The DOI matches its Crossref record; 75 of the 76 references it cites were found in a registry or an index; none of the 22 sources its claims cite is checked for support yet.
Hypothalamic–pituitary–adrenal axis dysregulation in depressed children and adolescents: A meta-analysis
Open accessAbstract
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.
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In the paper
“Furthermore, Rao et al (2008) compared the cortisol response of depressed adolescents and a non-psychiatric control group after a social stress task and found mean effect size differences of .66 in peak cortisol levels, and of .91 to .96 during recovery.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Psychological (or naturally occurring) Challenge Studies
What the sources say
- Not checked yetcites Rao et al (2008)
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Furthermore, data on HPA-axis response to psychological stressors in this clinical population were noticeably scant.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Surprisingly, we found only three relevant studies of HPA-axis reactivity to psychological stressors in children or adolescents with depression.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Psychological (or naturally occurring) Challenge Studies
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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None of the sources cited for this claim have been checked yet.
In the paper
“Four studies compared cortisol levels post CRH infusion, but none found a significant difference in cortisol or ACTH secretion between MDD and non-MDD groups (Birmaher et al., 1996; Dorn et al., 1996; Kaufman et al., 1997; Ronsaville et al., 2006).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Additional Descriptive Analysis of HPA-Axis Probes
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
- Also stated in: § Basal HPA Axis Functioning Studies: Meta Analysis · plain
“None of the factors examined predicted average effect size differences between the MDD and control groups.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Abstract
plain- Asserted: passes — The authors put it forward as true.
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- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Basal HPA Axis Functioning Studies: Meta Analysis · plain
In the paper
“Luby et al. (2004) also compared cortisol responses to a laboratory stressor in young children and found reduced percentage change in the MDD group when compared to healthy controls.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Psychological (or naturally occurring) Challenge Studies
What the sources say
- Not checked yetcites Luby et al. (2004) source
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Finally, the three studies of HPA-axis reactivity to psychological stressors (Luby et al., 2003, 2004; Rao et al., 2008) reported equivocal results.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, due to limited variance between the studies, we were unable to examine factors that had been proposed as possible moderators of the HPA-depression relation, such as depression severity, endogenous subtype, and atypicality (eg., Dahl et al., 1992; Nelson & Davis, 1997), and exposure to traumatic events (e.g., Kaufman et al., 1997; Rao et al., 2008).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we found no evidence of a dysregulated response to corticotropin releasing hormone in depressed pediatric samples.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Therefore, the DST appears to provide a more sensitive index of hypercortisolaemia in pediatric depression than baseline cortisol measures, extending the extant adult literature.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“First, although we examined the effects of the type of comparison group (psychiatric vs. normative), we could not control for diagnostic differences within the psychiatric samples. Unfortunately, most of the psychiatric samples included participants with various diagnoses resulting in diagnostic heterogeneity.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“No missing studies in the direction of the null hypothesis were detected via the trim and fill method (Duval & Tweedie, 2000; Cluster Lo = -0.40 after 1 iteration).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Dexamethasone Suppression Test: Meta-Analysis
What the sources say
- Not checked yetcites Duval & Tweedie, 2000 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“No missing studies in the direction of the null hypothesis were detected via the trim and fill method (Duval & Tweedie, 2000; Cluster L0 = -1.0 after 1 iteration).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Basal HPA Axis Functioning Studies: Meta Analysis
What the sources say
- Not checked yetcites Duval & Tweedie, 2000 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Second, although we only included comparisons between participants with documented MDD against controls, we could not control for comorbidity of other disorders within the MDD groups.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Evidence for a dysregulated response to psychological stressors is less clear however, as extant research is extremely limited.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“For example, while Rao et al. (1997) reported significant reductions in basal cortisol after remission from an MDD episode, indicating that HPA-Axis dysregulation may be accentuated during depressive states, there is also evidence that HPA dysregulation is already present prior to the onset of depressive symptoms (Halligan et al., 2007) or MDD (Goodyer et al., 2000b).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
- Not checked yetcites Halligan et al., 2007 source
- Not checked yetcites Goodyer et al., 2000b
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Finally, due to our strict selection criteria, a number of informative studies were omitted from the meta-analysis (see for example Goodyer et al., 1998, 2003, 2000a, 2000b, 2001, 1991; Halligan et al., 2007; Herbert et al., 1996; Rao et al., 1999, 1996, 1997).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Results of our meta-analyses support an association between HPA-axis dysregulation and pediatric depression.”
