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Cited by 316Stress Responses and CortisolAnxiety, Depression, Psychometrics, Treatment, Cognitive ProcessesChild and Adolescent Psychosocial and Emotional Development

Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence

Open access
Adam, Emma K., Doane, Leah D., Zinbarg, Richard E., Mineka, Susan, Craske, Michelle G., Griffith, James W.·2010·Psychoneuroendocrinology
DOI 10.1016/j.psyneuen.2009.12.007PMC PMC2875344
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Abstract

Levels of the stress-sensitive hormone cortisol increase dramatically in the first 30-40 minutes after waking, an effect known as the cortisol awakening response (CAR). There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR, and the CAR has been found to be altered in the presence of stress-related diseases, including Major Depressive Disorder (MDD). To date, no prospective longitudinal studies have examined whether individual differences in the CAR serve as a premorbid risk factor for MDD. In a sample of 230 late adolescents, clinical diagnoses of MDD were predicted from the CAR as well as other indicators of basal cortisol functioning gathered one year earlier, including: waking cortisol levels, bedtime cortisol levels, the size of the CAR, average cortisol, and the slope of the diurnal cortisol rhythm across the waking day. Age and gender, health and health behaviors, baseline neuroticism, exposure to stressful life events and past episodes of mood and anxiety disorders were included as covariates, to help ensure effects are attributable to the CAR rather than related variables. A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up, even when excluding individuals with baseline MDD. No other baseline cortisol measures were significant prospective predictors of MDD. In summary, the CAR is a significant prospective risk factor for the development of MDD in young adults, providing some support for the possibility that a heightened CAR may play a role in the etiology of Major Depressive Disorder.

AI snapshot

Written from the paper’s full text.

TL;DR

In a prospective sample of 230 late adolescents, a higher cortisol awakening response (CAR) at baseline predicted increased risk of developing major depressive disorder (MDD) by one-year follow-up. Other baseline cortisol measures did not significantly predict MDD, suggesting the CAR may be a premorbid risk marker.

Key findings

  • A higher baseline CAR significantly predicted clinical MDD over follow-up (OR = 3.0, p = .04), and remained predictive after excluding the 16 participants with current MDD at baseline (OR = 4.0, p = .05; N = 214, 15 developed MDD).
  • No other baseline cortisol measure was a significant prospective predictor: wakeup cortisol OR = .93, p = .85; wakeup + 40 min OR = 1.3, p = .59; bedtime cortisol OR = .49, p = .10; diurnal slope and average cortisol (AUC) were also non-significant.
  • The CAR also predicted a larger outcome group including clinical and subclinical MDD (OR = 2.5, p = .02), and without covariates it predicted clinical MDD (OR = 2.17, p = .02) and clinical/subclinical MDD (OR = 2.0, p = .002); after removing lifetime MDD cases, it predicted new onsets of clinical/subclinical MDD (OR = 2.22, p = .01).
  • In the clinical MDD model, the CAR–MDD association was weaker for men than women (OR = .02, p = .04), but only two men developed clinical MDD; no gender interaction appeared in the larger clinical/subclinical outcome model. Baseline life stress (OR = 4.0, p = .04) and increases in life stress (OR = 16.7, p = .001) independently predicted MDD, with no evidence that the CAR mediated life stress effects.

Methods

  • Prospective longitudinal study of older adolescents (average age 17.0 years) from two public high schools; 230 participants (173 female, 57 male) were analyzed after exclusions. High-neuroticism youth were oversampled, with 60% of the sample scoring in the top third of neuroticism.
  • Salivary cortisol was collected six times per day over three consecutive weekdays: at wake-up, 40 minutes after waking, approximately 3, 8, and 12 hours post-awakening, and bedtime. CAR was calculated as wake-up + 40 min minus wake-up cortisol, averaged across three days and log-transformed.
  • MDD diagnoses were assessed with the SCID at baseline and follow-up (average 368 days after cortisol assessment). Logistic regression predicted MDD from baseline cortisol measures with covariates including past/current MDD, other mood and anxiety disorders, life stress, neuroticism, negative mood, age, gender, and health variables; robustness analyses excluded baseline MDD, removed covariates, and included subclinical cases.

