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Sensitivity to stress among the offspring of parents with bipolar disorder: a study of daytime cortisol levels

  • C. S. Ostiguy (a1), M. A. Ellenbogen (a1), C.-D. Walker (a2), E. F. Walker (a3) and S. Hodgins (a4) (a5) (a6)...

It is well known that the hypothalamic–pituitary–adrenal (HPA) axis is compromised in major depression and bipolar disorder. There is increasing evidence that subtle HPA abnormalities, such as elevated cortisol levels, precede the development of an affective disorder. Interpersonal stress is also associated with the development of affective disorders. The present study sought to determine whether interpersonal chronic and episodic stress moderated the relationship between cortisol levels in the natural environment and risk status, defined as having a parent with bipolar disorder.


Sixty-two offspring of parents with bipolar disorder (OBD) and 60 offspring with no family history of affective disorders (OFH−), aged 19.48 years (s.d.=3.38, range 14–28), completed interviews assessing mental disorders and chronic and episodic stress, and provided saliva samples over 3 days.


Regression analyses revealed that the OBD who experienced high interpersonal chronic stress displayed a larger cortisol rise following awakening than the OBD reporting low interpersonal chronic stress. The same relationship was also found for levels of non-interpersonal chronic stress. The OBD who reported experiencing severe interpersonal episodic stress exhibited higher levels of daytime cortisol than the OBD reporting interpersonal episodic stress of mild severity. Importantly, none of the above relationships were detected in the OFH−. Each of the interactions between family history of affective disorders and stress remained after controlling for age, gender and offspring lifetime affective disorders and current non-affective disorders.


A biological sensitivity to stress may underlie the susceptibility to affective disorders among the OBD.

Corresponding author
*Address for correspondence: M. A. Ellenbogen, Ph.D., Concordia University, Department of Psychology, 7141 Sherbrooke W., Montréal, QC, CanadaH4B 1R6. (Email:
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C Adrian , C Hammen (1993). Stress exposure and stress generation in children of depressed mothers. Journal of Consulting and Clinical Psychology 61, 354359.

LB Alloy , LY Abramson , PD Walshaw , J Keyser , RK Gerstein (2006). A cognitive vulnerability-stress perspective on bipolar spectrum disorders in a normative adolescent brain, cognitive, and emotional development context. Development and Psychopathology 18, 10551103.

SB Ashman , G Dawson , H Panagiotides , E Yamada , CW Wilkinson (2002). Stress hormone levels of children of depressed mothers. Development and Psychopathology 14, 333349.

Z Bhagwagar , S Hafizi , PJ Cowen (2005). Increased salivary cortisol after waking in depression. Psychopharmacology 182, 5457.

B Birmaher , D Axelson , K Monk , C Kalas , B Goldstein , MB Hickey , M Obreja , M Ehmann , S Iyengar , W Shamseddeen , D Kupfer , D Brent (2009). Lifetime psychiatric disorders in school-aged offspring of parents with bipolar disorder: the Pittsburgh Bipolar Offspring study. Archives of General Psychiatry 66, 287296.

A Caspi , K Sugden , TE Moffitt , A Taylor , IW Craig , H Harrington , J McClay , J Mill , J Martin , A Braithwaite , R Poulton (2003). Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 301, 386389.

KD Chang , C Blasey , TA Ketter , H Steiner (2001). Family environment of children and adolescents with bipolar parents. Bipolar Disorders 3, 7378.

Y Chida , A Steptoe (2009). Cortisol awakening response and psychosocial factors: a systematic review and meta-analysis. Biological Psychology 80, 265278.

A Clow , L Thorn , P Evans , F Hucklebridge (2004). The awakening cortisol response: methodological issues and significance. Stress 7, 2937.

ER de Kloet , H Karst , M Joels (2008). Corticosteroid hormones in the central stress response: quick-and-slow. Frontiers in Neuroendocrinology 29, 268272.

NK Eberhart , CL Hammen (2006). Interpersonal predictors of onset of depression during the transition to adulthood. Personal Relationships 13, 195206.

S Edwards , A Clow , P Evans , F Hucklebridge (2001). Exploration of the awakening cortisol response in relation to diurnal cortisol secretory activity. Life Sciences 68, 20932103.

MA Ellenbogen , S Hodgins (2004). The impact of high neuroticism in parents on children's psychosocial functioning in a population at high risk for major affective disorder: a family-environmental pathway of intergenerational risk. Development and Psychopathology 16, 113136.

MA Ellenbogen , S Hodgins (2009). Structure provided by parents in middle childhood predicts cortisol reactivity in adolescence among the offspring of parents with bipolar disorder and controls. Psychoneuroendocrinology 34, 773785.

MA Ellenbogen , S Hodgins , A-M Linnen , CS Ostiguy (2011). Elevated daytime cortisol levels: a biomarker of subsequent major affective disorders? Journal of Affective Disorders. Published online: 15 February 2011. doi: 10.1016/j.jad.2011.01.007.

