Genetic factors, perceived chronic stress, and the free cortisol response to awakening

Psychoneuroendocrinology. 2000 Oct;25(7):707-20. doi: 10.1016/s0306-4530(00)00021-4.


Recent studies have demonstrated that the free cortisol response to awakening can serve as a useful index of hypothalamus-pituitary-adrenal axis (HPA) activity. This endocrine marker is rather consistent, shows good intraindividual stability across time and appears to be able to uncover subtle changes in HPA regulation. The present twin study investigated genetic factors as sources of the interindividual variation of the cortisol awakening response. Furthermore, the relationship between psychological variables and morning cortisol levels was studied. On two consecutive days saliva samples were collected 0, 30, 45 and 60 minutes after awakening in 52 monozygotic and 52 dizygotic twin pairs. Moreover, samples were obtained at 0800, 1100, 1500 and 2000 h. ('short day-time profile'). Additionally, the participants filled out questionnaires assessing chronic stress load, self-esteem and self-efficacy.Heritability estimates of h(2)=0.40 for the mean increase and of h(2)=0.48 for the area under the response curve indicate a significant impact of genetic factors on cortisol levels after awakening. However, no genetic influence on the short day-time profile could be observed. Furthermore, several aspects of perceived chronic stress, namely 'worries', 'social stress' and 'lack of social recognition' were significantly associated with the awakening cortisol response. The evidence for a medium-sized, yet distinct genetic influence on cortisol levels after awakening is discussed with regard to a potential clinical relevance of genetic determinants of HPA (re)activity. In line with several recent studies, the present findings further support the view that the cortisol awakening responses is consistently enhanced under chronic stress conditions.

Publication types

  • Twin Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Arousal / genetics*
  • Arousal / physiology
  • Child
  • Circadian Rhythm / genetics
  • Circadian Rhythm / physiology
  • Female
  • Genotype*
  • Humans
  • Hydrocortisone / blood*
  • Hypothalamo-Hypophyseal System / physiopathology
  • Male
  • Middle Aged
  • Pituitary-Adrenal System / physiopathology
  • Stress, Psychological / complications*
  • Stress, Psychological / physiopathology
  • Twins, Dizygotic / genetics
  • Twins, Monozygotic / genetics
  • Wakefulness / genetics*
  • Wakefulness / physiology


  • Hydrocortisone