Limitations

  • The paper states a time delay of just over one month on average between baseline interview and cortisol sampling, so some individuals may have developed MDD in that interval; diary negative affect was included as a covariate to help address this.
  • The paper states the CAR protocol was simplified to two samples (wake-up and 40 minutes), less precise than intensive 10–15 minute sampling or a 0/30/60-minute protocol, and did not allow measuring CAR area under the curve or separating CAR increase from recovery speed.
  • The paper states reliance on noninvasive daytime cortisol rather than pharmacological challenges, and notes the gender finding is cautious because only two men developed clinical MDD; too few first onsets (9 cases) prevented formally comparing first onsets versus recurrences.
  • Evident from the text: the sample was predominantly female and oversampled for high neuroticism, producing higher MDD rates than typical adolescent samples, which may limit generalizability; the observational design cannot establish causality or mechanism.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.psyneuen.2009.12.007

Cites

64 of 64 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

0 of 35 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    No other baseline cortisol measures (waking cortisol, bedtime cortisol, average cortisol, diurnal cortisol slope) were significant prospective predictors of MDD.

    “No other baseline cortisol measures were significant prospective predictors of MDD.”
    • Also stated in: § Prospective prediction of MDD · plain
      “Steeper diurnal cortisol slopes, and average cortisol across the day (AUC), were not significantly related to later MDD, nor were gender differences in the effects of these measures observed.”
    • Also stated in: § Prospective prediction of MDD · plain
      “None of these variables (wakeup, wakeup plus 40 minute, and bedtime cortisol levels) were significant predictors of the development of MDD over the followup period (ORs = .93, p = .85; OR = 1.3, p = .59; and OR = .49, p = .10 for wakeup, wakeup plus 40 minute and bedtime cortisol levels, respectively).”
    Quote in the paperSubstantial claim
  • Findingown data

    A higher baseline cortisol awakening response (CAR) is associated with a significantly increased risk of developing Major Depressive Disorder (MDD) by follow-up in late adolescents.

    “A higher baseline CAR was associated with a significantly increased risk of developing MDD by follow-up, even when excluding individuals with baseline MDD.”
    • Also stated in: § Prospective prediction of MDD · plain
      “Beyond these effects, the size of the CAR significantly predicted later MDD, with a higher CAR associated with increased odds of having an episode of MDD over the follow-up period (OR = 3.0, p = .04).”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The CAR protocol used (wake-up and 40 minutes post-waking) is a valid measure of the cortisol awakening response for predicting MDD, despite being less intensive than the original protocol.
    • Rests on an assumption: The baseline cortisol assessment on three consecutive weekdays captures stable individual differences in CAR that are relevant to MDD risk over the following year.
  • Findingown data

    The association between the CAR and later MDD was significantly weaker for men than for women (OR = .02, p = .04).

    “An examination of the gender interaction indicated that the association between the CAR and later MDD was significantly weaker for men than for women (OR = .02, p = .04).”
    Quote in the paperNot a substantial claim
  • Findingown data

    Individuals with either past or baseline episodes of MDD were significantly more likely to have another episode by follow-up (OR = 6.9, p = .04).

    “Not surprisingly, individuals with either past or baseline episodes of MDD were significantly more likely to have another episode by followup (OR = 6.9, p = .04).”
    Quote in the paperNot a substantial claim
  • Findingown data

    There was a trend for youth with a later average time of waking to be related to an increased odds (OR = 4.95, p = .06) of developing MDD.

    “There was also a trend for youth with a later average time of waking (6:50 AM for those who develop MDD by followup; 6:44 AM for those who do not) to be related to an increased odds (OR = 4.95, p = .06) of developing MDD.”
    Quote in the paperNot a substantial claim
  • May combine two claims. 29
  • Classified as probably not a substantial claim. 22

  • May combine two claims.

