Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
, 34 (9), 1272-83

Hypothalamic-pituitary-adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis

Affiliations
Review

Hypothalamic-pituitary-adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis

Nestor L Lopez-Duran et al. Psychoneuroendocrinology.

Abstract

Research 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 (DST) in depressed youth (DST; N=926) and (b) 17 studies of basal HPA-axis functioning (N=1332). 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 HPA-axis response to the DST between depressed and non-depressed youth was 0.57, z=4.18, p<0.01. The global standardized mean difference effect size in basal HPA-axis functioning was 0.20, z=4.53, p<0.01. 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 non-depressed 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.

Conflict of interest statement

Conflict of Interest: All authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Forrest plot of standardized effect size and 95% confident intervals for comparative studies examining response to DST between depressed and non-depressed children and adolescents.
Figure 2
Figure 2
Inverse standard error vs. effect size in DST cortisol studies. Connected dots represent comparisons in the same sample/cluster. Circles represent average effect size and pooled precision of each cluster.
Figure 3
Figure 3
Forrest plot of standardized effect size and 95% confident intervals for comparative studies examining basal cortisol levels between depressed and non-depressed children and adolescents.
Figure 4
Figure 4
Inverse standard error vs. effect size in basal cortisol studies. Connected dots represent comparisons in the same sample/cluster. Circles represent average effect size and pooled precision of each cluster.

Similar articles

See all similar articles

Cited by 113 PubMed Central articles

See all "Cited by" articles
Feedback