Archives of Women's Mental Health

, Volume 19, Issue 5, pp 789–797 | Cite as

Cortisol response to the Trier Social Stress Test in pregnant women at risk for postpartum depression

  • Kristina M. Deligiannidis
  • Aimee R. Kroll-Desrosiers
  • Abby Svenson
  • Nina Jaitly
  • Bruce A. Barton
  • Janet E. Hall
  • Anthony J. Rothschild
Original Article


Antepartum depression and anxiety are risk factors for postpartum depression (PPD). Postpartum abnormalities in hypothalamic-pituitary-adrenal (HPA) reactivity are associated with PPD. It is not known if antepartum HPA abnormalities exist in women at risk for PPD (AR-PPD). We measured salivary cortisol response to the Trier Social Stress Test (TSST) in 44 (24 AR-PPD, 20 healthy comparison) pregnant women. Depression and anxiety were measured using the Edinburgh Postnatal Depression Scale (EPDS) and Spielberger State-Trait Anxiety Inventory-State (STAI-S). We analyzed longitudinal changes in cortisol using generalized estimating equation methods to control for the correlation within subjects at the six TSST time points. Group differences in area under the curve (AUC) were examined. A majority (70.8 %) of the AR-PPD had prior depression. EPDS total score was higher in AR-PPD vs. comparison women (mean EPDS = 9.8 ± 4.9 vs. mean EPDS = 2.4 ± 2.0 respectively, p < 0.001). Mean STAI-S total score was higher in AR-PPD vs. comparison women at all TSST time points and over time (z = 2.71, df = 1, p = 0.007). There was no significant difference in cortisol concentration over time between groups. We observed no detectable difference in cortisol response to psychosocial stress induced by the TSST despite clinically significant between-group differences in current/past depression and current symptomatology.


