Prognostic accuracy and clinical utility of psychometric instruments for individuals at clinical high-risk of psychosis: a systematic review and meta-analysis

Accurate prognostication of individuals at clinical high-risk for psychosis (CHR-P) is an essential initial step for effective primary indicated prevention. We aimed to summarise the prognostic accuracy and clinical utility of CHR-P assessments for primary indicated psychosis prevention. Web of Knowledge databases were searched until 1st January 2022 for longitudinal studies following-up individuals undergoing a psychometric or diagnostic CHR-P assessment, reporting transition to psychotic disorders in both those who meet CHR-P criteria (CHR-P + ) or not (CHR-P-). Prognostic accuracy meta-analysis was conducted following relevant guidelines. Primary outcome was prognostic accuracy, indexed by area-under-the-curve (AUC), sensitivity and specificity, estimated by the number of true positives, false positives, false negatives and true negatives at the longest available follow-up time. Clinical utility analyses included: likelihood ratios, Fagan's nomogram, and population-level preventive capacity (Population Attributable Fraction, PAF). A total of 22 studies (n = 4 966, 47.5% female, age range 12-40) were included. There were not enough meta-analysable studies on CHR-P diagnostic criteria (DSM-5 Attenuated Psychosis Syndrome) or non-clinical samples. Prognostic accuracy of CHR-P psychometric instruments in clinical samples (individuals referred to CHR-P services or diagnosed with 22q.11.2 deletion syndrome) was excellent: AUC = 0.85 (95% CI: 0.81-0.88) at a mean follow-up time of 34 months. This result was driven by outstanding sensitivity (0.93, 95% CI: 0.87-0.96) and poor specificity (0.58, 95% CI: 0.50-0.66). Being CHR-P + was associated with a small likelihood ratio LR + (2.17, 95% CI: 1.81-2.60) for developing psychosis. Being CHR-P- was associated with a large LR- (0.11, 95%CI: 0.06-0.21) for developing psychosis. Fagan's nomogram indicated a low positive (0.0017%) and negative (0.0001%) post-test risk in non-clinical general population samples. The PAF of the CHR-P state is 10.9% (95% CI: 4.1-25.5%). These findings consolidate the use of psychometric instruments for CHR-P in clinical samples for primary indicated prevention of psychosis. Future research should improve the ability to rule in psychosis risk.