The so-called “extreme male brain” hypothesis is one of the proposed triggers for autism and thought to be a result of higher prenatal exposure to testosterone. However, a new paper published on 4 September in Proceedings of the Royal Society B, a peer-reviewed journal may have provided evidence to challenge this theory (1).
The controversial hypothesis postulates that excess testosterone exposure in the uterus may lead to a hypermasculine view of the world in both women and men — including lower cognitive empathy — and in some cases may lead to autism spectrum disorders (ATDs).
Cognitive empathy — sometimes referred to as “perspective-taking” — is defined as the capacity to interpret others’ emotions and understand their behaviour based on their emotional state. This differs from emotional empathy or the ability to simply feel others’ emotions along with them and is essential for social interactions between humans, and indeed, any species. Impairment of cognitive empathy is linked to a broad range of psychopathological conditions including many autistic disorders as well as schizophrenia.
The extreme male brain hypothesis was first proposed in 2011 by Simon Baron-Cohen, a psychologist at the University of Cambridge in the United Kingdom, who observed that women administered large doses of testosterone performed significantly worse on the Reading the Mind in the Eyes test (RMET), a test that requires participants to match the mental state of a person to their facial expressions.
Males are four times more likely to have autism than females, according to the Centers for Disease Control and Prevention (CDC), and as with any trait or disorder differentiated by sex, has provided the motivation for this testosterone-based line of thought. But reasons for the sex-related difference in ATD incidence remain elusive.
Earlier studies — based on small samples and relying on observations — suggested a possible link between testosterone and lower cognitive empathy. But smaller follow-up studies were unable to replicate the findings, leading some scientists to express doubts. Now, two large randomised controlled trials “unequivocally show that there is not a linear causal relation between testosterone exposure and cognitive empathy”, says lead author Dr Amos Nadler, previously at Western University in Canada and now based at the University of Toronto.
So, to test the hypothesis — i.e. the link between cognitive empathy and testosterone — the researchers carried out a much larger study with more than 600 male participants. The men were given a single dose of testosterone applied to the shoulder or as a nasal gel or a placebo and took the RMET both before and after. In addition, they looked at a controversial metric, the 2D:4D ratio, which is based on the idea that the ring finger of people with autism (mostly men) is often longer than their index finger.
Interestingly, unlike Baron-Cohen’s study, the team found no differences in performance on cognitive empathy tests, before and after, and could not find any detectable pattern in 2D:4D ratios that could link testosterone exposure in the womb to empathy levels.
Senior study author Dr Gideon Nave points out that while the authors found no evidence to support this effect of testosterone, the study does not rule out any possible effects. In other words, the absence of evidence is not the same as evidence of absence. However, they do hope the findings will banish any misconceptions that controlling testosterone, for example, by blocking the hormone in pregnant women, can prevent autism.
(1) Nadler, A. et al. Does testosterone impair men’s cognitive empathy? Evidence from two large-scale randomized controlled trials. Proceedings of the Royal Society B (2019). DOI: 10.1098/rspb.2019.1062