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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- Findingcitation
Rao et al. (2008) found mean effect-size differences of .66 in peak cortisol and .91 to .96 during recovery between depressed adolescents and non-psychiatric controls after a social stress task.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rao et al (2008)
Not checked in the free run.
- Findingown data
Data on HPA-axis response to psychological stressors in depressed pediatric populations are scant.
“Furthermore, data on HPA-axis response to psychological stressors in this clinical population were noticeably scant.”
Quote in the paperNot a substantial claim - Findingown data
Only three relevant studies of HPA-axis reactivity to psychological stressors in depressed children or adolescents were found.
“Surprisingly, we found only three relevant studies of HPA-axis reactivity to psychological stressors in children or adolescents with depression.”
Quote in the paperNot a substantial claim - Findingcitation
Four CRH infusion studies found no significant difference in cortisol or ACTH secretion between MDD and non-MDD groups.
“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).”
Quote in the paperNot a substantial claim0 of 3 sources checked - Findingown data
None of the examined factors predicted average basal cortisol effect-size differences between MDD and control groups.
“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.”
Quote in the paperSubstantial claim - Also stated in: § Basal HPA Axis Functioning Studies: Meta Analysis · plain
- Findingcitation
Luby et al. (2004) found reduced percentage change in cortisol response to a laboratory stressor in young depressed children compared with healthy controls.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Luby et al. (2004) source
Not checked in the free run.
- Findingreasoning
The three psychological stress studies reported equivocal results.
“Finally, the three studies of HPA-axis reactivity to psychological stressors (Luby et al., 2003, 2004; Rao et al., 2008) reported equivocal results.”
Quote in the paperNot a substantial claim - Study design and conductown data
Due to limited variance between studies, the meta-analysis could not examine proposed moderators such as depression severity, endogenous subtype, atypicality, and trauma exposure.
“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).”
Quote in the paperNot a substantial claim - Interpretationown data
The meta-analysis found no evidence of a dysregulated cortisol response to CRH in depressed pediatric samples.
“However, we found no evidence of a dysregulated response to corticotropin releasing hormone in depressed pediatric samples.”
Quote in the paperSubstantial claim - Interpretationreasoning
The DST appears to be a more sensitive index of hypercortisolaemia in pediatric depression than baseline cortisol measures, extending adult literature.
“Therefore, the DST appears to provide a more sensitive index of hypercortisolaemia in pediatric depression than baseline cortisol measures, extending the extant adult literature.”
Quote in the paperSubstantial claim - Study design and conductown data
The meta-analysis could not control for diagnostic differences within psychiatric comparison samples, which had diagnostic heterogeneity.
“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.”
Quote in the paperNot a substantial claim - Study design and conductown data
Trim-and-fill analysis for DST studies detected no missing studies in the null direction (Cluster Lo=-0.40 after 1 iteration).
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Duval & Tweedie, 2000 source
Not checked in the free run.
- Study design and conductown data
Trim-and-fill analysis for basal studies detected no missing studies in the null direction (Cluster L0=-1.0 after 1 iteration).
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Duval & Tweedie, 2000 source
Not checked in the free run.
- Study design and conductown data
The meta-analysis could not control for comorbidity within MDD groups.
“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.”
Quote in the paperNot a substantial claim - Interpretationreasoning
Evidence for a dysregulated response to psychological stressors is less clear because extant research is extremely limited.
“Evidence for a dysregulated response to psychological stressors is less clear however, as extant research is extremely limited.”
Quote in the paperSubstantial claim - Premisecitation
Evidence indicates HPA dysregulation is already present prior to onset of depressive symptoms or MDD.
“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).”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites Halligan et al., 2007 source
Not checked in the free run.
- cites Goodyer et al., 2000b
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- Study design and conductreasoning
Due to strict selection criteria, a number of informative studies were omitted from the meta-analysis.
“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).”
Quote in the paperNot a substantial claim - Interpretationown data
The meta-analyses support an association between HPA-axis dysregulation and pediatric depression.
“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.”
Quote in the paperSubstantial claim - Also stated in: § Abstract · hedged
- May combine two claims. 26
- Classified as probably not a substantial claim. 1
May combine two claims.
Findingown dataThe analysis found no significant effects of sampling time or control-group type.
“Likewise, we found no significant effects of time of sampling and type of control group (psychiatric vs. healthy peers).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataBaseline cortisol group differences were not a function of sex, age, control-group type, or sample collection time.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataBasal cortisol effect sizes showed non-significant heterogeneity (.0000, z=.00, p>.20), indicating limited between-study variability.
“The estimate of heterogeneity was not significant (.0000), z = .00, p > .20, suggesting limited between-study variability.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn a meta-analysis of 17 basal cortisol studies (27 samples, N=1,332, 28 effect sizes; pooled k=36), depressed youth had a pooled standardized mean difference of .20 (z=4.53, p<.01, 95% CI .11-.29) versus non-depressed controls, indicating higher basal cortisol.
“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.”
Quote in the paperSubstantial claim- Also stated in: § Basal HPA Axis Functioning Studies: Meta Analysis · hedged
May combine two claims.
FindingcitationLuby et al. (2003) found mean effect-size differences of .30 versus psychiatric controls and .21 versus healthy controls at 30 minutes post-stress, suggesting higher post-stress cortisol in the depressed group.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Luby et al. (2003) source
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Findingown dataDST effect sizes showed significant heterogeneity (.26, z=2.33, p<.01), indicating large between-study variability.
“The estimate of heterogeneity was significant (.26), z = 2.33, p < .01, suggesting large between-study variability.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe analysis found no significant age differences in HPA-axis response, contrary to previous descriptive reviews.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataAge, sex, sampling time, dexamethasone dose, and control-group type did not significantly predict DST effect sizes.
“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.”
Quote in the paperNot a substantial claim- Also stated in: § Dexamethasone Suppression Test: Meta-Analysis · plain
May combine two claims.
Findingown dataIn a meta-analysis of 17 DST studies (18 samples, N=926, 49 effect sizes), depressed children and adolescents showed a pooled standardized mean difference of .57 (z=4.18, p<.01, 95% CI .28-.86) versus non-depressed controls, indicating greater post-DST cortisol production or less suppression.
“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.”
Quote in the paperSubstantial claim- Also stated in: § Dexamethasone Suppression Test: Meta-Analysis · hedged
May combine two claims.
FindingcitationEffect sizes from Kaufman et al. (1997) for CRH infusion were -.13 for total cortisol production, -.14 for peak cortisol, and -.11 for pre-to-post change.
“The effect sizes were -.13, -.14, and -.11, respectively.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Kaufman et al., 1997 source
Not checked in the free run.
May combine two claims.
Interpretationown dataThe DST and basal findings point toward possible anomalies in the HPA-axis tonic system.
“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.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · hedged
May combine two claims.
Interpretationown dataCompared with non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors.
