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 P.
AU - Nenadić, Igor
AU - Krug, Axel
AU - Dannlowski, Udo
AU - Repple, Jonathan
AU - Kircher, Tilo
N1 - Funding Information: 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. Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2023 Society of Biological Psychiatry
PY - 2024/4
Y1 - 2024/4
N2 - 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.
AB - 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.
KW - Connectome
KW - Gray matter
KW - Speech
KW - Structural
KW - Transdiagnostic
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85163872303&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.biopsych.2023.05.010
DO - https://doi.org/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 -