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

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.

Salivary testosterone in male and female youth with and without autism spectrum disorder: considerations of development, sex, and diagnosis

“…On the surface, these results do not appear to align with a recent study comparing prenatal testosterone (pT) to autistic traits in adolescents and young adults aged 13 to 21 [68]. Similar to our current report, there were no direct associations between pT and autistic traits.…”

“…Earlier pubertal timing was also observed in males with ASD albeit during middle adolescence [70]}, which again seems to align with the rise in testosterone in males. Despite this intriguing connection between pubertal testosterone, autism, and sex, there are notable differences in methods between the current study and Dooley et al (2022), which include: sample differences (confirmed ASD diagnosis vs. self/parent-report of autistic traits), sample age (10-13 years vs. 13-21 years), testosterone effects (pubertal/activational vs. prenatal/organizational), and pubertal development (Physical Exam Tanner staging vs. PDS questionnaire), respectively. Furthermore, while the current study did not find any relationship between ASD diagnosis and testosterone at varying developmental stages, we did not explore differences according to early-, normative-, or late-pubertal timing, nor did we examine a relationship with age of menarche in females.…”

“…Similar to our current report, there were no direct associations between pT and autistic traits. In contrast, however, exploratory analysis suggested a positive correlation between autistic traits and pT in those with earlier pubertal timing, which was stronger in males [ 68 ]. As such, there may be unique associations between pubertal timing, ASD symptoms, and biological sex.…”

“…Future longitudinal studies of steroid levels from the prenatal to the pubertal period would provide more insight into both organizational and activational roles for testosterone in ASD. This notion is important to consider especially since findings during childhood and adolescence are mixed (e.g., [ 24 , 31 , 32 , 39 , 40 , 68 ]). It is plausible there exists a more nuanced effect in which elevations in testosterone are observed in a subset of youth, such as those with earlier pubertal onset.…”

Inter-Network Brain Functional Connectivity in Adolescents Assigned Female at Birth Who Experience Gender Dysphoria

“…A second theoretical perspective is the neurohormonal hypothesis, which posits that prenatal androgen exposure organizes parts of the brain (in terms of structure (23) and function (24)) as well as sex-differentiated psychological and behavioral characteristics (25), including gender identity and sexual orientation. The surge in sex hormones during adolescence is argued to influence parts of the brain to be further expressed in a relatively male-or female-typical manner, based on the earlier prenatal brain organization (6)(7)(8)(9)(26)(27)(28).…”