Meta-Analysis

. 2023 Jul;223(1):282-294.

doi: 10.1192/bjp.2022.203.

Negative symptoms in children and adolescents with early-onset psychosis and at clinical high-risk for psychosis: systematic review and meta-analysis

Gonzalo Salazar de Pablo¹, Ana Catalan², Julio Vaquerizo Serrano³, Borja Pedruzo⁴, Luis Alameda⁵, Veronica Sandroni⁶, Alvaro Armendariz⁷, Victoria Rodriguez⁸, Celso Arango⁹, Carmen Moreno⁹, Johnny Downs³, Chris Abbott¹⁰, Jae Il Shin¹¹, Marco Solmi¹², Paolo Fusar-Poli¹³, Christoph U Correll¹⁴

Affiliations

¹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK; and Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
² Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; and Mental 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, Vizcaya, Spain.
³ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Department of Psychiatry, Basurto University Hospital, Bilbao, Spain.
⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Service of General Psychiatry, Treatment and Early Intervention in Psychosis Program, University Hospital (CHUV), Lausanne, Switzerland; and Centro Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio, Departamento de Psiquiatria, Universidad de Sevilla, Sevilla, Spain.
⁶ Department of Psychiatry, Faculty of Medicine, Université Paris Cité, Paris, France; and Department of Psychiatry, Groupe Hospitalier Paul Guiraud, Villejuif, France.
⁷ Department of Psychiatry and Psychology, Hospital Sant Joan de Déu de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
⁸ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
¹⁰ Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK.
¹¹ Department of Paediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
¹² Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada; Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada; and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.
¹³ Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; and National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁴ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; Department of Psychiatry, Northwell Health, The Zucker Hillside Hospital, Glen Oaks, New York, USA; Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/ Northwell, Hempstead, New York, USA; and Center for Psychiatric Neuroscience, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.

PMID: 37194556
PMCID: PMC10331322
DOI: 10.1192/bjp.2022.203

Meta-Analysis

Negative symptoms in children and adolescents with early-onset psychosis and at clinical high-risk for psychosis: systematic review and meta-analysis

Gonzalo Salazar de Pablo et al. Br J Psychiatry. 2023 Jul.

. 2023 Jul;223(1):282-294.

doi: 10.1192/bjp.2022.203.

Authors

Affiliations

¹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK; and Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
² Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; and Mental 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, Vizcaya, Spain.
³ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
⁴ Department of Psychiatry, Basurto University Hospital, Bilbao, Spain.
⁵ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK; Service of General Psychiatry, Treatment and Early Intervention in Psychosis Program, University Hospital (CHUV), Lausanne, Switzerland; and Centro Investigacion Biomedica en Red de Salud Mental (CIBERSAM), Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocio, Departamento de Psiquiatria, Universidad de Sevilla, Sevilla, Spain.
⁶ Department of Psychiatry, Faculty of Medicine, Université Paris Cité, Paris, France; and Department of Psychiatry, Groupe Hospitalier Paul Guiraud, Villejuif, France.
⁷ Department of Psychiatry and Psychology, Hospital Sant Joan de Déu de Barcelona, L'Hospitalet de Llobregat, Barcelona, Spain.
⁸ Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
⁹ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain.
¹⁰ Child and Adolescent Mental Health Services, South London and Maudsley NHS Foundation Trust, London, UK.
¹¹ Department of Paediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
¹² Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Psychiatry, University of Ottawa, Ottawa, Ontario, Canada; Department of Mental Health, The Ottawa Hospital, Ottawa, Ontario, Canada; and Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany.
¹³ Early Psychosis: Interventions and Clinical Detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK; Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy; OASIS service, South London and Maudsley NHS Foundation Trust, London, UK; and National Institute for Health Research, Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, London, UK.
¹⁴ Department of Child and Adolescent Psychiatry, Charité Universitätsmedizin, Berlin, Germany; Department of Psychiatry, Northwell Health, The Zucker Hillside Hospital, Glen Oaks, New York, USA; Department of Psychiatry and Molecular Medicine, Zucker School of Medicine at Hofstra/ Northwell, Hempstead, New York, USA; and Center for Psychiatric Neuroscience, The Feinstein Institutes for Medical Research, Manhasset, New York, USA.

PMID: 37194556
PMCID: PMC10331322
DOI: 10.1192/bjp.2022.203

Abstract

Background: Early-onset psychosis (EOP) refers to the development of a first episode of psychosis before 18 years of age. Individuals at clinical high risk for psychosis (CHR-P) include adolescents and young adults, although most evidence has focused on adults. Negative symptoms are important prognostic indicators in psychosis. However, research focusing on children and adolescents is limited.

Aims: To provide meta-analytical evidence and a comprehensive review of the status and advances in the diagnosis, prognosis and treatment of negative symptoms in children and adolescents with EOP and at CHR-P.

