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

Author:

Kirschner MatthiasORCID,Hodzic-Santor Benazir,Kennedy Leda,Hansen Justine Y.,Antoniades Mathilde,Nenadić Igor,Kircher Tilo,Krug Axel,Meller Tina,Dannlowski Udo,Grotegerd Dominik,Flinkenflügel Kira,Meinert Susanne,Borgers Tiana,Goltermann JanikORCID,Hahn Tim,Böhnlein Joscha,Leehr Elisabeth J.,Barkhau Carlotta,Fornito Alex,Arnatkeviciute AurinaORCID,Bellgrove Mark A.,Tiego Jeggan,DeRosse Pamela,Green Melissa,Quidé YannORCID,Pantelis Christos,Chan Raymond,Wang Yi,Ettinger Ulrich,Debbané Martin,Derome Melodie,Gaser Christian,Besteher Bianca,Diederen Kelly,Spencer Tom J.,Houenou Josselin,Pomarol-Clotet Edith,Salvador Raymond,Rössler Wulf,Smigielski Lukasz,Kumari Veena,Premkumar Preethi,Park Haeme R. P.,Wiebels Kristina,Lemmers-Jansen Imke,Gilleen James,Allen Paul,Marsman Jan-Bernard,Lebedeva Irina,Tomyshev Alexander,Fett Anne-Kathrin,Sommer Iris,Koops Sanne,Grant Phillip,Bègue IndritORCID,Hernaus Dennis,Jalbrzikowski Maria,Paquola Casey,Larivière Sara,Bernhardt BorisORCID,Valk Sofie,Misic Bratislav,van Erp Theo G. M.,Turner Jessica A.,Thompson Paul M.,Aleman Andre,Dagher Alain,Kaiser Stefan,Modinos GemmaORCID

Abstract

AbstractPositive 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.

Publisher

Cold Spring Harbor Laboratory

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