- Also stated in: § Abstract · hedged
“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.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Also stated in: § Abstract · hedged
- It may state two separate claims as one. 26
- Probably not a substantial claim. 1
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Likewise, we found no significant effects of time of sampling and type of control group (psychiatric vs. healthy peers).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, group differences in baseline cortisol did not appear to be a function of sex, age, type of control group, or time of the sample collection.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The estimate of heterogeneity was not significant (.0000), z = .00, p > .20, suggesting limited between-study variability.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Basal HPA Axis Functioning Studies: Meta Analysis
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The global standardized mean difference effect size in basal HPA-axis functioning was .20, z = 4.53, p < .01.”
- Also stated in: § Basal HPA Axis Functioning Studies: Meta Analysis · hedged
“Using a random effects model, the pooled effect size (k = 36) for group differences in basal cortisol levels was .20 (z = 4.53, p < .01; 95% CI .11 – .29) indicating a tendency for depressed children and adolescents to have higher basal cortisol levels than non-MDD controls.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Abstract
plaincorrelationaln = 1,332 ·- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Basal HPA Axis Functioning Studies: Meta Analysis · hedged
In the paper
“For Luby et al. (2003), the mean effect size differences between the MDD group and psychiatric and healthy controls at 30 minutes post-stress were .30 and .21, suggesting higher post stress cortisol in the depressed group.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Psychological (or naturally occurring) Challenge Studies
What the sources say
- Not checked yetcites Luby et al. (2003) source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The estimate of heterogeneity was significant (.26), z = 2.33, p < .01, suggesting large between-study variability.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Dexamethasone Suppression Test: Meta-Analysis
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, contrary to previous descriptive reviews, which proposed that age influences HPA axis response in depressed youngsters (Birmaher & Heydl, 2001), our analysis found no significant age differences.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
- Also stated in: § Dexamethasone Suppression Test: Meta-Analysis · plain
“None of the factors examined significantly predicted effect sizes in DST response.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Abstract
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Dexamethasone Suppression Test: Meta-Analysis · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The global standardized mean effect size difference in HPA-axis response to the DST between depressed and non-depressed youth was .57, z = 4.18 p< .01.”
- Also stated in: § Dexamethasone Suppression Test: Meta-Analysis · hedged
“Using a mixed, random effects model, the pooled effect size (k = 49) for group differences in DST response was .57 (z = 4.18, p < .01; 95% CI .28 – .86) indicating greater cortisol production (or less suppression) after the DST among depressed children and adolescents than among non-MDD controls.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Abstract
plaincorrelationaln = 926- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Dexamethasone Suppression Test: Meta-Analysis · hedged
In the paper
“The effect sizes were -.13, -.14, and -.11, respectively.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Additional Descriptive Analysis of HPA-Axis Probes
What the sources say
- Not checked yetcites Kaufman et al., 1997 source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Depressed youth's dysregulated HPA-axis response to the DST suggests possible alterations in the mechanism in charge of regulating tonic cortisol levels.”
- Also stated in: § Discussion · hedged
“All in all, our results point towards possible anomalies within HPA-axis tonic system as reflected by dysregulated response to the DST and elevated basal cortisol levels.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · hedged
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“In addition, when compared to non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Abstract
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These contradictory findings are possibly due to group differences in baseline cortisol levels prior to the stress tasks, with the depressed preschool groups showing higher cortisol levels across the entire protocol (whether because of elevated tonic levels or chronic stress response to the entire laboratory experience), which could constrain the stress response to specific tasks.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“However, Luby et al. (2003) reported blunted reactivity (percentage change) in the depressed group, likely due to already elevated baseline values.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Psychological (or naturally occurring) Challenge Studies
What the sources say
- Not checked yetcites Luby et al. (2003) source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The lack of timing effects are particularly remarkable, as this indicates that the dysregulation is not specific to any time point, as would be expected if the dysregulation was driven by anomalies within circadian systems.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Consistent with the DST results, our meta-analysis suggests that depressed youth have higher cortisol levels throughout the day than do non-depressed youth, also reflecting hypercortisolaemia.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“For example, while Rao et al. (1997) reported significant reductions in basal cortisol after remission from an MDD episode, indicating that HPA-Axis dysregulation may be accentuated during depressive states, there is also evidence that HPA dysregulation is already present prior to the onset of depressive symptoms (Halligan et al., 2007) or MDD (Goodyer et al., 2000b).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
