Functional connectivity analyses of individual hippocampal subregions in major depressive disorder with electroconvulsive therapy

Background: The hippocampus has been widely reported to be involved in the neuropathology of major depressive disorder (MDD). All the previous researches adopted group-level hippocampus subregions atlas to investigate abnormal functional connectivities in MDD in absence of capturing individual variability. In addition, the molecular basis of functional impairments of hippocampal subregions in MDD remains elusive.

Objective: We aimed to reveal functional disruptions and recovery of individual hippocampal subregions in MDD patients before and after ECT and linked these functional connectivity differences to transcriptomic profiles to reveal molecular mechanism.

Methods: we used group guided individual functional parcellation approach to define individual subregions of hippocampus for each participant. Resting-state functional connectivity (FC) analysis of individual hippocampal subregions was conducted to investigate functional disruptions and recovery in MDD patients before and after ECT. Spatial association between functional connectivity differences and transcriptomic profiles was employed to reveal molecular mechanism.

Results: MDD patients showed increased FCs of the left tail part of hippocampus with dorsolateral prefrontal cortex and middle temporal gyrus while decreased FC with primary visual cortex. These abnormal FCs in MDD patients were normalized after ECT. In addition, we found that functional disruptions of the left tail part of hippocampus in MDD were mainly related to synaptic signaling and transmission, ion transport, cell-cell signaling and neurogenesis.

Conclusion: Our findings provide initial evidence for functional connectome disruption of individual hippocampal subregions and their molecular basis in MDD.