Changes in Brain Structure Associated with Adrenarche in Typically Developing Prepubertal Children

Abstract

Adrenarche is marked by increases in neuroactive adrenal androgens, including dehydroepiandrosterone sulfate (DHEAS). However, the specific impact of DHEAS on neurodevelopment is difficult to disambiguate from that of gonadal hormones as both systems overlap in maturational trajectories. Here, we investigate the relationship between DHEAS concentrations and gray matter volume in prepubertal children studied prior to increases in gonadal hormones (i.e., gonadarche). Fasting morning blood samples and neuroimaging data were collected on ninety-two healthy children (55 boys, 8.6±.3years; 37 girls, 8.6±.3years) ascertained by physical examination to be prepubertal. Children underwent structural T1-weighted MRI in a 3 T scanner, and serum DHEAS concentrations were measured with liquid chromatography-tandem mass-spectrometry. A whole-brain, voxel-wise multivariate-model analysis (AFNI) was used to examine log-transformed DHEAS effects on gray matter volume, controlling for sex and total brain volume. Post-hoc non-parametric correlations were conducted in SPSS. There was an effect of DHEAS on gray matter volume in the right superior frontal gyrus, anterior cingulate cortex, and right amygdala (p’s<0.001). Post-hoc analyses showed that DHEAS correlated positively with gray matter volume in the right superior frontal gyrus (p=0.002) and anterior cingulate cortex (p=0.003), but negatively in the right amygdala (p=0.001). Our results identified an association between serum DHEAS and gray matter volume prior to gonadarche and support previous studies documenting associations between DHEA and cortical thickness in prepubertal children. These data suggest that DHEA(S) may play a role in extending the window of neurodevelopmental plasticity commonly associated with gonadarche.