Unraveling age, puberty and testosterone effects on subcortical brain development across adolescence

The onset of adolescence in humans is marked by hormonal changes that give rise to secondary sexual characteristics, noted as puberty. It has, however, proven challenging to unravel to what extent pubertal changes may have organizing effects on the brain beyond chronological age, as reported in animal studies. The present longitudinal study aimed to characterize the unique effects of age and puberty on subcortical brain volumes and included three waves of data collection at two-year intervals and 680 T1-weighted MRI scans of 271 participants (54% females) aged between 8 and 29 years old. Generalized additive mixed model procedures were used to assess the effects of age, self-report pubertal status and testosterone level on basal ganglia, thalamus, hippocampus, amygdala and cerebellum gray matter volumes. We observed age-related increases in putamen and pallidum volumes, and decreases in accumbens and thalamus volumes, all show larger volumes in boys than girls. Only the cerebellum showed an interaction effect of age by sex, such that males showed prolonged increases in cerebellar volume than females. Next, we showed that changes in self-report puberty status better described developmental change than chronological age for most structures in males, and for caudate, pallidum and hippocampal volumes in females. Furthermore, changes in testosterone level were related to development of pallidum, accumbens, hippocampus and amygdala volumes in males and caudate and hippocampal volumes in females. The modeling approach of the present study allowed us to characterize the complex interactions between chronological age and pubertal maturational changes, and the findings indicate puberty unique changes in brain structure that are sex specific.