- Not checked yetcites Rao et al. (1997) source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The three available studies suggest that, compared to non-depressed peers, depressed preschoolers show blunted reactivity (percentage change) but higher peak cortisol levels, while depressed adolescents show higher reactivity and delayed recovery.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Hypercortisolemia has been consistently found in depressed adults (Christensen & Kessing, 2001; Gillespie & Nemeroff, 2005), and has been examined as a potential predictor of various outcomes (e.g., treatment response; Ribeiro et al., 1993) as well as one cause of the brain structural anomalies observed in depressed patients (Videbech & Ravnkilde, 2004).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Group differences in baseline cortisol also appear to be markedly less robust than differences in DST responses, suggesting that dysregulated responses to the DST do not necessarily translate to tonic HPA-axis dysregulation.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“However, most longitudinal studies were conducted with children who were “at-risk” due to the presence of subclinical signs of depression, raising the possibility that the observed cortisol differences prior to MDD onset may have reflected the disease process already underway (see for example Goodyer et al., 2003, 2000a, 2000b).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
- Not checked yetcites Goodyer et al., 2003 source
- Not checked yetcites Goodyer et al., 2000a
- Not checked yetcites Goodyer et al., 2000b
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Specifically, as compared to control peers, depressed youth tend to have a dysregulated response to the dexamethasone suppression test and moderately higher cortisol levels throughout the day.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“In their meta-analysis, the mean cortisol difference between the depressed and non-depressed groups was .27 in stress response and 1.39 during recovery.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
- Not checked yetcites Burke et al. (2005) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This is of great importance given that HPA-axis dysregulation is not unique to depression and is observed in many other disorders, such as post-traumatic stress disorder (de Kloet et al., 2006) and social anxiety (Beaton et al., 2006).”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Abstract
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
In the paper
“This is consistent with our findings on pediatric samples using psychological stressors that show a modest group difference in reactivity but much stronger difference during recovery.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
What the sources say
- Not checked yetcites Burke et al. (2005) source
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This normative cortisol response to CRH infusion among depressed youngsters suggests intact hypothalamic sensitivity to CRH and/or intact adrenal sensitivity to ACTH.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Rests on an assumption: Relative suppression of ACTH and cortisol after CRH infusion indicates pituitary under-sensitivity to CRH.
The paper relies on this without support.
Relative suppression of ACTH and cortisol after CRH infusion indicates pituitary under-sensitivity to CRH.
“Relative suppression (limited increase) of ACTH and cortisol release after CRH infusion suggests pituitary under-sensitivity to CRH.”
The paper relies on this without support.
Responses to psychological probes can reflect negative feedback dysregulation, oversensitivity to CRH or ACTH, and/or cognitive factors.
“responses to psychological probes may reflect differences within various HPA-axis components, including dysregulation of the negative feedback system, oversensitivity to CRH or ACTH, and/or differences in cognitive factors (e.g., attention, depressive rumination) that could lead to acute activation of the HPA-axis.”
The paper relies on this without support.
The general findings of studies omitted by the strict selection criteria are consistent with the meta-analysis results.
“Yet, the general findings of the omitted studies are consistent with our results, suggesting HPA-axis dysregulation in pediatric depression.”
The paper relies on this without support.
High total cortisol production over a 24-hour cycle indicates possible tonic hypercortisolaemia.
“For example, while high levels of total cortisol production during a 24-hour cycle indicate possible tonic hypercortisolaemia, samples obtained upon awakening (during the cortisol awakening response) are not necessarily reflective of tonic HPA-axis functioning and instead reflect stress reactivity (Edwards et al., 2001; Schmidt-Reinwald et al., 1999).”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Psychological distress, including symptoms of depression and anxiety, have shown an inconsistent relationship with cortisol response.”
From Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls At-Risk for Type 2 Diabetes. (2018) · cites this paper as Lopez-Duran, Kovacs, & George, 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“However, other studies suggest that depressive and anxiety symptoms relate to hyper or prolonged cortisol response to acute stress (Lopez-Duran, Kovacs, & George, 2009).”
