Identification of key hubs and aberrant connectivity patterns in depression associated with white matter...

There is a significant association between white matter hyperintensities (WMH) and the onset of depression. This study aimed to elucidate the underlying pathological mechanism underpinning WMH-related vulnerability to depression through multimodal neuroimaging analyses of brain structural and functional network alterations.

We recruited 48 WMH patients with depressive symptoms (WMH-D), 47 WMH patients without depressive symptoms (WMH-ND), and 50 demographically matched healthy controls (HC). We first compared global functional connectivity (FC) derived from the amplitude of low-frequency fluctuations (ALFF) and whole-brain voxel-based morphometry (VBM) analyses across groups. Subsequent correlation analyses were performed to examine the relationships between neuroimaging findings and clinical characteristics.

WMH-D patients exhibited significantly reduced FC between the central executive network (CEN) and default mode network (DMN), coupled with enhanced CEN-salience network (SN) connectivity, suggesting a characteristic triple-network dysregulation pattern. Additionally, concurrent functional and structural alterations in the right superior temporal gyrus (STG) demonstrated positive correlations with both depressive severity (r = 0.371, p < 0.009) and disease duration (r = 0.302, p = 0.037).

The study identifies a triple-network (DMN-SN-CEN) functional connectivity signature in WMH-related depression, suggesting potential neuroimaging biomarkers for clinical diagnosis. The identified STG abnormalities, manifesting as concurrent structural-functional deficits, may constitute the neural substrate linking cerebrovascular pathology to depressive symptomatology. These overlapping alterations provide a promising therapeutic target for early intervention strategies.