Structural and dynamic functional connectivity alterations of cerebellum associated with family history in major depressive disorder

Family history (FH) of major depressive disorder (MDD) significantly influences the progress of this illness. However, the underlying neural mechanism of FH remains unclear. This study aimed to examine the brain structural and connectivity alterations associated with FH in MDD. A total of 134 MDD patients with (FH group, n = 43) and without (NFH group, n = 91) first-degree FH, and 96 demographic matched healthy controls (HCs) underwent structural and resting-state functional magnetic resonance imaging examination. Voxel-based morphometry and sliding-window dynamic functional connectivity (dFC) analyses were performed, and altered gray matter volume (GMV) and dFC were further used to differentiate between FH and NFH. Compared with HCs, both FH and NFH groups showed decreased GMV of left cerebellum and increased dFC between cerebellum and left inferior parietal lobule (IPL). FH group showed increased dFC between cerebellum and medial prefrontal cortex (mPFC) compared with NFH and HCs. The GMV of cerebellum was positively correlated with C-reactive protein in the NFH group, while the dFC between cerebellum and mPFC was positively correlated with interleukin-6 in the FH group. Moreover, the combination of structure and dynamic connectomes is powerful to successfully distinguish FH from NFH patients. Altogether, the current results suggest that cerebellar structure and function differ as a function of FH of MDD and may somehow be related to inflammatory factors. Furthermore, the findings might provide new insight into the underlying pathogenetic mechanisms of MDD, yet future longitudinal study is required. Keywords: Major depressive disorder, family history, cerebellum, voxel-based morphometry, dynamic functional connectivity