Postpartum Cortisol Depression Anxiety 


  1. Austin MP, Hadzi-Pavlovic D, Priest SR, Reilly N, Wilhelm K, Saint K, Parker G (2010) Depressive and anxiety disorders in the postpartum period: how prevalent are they and can we improve their detection? Arch Womens Ment Health 13:395–401. doi:10.1007/s00737-010-0153-7 CrossRefPubMedGoogle Scholar
  2. Beck CT (2001) Predictors of postpartum depression: an update. Nurs Res 50:275–285CrossRefPubMedGoogle Scholar
  3. Bernstein DP, Fink L (1997) Childhood Trauma Questionnaire.
  4. Berrettini WH, Nurnberger JI Jr, Worthington EK, Simmons-Alling S, Gershon ES (1982) Platelet vasopressin receptors in bipolar affective illness. Psychiatry Res 7:83–86CrossRefPubMedGoogle Scholar
  5. Bloch M, Rubinow DR, Schmidt PJ, Lotsikas A, Chrousos GP, Cizza G (2005) Cortisol response to ovine corticotropin-releasing hormone in a model of pregnancy and parturition in euthymic women with and without a history of postpartum depression. J Clin Endocrinol Metab 90:695–699. doi:10.1210/jc.2004-1388 CrossRefPubMedGoogle Scholar
  6. Bolten M, Nast I, Skrundz M, Stadler C, Hellhammer DH, Meinlschmidt G (2013) Prenatal programming of emotion regulation: neonatal reactivity as a differential susceptibility factor moderating the outcome of prenatal cortisol levels. J Psychosom Res 75:351–357. doi:10.1016/j.jpsychores.2013.04.014 CrossRefPubMedGoogle Scholar
  7. Brunton PJ, Russell JA, Douglas AJ (2008) Adaptive responses of the maternal hypothalamic-pituitary-adrenal axis during pregnancy and lactation. J Neuroendocrinol 20:764–776. doi:10.1111/j.1365-2826.2008.01735.x CrossRefPubMedGoogle Scholar
  8. Buske-Kirschbaum A, von Auer K, Krieger S, Weis S, Rauh W, Hellhammer D (2003) Blunted cortisol responses to psychosocial stress in asthmatic children: a general feature of atopic disease? Psychosom Med 65:806–810CrossRefPubMedGoogle Scholar
  9. Buss C, Entringer S, Reyes JF, Chicz-DeMet A, Sandman CA, Waffarn F, Wadhwa PD (2009) The maternal cortisol awakening response in human pregnancy is associated with the length of gestation. Am J Obstet Gynecol 201(398):e391–398. doi:10.1016/j.ajog.2009.06.063 Google Scholar
  10. Carpenter LL et al (2007) Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol Psychiatry 62:1080–1087. doi:10.1016/j.biopsych.2007.05.002 CrossRefPubMedPubMedCentralGoogle Scholar
  11. Carpenter LL, Shattuck TT, Tyrka AR, Geracioti TD, Price LH (2011) Effect of childhood physical abuse on cortisol stress response. Psychopharmacol (Berl) 214:367–375. doi:10.1007/s00213-010-2007-4 CrossRefGoogle Scholar
  12. Cox JL, Holden JM, Sagovsky R (1987) Detection of postnatal depression. Development of the 10-item Edinburgh postnatal depression scale. Br J Psychiatry 150:782–786CrossRefPubMedGoogle Scholar
  13. Cox JL, Murray D, Chapman G (1993) A controlled study of the onset, duration and prevalence of postnatal depression. Br J Psychiatry 163:27–31CrossRefPubMedGoogle Scholar
  14. Cox EQ, Stuebe A, Pearson B, Grewen K, Rubinow D, Meltzer-Brody S (2015) Oxytocin and HPA stress axis reactivity in postpartum women. Psychoneuroendocrinology doi:
  15. De Weerth C, Wied GD, Jansen LM, Buitelaar JK (2007) Cardiovascular and cortisol responses to a psychological stressor during pregnancy. Acta Obstet Gynecol Scand 86:1181–1192. doi:10.1080/00016340701547442 CrossRefPubMedGoogle Scholar
  16. Diagnostic and Statistical Manual of Mental Disorders, DSM-5 (American Psychiatric Association, 2013). 5th Edition edn. American Psychiatric Publishing, Washington, D.C.Google Scholar
  17. Entringer S et al (2010) Attenuation of maternal psychophysiological stress responses and the maternal cortisol awakening response over the course of human pregnancy. Stress 13:258–268. doi:10.3109/10253890903349501 CrossRefPubMedPubMedCentralGoogle Scholar
  18. First MB, Spitzer RL, Gibbon M, Williams JBW (2001) Structured clinical interview for DSM-IV-TR axis I disorders—patient edition. Biometrics Research Department, New York State Psychiatric Institute, New YorkGoogle Scholar
  19. Fisher PA, Kim HK, Bruce J, Pears KC (2012) Cumulative effects of prenatal substance exposure and early adversity on foster children’s HPA axis reactivity during a psychosocial stressor. Int J Behav Dev 36:29–35. doi:10.1177/0165025411406863 CrossRefPubMedGoogle Scholar
  20. Giesbrecht GF, Campbell T, Letourneau N, Kaplan BJ (2013) Advancing gestation does not attenuate biobehavioural coherence between psychological distress and cortisol. Biol Psychol 93:45–51. doi:10.1016/j.biopsycho.2013.01.019 CrossRefPubMedGoogle Scholar
  21. Glynn LM, Wadhwa PD, Dunkel-Schetter C, Chicz-Demet A, Sandman CA (2001) When stress happens matters: effects of earthquake timing on stress responsivity in pregnancy. Am J Obstet Gynecol 184:637–642. doi:10.1067/mob.2001.111066 CrossRefPubMedGoogle Scholar
