{"doi":"10.1093/schbul/sbab125","title":"Morphometric Analysis of Structural MRI Using Schizophrenia Meta-analytic Priors Distinguish Patients from Controls in Two Independent Samples and in a Sample of Individuals With High Polygenic Risk","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Schizophrenia (SCZ) is associated with structural brain changes, with considerable variation in the extent to which these cortical regions are influenced. We present a novel metric that summarises individual structural variation across the brain, while considering prior effect sizes, established via meta-analysis. We determine individual participant deviation from a within-sample-norm across structural MRI regions of interest (ROIs). For each participant, we weight the normalised deviation of each ROI by the effect size (Cohen’s d) of the difference between SCZ/control for the corresponding ROI from the SCZ Enhancing Neuroimaging Genomics through Meta-Analysis working group. We generate a morphometric risk score (MRS) representing the average of these weighted deviations. We investigate if SCZ-MRS is elevated in a SCZ case/control sample (NCASE = 50; NCONTROL = 125), a replication sample (NCASE = 23; NCONTROL = 20) and a sample of asymptomatic young adults with extreme SCZ polygenic risk (NHIGH-SCZ-PRS = 95; NLOW-SCZ-PRS = 94). SCZ cases had higher SCZ-MRS than healthy controls in both samples (Study 1: β = 0.62, P &amp;lt; 0.001; Study 2: β = 0.81, P = 0.018). The high liability SCZ-PRS group also had a higher SCZ-MRS (Study 3: β = 0.29, P = 0.044). Furthermore, the SCZ-MRS was uniquely associated with SCZ status, but not attention-deficit hyperactivity disorder (ADHD), whereas an ADHD-MRS was linked to ADHD status, but not SCZ. This approach provides a promising solution when considering individual heterogeneity in SCZ-related brain alterations by identifying individual’s patterns of structural brain-wide alterations.</jats:p>","journal":"Schizophrenia Bulletin","year":2022,"id":629015,"datarank":0.38474240361923057,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"self_citation_contribution":0.38474240361923057,"citation_network_contribution":0.0,"self_endowment_contribution":0.38474240361923057,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1628892,"name":"Stavros I Dimitriadis","orcid":null,"position":1,"is_corresponding":false},{"id":401414,"name":"Gavin Perry","orcid":"0000-0003-0468-0421","position":2,"is_corresponding":false},{"id":1628893,"name":"Stan Zammit","orcid":null,"position":3,"is_corresponding":false},{"id":1628895,"name":"Michael C O’Donovan","orcid":null,"position":4,"is_corresponding":false},{"id":1628896,"name":"David E Linden","orcid":null,"position":5,"is_corresponding":false},{"id":1628891,"name":"Thomas M Lancaster","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Morphometric Analysis of Structural MRI Using Schizophrenia Meta-analytic Priors Distinguish Patients from Controls in Two Independent Samples and in a Sample of Individuals With High Polygenic Risk","abstract":"<jats:title>Abstract</jats:title>\n               <jats:p>Schizophrenia (SCZ) is associated with structural brain changes, with considerable variation in the extent to which these cortical regions are influenced. We present a novel metric that summarises individual structural variation across the brain, while considering prior effect sizes, established via meta-analysis. We determine individual participant deviation from a within-sample-norm across structural MRI regions of interest (ROIs). For each participant, we weight the normalised deviation of each ROI by the effect size (Cohen’s d) of the difference between SCZ/control for the corresponding ROI from the SCZ Enhancing Neuroimaging Genomics through Meta-Analysis working group. We generate a morphometric risk score (MRS) representing the average of these weighted deviations. We investigate if SCZ-MRS is elevated in a SCZ case/control sample (NCASE = 50; NCONTROL = 125), a replication sample (NCASE = 23; NCONTROL = 20) and a sample of asymptomatic young adults with extreme SCZ polygenic risk (NHIGH-SCZ-PRS = 95; NLOW-SCZ-PRS = 94). SCZ cases had higher SCZ-MRS than healthy controls in both samples (Study 1: β = 0.62, P &amp;lt; 0.001; Study 2: β = 0.81, P = 0.018). The high liability SCZ-PRS group also had a higher SCZ-MRS (Study 3: β = 0.29, P = 0.044). Furthermore, the SCZ-MRS was uniquely associated with SCZ status, but not attention-deficit hyperactivity disorder (ADHD), whereas an ADHD-MRS was linked to ADHD status, but not SCZ. This approach provides a promising solution when considering individual heterogeneity in SCZ-related brain alterations by identifying individual’s patterns of structural brain-wide alterations.