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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)...
Abstract
Background

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.

Aims

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

Method

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.

Results

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.

Conclusions

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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Copyright
Corresponding author
Rebecca Carnegie, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK. Email: rebecca.carnegie@bristol.ac.uk
Footnotes
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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

None.

Footnotes
References
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1 Bhagwagar, Z, Hafizi, S, Cowen, PJ. Increased salivary cortisol after waking in depression. Psychopharmacology 2005; 182: 54–7.
2 Vreeburg, SA, Hoogendijk, WJ, van, Pelt J, Derijk, RH, Verhagen, JC, van, Dyck R, et al. Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry 2009; 66: 617–26.
3 Bhagwagar, Z, Hafizi, S, Cowen, PJ. Increase in concentration of waking salivary cortisol in recovered patients with depression. Am J Psychiatry 2003; 160: 1890–1.
4 Dougherty, LR, Klein, DN, Olino, TM, Dyson, M, Rose, S. Increased waking salivary cortisol and depression risk in preschoolers: the role of maternal history of melancholic depression and early child temperament. J Child Psychol Psychiatry 2009; 50: 1495–503.
5 Young, EA, Vazquez, D, Jiang, H, Pfeffer, CR. Saliva cortisol and response to dexamethasone in children of depressed parents. Biol Psychiatry 2006; 60: 831–6.
6 Vreeburg, SA, Hartman, CA, Hoogendijk, WJG, van, Dyck R, Zitman, FG, Ormel, J, et al. Parental history of depression or anxiety and the cortisol awakening response. Br J Psychiatry 2010; 197: 180–5.
7 Vinberg, M, Bennike, B, Kyvik, KO, Andersen, PK, Kessing, LV. Salivary cortisol in unaffected twins discordant for affective disorder. Psychiatry Res 2008; 161: 292301.
8 Mannie, ZN, Harmer, CJ, Cowen, PJ. Increased waking salivary cortisol levels in young people at familial risk of depression. Am J Psychiatry 2007; 164: 617–21.
9 van, Santen A, Vreeburg, SA, Van, der Does AJ, Spinhoven, P, Zitman, FG, Penninx, BW. Psychological traits and the cortisol awakening response: results from the Netherlands Study of Depression and Anxiety. Psychoneuroendocrinology 2011; 36: 240–8.
10 Pereira, AM, Tiemensma, J, Romijn, JA. Neuropsychiatric disorders in Cushing's syndrome. Neuroendocrinology 2010; 92 (suppl 1): 6570.
11 Patten, SB. Exogenous corticosteroids and major depression in the general population. J Psychosom Res 2000; 49: 447–9.
12 Halligan, SL, Herbert, J, Goodyer, I, Murray, L. Disturbances in morning cortisol secretion in association with maternal postnatal depression predict subsequent depressive symptomatology in adolescents. Biol Psychiatry 2007; 62: 40–6.
13 Ellenbogen, MA, Hodgins, S, Linnen, AM, Ostiguy, CS. Elevated daytime cortisol levels: a biomarker of subsequent major affective disorder? J Affect Disord 2011; 132: 265–9.
14 Goodyer, IM, Tamplin, A, Herbert, J, Altham, PME. Recent life events, cortisol, dehydroepiandrosterone and the onset of major depression in high-risk adolescents. Br J Psychiatry 2000; 177: 499504.
15 Harris, TO, Borsanyi, S, Messari, S, Stanford, K, Brown, GW, Cleary, SE, et al. Morning cortisol as a risk factor for subsequent major depressive disorder in adult women. Br J Psychiatry 2000; 177: 505–10.
16 Goodyer, IM, Bacon, A, Ban, M, Croudace, T, Herbert, J. Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents. Br J Psychiatry 2009; 195: 3945.
17 Adam, EK, Doane, LD, Zinbarg, RE, Mineka, S, Craske, MG, Griffith, JW. Prospective prediction of major depressive disorder from cortisol awakening responses in adolescence. Psychoneuroendocrinology 2010; 35: 921–31.
18 Herbert, J, Ban, M, Brown, GW, Harris, TO, Ogilvie, A, Uher, R, et al. Interaction between the BDNF gene Val/66/Met polymorphism and morning cortisol levels as a predictor of depression in adult women. Br J Psychiatry 2012; 201: 313–9.
19 Pariante, CM, Lightman, SL. The HPA axis in major depression: classical theories and new developments. Trends Neurosci 2008; 31: 464–8.
