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

Abstract

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.

Fig. 1. Study selection and inclusion for the current meta-analysis.

n = 8 of the n = 11 studies from the previous meta-analysis were included in this analysis [–60], with the other n = 3 samples [21, 42, 100] being replaced by more recent publications with larger overlapping samples and/or longer follow-up of the original sample [42, 46, 50].

Fig. 2. Meta-analytical summary receiver operating characteristic (SROC) curve.

Summarises the prognostic accuracy of clinical high risk for psychosis (CHR-P) psychometric instruments in clinical samples at an average follow-up time of 34 months. N.B. x-axis for Sp runs reversed. Se – sensitivity, Sp – specificity, AUC – area under the curve, 1 – Klosterkötter et al. [53], 2 - Kobayashi et al. [39], 3 – Yung et al. [54], 4 – Woods et al. [55], 5– Liu et al. [56], 6 – Addington et al. [57], 7 – Simon et al. [58], 8 – Lee et al. [59], 9 – Lindgren et al. [40], 10 – Schultze-Lutter et al. [60], 11 – Kline et al. [41], 12 – Kotlicka-Antczak et al. [42], 13 - Fusar-Poli et al. [44], 14 – Francesconi et al. [43], 15 – Pelizza et al. [48], 16 – Xu et al. [47], 17 – Papmeyer et al. [46], 18 - Masillo et al. [45], 19 – Schneider et al. [49], 20 - Mensi et al. [50].

Fig. 3. Meta-analytical probability-modifying plot.

This plot llustrates the relationship between pre-test probability (PreTP) (6.7–14.1% psychosis risk at 34 months in clinical samples) and post-test probability (PostTP) (psychosis risk at 34 months in clinical samples based on clinical high risk psychometric interviews), computed as the likelihood of a positive (above diagonal line; LR + ) or negative (below diagonal line, LR−) test result over the 0–1 range of PreTP.

Fig. 4. Fagan’s nomogram.

This plot illustrates the meta-analytical clinical value (post-test probability) of clinical high risk for psychosis (CHR-P) psychometric instruments in order to predict risk of psychosis at 34 months in the general population.