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Published Online: 1 July 2016

An Individualized Risk Calculator for Research in Prodromal Psychosis

Tyrone D. Cannon, Ph.D., Changhong Yu, M.S., Jean Addington, Ph.D., Carrie E. Bearden, Ph.D., Kristin S. Cadenhead, M.D., Barbara A. Cornblatt, Ph.D., Robert Heinssen, Ph.D., Clark D. Jeffries, Ph.D., Daniel H. Mathalon, Ph.D., M.D., Thomas H. McGlashan, M.D., Diana O. Perkins, M.D., M.P.H., Larry J. Seidman, Ph.D., Ming T. Tsuang, M.D., Ph.D., Elaine F. Walker, Ph.D., Scott W. Woods, M.D., and Michael W. Kattan, Ph.D.Authors Info & Affiliations
Publication: American Journal of Psychiatry
Volume 173, Number 10
https://doi.org/10.1176/appi.ajp.2016.15070890
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Abstract

Objective:

Approximately 20%–35% of individuals 12–35 years old who meet criteria for a prodromal risk syndrome convert to psychosis within 2 years. However, this estimate ignores the fact that clinical high-risk cases vary considerably in risk. The authors sought to create a risk calculator, based on profiles of risk indicators, that can ascertain the probability of conversion to psychosis in individual patients.

Method:

The study subjects were 596 clinical high-risk participants from the second phase of the North American Prodrome Longitudinal Study who were followed up to the time of conversion to psychosis or last contact (up to 2 years). The predictors examined were limited to those that are supported by previous studies and are readily obtainable in general clinical settings. Time-to-event regression was used to build a multivariate model predicting conversion, with internal validation using 1,000 bootstrap resamples.

Results:

The 2-year probability of conversion to psychosis was 16%. Higher levels of unusual thought content and suspiciousness, greater decline in social functioning, lower verbal learning and memory performance, slower speed of processing, and younger age at baseline each contributed to individual risk for psychosis. Stressful life events, trauma, and family history of schizophrenia were not significant predictors. The multivariate model achieved a concordance index of 0.71 and, as reported in an article by Carrión et al., published concurrently with this one, was validated in an independent external data set. The results are instantiated in a web-based risk prediction tool envisioned to be most useful in research protocols involving the psychosis prodrome.

Conclusions:

A risk calculator comparable in accuracy to those for cardiovascular disease and cancer is available to predict individualized conversion risks in newly ascertained clinical high-risk cases. Given that the risk calculator can be validly applied only for patients who screen positive on the Structured Clinical Interview for Psychosis Risk Syndromes, which requires training to administer, its most immediate uses will be in research on psychosis risk factors and in research-driven clinical (prevention) trials.

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Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Volume 173 • Number 10 • October 01, 2016
Pages: 980 - 988
PubMed: 27363508

History

Received: 8 July 2015
Revision received: 14 December 2015
Revision received: 8 March 2016
Accepted: 30 March 2016
Published online: 1 July 2016
Published in print: October 01, 2016

Authors

Affiliations

Tyrone D. Cannon, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Changhong Yu, M.S.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Jean Addington, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Carrie E. Bearden, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Kristin S. Cadenhead, M.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Barbara A. Cornblatt, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Robert Heinssen, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Clark D. Jeffries, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Daniel H. Mathalon, Ph.D., M.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Thomas H. McGlashan, M.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Diana O. Perkins, M.D., M.P.H.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Larry J. Seidman, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Ming T. Tsuang, M.D., Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Elaine F. Walker, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Scott W. Woods, M.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Michael W. Kattan, Ph.D.
From the Departments of Psychology and Psychiatry, Yale University, New Haven, Conn.; the Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland; the Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Alberta; the Departments of Psychiatry and Biobehavioral Sciences and Psychology, UCLA, Los Angeles; the Department of Psychiatry, UCSD, San Diego; the Department of Psychiatry, Zucker Hillside Hospital, Glen Oaks, New York; NIMH, Bethesda, Md.; the Renaissance Computing Institute, University of North Carolina, Chapel Hill; the Department of Psychiatry, UCSF, San Francisco; the Department of Psychiatry, University of North Carolina, Chapel Hill; the Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston; the Center for Behavioral Genomics, the Department of Psychiatry, and the Institute of Genomic Medicine, UCSD, La Jolla; and the Departments of Psychology and Psychiatry, Emory University, Atlanta.
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Notes

Address correspondence to Dr. Cannon ([email protected]).

Funding Information

National Institute of Mental Health10.13039/100000025: P50MH066286, U01MH081857, U01MH081902
Supported by NIH grants U01 MH081902 (to Dr. Cannon), P50 MH066286 (to Dr. Bearden), U01 MH081857 (to Dr. Cornblatt), U01 MH82022 (to Dr. Woods), U01 MH066134 (to Dr. Addington), U01 MH081944 (to Dr. Cadenhead), R01 U01 MH066069 (to Dr. Perkins), R01 MH076989 (to Dr. Mathalon), U01 MH081928 (to Dr. Seidman), and U01 MH081988 (to Dr. Walker).

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