    Findingown data

    Adolescent age (OR = 3.8, p = .03), presence of asthma at baseline (OR = 12.9, p = .02), and diary reports of fatigue (OR = 2.7, p = .04) were significantly related to later MDD.

    “Adolescent age (OR = 3.8, p = .03), the presence of asthma at baseline (OR = 12.9, p = .02), and diary reports of fatigue (OR = 2.7, p = .04) at the time of cortisol testing were also significantly related to later MDD.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There was a non-significant trend for male gender to predict reduced odds (OR = .02, p = .09) of developing MDD over follow-up.

    “Of the other covariates, there was a non-significant trend for male gender to predict reduced odds (OR = .02, p = .09) of developing MDD over the followup.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Of 230 participants, 56 (24%) were diagnosed with past or current MDD at baseline; 16 (7%) were current; 41 (18%) with a past or current anxiety disorder; and 25 (11%) with another mood disorder.

    “Of the 230 participants, 56 (24%) were diagnosed with either past or current MDD at the time of the baseline assessment (16 youth or 7% were current); 41 (18%) were diagnosed with a past or current anxiety disorder, and 25 (11%) with another mood disorder.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Baseline levels of life stress (OR = 4.0, p = .04) and increases in life stress from baseline to follow-up (OR = 16.7, p = .001) were significantly related to the development of MDD over follow-up.

    “As seen in Table 2, net of the other variables in the model, both baseline levels of life stress (OR = 4.0, p = .04), and increases in life stress from baseline to followup (OR = 16.7, p = .001) were significantly related to the development of MDD over followup.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    By follow-up, 18 (8%) youth met criteria for a clinical MDD diagnosis over the intervening period (9 first onsets, 9 recurrences; 16 of 18 female), and an additional 20 met subclinical criteria, for a total of 38 individuals.

    “By follow-up, 18 (8%) youth met the symptom and severity criteria for a clinical MDD diagnsosis over the intervening time period (9 first onsets, 9 recurrences; 16 out of 18 were female), and an additional 20 (12 female, 8 male) met subclinical criteria, for a total of 38 individuals (28 female, 10 male) meeting criteria for either a clinical or a subclinical episode over the followup period.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingown data

    Cortisol values followed the typical daily pattern: high upon waking (11.99 nmol/L), increased sharply to 16.82 nmol/L at 40 min post-awakening, and declined to a nadir at bedtime (2.85 nmol/L).

    “On average, cortisol values followed the typical daily pattern: they were high upon waking (11.99 nmol/L), increased sharply immediately after waking (to 16.82 nmol/L at 40 min post-awakening), and then declined rapidly at first, and then more slowly thereafter, to reach a nadir at bedtime (2.85 nmol/L).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    There was substantial variability in cortisol values at each sampling point and in the parameters (average cortisol, diurnal cortisol slope, CAR) used to describe baseline diurnal cortisol patterns.

    “There was, however, substantial variability in cortisol values at each sampling point, and in the parameters (average cortisol, diurnal cortisol slope, CAR) used to describe baseline diurnal cortisol patterns.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Wakeup, wakeup plus 40 minute, and bedtime cortisol levels were not significant predictors of the development of MDD over follow-up (ORs = .93, p = .85; OR = 1.3, p = .59; and OR = .49, p = .10, respectively).

    “None of these variables (wakeup, wakeup plus 40 minute, and bedtime cortisol levels) were significant predictors of the development of MDD over the followup period (ORs = .93, p = .85; OR = 1.3, p = .59; and OR = .49, p = .10 for wakeup, wakeup plus 40 minute and bedtime cortisol levels, respectively).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Steeper diurnal cortisol slopes and average cortisol across the day (AUC) were not significantly related to later MDD, nor were gender differences in the effects of these measures observed.

    “Steeper diurnal cortisol slopes, and average cortisol across the day (AUC), were not significantly related to later MDD, nor were gender differences in the effects of these measures observed.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Both new onset cases and recurrent cases of MDD are characterized by the high baseline CAR pattern, based on visual inspection of Figure 2.