MA Ellenbogen , S Hodgins , CD Walker , S Couture , S Adam (2006). Daytime cortisol and stress reactivity in the offspring of parents with bipolar disorder. Psychoneuroendocrinology 31, 11641180.

MA Ellenbogen , JB Santo , AM Linnen , CD Walker , S Hodgins (2010). High cortisol levels in the offspring of parents with bipolar disorder during two weeks of daily sampling. Bipolar Disorders 12, 7786.

EP Espejo , CL Hammen , NP Connolly , PA Brennan , JM Najman , W Bor (2006). Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders. Journal of Abnormal Child Psychology 35, 287299.

P Gallagher , S Watson , MS Smith , AH Young , IN Ferrier (2007). Plasma cortisol-dehydroepiandrosterone (DHEA) ratios in schizophrenia and bipolar disorder. Schizophrenia Research 90, 258265.

IM Goodyer , A Bacon , M Ban , T Croudace , J Herbert (2009). Serotonin transporter genotype, morning cortisol and subsequent depression in adolescents. British Journal of Psychiatry 195, 3945.

IM Goodyer , J Herbert , A Tamplin , PM Altham (2000). Recent life events, cortisol, dehydroepiandrosterone and the onset of major depression in high-risk adolescents. British Journal of Psychiatry 177, 499504.

IH Gotlib , J Joormann , KL Minor , J Hallmayer (2008). HPA axis reactivity: a mechanism underlying the associations among 5-HTTLPR, stress, and depression. Biological Psychiatry 63, 847851.

SL Halligan , J Herbert , IM Goodyer , L Murray (2004). Exposure to postnatal depression predicts elevated cortisol in adolescent offspring. Biological Psychiatry 55, 376381.

C Hammen (1991). Generation of stress in the course of unipolar depression. Journal of Abnormal Psychology 100, 555561.

C Hammen (2003). Social stress and women's risk for recurrent depression. Archives of Women's Mental Health 6, 9–13.

C Hammen (2005). Stress and depression. Annual Review of Clinical Psychology 1, 293319.

C Hammen , EY Kim , NK Eberhart , PA Brennan (2009). Chronic and acute stress and the prediction of major depression in women. Depression and Anxiety 26, 718723.

C Hammen , J Shih , T Altman , PA Brennan (2003). Interpersonal impairment and the prediction of depressive symptoms in adolescent children of depressed and nondepressed mothers. Journal of the American Academy of Child and Adolescent Psychiatry 42, 571577.

BL Hankin (2008). Cognitive vulnerability-stress model of depression during adolescence: investigating depressive symptom specificity in a multi-wave prospective study. Journal of Abnormal Child Psychology 36, 999–1014.

BL Hankin , LS Badanes , JR Abela , SE Watamura (2010). Hypothalamic-pituitary-adrenal axis dysregulation in dysphoric children and adolescents: cortisol reactivity to psychosocial stress from preschool through middle adolescence. Biological Psychiatry 68, 484490.

MH Hillegers , H Burger , M Wals , CG Reichart , FC Verhulst , WA Nolen , J Ormel (2004). Impact of stressful life events, familial loading and their interaction on the onset of mood disorders: study in a high-risk cohort of adolescent offspring of parents with bipolar disorder. British Journal of Psychiatry 185, 97–101.

M Ising , CJ Lauer , F Holsboer , S Modell (2005). The Munich vulnerability study on affective disorders: premorbid neuroendocrine profile of affected high-risk probands. Journal of Psychiatric Research 39, 2128.

J Kaufman , B Birmaher , D Brent , U Rao (1997). Schedule for Affective Disorders and Schizophrenia for School-Age Children – Present and Lifetime version (K-SADS-PL): initial reliability and validity data. Journal of the American Academy of Child and Adolescent Psychiatry 36, 980988.

KS Kendler , LM Karkowski , CA Prescott (1999). Causal relationship between stressful life events and the onset of major depression. American Journal of Psychiatry 156, 837841.

KS Kendler , L Karkowski-Shuman (1997). Stressful life events and genetic liability to major depression: genetic control of exposure to the environment? Psychological Medicine 27, 539547.

KS Kendler , JW Kuhn , J Vittum , CA Prescott , B Riley (2005). The interaction of stressful life events and a serotonin transporter polymorphism in the prediction of episodes of major depression: a replication. Archives of General Psychiatry 62, 529535.

RC Kessler (1997). The effects of stressful life events on depression. Annual Review of Psychology 48, 191214.

EY Kim , DJ Miklowitz , A Biuckians , K Mullen (2007). Life stress and the course of early-onset bipolar disorder. Journal of Affective Disorders 99, 3744.

N Kupper , EJ de Geus , M van den Berg , C Kirschbaum , DI Boomsma , G Willemsen (2005). Familial influences on basal salivary cortisol in an adult population. Psychoneuroendocrinology 30, 857868.

