The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history

Classified as probably not a substantial claim.

The CAR captures a large and rapid increase on top of already elevated waking cortisol levels.

“The CAR is thought to be an important indicator of risk for major depressive episodes (MDE) in part because it captures a large and rapid increase on top of already elevated waking cortisol levels (Adam et al. 2010)”

• cites Adam et al. 2010 sourceSupported

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

The CAR serves to mobilize resources to meet the perceived demands of the upcoming day.

“current theory suggests that it serves to mobilize resources to meet the perceived demands of the upcoming day (e.g. Adam et al. 2006; Fries et al. 2009).”

• cites Adam et al. 2006 sourceSupported
• cites Fries et al. 2009 sourceNot checked — no full text of the source

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

Current theory posits that the CAR functions to prepare the individual to rise to the expected demands of the upcoming day.

“Current theory posits that the CAR functions to prepare the individual to rise to the expected demands of the upcoming day (Adam et al. 2006; Fries et al. 2009); thus, the presence of the CAR can be seen as adaptive.”

• cites Adam et al. 2006 sourceSupported
• cites Fries et al. 2009 sourceNot checked — no full text of the source

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

Flattened diurnal cortisol slopes may serve as a marker of the day's levels of negative emotions such as tension and anger, leading to elevated evening cortisol levels.

“By contrast, flattened diurnal cortisol slopes may serve as a marker of the day’s levels of negative emotions such as tension and anger, leading to elevated evening cortisol levels (Adam et al. 2006).”

• cites Adam et al. 2006 sourceSupported

Classified as probably not a substantial claim.

Our prior report after a 1-year follow-up presented descriptive data supporting that both first onsets and recurrences of MDE were predicted by elevations in the CAR.

“While our prior report after a 1-year follow-up presented descriptive data supporting that both first onsets and recurrences of MDE were predicted by elevations in the CAR (Adam et al. 2010)”

• cites Adam et al. 2010 sourceSupported

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

Prior research has demonstrated unique effects of elevated morning cortisol and of stressful life events in the month prior to depressive onset.

“prior research has demonstrated unique effects of elevated morning cortisol and of stressful life events in the month prior to depressive onset (Goodyer et al. 2000)”

• cites Goodyer et al. 2000 sourcePartly supported

  In “Peak hormones, life events and depressive symptoms at entry” (page unavailable), the paper reports separate associations of 08.00 h cortisol peaks and disappointments or losses in the month closest to onset with subsequent depression. The claim is broader than the finding: the predictive cortisol measure was a peak, not elevated absolute cortisol levels, and the significant life events were specifically disappointments and losses. (LLM, conf=0.84)

  Experimental — accuracy not yet measured

May combine two claims.

The CAR × time interaction was significant; the predictive power of the CAR degraded about 3% per month with successive months.

“The CAR × time interaction was also significant; the predictive power of the CAR degraded (about 3% per month) with successive months (Table 3, model 1).”

May combine two claims.

The simple main effect of CAR, indicating its relationship to first onsets of MDE, remained significant, as did the CAR × time interaction.

“When this MDE history × CAR interaction was added, the simple main effect of CAR, indicating its relationship to first onsets of MDE, remained significant, as did the CAR × time interaction.”

May combine two claims.

When a maximum of one prospective MDE onset per person is considered, the CAR significantly predicts both first onsets and recurrences of depression, but predicts recurrences with greater strength than first onsets.

“In addition, the results showed that when a single prospective MDE onset per person is considered, the CAR significantly predicts both first onsets and recurrences of depression, but that the CAR predicts recurrences with greater strength than it predicts first onsets.”

• Also stated in: § Conclusions · plain

  “Third, while the CAR predicts both first onsets and recurrences of depression when a maximum of one prospective MDE onset per person is considered, it predicts recurrences with greater strength than first onsets.”

May combine two claims.

After adding other known predictors and potential confounders (neuroticism, anxiety/history of MDE, life stress, negative affect/fatigue), the CAR and its interaction with time remained significant predictors of MDEs with very similar hazard ratios as in the primary model.

“Although in each case the additional block made a significant contribution to predicting onsets of MDE [all block changes in χ2 (df≤2) ≥13.60, all p’s <0.05], the CAR and its interaction with time remained significant predictors of MDEs with very similar HRs as in the primary model.”

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

A total of 10,723 person-months were available for analysis of MDE onsets for the primary model.

“A total of 10 723 person-months were available for analysis of MDE onsets for the primary model.”

May combine two claims.

Elevated CARs significantly predicted first onsets, but predicted recurrences with greater strength.

“Whereas elevated CARs significantly predicted first onsets, they predicted recurrences with greater strength.”

• Also stated in: § Discussion · plain

  “In addition, the results showed that when a single prospective MDE onset per person is considered, the CAR significantly predicts both first onsets and recurrences of depression, but that the CAR predicts recurrences with greater strength than it predicts first onsets.”

