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<p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月18日

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  • 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,
  • Carlotta Barkhau,
  • Alex Fornito,
  • Aurina Arnatkeviciute,
  • Mark A. Bellgrove,
  • Jeggan Tiego,
  • Pamela DeRosse,
  • Melissa Green,
  • Yann Quidé,
  • Christos Pantelis,
  • Raymond C. K. Chan,
  • Yi Wang,
  • Ulrich Ettinger,
  • Martin Debbané,
  • Melodie 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 Fett,
  • Iris Sommer,
  • Sanne Koops,
  • Phillip Grant,
  • Asia Ferrari,
  • Bin Wan,
  • Indrit Bègue,
  • Dennis Hernaus,
  • Maria Jalbrzikowski,
  • Casey Paquola,
  • Sara Larivière,
  • Boris Bernhardt,
  • Sofie L. Valk,
  • Bratislav Misic,
  • Theo G. M. van Erp,
  • Jessica A. Turner,
  • Paul M. Thompson,
  • Andre Aleman,
  • Alain Dagher,
  • Stefan Kaiser,
  • Gemma Modinos

摘要

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.