An aberrant hippocampal subregional network, rather than structure, characterizes major depressive disorder

Behavioral and neuroimaging studies have implicated the hippocampus as a cardinal neural structure in major depressive disorder (MDD) pathogenesis. The hippocampal subregion-specific structural and functional abnormalities in MDD remain unknown.

Multimodal magnetic resonance imaging (MRI) was acquired in 140 patients with MDD and 44 age- and sex-matched healthy controls (HCs). We quantified hippocampal subregional volumes and fractional anisotropy (FA) following a structural and diffusion MRI data analysis processing stream. Hippocampal subregional networks were established using seed-based functional connectivity (FC) analysis. Univariate analysis was used to investigate the differences between the two groups. Significant subfield metrics were correlated with depression severity.

Compared with HCs, we did not find significant differences in subregional volumes or FA metrics in the MDD group. The MDD group exhibited a significantly weaker connectivity of the right hippocampal subregional networks with the temporal cortex (extending to the insula) and basal ganglia but showed increased connectivity of the right subiculum to the bilateral lingual gyrus. The FC between the right cornu ammonis 1 and right fusiform, between the right hippocampal amygdala transition area and the bilateral basal ganglia, were negatively correlated with depression severity (r = -0.224, p = 0.010; r = -0.196, p = 0.025, respectively) in the MDD group.

This study did not consider the longitudinal changes in the structure and functional connectivity of the hippocampal subregion.

These findings advance our understanding of the neurobiological basis of depression by identifying the hippocampal subregional structural and functional abnormalities.