Brain Structural Network Connectivity of Formal Thought Disorder Dimensions in Affective and Psychotic Disorders

Frederike Stein, Marius Gruber, Marco Mauritz, Katharina Brosch, Julia-Katharina Pfarr, Kai G. Ringwald, Florian Thomas-Odenthal, Adrian Wroblewski, Ulrika Evermann, Olaf Steinsträter, Pascal Grumbach, Katharina Thiel, Alexandra Winter, Linda M. Bonnekoh, Kira Flinkenflügel, Janik Goltermann, Susanne Meinert, Dominik Grotegerd, Jochen Bauer, Nils OpelTim Hahn, Elisabeth J. Leehr, Andreas Jansen, Siemon C. de Lange, Martijn P. van den Heuvel, Igor Nenadić, Axel Krug, Udo Dannlowski, Jonathan Repple, Tilo Kircher

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Background: The psychopathological syndrome of formal thought disorder (FTD) is not only present in schizophrenia (SZ), but also highly prevalent in major depressive disorder and bipolar disorder. It remains unknown how alterations in the structural white matter connectome of the brain correlate with psychopathological FTD dimensions across affective and psychotic disorders. Methods: Using FTD items of the Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms, we performed exploratory and confirmatory factor analyses in 864 patients with major depressive disorder (n = 689), bipolar disorder (n = 108), or SZ (n = 67) to identify psychopathological FTD dimensions. We used T1- and diffusion-weighted magnetic resonance imaging to reconstruct the structural connectome of the brain. To investigate the association of FTD subdimensions and global structural connectome measures, we employed linear regression models. We used network-based statistic to identify subnetworks of white matter fiber tracts associated with FTD symptomatology. Results: Three psychopathological FTD dimensions were delineated, i.e., disorganization, emptiness, and incoherence. Disorganization and incoherence were associated with global dysconnectivity. Network-based statistics identified subnetworks associated with the FTD dimensions disorganization and emptiness but not with the FTD dimension incoherence. Post hoc analyses on subnetworks did not reveal diagnosis × FTD dimension interaction effects. Results remained stable after correcting for medication and disease severity. Confirmatory analyses showed a substantial overlap of nodes from both subnetworks with cortical brain regions previously associated with FTD in SZ. Conclusions: We demonstrated white matter subnetwork dysconnectivity in major depressive disorder, bipolar disorder, and SZ associated with FTD dimensions that predominantly comprise brain regions implicated in speech. Results open an avenue for transdiagnostic, psychopathology-informed, dimensional studies in pathogenetic research.
Original languageEnglish
Pages (from-to)629-638
JournalBiological Psychiatry
Issue number7
Early online date17 May 2023
Publication statusPublished - Apr 2024


  • Connectome
  • Gray matter
  • Speech
  • Structural
  • Transdiagnostic
  • White matter

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