Discriminative validity of Clinical High-Risk Status for Psychosis among help-seekers: a systematic review and meta-analysis

Schizophrenia (Heidelb). 2026 Jul 16. doi: 10.1038/s41537-026-00785-4. Online ahead of print.

ABSTRACT

The Clinical High-Risk for Psychosis (CHR-P) paradigm underpins early detection strategies and informs the DSM-5 construct of Attenuated Psychosis Syndrome (APS), yet its discriminative predictive validity relative to CHR-P-negative help-seekers has not been systematically quantified. We conducted a systematic review and meta-analysis of longitudinal studies comparing transition to psychosis among help-seeking individuals according to CHR-P status. PubMed/MEDLINE and the Cochrane Library were searched from inception to June 22, 2026. Eligible studies included help-seeking samples assessed with validated CHR-P instruments and reporting psychosis transition outcomes separately for CHR-P-positive and CHR-P-negative participants. Random-effects meta-analyses estimated transition prevalence and relative risks (RRs), while heterogeneity, publication bias, and moderators were examined. 14 studies including 4477 participants (2220 CHR-P-positive and 2257 CHR-P-negative) met inclusion criteria. Estimated transition rates were 14.7% [95% CI, 9.7-21.7%) among CHR-P-positive individuals and 1.6% (95% CI, 0.8-3.2%) among CHR-P-negative individuals. CHR-P status was associated with an almost ten-fold increased risk of transition to psychosis (RR, 9.8; 95% CI, 4.5-21.82), with no significant moderation by follow-up duration or sample characteristics. These findings demonstrate strong discriminative and predictive validity of CHR-P criteria among help-seekers, supporting attenuated psychotic symptoms as a clinically meaningful pre-psychotic phenotype. Results support consideration of APS in DSM-6 within a prognostically grounded, stepped-care framework rather than as a categorical disorder.

PMID:42463671 | DOI:10.1038/s41537-026-00785-4