RETRACTED: Dynamic Prediction of Outcomes for Youth at Clinical High Risk for Psychosis

Author:

Worthington Michelle A.1,Addington Jean2,Bearden Carrie E.3,Cadenhead Kristin S.4,Cornblatt Barbara A.5,Keshavan Matcheri6,Lympus Cole A.7,Mathalon Daniel H.8,Perkins Diana O.9,Stone William S.6,Walker Elaine F.1011,Woods Scott W.12,Zhao Yize13,Cannon Tyrone D.112

Affiliation:

1. Department of Psychology, Yale University, New Haven, Connecticut

2. Hotchkiss Brain Institute, Department of Psychiatry, University of Calgary, Calgary, Alberta, Canada

3. Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, Department of Psychology, University of California, Los Angeles

4. Department of Psychiatry, University of California, San Diego

5. Department of Psychiatry, Zucker Hillside Hospital, Long Island, New York

6. Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center and Massachusetts General Hospital, Boston

7. Department of Psychology, Rutgers University, New Brunswick, New Jersey

8. Department of Psychiatry, San Francisco VA Medical Center, University of California, San Francisco

9. Department of Psychiatry, University of North Carolina, Chapel Hill

10. Department of Psychology, Emory University, Atlanta, Georgia

11. Department of Psychiatry, Emory University, Atlanta, Georgia

12. Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut

13. Department of Biostatistics, Yale University School of Public Health, New Haven, Connecticut

Abstract

ImportanceLeveraging the dynamic nature of clinical variables in the clinical high risk for psychosis (CHR-P) population has the potential to significantly improve the performance of outcome prediction models.ObjectiveTo improve performance of prediction models and elucidate dynamic clinical profiles using joint modeling to predict conversion to psychosis and symptom remission.Design, Setting, and ParticipantsData were collected as part of the third wave of the North American Prodrome Longitudinal Study (NAPLS 3), which is a 9-site prospective longitudinal study. Participants were individuals aged 12 to 30 years who met criteria for a psychosis-risk syndrome. Clinical, neurocognitive, and demographic variables were collected at baseline and at multiple follow-up visits, beginning at 2 months and up to 24 months. An initial feature selection process identified longitudinal clinical variables that showed differential change for each outcome group across 2 months. With these variables, a joint modeling framework was used to estimate the likelihood of eventual outcomes. Models were developed and tested in a 10-fold cross-validation framework. Clinical data were collected between February 2015 and November 2018, and data were analyzed from February 2022 to December 2023.Main Outcomes and MeasuresPrediction models were built to predict conversion to psychosis and symptom remission. Participants met criteria for conversion if their positive symptoms reached the fully psychotic range and for symptom remission if they were subprodromal on the Scale of Psychosis-Risk Symptoms for a duration of 6 months or more.ResultsOf 488 included NAPLS 3 participants, 232 (47.5%) were female, and the mean (SD) age was 18.2 (3.4) years. Joint models achieved a high level of accuracy in predicting conversion (balanced accuracy [BAC], 0.91) and remission (BAC, 0.99) compared with baseline models (conversion: BAC, 0.65; remission: BAC, 0.60). Clinical variables that showed differential change between outcome groups across a 2-month span, including measures of symptom severity and aspects of functioning, were also identified. Further, intra-individual risks for each outcome were more negatively correlated when using joint models (r = −0.92; P < .001) compared with baseline models (r = −0.50; P < .001).Conclusions and RelevanceIn this study, joint models significantly outperformed baseline models in predicting both conversion and remission, demonstrating that monitoring short-term clinical change may help to parse heterogeneous dynamic clinical trajectories in a CHR-P population. These findings could inform additional study of targeted treatment selection and could move the field closer to clinical implementation of prediction models.

Publisher

American Medical Association (AMA)

Subject

Psychiatry and Mental health

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