“In addition, when compared to non-depressed peers, depressed youth have a normative response to CRH infusion but an overactive response to psychological stressors.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningContradictory psychological stress findings may be due to baseline cortisol differences before stress tasks, with depressed preschoolers showing higher cortisol across the protocol, which could constrain stress response.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationreasoningLuby et al. (2003) reported blunted percentage-change reactivity in the depressed group, likely because baseline values were already elevated.
“However, Luby et al. (2003) reported blunted reactivity (percentage change) in the depressed group, likely due to already elevated baseline values.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Luby et al. (2003) source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe lack of timing effects indicates the dysregulation is not specific to any time point, as would be expected if driven by circadian anomalies.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataDepressed youth have higher cortisol levels throughout the day than non-depressed youth, reflecting hypercortisolaemia.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationRao et al. (1997) reported significant reductions in basal cortisol after remission from an MDD episode, indicating HPA-axis dysregulation may be accentuated during depressive states.
“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).”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Rao et al. (1997) source
Not checked in the free run.
May combine two claims.
InterpretationcitationThe three available psychological stress studies suggest depressed preschoolers show blunted percentage-change reactivity but higher peak cortisol, while depressed adolescents show higher reactivity and delayed recovery.
“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.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationHypercortisolemia has been consistently found in depressed adults.
“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).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
Interpretationown dataBaseline cortisol group differences are markedly less robust than DST response differences, suggesting dysregulated DST responses do not necessarily translate to tonic HPA-axis dysregulation.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationMost longitudinal studies were conducted with children at risk due to subclinical signs of depression, raising the possibility that observed cortisol differences before MDD onset reflected an already underway disease process.
“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).”
Quote in the paperSubstantial claim0 of 3 sources checked- cites Goodyer et al., 2003 source
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- cites Goodyer et al., 2000a
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- cites Goodyer et al., 2000b
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May combine two claims.
Interpretationown dataDepressed youth tend to have a dysregulated DST response and moderately higher daily cortisol levels than controls.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationBurke et al. (2005) found mean cortisol differences between depressed and non-depressed adults of .27 during stress response and 1.39 during recovery.
“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.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites Burke et al. (2005) source
Not checked in the free run.
May combine two claims.
PremisecitationHPA-axis dysregulation is not unique to depression and is observed in other disorders such as PTSD and social anxiety.
“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).”
Quote in the paperNot a substantial claim0 of 2 sources checkedMay combine two claims.
InterpretationreasoningThe pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.
“This pattern of dysregulation suggests anomalies within the axis's negative feedback system and CRH production, but intact pituitary and adrenal sensitivity.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe pediatric psychological stress findings are consistent with Burke et al.'s adult findings, showing a modest reactivity difference but much stronger recovery difference.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites Burke et al. (2005) source
Not checked in the free run.
May combine two claims.
InterpretationreasoningThe normative cortisol response to CRH infusion among depressed youngsters suggests intact hypothalamic sensitivity to CRH and/or intact adrenal sensitivity to ACTH.
“This normative cortisol response to CRH infusion among depressed youngsters suggests intact hypothalamic sensitivity to CRH and/or intact adrenal sensitivity to ACTH.”
Quote in the paperSubstantial claim- 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 link between psychological distress-depression and anxiety symptoms-and cortisol reactivity is inconsistent.
“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
The Results section on psychological challenge studies and the Discussion describe differing cortisol responses among depressed preschoolers and adolescents, supporting an inconsistent picture for pediatric depression. The paper does not establish the claimed relationship for anxiety symptoms or psychological distress generally; it focuses on depression in children and adolescents. (LLM, conf=0.88)
Experimental — accuracy not yet measuredOther work indicates that depression and anxiety symptoms are tied to exaggerated or extended cortisol reactions to acute stress.
“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
The Results and Discussion sections report higher cortisol responses and delayed recovery after psychological stress in depressed adolescents. But the evidence concerns depressed youth, not anxiety symptoms; the Discussion also reports blunted reactivity in depressed preschoolers and says evidence on psychological stress responses is limited. Page numbers are not available in our copy. (LLM, conf=0.87)
Experimental — accuracy not yet measuredA meta-analysis of 651 depressed children and adolescents found greater basal cortisol levels in MDD children and adolescents compared to controls.
“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]
The Results section (Basal HPA Axis Functioning Studies: Meta Analysis; page unavailable) reports that depressed children and adolescents tended to have higher basal cortisol levels than non-MDD controls. It gives N = 1,332 across the compared groups, but does not substantiate the claim that 651 of them were depressed children and adolescents. (LLM, conf=0.85)
Experimental — accuracy not yet measuredDepressed children and adolescents (N = 388) revealed higher cortisol post DST in a meta-analysis, while cortisol and ACTH levels post-CRH infusion were non-significant between groups.
“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]
The Results section, “Dexamethasone Suppression Test: Meta-Analysis” (page not provided), reports higher post-DST cortisol in depressed youth, but the analysis included N = 926, not 388. “Additional Descriptive Analysis of HPA-Axis Probes” reports no significant post-CRH cortisol or ACTH differences between groups; the Methods clarify that too few CRH studies were available for a formal meta-analysis. (LLM, conf=0.92)
Experimental — accuracy not yet measuredInflammatory cytokines may indirectly upregulate glucocorticoids by interfering with glucocorticoid receptor function, leading to continued CRH synthesis and sustained HPA-axis activation.
“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
The pathophysiology of major depressive disorder is related to several neurobiological changes, including hypothalamic-pituitary-adrenal (HPA) axis malfunction and consequent increase or decrease in basal cortisol levels.
“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.
Basal-analysis effect-size count changes from 28 to 36
MinorThe same results paragraph says the basal studies contributed 28 effect sizes but gives k = 36 for the pooled analysis, without explaining a change in the set analyzed.
“The studies contributed a total of 28 effect sizes.”
“Using a random effects model, the pooled effect size (k = 36) for group differences in basal cortisol levels was .20”
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“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).”
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“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).”
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“…(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).”
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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× · see citing works
“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. V. (1982) · Psychological Bulletin · doi:10.1037/0033-2909.92.2.490 · Cited by 1,065 · cited 2× · see citing works
“…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 · see citing works
Effect sizes for research: A broad practical approach.
Grissom, R. J., & Kim, J. J. (2005) · Cited by 732 · see citing works
Interpretation of tests of heterogeneity and bias in meta-analysis
Ioannidis, J. P. A. (2008) · Journal of Evaluation in Clinical Practice · doi:10.1111/j.1365-2753.2008.00986.x · Cited by 696 · cited 2× · see citing works
“…factors that explain differences between studies even if heterogeneity was not observed, as estimates of heterogeneity have some limitations (Ioannidis, 2008), and significant moderating factors may be present even when the variability between studies is not large (see Hall and Rosenthal,…”
BackgroundApplication of a Method of Estimating DIF for Polytomous Test Items
Camilli, G., & Congdon, P. D. (1999) · Journal of Educational and Behavioral Statistics · doi:10.3102/10769986024004323 · Cited by 607 · see citing works
de Kloet, C. S., Vermetten, E., Geuze, E., Kavelaars, A., Heijnen, C. J., & Westenberg, H. G. M. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2005.08.002 · Cited by 503 · cited 1× · see citing works
“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).”
