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

Article Article scientifique Article Multiscale characterization of cortical signatures in positive and negative schizotypy : a worldwide ENIGMA study eng 2026-04-18 author Kirschner Matthias 0000-0002-9486-1439 Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.,McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.,Synapsy Center for Neuroscience and Mental Health Research, University of Geneva, Geneva, Switzerland.,Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland. 403290 Département de psychiatrie (PSYAT) author Hodzic-Santor Benazir McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. author Kennedy Leda Department of Psychiatry, University of California San Diego, San Diego, CA, USA. author Hansen Justine Y 0000-0003-3142-7480 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.,Children's Hospital of Philadelphia, University of Pennsylvania, Philadelphia, USA. author Antoniades Mathilde Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. author Nenadić Igor 0000-0002-0749-7473 University of Marburg, Marburg, Germany. author Kircher Tilo 0000-0002-2514-2625 University of Marburg, Marburg, Germany. author Krug Axel 0000-0002-0564-2497 University of Marburg, Marburg, Germany.,Department of Psychiatry and Psychotherapy, University Hospital Bonn, Bonn, Germany. author Meller Tina University of Marburg, Marburg, Germany. author Dannlowski Udo 0000-0002-0623-3759 Institute for Translational Psychiatry, University of Münster, Münster, Germany.,Department of Psychiatry, Medical School and University Medical Center OWL, Protestant Hospital of the Bethel Foundation, Bielefeld University, Bielefeld, Germany.,German Center for Mental Health (DZPG), Site Jena Magdeburg Halle, Jena, Germany.,Center for Intervention and Research on Adaptive and Maladaptive Brain Circuits Underlying Mental Health (C-I-R-C), Site Jena Magdeburg Halle, Jena, Germany. author Grotegerd Dominik Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Flinkenflügel Kira 0000-0001-7738-5429 Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Meinert Susanne 0000-0003-2177-7161 Institute for Translational Psychiatry, University of Münster, Münster, Germany.,Institute for Translational Neuroscience, University of Münster, Münster, Germany. author Borgers Tiana Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Goltermann Janik 0000-0003-3087-1002 Institute for Translational Psychiatry, University of Münster, Münster, Germany.,Department of Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany. author Hahn Tim 0000-0001-6541-3795 Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Böhnlein Joscha 0000-0002-9870-5599 Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Leehr Elisabeth J 0000-0002-9264-5003 Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Barkhau Carlotta 0000-0002-7546-9183 Institute for Translational Psychiatry, University of Münster, Münster, Germany. author Fornito Alex Turner Institute for Brain and Mental Health, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, VIC, Australia. author Arnatkeviciute Aurina 0000-0003-4098-7084 Turner Institute for Brain and Mental Health, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, VIC, Australia. author Bellgrove Mark A 0000-0003-0186-8349 Turner Institute for Brain and Mental Health, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, VIC, Australia. author Tiego Jeggan 0000-0001-7835-6398 Turner Institute for Brain and Mental Health, School of Psychological Sciences and Monash Biomedical Imaging, Monash University, Melbourne, VIC, Australia. author DeRosse Pamela Stony Brook University, Stony Brook, NY, USA.,Division of Psychiatry Research, Zucker Hillside Hospital, Northwell Health, Glen Oaks, NY, USA.,The Feinstein Institutes for Medical Research, Center for Psychiatric Neuroscience, Manhasset, NY, USA.,Department of Psychiatry, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, USA. author Green Melissa 0000-0002-9361-4874 School of Clinical Medicine, University of New South Wales (UNSW), Sydney, NSW, Australia. author Quidé Yann 0000-0002-8569-7139 School of Psychology, The University of New South Wales (UNSW), Sydney, NSW, Australia.,Neuroscience Research Australia (NeuRA), Randwick, NSW, Australia. author Pantelis Christos 0000-0002-9565-0238 Department of