William S Stone1, Bing Cai2, Xinhua Liu3, Margaux M-R Grivel4, Gary Yu5, Yangmu Xu1, Xinyi Ouyang2, Hanhui Chen2, Fei Deng2, Fang Xue2, Huijun Li6, Jeffrey A Lieberman7,8, Matcheri S Keshavan1, Ezra S Susser9, Lawrence H Yang4,9, Michael R Phillips2,7,8,9. 1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts. 2. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, China. 3. Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, New York. 4. Department of Social and Behavioral Sciences, New York University School of Global Public Health, New York, New York. 5. Rory Meyers College of Nursing, New York University, New York, New York. 6. Department of Psychology, Florida A&M University, Tallahassee. 7. Department of Psychiatry, Columbia University, New York, New York. 8. New York State Psychiatric Institute, New York. 9. Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
Abstract
Importance: Cognitive deficits constitute core features of schizophrenia, but the trajectories of cognitive difficulties in chronic untreated schizophrenia remain unclear. Objective: To assess the association of neuropsychological deficits with duration of untreated psychosis in individuals with chronic untreated schizophrenia. Design, Setting, and Participants: Community-dwelling individuals with chronic untreated schizophrenia (untreated patient group) and individuals without mental illness (control group) were recruited from predominantly rural communities in Ningxia, China between June 20, 2016, and August 6, 2019, and administered the Structured Clinical Interview for DSM-IV, the Mini-Mental State Examination, an 8-test version of the MATRICS Consensus Cognition Battery adapted for use in individuals with low levels of education, and a measure of social cognition. Main Outcomes and Measures: Comparison of cognitive test scores between the two groups and association of cognitive test scores with duration of untreated schizophrenia. Results: The patient group included 197 individuals with chronic untreated schizophrenia (101 men [51.3%]; mean [SD] age, 52.1 [11.8] years; median [interquartile range] years of schooling, 3 [0-6] years; median [interquartile range] years of untreated psychosis, 22.9 [14.9-32.8] years). The control group included 220 individuals (118 men [53.6%]; mean [SD] age, 52.1 [11.2] years; median [interquartile range] years of schooling, 4 [0-6] years). The untreated patient group performed significantly worse than the control group on all cognitive measures (adjusted partial Spearman correlation coefficient [Spearman ρ] ranged from -0.35 for the revised Chinese version of the Reading the Mind in the Eyes Test to -0.60 for the Brief Visuospatial Memory Test-Revised; P < .001 for all comparisons). Longer durations of untreated psychosis were associated with lower performance in 3 MATRICS Consensus Cognition Battery measures assessing different aspects of executive functioning (Brief Visuospatial Memory Test-Revised [ρ = -0.20; P = .04]; Brief Assessment of Cognition in Schizophrenia, Symbol Coding subtest [ρ = -0.35; P < .001]; and Neuropsychological Assessment Battery, Mazes subtest [ρ = -0.24; P = .01]). The median duration of untreated psychosis (22.9 years) was associated with estimated score reductions in the 3 measures of 34% (95% CI, 10%-52%), 43% (95% CI, 28%-55%), and 57% (95% CI, 31%-73%), respectively. Conclusions and Relevance: The findings of this study suggest that long-term untreated schizophrenia was associated with decreases in selective cognitive abilities; both neurodegenerative pathology and neurodevelopmental dysfunction may be factors in cognition in persistent psychosis. Expanding research to include cohorts of patients from underserved rural communities in low- and middle-income countries may provide new insights about the etiological factors, disease course, and management of schizophrenia.
Importance: Cognitive deficits constitute core features of schizophrenia, but the trajectories of cognitive difficulties in chronic untreated schizophrenia remain unclear. Objective: To assess the association of neuropsychological deficits with duration of untreated psychosis in individuals with chronic untreated schizophrenia. Design, Setting, and Participants: Community-dwelling individuals with chronic untreated schizophrenia (untreated patient group) and individuals without mental illness (control group) were recruited from predominantly rural communities in Ningxia, China between June 20, 2016, and August 6, 2019, and administered the Structured Clinical Interview for DSM-IV, the Mini-Mental State Examination, an 8-test version of the MATRICS Consensus Cognition Battery adapted for use in individuals with low levels of education, and a measure of social cognition. Main Outcomes and Measures: Comparison of cognitive test scores between the two groups and association of cognitive test scores with duration of untreated schizophrenia. Results: The patient group included 197 individuals with chronic untreated schizophrenia (101 men [51.3%]; mean [SD] age, 52.1 [11.8] years; median [interquartile range] years of schooling, 3 [0-6] years; median [interquartile range] years of untreated psychosis, 22.9 [14.9-32.8] years). The control group included 220 individuals (118 men [53.6%]; mean [SD] age, 52.1 [11.2] years; median [interquartile range] years of schooling, 4 [0-6] years). The untreated patient group performed significantly worse than the control group on all cognitive measures (adjusted partial Spearman correlation coefficient [Spearman ρ] ranged from -0.35 for the revised Chinese version of the Reading the Mind in the Eyes Test to -0.60 for the Brief Visuospatial Memory Test-Revised; P < .001 for all comparisons). Longer durations of untreated psychosis were associated with lower performance in 3 MATRICS Consensus Cognition Battery measures assessing different aspects of executive functioning (Brief Visuospatial Memory Test-Revised [ρ = -0.20; P = .04]; Brief Assessment of Cognition in Schizophrenia, Symbol Coding subtest [ρ = -0.35; P < .001]; and Neuropsychological Assessment Battery, Mazes subtest [ρ = -0.24; P = .01]). The median duration of untreated psychosis (22.9 years) was associated with estimated score reductions in the 3 measures of 34% (95% CI, 10%-52%), 43% (95% CI, 28%-55%), and 57% (95% CI, 31%-73%), respectively. Conclusions and Relevance: The findings of this study suggest that long-term untreated schizophrenia was associated with decreases in selective cognitive abilities; both neurodegenerative pathology and neurodevelopmental dysfunction may be factors in cognition in persistent psychosis. Expanding research to include cohorts of patients from underserved rural communities in low- and middle-income countries may provide new insights about the etiological factors, disease course, and management of schizophrenia.
Authors: Alfredo Ramos-Miguel; Andrea A Jones; Vladislav A Petyuk; Vilte E Barakauskas; Alasdair M Barr; Sue E Leurgans; Philip L De Jager; Kaitlin B Casaletto; Julie A Schneider; David A Bennett; William G Honer Journal: Acta Neuropathol Date: 2021-03-01 Impact factor: 17.088
Authors: William S Stone; Michael R Phillips; Lawrence H Yang; Lawrence S Kegeles; Ezra S Susser; Jeffrey A Lieberman Journal: Schizophr Res Date: 2022-03-25 Impact factor: 4.662
Authors: Anthony W Zoghbi; Ryan S Dhindsa; Terry E Goldberg; Aydan Mehralizade; Joshua E Motelow; Xinchen Wang; Anna Alkelai; Matthew B Harms; Jeffrey A Lieberman; Sander Markx; David B Goldstein Journal: Proc Natl Acad Sci U S A Date: 2021-12-21 Impact factor: 12.779