BackgroundGoodyer, I. M., Herbert, J., Tamplin, A., & Altham, P. M. E. (2000) · British Journal of Psychiatry · doi:10.1192/bjp.177.6.499 · Cited by 436 · cited 3× · see citing works
“…basal cortisol after remission from anMDD 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).”
BackgroundSchmidt-Reinwald, A., Pruessner, J. C., Hellhammer, D. H., Federenko, I., Rohleder, N., Schürmeyer, T. H., & Kirschbaum, C. (1999) · Life Sciences · doi:10.1016/s0024-3205(99)00103-4 · Cited by 367 · cited 2× · see citing works
“For example, while high levels of total cortisol production during a 24-h 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;…”
BackgroundExploration of the awakening cortisol response in relation to diurnal cortisol secretory activity.
Edwards, S., Clow, A., Evans, P., & Hucklebridge, F. (2001) · Life Science · doi:10.1016/s0024-3205(01)00996-1 · Cited by 364 · cited 2× · see citing works
“For example, while high levels of total cortisol production during a 24-h 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;…”
BackgroundHypercortisolemia and depression
Gillespie, C. F., & Nemeroff, C. B. (2005) · Psychosomatic Medicine · doi:10.1097/01.psy.0000163456.22154.d2 · Cited by 361 · cited 2× · see citing works
“Hypercortisolaemia has been consistently found in depressed adults (Christensen and Kessing, 2001; Gillespie and Nemeroff, 2005), and has been examined as a potential predictor of various outcomes (e.”
BackgroundDST Studies in Psychotic Depression: A Meta-Analysis
Nelson, J. C., & Davis, J. M. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.11.1497 · Cited by 356 · cited 2× · see citing works
“…to examine factors that had been proposed as possible moderators of the HPA-depression relation, such as depression severity, endogenous subtype, and atypicality (e.g., Dahl et al., 1992; Nelson and Davis, 1997), and exposure to traumatic events (e.g., Kaufman et al., 1997; Rao et al., 2008).”
BackgroundMethodThe DST as a predictor of outcome in depression: a meta-analysis
Ribeiro, S. C. M., Tandon, R., Grunhaus, L. J., & Greden, J. F. (1993) · American Journal of Psychiatry · doi:10.1176/ajp.150.11.1618 · Cited by 321 · cited 3× · see citing works
“…(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).”
BackgroundMethodResultGoodyer, I. M., Herbert, J., ALTHAM, P. M. E., Pearson, J., SECHER, S. M., & Shiers, H. M. (1996) · Psychological Medicine · doi:10.1017/s0033291700034644 · Cited by 284 · see citing works
Are child-, adolescent-, and adult-onset depression one and the same disorder?
Kaufman, J., Martin, A., King, R. A., & Charney, D. S. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01127-1 · Cited by 269 · cited 3× · see citing works
“Our results indicate that such HPA-axis dysregulation can also be found in children and adolescents, a conclusion that is in line with, and extends previous reviews by Casat et al. (1989) and Kaufman et al. (2001).”
ResultKaufman, J., Birmaher, B., Perel, J., Dahl, R. E., Moreci, P., Nelson, B., Wells, W., & Ryan, N. D. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00470-2 · Cited by 263 · cited 4× · see citing works
“CRH infusion studies 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., 1996a,b; Dorn et al., 1996; Kaufman et al., 1997; Ronsaville et al., 2006).”
BackgroundInfluentialA multivariate mixed linear model for meta-analysis.
Kalaian, H. A., & Raudenbush, S. W. (1996) · Psychological Methods · doi:10.1037/1082-989x.1.3.227 · Cited by 229 · cited 1× · see citing works
“We used a hierarchical multi-level mixed-model approach (Kalaian and Raudenbush, 1996) similar to that employed by Dickerson and Kemeny (2004).”
MethodHalligan, S. L., Herbert, J., Goodyer, I., & Murray, L. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.09.011 · Cited by 217 · cited 3× · see citing works
“(1997) reported significant reductions in basal cortisol after remission from anMDD 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 (Goo…”
BackgroundCan biological tests assist prediction of suicide in mood disorders?
Mann, J. J., Currier, D., Stanley, B., Oquendo, M. A., Amsel, L. V., & Ellis, S. P. (2006) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145705005687 · Cited by 215 · cited 1× · see citing works
“While some meta-analyses of the DST in adult depression exist (see for example, Mann et al., 2006; Nelson and Davis, 1997; Ribeiro et al., 1993), none of them focused on the DST responses or hypercortisolaemiaof depressedvs. non-depressedadults.”
MethodRao, U., Hammen, C. L., Ortiz, L. R., Chen, L.-A., & Poland, R. E. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.012 · Cited by 210 · cited 5× · see citing works
“, 1992; Nelson and Davis, 1997), and exposure to traumatic events (e.g., Kaufman et al., 1997; Rao et al., 2008).”
BackgroundResultInfluentialIncreased Waking Salivary Cortisol Levels in Young People at Familial Risk of Depression
Mannie, Z. N., Harmer, C. J., & Cowen, P. J. (2007) · American Journal of Psychiatry · doi:10.1176/ajp.2007.164.4.617 · Cited by 192 · cited 2× · see citing works
“…have contributed to the inconsistencies of past findings, such as age (e.g., Dahl et al., 1992), time of data collection (e.g., Forbes et al., 2006; Mannie et al., 2007), or whether the comparison group consisted of youths with psychiatric diagnoses other than depression (e.g., Casat et al., 1994)…”
BackgroundGoodyer, I. M., HERBERT, J., & ALTHAM, P. M. E. (1998) · Psychological Medicine · doi:10.1017/s0033291797006314 · Cited by 189 · cited 1× · see citing works
“Finally, due to our strict selection criteria, a number of informative studies were omitted from the meta-analysis (see for example Goodyer et al., 1991, 1998, 2000a,b, 2001, 2003; Halligan et al., 2007; Herbert et al., 1996; Rao et al., 1996, 1997, 1999).”
BackgroundLuby, J. L., Heffelfinger, A., Mrakotsky, C., Brown, K., Hessler, M., & Spitznagel, E. (2003) · Archives of General Psychiatry · doi:10.1001/archpsyc.60.12.1248 · Cited by 184 · cited 5× · see citing works
“Finally, the three studies of HPA-axis reactivity to psychological stressors (Luby et al., 2003, 2004; Rao et al., 2008) reported equivocal results.”
BackgroundResultInfluentialGoodyer, I. M., Herbert, J., Tamplin, A., & Altham, P. M. E. (2000) · British Journal of Psychiatry · doi:10.1192/bjp.176.2.142 · Cited by 172 · cited 3× · see citing works
“…basal cortisol after remission from anMDD 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).”