20 Knorr, U, Vinberg, M, Kessing, LV, Wetterslev, J. Salivary cortisol in depressed patients versus control persons: a systematic review and meta-analysis. Psychoneuroendocrinology 2010; 35: 1275–86.
21 Burke, HM, Davis, MC, Otte, C, Mohr, DC. Depression and cortisol responses to psychological stress: a meta-analysis. Psychoneuroendocrinology 2005; 30: 846–56.
22 Lopez-Duran, NL, Kovacs, M, George, CJ. Hypothalamic-pituitary-adrenal axis dysregulation in depressed children and adolescents: a meta-analysis. Psychoneuroendocrinology 2009; 34: 1272–83.
23 Adam, EK, Kumari, M. Assessing salivary cortisol in large-scale, epidemiological research. Psychoneuroendocrinology 2009; 34: 1423–36.
24 Wust, S, Federenko, I, Hellhammer, DH, Kirschbaum, C. Genetic factors, perceived chronic stress, and the free cortisol response to awakening. Psychoneuroendocrinology 2000; 25: 707–20.
25 Kuehner, C, Holzhauer, S, Huffziger, S. Decreased cortisol response to awakening is associated with cognitive vulnerability to depression in a nonclinical sample of young adults. Psychoneuroendocrinology 2007; 32: 199209.
26 Vrshek-Schallhorn, S, Doane, LD, Mineka, S, Zinbarg, RE, Craske, MG, Adam, EK. The cortisol awakening response predicts major depression: predictive stability over a 4-year follow-up and effect of depression history. Psychol Med 2013; 43: 483–93.
27 Halpern, CT, Whitsel, EA, Wagner, B, Harris, KM. Challenges of measuring diurnal cortisol concentrations in a large population-based field study. Psychoneuroendocrinology 2012; 37: 499508.
28 Boyd, A, Golding, J, Macleod, J, Lawlor, DA, Fraser, A, Henderson, J, et al. Cohort profile: the ‘Children of the 90s’–the index offspring of the Avon Longitudinal Study of Parents and Children. Int J Epidemiol 2013; 42: 111–27.
29 Fraser, A, Macdonald-Wallis, C, Tilling, K, Boyd, A, Golding, J, Davey, Smith G, et al. cohort profile: the Avon Longitudinal Study of Parents and Children: ALSPAC mothers cohort. Int J Epidemiol 2013; 42: 97110.
30 Lewis, G, Pelosi, AJ, Araya, R, Dunn, G. Measuring psychiatric disorder in the community: a standardized assessment for use by lay interviewers. Psychol Med 1992; 22: 465–86.
31 O'Donnell, KJ, Glover, V, Jenkins, J, Browne, D, Ben-Shlomo, Y, Golding, J, et al. Prenatal maternal mood is associated with altered diurnal cortisol in adolescence. Psychoneuroendocrinology 2013; 38: 1630–8.
32 Goodman, A, Heiervang, E, Collishaw, S, Goodman, R. The ‘DAWBA bands’ as an ordered-categorical measure of child mental health: description and validation in British and Norwegian samples. Soc Psychiatry Psychiatr Epidemiol 2011; 46: 521–32.
33 Angold, A, Costello, EJ, Messer, SC, Pickles, A, Winder, F, Silver, D. Development of a short questionnaire for use in epidemiological studies of depression in children and adolescents. Int J Method Psych 1995; 5: 237–49.
34 Cox, JL, Holden, JM, Sagovsky, R. Detection of postnatal depression. Development of the 10-Item Edinburgh Postnatal Depression Scale. Br J Psychiatry 1987; 150: 782–6.
35 World Health Organization. The ICD-10 Classification of Mental and Behavioural Disorders: Clinical Descriptions and Diagnostic Guidelines. WHO, 1992.
36 Hellhammer, J, Fries, E, Schweisthal, OW, Schlotz, W, Stone, AA, Hagemann, D. Several daily measurements are necessary to reliably assess the cortisol rise after awakening: state- and trait components. Psychoneuroendocrinology 2007; 32: 80–6.
37 O'Connor, TG, Ben-Shlomo, Y, Heron, J, Golding, J, Adams, D, Glover, V. Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children. Biol Psychiatry 2005; 58: 211–7.
38 White, IR, Royston, P, Wood, AM. Multiple imputation using chained equations: issues and guidance for practice. Stat Med 2011; 30: 377–99.
39 Moffitt, TE, Harrington, H, Caspi, A, Kim-Cohen, J, Goldberg, D, Gregory, AM, et al. Depression and generalized anxiety disorder - cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Arch Gen Psychiatry 2007; 64: 651–60.
40 Antonijevic, IA. Depressive disorders – is it time to endorse different pathophysiologies? Psychoneuroendocrinology 2006; 31: 115.
41 Hellhammer, DH, Wust, S, Kudielka, BM. Salivary cortisol as a biomarker in stress research. Psychoneuroendocrinology 2009; 34: 163–71.
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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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eLetters

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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