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Original Investigation
July 14, 2021

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

Author Affiliations
  • 1Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology & Neuroscience, Department of Psychosis Studies, King’s College London, London, United Kingdom
  • 2Imaging of Mood- and Anxiety-Related Disorders (IMARD) Group, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Barcelona, Spain
  • 3Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden
  • 4Centro Hospitalar Psiquiátrico de Lisboa, Lisbon, Portugal
  • 5Institute of Psychiatry, Psychology & Neuroscience, Department of Psychosis Studies, King’s College London, London, United Kingdom
  • 6Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
  • 7Department of Neurology and Psychiatry, University of Rome La Sapienza, Rome, Italy
  • 8Institute of Neurosciences, University of Barcelona, Barcelona, Spain
  • 9Mental Health Department, Biocruces Bizkaia Health Research Institute, Basurto University Hospital, Facultad de Medicina y Odontología, Campus de Leioa, University of the Basque Country, UPV/EHU, Bizkaia, Spain
  • 10Institute of Psychiatry and Mental Health, Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Madrid, Spain
  • 11Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
  • 12Department of Paediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea
  • 13Neurosciences Department, University of Padova, Padova, Italy
  • 14OASIS service, South London and Maudsley NHS Foundation Trust, London, United Kingdom
JAMA Psychiatry. Published online July 14, 2021. doi:10.1001/jamapsychiatry.2021.0830
Key Points

Question  What is the current likelihood of transitioning to psychosis in individuals at clinical high risk?

Findings  In this meta-analysis of 130 longitudinal studies, including 9222 individuals at clinical high risk for psychosis from 74 cohorts, the risk of developing psychosis continued increasing after 2 years, cumulating to 25% at 3 years and reaching 35% at 10 years. Risk of transitioning to psychosis was higher in studies with a lower proportion of female individuals and a higher proportion of individuals presenting with brief limited intermittent psychotic symptoms.

Meaning  This updated meta-analysis indicates that the probability of transitioning to psychosis in individuals at clinical high risk is substantial and continues increasing in the long term, suggesting that an extended duration of clinical monitoring and preventive care may be beneficial.

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.

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