Background24-Hour cortisol measures in adolescents with major depression: A controlled study
Dahl, R. E., Ryan, N. D., Puig-Antich, J., Nguyen, N., Al-Shabbout, M., MEYER, V., & Perel, J. M. (1991) · Biological Psychiatry · doi:10.1016/0006-3223(91)90067-v · Cited by 165 · see citing works
GOODYER, I. M., HERBERT, J., & TAMPLIN, A. (2003) · Psychological Medicine · doi:10.1017/s0033291702007286 · Cited by 146 · see citing works
Luby, J. L., Mrakotsky, C., Heffelfinger, A., Brown, K., & Spitznagel, E. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.11.1998 · Cited by 137 · cited 2× · see citing works
“Finally, the three studies of HPA-axis reactivity to psychological stressors (Luby et al., 2003, 2004; Rao et al., 2008) reported equivocal results.”
BackgroundResultPsychosocial and endocrine features of chronic first-episode major depression in 8–16 year olds
Goodyer, I. M., Park, R. J., & Herbert, J. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01120-9 · Cited by 130 · see citing works
Rao, U., Dahl, R. E., Ryan, N. D., Birmaher, B. B., Williamson, D. E., Giles, D. E., Rao, R., Kaufman, J., & Nelson, B. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00481-5 · Cited by 123 · cited 1× · see citing works
“Finally, due to our strict selection criteria, a number of informative studies were omitted from the meta-analysis (see for example Goodyer et al., 1991, 1998, 2000a,b, 2001, 2003; Halligan et al., 2007; Herbert et al., 1996; Rao et al., 1996, 1997, 1999).”
BackgroundPeri-sleep-onset cortisol levels in children and adolescents with affective disorders.
Forbes, E. E., Williamson, D., Ryan, N., Birmaher, B., Axelson, D., & Dahl, R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.06.002 · Cited by 122 · cited 3× · see citing works
“…(e.g., Dahl et al., 1992), time of data collection (e.g., Forbes et al., 2006; Mannie et al., 2007), or whether the comparison group consisted of youths with psychiatric diagnoses other than depression (e.g., Casat et al., 1994) or normal controls (e.g., Feder et al., 2004; Forbes et al., 2006).”
BackgroundResultThe dexamethasone suppression test in prepubertal depressed children
Poznanski, E. O., Carroll, B. J., Banegas, M., et al. (1982) · American Journal of Psychiatry · doi:10.1176/ajp.139.3.321 · Cited by 120 · see citing works
Factors Associated With the Development of Substance Use Disorder in Depressed Adolescents
Rao, U., Ryan, N. D., Dahl, R. E., Birmaher, B. B., Rao, R., Williamson, D. E., & Perel, J. M. (1999) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199909000-00014 · Cited by 110 · see citing works
The Neuroendocrinology of Mood Disorders
Rubín, R. T., & Carroll, B. J. (2009) · Elsevier eBooks · doi:10.1016/b978-008088783-8.00092-9 · Cited by 103 · see citing works
Feder, A., Coplan, J. D., Goetz, R. R., Mathew, S. J., Pine, D. S., Dahl, R. E., Ryan, N. D., Greenwald†, S., & Weissman, M. M. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.05.005 · Cited by 103 · cited 1× · see citing works
“…(e.g., Dahl et al., 1992), time of data collection (e.g., Forbes et al., 2006; Mannie et al., 2007), or whether the comparison group consisted of youths with psychiatric diagnoses other than depression (e.g., Casat et al., 1994) or normal controls (e.g., Feder et al., 2004; Forbes et al., 2006).”
BackgroundCortisol Secretion in Prepubertal Children With Major Depressive Disorder
Puig-Antich, J., Dahl, R. E., Ryan, N. D., NOVACENKO, H., Goetz, D. M., Goetz, R. R., TWOMEY, J., & Klepper, T. P. (1989) · Archives of General Psychiatry · doi:10.1001/archpsyc.1989.01810090043008 · Cited by 94 · see citing works
Neuroendocrinology of mood disorders.
Mazza, M., Satta, M. A., Bria, P., & Mazza, S. (2004) · PubMed · Cited by 79 · see citing works
Interpreting and Evaluating Meta-Analysis
Hall, J. A., & Rosenthal, R. (1995) · Evaluation & the Health Professions · doi:10.1177/016327879501800404 · Cited by 75 · cited 1× · see citing works
“…factors that explain differences between studies even if heterogeneity was not observed, as estimates of heterogeneity have some limitations (Ioannidis, 2008), and significant moderating factors may be present even when the variability between studies is not large (see Hall and Rosenthal, 1995).”
BackgroundCortisol secretion in adolescents with major depressive disorder
Dahl, R. E., Puig-Antich, J., Ryan, N. D., Nelson, B., NOVACENKO, H., TWOMEY, J., Williamson, D. E., Goetz, R. R., & Ambrosini, P. J. (1989) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1989.tb01295.x · Cited by 67 · see citing works
Herbert, J., Goodyer, I. M., ALTHAM, P. M. E., Pearson, J., SECHER, S. M., & Shiers, H. M. (1996) · Psychological Medicine · doi:10.1017/s0033291700034656 · Cited by 65 · cited 1× · see citing works
“Finally, due to our strict selection criteria, a number of informative studies were omitted from the meta-analysis (see for example Goodyer et al., 1991, 1998, 2000a,b, 2001, 2003; Halligan et al., 2007; Herbert et al., 1996; Rao et al., 1996, 1997, 1999).”
BackgroundCorticotropin-releasing hormone challenge in prepubertal major depression
Birmaher, B. B., Dahl, R. E., Perel, J. M., Williamson, D. E., Nelson, B., Stull, S. D., Kaufman, J., Waterman, G. S., Rao, U., Nguyen, N., et al. (1996) · Biological Psychiatry · doi:10.1016/0006-3223(95)00177-8 · Cited by 62 · cited 6× · see citing works
“…findings, with some reviewers concluding that the association between dysregulated HPA-axis and child depression is inconclusive at best (Birmaher et al., 1996a,b; Birmaher and Heydl, 2001), while others suggesting that HPA-dysregulation in pediatric depression is consistent with that…”
BackgroundResultInfluentialBeaton, E. A., Schmidt, L. A., Ashbaugh, A. R., Santesso, D. L., Antony, M. M., McCabe, R. E., Segalowitz, S. J., & Schulkin, J. (2006) · Personality and Individual Differences · doi:10.1016/j.paid.2006.02.020 · Cited by 61 · cited 1× · see citing works
“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).”
BackgroundThe Dexamethasone Suppression Test in children and adolescents: A review and a controlled study
Dahl, R. E., Kaufman, J., Ryan, N. D., Perel, J. M., Al-Shabbout, M., Birmaher, B. B., Nelson, B., & Puig-Antich, J. (1992) · Biological Psychiatry · doi:10.1016/0006-3223(92)90015-r · Cited by 57 · cited 2× · see citing works
“…studies have also differed along a number of dimensions that may have contributed to the inconsistencies of past findings, such as age (e.g., Dahl et al., 1992), time of data collection (e.g., Forbes et al., 2006; Mannie et al., 2007), or whether the comparison group consisted of youths…”
BackgroundResultResponse to oCRH in depressed and nondepressed adolescents: does gender make a difference?
