Perceived stress and hair cortisol: Differences in bipolar disorder and schizophrenia

Psychoneuroendocrinology. 2016 Jul:69:26-34. doi: 10.1016/j.psyneuen.2016.03.010. Epub 2016 Mar 17.


Introduction: Bipolar disorder (BD) and schizophrenia (SCZ) are psychiatric disorders with shared and distinct clinical and genetic features. In both disorders, stress increases the risk for onset or relapse and dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis has been reported. The latter is frequently investigated by measuring changes in the hormonal end product of the HPA axis, i.e., the glucocorticoid cortisol, whose concentration exhibits diurnal variation. The analysis of hair cortisol concentration (HCC) is a new method, which allows assessment of cumulative cortisol secretion over the preceding three months.

Aims: To explore whether perceived stress and HCC: (i) differ between BD patients, SCZ patients, and controls; (ii) change over disease course; and iii) are associated with an increased genetic risk for BD or SCZ.

Methods: 159 SCZ patients, 61 BD patients and 82 controls were included. Assessment included psychopathology, perceived stress, and HCC. Inpatients with an acute episode (38 BD and 77 SCZ) were assessed shortly after admission to hospital and at 3 and 6 months follow-up. Outpatients in remission and controls were assessed at one time point only. Polygenic risk scores for BD and SCZ were calculated based on results of the Psychiatric Genomic Consortium.

Results: (i) Perceived stress was higher in BD and SCZ patients compared to controls (p<0.02), and was lower in outpatients in remission compared to inpatients on admission. HCC was higher in BD patients compared to SCZ patients and controls (p<0.02), and higher in inpatients on admission than in outpatients in remission (p=0.0012). In BD patients (r=0.29; p=0.033) and SCZ patients (r=0.20; p=0.024) manic symptoms were correlated with HCC. (ii) In both BD and SCZ inpatients, perceived stress decreased over the 6 month study period (p=0.048), while HCC did not change significantly over the 6 month study period. (iii) In controls, but not in the patient groups, the genetic risk score for BD was associated with HCC (r=0.28, p=0.023).

Conclusions: While our results are consistent with previous reports of increased perceived stress in BD and SCZ, they suggest differential involvement of the HPA axis in the two disorders. The genetic study supports this latter finding, and suggests that this effect is present below the threshold of manifest disorder.

Keywords: Bipolar disorder; Genetic risk; Hair cortisol; Perceived stress; Schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bipolar Disorder / metabolism
  • Bosnia and Herzegovina
  • Female
  • Genetic Predisposition to Disease
  • Hair / chemistry
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / genetics
  • Hydrocortisone / metabolism*
  • Hypothalamo-Hypophyseal System / metabolism
  • Male
  • Middle Aged
  • Multifactorial Inheritance
  • Pituitary-Adrenal System / metabolism
  • Risk Factors
  • Schizophrenia / metabolism
  • Stress, Psychological / metabolism*


  • Hydrocortisone