Disentangling the Unique Contributions of Age, Pubertal Stage, and Pubertal Hormones to Brain Structure in Childhood and Adolescence

Puberty and associated changes in pubertal hormones influence structural brain development. Hormones such as dehydroepiandrosterone (DHEA) and progesterone remain understudied, and it remains unclear how these aspects of puberty contribute uniquely to structural brain development. We used the Human Connectome Project in Development cross-sectional sample of 1304 youth (aged 5-21 years) to investigate unique contributions of sex, age, pubertal stage, DHEA, testosterone, estradiol, and progesterone to cortical thickness, surface area, and subcortical volume development within functionally-relevant networks. Sex and age explain the most unique variance in all three aspects of structural development. Pubertal stage and pubertal hormones uniquely contribute more to cortical surface area, compared to thickness. Among the pubertal hormones, progesterone contributed unique variance to surface area in the default mode network, as well as to thickness in the orbito-affective network. Pubertal mechanisms also contributed unique variance to subcortical volumes. This demonstrates unique relations of understudied pubertal hormones to brain structure development and may help understand risk for psychopathology.