DORN, L. D., BURGESS, E. S., SUSMAN, E. J., von EYE, A., DeBELLIS, M. D., GOLD, P. W., & CHROUSOS, G. P. (1996) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1097/00004583-199606000-00016 · Cited by 56 · cited 4× · see citing works
“The 4 published studies that used infusion of corticotropin releasing hormone failed to find a difference in cortisol response between the depressed and control groups (Birmaher et al., 1996; Dorn et al., 1996; Kaufman et al., 1997; Ronsaville et al., 2006).”
BackgroundInfluentialThe dexamethasone suppression test in depressed adolescents
Extein, I., Rosenberg, G., Pottash, A. L., et al. (1982) · American Journal of Psychiatry · doi:10.1176/ajp.139.12.1617 · Cited by 55 · see citing works
Saliva Cortisol and Response to Dexamethasone in Children of Depressed Parents
Young, E. A., Vázquez, D. M., Jiang, H., & Pfeffer, C. R. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2006.03.077 · Cited by 51 · see citing works
The dexamethasone suppression test in adolescent psychiatric inpatients
Targum, S. D., & Capodanno, A. E. (1983) · American Journal of Psychiatry · doi:10.1176/ajp.140.5.589 · Cited by 47 · see citing works
Rao, U., & Poland, R. E. (2008) · Journal of Child and Adolescent Psychopharmacology · doi:10.1089/cap.2008.034 · Cited by 46 · see citing works
RONSAVILLE, D. S., MUNICCHI, G., LANEY, C., CIZZA, G., MEYER, S. E., HAIM, A., RADKE-YARROW, M., CHROUSOS, G., GOLD, P. W., & MARTINEZ, P. E. (2006) · Development and Psychopathology · doi:10.1017/s095457940606010x · Cited by 42 · cited 2× · see citing works
“CRH infusion studies 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., 1996a,b; Dorn et al., 1996; Kaufman et al., 1997; Ronsaville et al., 2006).”
BackgroundBiological studies in depressed children and adolescents
Birmaher, B. B., & Heydl, P. (2001) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145701002358 · Cited by 38 · cited 4× · see citing works
“However, contrary to previous descriptive reviews, which proposed that age influences HPA-axis response in depressed youngsters (Birmaher and Heydl, 2001), our ana- lysis found no significant age differences.”
ResultInfluentialSalivary cortisol concentrations before and after carbon-dioxide inhalations in children
Coplan, J. D., Moreau, D., CHAPUT, F., Martinez, J. M., Hoven, C. W., Mandell, D. J., Gorman, J. M., & Pine, D. S. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01250-1 · Cited by 38 · see citing works
Increased Waking Salivary Cortisol Levels in Young People at Familial Risk of Depression
Mannie, Z. N. (2007) · American Journal of Psychiatry · doi:10.1176/appi.ajp.164.4.617 · Cited by 37 · see citing works
Cortisol hypersecretion in depressed school-aged children and adolescents
Goodyer, I. M., Herbert, J., Moor, S., & ALTHAM, P. M. E. (1991) · Psychiatry Research · doi:10.1016/0165-1781(91)90060-3 · Cited by 36 · cited 1× · see citing works
“Finally, due to our strict selection criteria, a number of informative studies were omitted from the meta-analysis (see for example Goodyer et al., 1991, 1998, 2000a,b, 2001, 2003; Halligan et al., 2007; Herbert et al., 1996; Rao et al., 1996, 1997, 1999).”
BackgroundThe dexamethasone suppression test in depressed, dysthymic, and nondepressed children
Petty, L. K., Asarnow, J. R., Carlson, G. A., et al. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.5.631 · Cited by 36 · see citing works
Abnormal dexamethasone suppression test results in depressed and nondepressed children
LIVINGSTON, R. L., Reis, C., & Ringdahl, I. C. (1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.1.106 · Cited by 36 · see citing works
The Dexamethasone Suppression Test in Psychiatrically Hospitalized Adolescents
Robbins, D. R., Alessi, N. E., YANCHYSHYN, G. W., et al. (1983) · Journal of the American Academy of Child Psychiatry · doi:10.1016/s0002-7138(09)61510-7 · Cited by 35 · see citing works
The dexamethasone suppression test in adolescent outpatients with major depressive disorder
Birmaher, B. B., Dahl, R. E., Ryan, N. D., RABINOVICH, H., Ambrosini, P. J., Al-Shabbout, M., NOVACENKO, H., Nelson, B., & Puig-Antich, J. (1992) · American Journal of Psychiatry · doi:10.1176/ajp.149.8.1040 · Cited by 33 · see citing works
The dexamethasone suppression test in adolescent psychiatric patients
Hà, H. T., Kaplan, S., & Foley, C. A. (1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.3.421 · Cited by 32 · see citing works
Doherty, M. B., Madansky, D. L., Kraft, J. N., et al. (1986) · Journal of the American Academy of Child Psychiatry · doi:10.1016/s0002-7138(09)60263-6 · Cited by 31 · see citing works
The Dexamethasone Suppression Test in Adolescent Depression
Hsu, L. K. G., Molcan, K., Cashman, M. A., et al. (1983) · Journal of the American Academy of Child Psychiatry · doi:10.1016/s0002-7138(09)61511-9 · Cited by 28 · see citing works
The DST in children and adolescents with major depressive disorder
Casat, C. D., Arana, G. W., & Powell, K. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.4.503 · Cited by 26 · cited 1× · see citing works
“Our results indicate that such HPA-axis dysregulation can also be found in children and adolescents, a conclusion that is in line with, and extends previous reviews by Casat et al. (1989) and Kaufman et al. (2001).”
ResultRao, U., McCracken, J. T., Lutchmansingh, P., Edwards, C., & Poland, R. E. (1997) · Biological Psychiatry · doi:10.1016/s0006-3223(96)00430-1 · Cited by 25 · cited 2× · see citing works
“For example, while Rao et al. (1997) reported significant reductions in basal cortisol after remission from anMDD 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…”
BackgroundThe hypothalamo–pituitary–adrenal axis in major affective disorder: a review
Christensen, M. V., & Kessing, L. V. (2001) · Nordic Journal of Psychiatry · doi:10.1080/080394801317080873 · Cited by 25 · cited 2× · see citing works
“Hypercortisolaemia has been consistently found in depressed adults (Christensen and Kessing, 2001; Gillespie and Nemeroff, 2005), and has been examined as a potential predictor of various outcomes (e.”
