Examining the variability of neurocognitive functioning in individuals at clinical high risk for psychosis: a meta-analysis

Abstract

This study aims to meta-analytically characterize the presence and magnitude of within-group variability across neurocognitive functioning in young people at Clinical High-Risk for psychosis (CHR-P) and comparison groups. Multistep, PRISMA/MOOSE-compliant systematic review (PROSPERO-CRD42020192826) of the Web of Science database, Cochrane Central Register of Reviews and Ovid/PsycINFO and trial registries up to July 1, 2020. The risk of bias was assessed using a modified version of the NOS for cohort and cross-sectional studies. Original studies reporting neurocognitive functioning in individuals at CHR-P compared to healthy controls (HC) or first-episode psychosis (FEP) patients were included. The primary outcome was the random-effect meta-analytic variability ratios (VR). Secondary outcomes included the coefficient of variation ratios (CVR). Seventy-eight studies were included, relating to 5162 CHR-P individuals, 2865 HC and 486 FEP. The CHR-P group demonstrated higher variability compared to HC (in descending order of magnitude) in visual memory (VR: 1.41, 95% CI 1.02-1.94), executive functioning (VR: 1.31, 95% CI 1.18-1.45), verbal learning (VR: 1.29, 95% CI 1.15-1.45), premorbid IQ (VR: 1.27, 95% CI 1.09-1.49), processing speed (VR: 1.26, 95% CI 1.07-1.48), visual learning (VR: 1.20, 95% CI 1.07-1.34), and reasoning and problem solving (VR: 1.17, 95% CI 1.03-1.34). In the CVR analyses the variability in CHR-P population remains in the previous neurocognitive domains and emerged in attention/vigilance, working memory, social cognition, and visuospatial ability. The CHR-P group transitioning to psychosis showed greater VR in executive functioning compared to those not developing psychosis and compared to FEP groups. Clinical high risk for psychosis subjects shows increased variability in neurocognitive performance compared to HC. The main limitation of this study is the validity of the VR and CVR as an index of variability which has received debate. This finding should be explored by further individual-participant data research and support precision medicine approaches.

Fig. 1. PRISMA Flow Diagram.

Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart outlining the study selection process.

Fig. 2. Variability ratio (VR) of neurocognitive functioning between CHR-P vs HC.

CHR-P Clinical high risk for Psychosis, HC Healthy Controls, BACS SC indicates Brief Assessment of Cognition Scale Symbol Coding, DST digit symbol coding test, Stroop C Stroop color naming task, StroopW Stroop color word reading task, TMT-A Trail Making Test-Part A, CPT-IP Continuous Performance Test–Identical Pairs, LNS Letter Number Span, LNST Letter Number Sequencing Test, SOPT Self-ordered Pointing Test, WMS-III: SS Wechsler Memory Scale III: Spatial Span, CVLT California Verbal Learning Test, RAVLT Rey Auditory Verbal Learning Test, HVLT-R Hopkins Verbal Learning Test-Revised, BVMT-R Brief Visuospatial Memory Test-Revised, WMS VM Wechsler Memory Scale Immediate Visual Memory, ROCF Rey-Osterrieth Complex Figure Immediate Recall, NAB Mazes Neuropsychological Assessment Battery Mazes, DFAR Degraded Facial Affect Recognition, RMET Reading the Mind in the Eyes Test.

Fig. 3. Variability ratio (VR) of neurocognitive functioning between CHR-P vs HC.

CHR-P Clinical high risk for Psychosis, HC Healthy Controls, IQ Wechsler Intelligence Scales full, IQ verbal Wechsler Intelligence Scales verbal, IQ performance Wechsler Intelligence Scales performance, NART National Adult Reading Test, MWT-B Mehrfach-Wortschaftz-Intelligenz Test-Part B, RAVLT DR Rey Auditory Verbal Learning Test Delayed Recall, ROCF DR Rey- Osterrieth Complex Figure Test Delayed Recall, WMS VR Weschler Memory Scale Visual Reproduction Delayed Recall, TMT-B Trail Making Test-Part B, WCST categories Wisconsin Card Sorting Test categories, WCST number of correct responses Wisconsin Card Sorting Test number of correct responses, WCST perseverative errors Wisconsin Card Sorting Test perseverative errors, WCST perseverative responses Wisconsin Card Sorting Test perseverative responses, UPSIT University of Pennsylvania Smell Identification Test.

Fig. 4. Variability ratio (VR) of neurocognitive functioning between CHR-P transitioning to psychosis vs CHR-P not transitioning to psychosis.

CHR-P Clinical high risk for Psychosis, DST Digit Symbol Coding Test, TMT-A Trail Making Test-Part A, CPT Continuous Performance Test-Identical Pairs, CVLT California Verbal Learning Test, IQ Wechsler Intelligence Scales full, ROCF DR Rey-Osterrieth Complex Figure Test Delayed Recall, LNST Letter Number Sequencing Test, UPSIT University of Pennsylvania Smell Identification Test, WCST perseverative errors Wisconsin Card Sorting Test perseverative errors, NART National Adult Reading Test.

Fig. 5. Variability ratio (VR) of neurocognitive functioning between CHR-P vs FEP.

CHR-P Clinical high risk for Psychosis, FEP First Episode Psychosis, TMT-A Trail Making Test Part A, HVLT-R Hopkins Verbal Learning Test-Revised, CVLT California Verbal Learning Test, IQ Wechsler Intelligence Scales full, NART National Adult Reading Test, TMT-B Trail Making Test-Part B, WCST categories Wisconsin Card Sorting Test categories, WCST perseverative errors Wisconsin Card Sorting Test perseverative errors.