Psychiatry, University of Melbourne, Carlton South, VIC, Australia. author Chan Raymond C K 0000-0001-7571-6933 State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. author Wang Yi 0000-0001-6880-5831 State Key Laboratory of Cognitive Science and Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China. author Ettinger Ulrich 0000-0002-0160-0281 University of Bonn, Bonn, Germany. author Debbané Martin 0000-0002-4677-8753 Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland.,Research Department of Clinical, Educational and Health Psychology, University College London, London, UK. 543333 Section de psychologie (PSICO) author Derome Melodie Faculty of Psychology and Educational Sciences, University of Geneva, Geneva, Switzerland. 846041 Département de psychiatrie (PSYAT) author Gaser Christian 0000-0002-9940-099X German Center for Mental Health (DZPG), Site Jena Magdeburg Halle, Jena, Germany.,Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany.,Department of Neurology, Jena University Hospital, Jena, Germany. author Besteher Bianca 0000-0001-7989-9298 German Center for Mental Health (DZPG), Site Jena Magdeburg Halle, Jena, Germany.,Department of Psychiatry and Psychotherapy, Jena University Hospital, Jena, Germany. author Diederen Kelly Department of Psychosis Studies, King's College London, London, UK. author Spencer Tom J Department of Psychosis Studies, King's College London, London, UK. author Houenou Josselin 0000-0003-3166-5606 Department of Psychiatry, University of Melbourne and Mental Services, Northern Health, Victoria, Australia. author Pomarol-Clotet Edith FIDMAG Germanes Hospitalàries Research Foundation & CIBERSAM, ISCIII, Barcelona, Spain. author Salvador Raymond FIDMAG Germanes Hospitalàries Research Foundation & CIBERSAM, ISCIII, Barcelona, Spain. author Rössler Wulf Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland.,Department of Psychiatry and Psychotherapy, Charité University Medicine, Berlin, Germany.,Institute of Psychiatry, School of Medicine, University of Sao Paulo, Sao Paulo, Brazil. author Smigielski Lukasz 0000-0002-7428-7644 Psychiatric University Hospital Zurich, University of Zurich, Zurich, Switzerland. author Kumari Veena 0000-0002-9635-5505 Brunel University London, Uxbridge, UK. author Premkumar Preethi Brunel University London, Uxbridge, UK. author Park Haeme R P 0000-0002-8680-4346 School of Psychology, University of Auckland, Auckland, New Zealand. author Wiebels Kristina School of Psychology, University of Auckland, Auckland, New Zealand. author Jansen Imke 0000-0001-9044-6468 Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. author Gilleen James 0000-0003-1095-9058 University of Manchester, Manchester, UK. author Allen Paul Neuroimaging, Institute of Psychiatry, Psychology, Neuroscience, King's College London, London, UK. author Marsman Jan-Bernard Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. author Lebedeva Irina Mental Health Research Center, Moscow, Russian Federation. author Tomyshev Alexander Mental Health Research Center, Moscow, Russian Federation. author Fett Anne-Kathrin 0000-0003-0282-273X Department of Psychosis Studies, King's College London, London, UK.,Department of Psychology and Neuroscience, City St George's, University of London, School of Health and Medical Sciences, London, UK. author Sommer Iris Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. author Koops Sanne Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands. author Grant Phillip Fresenius University of Applied Sciences, Frankfurt am Main, Germany. author Ferrari Asia 0009-0001-3227-9443 Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. 431841 Département de psychiatrie (PSYAT) author Wan Bin Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland. 431135 Département de psychiatrie (PSYAT) author Bègue Indrit 0000-0001-5350-4454 Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.,Synapsy Center for Neuroscience and Mental Health Research, University of Geneva, Geneva, Switzerland. 