Neurocognitive Functioning in Individuals at Clinical High Risk for Psychosis: A Systematic Review and Meta-analysis

Abstract

Importance: Neurocognitive functioning is a potential biomarker to advance detection, prognosis, and preventive care for individuals at clinical high risk for psychosis (CHR-P). The current consistency and magnitude of neurocognitive functioning in individuals at CHR-P are undetermined.

Objective: To provide an updated synthesis of evidence on the consistency and magnitude of neurocognitive functioning in individuals at CHR-P.

Data sources: Web of Science database, Cochrane Central Register of Reviews, and Ovid/PsycINFO and trial registries up to July 1, 2020.

Study selection: Multistep literature search compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses and Meta-analysis of Observational Studies in Epidemiology performed by independent researchers to identify original studies reporting on neurocognitive functioning in individuals at CHR-P.

Data extraction and synthesis: Independent researchers extracted the data, clustering the neurocognitive tasks according to 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) domains and 8 CHR-P domains. Random-effect model meta-analyses, assessment of publication biases and study quality, and meta-regressions were conducted.

Main outcomes and measures: The primary effect size measure was Hedges g of neurocognitive functioning in individuals at CHR-P (1) compared with healthy control (HC) individuals or (2) compared with individuals with first-episode psychosis (FEP) or (3) stratified for the longitudinal transition to psychosis.

Results: A total of 78 independent studies were included, consisting of 5162 individuals at CHR-P (mean [SD; range] age, 20.2 [3.3; 12.0-29.0] years; 2529 [49.0%] were female), 2865 HC individuals (mean [SD; range] age, 21.1 [3.6; 12.6-29.2] years; 1490 [52.0%] were female), and 486 individuals with FEP (mean [SD; range] age, 23.0 [2.0; 19.1-26.4] years; 267 [55.9%] were female). Compared with HC individuals, individuals at CHR-P showed medium to large deficits on the Stroop color word reading task (g = -1.17; 95% CI, -1.86 to -0.48), Hopkins Verbal Learning Test-Revised (g = -0.86; 95% CI, -1.43 to -0.28), digit symbol coding test (g = -0.74; 95% CI, -1.19 to -0.29), Brief Assessment of Cognition Scale Symbol Coding (g = -0.67; 95% CI, -0.95 to -0.39), University of Pennsylvania Smell Identification Test (g = -0.55; 95% CI, -0.97 to -0.12), Hinting Task (g = -0.53; 95% CI, -0.77 to -0.28), Rey Auditory Verbal Learning Test (g = -0.50; 95% CI, -0.78 to -0.21), California Verbal Learning Test (CVLT) (g = -0.50; 95% CI, -0.64 to -0.36), and National Adult Reading Test (g = -0.52; 95% CI, -1.01 to -0.03). Individuals at CHR-P were less impaired than individuals with FEP. Longitudinal transition to psychosis from a CHR-P state was associated with medium to large deficits in the CVLT task (g = -0.58; 95% CI, -1.12 to -0.05). Meta-regressions found significant effects for age and education on processing speed.

Conclusions and relevance: Findings from this meta-analysis support neurocognitive dysfunction as a potential detection and prognostic biomarker in individuals at CHR-P. These findings may advance clinical research and inform preventive approaches.

Figure 1.. PRISMA Flowchart Outlining the Study Selection Process

Figure 2.. Neurocognitive Task-Level Functioning of Individuals at Clinical High Risk for Psychosis (CHR-P) Compared With Healthy Control (HC) Individuals Across the 7 Measurement and Treatment Research to Improve Cognition in Schizophrenia Domains

