatal effects on autistic traits. The current study examines if pT relates to autistic traits in a non-clinical sample of adolescents and young adults (N = 97, 170 observations; age 13–21 years old). It also explores pT interactions with pubertal stage and timing. PT concentrations were measured from amniotic fluid extracted in the 2nd trimester of gestation via amniocentesis conducted for clinical purposes. Autistic traits were measured by self- and parent-reports on the Autism Spectrum Quotient (AQ) which provides a total score and 5 sub-scores (social skills, communication, imagination, attention switching and attention to detail). Self-reported pubertal stage was regressed on age to provide a measure of relative timing. We found no statistical evidence for a direct association between pT and autistic traits in this adolescent sample (males, females or full sample). Exploratory analyses suggested that pT correlated positively with autistic traits in adolescents with earlier puberty-onset, but statistical robustness of this finding was limited. Further exploratory post-hoc tests suggested the pT-by-pubertal timing interaction was stronger in males relative to females, in self-reported compared to parent-reported AQ and specifically for social traits. These findings require replication in larger samples. Findings have implications for understanding the effects of pT on human behavior, specifically existence of effects in adolescence.

Highlights

Autism Spectrum Conditions are the spectrum of phenotypes characterized by differences in social interaction, communication, adjusting to unexpected change, alongside unusually restricted and repetitive behavior, focused or intense interests, and sensory differences
We explore the relative effects of Prenatal testosterone (pT) on each Autism Spectrum Quotient (AQ) subscale and whether pubertal factors have any effect on the pT-AQ relationship
Exploratory findings indicated that the effects of pT were moderated by pubertal timing, in males, such that having both high pT and early/fast pubertal development was linked with the highest AQ scores while having both high pT and slow/ late puberty was linked with lowest AQ scores (Fig. 3)

Summary

Introduction

Autism Spectrum Conditions (autism) are the spectrum of phenotypes characterized by differences in social interaction, communication, adjusting to unexpected change, alongside unusually restricted and repetitive behavior, focused or intense interests, and sensory differences. Males report more autistic traits than females (Baron-Cohen et al, 2001; Greenberg et al, 2018) This has raised the question whether prenatal testosterone (pT), a masculinizing factor, contributes to the develop ment of autism (Baron-Cohen et al, 2011). Congenital Adrenal Hyperplasia (CAH) is an autosomal recessive disorder characterized by cortisol deficiency and elevated androgens beginning prenatally. Not all studies have found associations between male-typical morphology and autistic traits in a direction consistent with increased pT (Kung et al, 2021; Smith et al, 2019; Alaerts et al, 2016; Lee et al, 2020; Bejerot et al, 2012)

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