Longitudinal outcome of attenuated positive symptoms, negative symptoms, functioning and remission in people at clinical high risk for psychosis: a meta-analysis

[EN] Background: Little is known about clinical outcomes other than transition to psychosis in people at Clinical High-Risk for psychosis (CHR-P). Our aim was to comprehensively meta-analytically evaluate for the first time a wide range of clinical and functional outcomes beyond transition to psychosis in CHR-P individuals. Methods: PubMed and Web of Science were searched until November 2020 in this PRISMA compliant metaanalysis (PROSPERO:CRD42020206271). Individual longitudinal studies conducted in individuals at CHR-P providing data on at least one of our outcomes of interest were included. We carried out random-effects pairwise meta-analyses, meta-regressions, and assessed publication bias and study quality. Analyses were twotailed with a=0.05. Findings: 75 prospective studies were included (n=5,288, age=20.0 years, females=44.5%). Attenuated positive symptoms improved at 12 (Hedges’ g=0.753, 95%CI=0.495-1.012) and 24 (Hedges’ g=0.836, 95%CI=0.463- 1.209), but not 36 months (Hedges’ g=0.315. 95%CI=-0.176 0.806). Negative symptoms improved at 12 (Hedges’ g=0.496, 95%CI=0.315 0.678), but not 24 (Hedges’ g=0.499, 95%CI=-0.137 1.134) or 36 months (Hedges’ g=0.033, 95%CI=-0.439 0.505). Depressive symptoms improved at 12 (Hedges’ g=0.611, 95%CI=0.441 0.782) and 24 (Hedges’ g=0.583, 95%CI=0.364 0.803), but not 36 months (Hedges’ g=0.512 95%CI=-0.337 1.361). Functioning improved at 12 (Hedges’ g=0.711, 95%CI=0.488 0.934), 24 (Hedges’ g=0.930, 95%CI=0.553 1.306) and 36 months (Hedges’ g=0.392, 95%CI=0.117 0.667). Remission from CHRP status occurred in 33.4% (95%CI=22.6 44.1%) at 12 months, 41.4% (95%CI=32.3 50.5%) at 24 months and 42.4% (95%CI=23.4 61.3%) at 36 months. Heterogeneity across the included studies was significant and ranged from I2=53.6% to I2=96.9%. The quality of the included studies (mean§SD) was 4.6§1.1 (range=2-8). Interpretation: CHR-P individuals improve on symptomatic and functional outcomes over time, but these improvements are not maintained in the longer term, and less than half fully remit. ...