Hypothalamic-pituitary-adrenal axis dysregulation in dysphoric children and adolescents: cortisol reactivity to psychosocial stress from preschool through middle adolescence.

摘要

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.