From Relationship of Mindfulness to Distress and Cortisol Response in Adolescent Girls At-Risk for Type 2 Diabetes. (2018) · cites this paper as Lopez-Duran, Kovacs, & George, 2009
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“A meta-analysis of 651 depressed children and adolescents found greater basal cortisol levels in MDD children and adolescents compared to controls (156).”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [156]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Depressed children and adolescents (N = 388) revealed higher cortisol post DST in a metaanalysis. Conversely, cortisol and ACTH levels post-CRH infusion were non-significant between groups (156).”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [156]
Experimental — accuracy not yet measuredIn the citing paper
“Inflammatory cytokines may indirectly upregulate glucocorticoids in the body by interfering with the functional capacity of the glucocorticoid receptor (Pace, Hu, & Miller, 2007; Raison & Miller, 2003), resulting in continued synthesis of corticotropin releasing hormone (CRH) and sustained activation of the HPA-axis which has long been implicated in the pathogenesis of depression (Lopez-Duran et a”
From The role of inflammation in core features of depression: Insights from paradigms using exogenously-induced inflammation. (2018) · cites this paper as Lopez-Duran et al., 2009
In the citing paper
“The pathophysiology of MDD is related to several neurobiological changes, including hypothalamic-pituitary-adrenal (HPA) axis malfunction and consequent increase [2][3][4] or decrease [5][6][7] in basal cortisol levels.”
From Can physical exercise modulate cortisol level in subjects with depression? A systematic review and meta-analysis (2018) · cites this paper as [4]
Statistics recomputed
Every reported test result, recomputed from its test statistic and degrees of freedom. A result shows as not adding up only once an independent check has confirmed it.
- Not confirmedz = 2.33reported p < .01 · recomputed p = .020
“z = 2.33, p < .01”
- Consistentz = 4.53reported p < .01 · recomputed p < .001
“z = 4.53, p < .01”
- Consistentz = 4.18reported p < .01 · recomputed p < .001
“(z = 4.18, p < .01”
- Consistentz = 4.53reported p < .01 · recomputed p < .001
“(z = 4.53, p < .01”
- Consistentz = 0reported p > .2 · recomputed p = 1.000
“z = .00, p > .20”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Basal HPA Axis Functioning Studies: Meta Analysis
“The studies contributed a total of 28 effect sizes.”
§ Hypothalamic-Pituitary-Adrenal Axis Dysregulation in Depressed Children and Adolescents: A Meta-Analysis > Results > Basal HPA Axis Functioning Studies: Meta Analysis
“Using a random effects model, the pooled effect size (k = 36) for group differences in basal cortisol levels was .20”
Citations
Cites
Duval, S., & Tweedie, R. (2000) · Biometrics · doi:10.1111/j.0006-341x.2000.00455.x · Cited by 14,099 · cited 4×
“Nomissing studies in the direction of the null hypothesis were detected via the Trim and Fill method (Duval and Tweedie, 2000; cluster L0 = 0.40 after 1 iteration).”
MethodInfluentialDickerson, S. S., & Kemeny, M. E. (2004) · Psychological Bulletin · doi:10.1037/0033-2909.130.3.355 · Cited by 5,881 · cited 1×
“We used a hierarchical multi-level mixed-model approach (Kalaian and Raudenbush, 1996) similar to that employed by Dickerson and Kemeny (2004).”
MethodPsychopharmacology: The Fourth Generation of Progress
Bloom, F. E., & Kupfer, D. J. (1995) · Medical Entomology and Zoology · Cited by 2,985
Childhood and adolescent depression: a review of the past 10 years, Part I
BIRMAHER, B., RYAN, N. D., WILLIAMSON, D. E., BRENT, D. A., KAUFMAN, J., DAHL, R. E., PEREL, J., & NELSON, B. (1996) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199611000-00011 · Cited by 2,076 · cited 3×
“Four studies compared cortisol levels post CRH infusion, but none found a significant difference in cortisol or ACTH secre- tion between MDD and non-MDD groups (Birmaher et al., 1996a,b; Dorn et al., 1996; Kaufman et al., 1997; Ronsaville et al., 2006).”
BackgroundResultAdvanced methods in meta‐analysis: multivariate approach and meta‐regression
van Houwelingen, H. C., Arends, L. R., & Stijnen, T. (2002) · Statistics in Medicine · doi:10.1002/sim.1040 · Cited by 1,599 · cited 1×
“For all computations we used SAS PROC MIXED syntax designed for multilevel models (Singer, 1998) with special application for meta-analysis (van Houwelingen et al., 2002; Normand, 1999).”
MethodHippocampal volume and depression: a meta-analysis of MRI studies
Videbech, P., & Ravnkilde, B. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.11.1957 · Cited by 1,590 · cited 2×
“…(Christensen and Kessing, 2001; Gillespie and Nemeroff, 2005), and has been examined as a potential predictor of various outcomes (e.g., treatment response; Ribeiro et al., 1993) as well as one cause of the brain structural anomalies observed in depressed patients (Videbech and Ravnkilde, 2004).”
