Cortical gyrification in women and men and the (missing) link to prenatal androgens.

Previous studies have reported sex differences in cortical gyrification. Since most cortical folding is principally defined in utero, sex chromosomes as well as gonadal hormones are likely to influence sex-specific aspects of local gyrification. Classic congenital adrenal hyperplasia (CAH) causes high levels of androgens during gestation in females, whereas levels in males are largely within the typical male range. Therefore, CAH provides an opportunity to study the possible effects of prenatal androgens on cortical gyrification. Here, we examined the vertex-wise absolute mean curvature-a common estimate for cortical gyrification-in individuals with CAH (33 women and 20 men) and pair-wise matched controls (33 women and 20 men). There was no significant main effect of CAH and no significant CAH-by-sex interaction. However, there was a significant main effect of sex in five cortical regions, where gyrification was increased in women compared to men. These regions were located on the lateral surface of the brain, specifically left middle frontal (rostral and caudal), right inferior frontal, left inferior parietal, and right occipital. There was no cortical region where gyrification was increased in men compared to women. Our findings do not only confirm prior reports of increased cortical gyrification in female brains but also suggest that cortical gyrification is not significantly affected by prenatal androgen exposure. Instead, cortical gyrification might be determined by sex chromosomes either directly or indirectly-the latter potentially by affecting the underlying architecture of the cortex or the size of the intracranial cavity, which is smaller in women.

Prenatal androgen exposure and sex-typical play behaviour: A meta-analysis of classic congenital adrenal hyperplasia studies.

Thousands of non-human mammal experiments have demonstrated that early androgen exposure exerts long-lasting effects on neurobehavioural sexual differentiation. In humans, females with classic congenital adrenal hyperplasia (CAH) are exposed to unusually high concentrations of androgens prenatally, whereas prenatal concentrations of androgens in males with CAH are largely normal. The current meta-analysis included 20 independent samples and employed multi-level meta-analytic models. Consistently across all 7 male-typical and female-typical play outcomes, in the expected directions, the present study found significant and large average differences between control males and control females (gs = 0.83-2.78) as well as between females with CAH and control females (gs = 0.95-1.08), but differences between males with CAH and control males were mostly negligible and were non-significant for 6 of the 7 outcomes (gs = 0.04-0.27). These meta-analytic findings suggest that prenatal androgen exposure masculinises and defeminises play behaviour in humans. Broader implications in relation to sex chromosomes, brain development, oestrogens, socio-cognitive influences, other aspects of sex-related behavioural development, and gender nonconformity are discussed.