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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

Lancaster, Thomas, Dimitriadis, Stavros, Perry, Gavin, Zammit, Stanley, O'Donovan, Michael and Linden, David 2022. 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. Schizophrenia Bulletin 48 (2) , pp. 524-532. 10.1093/schbul/sbab125

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Abstract

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 < 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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Cardiff University Brain Research Imaging Centre (CUBRIC)
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Additional Information: This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/)
Publisher: Oxford University Press
ISSN: 0586-7614
Date of First Compliant Deposit: 29 September 2021
Date of Acceptance: 21 September 2021
Last Modified: 29 Jun 2022 07:53
URI: https://orca.cardiff.ac.uk/id/eprint/144528

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