Organizational effects of fetal testosterone on human corpus callosum size and asymmetry

Previous theory and research in animals has identified the critical role that fetal testosterone (FT) plays in organizing sexually dimorphic brain development. However, to date there are no studies in humans directly testing the organizational effects of FT on structural brain development. In the current study we investigated the effects of FT on corpus callosum size and asymmetry. High-resolution structural magnetic resonance images (MRI) of the brain were obtained on 28 8-11-year-old boys whose exposure to FT had been previously measured in utero via amniocentesis conducted during the second trimester. Although there was no relationship between FT and midsaggital corpus callosum size, increasing FT was significantly related to increasing rightward asymmetry (e.g., Right>Left) of a posterior subsection of the callosum, the isthmus, that projects mainly to parietal and superior temporal areas. This potential organizational effect of FT on rightward callosal asymmetry may be working through enhancing the neuroprotective effects of FT and result in an asymmetric distribution of callosal axons. We suggest that this possible organizational effect of FT on callosal asymmetry may also play a role in shaping sexual dimorphism in functional and structural brain development, cognition, and behavior.

Why are autism spectrum conditions more prevalent in males?

Autism Spectrum Conditions (ASC) are much more common in males, a bias that may offer clues to the etiology of this condition. Although the cause of this bias remains a mystery, we argue that it occurs because ASC is an extreme manifestation of the male brain. The extreme male brain (EMB) theory, first proposed in 1997, is an extension of the Empathizing-Systemizing (E-S) theory of typical sex differences that proposes that females on average have a stronger drive to empathize while males on average have a stronger drive to systemize. In this first major update since 2005, we describe some of the evidence relating to the EMB theory of ASC and consider how typical sex differences in brain structure may be relevant to ASC. One possible biological mechanism to account for the male bias is the effect of fetal testosterone (fT). We also consider alternative biological theories, the X and Y chromosome theories, and the reduced autosomal penetrance theory. None of these theories has yet been fully confirmed or refuted, though the weight of evidence in favor of the fT theory is growing from converging sources (longitudinal amniocentesis studies from pregnancy to age 10 years old, current hormone studies, and genetic association studies of SNPs in the sex steroid pathways). Ultimately, as these theories are not mutually exclusive and ASC is multi-factorial, they may help explain the male prevalence of ASC.