Dehydroepiandrosterone mediates associations between trauma-related symptoms and anterior pituitary volume in children and adolescents

Introduction: The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples. Methods: High-resolution T1-weighted MRI scans were collected from 137 healthy youth (9-17 years; M-age = 12.99 (SD = 1.87); 49% female; 85% White, 4% Indigenous, 1% Asian, 4% Black, 4% multiracial, 2% not reported). The anterior and posterior PGs were manually traced by trained raters. We examined the mediating effects of salivary DHEA on trauma-related symptoms (i.e., anxiety, depression, and posttraumatic) and PG volumes as well as an alternative model examining mediating effects of PG volume on DHEA and trauma-related symptoms. Results: DHEA mediated the association between anxiety symptoms and anterior PG volume. Specifically, higher anxiety symptoms related to lower DHEA levels, which in turn were related to smaller anterior PG. Conclusions: These results shed light on the neurobiological sequelae of elevated anxiety in youth and are consistent with adult findings showing suppressed levels of DHEA in those with greater comorbid anxiety and depression. Specifically, adolescents with greater subclinical anxiety may exhibit diminished levels of DHEA during the pubertal window, which may be associated with disruptions in anterior PG growth.

Automated summary

This study found an association between anxiety symptoms and anterior pituitary volume in adolescents, and this association was mediated by DHEA levels. Specifically, higher anxiety symptoms were related to lower DHEA levels, which in turn were related to smaller anterior pituitary volume.