Cortical surface abnormalities are different depending on the stage of schizophrenia: A cross-sectional vertexwise mega-analysis of thickness, area and gyrification

Background: Brain magnetic resonance imaging studies have not investigated the cortical surface comprehensively in schizophrenia subjects by assessing thickness, surface area and gyrification separately during the first episode of psychosis (FEP) or chronic schizophrenia (ChSch). Methods: We investigated cortical surface abnormalities in 137 FEP patients and 240 ChSch subjects compared to 297 Healthy Controls (HC) contributed by five cohorts. Maps showing results of vertexwise between-group comparisons of cortical thickness, area, and gyrification were produced using T1-weighted datasets processed using FreeSurfer 5.3, followed by validated quality control protocols. Results: FEP subjects showed large clusters of increased area and gyrification relative to HC in prefrontal and insuli cortices (Cohen's d: 0.049 to 0.28). These between-group differences occurred partially beyond the effect of sample. ChSch subjects displayed reduced cortical thickness relative to HC in smaller fronto-temporal foci (d:-0.73 to-0.35), but not beyond the effect of sample. Differences between FEP and HC subjects were associated with male gender, younger age, and earlier illness onset, while differences between ChSch and HC were associated with treatment-resistance and first-generation antipsychotic (FGA) intake independently of sample effect. Conclusions: Separate assessments of FEP and ChSch revealed abnormalities that differed in regional distribution, phenotypes affected and effect size. In FEP, associations of greater cortical area and gyrification abnormalities with earlier age of onset suggest an origin on anomalous neurodevelopment, while thickness reductions in ChSch are at least partially explained by treatment-resistance and FGA intake. Associations of between-group differences with clinical variables retained statistical significance beyond the effect of sample.

Automated summary

Brain MRI studies on schizophrenia patients showed significant differences in cortical surface characteristics, such as increased area and gyrification in FEP subjects and reduced thickness in ChSch subjects. These abnormalities were associated with clinical variables such as age of onset and treatment-resistance, indicating potential origins of neurodevelopmental anomalies in FEP and medication effects in ChSch.