BackgroundPsychopathology and plasma cortisol responses to dexamethasone in prepubertal psychiatric inpatients
Pfeffer, C. R., Stokes, P. E., Weiner, A. S., Shindledecker, R. D., Faughnan, L., Mintz, M., Stoll, P., & Heiligenstein, E. L. (1989) · Biological Psychiatry · doi:10.1016/0006-3223(89)90102-9 · Cited by 22 · see citing works
Self-report vs. biological markers in assessment of childhood depression
Fristad, M. A., Weller, E. B., Weller, R. A., et al. (1988) · Journal of Affective Disorders · doi:10.1016/0165-0327(88)90030-4 · Cited by 20 · see citing works
Plasma dexamethasone levels in children given the dexamethasone suppression test
Naylor, M. W., Greden, J. F., & Alessi, N. E. (1990) · Biological Psychiatry · doi:10.1016/0006-3223(90)90526-8 · Cited by 15 · see citing works
Steingard, R. J., Biederman, J., Keenan, K. E., et al. (1990) · Biological Psychiatry · doi:10.1016/0006-3223(90)90574-l · Cited by 14 · see citing works
Serial dexamethasone suppression tests (DST) in recently hospitalized children
Casat, C. D., Pearson, D. A., Ruiz-Nazario, J., et al. (1994) · Biological Psychiatry · doi:10.1016/0006-3223(94)91227-0 · Cited by 4 · cited 1× · see citing works
“…(e.g., Dahl et al., 1992), time of data collection (e.g., Forbes et al., 2006; Mannie et al., 2007), or whether the comparison group consisted of youths with psychiatric diagnoses other than depression (e.g., Casat et al., 1994) or normal controls (e.g., Feder et al., 2004; Forbes et al., 2006).”
BackgroundMeta-analysis: formulating, evaluating, combining, and reporting
Normand, S.-L. T. (1999) · Statistics in Medicine · doi:10.1002/(sici)1097-0258(19990215)18:3 · 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).”
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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 · see citing works
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 · see citing works
“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 698 · see citing works
“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 · see citing works
Antidepressants recruit new neurons to improve stress response regulation
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Sex differences in depression: Insights from clinical and preclinical studies
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HPA axis and aging in depression: Systematic review and meta-analysis
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Depression during pregnancy and postpartum: Contribution of stress and ovarian hormones
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The neurobiology of depression
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The Hippocampus, Neurotrophic Factors and Depression
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Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity
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Allostasis and allostatic load in the context of poverty in early childhood
Blair, C., Raver, C. C., Granger, D. A., Mills-Koonce, R., Hibel, L. C., & The Family Life Project Key Investigators (2011) · Development and Psychopathology · doi:10.1017/s0954579411000344 · Cited by 240 · see citing works
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“…recent work showing an impact of childhood cortisol levels on adult functional connectivity (Burghy et al, 2012) and evidence of the importance of stressful life events and abnormal stress reactivity in the genesis and maintenance of depression (eg, Kendler et al, 1999; Lopez-Duran et al, 2009).”
BackgroundHarkness, K. L., Stewart, J. G., & Wynne‐Edwards, K. E. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2010.07.006 · Cited by 200 · see citing works
“Nevertheless, what is consistent across most studies using challenge paradigms in adult and pediatric MDD is a much larger variability in cortisol response within the depressed group versus the non-depressed individuals (Lopez-Duran et al., 2009).”
In Search of HPA Axis Dysregulation in Child and Adolescent Depression
Guerry, J. D., & Hastings, P. D. (2011) · Clinical Child and Family Psychology Review · doi:10.1007/s10567-011-0084-5 · Cited by 195 · see citing works
“More recent research, however, has led some to the more nuanced conclusion that the association appears to be stronger or weaker depending upon which index of HPA functioning is examined and at what age depression is manifested (Lopez-Duran et al. 2009; Kaufman et al. 2001).”
BackgroundResultInfluentialChen, C., Nakagawa, S., An, Y., Ito, K., Kitaichi, Y., & Kusumi, I. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.12.001 · Cited by 191 · see citing works
“…et al 2006), and demonstrate an overall increased CORT response to stress, which is more pronounced in young adults than in aged patients (Burke et al 2005; Lopez-Duran et al 2009) and is also normalized after successful treatment (Kunugi et al 2006; Holsboer and Ising 2010; ter Heegde et al 2015).”
Zajkowska, Z., Gullett, N., Walsh, A. E. L., Zonca, V., Pedersen, G. A., Souza, L., Kieling, C., Fisher, H. L., Kohrt, B. A., & Mondelli, V. (2021) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2021.105625 · Cited by 191 · see citing works
“Lopez and colleagues (Lopez-Duran et al., 2009) showed higher cortisol levels in children and adolescents with depression compared with healthy volunteers.”
InfluentialHankin, B. L., Badanes, L. S., Abela, J. R. Z., & Watamura, S. E. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.04.004 · Cited by 185 · see citing works
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“In addition, much less research has looked at the long-term effects of developmental SSRI exposure during adolescence, a time of vulnerability to stress [38,39,40,41,42].”
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Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis
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Developmental origins of the human hypothalamic-pituitary-adrenal axis
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“A similar study reported that even non-depressed individuals with an incidence of early childhood abuse exhibit an increase in ACTH, but have normal cortisol concentrations [35].”
BackgroundLogan, R. W., Edgar, N. M., Gillman, A. G., Hoffman, D., Zhu, X., & McClung, C. A. (2015) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.01.011 · Cited by 154 · see citing works
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“Prior cross-sectional research relating cortisol to major depression in adolescents found that lower morning values, elevated evening values, and flatter cortisol slopes across the waking day were associated with the presence of MDD (for review and meta-analysis, see Lopez-Duran et al., 2009).”
BackgroundHakamata, Y., Suzuki, Y., Kobashikawa, H., & Hori, H. (2022) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2022.100994 · Cited by 141 · see citing works
“Basal cortisol levels are found to be decreased in PTSD (Meewisse et al., 2007; Morris et al., 2012; Schumacher et al., 2019), whereas they are elevated in MDD (Lopez-Duran et al., 2009; Psarraki et al., 2021; Stetler and Miller, 2011).”
How to Improve Adolescent Stress Responses
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The social ecology of childhood and early life adversity
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“Abnormal HPA axis function has been implicated in depressive and anxiety disorders, conceptualised in part as an inappropriate, often prolonged, stress response (Lopez-Duran et al. 2009).”
BackgroundGraham, A. M., Fisher, P. A., & Pfeifer, J. H. (2013) · Psychological Science · doi:10.1177/0956797612458803 · Cited by 125 · see citing works
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“Both IL-6 and hypercortisolemia have been linked to depression (Dowlati et al., 2010; Howren et al., 2009; Liu et al., 2011; Lopez-Duran et al., 2009; Stetler and Miller, 2011) and disruption of cortisol rhythms has been linked to depression in breast and ovarian cancer populations (Abercrombie et al.”
BackgroundRoberts, A. G., & Lopez‐Duran, N. L. (2018) · Comprehensive Psychiatry · doi:10.1016/j.comppsych.2018.10.008 · Cited by 131 · see citing works
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Mood-stabilizing drugs: mechanisms of action
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Delineating the Genetic Component of Gene Expression in Major Depression
Dall’Aglio, L., Lewis, C. M., & Pain, O. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.09.010 · Cited by 103 · see citing works
Adam, E. K., Vrshek‐Schallhorn, S., Kendall, A. D., Mineka, S., Zinbarg, R. E., & Craske, M. G. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2014.02.014 · Cited by 110 · see citing works
“Recent meta-analytic evidence suggests that depressed individuals show higher basal cortisol, on average, than individuals without depression (Lopez-Duran et al., 2009; Knorr et al., 2010).”
