Stein Frederike, Gruber Marius, Mauritz Marco, Brosch Katharina, Pfarr Julia-Katharina, Ringwald Kai G, Thomas-Odenthal Florian, Wroblewski Adrian, Evermann Ulrika, Steinsträter Olaf, Grumbach Pascal, Thiel Katharina, Winter Alexandra, Bonnekoh Linda M, Flinkenflügel Kira, Goltermann Janik, Meinert Susanne, Grotegerd Dominik, Bauer Jochen, Opel Nils, Hahn Tim, Leehr Elisabeth J, Jansen Andreas, de Lange Siemon C, van den Heuvel Martijn P, Nenadić Igor, Krug Axel, Dannlowski Udo, Repple Jonathan, Kircher Tilo
Department of Psychiatry and Psychotherapy, University of Marburg, Marburg, Germany; Center for Mind, Brain and Behavior, University of Marburg, Marburg, Germany.
Institute for Translational Psychiatry, University of Münster, Münster, Germany; Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
Biol Psychiatry. 2024 Apr 1;95(7):629-638. doi: 10.1016/j.biopsych.2023.05.010. Epub 2023 May 18.
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.
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.
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.
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.
形式思维障碍（FTD）的精神病理综合征不仅存在于精神分裂症（SZ）中，在重度抑郁症和双相情感障碍中也高度普遍。目前尚不清楚大脑结构白质连接组的改变如何与情感障碍和精神障碍中的精神病理FTD维度相关。
我们使用阳性症状评估量表和阴性症状评估量表中的FTD项目，对864例重度抑郁症患者（n = 689）、双相情感障碍患者（n = 108）或SZ患者（n = 67）进行探索性和验证性因素分析，以确定精神病理FTD维度。我们使用T1加权和扩散加权磁共振成像来重建大脑的结构连接组。为了研究FTD子维度与整体结构连接组测量值之间的关联，我们采用了线性回归模型。我们使用基于网络的统计方法来识别与FTD症状相关的白质纤维束子网。
确定了三个精神病理FTD维度，即紊乱、空洞和语无伦次。紊乱和语无伦次与整体连接性障碍有关。基于网络的统计方法识别出与FTD维度紊乱和空洞相关的子网，但与FTD维度语无伦次无关。对子网的事后分析未发现诊断×FTD维度的交互作用。在校正药物治疗和疾病严重程度后，结果保持稳定。验证性分析表明，两个子网的节点与先前在SZ中与FTD相关的皮质脑区有大量重叠。
我们证明了在重度抑郁症、双相情感障碍和SZ中，白质子网连接性障碍与主要包括涉及言语的脑区的FTD维度相关。研究结果为病因学研究中的跨诊断、基于精神病理学的维度研究开辟了一条途径。
