Distinguished Frontal White Matter Abnormalities Between Psychotic and Nonpsychotic Bipolar Disorders in a Pilot...

Recent studies indicate extensive shared white matter (WM) abnormalities between bipolar disorder (BD) and schizophrenia (SZ). However, the heterogeneity of WM in BD in terms of the presence of psychosis remains a critical issue for exploring the boundaries between BD and SZ. Previous studies comparing WM microstructures in psychotic and nonpsychotic BDs (PBD and NPBD) have resulted in limited findings, probably due to subtle changes, emphasizing the need for further investigation.

Diffusion tensor imaging measures were obtained from 8 individuals with PBD, 8 with NPBD, and 22 healthy controls (HC), matched for age, gender, handedness, and educational years. Group comparisons were conducted using tract-based spatial statistics (TBSS). The most significant voxels showing differences between PBD and HC in the TBSS analyses were defined as a TBSS-ROI and subsequently analyzed.

Increased radial diffusivity (RD) in PBD compared to NPBD (p < 0.006; d = 1.706) was observed in TBSS-ROI, distributed in the confined regions of some WM tracts, including the body of the corpus callosum (bCC), the left genu of the CC (gCC), and the anterior and superior corona radiata (ACR and SCR). Additionally, NPBD exhibited significant age-associated RD increases (R² = 0.822, p < 0.001), whereas the greater RD observed in PBD compared to NPBD remained consistent across middle age.

Preliminary findings from this small sample suggest severe frontal WM disconnection in the anterior interhemispheric communication, left fronto-limbic circuits, and cortico-striatal-thalamic loop in PBD compared to NPBD. While these results require replication and validation in larger and controlled samples, they provide insights into the pathophysiology of PBD, which is diagnostically located at the boundary between BD and SZ.