Hedges g scores (mean and 95% CI) are given (negative values indicate worse performance among individuals at CHR-P vs HC individuals), along with the number of studies (k) included and sample size. BACS SC indicates Brief Assessment of Cognition Scale Symbol Coding; BVMT-R, Brief Visuospatial Memory Test–Revised; CPT-IP, Continuous Performance Test–Identical Pairs; CVLT, California Verbal Learning Test; DFAR, Degraded Facial Affect Recognition; DST, digit symbol coding test; HVLT-R, Hopkins Verbal Learning Test–Revised; LNS, Letter Number Span; LNST, Letter Number Sequencing Test; NAB Mazes, Neuropsychological Assessment Battery Mazes; RAVLT, Rey Auditory Verbal Learning Test; RMET, Reading the Mind in the Eyes Test; ROCF, Rey-Osterrieth Complex Figure Immediate Recall; SOPT, Self-ordered Pointing Test; Stroop C, Stroop color naming task; Stroop W, Stroop color word reading task; TMT-A, Trail Making Test–Part A; WMS-III: SS, Wechsler Memory Scale III: Spatial Span; WMS VM, Wechsler Memory Scale Immediate Visual Memory.

Figure 3.. Neurocognitive Task-Level Functioning of Individuals at Clinical High Risk for Psychosis (CHR-P) Compared With Healthy Control (HC) Individuals Across the CHR-P Domains

Hedges g scores (mean and 95% CI) are given (negative values indicate worse performance in individuals at CHR-P vs HC individuals), along with the number of studies included (k) and sample size. IQ indicates Wechsler Intelligence Scales (full); Verbal IQ, Wechsler Intelligence Scales (verbal); Performance IQ, Wechsler Intelligence Scales performance; MWT-B, Mehrfach-Wortschaftz-Intelligenz Test–Part B; NART, National Adult Reading Test; RAVLT DR, Rey Auditory Verbal Learning Test Delayed Recall; ROCF DR, Rey-Osterrieth Complex Figure Delayed Recall; TMT-B, Trail Making Test–Part B; UPSIT, University of Pennsylvania Smell Identification Test; WAIS/WISC BD, Wechsler Adult Intelligence Scale/Wechsler Intelligence Scale for Children Block Design; WCST, Wisconsin Card Sorting Test; WMS VR, Wechsler Memory Scale Visual Reproduction Delayed Recall. ^aAffected by publication bias.

Figure 4.. Neurocognitive Task-Level Functioning of Individuals at Clinical High Risk for Psychosis (CHR-P) Developing Psychosis Compared With Those Not Developing Psychosis Across the Measurement and Treatment Research to Improve Cognition in Schizophrenia and CHR-P Domains

Hedges g scores (mean and 95% CI) are given (negative values indicate worse performance in individuals at CHR-P who transitioned to psychosis [CHR-T] vs individuals at CHR-P who did not transition to psychosis [CHR-NT] groups), along with the number of studies included (k) and sample size. CPT-IP indicates Continuous Performance Test–Identical Pairs; CVLT, California Verbal Learning Test; DST, digit symbol coding test; IQ, Wechsler Intelligence Scales (full); LNST, Letter Number Sequencing Test; NART, National Adult Reading Test; ROCF DR, Rey-Osterrieth Complex Figure Delayed Recall; TMT-A, Trail Making Test–Part A; UPSIT, University of Pennsylvania Smell Identification Test; WCST, Wisconsin Card Sorting Test. ^aAffected by publication bias.

Figure 5.. Neurocognitive Task-Level Functioning of Individuals at Clinical High Risk for Psychosis (CHR-P) Compared With Individuals With First-Episode Psychosis (FEP) Across Measurement and Treatment Research to Improve Cognition in Schizophrenia and CHR-P Domains

Hedges g scores (mean and 95% CI) across neurocognitive tasks are given (negative values indicate worse performance in individuals at CHR-P compared with individuals with FEP) along with the number of studies included (k) and sample size. CVLT indicates California Verbal Learning Test; HVLT-R, Hopkins Verbal Learning Test–Revised; IQ, Wechsler Intelligence Scales (full); NART, National Adult Reading Test; TMT-A, Trail Making Test–Part A; TMT-B, Trail Making Test–Part B; WCST, Wisconsin Card Sorting Test. ^aAffected by publication bias.