B Lundy , N Jones , T Field , G Nearing , M Davalos , P Pietro , S Schanberg , C Kuhn (1999). Prenatal depression effects on neonates. Infant Behavior and Development 22, 119129.

SJ Lupien , S King , MJ Meaney , BS McEwen (2000). Child's stress hormone levels correlate with mother's socioeconomic status and depressive state. Biological Psychiatry 48, 976980.

ZN Mannie , CJ Harmer , PJ Cowen (2007). Increased waking salivary cortisol levels in young people at familial risk of depression. American Journal of Psychiatry 164, 617621.

TJ Marin , TM Martin , E Blackwell , C Stetler , GE Miller (2007). Differentiating the impact of episodic and chronic stressors on hypothalamic-pituitary-adrenocortical axis regulation in young women. Health Psychology 26, 447455.

BS McEwen (2008). Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. European Journal of Pharmacology 583, 174185.

KA McGonagle , RC Kessler (1990). Chronic stress, acute stress, and depressive symptoms. American Journal of Community Psychology 18, 681706.

G Meinlschmidt , C Heim (2005). Decreased cortisol awakening response after early loss experience. Psychoneuroendocrinology 30, 568576.

SE Meyer , GP Chrousos , PW Gold (2001). Major depression and the stress system: a life span perspective. Development and Psychopathology 13, 565580.

S Modell , CJ Lauer , W Schreiber , J Huber , JC Krieg , F Holsboer (1998). Hormonal response pattern in the combined DEX-CRH test is stable over time in subjects at high familial risk for affective disorders. Neuropsychopharmacology 18, 253262.

TG O'Connor , Y Ben-Shlomo , J Heron , D Adams , V Glover , J Golding (2005). Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children. Biological Psychiatry 58, 211217.

CS Ostiguy , MA Ellenbogen , AM Linnen , EF Walker , C Hammen , S Hodgins (2009). Chronic stress and stressful life events in the offspring of parents with bipolar disorder. Journal of Affective Disorders 114, 7484.

K Pajer , W Gardner , RT Rubin , J Perel , S Neal (2001). Decreased cortisol levels in adolescent girls with conduct disorder. Archives of General Psychiatry 58, 297302.

JC Pruessner , DH Hellhammer , C Kirschbaum (1999). Burnout, perceived stress, and cortisol responses to awakening. Psychosomatic Medicine 61, 197204.

JC Pruessner , C Kirschbaum , G Meinlschmid , DH Hellhammer (2003). Two formulas for computation of the area under the curve represent measures of total hormone concentration versus time-dependent change. Psychoneuroendocrinology 28, 916931.

RM Sapolsky , LM Romero , AU Munck (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews 21, 5589.

J Schmider , CH Lammers , U Gotthardt , M Dettling , F Holsboer , IJ Heuser (1995). Combined dexamethasone/corticotropin-releasing hormone test in acute and remitted manic patients, in acute depression, and in normal controls: I. Biological Psychiatry 38, 797802.

JE Schreiber , E Shirtcliff , C Van Hulle , K Lemery-Chalfant , MH Klein , NH Kalin , MJ Essex , HH Goldsmith (2006). Environmental influences on family similarity in afternoon cortisol levels: twin and parent-offspring designs. Psychoneuroendocrinology 31, 11311137.

TE Seeman , BS McEwen (1996). Impact of social environment characteristics on neuroendocrine regulation. Psychosomatic Medicine 58, 459471.

RL Spitzer , JB Williams , M Gibbon , MB First (1992). The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Archives of General Psychiatry 49, 624629.

C Stetler , GE Miller (2008). Social integration of daily activities and cortisol secretion: a laboratory based manipulation. Journal of Behavioral Medicine 31, 249257.

F Therrien , V Drapeau , SJ Lupien , S Beaulieu , J Dore , A Tremblay , D Richard (2008). Awakening cortisol response in relation to psychosocial profiles and eating behaviors. Physiology and Behavior 93, 282288.

M Wals , MH Hillegers , CG Reichart , FC Verhulst , WA Nolen , J Ormel (2005). Stressful life events and onset of mood disorders in children of bipolar parents during 14-month follow-up. Journal of Affective Disorders 87, 253263.

IC Weaver , N Cervoni , FA Champagne , AC D'Alessio , S Sharma , JR Seckl , S Dymov , M Szyf , MJ Meaney (2004). Epigenetic programming by maternal behavior. Nature Neuroscience 7, 847854.

M Wichers , N Geschwind , N Jacobs , G Kenis , F Peeters , C Derom , E Thiery , P Delespaul , J van Os (2009). Transition from stress sensitivity to a depressive state: longitudinal twin study. British Journal of Psychiatry 195, 498503.

S Wüst , IS Federenko , EFC Van Rossum , R Kumsta , DH Hellhammer , S Entringer , JW Koper , R Yehuda , B McEwen (2004). A psychobiological perspective on genetic determinants of hypothalamus-pituitary-adrenal axis activity. Annals of the New York Academy of Sciences 1032, 5262.

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