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 Opel; Tim Hahn; Elisabeth J Leehr; Andreas Jansen; Siemon C de Lange; Martijn van den Heuvel; Igor Nenadić; Axel Krug; Udo Dannlowski; Jonathan Repple; Tilo Kircher

doi:10.1016/j.biopsych.2023.05.010

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 van den Heuvel, Igor Nenadić, Axel Krug, Udo Dannlowski, Jonathan Repple, Tilo Kircher

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Abstract

BACKGROUND: The psychopathological syndrome of formal thought disorder (FTD) is present in schizophrenia (SZ) but is also highly prevalent in major depression (MDD) and bipolar disorder (BD). 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 SAPS and SANS, we performed exploratory and confirmatory factor analyses in N=864 patients with MDD (n=689), BD (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 sub-dimensions and global structural connectome measures, we employed linear regression models. We used network-based statistic (NBS) 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. NBS identified subnetworks associated with FTD dimensions "disorganization" and "emptiness" but not with "incoherence". Post-hoc analyses on subnetworks did not reveal diagnosis x 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 MDD, BD and SZ associated with FTD dimensions that comprise predominantly brain regions implicated in speech. Results open an avenue for transdiagnostic, psychopathology informed, dimensional studies in pathogenetic research.

Original language	English
Pages (from-to)	629-638
Number of pages	10
Journal	Biological psychiatry
Volume	95
Issue number	7
Early online date	18 May 2023
DOIs	https://doi.org/10.1016/j.biopsych.2023.05.010
Publication status	Published - 1 Apr 2024

Bibliographical note

Funding

TK has received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, and Neuraxpharm. All other authors report no biomedical financial interests or potential conflicts of interest. This work is part of the German multicentre consortium “Neurobiology of Affective Disorders. A translational perspective on brain structure and function,” funded by the German Research Foundation (Research Unit FOR2107). The principal investigators are TK (Grant Nos. KI588/14-1, KI588/14-2, KI588/20-1, KI588/22-1), UD (Grant Nos. DA1151/5-1, DA1151/5-2), AK (Grant Nos KR3822/5-1, KR3822/7-2), IN (Grant Nos. NE2254/1-2, NE2254/3-1, NE2254/4-1), and CK (Grant No. KO4291/3-1). The study was in part supported by grants from UKGM and Forschungscampus Mittelhessen to IN. SCdL was funded by ZonMw Open Competition, project REMOVE Grant No. 09120011910032. This work is part of the German multicentre consortium “Neurobiology of Affective Disorders. A translational perspective on brain structure and function,” funded by the German Research Foundation (Research Unit FOR2107). The principal investigators are TK (Grant Nos. KI588/14-1, KI588/14-2, KI588/20-1, KI588/22-1), UD (Grant Nos. DA1151/5-1, DA1151/5-2), AK (Grant Nos KR3822/5-1, KR3822/7-2), IN (Grant Nos. NE2254/1-2, NE2254/3-1, NE2254/4-1), and CK (Grant No. KO4291/3-1). The study was in part supported by grants from UKGM and Forschungscampus Mittelhessen to IN. SCdL was funded by ZonMw Open Competition, project REMOVE Grant No. 09120011910032. The FOR2107 cohort project was approved by the Ethics Committees of the Medical Faculties, University of Marburg (AZ:07/14) and University of Münster (AZ:2014-422-b-S). We are deeply indebted to all study participants and staff. A list of acknowledgments can be found online ( www.for2107.de/acknowledgements). TK has received unrestricted educational grants from Servier, Janssen, Recordati, Aristo, Otsuka, and Neuraxpharm. All other authors report no biomedical financial interests or potential conflicts of interest.

Funders	Funder number
Forschungscampus Mittelhessen
ZonMw Open Competition	09120011910032
Janssen Pharmaceutica
Philipps-Universität Marburg	AZ:07/14
Philipps-Universität Marburg
Deutsche Forschungsgemeinschaft	KI588/14-1, KO4291/3-1, DA1151/5-2, DA1151/5-1, KR3822/5-1, KR3822/7-2, FOR2107, NE2254/1-2, NE2254/3-1, NE2254/4-1, KI588/20-1, KI588/22-1, KI588/14-2
Deutsche Forschungsgemeinschaft
Westfälische Wilhelms-Universität Münster	AZ:2014-422-b-S
Westfälische Wilhelms-Universität Münster
Uniklinikum Giessen und Marburg
Servier

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10.1016/j.biopsych.2023.05.010

Brain structural network connectivity of formal thought disorder dimensions in affective and psychotic disordersFinal published version, 1.09 MBLicence: Article 25fa Dutch Copyright Act

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Stein, F., Gruber, M., Mauritz, M., Brosch, K., Pfarr, J.-K., Ringwald, K. G., Thomas-Odenthal, F., Wroblewski, A., Evermann, U., Steinsträter, O., Grumbach, P., Thiel, K., Winter, A., Bonnekoh, L. M., Flinkenflügel, K., Goltermann, J., Meinert, S., Grotegerd, D., Bauer, J., ... Kircher, T. (2024). Brain structural network connectivity of formal thought disorder dimensions in affective and psychotic disorders. Biological psychiatry, 95(7), 629-638. https://doi.org/10.1016/j.biopsych.2023.05.010

