Toward Generalizable and Transdiagnostic Tools for Psychosis Prediction: An Independent Validation and Improvement of the NAPLS-2 Risk Calculator in the Multisite PRONIA Cohort.

Clinical high-risk states First-episode depression Machine learning Psychosis prediction Reciprocal external validation Risk calculators

Journal

Biological psychiatry
ISSN: 1873-2402
Titre abrégé: Biol Psychiatry
Pays: United States
ID NLM: 0213264

Informations de publication

Date de publication:
01 11 2021
Historique:
received: 05 02 2021
revised: 03 06 2021
accepted: 27 06 2021
pubmed: 7 9 2021
medline: 3 11 2021
entrez: 6 9 2021
Statut: ppublish

Résumé

Transition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes. We validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation. After calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts. Clinical-neurocognitive machine learning models operating in young patients with affective and CHR syndromes facilitate a more precise and generalizable prediction of psychosis. Future studies should investigate their therapeutic utility in large-scale clinical trials.

Sections du résumé

BACKGROUND
Transition to psychosis is among the most adverse outcomes of clinical high-risk (CHR) syndromes encompassing ultra-high risk (UHR) and basic symptom states. Clinical risk calculators may facilitate an early and individualized interception of psychosis, but their real-world implementation requires thorough validation across diverse risk populations, including young patients with depressive syndromes.
METHODS
We validated the previously described NAPLS-2 (North American Prodrome Longitudinal Study 2) calculator in 334 patients (26 with transition to psychosis) with CHR or recent-onset depression (ROD) drawn from the multisite European PRONIA (Personalised Prognostic Tools for Early Psychosis Management) study. Patients were categorized into three risk enrichment levels, ranging from UHR, over CHR, to a broad-risk population comprising patients with CHR or ROD (CHR|ROD). We assessed how risk enrichment and different predictive algorithms influenced prognostic performance using reciprocal external validation.
RESULTS
After calibration, the NAPLS-2 model predicted psychosis with a balanced accuracy (BAC) (sensitivity, specificity) of 68% (73%, 63%) in the PRONIA-UHR cohort, 67% (74%, 60%) in the CHR cohort, and 70% (73%, 66%) in patients with CHR|ROD. Multiple model derivation in PRONIA-CHR|ROD and validation in NAPLS-2-UHR patients confirmed that broader risk definitions produced more accurate risk calculators (CHR|ROD-based vs. UHR-based performance: 67% [68%, 66%] vs. 58% [61%, 56%]). Support vector machines were superior in CHR|ROD (BAC = 71%), while ridge logistic regression and support vector machines performed similarly in CHR (BAC = 67%) and UHR cohorts (BAC = 65%). Attenuated psychotic symptoms predicted psychosis across risk levels, while younger age and reduced processing speed became increasingly relevant for broader risk cohorts.
CONCLUSIONS
Clinical-neurocognitive machine learning models operating in young patients with affective and CHR syndromes facilitate a more precise and generalizable prediction of psychosis. Future studies should investigate their therapeutic utility in large-scale clinical trials.

Identifiants

pubmed: 34482951
pii: S0006-3223(21)01433-5
doi: 10.1016/j.biopsych.2021.06.023
pmc: PMC8500930
mid: NIHMS1721825
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

632-642

Subventions

Organisme : NIMH NIH HHS
ID : U01 MH082022
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001863
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH081902
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH076989
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH081988
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH066069
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH066286
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH119219
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH066134
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH081928
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH081857
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH081944
Pays : United States

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

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Auteurs

Nikolaos Koutsouleris (N)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Max-Planck Institute of Psychiatry, Munich, Germany; Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, United Kingdom. Electronic address: nikolaos.koutsouleris@med.uni-muenchen.de.

Michelle Worthington (M)

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

Dominic B Dwyer (DB)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.

Lana Kambeitz-Ilankovic (L)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany; Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Rachele Sanfelici (R)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.

Paolo Fusar-Poli (P)

Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, United Kingdom.

Marlene Rosen (M)

Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Stephan Ruhrmann (S)

Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Alan Anticevic (A)

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

Jean Addington (J)

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

Diana O Perkins (DO)

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

Carrie E Bearden (CE)

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

Barbara A Cornblatt (BA)

Zucker Hillside Hospital, Northwell Health, Queens, New York.

Kristin S Cadenhead (KS)

University of California San Diego, San Diego, California.

Daniel H Mathalon (DH)

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

Thomas McGlashan (T)

Department of Psychiatry, Yale University, New Haven, Connecticut.

Larry Seidman (L)

Department of Psychiatry, Harvard Medical School at Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Ming Tsuang (M)

University of California San Diego, San Diego, California.

Elaine F Walker (EF)

Department of Psychology and Psychiatry, Emory University, Atlanta, Georgia.

Scott W Woods (SW)

Department of Psychiatry, Yale University, New Haven, Connecticut.

Peter Falkai (P)

Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich, Germany.

Rebekka Lencer (R)

Department of Psychiatry and Psychotherapy, University of Münster, Münster, Germany; Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany.

Alessandro Bertolino (A)

Department of Basic Medical Science, Neuroscience and Sense Organs, University of Bari Aldo Moro, Bari, Italy.

Joseph Kambeitz (J)

Department of Psychiatry and Psychotherapy, Faculty of Medicine and University Hospital, University of Cologne, Cologne, Germany.

Frauke Schultze-Lutter (F)

Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Germany.

Eva Meisenzahl (E)

Department of Psychiatry and Psychotherapy, Medical Faculty, Heinrich-Heine-Universität Düsseldorf, Germany.

Raimo K R Salokangas (RKR)

Department of Psychiatry, University of Turku, Turku, Finland.

Jarmo Hietala (J)

Department of Psychiatry, University of Turku, Turku, Finland.

Paolo Brambilla (P)

Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.

Rachel Upthegrove (R)

Institute of Mental Health, University of Birmingham, Birmingham, United Kingdom; School of Psychology, University of Birmingham, Birmingham, United Kingdom.

Stefan Borgwardt (S)

Department of Psychiatry and Psychotherapy, University of Lübeck, Lübeck, Germany; Department of Psychiatry (Psychiatric University Hospital, UPK), University of Basel, Basel, Switzerland.

Stephen Wood (S)

Centre for Youth Mental Health, University of Melbourne, Melbourne, Victoria, Australia; Orygen, National Centre of Excellence for Youth Mental Health, Melbourne, Victoria, Australia.

Raquel E Gur (RE)

Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Philip McGuire (P)

Institute of Psychiatry, Psychology and Neurosciences, King's College London, London, United Kingdom.

Tyrone D Cannon (TD)

Department of Psychology, Yale University, New Haven, Connecticut; Department of Psychiatry, Yale University, New Haven, Connecticut.

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