Multiscale characterization of cortical signatures in positive and negative schizotypy:a worldwide ENIGMA study
Abstract
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 2730 unmedicated healthy individuals, we identified neuroanatomical profiles of positive and negative schizotypy and systematically compared them with disorder-specific, microarchitectural, neurotransmitter-level, and connectome measures. Positive and negative schizotypy were associated with distinct cortical signatures, of predominantly thinner frontal and thicker paralimbic cortical areas, respectively. These cortical signatures of positive and negative schizotypy were differentially linked to brain-wide cortical patterns of schizophrenia-spectrum (clinical high-risk for psychosis, schizophrenia) and neurodevelopmental conditions (ADHD, autism spectrum disorder and 22q11.2 deletion syndrome). Additionally, the positive and negative schizotypy-related cortical profiles mapped onto different local attributes of gene expression, cortical myelination, D1, and histamine receptor distributions. Network models further showed that positive and negative schizotypy cortical signatures were spatially associated with cortical hubs, suggesting that highly interconnected regions are more vulnerable to the morphological differences associated with both schizotypy dimensions. Finally, predominantly sensorimotor-to-association and paralimbic areas emerged as epicenters with connectivity profiles significantly linked to the schizotypy-related cortical patterns. Collectively, this study identified cortical signatures of positive and negative schizotypy traits that are embedded along multiple scales of cortical organization and neuropsychiatric pathologies. Our work yields novel insights into how neurobiology and brain architecture may guide neuroanatomical vulnerability and resilience to psychopathology in the general population.
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Authors: Matthias Kirschner, Benazir Hodzic-Santor, Leda Kennedy, Justine Y. Hansen, Mathilde Antoniades, Igor Nenadić, Tilo Kircher, Axel Krug, Tina Meller, Udo Dannlowski, Dominik Grotegerd, Kira Flinkenflügel, Susanne Meinert, Tiana Borgers, Janik Goltermann, Tim Hahn, Joscha Böhnlein, Elisabeth J. Leehr, C. Barkhau, Alex Fornito, Aurina Arnatkevičiūtė, Mark A. Bellgrove, Jeggan Tiego, Pamela DeRosse, Melissa Green, Yann Quidé, Christos Pantelis, Raymond Chan, Yi Wang, Ulrich Ettinger, Martin Debbané, Mélodie Derome, Christian Gaser, Bianca Besteher, Kelly Diederen, Tom J. Spencer, Josselin Houenou, Edith Pomarol-Clotet, Raymond Salvador, Wulf Rössler, Lukasz Smigielski, Veena Kumari, Preethi Premkumar, Haeme R. P. Park, Kristina Wiebels, Imke Jansen, James Gilleen, Paul Allen, Jan Bernard Marsman, Irina Lebedeva, Alexander Tomyshev, Anne Kathrin; id_orcid 0000-0003-0282-273X Fett, Iris Sommer, Sanne Koops, Phillip Grant, Asia Ferrari, Bin Wan, Indrit Bègue, Dennis Hernaus, Maria Jalbrzikowski, Casey Paquola, Sara Larivière, Boris Bernhardt, S. L. Valk, Bratislav Misic, Theo G.M. van Erp, Jessica A. Turner, Paul M. Thompson, Andre Aleman, Alain Dagher, Stefan Kaiser, Gemma Modinos
Institutions: University of California San Diego, University of Groningen, Charité - Universitätsmedizin Berlin, Universidade de São Paulo, The University of Melbourne, The Ohio State University, Vrije Universiteit Amsterdam, University of Manchester, Heinrich Heine University Düsseldorf, UNSW Sydney, University of Southern California, University College London, Monash University, Maastricht University, Stony Brook University, University of Geneva, University of Bonn, Harvard University Press, University of Münster, California University of Pennsylvania, Philipps University of Marburg, University of California, Irvine, University of Zurich, Hofstra University, Zucker Hillside Hospital, Université de Sherbrooke, Russian Academy of Sciences, Australian Regenerative Medicine Institute, Friedrich Schiller University Jena, King's College London, University of Auckland, Bielefeld University, Forschungszentrum Jülich, Brunel University of London, California Southern University, Ernst Ruska Centre, Neuroscience Research Australia, Hochschule Fresenius, Center for Neurosciences, Institute of Psychology, Chinese Academy of Sciences, Max Planck Institute for Human Cognitive and Brain Sciences, Academy of Medical Sciences, IntellADAPT (United States), Fidmag Sisters Hospitallers, Institute of Developmental Physiology