Disentangling the Unique Associations of Age, Pubertal Stage, and Pubertal Hormones with White Matter Microstructure in Childhood and Adolescence

Puberty is associated with hormone level changes that influence white matter development. It remains unclear how pubertal stage and pubertal hormones uniquely relate to white matter microstructure development. Further, it is unclear if white matter tracts develop along a hierarchical sensorimotor-association (S-A) axis, similar to other aspects of brain development. We used the Human Connectome Project in Development cross-sectional sample of 1,105 youth (aged 5-21 years) to investigate unique associations of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone with fractional anisotropy (FA) within canonical white matter tracts. The average S-A axis rank was calculated for tract cortical endpoints. Age was the best-fit model for 17 tracts with prefrontal, parietal, and temporal connections. The Pubertal Timing model (age-adjusted pubertal stage) was the best fit for the superior longitudinal fasciculus 1. The DHEA model was the best fit for the splenium, genu, and prefrontal body of the corpus callosum. The Estradiol model was the best fit for the ventral cingulum bundle, extreme capsule, inferior longitudinal fasciculus and uncinate fasciculus. The Full model was the best fit for the rostrum. Radial diffusivity explained more FA variability than axial diffusivity in all tracts. Pubertal Timing and DHEA were more related to FA in association-related tracts than sensorimotor-related tracts. Thus, during childhood and adolescence, Pubertal timing and DHEA may be uniquely related to white matter tract microstructure in association-related tracts.