Insula-cerebellar functional connectivity associated with somatic symptoms in mood disorders: Differential patterns and longitudinal evidence in major depressive disorder.

AIM: This study aimed to identify the resting-state functional connectivity (rsFC) of insula subregions associated with nonspecific somatic symptoms in mood disorders and to examine whether these connections are state-dependent. METHODS: In Phase 1, seed-based rsFC analyses were performed using 12 insula subregions from the Brainnetome Atlas in patients with major depressive disorder (MDD), bipolar disorder (BD), and healthy controls. Associations between rsFC and the somatic factor of the Beck Depression Inventory-II (BDI_S) were examined in each group. In Phase 2, insula connections significantly associated with BDI_S in the MDD group were selected as regions of interest, and longitudinal changes in rsFC over 6 weeks were tested for associations with changes in BDI_S. RESULTS: In Phase 1, rsFC between several insular subregions and the left cerebellar lobule VIII (Cereb 8_L) showed modest negative correlations with BDI_S in the MDD group, while rsFC involving the right superior lateral occipital cortex or Cereb 8_L showed positive correlations in the BD group. In MDD and BD, the rsFC between the right dorsal granular insula (dIg_R) and Cereb 8_L showed opposite relationships with BDI_S in the cross-sectional analysis. In Phase 2, increases in dIg_R-Cereb 8_L were significantly associated with reductions in BDI_S in MDD with a modest effect size. CONCLUSION: Insula-cerebellum rsFC, particularly between dIg_R and Cereb 8_L, may serve as a potential state-related neural correlate of nonspecific somatic symptoms in MDD, with potentially distinct functional roles in MDD versus BD.