Neurogenetics of depression: A focus on reward processing and stress sensitivity
Bogdan, R., Nikolova, Y. S., & Pizzagalli, D. A. (2012) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.05.007 · Cited by 105 · see citing works
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Glucocorticoid resistance in chronic diseases
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“Although associations are less consistent, depression in adolescents has also been associated with alterations along the HPA axis, particularly increased basal cortisol prior to sleep onset dexamethasone nonsuppression, higher cortisol—DHEA ratios, alterations in free cortisol, and altered response to psychological ch…”
BackgroundSequeira, A., Morgan, L. Z., Walsh, D. M. A., Cartagena, P. M., Choudary, P. V., Li, J. Z., Schatzberg, A. F., Watson, S. J., Akil, H., Myers, R., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035367 · Cited by 91 · see citing works
Depressive disorders in childhood and adolescence
Brent, D. A., & Maalouf, F. (2015) · Wiley eBooks · doi:10.1002/9781118381953.ch63 · Cited by 94 · see citing works
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Longitudinal Patterns of Cortisol Regulation Differ in Maltreated and Nonmaltreated Children
Doom, J. R., Cicchetti, D., & Rogosch, F. A. (2014) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2014.08.006 · Cited by 98 · see citing works
Hypothalamic-pituitary-adrenal axis functioning in borderline personality disorder: A meta-analysis
Drews, E., Fertuck, E. A., Koenig, J., Kaess, M., & Arntz, A. R. (2018) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2018.11.008 · Cited by 93 · see citing works
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Bone density in peripubertal boys with Autism Spectrum Disorders
Neumeyer, A. M., Gates, A., Ferrone, C., Lee, H., & Misra, M. (2013) · Journal of Autism and Developmental Disorders · doi:10.1007/s10803-012-1709-3 · Cited by 91 · see citing works
“Children with ASD have high rates of co-morbid neurologic and psychiatric illnesses, including epilepsy and mood disorders, which may be associated with increased cortisol levels, exacerbating the risk for low bone density (Greaves-Lord et al. 2009; Lopez-Duran et al. 2009; Sheth et al. 2008).”
BackgroundDavis, E. P., Hankin, B. L., Swales, D. A., & Hoffman, M. C. (2018) · Development and Psychopathology · doi:10.1017/s0954579418000470 · Cited by 90 · see citing works
Rumination and Impaired Cortisol Recovery Following a Social Stressor in Adolescent Depression
Stewart, J. G., Mazurka, R., Bond, L., Wynne‐Edwards, K. E., & Harkness, K. L. (2013) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-013-9740-1 · Cited by 90 · see citing works
Harkness, K. L., Hayden, E. P., & Lopez‐Duran, N. L. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000041 · Cited by 90 · see citing works
Self-citationThe microbiome as a novel paradigm in studying stress and mental health.
Liu, R. T. (2017) · American Psychologist · doi:10.1037/amp0000058 · Cited by 89 · see citing works
“With a normally functioning HPA system, DST administration leads to a suppression of CRH and ACTH production, and a resulting decrease in circulating cortisol.”
BackgroundEisenlohr-Moul, T. A., Miller, A. B., Giletta, M., Hastings, P. D., Rudolph, K. D., Nock, M. K., & Prinstein, M. J. (2018) · Neuropsychopharmacology · doi:10.1038/s41386-018-0206-6 · Cited by 87 · see citing works
Calhoun, C. D., Helms, S. W., Heilbron, N., Rudolph, K. D., Hastings, P. D., & Prinstein, M. J. (2014) · Development and Psychopathology · doi:10.1017/s0954579414000261 · Cited by 89 · see citing works
“, 2006; Shirtcliff & Essex, 2008), corticosteroid medications (Hastings, Fortier, Utendale, Simard, & Robaey, 2009), birth control (Bouma, Riese, Ormel, Verhulst, & Oldehinkel, 2009), depressive symptoms (Guerry & Hastings, 2011; Lopez-Duran et al., 2009), and negative life events (Lupien et al.”
Giletta, M., Slavich, G. M., Rudolph, K. D., Hastings, P. D., Nock, M. K., & Prinstein, M. J. (2018) · Journal of Child Psychology and Psychiatry · doi:10.1111/jcpp.12804 · Cited by 87 · see citing works
Martinez‐Torteya, C., Bogat, G. A., Levendosky, A. A., & von Eye, A. (2015) · Development and Psychopathology · doi:10.1017/s0954579415000280 · Cited by 85 · see citing works
“to psychosocial stress and higher resting cortisol levels (Essex et al., 2002; Lopez-Duran et al., 2009), as compared to”
BackgroundResultInfluentialDietrich, A., Ormel, J., Buitelaar, J. K., Verhulst, F. C., Hoekstra, P. J., & Hartman, C. A. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.11.013 · Cited by 84 · see citing works
“…symptoms not only in adults (Vreeburg et al., 2009, 2010; Knorr et al., 2010; Stetler and Miller, 2011) but also in children and adolescents (Lopez-Duran et al., 2009a; Ruttle et al., 2011; Stetler and Miller, 2011; Garcia de Miguel et al., 2012), albeit relationships in children are less…”
BackgroundWainwright, S. R., Lieblich, S. E., & Galea, L. A. M. (2011) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.03.004 · Cited by 81 · see citing works
Zajkowska, Z., Walsh, A. E. L., Zonca, V., Gullett, N., Pedersen, G. A., Kieling, C., Swartz, J. R., Karmacharya, R., Fisher, H. L., Kohrt, B. A., et al. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.04.003 · Cited by 82 · see citing works
Prevalence of the metabolic syndrome in unipolar major depression
Kahl, K. G., Greggersen, W., Schweiger, U., Cordes, J., Balijepalli, C., Lösch, C., & Moebus, S. (2012) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-011-0277-4 · Cited by 79 · see citing works
Hastings, P. D., Shirtcliff, E. A., Klimes‐Dougan, B., Allison, A. L., DeRose, L. M., Kendziora, K. T., Usher, B. A., & Zahn‐Waxler, C. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000538 · Cited by 80 · see citing works
Latent trait cortisol (LTC) levels: Reliability, validity, and stability
Doane, L. D., Chen, F. R., Sladek, M. R., Van Lenten, S. A., & Granger, D. A. (2015) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2015.01.017 · Cited by 79 · see citing works
Dougherty, L. R., Tolep, M. R., Smith, V. C., & Rose, S. (2013) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-013-9763-7 · Cited by 77 · see citing works
“…greater cortisol reactivity in our high-risk sample of preschool-age children is consistent with the literature documenting elevated cortisol reactivity in depressed adults (Burke et al. 2005) and youth (Lopez-Duran et al. 2009), as well as offspring of depressed parents (e.g. Brennan et al. 2008).”
