Ana Catalan1,2,3,4, Gonzalo Salazar de Pablo4,5,6, Claudia Aymerich1, Stefano Damiani7, Veronica Sordi7, Joaquim Radua4,8,9, Dominic Oliver4, Philip McGuire10,11,12, Anthony J Giuliano13, William S Stone14, Paolo Fusar-Poli4,7,10,12. 1. Psychiatry Department, Basurto University Hospital, Bilbao, Spain. 2. Biocruces Bizkaia Health Research Institute, Barakaldo, Spain. 3. Facultad de Medicina y Odontología. University of the Basque Country, UPV/EHU, Leioa, Spain. 4. Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. 5. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health. Hospital General Universitario Gregorio Marañón, Madrid, Spain. 6. School of Medicine, Universidad Complutense, IiSGM, CIBERSAM, Madrid, Spain. 7. Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. 8. Imaging of Mood- and Anxiety-Related Disorders Group, Mental Health Research Networking Center, Institut d'Investigacions Biomèdiques August Pi i Sunyer, CIBERSAM, Barcelona, Spain. 9. Department of Clinical Neuroscience, Centre for Psychiatric Research and Education, Karolinska Institutet, Stockholm, Sweden. 10. National Institute for Health Research Biomedical Research Centre, London, United Kingdom. 11. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. 12. Outreach and Support in South London Service, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom. 13. Worcester Recovery Center & Hospital, Massachusetts Department of Mental Health, Boston. 14. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
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.
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.
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