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

Psychol Med. 2011 Nov;41(11):2447-57. doi: 10.1017/S0033291711000523. Epub 2011 Apr 28.


Background: 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.

Method: 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.

Results: 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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Bipolar Disorder*
  • Child of Impaired Parents / psychology*
  • Chronic Disease
  • Female
  • Humans
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Hypothalamo-Hypophyseal System / physiopathology
  • Longitudinal Studies
  • Male
  • Mood Disorders / etiology
  • Mood Disorders / physiopathology*
  • Multivariate Analysis
  • Pituitary-Adrenal System / metabolism
  • Pituitary-Adrenal System / physiopathology
  • Quebec
  • Risk
  • Saliva / metabolism
  • Stress, Psychological / metabolism*
  • Stress, Psychological / psychology
  • Young Adult


  • Hydrocortisone