Method: PRISMA/MOOSE-compliant systematic review (PROSPERO: CRD42022360925) from inception to 18 August 2022, in any language, to identify individual studies conducted in EOP/CHR-P children and adolescents (mean age <18 years) providing findings on negative symptoms. Findings were systematically appraised. Random-effects meta-analyses were performed on the prevalence of negative symptoms, carrying out sensitivity analyses, heterogeneity analyses, publication bias assessment and quality assessment using the Newcastle-Ottawa Scale.

Results: Of 3289 articles, 133 were included (n = 6776 EOP, mean age 15.3 years (s.d. = 1.6), males = 56.1%; n = 2138 CHR-P, mean age 16.1 years (s.d. = 1.0), males = 48.6%). There were negative symptoms in 60.8% (95% CI 46.4%-75.2%) of the children and adolescents with EOP and 79.6% (95% CI 66.3-92.9%) of those at CHR-P. Prevalence and severity of negative symptoms were associated with poor clinical, functional and intervention outcomes in both groups. Different interventions were piloted, with variable results requiring further replication.

Conclusions: Negative symptoms are common in children and adolescents at early stages of psychosis, particularly in those at CHR-P, and are associated with poor outcomes. Future intervention research is required so that evidence-based treatments will become available.

Keywords: Early-onset psychosis; clinical high risk of psychosis; meta-analysis; prevention; psychotic disorders.

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Conflict of interest statement

G.S.P. has received personal fees from Janssen Cilag and Menarini. A.C. has received personal fees from Janssen and is supported by the Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness. C.A. has been a consultant to or has received honoraria or grants from Acadia, Angelini, Boehringer, Gedeon Richter, Janssen Cilag, Lundbeck, Minerva, Otsuka, Pfizer, Roche, Sage, Servier, Shire, Schering Plough, Sumitomo Dainippon Pharma, Sunovion and Takeda. C.M. has received honoraria as a consultant and/or advisor and/or for lectures from Angelini, Esteve, Exeltis Janssen, Lundbeck, Neuraxpharm, Nuvelution, Otsuka, Pfizer, Servier and Sunovion outside the submitted work. P.F.P. has received research or personal fees from Lundbeck, Angelini, Menarini and Boehringer Ingelheim. C.A. and C.M. are supported by the Spanish Ministry of Science, Innovation, and Universities, Instituto de Salud Carlos III, European Regional Development Fund ‘A way of making Europe’, Centro de Investigación Biomédica en Red Salud Mental, Madrid Regional Government; and Fundación Mutua Madrileña. J.D. is supported by NIHR Clinician Science Fellowship award and has received support from a Medical Research Council Clinical Research Training Fellowship and Psychiatry Research Trust Peggy Pollak Research Fellowship in Developmental Psychiatry. C.U.C. has been a consultant and/or advisor to or has received honoraria from AbbVie, Acadia, Alkermes, Allergan, Angelini, Aristo, Boehringer-Ingelheim, Cardio Diagnostics, Cerevel, CNX Therapeutics, Compass Pathways, Darnitsa, Gedeon Richter, Hikma, Holmusk, IntraCellular Therapies, Janssen/J&J, Karuna, LB Pharma, Lundbeck, MedAvante-ProPhase, MedInCell, Merck, Mindpax, Mitsubishi Tanabe Pharma, Mylan, Neurocrine, Newron, Noven, Otsuka, Pharmabrain, PPD Biotech, Recordati, Relmada, Reviva, Rovi, Seqirus, SK Life Science, Sunovion, Sun Pharma, Supernus, Takeda, Teva, and Viatris; he provided expert testimony for Janssen and Otsuka; he served on a Data Safety Monitoring Board for Lundbeck, Relmada, Reviva, Rovi, Supernus, and Teva; he has received grant support from Janssen and Takeda and royalties from UpToDate and is a stock option holder of Cardio Diagnostics, Mindpax, LB Pharma and Quantic.

Figures

**Fig. 1**
Preferred reporting items for systematic reviews and meta-analyses (PRISMA) flowchart outlining the study selection process.

**Fig. 2**
Negative symptom prevalence in children and adolescents with early-onset psychosis.

**Fig. 3**
Negative symptom prevalence in children and adolescents at clinical high-risk for psychosis.

See this image and copyright information in PMC

Comment in

The emergence of primary negative symptoms: relevance of timing?
Chen EYH, Wong SMY, Hui CLM, Suen YN, Chan SKW. Chen EYH, et al. Br J Psychiatry. 2023 Jul;223(1):280-281. doi: 10.1192/bjp.2023.51. Br J Psychiatry. 2023. PMID: 37184101

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Negative symptoms in children and adolescents with early-onset psychosis and at clinical high-risk for psychosis: systematic review and meta-analysis

Affiliations

Negative symptoms in children and adolescents with early-onset psychosis and at clinical high-risk for psychosis: systematic review and meta-analysis

Authors

Affiliations

Abstract

Conflict of interest statement

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