  22. Gozansky WS, Lynn JS, Laudenslager ML, Kohrt WM (2005) Salivary cortisol determined by enzyme immunoassay is preferable to serum total cortisol for assessment of dynamic hypothalamic-pituitary-adrenal axis activity. Clin Endocrinol 63:336–341. doi:10.1111/j.1365-2265.2005.02349.x CrossRefGoogle Scholar
  23. Hampson E, Phillips SD, Soares CN, Steiner M (2013) Steroid concentrations in antepartum and postpartum saliva: normative values in women and correlations with serum. Biol Sex Differ 4:7. doi:10.1186/2042-6410-4-7 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Hansen AM, Garde AH, Persson R (2008) Measurement of salivary cortisol—effects of replacing polyester with cotton and switching antibody. Scand J Clin Lab Invest 68:826–829. doi:10.1080/00365510802056207 CrossRefPubMedGoogle Scholar
  25. Harville EW, Savitz DA, Dole N, Herring AH, Thorp JM (2009) Stress questionnaires and stress biomarkers during pregnancy. J Womens Health (Larchmt) 18:1425–1433CrossRefGoogle Scholar
  26. Heim C et al (2000) Pituitary-adrenal and autonomic responses to stress in women after sexual and physical abuse in childhood. Jama 284:592–597CrossRefPubMedGoogle Scholar
  27. Hellgren C, Akerud H, Skalkidou A, Sundstrom-Poromaa I (2013) Cortisol awakening response in late pregnancy in women with previous or ongoing depression. Psychoneuroendocrinology 38:3150–3154. doi:10.1016/j.psyneuen.2013.08.007 CrossRefPubMedGoogle Scholar
  28. Hoenig JM, Heisey DM (2001) The abuse of power: the pervasive fallacy of power calculations for data analysis. Am Stat 55:19–24CrossRefGoogle Scholar
  29. Kane HS, Dunkel Schetter C, Glynn LM, Hobel CJ, Sandman CA (2014) Pregnancy anxiety and prenatal cortisol trajectories. Biol Psychol 100:13–19. doi:10.1016/j.biopsycho.2014.04.003 CrossRefPubMedPubMedCentralGoogle Scholar
  30. King NM, Chambers J, O'Donnell K, Jayaweera SR, Williamson C, Glover VA (2010) Anxiety, depression and saliva cortisol in women with a medical disorder during pregnancy. Arch Womens Ment Health 13:339–345. doi:10.1007/s00737-009-0139-5 CrossRefPubMedGoogle Scholar
  31. Kirschbaum C, Pirke K, Hellhammer D (1993) The ‘Trier Social Stress Test’—a tool for investigating psychobiological stress responses in a laboratory setting. Neuropsychobiology 28:76–81CrossRefPubMedGoogle Scholar
  32. Labad J et al (2011) Increased morning adrenocorticotrophin hormone (ACTH) levels in women with postpartum thoughts of harming the infant. Psychoneuroendocrinology 36:924–928. doi:10.1016/j.psyneuen.2010.11.006 CrossRefPubMedGoogle Scholar
  33. Lord C, Hall G, Soares CN, Steiner M (2011) Physiological stress response in postpartum women with obsessive-compulsive disorder: a pilot study. Psychoneuroendocrinology 36:133–138. doi:10.1016/j.psyneuen.2010.04.014 CrossRefPubMedGoogle Scholar
  34. Lydsdottir LB, Howard LM, Olafsdottir H, Thome M, Tyrfingsson P, Sigurdsson JF (2014) The mental health characteristics of pregnant women with depressive symptoms identified by the Edinburgh postnatal depression scale. J Clin Psychiatry 75:393–398. doi:10.4088/JCP.13m08646 CrossRefPubMedGoogle Scholar
  35. Magiakou MA, Mastorakos G, Rabin D, Dubbert B, Gold PW, Chrousos GP (1996) Hypothalamic corticotropin-releasing hormone suppression during the postpartum period: implications for the increase in psychiatric manifestations at this time. J Clin Endocrinol Metab 81:1912–1917PubMedGoogle Scholar
  36. Mastorakos G, Ilias I (2003) Maternal and fetal hypothalamic-pituitary-adrenal axes during pregnancy and postpartum. Ann N Y Acad Sci 997:136–149CrossRefPubMedGoogle Scholar
  37. Meijer JL et al (2014) Predictive accuracy of Edinburgh postnatal depression scale assessment during pregnancy for the risk of developing postpartum depressive symptoms: a prospective cohort study. BJOG:Int J Obstet Gynaecol 121:1604–1610. doi:10.1111/1471-0528.12759 CrossRefGoogle Scholar
  38. Meinlschmidt G, Martin C, Neumann ID, Heinrichs M (2010) Maternal cortisol in late pregnancy and hypothalamic-pituitary-adrenal reactivity to psychosocial stress postpartum in women. Stress 13:163–171. doi:10.3109/10253890903128632 CrossRefPubMedGoogle Scholar
  39. Milgrom J et al (2008) Antenatal risk factors for postnatal depression: a large prospective study. J Affect Disord 108:147–157. doi:10.1016/j.jad.2007.10.014 CrossRefPubMedGoogle Scholar
  40. Nierop A, Bratsikas A, Klinkenberg A, Nater UM, Zimmermann R, Ehlert U (2006a) Prolonged salivary cortisol recovery in second-trimester pregnant women and attenuated salivary alpha-amylase responses to psychosocial stress in human pregnancy. J Clin Endocrinol Metab 91:1329–1335. doi:10.1210/jc.2005-1816 CrossRefPubMedGoogle Scholar
