open access publication

Article, Early Access, 2024

Cognitive Function and Variability in Antipsychotic Drug-Naive Patients With First-Episode Psychosis

JAMA PSYCHIATRY, ISSN 2168-622X, 2168-622X, 10.1001/jamapsychiatry.2024.0016


Lee, Maria (Corresponding author) [1] [2] [3] Cernvall, Martin [4] Borg, Jacqueline [2] [3] Plaven-Sigray, Pontus [2] [3] [5] Larsson, Cornelia [2] [3] Erhardt, Sophie [2] Sellgren, Carl M. [2] [3] Fatouros-Bergman, Helena [2] [3] Cervenka, Simon [2] [3] [4]


  1. [1] Ctr Psychiat Res, Dept Clin Neurosci, Bioclinicum, Akadem Straket 1,J4-14, S-17176 Stockholm, Sweden
  2. [NORA names: Sweden; Europe, EU; Nordic; OECD];
  3. [2] Karolinska Inst, Ctr Cognit & Computat Neuropsychiat, Dept Clin Neurosci, Stockholm, Sweden
  4. [NORA names: Sweden; Europe, EU; Nordic; OECD];
  5. [3] Stockholm Hlth Care Serv, Stockholm, Sweden
  6. [NORA names: Sweden; Europe, EU; Nordic; OECD];
  7. [4] Uppsala Univ, Dept Med Sci Psychiat, Uppsala, Sweden
  8. [NORA names: Sweden; Europe, EU; Nordic; OECD];
  9. [5] Copenhagen Univ Hosp, Neurobiol Res Unit, Rigshospitalet, Copenhagen, Denmark
  10. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD]


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.

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