Cortisol levels and risk for psychosis: initial findings from the North American prodrome longitudinal study

Biol Psychiatry. 2013 Sep 15;74(6):410-7. doi: 10.1016/j.biopsych.2013.02.016. Epub 2013 Apr 3.


Background: Studies of biomarkers of hypothalamic-pituitary-adrenal activity indicate that psychotic disorders are associated with elevated cortisol. This study examined cortisol levels in healthy control subjects and individuals who met clinical high-risk (CHR) criteria for psychosis. It was hypothesized that cortisol levels would be 1) elevated in the CHR group relative to control subjects, 2) positively correlated with symptom severity, and 3) most elevated in CHR patients who transition to psychotic level severity.

Methods: Baseline assessments were conducted at eight centers in the North American Prodrome Longitudinal Study. The present CHR sample included 256 individuals meeting the Scale for Prodromal Symptoms criteria and 141 control subjects, all of whom underwent baseline assessment and measurement of salivary cortisol.

Results: Consistent with previous reports, there was an effect of age on cortisol, with increases through the adolescent/early adult years. Analysis of covariance showed a main effect of diagnostic group, with the CHR group showing higher cortisol. There were modest, positive correlations of cortisol with baseline symptom severity, and analysis of covariance revealed higher baseline cortisol in those who transitioned to psychotic level symptoms when compared with healthy control subjects and CHR subjects who remitted.

Conclusions: The present findings add to accumulating evidence of heightened cortisol secretion in CHR individuals. The findings also indicate nonspecific associations between cortisol levels and symptom severity, as well as symptom progression. The role of hypothalamic-pituitary-adrenal activity in prediction of conversion to psychosis and its relation with other biomarkers of risk should receive attention in future research.

Keywords: Cortisol; high-risk; longitudinal; prodrome; psychosis; stress.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Female
  • Humans
  • Hydrocortisone / analysis*
  • Longitudinal Studies
  • Male
  • North America
  • Prodromal Symptoms
  • Psychotic Disorders / diagnosis*
  • Risk Factors
  • Young Adult


  • Hydrocortisone