Altered whole brain functional connectivity pattern homogeneity in medication-free major depressive disorder

Many previous studies have revealed abnormal functional connectivity patterns between brain areas underlying the onset of major depressive disorder (MDD) using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to exactly characterize the voxel-wise whole brain functional connectivity pattern changes in MDD remains unclear, which will provide more convincing evidence for localizing the exactly functional connectivity abnormality in MDD.

In this study, we employed our newly developed whole brain functional connectivity homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 27 medication-free MDD patients and 34 gender-, age-, and education level-matched healthy controls (HC). Furthermore, seed-based functional connectivity analysis was then used to identify the alteration of corresponding functional connectivity.

Significantly decreased FcHo values in right ventral anterior insula (INS) and medial prefrontal cortex (MPFC) were identified in MDD patients. The ensuing functional connectivity analyses identified decreased functional connectivity between MPFC and left angular gyrus (AG) in MDD patients. Moreover, both decreased FcHo values in INS, MPFC and functional connectivity between MPFC and left AG showed significant negative correlations with Hamilton depression rating scale (HDRS) scores. The FcHo values in INS were also negatively correlated with disease duration. Finally, meta-analysis based functional characterization found that these brain areas are mainly involved in emotion, theory of mind and reward processing.

Our findings revealed abnormal whole brain FcHo in INS and MPFC and functional interactions between MPFC and AG in MDD and suggested that dysfunctions of INS and MPFC play an important role in the neuropathology of MDD.