</jats:p>","is_dataset_classified":null,"base_score":2.5649493574615367,"endowment":2.5649493574615367,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"34662406","pmcid":"PMC8886591","openalex_id":"https://openalex.org/W3205699182","authors":[],"funders":[{"funder_name":"Medical Research Council","grant_id":"MR/K004360/1","title":"Behavioural and neurophysiological effects of schizophrenia risk genes: a multi-locus, pathway based approach"},{"funder_name":"Wellcome Trust","grant_id":"217065/Z/19/Z","title":null},{"funder_name":"Medical Research Council","grant_id":"G9815508","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_15018","title":null},{"funder_name":"Medical Research Council","grant_id":"MC_PC_19009","title":null},{"funder_name":"Medical Research Council","grant_id":"MR/L010305/1","title":null},{"funder_name":"Medical Research Council","grant_id":"G0800509","title":"Molecular Genetics of Schizophrenia"},{"funder_name":"Wellcome Trust","grant_id":"217065","title":"The Avon Longitudinal Study of Parents and Children (ALSPAC): A multi-generation, longitudinal resource focusing on life course health and well-being."},{"funder_name":"National Institute for Health Research (NIHR)","grant_id":"","title":null},{"funder_name":"Department of Health","grant_id":"","title":null}],"total_grants":10,"fwci":1.1413,"citation_percentile":0.77741305,"influential_citations":0,"citation_trend":[{"year":2022,"count":3},{"year":2023,"count":5},{"year":2024,"count":1},{"year":2025,"count":2},{"year":2026,"count":1}],"oa_status":"hybrid","license":"cc-by-nc","oa_locations":[{"url":"https://academic.oup.com/schizophreniabulletin/article-pdf/48/2/524/42645816/sbab125.pdf","host_type":"journal"},{"url":"https://academic.oup.com/schizophreniabulletin/article-pdf/48/2/524/42645816/sbab125.pdf","host_type":"HYBRID"},{"url":"https://academic.oup.com/schizophreniabulletin/article-pdf/48/2/524/42645816/sbab125.pdf","host_type":"publisher"},{"url":"https://academic.oup.com/schizophreniabulletin/article-pdf/48/2/524/50021049/sbab125.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/schbul/sbab125","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/34662406","host_type":"repository"},{"url":"https://cris.maastrichtuniversity.nl/en/publications/0a791fce-1623-459e-923f-d00ea584ade6","host_type":"repository"},{"url":"https://research-information.bris.ac.uk/en/publications/4e7874aa-9ca6-409d-8f0f-cff3cccb900a","host_type":"repository"},{"url":"https://hdl.handle.net/1983/4e7874aa-9ca6-409d-8f0f-cff3cccb900a","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/8886591","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC8886591","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC8886591?pdf=render","host_type":"Europe_PMC"},{"url":"https://academic.oup.com/schizophreniabulletin/advance-article-pdf/doi/10.1093/schbul/sbab125/40722495/sbab125.pdf","host_type":""},{"url":"http://dx.doi.org/10.1093/schbul/sbab125","host_type":""},{"url":"https://orca.cardiff.ac.uk/id/eprint/144528/17/sbab125.pdf","host_type":""},{"url":"https://dx.doi.org/10.1093/schbul/sbab125","host_type":""},{"url":"https://research-information.bris.ac.uk/ws/files/310577106/sbab125.pdf","host_type":""},{"url":"https://doi.org/https://doi.org/10.1093/schbul/sbab125","host_type":""}],"fields_of_study":["Advanced Neuroimaging Techniques and Applications","Functional Brain Connectivity Studies","Advanced MRI Techniques and Applications","Psychology","Medicine","03 medical and health sciences","0302 clinical medicine","Adult","Case-Control Studies","Female","Genetic Predisposition to Disease","Humans","Magnetic Resonance Imaging","Male","Middle Aged","Neuroimaging","Schizophrenia"],"mesh_terms":["Adult","Female","Humans","Magnetic Resonance Imaging","Male","Middle Aged","Schizophrenia","Case-Control Studies","Genetic Predisposition to Disease","Neuroimaging"],"keywords":["Neuroimaging","Schizophrenia (object-oriented programming)","Sample size determination","Polygenic risk score","Psychology","Multiple comparisons problem","Meta-analysis","Medicine","Internal medicine","Neuroscience","Psychiatry","Biology","Single-nucleotide polymorphism","Statistics","Genetics","Mathematics","Schizophrenia","Heterogeneity","MRI","Multivariate","Polygenic","Normative Modelling","DISORDER","Adult","Male","610","Humans","Genetic Predisposition to Disease","BRAIN","600","ADULTS","ASSOCIATION","Middle Aged","Magnetic Resonance Imaging","Case-Control Studies","Female","Regular Articles"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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