    “a visual inspection of Figure 2 suggests that both the new onset cases (dark hatched line) and the recurrent cases (light hatched line) are characterized the high baseline CAR pattern.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    For both genders, the cortisol awakening response is more pronounced for youth who go on to develop MDD by follow-up, although overall diurnal cortisol curves appear lower for males than for females.

    “Although the overall diurnal cortisol curves appear lower for males than for females, for both genders, the cortisol awakening responses is more pronounced for youth who go on to develop MDD by followup.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Baseline life stress and increase in life stress were both significantly related to MDD at follow-up.

    “Our measure of baseline life stress (which assessed life stress over the prior year), and our measure of increase in life stress over the year between baseline and followup were both significantly related to MDD at followup”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    When predicting to clinical cases of MDD, the CAR was a significant prospective predictor for females, but not males.

    “When predicting to clinical cases of MDD, we found that the CAR was a significant prospective predictor for females, but not males”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Psychosocial stress is associated with an increased cortisol awakening response (CAR).

    “There is considerable cross-sectional evidence that psychosocial stress is associated with an increased CAR”
    • Also stated in: § Introduction · plain
      “In particular, a larger CAR has been associated with higher levels of both acute and chronic life stress (Adam et al., 2006; Schlotz et al., 2004).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Adam et al., 2006

      Not checked in the free run.

    • cites Schlotz et al., 2004 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    It is not yet clearly established whether HPA-axis alterations in MDD are correlates or consequences of depressive disorder/treatments or risk factors present before onset.

    “It is not yet clearly established in human populations whether such alterations are correlates or consequences of the experience of depressive disorder and/or its treatments, or whether they reflect risk or vulnerability factors that are present prior to the onset of disorder, thus potentially playing a role in the pathophysiology of MDD (Bhagwagar and Cowen, 2007).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Bhagwagar and Cowen, 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    A larger CAR is associated with higher levels of both acute and chronic life stress.

    “In particular, a larger CAR has been associated with higher levels of both acute and chronic life stress (Adam et al., 2006; Schlotz et al., 2004).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Adam et al., 2006

      Not checked in the free run.

    • cites Schlotz et al., 2004 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Cortisol diurnal rhythms vary according to individual sleep-wake schedules, being high upon waking, peaking approximately 30-40 minutes after waking, and declining to a nadir around bedtime.

    “Cortisol diurnal rhythms vary according to individual sleep-wake schedules, being high upon waking, increasing to peak levels approximately 30-40 minutes after waking, and declining to a nadir around bedtime (Kirschbaum and Helhammer, 2000; Pruessner et al., 1997; Wilhelm et al., 2007).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Kirschbaum and Helhammer, 2000

      Not checked in the free run.

    • cites Pruessner et al., 1997 source

      Not checked in the free run.

    • cites Wilhelm et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    CAR increases are large (on average 50-60% above waking levels) and highly variable across individuals.

    “CAR increases are large (on average 50-60% above waking levels) and highly variable across individuals; as a result, individual differences in the size of this indicator can be easily detected and modeled statistically, and are of a magnitude that is likely to be physiologically meaningful (Adam et al., 2006; Clow et al., 2004).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Adam et al., 2006

      Not checked in the free run.

    • cites Clow et al., 2004 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Past prospective studies examined morning cortisol at fixed clock times rather than in relation to person-specific waketimes, so they could not identify whether the size of the CAR serves as a risk factor for MDD.

    “Because all of the past prospective studies examined morning cortisol levels at fixed clock times (8 AM), rather than in relation to person-specific waketimes (Halligan et al., 2007), they were not in a position to identify whether the size of the cortisol awakening response serves as a risk factor for MDD.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Halligan et al., 2007 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Cross-sectional associations between the CAR and depression are mixed: some studies find lower CARs in current MDD, others find current MDD or high depressive symptoms associated with higher CARs.

