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

Thomas M. Lancaster, Stavros I. Dimitriadis, Gavin Perry, Stan Zammit, Michael C. O'Donovan, David E. Linden

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)524-532
Number of pages9
JournalSchizophrenia Bulletin
Volume48
Issue number2
Early online date18 Oct 2021
DOIs
Publication statusPublished - 31 Mar 2022

Keywords

  • heterogeneity
  • MRI
  • multivariate
  • normative modelling
  • polygenic
  • schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health

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