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Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

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Fusar-Poli, Paolo, Cappucciati, Marco, Borgwardt, Stefan, Woods, Scott W., Addington, Jean, Nelson, Barnaby, Nieman, Dorien H., Stahl, Daniel R., Rutigliano, Grazia, Riecher-Rössler, Anita, Simon, Andor E., Mizuno, Masafumi, Lee, Tae Young, Kwon, Jun Soo, Lam, May M. L., Perez, Jesus, Keri, Szabolcs, Amminger, Paul, Metzler, Sibylle, Kawohl, Wolfram, Rössler, Wulf, Lee, Jimmy, Labad, Javier, Ziermans, Tim, An, Suk Kyoon, Liu, Chen-Chung, Woodberry, Kristen A., Braham, Amel, Corcoran, Cheryl, McGorry, Patrick, Yung, Alison R., McGuire, Philip K.·2016·JAMA Psychiatry

DOI 10.1001/jamapsychiatry.2015.2324

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Abstract

IMPORTANCE: Individuals can be classified as being at clinical high risk (CHR) for psychosis if they meet at least one of the ultra-high-risk (UHR) inclusion criteria (brief limited intermittent psychotic symptoms [BLIPS] and/or attenuated psychotic symptoms [APS] and/or genetic risk and deterioration syndrome [GRD]) and/or basic symptoms [BS]. The meta-analytical risk of psychosis of these different subgroups is still unknown. OBJECTIVE: To compare the risk of psychosis in CHR individuals who met at least one of the major inclusion criteria and in individuals not at CHR for psychosis (CHR-). DATA SOURCES: Electronic databases (Web of Science, MEDLINE, Scopus) were searched until June 18, 2015, along with investigation of citations of previous publications and a manual search of the reference lists of retrieved articles. STUDY SELECTION: We included original follow-up studies of CHR individuals who reported the risk of psychosis classified according to the presence of any BLIPS, APS and GRD, APS alone, GRD alone, BS, and CHR-. DATA EXTRACTION AND SYNTHESIS: Independent extraction by multiple observers and random-effects meta-analysis of proportions. Moderators were tested with meta-regression analyses (Bonferroni corrected). Heterogeneity was assessed with the I2 index. Sensitivity analyses tested robustness of results. Publication biases were assessed with funnel plots and the Egger test. MAIN OUTCOMES AND MEASURES: The proportion of each subgroup with any psychotic disorder at 6, 12, 24, 36, and 48 or more months of follow-up. RESULTS: Thirty-three independent studies comprising up to 4227 individuals were included. The meta-analytical proportion of individuals meeting each UHR subgroup at intake was: 0.85 APS (95%CI, 0.79-0.90), 0.1 BLIPS (95%CI, 0.06-0.14), and 0.05 GRD (95%CI, 0.03-0.07). There were no significant differences in psychosis risk at any time point between the APS and GRD and the APS-alone subgroups. There was a higher risk of psychosis in the any BLIPS greater than APS greater than GRD-alone subgroups at 24, 36, and 48 or more months of follow-up. There was no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too few BS or BS and UHR studies to allow robust conclusions. CONCLUSIONS AND RELEVANCE: There is meta-analytical evidence that BLIPS represents separate risk subgroup compared with the APS. The GRD subgroup is infrequent and not associated with an increased risk of psychosis. Future studies are advised to stratify their findings across these different subgroups. The CHR guidelines should be updated to reflect these differences.

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Authors: Fusar-Poli, P., Cappucciati, M., Borgwardt, S., Woods, S. W., Addington, J., Nelson, B., Nieman, D. H., Stahl, D. R., Rutigliano, G., Riecher-Rössler, A., Simon, A. E., Mizuno, M., Lee, T. Y., Kwon, J. S., Lam, M. M. L., Perez, J., Keri, S., Amminger, P., Metzler, S., Kawohl, W., Rössler, W., Lee, J., Labad, J., Ziermans, T., An, S. K., Liu, C.-C., Woodberry, K. A., Braham, A., Corcoran, C., McGorry, P., Yung, A. R., & McGuire, P. K.
Affiliations: Institute of Psychiatry, Psychology, and Neuroscience, King’s College, London, United Kingdom2OASIS Clinic, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom
King's College London (GB)
University of Basel (CH)
Yale University (US)
University of Calgary (CA)
The University of Melbourne (AU)
Amsterdam UMC Location University of Amsterdam (NL)
University of Basel Psychiatric Clinics, Basel, Switzerland
Toho University (JP)
Seoul National University (KR)
Kwai Chung Hospital (CN)
Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom
Nyiro Gyula Hospital, National Institute of Psychiatry and Addictions, Budapest, Hungary
Orygen, the National Centre of Excellence in Youth Mental Health, and Centre for Youth Mental Health, the University of Melbourne, Parkville, Australia
University Hospital Zurich (CH)
Centre for Social Psychiatry, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, Zurich, Switzerland
Institute of Mental Health (SG)
Corporació Sanitària Parc Taulí (ES)
Leiden University (NL)
Yonsei University (KR)
National Taiwan University (TW)
Beth Israel Deaconess Medical Center (US)
Hôpital Farhat Hached (TN)
Columbia University (US)
University of Manchester (GB)
ORCID: Cappucciati, Marco
Borgwardt, Stefan
Woods, Scott W.
Addington, Jean
Nelson, Barnaby
Nieman, Dorien H.
Stahl, Daniel R.
Rutigliano, Grazia
Simon, Andor E.
Lee, Tae Young
Kwon, Jun Soo
Kawohl, Wolfram
Lee, Jimmy
Labad, Javier
Ziermans, Tim
An, Suk Kyoon
Liu, Chen-Chung
Woodberry, Kristen A.
Braham, Amel
Corcoran, Cheryl
McGorry, Patrick
Yung, Alison R.
McGuire, Philip K.
Venue: JAMA Psychiatry
Publisher: American Medical Association (AMA)
Published: 2016-02-01
Volume: 73
Issue: 2
Pages: 113
ISSN: 2168-622X (ISSN-L)
DOI: 10.1001/jamapsychiatry.2015.2324
OpenAlex: W2207056170
Cited by: 440
References: 65
Citations by year: 2026: 22 · 2025: 32 · 2024: 27 · 2023: 36 · 2022: 36 · 2021: 59 · 2020: 66 · 2019: 70 · 2018: 36 · 2017: 31 · 2016: 23
FWCI: 24.33
Type: journal article
Language: en
Open access: green
pure.amsterdamumc.nl
Licence: other-oa
Locations: JAMA Psychiatry (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
CINECA IRIS Institutial research information system (University of Pisa) (submittedVersion)
YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
Data Archiving and Networked Services (DANS) (submittedVersion)
Leiden Repository (Leiden University) (submittedVersion)
Own your potential (DEAKIN) (submittedVersion)
edoc (University of Basel) (submittedVersion)
Figshare (submittedVersion)
Research Portal (King's College London) (submittedVersion, other-oa)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
Funders: National Institute of Mental Health (K23MH066279, U01MH066160, R03MH108933)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
Social Sciences › Psychology › Clinical Psychology › Psychopathy, Forensic Psychiatry, Sexual Offending
Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Keywords: clinical high risk for psychosis, attenuated psychotic symptoms, basic symptoms, transition to psychosis, bipolar disorder, psychosis spectrum disorders
MeSH terms: Humans, Psychotic Disorders, Risk

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Heterogeneity of Psychosis Risk Within Individuals at Clinical High Risk: A Meta-analytical Stratification

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