Cognitive Function and Variability in Antipsychotic Drug-Naive Patients With First-Episode Psychosis: A Systematic Review and Meta-Analysis

Abstract

Importance: Cognitive impairment contributes significantly to clinical outcome and level of function in individuals with psychotic disorders. These impairments are present already at psychosis onset at a group level; however, the question of heterogeneity in cognitive function among patients has not been systematically investigated.

Objective: To provide an updated quantification of cognitive impairment at psychosis onset before patients receive potentially confounding antipsychotic treatment, and to investigate variability in cognitive function compared with healthy controls.

Data sources: In this systematic review and meta-analysis, PubMed articles were searched up to September 15, 2022.

Study selection: Original studies reporting data on cognitive function in antipsychotic drug-naive patients with first-episode psychosis (FEP) were included.

Data extraction and synthesis: Data were independently extracted by 2 researchers. Cognitive tasks were clustered according to 6 domains of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery and the domain of executive function. Random-effects model meta-analyses of mean differences and coefficient of variation ratios (CVRs) were performed, as well as meta-regressions, assessment of study quality, and publication bias.

Main outcomes and measures: The main outcome measure was Hedges g for mean differences in cognition and CVR for within-group variability.

Results: Fifty studies were included in the analysis with a total of 2625 individuals with FEP (mean [SD] age, 25.2 [3.6] years, 60% male; 40% female) and 2917 healthy controls (mean [SD] age, 26.0 [4.6]; 55% male; 45% female). In all cognitive domains, the FEP group displayed significant impairment compared with controls (speed of processing: Hedges g = -1.16; 95% CI, -1.35 to -0.98; verbal learning: Hedges g = -1.08; 95% CI, -1.28 to -0.88; visual learning: Hedges g = -1.05; 95% CI, -1.27 to -0.82; working memory: Hedges g = -1.04; 95% CI, -1.35 to -0.73; attention: Hedges g = -1.03; 95% CI, -1.24 to -0.82; reasoning/problem solving: Hedges g = -0.90; 95% CI, -1.12 to -0.68; executive function: Hedges g = -0.88; 95% CI, -1.07 to -0.69). Individuals with FEP also exhibited a larger variability across all domains (CVR range, 1.34-1.92).

Conclusions and relevance: Results of this systematic review and meta-analysis identified cognitive impairment in FEP before the initiation of antipsychotic treatment, with large effect sizes. The high variability within the FEP group suggests the need to identify those individuals with more severe cognitive problems who risk worse outcomes and could benefit the most from cognitive remediation.

Figure 1.. Adapted Version of the PRISMA 2020 Flow Diagram for Updated Systematic Reviews Including Searches of Databases, Registers, and Other Sources

DUP indicates duration of untreated psychosis; MCCB, Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery.

Figure 2.. Combined Forest Plot of Mean Differences in Cognitive Ability for Speed of Processing, Verbal Learning, and Visual Learning Domains in Drug-Naive Patients With First-Episode Psychosis (FEP) Compared With Controls

The lines extending from the pooled estimates indicate prediction interval. BACS indicates Brief Assessment of Cognition in Schizophrenia; BSRT, Buschke Selective Reminding Test; BVMT-R, Brief Visuospatial Memory Test–Revised; CANTAB PRM, Cambridge Neuropsychological Test Automated Battery Pattern Recognition Memory; CVLT, California Verbal Learning Test; HVLT-R, Hopkins Verbal Learning Test–Revised; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; RCFT, Rey-Osterrieth Complex Figure Test; SMD, standardized mean difference; SVLT, Serial Verbal Learning Task; TMT-A, Trail Making Test Part A; WAIS, Wechsler Adult Intelligence Scale; WMS, Wechsler Memory Scale.

Figure 3.. Combined Forest Plot of Mean Differences in Cognitive Ability for Working Memory, Attention, Reasoning/Problem Solving, and Executive Function Domains in Drug-Naive Patients With First-Episode Psychosis (FEP) Compared With Controls

The lines extending from the pooled estimates indicate prediction interval. BACS indicates Brief Assessment of Cognition in Schizophrenia; CANTAB IED, Cambridge Neuropsychological Test Automated Battery intradimensional/extradimensional set shifting; CANTAB SOC, CANTAB Stockings of Cambridge; CANTAB SWM, CANTAB Spatial Working Memory; CPT, Continuous Performance Test; CPT-IP, Continuous Performance Test–Identical Pairs; LNS, Letter Number Sequencing; PASAT, Paced Auditory Serial Addition Test; SMD, standardized mean difference; TMT-B, Trail Making Test Part B; WAIS, Wechsler Adult Intelligence Scale; WCST, Wisconsin Card Sorting Test.

Figure 4.. Combined Forest Plot of Within-Group Variability in Cognitive Ability for Speed of Processing, Verbal Learning, and Visual Learning Domains in Drug-Naive Patients With First-Episode Psychosis (FEP) Compared With Controls

BACS indicates Brief Assessment of Cognition in Schizophrenia; BSRT, Buschke Selective Reminding Test; BVMT-R, Brief Visuospatial Memory Test-Revised; CANTAB PRM, Cambridge Neuropsychological Test Automated Battery Pattern Recognition Memory; CVLT, California Verbal Learning Test; HVLT-R, Hopkins Verbal Learning Test–Revised; RBANS, Repeatable Battery for the Assessment of Neuropsychological Status; RCFT, Rey-Osterrieth Complex Figure Test; SMD, standardized mean difference; SVLT, Serial Verbal Learning Task; TMT-A, Trail Making Test Part A; WAIS, Wechsler Adult Intelligence Scale; WMS, Wechsler Memory Scale.

Figure 5.. Combined Forest Plot of Within-Group Variability in Cognitive Ability for Working Memory, Attention, Reasoning/Problem Solving, and Executive Function Domains in Drug-Naive Patients With First-Episode Psychosis (FEP) Compared With Controls

BACS indicates Brief Assessment of Cognition in Schizophrenia; CANTAB IED, Cambridge Neuropsychological Test Automated Battery intradimensional/extradimensional set shifting; CANTAB SOC, CANTAB Stockings of Cambridge; CANTAB SWM, CANTAB Spatial Working Memory; CPT, Continuous Performance Test; CPT-IP, Continuous Performance Test–Identical Pairs; CVR, coefficient of variation ratio; LNS, Letter Number Sequencing; PASAT, Paced Auditory Serial Addition Test; TMT-B, Trail Making Test Part B; WAIS, Wechsler Adult Intelligence Scale; WCST, Wisconsin Card Sorting Test.