    “Studies examining cross-sectional associations between the CAR and depression have found mixed results: some have found significantly lower CARs in individuals with current MDD diagnoses (Huber et al., 2006; Stetler and Miller, 2005), whereas others have found current MDD or high depressive symptoms to be associated with higher CARs (Bhagwagar et al., 2005; Pruessner et al., 2003).”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Huber et al., 2006 source

      Not checked in the free run.

    • cites Stetler and Miller, 2005

      Not checked in the free run.

    • cites Bhagwagar et al., 2005 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Assays were conducted in duplicate using a time-resolved immunoassay with fluorometric detection (DELFIA), with intra-assay coefficients of variation between 4.0% and 6.7% and inter-assay coefficients of variation from 7.1% to 9.0%.

    “Assays were conducted in duplicate using a time-resolved immunoassay with fluorometric detection (DELFIA) (Dressendorfer et al., 1992). Intra-assay coefficients of variation (CVs) were between 4.0% and 6.7%, and inter-assay CVs ranged from 7.1% to 9.0%.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Dressendorfer et al., 1992 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    For 69 cases, a second interviewer observed the SCID and provided independent diagnoses, with Cohen's kappas of .72 and .94 for mood and anxiety disorders, and correlations between .74 and .97 for CSR severity ratings.

    “For 69 cases, a second interviewer observed the SCID and provided independent diagnoses, with Cohen's kappas of .72 and .94 for mood and anxiety disorders, and correlations between .74 and .97 for CSR severity ratings (Zinbarg et al., 2009).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Zinbarg et al., 2009

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Trait neuroticism was assessed using four personality questionnaires, and measures were standardized and averaged to form a composite with a Cronbach's alpha of .85.

    “Measures were standardized and averaged to form a N composite, with a Cronbach's alpha of .85 (Griffith et al., 2007; Zinbarg et al., 2009).”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Eysenck et al., 1985 source

      Not checked in the free run.

    • cites Goldberg, 1992 source

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    • cites Carver and White, 1994 source

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Chronic and episodic stress were assessed using the Life Stress Interview, with inter-rater reliability (intraclass correlations) of .88 for chronic stress and .79 for episodic stress.

    “Inter-rater reliability (intraclass correlations examining absolute agreement) was .88 for chronic stress and .79 for episodic stress.”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Hammen et al., 1987 source

      Not checked in the free run.

    • cites Hammen, 1991

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    A comprehensive set of covariates was included to ensure that associations between cortisol and later MDD were attributable to baseline cortisol rather than to other risk factors for MDD or health confounds related to cortisol.

    “A comprehensive set of covariates was included to ensure that associations between cortisol and later MDD were attributable to baseline cortisol, rather than to other risk factors for MDD or health confounds that may be related to cortisol.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    Diagnostic status for clinical MDD required meeting DSM-IV symptom criteria for a Major Depressive Episode with no history of manic, hypomanic or mixed episodes.

    “Diagnostic status for clinical MDD required meeting DSM-IV symptom criteria for a Major Depressive Episode (MDE) with no history of manic, hypomanic or mixed episodes.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Some covariates, such as nicotine use and time of waking, were included in the model regardless of their statistical significance in predicting MDD because past research found strong associations with diurnal cortisol patterns.

    “Some covariates, such as nicotine use and time of waking, were included the model regardless of their level of statistical significance in predicting MDD, as they have been found in past research to have strong associations with diurnal cortisol patterns.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Only cases with a Clinical Severity Rating (CSR) of four or greater were included in the primary analyses because this score corresponded to clinically significant distress or impairment.

    “Only cases with a CSR of four or greater were included in the primary analyses because this score corresponded to clinically significant distress or impairment (caseness).”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    The CAR protocol used in this study was less intensive and thus less precise than the original CAR protocol, in which cortisol levels were obtained every 10 to 15 minutes after awakening.

    “It is important to note that this study was originally designed to examine multiple elements of the cortisol diurnal rhythm across the day, in addition to the CAR. As a result, in order to reduce participant burden, the protocol for the CAR is less intensive, and thus less precise, than the original CAR protocol, in which cortisol levels were obtained every 10 to 15 minutes after awakening (Pruess”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Pruessner et al., 1997 source

      Not checked in the free run.

