Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis

Gonzalo Salazar De Pablo; Joaquim Radua; Joana Pereira; Ilaria Bonoldi; Vincenzo Arienti; Filippo Besana; Livia Soardo; Anna Cabras; Lydia Fortea; Ana Catalan; Julio Vaquerizo-Serrano; Francesco Coronelli; Simi Kaur; Josette Da Silva; Jae Il Shin; Marco Solmi; Natascia Brondino; Pierluigi Politi; Philip McGuire; Paolo Fusar-Poli

doi:10.1001/jamapsychiatry.2021.0830

Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis

Gonzalo Salazar De Pablo, Joaquim Radua, Joana Pereira, Ilaria Bonoldi, Vincenzo Arienti, Filippo Besana, Livia Soardo, Anna Cabras, Lydia Fortea, Ana Catalan, Julio Vaquerizo-Serrano, Francesco Coronelli, Simi Kaur, Josette Da Silva, Jae Il Shin, Marco Solmi, Natascia Brondino, Pierluigi Politi, Philip McGuire, Paolo Fusar-Poli

Department of Pediatrics

Research output: Contribution to journal › Review article › peer-review

51 Citations (Scopus)

Abstract

Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P. Data Extraction and Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Main Outcome and Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). Conclusions and Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

Original language	English
Pages (from-to)	970-978
Number of pages	9
Journal	JAMA Psychiatry
Volume	78
Issue number	9
DOIs	https://doi.org/10.1001/jamapsychiatry.2021.0830
Publication status	Published - 2021 Sept

Bibliographical note

Funding Information:
Pablo reports honoraria from Janssen-Cilag and grants from the Alicia Koplowitz Foundation outside the submitted work. Dr Catalan reports personal fees from Janssen-Cilag outside the submitted work. Dr Vaquerizo-Serrano reports grants from the Alicia Koplowitz Foundation outside the submitted work. Dr Solmi reports support for serving on the Angelini Pharma advisory board and honoraria from Lundbeck outside the submitted work. Dr Fusar-Poli reports research fees from Lundbeck and honoraria from Lundbeck, Angelini Pharma, Menarini, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported.

Funding Information:
by the Alicia Koplowitz Foundation. Drs McGuire and Fusar-Poli received support for this study from the PSYSCAN project through the European Commission.

Publisher Copyright:
© 2021 American Medical Association. All rights reserved.

All Science Journal Classification (ASJC) codes

Psychiatry and Mental health

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1001/jamapsychiatry.2021.0830

Cite this

Salazar De Pablo, G., Radua, J., Pereira, J., Bonoldi, I., Arienti, V., Besana, F., Soardo, L., Cabras, A., Fortea, L., Catalan, A., Vaquerizo-Serrano, J., Coronelli, F., Kaur, S., Da Silva, J., Shin, J. I., Solmi, M., Brondino, N., Politi, P., McGuire, P., & Fusar-Poli, P. (2021). Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis. JAMA Psychiatry, 78(9), 970-978. https://doi.org/10.1001/jamapsychiatry.2021.0830

@article{4528e097093741648e415486d46ed0b2,

title = "Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis",

abstract = "Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P. Data Extraction and Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Main Outcome and Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). Conclusions and Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.",

author = "{Salazar De Pablo}, Gonzalo and Joaquim Radua and Joana Pereira and Ilaria Bonoldi and Vincenzo Arienti and Filippo Besana and Livia Soardo and Anna Cabras and Lydia Fortea and Ana Catalan and Julio Vaquerizo-Serrano and Francesco Coronelli and Simi Kaur and {Da Silva}, Josette and Shin, {Jae Il} and Marco Solmi and Natascia Brondino and Pierluigi Politi and Philip McGuire and Paolo Fusar-Poli",

note = "Funding Information: Pablo reports honoraria from Janssen-Cilag and grants from the Alicia Koplowitz Foundation outside the submitted work. Dr Catalan reports personal fees from Janssen-Cilag outside the submitted work. Dr Vaquerizo-Serrano reports grants from the Alicia Koplowitz Foundation outside the submitted work. Dr Solmi reports support for serving on the Angelini Pharma advisory board and honoraria from Lundbeck outside the submitted work. Dr Fusar-Poli reports research fees from Lundbeck and honoraria from Lundbeck, Angelini Pharma, Menarini, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported. Funding Information: by the Alicia Koplowitz Foundation. Drs McGuire and Fusar-Poli received support for this study from the PSYSCAN project through the European Commission. Publisher Copyright: {\textcopyright} 2021 American Medical Association. All rights reserved.",

year = "2021",

month = sep,

doi = "10.1001/jamapsychiatry.2021.0830",

language = "English",

volume = "78",

pages = "970--978",

journal = "JAMA Psychiatry",

issn = "2168-622X",

publisher = "American Medical Association",

number = "9",

}

Salazar De Pablo, G, Radua, J, Pereira, J, Bonoldi, I, Arienti, V, Besana, F, Soardo, L, Cabras, A, Fortea, L, Catalan, A, Vaquerizo-Serrano, J, Coronelli, F, Kaur, S, Da Silva, J, Shin, JI, Solmi, M, Brondino, N, Politi, P, McGuire, P & Fusar-Poli, P 2021, 'Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis', JAMA Psychiatry, vol. 78, no. 9, pp. 970-978. https://doi.org/10.1001/jamapsychiatry.2021.0830

