Michelle A Worthington1, Elaine F Walker2, Jean Addington3, Carrie E Bearden4, Kristin S Cadenhead5, Barbara A Cornblatt6, Daniel H Mathalon7, Thomas H McGlashan8, Diana O Perkins9, Larry J Seidman10, Ming T Tsuang5, Scott W Woods8, Tyrone D Cannon11. 1. Department of Psychology, Yale University, New Haven, CT, United States of America. 2. Department of Psychology and Psychiatry, Emory University, Atlanta, GA, United States of America. 3. Department of Psychiatry, Hotchkiss Brain Institute, Calgary, Alberta, Canada. 4. Department of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles, CA, United States of America. 5. Department of Psychiatry, UCSD, San Diego, CA, United States of America. 6. Department of Psychiatry, Zucker Hillside Hospital, Long Island, NY, United States of America. 7. Department of Psychiatry, UCSF, SFVA Medical Center, San Francisco, CA, United States of America. 8. Department of Psychiatry, Yale University, New Haven, CT, United States of America. 9. Department of Psychiatry, University of North Carolina, Chapel Hill, NC, United States of America. 10. Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, MA, United States of America; Massachusetts General Hospital, Boston, MA, United States of America. 11. Department of Psychology, Yale University, New Haven, CT, United States of America; Department of Psychiatry, Yale University, New Haven, CT, United States of America. Electronic address: tyrone.cannon@yale.edu.
Abstract
BACKGROUND: Risk calculators are useful tools that can help clinicians and researchers better understand an individual's risk of conversion to psychosis. The North American Prodrome Longitudinal Study (NAPLS2) Individualized Risk Calculator has good predictive accuracy but could be potentially improved by the inclusion of a biomarker. Baseline cortisol, a measure of hypothalamic-pituitary-adrenal (HPA) axis functioning that is impacted by biological vulnerability to stress and exposure to environmental stressors, has been shown to be higher among individuals at clinical high-risk for psychosis (CHRP) who eventually convert to psychosis than those who do not. We sought to determine whether the addition of baseline cortisol to the NAPLS2 risk calculator improved the performance of the risk calculator. METHODS: Participants were drawn from the NAPLS2 study. A subset of NAPLS2 participants provided salivary cortisol samples. A multivariate Cox proportional hazards regression evaluated the likelihood of an individual's eventual conversion to psychosis based on demographic and clinical variables in addition to baseline cortisol levels. RESULTS: A total of 417 NAPLS2 participants provided salivary cortisol and were included in the analysis. Higher levels of cortisol were predictive of conversion to psychosis in a univariate model (C-index = 0.59, HR = 21.5, p-value = 0.004). The inclusion of cortisol in the risk calculator model resulted in a statistically significant improvement in performance from the original risk calculator model (C-index = 0.78, SE = 0.028). CONCLUSIONS: Salivary cortisol is an inexpensive and non-invasive biomarker that could improve individual predictions about conversion to psychosis and treatment decisions for CHR-P individuals.
BACKGROUND: Risk calculators are useful tools that can help clinicians and researchers better understand an individual's risk of conversion to psychosis. The North American Prodrome Longitudinal Study (NAPLS2) Individualized Risk Calculator has good predictive accuracy but could be potentially improved by the inclusion of a biomarker. Baseline cortisol, a measure of hypothalamic-pituitary-adrenal (HPA) axis functioning that is impacted by biological vulnerability to stress and exposure to environmental stressors, has been shown to be higher among individuals at clinical high-risk for psychosis (CHRP) who eventually convert to psychosis than those who do not. We sought to determine whether the addition of baseline cortisol to the NAPLS2 risk calculator improved the performance of the risk calculator. METHODS: Participants were drawn from the NAPLS2 study. A subset of NAPLS2 participants provided salivary cortisol samples. A multivariate Cox proportional hazards regression evaluated the likelihood of an individual's eventual conversion to psychosis based on demographic and clinical variables in addition to baseline cortisol levels. RESULTS: A total of 417 NAPLS2 participants provided salivary cortisol and were included in the analysis. Higher levels of cortisol were predictive of conversion to psychosis in a univariate model (C-index = 0.59, HR = 21.5, p-value = 0.004). The inclusion of cortisol in the risk calculator model resulted in a statistically significant improvement in performance from the original risk calculator model (C-index = 0.78, SE = 0.028). CONCLUSIONS: Salivary cortisol is an inexpensive and non-invasive biomarker that could improve individual predictions about conversion to psychosis and treatment decisions for CHR-P individuals.
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