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JAMA Psychiatry. 2020 Mar 11. doi: 10.1001/jamapsychiatry.2019.4779. [Epub ahead of print]

Prevention of Psychosis: Advances in Detection, Prognosis, and Intervention.

Author information

Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Institute of Psychiatry, Psychology & Neuroscience, Department of Psychosis Studies, King's College London, London, United Kingdom.
OASIS Service, South London and Maudsley National Health Service (NHS) Foundation Trust, London, United Kingdom.
Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy.
Maudsley Biomedical Research Centre, National Institute for Health Research, South London and Maudsley NHS Foundation Trust, London, United Kingdom.
Institute of Psychiatry and Mental Health, Department of Child and Adolescent Psychiatry, Hospital General Universitario Gregorio Marañón, Universidad Complutense, Centro de Investigación Biomédica en Red Salud Mental (CIBERSAM), Madrid, Spain.
The Zucker Hillside Hospital, Department of Psychiatry, Northwell Health, Glen Oaks, New York.
The Feinstein Institute for Medical Research, Center for Psychiatric Neuroscience, Manhasset, New York.
Charité Universitätsmedizin Berlin, Department of Child and Adolescent Psychiatry, Berlin, Germany.
Department of Psychiatry and Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York.
Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Centre for Therapeutic Innovation in Neuropsychiatry, Institut de Recherche Servier, Croissy sur Seine, Paris, France.
Department of Psychiatry, University of Basel, Basel, Switzerland.
Department of Psychiatry, Psychosomatics and Psychotherapy, University of Lübeck, Lübeck, Germany.
Department of Psychiatry, University of Campania L. Vanvitelli, Naples, Italy.
Department of Psychiatry, Psychotherapy and Psychosomatic Medicine with Early Intervention and Recognition Centre, Vivantes Klinikum Am Urban, Charité-Universitätsmedizin, Berlin, Germany.
Vivantes Klinikum im Friedrichshain, Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Charité-Universitätsmedizin, Berlin, Germany.
Department of Psychiatry and Psychotherapy, University of Cologne, Cologne, Germany.
Orygen, The National Centre of Excellence in Youth Mental Health, Melbourne, Victoria, Australia.
Department of Psychiatry and Psychotherapy, Carl Gustav Carus University Hospital, Medical Faculty, Technische Universität Dresden, Dresden, Germany.
Copenhagen Affective Disorder Research Center, Psychiatric Center Copenhagen, Rigshospitalet, Copenhagen, Denmark.
Department of Psychiatry and Neuropsychology, Maastricht University Medical Center School for Mental Health and Neuroscience, Maastricht, the Netherlands.
Amsterdam University Medical Centers, Academic Medical Center, Department of Psychiatry, Amsterdam, the Netherlands.
Department of Psychiatry and Psychotherapy, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
Center for Basics in NeuroModulation (NeuroModul), Medical Faculty, University of Freiburg, Germany.
INSERM, IPNP UMR S1266, Laboratoire de Physiopathologie des Maladies Psychiatriques, Université Paris Descartes, Université de Paris, CNRS, GDR3557-Institut de Psychiatrie, Paris, France.
Faculté de Médecine Paris Descartes, GHU Paris-Sainte-Anne, Service Hospitalo-Universitaire, Paris, France.
University Hospital, Department of Psychiatry and Psychotherapy, Ludwig Maximilian University of Munich, Munich, Germany.
Institute of Psychiatry, Psychology & Neuroscience, Department of Psychosis Studies, King's College London, London, United Kingdom.
Center for Psychiatric Neuroscience, Lausanne University Hospital, Lausanne-Prilly, Switzerland.



Detection, prognosis, and indicated interventions in individuals at clinical high risk for psychosis (CHR-P) are key components of preventive psychiatry.


To provide a comprehensive, evidence-based systematic appraisal of the advancements and limitations of detection, prognosis, and interventions for CHR-P individuals and to formulate updated recommendations.

Evidence Review:

Web of Science, Cochrane Central Register of Reviews, and Ovid/PsychINFO were searched for articles published from January 1, 2013, to June 30, 2019, to identify meta-analyses conducted in CHR-P individuals. MEDLINE was used to search the reference lists of retrieved articles. Data obtained from each article included first author, year of publication, topic investigated, type of publication, study design and number, sample size of CHR-P population and comparison group, type of comparison group, age and sex of CHR-P individuals, type of prognostic assessment, interventions, quality assessment (using AMSTAR [Assessing the Methodological Quality of Systematic Reviews]), and key findings with their effect sizes.


In total, 42 meta-analyses published in the past 6 years and encompassing 81 outcomes were included. For the detection component, CHR-P individuals were young (mean [SD] age, 20.6 [3.2] years), were more frequently male (58%), and predominantly presented with attenuated psychotic symptoms lasting for more than 1 year before their presentation at specialized services. CHR-P individuals accumulated several sociodemographic risk factors compared with control participants. Substance use (33% tobacco use and 27% cannabis use), comorbid mental disorders (41% with depressive disorders and 15% with anxiety disorders), suicidal ideation (66%), and self-harm (49%) were also frequently seen in CHR-P individuals. CHR-P individuals showed impairments in work (Cohen d = 0.57) or educational functioning (Cohen d = 0.21), social functioning (Cohen d = 1.25), and quality of life (Cohen d = 1.75). Several neurobiological and neurocognitive alterations were confirmed in this study. For the prognosis component, the prognostic accuracy of CHR-P instruments was good, provided they were used in clinical samples. Overall, risk of psychosis was 22% at 3 years, and the risk was the highest in the brief and limited intermittent psychotic symptoms subgroup (38%). Baseline severity of attenuated psychotic (Cohen d = 0.35) and negative symptoms (Cohen d = 0.39) as well as low functioning (Cohen d = 0.29) were associated with an increased risk of psychosis. Controlling risk enrichment and implementing sequential risk assessments can optimize prognostic accuracy. For the intervention component, no robust evidence yet exists to favor any indicated intervention over another (including needs-based interventions and control conditions) for preventing psychosis or ameliorating any other outcome in CHR-P individuals. However, because the uncertainty of this evidence is high, needs-based and psychological interventions should still be offered.

Conclusions and Relevance:

This review confirmed recent substantial advancements in the detection and prognosis of CHR-P individuals while suggesting that effective indicated interventions need to be identified. This evidence suggests a need for specialized services to detect CHR-P individuals in primary and secondary care settings, to formulate a prognosis with validated psychometric instruments, and to offer needs-based and psychological interventions.

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