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      Parsing neurobiological heterogeneity of the clinical high-risk state for psychosis: A pseudo-continuous arterial spin labelling study

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          Abstract

          Introduction

          The impact of the clinical high-risk for psychosis (CHR-P) construct is dependent on accurately predicting outcomes. Individuals with brief limited intermittent psychotic symptoms (BLIPS) have higher risk of developing a first episode of psychosis (FEP) compared to individuals with attenuated psychotic symptoms (APS). Supplementing subgroup stratification with information from candidate biomarkers based on neurobiological parameters, such as resting-state, regional cerebral blood flow (rCBF), may help refine risk estimates. Based on previous evidence, we hypothesized that individuals with BLIPS would exhibit increased rCBF compared to APS in key regions linked to dopaminergic pathways.

          Methods

          Data from four studies were combined using ComBat (to account for between-study differences) to analyse rCBF in 150 age- and sex-matched subjects ( n = 30 healthy controls [HCs], n = 80 APS, n = 20 BLIPS and n = 20 FEP). Global gray matter (GM) rCBF was examined in addition to region-of-interest (ROI) analyses in bilateral/left/right frontal cortex, hippocampus and striatum. Group differences were assessed using general linear models: (i) alone; (ii) with global GM rCBF as a covariate; (iii) with global GM rCBF and smoking status as covariates. Significance was set at p < 0.05.

          Results

          Whole-brain voxel-wise analyses and Bayesian ROI analyses were also conducted. No significant group differences were found in global [ F(3,143) = 1,41, p = 0.24], bilateral frontal cortex [ F(3,143) = 1.01, p = 0.39], hippocampus [ F(3,143) = 0.63, p = 0.60] or striatum [ F(3,143) = 0.52, p = 0.57] rCBF. Similar null findings were observed in lateralized ROIs ( p > 0.05). All results were robust to addition of covariates ( p > 0.05). No significant clusters were identified in whole-brain voxel-wise analyses ( p > 0.05 FWE). Weak-to-moderate evidence was found for an absence of rCBF differences between APS and BLIPS in Bayesian ROI analyses.

          Conclusion

          On this evidence, APS and BLIPS are unlikely to be neurobiologically distinct. Due to this and the weak-to-moderate evidence for the null hypothesis, future research should investigate larger samples of APS and BLIPS through collaboration across large-scale international consortia.

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          Most cited references79

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          mice: Multivariate Imputation by Chained Equations inR

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            Non-biological experimental variation or "batch effects" are commonly observed across multiple batches of microarray experiments, often rendering the task of combining data from these batches difficult. The ability to combine microarray data sets is advantageous to researchers to increase statistical power to detect biological phenomena from studies where logistical considerations restrict sample size or in studies that require the sequential hybridization of arrays. In general, it is inappropriate to combine data sets without adjusting for batch effects. Methods have been proposed to filter batch effects from data, but these are often complicated and require large batch sizes ( > 25) to implement. Because the majority of microarray studies are conducted using much smaller sample sizes, existing methods are not sufficient. We propose parametric and non-parametric empirical Bayes frameworks for adjusting data for batch effects that is robust to outliers in small sample sizes and performs comparable to existing methods for large samples. We illustrate our methods using two example data sets and show that our methods are justifiable, easy to apply, and useful in practice. Software for our method is freely available at: http://biosun1.harvard.edu/complab/batch/.
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              An automated method for segmenting magnetic resonance head images into brain and non-brain has been developed. It is very robust and accurate and has been tested on thousands of data sets from a wide variety of scanners and taken with a wide variety of MR sequences. The method, Brain Extraction Tool (BET), uses a deformable model that evolves to fit the brain's surface by the application of a set of locally adaptive model forces. The method is very fast and requires no preregistration or other pre-processing before being applied. We describe the new method and give examples of results and the results of extensive quantitative testing against "gold-standard" hand segmentations, and two other popular automated methods. Copyright 2002 Wiley-Liss, Inc.
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                Author and article information

                Contributors
                Journal
                Front Psychiatry
                Front Psychiatry
                Front. Psychiatry
                Frontiers in Psychiatry
                Frontiers Media S.A.
                1664-0640
                08 March 2023
                2023
                : 14
                : 1092213
                Affiliations
                [1] 1Early Psychosis: Interventions and Clinical-detection (EPIC) Lab, Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London , London, United Kingdom
                [2] 2Department of Psychiatry, University of Oxford , Oxford, United Kingdom
                [3] 3NIHR Oxford Health Biomedical Research Centre , Oxford, United Kingdom
                [4] 4Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London , London, United Kingdom
                [5] 5Department of Neuroimaging, Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London , London, United Kingdom
                [6] 6Department of Translational Biomedicine and Neuroscience (DiBraiN), University of Bari Aldo Moro , Bari, Italy
                [7] 7OASIS Service, South London and Maudsley NHS Foundation Trust , London, United Kingdom
                [8] 8Mental Health Department, Basurto University Hospital, Facultad de Medicina y Odontología, Campus de Leioa, Biocruces Bizkaia Health Research Institute, UPV/EHU, University of the Basque Country , Barakaldo, Spain
                [9] 9NIHR Mental Health Policy Research Unit, Division of Psychiatry, University College London , London, United Kingdom
                [10] 10Department of Psychiatry, School of Medicine, Pontificia Universidad Católica de Chile , Santiago, Chile
                [11] 11Department of Psychology, University of Roehampton , London, United Kingdom
                [12] 12Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London , London, United Kingdom
                [13] 13Maudsley Biomedical Research Centre, South London and Maudsley NHS Foundation Trust, National Institute for Health Research , London, United Kingdom
                [14] 14Department of Brain and Behavioral Sciences, University of Pavia , Pavia, Italy
                Author notes

                Edited by: Armando D’Agostino, University of Milan, Italy

                Reviewed by: Sebastian Walther, University Clinic for Psychiatry and Psychotherapy; University of Bern, Switzerland; Alessio Fracasso, University of Glasgow, United Kingdom

                *Correspondence: Paolo Fusar-Poli, paolo.fusar-poli@ 123456kcl.ac.uk

                This article was submitted to Schizophrenia, a section of the journal Frontiers in Psychiatry

                Article
                10.3389/fpsyt.2023.1092213
                10031088
                36970257
                ea8076e9-e8f9-4274-ad82-7a0582338e87
                Copyright © 2023 Oliver, Davies, Zelaya, Selvaggi, De Micheli, Catalan, Baldwin, Arribas, Modinos, Crossley, Allen, Egerton, Jauhar, Howes, McGuire and Fusar-Poli.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 07 November 2022
                : 15 February 2023
                Page count
                Figures: 2, Tables: 1, Equations: 0, References: 80, Pages: 11, Words: 8821
                Categories
                Psychiatry
                Original Research

                Clinical Psychology & Psychiatry
                clinical high risk for psychosis,brief limited intermittent psychotic symptoms,attenuated psychosis syndrome,arterial spin labelling,neuroimaging

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