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

When person-months without LSI data were excluded, 9645 person-months were available, including 39 MDE onsets.

“When person-months without LSI data were excluded, a total of 9645 person-months were available, including 39 MDE onsets.”

May combine two claims.

The CAR significantly predicts MDEs in the sample up to 30 months (2.5 years), but not significantly at 36 months and beyond.

“Results also indicate that the CAR significantly predicts MDEs in our sample up to 30 months, or 2.5 years, but not significantly so at 36 months and beyond.”

• Also stated in: § Conclusions · boosted

  “This is the first study to demonstrate that the CAR predicts depression onsets for 2.5 years of a 4-year follow-up, initially serving as a strong predictor but ‘decaying’ in its predictive ability with the passage of time.”

May combine two claims.

Maximal effects were seen shortly after cortisol measurement, with a one standard deviation increase in the CAR corresponding to a roughly 3.5-fold increase in risk for MDE onset.

“As implied by the linear decline in prediction over time, maximal effects were seen shortly after cortisol measurement, with a one standard deviation increase in the CAR corresponding to a roughly 3.5-fold increase in risk for MDE onset (Fig. 1).”

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

A total of 42 major depressive episodes (MDEs) were observed after participation in the cortisol protocol: 35 in females, 7 in males; 27 first onsets and 15 recurrences; time to onset ranged from less than 1 month to 53 months.

“A total of 42 MDEs were observed (35 in females, seven in males; 27 first onsets, 15 recurrences) after participation in the cortisol protocol, with time to onset ranging from less than 1 month to 53 months.”

May combine two claims.

Both the CAR and major stressful life events predict MDEs uniquely and independently of one another.

“The results indicate that both the CAR and major events predict MDEs uniquely and independently of one another.”

May combine two claims.

In the final primary model, the CAR was a significant prospective predictor of MDEs; at the median of time (21 months), any one standard deviation increase in the CAR is associated with approximately double the risk for MDE onset.

“In the final primary model, the CAR was a significant prospective predictor of MDEs; at the median of time (21 months), any one standard deviation increase in the CAR is associated with approximately double the risk for MDE onset.”

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

The CAR is a pronounced increase in cortisol level (on average 50-60%) that peaks approximately 30 to 40 min after waking.

“the cortisol awakening response (CAR) – the pronounced (on average, 50–60%) increase in cortisol level that peaks approximately 30 to 40 min after waking (Pruessner et al. 1997).”

• cites Pruessner et al. 1997 sourceNot checked — no full text of the source

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

The CAR represents a true response to waking, rather than an underlying diurnal rhythm.

“Experimental research indicates that the CAR represents a true response to waking, rather than an underlying diurnal rhythm (Wilhelm et al. 2007).”

• cites Wilhelm et al. 2007 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, and particularly the hormone cortisol, has been implicated in the etiology of major depressive disorder by animal and cross-sectional human research.

“Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, and particularly the hormone cortisol, has been implicated in the etiology of major depressive disorder by a large body of animal research and cross-sectional research in humans (Chrousos & Gold, 1992; Ehlert et al. 2001).”

• cites Chrousos & Gold, 1992Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Ehlert et al. 2001 sourceNot checked — no full text of the source

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

The CAR is frequently operationalized as the difference between salivary cortisol sampled immediately after waking and the level sampled 30 to 40 min after waking.

“The CAR is frequently operationalized as the difference between the level of salivary cortisol sampled immediately after waking and the level sampled 30 to 40 min after waking (Clow et al. 2010).”

• cites Clow et al. 2010 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Major stressful life events precipitate MDEs, often within the month after the event.

“Major stressful life events are known to precipitate MDEs, often within the month after the occurrence of an event (Kendler et al. 1999).”

• cites Kendler et al. 1999 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

All diagnoses reported were clinically significant manifestations.

“All diagnoses reported here were clinically significant manifestations.”

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

Inter-rater reliability for MDE diagnoses across five assessment periods was high (k ranged 0.82 to 0.94, mean 0.89, s.d. 0.05).

“Across the five assessment periods, k for individual interviewers’ diagnoses of MDEs, adjusted due to departure from equiprobability (R. Zinbarg et al. unpublished observations), ranged from 0.82 to 0.94 (mean = 0.89, s.d. = 0.05).”

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

Participants included in analyses did not differ significantly from those excluded in gender, minority race/ethnicity, or baseline Hollingshead socio-economic status.

“Participants who were included in analyses did not differ significantly from those who were excluded in: gender [χ2(1) = 0.79, n.s.]; minority race/ethnicity [χ2(1) = 3.29, n.s.]; or baseline Hollingshead socio-economic status level [F(1, 334) = 0.66, n.s.].”

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

Inter-rater reliability for episodic life stress severity ratings cross-site ranged from 0.69 to 0.76 (mean 0.72, s.d. 0.03).

“Inter-rater reliability (intra-class correlations) cross-site for the five interviews examined ranged from 0.69 to 0.76 (mean = 0.72, s.d. = 0.03).”

