SummaryResearch findings on the hypothalamic-pituitary-adrenal (HPA) axis and pediatric depression reflect a variety of methodological approaches that tap different facets of HPA-axis functions. Partly owing to the methodological heterogeneity of studies, descriptive reviews of this area have produced inconsistent conclusions. Therefore, we conducted formal meta-analyses of pertinent studies in order to advance our understanding of HPA-axis dysregulation in pediatric depression. We examined: a) 17 published studies of HPA-axis response to the dexamethasone suppression test in depressed youth (DST; N=926) and b) 17 studies of basal HPA-axis functioning (N=1,332). We also examined descriptively studies that used corticotropin releasing hormone (CRH) infusion, and those that used psychological probes of the HPA-axis. The global standardized mean effect size difference in HPAaxis response to the DST between depressed and non-depressed youth was .57, z = 4.18 p< .01. The global standardized mean difference effect size in basal HPA-axis functioning was .20, z = 4.53, p < .01. Age, sex, timing of sampling, dexamethasone dosage, or type of control group was not a significant source of variability for the DST or basal studies. In addition, when compared to nondepressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors. In conclusion, the HPA-axis system tends to be dysregulated in depressed youth, as evidenced by atypical responses to the DST, higher baseline cortisol values, and an overactive response to psychological stressors. This pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.
KeywordsHPA-Axis; Depression; Children; Adolescents; Dexamethasone Suppression TestIn the quest for biological markers of depression, researchers have explored the link between hypothalamic-pituitary-adrenal (HPA) axis functioning and adult depression for at least forty years, extending the inquiry to pediatric depression in more recent decades. Much of this work has involved the examination of cortisol response to biological and psychological probes or the assessment of basal cortisol levels. However, recent descriptive reviews of the pediatric literature have yielded inconsistent findings, with some reviewers concluding that the association between dysregulated HPA-axis and child depression is inconclusive at best Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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