Developmental Effects of Androgens in the Human Brain

Abstract

Neuroendocrine theories of brain development posit that androgens play a crucial role in sex-specific cortical growth, but little is known about the differential effects of testosterone and dehydroepiandrosterone (DHEA) on cortico-limbic development and cognition during adolescence. In this context, the NIH Study of Normal Brain Development, a longitudinal study of typically developing children and adolescents 4 to 24 years of age (n=433), offered a unique opportunity to examine the developmental effects of androgens on cortico-limbic maturation and cognition. Using data from this sample, our group found higher testosterone levels to be associated with left-sided decreases in cortical thickness (CTh) in post-pubertal boys, particularly in the prefrontal cortex, compared to right-sided increases in CTh in somatosensory areas in pre-pubertal girls. Prefrontal-amygdala and prefrontal-hippocampal structural covariance (thought to reflect structural connectivity) also varied according to testosterone levels, with the testosterone-related brain phenotype predicting higher aggression levels and lower executive function, particularly in boys. In contrast, DHEA was associated with a pre-pubertal increase in CTh of several regions involved in cognitive control in both boys and girls. Covariance within several cortico-amygdalar structural networks also varied as a function of DHEA levels, with the DHEA-related brain phenotype predicting improvements in visual attention in both boys and girls. DHEA-related cortico-hippocampal structural covariance, on the other hand, predicted higher scores on a test of working memory. Interestingly, there were significant interactions between testosterone and DHEA, such that DHEA tended to mitigate the anti-proliferative effects of testosterone on brain structure. In sum, testosterone-related effects on the developing brain may lead to detrimental effects on cortical functions (i.e. higher aggression and lower executive function), while DHEA-related effects may optimize cortical functions (i.e. better attention and working memory), perhaps by decreasing the influence of amygdalar and hippocampal afferents on cortical functions.

This article is protected by copyright. All rights reserved.

http://ift.tt/2pwzFKw