@article{d21853efa303417f9db3ef0aee38e6cd,

title = "Brain structural network connectivity of formal thought disorder dimensions in affective and psychotic disorders",

abstract = "BACKGROUND: The psychopathological syndrome of formal thought disorder (FTD) is present in schizophrenia (SZ) but is also highly prevalent in major depression (MDD) and bipolar disorder (BD). 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 SAPS and SANS, we performed exploratory and confirmatory factor analyses in N=864 patients with MDD (n=689), BD (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 sub-dimensions and global structural connectome measures, we employed linear regression models. We used network-based statistic (NBS) 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. NBS identified subnetworks associated with FTD dimensions {"}disorganization{"} and {"}emptiness{"} but not with {"}incoherence{"}. Post-hoc analyses on subnetworks did not reveal diagnosis x 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 MDD, BD and SZ associated with FTD dimensions that comprise predominantly brain regions implicated in speech. Results open an avenue for transdiagnostic, psychopathology informed, dimensional studies in pathogenetic research.",

author = "Frederike Stein and Marius Gruber and Marco Mauritz and Katharina Brosch and Julia-Katharina Pfarr and Ringwald, {Kai G} and Florian Thomas-Odenthal and Adrian Wroblewski and Ulrika Evermann and Olaf Steinstr{\"a}ter and Pascal Grumbach and Katharina Thiel and Alexandra Winter and Bonnekoh, {Linda M} and Kira Flinkenfl{\"u}gel and Janik Goltermann and Susanne Meinert and Dominik Grotegerd and Jochen Bauer and Nils Opel and Tim Hahn and Leehr, {Elisabeth J} and Andreas Jansen and {de Lange}, {Siemon C} and {van den Heuvel}, Martijn and Igor Nenadi{\'c} and Axel Krug and Udo Dannlowski and Jonathan Repple and Tilo Kircher",

note = "Copyright {\textcopyright} 2023. Published by Elsevier Inc.",

year = "2024",

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day = "1",

doi = "10.1016/j.biopsych.2023.05.010",

language = "English",

volume = "95",

pages = "629--638",

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Stein, F, Gruber, M, Mauritz, M, Brosch, K, Pfarr, J-K, Ringwald, KG, Thomas-Odenthal, F, Wroblewski, A, Evermann, U, Steinsträter, O, Grumbach, P, Thiel, K, Winter, A, Bonnekoh, LM, Flinkenflügel, K, Goltermann, J, Meinert, S, Grotegerd, D, Bauer, J, Opel, N, Hahn, T, Leehr, EJ, Jansen, A, de Lange, SC, van den Heuvel, M, Nenadić, I, Krug, A, Dannlowski, U, Repple, J & Kircher, T 2024, 'Brain structural network connectivity of formal thought disorder dimensions in affective and psychotic disorders', Biological psychiatry, vol. 95, no. 7, pp. 629-638. https://doi.org/10.1016/j.biopsych.2023.05.010

TY - JOUR

T1 - Brain structural network connectivity of formal thought disorder dimensions in affective and psychotic disorders

AU - Stein, Frederike

AU - Gruber, Marius

AU - Mauritz, Marco

AU - Brosch, Katharina

AU - Pfarr, Julia-Katharina

AU - Ringwald, Kai G

AU - Thomas-Odenthal, Florian

AU - Wroblewski, Adrian

AU - Evermann, Ulrika

AU - Steinsträter, Olaf

AU - Grumbach, Pascal

AU - Thiel, Katharina

AU - Winter, Alexandra

AU - Bonnekoh, Linda M

AU - Flinkenflügel, Kira

AU - Goltermann, Janik

AU - Meinert, Susanne

AU - Grotegerd, Dominik

AU - Bauer, Jochen

AU - Opel, Nils

AU - Hahn, Tim

AU - Leehr, Elisabeth J

AU - Jansen, Andreas

AU - de Lange, Siemon C

AU - van den Heuvel, Martijn

AU - Nenadić, Igor

AU - Krug, Axel

AU - Dannlowski, Udo

AU - Repple, Jonathan

AU - Kircher, Tilo

PY - 2024/4/1

Y1 - 2024/4/1

N2 - BACKGROUND: The psychopathological syndrome of formal thought disorder (FTD) is present in schizophrenia (SZ) but is also highly prevalent in major depression (MDD) and bipolar disorder (BD). 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 SAPS and SANS, we performed exploratory and confirmatory factor analyses in N=864 patients with MDD (n=689), BD (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 sub-dimensions and global structural connectome measures, we employed linear regression models. We used network-based statistic (NBS) 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. NBS identified subnetworks associated with FTD dimensions "disorganization" and "emptiness" but not with "incoherence". Post-hoc analyses on subnetworks did not reveal diagnosis x 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 MDD, BD and SZ associated with FTD dimensions that comprise predominantly brain regions implicated in speech. Results open an avenue for transdiagnostic, psychopathology informed, dimensional studies in pathogenetic research.

AB - BACKGROUND: The psychopathological syndrome of formal thought disorder (FTD) is present in schizophrenia (SZ) but is also highly prevalent in major depression (MDD) and bipolar disorder (BD). 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 SAPS and SANS, we performed exploratory and confirmatory factor analyses in N=864 patients with MDD (n=689), BD (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 sub-dimensions and global structural connectome measures, we employed linear regression models. We used network-based statistic (NBS) 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. NBS identified subnetworks associated with FTD dimensions "disorganization" and "emptiness" but not with "incoherence". Post-hoc analyses on subnetworks did not reveal diagnosis x 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 MDD, BD and SZ associated with FTD dimensions that comprise predominantly brain regions implicated in speech. Results open an avenue for transdiagnostic, psychopathology informed, dimensional studies in pathogenetic research.

U2 - 10.1016/j.biopsych.2023.05.010

DO - 10.1016/j.biopsych.2023.05.010

M3 - Article

C2 - 37207935

SN - 0006-3223

VL - 95

SP - 629

EP - 638

JO - Biological psychiatry

JF - Biological psychiatry

IS - 7

ER -

Brain structural network connectivity of formal thought disorder dimensions in affective and psychotic disorders

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