  41. Nierop A, Bratsikas A, Zimmermann R, Ehlert U (2006b) Are stress-induced cortisol changes during pregnancy associated with postpartum depressive symptoms? Psychosom Med 68:931–937. doi:10.1097/01.psy.0000244385.93141.3b CrossRefPubMedGoogle Scholar
  42. Nolten WE, Lindheimer MD, Rueckert PA, Oparil S, Ehrlich EN (1980) Diurnal patterns and regulation of cortisol secretion in pregnancy. J Clin Endocrinol Metab 51:466–472CrossRefPubMedGoogle Scholar
  43. O'Connor TG, Tang W, Gilchrist MA, Moynihan JA, Pressman EK, Blackmore ER (2014) Diurnal cortisol patterns and psychiatric symptoms in pregnancy: short-term longitudinal study. Biol Psychol 96:35–41. doi:10.1016/j.biopsycho.2013.11.002 CrossRefPubMedGoogle Scholar
  44. O'Hara MW, Swain A (1996) Rates and risk of postpartum depression—a meta-analysis. Int Rev Psychiatry 8:37–54CrossRefGoogle Scholar
  45. O'Keane V et al (2011) Increased pituitary-adrenal activation and shortened gestation in a sample of depressed pregnant women: a pilot study. J Affect Disord 130:300–305. doi:10.1016/j.jad.2010.10.004 CrossRefPubMedGoogle Scholar
  46. Ostergaard SD, Fava M, Rothschild AJ, Deligiannidis KM (2014) The implications of the national institute of mental health research domain criteria for researchers and clinicians. Acta Psychiatr Scand 130:409–414. doi:10.1111/acps.12331 CrossRefPubMedGoogle Scholar
  47. Pruessner JC, Kirschbaum C, Meinlschmid G, Hellhammer DH (2003) Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28:916–931CrossRefPubMedGoogle Scholar
  48. Righetti-Veltema M, Conne-Perreard E, Bousquet A, Manzano J (1998) Risk factors and predictive signs of postpartum depression. J Affect Disord 49:167–180CrossRefPubMedGoogle Scholar
  49. Rothenberger SE, Moehler E, Reck C, Resch F (2011) Prenatal stress: course and interrelation of emotional and physiological stress measures. Psychopathology 44:60–67. doi:10.1159/000319309 CrossRefPubMedGoogle Scholar
  50. Schiller CE, Meltzer-Brody S, Rubinow DR (2014) The role of reproductive hormones in postpartum depression. CNS Spectr 20:1–12. doi:10.1017/s1092852914000480 Google Scholar
  51. Schulte HM, Weisner D, Allolio B (1990) The corticotrophin releasing hormone test in late pregnancy: lack of adrenocorticotrophin and cortisol response. Clin Endocrinol 33:99–106CrossRefGoogle Scholar
  52. Shea AK, Streiner DL, Fleming A, Kamath MV, Broad K, Steiner M (2007) The effect of depression, anxiety and early life trauma on the cortisol awakening response during pregnancy: preliminary results. Psychoneuroendocrinology 32:1013–1020. doi:10.1016/j.psyneuen.2007.07.006 CrossRefPubMedGoogle Scholar
  53. Simon R (1986) Confidence intervals for reporting results of clinical trials. Ann Intern Med 105:429–435CrossRefPubMedGoogle Scholar
  54. Smith R et al (1990) Mood changes, obstetric experience and alterations in plasma cortisol, beta-endorphin and corticotrophin releasing hormone during pregnancy and the puerperium. J Psychosom Res 34:53–69CrossRefPubMedGoogle Scholar
  55. Stowe ZN, Nemeroff CB (1995) Women at risk for postpartum-onset major depression. Am J Obstet Gynecol 173:639–645CrossRefPubMedGoogle Scholar
  56. Taylor A, Glover V, Marks M, Kammerer M (2009) Diurnal pattern of cortisol output in postnatal depression. Psychoneuroendocrinology 34:1184–1188. doi:10.1016/j.psyneuen.2009.03.004 CrossRefPubMedGoogle Scholar
  57. Tu MT, Lupien SJ, Walker CD (2005) Measuring stress responses in postpartum mothers: perspectives from studies in human and animal populations. Stress 8:19–34. doi:10.1080/10253890500103806 CrossRefPubMedGoogle Scholar
  58. Voegtline KM, Costigan KA, Kivlighan KT, Laudenslager ML, Henderson JL, DiPietro JA (2013) Concurrent levels of maternal salivary cortisol are unrelated to self-reported psychological measures in low-risk pregnant women. Arch Womens Ment Health 16:101–108. doi:10.1007/s00737-012-0321-z CrossRefPubMedGoogle Scholar
  59. Vreeburg SA et al (2009) Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study. Arch Gen Psychiatry 66:617–626. doi:10.1001/archgenpsychiatry.2009.50 CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Wien 2016

Authors and Affiliations

  1. 1.Center for Psychopharmacologic Research and Treatment, Department of PsychiatryUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Women’s Mental Health Program, Departments of Psychiatry and Obstetrics and GynecologyUniversity of Massachusetts Medical School, UMass Memorial Medical CenterWorcesterUSA
  3. 3.Department of Quantitative Health SciencesUniversity of Massachusetts Medical SchoolWorcesterUSA
  4. 4.National Institute of Environmental Health Sciences, National Institutes of HealthResearch Triangle ParkUSA
  5. 5.Reproductive Endocrine UnitMassachusetts General Hospital/Harvard Medical SchoolBostonUSA

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