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

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.