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

ABSTRACT: 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).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.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.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.

SUBMITTER: Hankin BL

PROVIDER: S-EPMC2921478 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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

Hankin Benjamin L BL Badanes Lisa S LS Abela John R Z JR Watamura Sarah E SE

Biological psychiatry 20100523 5

<h4>Background</h4>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 developmentall ...[more]

PMID: 20497900

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Project description:OBJECTIVE:To identify predictors of hypothalamic-pituitary-adrenal (HPA) axis recovery interval and severity of glucocorticoid withdrawal symptoms (GWS) in patients undergoing adrenalectomy for corticotropin-independent cortisol excess. DESIGN:This is a retrospective study of patients with mild autonomous cortisol excess (MACE), moderate and severe Cushing syndrome (CS) who developed adrenal insufficiency after unilateral adrenalectomy between 1998 and 2017. RESULTS:Adrenalectomy was performed in 81 patients (79% women, median age 52 years [IQR 42-62]). HPA axis recovery occurred at a median of 4.3 months (IQR 1.6-11.4) after adrenalectomy (severe CS vs moderate CS vs MACE: median 11.4 vs 2.8 vs 2.1 months, P < 0.01). Main predictors of HPA axis recovery interval included: preoperative serum cortisol concentration after 1-mg overnight dexamethasone suppression test >10 ?g/dL or >276 nmol/L (9.7 vs 1.3 months if cortisol ?10 ?g/dL or ?276 nmol/L, P < 0.01); body mass index (for every 3 kg/m2 decrease, glucocorticoid taper increased by 1 month, P < 0.05); age <45 (11.4 vs 2.3 months if ?45 years, P < 0.05); duration of symptoms prior to diagnosis >1 year (11.4 vs 2.8 months if ?1 year); moon facies (11.4 vs 2.2 months if no rounding of the face); and myopathy (13.1 vs 2.7 months if no myopathy, P < 0.05). Patients with severe CS had a higher incidence of GWS compared to patients with MACE (66.7% vs 40.0%, P < 0.05) with a median of 1 and 0 events/patient, respectively. CONCLUSIONS:The HPA axis recovery interval was the longest for patients with severe CS. Surprisingly, patients with moderate CS recovered their HPA axis as quickly as those with MACE. Glucocorticoid withdrawal symptoms were observed in all groups, with more events in patients with severe CS. This study emphasizes the need to counsel patients on expectations for HPA axis recovery and address intervention for GWS based on individual preoperative parameters.

Dataset Information

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

Publications

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

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