Sex differences in the effects of gonadal hormones on white matter microstructure development in adolescence

Abstract

Adolescence, the transition between childhood and adulthood, is characterized by rapid brain development in white matter (WM) that is attributed in part to surges in gonadal hormones. To date, however, there have been no longitudinal investigations of the effects of gonadal hormones on WM development in adolescents. We acquired T1-weighted and diffusion-weighted MRIs at two timepoints and saliva samples from 80 adolescents (52 females [11.10{+/-}1.05 years at Time 1; 12.75{+/-}1.37 years at Time 2] and 28 males [ages 11.91{+/-}0.88 years at Time 1; 13.79{+/-}0.95 years at Time 2] who were matched on pubertal stage at Time 1. We estimated mean fractional anisotropy (FA) from 10 major WM tracts and assayed levels of testosterone (in both sexes) and estradiol (in females only). We used linear regression models to test whether interactions between sex and changes in testosterone levels significantly explained changes in FA. Sex significantly moderated the associations between changes in testosterone and changes in FA within the corpus callosum, inferior fronto-occipital fasciculus (IFOF), uncinate fasciculus (UF), and cingulum cingulate (all ps<0.05): whereas these associations were positive in females, they were not significant in males. Females also exhibited positive associations between changes in estradiol and changes in UF, IFOF, and corticospinal FA (all ps<0.05). Our findings indicate that sex differences in WM microstructure of tracts supporting cognitive control, response inhibition, and emotion regulation are explained by differences in changes in testosterone, and have important implications for understanding sex differences in brain development and psychosocial behaviors during the pubertal transition.