715639 Département de psychiatrie (PSYAT) author Hernaus Dennis 0000-0002-8370-5756 Department of Psychiatry & Neuropsychology, Mental Health and Neuroscience (MHeNs) Research Institute, Maastricht University, Maastricht, Netherlands. author Jalbrzikowski Maria 0000-0001-6574-9432 Department of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA, USA.,Department of Psychiatry, Harvard Medical School, MA, Boston, USA. author Paquola Casey Institute of Neuroscience and Medicine (INM-7: Brain & Behaviour) Research Centre Jülich, Jülich, Germany. author Larivière Sara 0000-0001-5701-1307 Department of Medical Imaging and Radiation Sciences, Université de Sherbrooke, Sherbrooke, QC, Canada. author Bernhardt Boris 0000-0001-9256-6041 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. author Valk Sofie L Institute of Neuroscience and Medicine (INM-7: Brain & Behaviour) Research Centre Jülich, Jülich, Germany.,Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.,Institute of Systems Neuroscience, Heinrich Heine University Düsseldorf, Düsseldorf, Germany. author Misic Bratislav 0000-0003-0307-2862 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. author van Erp Theo G M Clinical Translational Neuroscience Laboratory, Department of Psychiatry and Human Behavior, University of California Irvine, Irvine, CA, USA.,Center for the Neurobiology of Learning and Memory, University of California Irvine, Irvine, CA, USA. author Turner Jessica A 0000-0003-0076-8434 Department of Psychiatry and Behavioral Health, the Ohio State University, Columbus, OH, USA. author Thompson Paul M Imaging Genetics Center, Mark and Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine of the University of Southern California, Marina del Rey, CA, USA. author Aleman Andre Department of Biomedical Sciences of Cells and Systems, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.,Department of Neuropsychology and Psychopharmacology, Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, the Netherlands. author Dagher Alain 0000-0002-0945-5779 McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, QC, Canada. author Kaiser Stefan 0000-0002-3013-2034 Department of Psychiatry, University Hospitals of Geneva, Geneva, Switzerland.,Synapsy Center for Neuroscience and Mental Health Research, University of Geneva, Geneva, Switzerland. 868946 Département de psychiatrie (PSYAT) author Modinos Gemma 0000-0002-7870-066X Department of Psychological Medicine, Institute of Psychiatry, Psychology, and Neuroscience, King's College London, London, UK. gemma.modinos@kcl.ac.uk.,MRC Centre for Neurodevelopmental Disorders, King's College London, London, UK. gemma.modinos@kcl.ac.uk. 10.1038/s41380-026-03547-x 42000906 1359-4184 https://www.nature.com/articles/s41380-026-03547-x 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. Dewey 616.89 Dewey 150 Swiss National Science Foundation Modulating the neural processing of internal and external rewards - a multimodal approach combining neuroimaging, TMS and pharmacological challenge 178175 CH Swiss National Science Foundation Linking inflammation and oxidative stress to motivational deficits in schizophrenia 219240 CH Swiss National Science Foundation From schizotypy to clinical high-risk for psychosis: an integrative longitudinal study 159440 CH 60 Département de psychiatrie 225 108 Section de psychologie 71 false 1465 Neurosciences transdiagnostiques et multimodales 1075 1236 Psychopathologie clinique et expérimentale 987 603 Unité de psychologie clinique développementale (UPCD) 1431 Neuroimagerie et psychiatrie translationnelle 1058 1284 NCCR Synapsy https://enigma-toolbox.readthedocs.io/en/latest/ https://github.com/netneurolab/hansen_crossdisorder_vulnerability https://github.com/netneurolab/hansen_receptors https://github.com/ENIGMA-git Molecular psychiatry 784aa4d6-aef3-42fa-a104-223a372a0ce3 Article (Published version) Public Article_scientifique_from_unpaywall.pdf 5033993 application/pdf CC BY-4.0 5e77fbcefd77db7874661d9d7bd4308f4789fe35f233a3ae170624e1872eb2a8 2dd836c7-a1b7-4fce-bb45-72a7e477d095 Supplemental data Public 41380_2026_3547_MOESM1_ESM.docx 1772738 application/vnd.openxmlformats-officedocument.wordprocessingml.document b0ff152eeadc3c7fcabd5d5d54d9e0bb4625fb978ec74f015d4f8f48c77b2e9d openAccess Faculté de médecine / Section de médecine clinique / Département de psychiatrie Faculté de psychologie et des sciences de l'éducation / Section de psychologie

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Multiscale characterization of cortical signatures in positive and negative schizotypy : a worldwide ENIGMA study	Molecular psychiatry			2026	1	0

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