Cortical and subcortical neuroanatomical signatures ofschizotypy in 3004 individuals assessed in a worldwide ENIGMA study

Matthias Kirschner, Paul Allen, ENIGMA Schizotypy Group

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Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early andchronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authorsconducted thefirst large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals,and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy workinggroup. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Patternsimilarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons ofschizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r=0.067,pFDR=0.02). The corticalthickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r=0.285,pspin=0.024), but not BD (r=0.166,pspin=0.205) or MDD (r=−0.274,pspin=0.073). The schizotypy-related subcortical volume pattern was negativelycorrelated with subcortical abnormalities in SZ (rho=−0.690,pspin=0.006), BD (rho=−0.672,pspin=0.009), and MDD (rho=−0.692,pspin=0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed asignificant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due toantipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields newinsights into a dimensional neurobiological continuity across the extended psychosis phenotype.

© 2021, The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. See
Original languageEnglish
Early online date27 Oct 2021
Publication statusPublished - 4 Jan 2022

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