Differences in the neural correlates of schizophrenia with positive and negative formal thought disorder in patients with schizophrenia in the ENIGMA dataset

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Rachel J. Sharkey - , University of Iowa (Author)
  • Chelsea Bacon - , University of Iowa (Author)
  • Zeru Peterson - , University of Iowa (Author)
  • Kelly Rootes-Murdy - , Georgia State University (Author)
  • Raymond Salvador - , Sisters Hospitallers Research Foundation (Author)
  • Edith Pomarol-Clotet - , Sisters Hospitallers Research Foundation (Author)
  • Andriana Karuk - , Sisters Hospitallers Research Foundation (Author)
  • Philipp Homan - , University of Zurich (Author)
  • Ellen Ji - , University of Zurich (Author)
  • Wolfgang Omlor - , University of Zurich (Author)
  • Stephanie Homan - , University of Zurich (Author)
  • Foivos Georgiadis - , University of Zurich (Author)
  • Stefan Kaiser - , Geneva University Hospitals (Author)
  • Matthias Kirschner - , Geneva University Hospitals (Author)
  • Stefan Ehrlich - , Division of Psychological and Social Medicine and Developmental Neurosciences (Author)
  • Udo Dannlowski - , University of Münster (Author)
  • Dominik Grotegerd - , University of Münster (Author)
  • Janik Goltermann - , University of Münster (Author)
  • Susanne Meinert - , University of Münster (Author)
  • Tilo Kircher - , University of Marburg (Author)
  • Frederike Stein - , University of Marburg (Author)
  • Katharina Brosch - , University of Marburg (Author)
  • Axel Krug - , University of Bonn (Author)
  • Igor Nenadic - , University of Marburg (Author)
  • Kang Sim - , Singapore Institute of Mental Health (Author)
  • Gianfranco Spalletta - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • Nerisa Banaj - , IRCCS Fondazione Santa Lucia - Roma (Author)
  • Scott R. Sponheim - , University of Minnesota System (Author)
  • Caroline Demro - , University of Minnesota System (Author)
  • Ian S. Ramsay - , University of Minnesota System (Author)
  • Margaret King - , The Mind Research Network (Author)
  • Yann Quidé - , University of New South Wales (Author)
  • Melissa Jane Green - , University of New South Wales (Author)
  • Dana Nguyen - , University of California at Irvine (Author)
  • Adrian Preda - , University of California at Irvine (Author)
  • Vince Calhoun - , Georgia State University (Author)
  • Jessica Turner - , Ohio State University (Author)
  • Theo van Erp - , University of California at Irvine (Author)
  • Thomas Nickl-Jockschat - , University of Iowa, Otto von Guericke University Magdeburg, German Center for Mental Health (DZPG) Partner Site Jena, Halle, Mageburg, C-I-R-C Center for Intervention and Research on adaptive and maladaptive brain Circuits underlying mental health (Author)

Abstract

Formal thought disorder (FTD) is a clinical key factor in schizophrenia, but the neurobiological underpinnings remain unclear. In particular, the relationship between FTD symptom dimensions and patterns of regional brain volume loss in schizophrenia remains to be established in large cohorts. Even less is known about the cellular basis of FTD. Our study addresses these major obstacles by enrolling a large multi-site cohort acquired by the ENIGMA Schizophrenia Working Group (752 schizophrenia patients and 1256 controls), to unravel the neuroanatomy of FTD in schizophrenia and using virtual histology tools on implicated brain regions to investigate the cellular basis. Based on the findings of previous clinical and neuroimaging studies, we decided to separately explore positive, negative and total formal thought disorder. We used virtual histology tools to relate brain structural changes associated with FTD to cellular distributions in cortical regions. We identified distinct neural networks positive and negative FTD. Both networks encompassed fronto-occipito-amygdalar brain regions, but positive and negative FTD demonstrated a dissociation: negative FTD showed a relative sparing of orbitofrontal cortical thickness, while positive FTD also affected lateral temporal cortices. Virtual histology identified distinct transcriptomic fingerprints associated for both symptom dimensions. Negative FTD was linked to neuronal and astrocyte fingerprints, while positive FTD also showed associations with microglial cell types. These results provide an important step towards linking FTD to brain structural changes and their cellular underpinnings, providing an avenue for a better mechanistic understanding of this syndrome.

Details

Original languageEnglish
Pages (from-to)3086-3096
Number of pages11
JournalMolecular psychiatry
Volume29(2024)
Issue number10
Publication statusPublished - Oct 2024
Peer-reviewedYes

External IDs

PubMed 38671214
ORCID /0000-0003-2132-4445/work/177360809