BackgroundResultFisher, P. A., Lester, B. M., DeGarmo, D. S., LaGasse, L. L., Lin, H., Shankaran, S., Bada, H. S., Bauer, C. R., Hammond, J. A., Whitaker, T. M., et al. (2011) · Development and Psychopathology · doi:10.1017/s0954579411000290 · Cited by 79 · see citing works
Hastings, P. D., Ruttle, P. L., Serbin, L. A., Mills, R. S. L., Stack, D. M., & Schwartzman, A. E. (2011) · Developmental Psychobiology · doi:10.1002/dev.20545 · Cited by 76 · see citing works
The role of inflammatory cytokines on the aetiopathogenesis of depression
Makhija, K., & Karunakaran, S. (2013) · Australian & New Zealand Journal of Psychiatry · doi:10.1177/0004867413488220 · Cited by 76 · see citing works
“…the HPA axis is appropriately activated in the body’s response to environmental stress, but some depressed patients appear to have an abnormal negative feedback system in the setting of intact pituitary and adrenal sensitivity leading to excessive cortisol secretion (Lopez-Duran et al., 2009).”
BackgroundVaillancourt, T., Duku, E., Becker, S., Schmidt, L. A., Nicol, J. R., Muir, C., & MacMillan, H. L. (2011) · Brain and Cognition · doi:10.1016/j.bandc.2011.06.012 · Cited by 74 · see citing works
“Depressed children typically have higher cortisol levels than non-depressed children (e.g., Lopez-Duran et al., 2009) and depressive symptoms have been linked to poorer memory in adults (Burt et al., 1995).”
BackgroundResultFrom Stress to Depression: Bringing Together Cognitive and Biological Science
LeMoult, J. (2020) · Current Directions in Psychological Science · doi:10.1177/0963721420964039 · Cited by 73 · see citing works
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Longitudinal Course of Adolescent Depression: Neuroendocrine and Psychosocial Predictors
Rao, U., Hammen, C. L., & Poland, R. E. (2010) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2009.09.008 · Cited by 67 · see citing works
Interaction between 5-HTTLPR and BDNF Val66Met polymorphisms on HPA axis reactivity in preschoolers
Dougherty, L. R., Klein, D. N., Congdon, E. L., Canli, T., & Hayden, E. P. (2009) · Biological Psychology · doi:10.1016/j.biopsycho.2009.10.009 · Cited by 64 · see citing works
“, 2001; McEwen, 2008), including depression (Burke et al., 2005; Lopez-Duran et al., 2009), anxiety disorders (Bremner et al.”
BackgroundBeauchaine, T. P., Crowell, S. E., & Hsiao, R. C.-J. (2014) · Research on Child and Adolescent Psychopathology · doi:10.1007/s10802-014-9933-2 · Cited by 66 · see citing works
“…comparing the three approaches across 34 child and adolescent samples (N=2258), the global standardized mean effect size for the DST between depressed and non-depressed youth (0.57) was almost three times larger than the mean effect size (0.20) for basal cortisol (Lopez-Duran et al. 2009).”
InfluentialCortisol awakening response and subsequent depression: prospective longitudinal study
Carnegie, R., Araya, R., Ben‐Shlomo, Y., Glover, V. A. S., O’Connor, T. G., O’Donnell, K. J., Pearson, R. M., & Lewis, G. (2013) · The British Journal of Psychiatry · doi:10.1192/bjp.bp.113.126250 · Cited by 63 · see citing works
“20,21 Methodological differences, including variation in salivary collection protocols, sample populations, outcome measures and varying adjustment for confounding factors 22 may account for some of the inconsistency.”
Relationship between psychological stress and recurrent miscarriage
Li, W., Newell-Price, J. D. C., Jones, G. L., Ledger, W. J., & Li, T. C. (2012) · Reproductive BioMedicine Online · doi:10.1016/j.rbmo.2012.03.012 · Cited by 62 · see citing works
“Nonsuppression of the DST has been found to be a sensitive measure of stress due to the development of a reversible glucocorticoid resistance with dysregulated feedback of the HPA axis (Faravelli et al., 2010; Herman and Cullinan, 1997; Lopez-Duran et al., 2009).”
BackgroundFisher, P. A., Kim, H. K., Bruce, J., & Pears, K. C. (2011) · International Journal of Behavioral Development · doi:10.1177/0165025411406863 · Cited by 63 · see citing works
“For example, MacMillan et al. (2009) compared a sample of 12- to 16-year-old females with histories of childhood maltreatment to a sample of aged-matched, nonmaltreated females.”
BackgroundInternalizing and externalizing behaviors predict elevated inflammatory markers in childhood
Slopen, N. B., Kubzansky, L. D., & Koenen, K. C. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.07.012 · Cited by 58 · see citing works
“Both internalizing and externalizing behaviors are associated with dysregulated hypothalamic—pituitary—adrenal axis (HPA) (Cappadocia et al., 2009; Lopez-Duran et al., 2009) and sympathetic nervous system (SNS) (Matthys et al., 2013; Obradović and Boyce, 2012) function, which could lead to the…”
BackgroundInfluentialNoonan, K., Carey, L. M., & Crewther, S. G. (2012) · Journal of Stroke and Cerebrovascular Diseases · doi:10.1016/j.jstrokecerebrovasdis.2012.09.008 · Cited by 62 · see citing works
Doolin, K., Farrell, C. M., Tozzi, L., Harkin, A., Frodl, T., & O’Keane, V. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18102226 · Cited by 64 · see citing works
“This is a finding that has been reported widely in the literature, and the results from this study are in accordance with the existing evidence that stress is central to the pathophysiology of depression [4,29].”
ResultPsychobiological responses to unpleasant emotions in cannabis users
Somaini, L., Manfredini, M., Amore, M., Zaimovic, A., Raggi, M. A., Leonardi, C., Gerra, M. L., Donnini, C., & Gerra, G. (2011) · European Archives of Psychiatry and Clinical Neuroscience · doi:10.1007/s00406-011-0223-5 · Cited by 60 · see citing works
“In contrast to our results, a meta-analysis on depressed youth not exposed to drugs evidenced an overactive response to psychological stressors and not a blunted one [23], underlying the possible role of cannabis itself in the impairment of emotional stress response.”
ResultZou, L., Wu, X., Tao, S., Xu, H., Xie, Y., Yang, Y., & Tao, F. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00822 · Cited by 63 · see citing works
Hankin, B., Badanes, L. S., Smolen, A., & Young, J. (2015) · Journal of Abnormal Psychology · doi:10.1037/abn0000030 · Cited by 56 · see citing works
Biomarkers in Child and Adolescent Depression
Zwolińska, W., Dmitrzak‐Węglarz, M., & Słopień, A. (2021) · Child Psychiatry & Human Development · doi:10.1007/s10578-021-01246-y · Cited by 61 · see citing works
Hypothalamic-Pituitary-Adrenal Axis Reactivity in the Preschool-Age Offspring of Depressed Parents
Dougherty, L. R., Klein, D. N., Rose, S., & Laptook, R. S. (2011) · Psychological Science · doi:10.1177/0956797611404084 · Cited by 57 · see citing works
- 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
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