TY - JOUR

T1 - Probability of Transition to Psychosis in Individuals at Clinical High Risk

T2 - An Updated Meta-analysis

AU - Salazar De Pablo, Gonzalo

AU - Radua, Joaquim

AU - Pereira, Joana

AU - Bonoldi, Ilaria

AU - Arienti, Vincenzo

AU - Besana, Filippo

AU - Soardo, Livia

AU - Cabras, Anna

AU - Fortea, Lydia

AU - Catalan, Ana

AU - Vaquerizo-Serrano, Julio

AU - Coronelli, Francesco

AU - Kaur, Simi

AU - Da Silva, Josette

AU - Shin, Jae Il

AU - Solmi, Marco

AU - Brondino, Natascia

AU - Politi, Pierluigi

AU - McGuire, Philip

AU - Fusar-Poli, Paolo

N1 - Funding Information: Pablo reports honoraria from Janssen-Cilag and grants from the Alicia Koplowitz Foundation outside the submitted work. Dr Catalan reports personal fees from Janssen-Cilag outside the submitted work. Dr Vaquerizo-Serrano reports grants from the Alicia Koplowitz Foundation outside the submitted work. Dr Solmi reports support for serving on the Angelini Pharma advisory board and honoraria from Lundbeck outside the submitted work. Dr Fusar-Poli reports research fees from Lundbeck and honoraria from Lundbeck, Angelini Pharma, Menarini, and Boehringer Ingelheim outside the submitted work. No other disclosures were reported. Funding Information: by the Alicia Koplowitz Foundation. Drs McGuire and Fusar-Poli received support for this study from the PSYSCAN project through the European Commission. Publisher Copyright: © 2021 American Medical Association. All rights reserved.

PY - 2021/9

Y1 - 2021/9

N2 - Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P. Data Extraction and Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Main Outcome and Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). Conclusions and Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

AB - Importance: Estimating the current likelihood of transitioning from a clinical high risk for psychosis (CHR-P) to psychosis holds paramount importance for preventive care and applied research. Objective: To quantitatively examine the consistency and magnitude of transition risk to psychosis in individuals at CHR-P. Data Sources: PubMed and Web of Science databases until November 1, 2020. Manual search of references from previous articles. Study Selection: Longitudinal studies reporting transition risks in individuals at CHR-P. Data Extraction and Synthesis: Meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines; independent data extraction, manually and through digitalization of Kaplan-Meier curves. Main Outcome and Measures: Primary effect size was cumulative risk of transition to psychosis at 0.5, 1, 1.5, 2, 2.5, 3, 4, and more than 4 years' follow-up, estimated using the numbers of individuals at CHR-P transitioning to psychosis at each time point. These analyses were complemented by meta-analytical Kaplan-Meier curves and speed of transition to psychosis (hazard rate). Random-effects meta-analysis, between-study heterogeneity analysis, study quality assessment, and meta-regressions were conducted. Results: A total of 130 studies and 9222 individuals at CHR-P were included. The mean (SD) age was 20.3 (4.4) years, and 5100 individuals (55.3%) were male. The cumulative transition risk was 0.09 (95% CI, 0.07-0.10; k = 37; n = 6485) at 0.5 years, 0.15 (95% CI, 0.13-0.16; k = 53; n = 7907) at 1 year, 0.20 (95% CI, 0.17-0.22; k = 30; n = 5488) at 1.5 years, 0.19 (95% CI, 0.17-0.22; k = 44; n = 7351) at 2 years, 0.25 (95% CI, 0.21-0.29; k = 19; n = 3114) at 2.5 years, 0.25 (95% CI, 0.22-0.29; k = 29; n = 4029) at 3 years, 0.27 (95% CI, 0.23-0.30; k = 16; n = 2926) at 4 years, and 0.28 (95% CI, 0.20-0.37; k = 14; n = 2301) at more than 4 years. The cumulative Kaplan-Meier transition risk was 0.08 (95% CI, 0.08-0.09; n = 4860) at 0.5 years, 0.14 (95% CI, 0.13-0.15; n = 3408) at 1 year, 0.17 (95% CI, 0.16-0.19; n = 2892) at 1.5 years, 0.20 (95% CI, 0.19-0.21; n = 2357) at 2 years, 0.25 (95% CI, 0.23-0.26; n = 1444) at 2.5 years, 0.27 (95% CI, 0.25-0.28; n = 1029) at 3 years, 0.28 (95% CI, 0.26-0.29; n = 808) at 3.5 years, 0.29 (95% CI, 0.27-0.30; n = 737) at 4 years, and 0.35 (95% CI, 0.32-0.38; n = 114) at 10 years. The hazard rate only plateaued at 4 years' follow-up. Meta-regressions showed that a lower proportion of female individuals (β = -0.02; 95% CI, -0.04 to -0.01) and a higher proportion of brief limited intermittent psychotic symptoms (β = 0.02; 95% CI, 0.01-0.03) were associated with an increase in transition risk. Heterogeneity across the studies was high (I2 range, 77.91% to 95.73%). Conclusions and Relevance: In this meta-analysis, 25% of individuals at CHR-P developed psychosis within 3 years. Transition risk continued increasing in the long term. Extended clinical monitoring and preventive care may be beneficial in this patient population.

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DO - 10.1001/jamapsychiatry.2021.0830

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Probability of Transition to Psychosis in Individuals at Clinical High Risk: An Updated Meta-analysis

Abstract

Bibliographical note

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UN SDGs

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