BackgroundDepression and cortisol responses to psychological stress: A meta-analysis
Burke, H. M., Davis, M. C., Otte, C., & Mohr, D. C. (2005) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2005.02.010 · Cited by 1,194 · cited 3×
“The non-suppression of cortisol after DST challenge indicates a dysregulation within the HPA-axis negative feedback mechanism (Burke et al., 2005).”
BackgroundInfluentialUsing SAS PROC MIXED to Fit Multilevel Models, Hierarchical Models, and Individual Growth Models
Singer, J. D. (1998) · Journal of Educational and Behavioral Statistics · doi:10.2307/1165280 · Cited by 1,092 · cited 2×
“For all computations we used SAS PROC MIXED syntax designed for multilevel models (Singer, 1998) with special application for meta-analysis (van Houwelingen et al.”
MethodEstimation of effect size from a series of independent experiments.
Hedges, L. (1982) · Psychological Bulletin · doi:10.1037/0033-2909.92.2.490 · Cited by 1,030 · cited 2×
“…for two types of outcome data, namely: (1) mean cortisol differences between MDD and control groups and (2) difference between MDD and control group in rate (x2) of suppression vs. non-suppression to the DST. Hedge’s G (Hedges, 1982) weighted effect size was used as metric for all mean comparison.”
MethodPsychopharmacology: The Fourth Generation of Progress
Kramlinger, K. G. (1995) · Mayo Clinic Proceedings · doi:10.4065/70.10.1021-a · Cited by 779
Cited by
Sorted by citations
Thapar, A., Collishaw, S., Pine, D. S., & Thapar, A. K. (2012) · The Lancet · doi:10.1016/s0140-6736(11)60871-4 · Cited by 2,365
Sex differences in stress-related psychiatric disorders: neurobiological perspectives
Bangasser, D. A., & Valentino, R. J. (2014) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2014.03.008 · Cited by 737
“Although dexamethasone suppression is influenced by menstrual cycle phase, sex differences in cortisol release when dexamethasone is administered alone are not typically reported [82; 83; 84; 85].”
BackgroundBraithwaite, I., Zhang, S., Kirkbride, J. B., Osborn, D., & Hayes, J. (2019) · Environmental Health Perspectives · doi:10.1289/ehp4595 · Cited by 728
“Hypothalamo– pituitary–adrenal (HPA) axis dysregulation has also been implicated in depression (Lopez-Duran et al. 2009).”
BackgroundKoss, K. J., & Gunnar, M. R. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12784 · Cited by 489
Antidepressants recruit new neurons to improve stress response regulation
Surget, A., Tanti, A., Leonardo, E. D., Laugeray, A., Rainer, Q., Touma, C., Palme, R., Griebel, G., Ibarguen-Vargas, Y., Hen, R., et al. (2011) · Molecular Psychiatry · doi:10.1038/mp.2011.48 · Cited by 471
Metadata
- Authors
- Lopez-Duran, N. L., Kovacs, M., & George, C. J.
- Affiliations
- University of Pittsburgh (US)
- ORCID
- George, Charles J.
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2009-10
- Volume
- 34
- Issue
- 9
- Pages
- 1272-1283
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC2796553
- OpenAlex
- W2059646524
- Cited by
- 425
- References
- 76
- Citations by year
- 2026: 16 · 2025: 21 · 2024: 19 · 2023: 16 · 2022: 20 · 2021: 37 · 2020: 25 · 2019: 21 · 2018: 23 · 2017: 33 · 2016: 33 · 2015: 30 · 2014: 30 · 2013: 35 · 2012: 27
- FWCI
- 1.15
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Department of Science and Technology, Ministry of Science and Technology, India
- National Institute of Mental Health (P01MH056193, MH 56193, T32MH018951, T32-MH18951)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- hypothalamic-pituitary-adrenal axis, childhood depression, children and adolescents, dexamethasone suppression test, basal cortisol, corticotropin-releasing factor, psychological stress response, HPA axis dysregulation, negative feedback, glucocorticoid receptor sensitivity
- MeSH terms
- Adolescent, Age Factors, Child, Corticotropin-Releasing Hormone, Major Depressive Disorder, Dexamethasone, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Pituitary-Adrenal System, Sex Factors, Stress, Psychological, Time Factors, Dysthymic Disorder
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-09-28, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-09-28 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
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