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An opportunity for primary prevention research in psychotic disorders.

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机构： [1]University of Chicago, Department of Psychiatry, United States of America [2]Australian Centre for Precision Health, University of South Australia Cancer Research Institute, University of South Australia, Adelaide, SA 5000, Australia [3]UniSA: Allied Health and Human Performance, University of South Australia, Adelaide, SA 5000, Australia [4]South Australian Health and Medical Research Institute, Adelaide, South Australia 5000, Australia [5]University of Texas Southwestern, United States of America [6]Yale University, Godfrey, United States of America [7]University of Georgia, United States of America [8]Harvard Medical School, United States of America [9]University of Chicago, United States of America [10]University of Cincinnati, Department of Psychiatry United States of America, Sichuan University, Hauxi Center for MR Research, China [11]Harvard Medical School, Boston Children's Hospital, United States of America [12]University of Muenster, Muenster, Germany [13]Rosalind Franklin University of Medicine and Science, United States of America [14]University of Chicago, Department of Human Genetics, United States of America [15]Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany

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关键词： Psychosis Prevention Diagnostic tests Prediction metrics Event-related potentials Cognition Eye movements Polygenic risk score

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An opportunity has opened for research into primary prevention of psychotic disorders, based on progress in endophenotypes, genetics, and genomics. Primary prevention requires reliable prediction of susceptibility before any symptoms are present. We studied a battery of measures where published data supports abnormalities of these measurements prior to appearance of initial psychosis symptoms. These neurobiological and behavioral measurements included cognition, eye movement tracking, Event Related Potentials, and polygenic risk scores. They generated an acceptably precise separation of healthy controls from outpatients with a psychotic disorder. METHODS: The Bipolar and Schizophrenia Network on Intermediate Phenotypes (B-SNIP) measured this battery in an ancestry-diverse series of consecutively recruited adult outpatients with a psychotic disorder and healthy controls. Participants include all genders, 16 to 50 years of age, 261 with psychotic disorders (Schizophrenia (SZ) 109, Bipolar with psychosis (BPP) 92, Schizoaffective disorder (SAD) 60), 110 healthy controls. Logistic Regression, and an extension of the Linear Mixed Model to include analysis of pairwise interactions between measures (Environmental kernel Relationship Matrices (ERM)) with multiple iterations, were performed to predict case-control status. Each regression analysis was validated with four-fold cross-validation. RESULTS AND CONCLUSIONS: Sensitivity, specificity, and Area Under the Curve of Receiver Operating Characteristic of 85%, 62%, and 86%, respectively, were obtained for both analytic methods. These prediction metrics demonstrate a promising diagnostic distinction based on premorbid risk variables. There were also statistically significant pairwise interactions between measures in the ERM model. The strong prediction metrics of both types of analytic model provide proof-of-principle for biologically-based laboratory tests as a first step toward primary prevention studies. Prospective studies of adolescents at elevated risk, vs. healthy adolescent controls, would be a next step toward development of primary prevention strategies.Copyright © 2021 Elsevier B.V. All rights reserved.

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出版当年[2021]版：

大类 | 2 区

医学

小类 | 2 区精神病学

最新[2023]版：

大类 | 2 区医学

小类 | 2 区精神病学

第一作者：

第一作者机构： [1]University of Chicago, Department of Psychiatry, United States of America [14]University of Chicago, Department of Human Genetics, United States of America [*1]924 E. 57th Street, Room LLR010, University of Chicago, Chicago, IL 60637, United States of America.

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通讯机构： [1]University of Chicago, Department of Psychiatry, United States of America [14]University of Chicago, Department of Human Genetics, United States of America [*1]924 E. 57th Street, Room LLR010, University of Chicago, Chicago, IL 60637, United States of America.

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An opportunity for primary prevention research in psychotic disorders.

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