Heterogeneity of psychosis risk within individuals at clinical high risk: A meta-analytical stratification

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

*Corresponding author for this work
249 Citations (Scopus)


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]. Themeta-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 individualswere included. The meta-analytical proportion of individuals meeting each UHR subgroup at intakewas: 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. Therewas 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. Therewas no evidence that the GRD subgroup has a higher risk of psychosis than the CHR- subgroup. There were too fewBS or BS and UHR studies to allowrobust 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.

Original languageEnglish
JournalJAMA Psychiatry
Issue number2
Pages (from-to)113-120
Number of pages8
Publication statusPublished - 02.2016


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