Lancaster TM, Dimitriadis SI, Perry G, et al. - Structural brain changes occur in correlation with occurrence of schizophrenia (SCZ), and considerable variation has been noted in the extent to which these cortical regions are influenced. Meta-analysis was performed to present a novel metric that summarizes individual structural variation across the brain, while considering prior effect sizes.

• A within-sample-norm across structural MRI regions of interest (ROIs) was used to determine individual participant deviation.

• The normalized deviation of each ROI was weighted for each participant 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.

• A morphometric risk score (MRS) was developed that represents the average of these weighted deviations.

• SCZ-MRS was determined 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).

• Relative to healthy controls, higher SCZ-MRS was recorded in SCZ cases in both samples.

• A higher SCZ-MRS was also recorded for the high liability SCZ-PRS group.

• In addition, a unique association of the SCZ-MRS was observed with SCZ status, but not with attention-deficit hyperactivity disorder (ADHD), whereas an ADHD-MRS was correlated with ADHD status, but not SCZ.

• This approach appears to be a promising solution when accounting individual heterogeneity in SCZ-related brain alterations by detecting individual’s patterns of structural brain-wide alterations.