Multiscale characterization of cortical signatures in positive and negative schizotypy: A worldwide ENIGMA study

Positive and negative schizotypy reflect distinct patterns of subclinical traits in the general population associated with neurodevelopmental and schizophrenia-spectrum pathologies. Yet, a comprehensive characterization of the unique and shared neuroanatomical signatures of these schizotypy dimensions is lacking. Leveraging 3D brain MRI data from 2,730 unmedicated healthy individuals, we identified neuroanatomical profiles of positive and negative schizotypy and systematically compared them to disorder-specific, micro-architectural, connectome, and neurotransmitter-level measures. Positive and negative schizotypy were associated with thinner frontal and thicker paralimbic cortical areas, respectively, and were differentially linked to cortical patterns of schizophrenia-spectrum and neurodevelopmental conditions. Furthermore, these schizotypal cortical patterns mapped onto local attributes of gene expression, cortical myelination, D1 and histamine receptor distributions. Network models identified cortical hub vulnerability to schizotypy-related thickness reduction and epicenters in sensorimotor-to-association and paralimbic areas. This study yields insights into the complex cortical signatures of schizotypy and their relationship to diverse features of cortical organization.