    • Rests on an assumption: The CAR protocol used (wake-up and 40 minutes post-waking) is a valid measure of the cortisol awakening response for predicting MDD, despite being less intensive than the original protocol.

  • May combine two claims.

    Interpretationown data

    Life stress (or at least life stress within the past year) and the CAR are independently associated with the development of MDD, rather than the CAR being a mediational pathway by which recent life stress influences the development of MDD.

    “Thus, there is no sign that introduction of the CAR variables reduces the coefficients for life stress, suggesting that life stress (or at least life stress within the past year) and the CAR are independently associated with the development of MDD, rather than the CAR being a meditational pathway by which recent life stress influences the development of MDD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    A larger outcome group including both clinical MDD cases and subclinical cases was examined to see whether results held for less severe cases.

    “Finally, to increase the sample size of the group considered “depressed” in the follow- up period, and to see whether our results held for less severe cases, we examined a larger outcome group including both the clinical MDD cases and the subclinical cases who, as described above, came close but did not quite meet either the symptom or severity criteria needed to qualify for MDD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    In a secondary analysis, individuals with current MDD at baseline were excluded rather than covaried to ensure that cortisol levels were predicting to new episodes of MDD rather than the continuity of MDD from baseline to follow-up.

    “In a secondary analysis, individuals with current MDD at baseline were excluded rather than covaried in order to ensure that cortisol levels were predicting to new episodes of MDD, rather than the continuity of MDD from baseline to follow-up.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    Results appear to generalize both to the prediction of subclinical MDD and appear to be similar for males and females.

    “Thus, results appear to generalize both to the prediction of subclinical MDD and appear to be similar for males and females.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    The ideal analysis would remove all individuals with a past history of MDD, predicting only to first onsets of clinical MDD, but this was not possible due to the relatively small number of new onset clinical MDD cases (9 cases).

    “It is important to note that the ideal analysis would involve removing all the individuals who had a past history of MDD from the analysis, and thus predicting only to first onsets of clinical MDD. This approach is not possible due to the relatively small number of new onset clinical MDD cases occurring over the followup period (9 cases).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    There was a time delay (on average just over one month) between the baseline interview and the cortisol sampling.

    “One disadvantage of our design was the time delay (on average just over one month) between the baseline interview and the cortisol sampling.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Elevated CARs prospectively predict both new onsets and recurrences of depression over the year follow-up period.

    “Descriptively, our results suggest that elevated CARs prospectively predict both new onsets and recurrences of depression over the year followup period”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductnone given

    The two-sample CAR protocol is less precise and did not allow measurement of the area under the curve of the CAR response or separation of the CAR increase from the speed of recovery from the CAR peak.

    “the two sample protocol is less precise, and did not allow us to measure the area under the curve of the CAR response, or to separate the CAR increase from the speed of recovery from the CAR peak.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The study relied on noninvasive measures of HPA-axis function (daytime diurnal cortisol rhythm) rather than pharmacological challenges such as the dexamethasone suppression test.

    “Another disadvantage is that we relied on noninvasive measures of HPA-axis function (i.e., daytime diurnal cortisol rhythm) rather than employing pharmacological challenges (such as the dexamethasone suppression test)(Young et al., 2006) that provide more nuanced insights regarding the integrity of central HPA-axis function.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Results were robust to the removal of individuals with baseline MDD, the presence vs. absence of the covariates, and to the prediction of subclinical symptoms as well as clinical cases of MDD.

    “Results were also robust to the removal of individuals with baseline MDD, the presence vs. absence of the covariates, and to the prediction of subclinical symptoms as well as clinical cases of MDD.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    The study employed a simplified, two-sample protocol for the assessment of the CAR, rather than a more intensive protocol.

    “Another limitation, as noted earlier, is that we employed a simplified, two-sample protocol for the assessment of the CAR, rather than a more intensive protocol in which measures are gathered every 10 to 15 minutes, or even a moderate intensity CAR protocol in which samples are gathered at 0, 30 and 60 minutes after waking.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Life events measures and baseline CAR measures appeared to be independent predictors of MDD.

