Cortical and Subcortical Neuroanatomical Signatures of Schizotypy in 2,952 Individuals Assessed in a Worldwide ENIGMA Study

Abstract

Background: Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first 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.

Methods: The sample comprised 2,952 unmedicated healthy individuals (12-68 years, 46.5% male) from 26 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls.

Results: Cortical thickness in the right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) showed a significant positive correlation with schizotypy scores (r=.07, pFDR=.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r=.33, pspin=.01), but not BD (r=.19, pspin=.16) or MDD (r=-.22, pspin=.10). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho=-.65, pspin=.01), BD (rho=-.63, pspin=.01), and MDD (rho=-.69, pspin=.004).

Conclusions: Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.