Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Dysphoric Children and Adolescents: Cortisol Reactivity to Psychosocial Stress from Preschool Through Middle Adolescence

Background: Most depressed adults exhibit dysregulation of the hypothalamic pituitary adrenal axis, including cortisol hyperreactivity to psychosocial challenge. In contrast, remarkably little is known about hypothalamic pituitary adrenal axis activity in response to psychosocial challenge among at-risk children and adolescents. This study examined cortisol response to psychosocial challenge in nondepressed, at-risk, dysphoric and nondysphoric control youth across different developmentally salient age groups (preschool, third-, sixth-, and ninth-graders). Methods: Two samples of youth (Study 1-preschoolers; Study 2-third-, sixth-, and ninth-graders) without a history of clinical depression were administered developmentally appropriate psychosocial challenges. Of these nondepressed children, we examined youth at high-risk (n = 60) and low-risk (n = 223) status, as defined by elevated but subthreshold dysphoric symptoms according to multiple informants. Cortisol levels were assessed before and after a psychosocial stressor. Results: Nondysphoric control youth at all ages displayed the expected cortisol rise to challenge followed by return to baseline. However, prepubertal, at-risk, dysphoric children-specifically preschoolers and third-graders-exhibited cortisol hyporeactivity to challenge, whereas postpubertal dysphoric adolescents (ninth-graders) displayed hyperreactivity to the stressor. Additional analyses revealed that this switch from cortisol hyporeactivity to hyperreactivity among at-risk, dysphoric youth occurred as a function of pubertal development. Conclusions: Findings suggest a developmental switch in cortisol response for at-risk, dysphoric youth from preschool through adolescence and have implications for a developmental pathophysiological understanding of how at-risk youth across the lifespan might develop depressive disorder.