    “Rather, our life events measures and baseline CAR measures appeared to be independent predictors of MDD.”
    Quote in the paperSubstantial claim

  • Classified as probably not a substantial claim. May combine two claims.

    Study design and conductnone given

    The study utilized a large sample size (N=230) and gathered multiple morning cortisol samples timed in relation to person-specific wake-times each day over the course of 3 days.

    “We utilized a large sample size (N=230) and gathered multiple morning cortisol samples timed in relation to person-specific wake-times each day over the course of 3 days.”
    Quote in the paperSubstantial claim
42 of 42

  • The paper relies on this without support.

    The CAR protocol used (wake-up and 40 minutes post-waking) is a valid measure of the cortisol awakening response for predicting MDD, despite being less intensive than the original protocol.

    “It is important to note that this study was originally designed to examine multiple elements of the cortisol diurnal rhythm across the day, in addition to the CAR. As a result, in order to reduce participant burden, the protocol for the CAR is less intensive, and thus less precise, than the original CAR protocol, in which cortisol levels were obtained every 10 to 15 minutes after awakening (Pruess”

  • The paper relies on this without support.

    The baseline cortisol assessment on three consecutive weekdays captures stable individual differences in CAR that are relevant to MDD risk over the following year.

    “Salivary cortisol was gathered six times per day over three consecutive typical weekdays during the school year: at wake-up, 40 minutes after waking, at approximately 3, 8, and 12 hours post-awakening (signaled by a programmed watch), and bedtime.”
    “Each measure was averaged across the 3 collection days.”
2 of 2

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?

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.

  • Consistentt(228) = -0.62reported p = .54 · recomputed p = .536

    “t(228) = -.62, p = .54”

  • Consistentt(228) = -0.26reported p = .79 · recomputed p = .795

    “t(228) = -.26, p = .79”

2 of 2

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Self-check results appear here once an independent check has confirmed them.

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. Kirschbaum, 2000, Salivary cortisol, vol. 3

Cited by

Sorted by citations

Related

Authors
Adam, E. K., Doane, L. D., Zinbarg, R. E., Mineka, S., Craske, M. G., & Griffith, J. W.
Affiliations
  • Northwestern University (US)
  • University of California, Los Angeles (US)
Corresponding author
Adam, Emma K.
ORCID
Venue
Psychoneuroendocrinology
Publisher
Elsevier BV
Published
2010-07
Volume
35
Issue
6
Pages
921-931
ISSN
0306-4530 (ISSN-L)
DOI
10.1016/j.psyneuen.2009.12.007
PMC
PMC2875344
OpenAlex
W2097291981
Semantic Scholar
11f41924688e8a0d05917bbe43937f0b848ae34e
Cited by
315
References
64
Citations by year
2026: 9 · 2025: 13 · 2024: 10 · 2023: 12 · 2022: 26 · 2021: 24 · 2020: 15 · 2019: 17 · 2018: 23 · 2017: 21 · 2016: 27 · 2015: 30 · 2014: 25 · 2013: 23 · 2012: 22
FWCI
8.68
Type
journal article
Language
en
Open access
Licence
Locations
  • Psychoneuroendocrinology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (R01MH065652, R03MH063269, R01MH065651, 1 R01 MH65651-01, R01 MH65652)
Topics
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
  • Social Sciences › Psychology › Clinical Psychology › Child and Adolescent Psychosocial and Emotional Development
Keywords
cortisol awakening response, major depressive disorder, depression risk prediction, late adolescence, diurnal cortisol rhythm, basal cortisol, psychosocial stress, etiology of depression, premorbid risk factors
MeSH terms
Adolescent, Circadian Rhythm, Major Depressive Disorder, Female, Humans, Hydrocortisone, Male, Pituitary-Adrenal Function Tests, Predictive Value of Tests, Prospective Studies, Risk Factors, Saliva, Stress, Psychological, Wakefulness

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.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.

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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