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

Inter-rater reliability for the baseline chronic stress composite score was 0.87 within site and 0.84 across sites.

“Inter-rater reliability (intra-class correlations) for the baseline chronic stress composite score was 0.87 within site and 0.84 across sites.”

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

Frequent large CAR values may indicate excessive perceived demands and/or insufficient perceived resources to meet those demands.

“However, frequent large CAR values may indicate excessive perceived demands and/or insufficient perceived resources (e.g. competencies and social support) to meet those demands.”

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

Cortisol assay intra-assay variation ranged from 4.0% to 6.7%, and inter-assay variation ranged from 7.1% to 9.0%.

“Intra-assay variation ranged from 4.0% to 6.7%, while inter-assay variation ranged from 7.1% to 9.0%.”

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

The study used non-proportional hazards models that do not assume the hazard associated with a predictor is constant across time, permitting examination of interactions with time.

“In order to examine the predictive stability of the CAR, non-proportional hazards models were employed. Unlike proportional hazards models, such models do not assume that the hazard associated with a particular predictor is constant across time, permitting the examination of interactions with time (Singer & Willett, 2003).”

• cites Singer & Willett, 2003 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Temporal precedence of stressful life events and MDE onsets was carefully scrutinized; events with indeterminate order or occurring after MDE onset were excluded.

“Whether life events indicated as occurring in the same month as MDE onsets in fact occurred before the MDE onsets (i.e. temporal precedence) was carefully scrutinized. When the order of the event and the MDE onset was indeterminate, or when the event clearly occurred after the MDE onset, that event was excluded from consideration.”

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

A maximum of one MDE onset per participant was included; once a participant experienced an MDE onset after cortisol measurement, their remaining months were not included.

“A maximum of one MDE onset per participant was included in the model, whether that MDE represented a first onset or a recurrence of MDE; that is, once a participant experienced an MDE onset after cortisol measurement, their remaining months were not included.”

Classified as probably not a substantial claim.

Earlier age of first onset is associated with a worse course of illness.

“Earlier age of first onset is associated with a worse course of illness (Boland & Keller, 2009) and may account for the observed effect.”

• cites Boland & Keller, 2009Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

A high CAR represents a time-limited risk factor for onsets of MDEs, which increases risk for depression independently of future major stressful life events.

“These results suggest that a high CAR represents a time-limited risk factor for onsets of MDEs, which increases risk for depression independently of future major stressful life events.”

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

Interviewers were blind to the results of previous assessments.

“Interviewers were blind to the results of previous assessments.”

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

Flattened diurnal slopes are suggested to serve as a 'scar' marker for prior depression.

“Flattened diurnal slopes are also suggested to serve as a ‘scar’ marker for prior depression (Doane et al. in press), suggesting they may indicate allostatic load associated with accommodating recent psychopathology, among other stressors.”

• cites Doane et al. in pressNot matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

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

Major stressful life events were examined in an aggregate fashion.

“Second, although the examination of stressful life events in person-month format represents an advancement over other approaches, we have examined major stressful life events in an aggregate fashion.”

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

Only two samples were collected to define the CAR (0 and 40 min after waking), rather than the original approach of samples taken every 10-15 min for 1 h after waking.

“First, due to concerns about feasibility with 17-year-olds and participant burden, only two samples were collected to define the CAR (0 and 40 min after waking), rather than the original approach, which relied on samples taken every 10–15 min for 1 h after waking (Pruessner et al. 1997).”

• cites Pruessner et al. 1997 sourceNot checked — no full text of the source

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

The study cannot rule out a developmental interpretation whereby the CAR's interaction with time indicates that the CAR was particularly important during the age range closest to the CAR measurement (roughly ages 17 to 19 years), rather than a decay in predictive ability.

“Third, we cannot rule out a developmental interpretation whereby the CAR’s interaction with time indicates that the CAR was particularly important during the age range closest to the CAR measurement (i.e. roughly ages 17 to 19 years), rather than a decay in predictive ability.”

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

The number of onsets among males remains too low to address whether the CAR's relation to prospective MDE onsets differed between males and females (seven cases).

“Fourth, we would have liked to examine whether the CAR’s relation to prospective MDE onsets differed between males and females, i.e. a gender × CAR interaction; however, the number of onsets among males remains too low to address this question (seven cases).”

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

The CAR appears to be regulated by a range of factors, including extra-pituitary efferent pathways from the suprachiasmatic nucleus to the adrenal influencing sensitivity to adrenocorticotropic hormone (ACTH), and a role for hippocampal functioning, perhaps particularly pre-awakening.

“Further, the CAR appears to be regulated by a range of factors, including extra-pituitary efferent pathways from the suprachiasmatic nucleus to the adrenal influencing sensitivity to adrenocorticotropic hormone (ACTH), and a role for hippocampal functioning, perhaps particularly pre-awakening (Clow et al. 2010).”

• cites Clow et al. 2010 sourceNot checked — no full text of the source