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Cortisol awakening response and subsequent depression: prospective longitudinal study

  • Rebecca Carnegie (a1), Ricardo Araya (a1), Yoav Ben-Shlomo (a2), Vivette Glover (a3), Thomas G. O'Connor (a4), Kieran J. O'Donnell (a5), Rebecca Pearson (a1) and Glyn Lewis (a6)...



Some studies have found an association between elevated cortisol and subsequent depression, but findings are inconsistent. The cortisol awakening response may be a more stable measure of hypothalamic–pituitary–adrenal function and potentially of stress reactivity.


To investigate whether salivary cortisol, particularly the cortisol awakening response, is associated with subsequent depression in a large population cohort.


Young people (aged 15 years, n = 841) from the Avon Longitudinal Study of Parents and Children (ALSPAC) collected salivary cortisol at four time points for 3 school days. Logistic regression was used to calculate odds ratios for developing depression meeting ICD-10 criteria at 18 years.


We found no evidence for an association between salivary cortisol and subsequent depression. Odds ratios for the cortisol awakening response were 1.24 per standard deviation (95% CI 0.93–1.66, P = 0.14) before and 1.12 (95% CI 0.73–1.72, P = 0.61) after adjustment for confounding factors. There was no evidence that the other cortisol measures, including cortisol at each time point, diurnal drop and area under the curve, were associated with subsequent depression.


Our findings do not support the hypothesis that elevated salivary cortisol increases the short-term risk of subsequent depressive illness. The results suggest that if an association does exist, it is small and unlikely to be of clinical significance.

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Corresponding author

Rebecca Carnegie, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. Email:


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The UK Medical Research Council (Grant reference: 74882), the Wellcome Trust (Grant reference: 076467) and the University of Bristol provide core support for ALSPAC. This research was supported by NIH grant R01 MH073842 to T.G.O'C., which funded the cortisol collection; Wellcome Trust grant 084268/2/07/Z to G.L., which funded the CIS-R; and the Wellcome Trust Institutional Strategic Support grant 097825.

Declaration of interest




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Cortisol awakening response and subsequent depression: prospective longitudinal study

  • Rebecca Carnegie (a1), Ricardo Araya (a1), Yoav Ben-Shlomo (a2), Vivette Glover (a3), Thomas G. O'Connor (a4), Kieran J. O'Donnell (a5), Rebecca Pearson (a1) and Glyn Lewis (a6)...
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Prospective exploration of the cortisol awakening response as a marker of vulnerability to depressive disorder

Richard Whale, Principal Lecturer, Consultant Psychiatrist
07 February 2014

We commend Carnegie et al., (1) for the methodological rigour and sample size of their study, and acknowledgement that interpretation of such data relies markedly on assumptions of adherence to cortisol sampling.

We raise their awareness to an earlier prospective study,(2) exploring a distinct subgroup as suggested by the authors, of patients highly vulnerable to depressive disorder within a period of months, having been exposed to interferon-alpha treatment. A greater pre-interferon-alpha treatment awakening cortisol response was observed in the group with treatment emergent major depressive disorder. Whilst interpretation and extrapolation to non iatrogenic depression is complex, the role of the cortisol awakening response in identifying depressive disorder vulnerability should not be excluded. We invite Carnegie et al. to comment on the effect of age on the cortisol awakening response and whether their study of an adolescent sample may bias against an association with later depression. A biological difference is potentially highlighted by the difference in efficacy of antidepressants between adolescent and adult samples.

(1)Carnegie R, Araya R, Ben-Shlomo Y, Glover V, O'Connor TG, O'Donnell KJ, Pearson R, Lewis G. Cortisol awakening response and subsequent depression: prospective longitudinal study.Br J Psychiatry 2014; 204: 165-168.

(2)Eccles J, Lallemant C, Mushtaq F, Greenwood M, Keller M, Golding B, Tibble J, Haq I, Whale R. Pre-treatment waking cortisol response and vulnerability to interferon alpha induced depression. Eur Neuropsychopharmacol 2012; 12: 892-896.

Richard Whale Principal Lecturer, Brighton and Sussex Medical SchoolConsultant Psychiatrist, Sussex Partnership NHS Foundation Trust

Division of Medical Education, Mayfield House, University of Brighton, Falmer BN1 9PH

Tel 01273 718682 Fax 01273 718683

Renata Fialho PhD Student, School of Psychology, University of Sussex, Brighton BN1 9RH

Jessica EcclesMRC Clinical Research Fellow Clinical Imaging Sciences Centre, Brighton and Sussex Medical School, Brighton BN1 9RR
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Conflict of interest: None declared

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