Dysfunction of the anterior and intermediate hippocampal functional network in major depressive disorders across the adult lifespan

Accumulating evidence indicates that structural and functional abnormalities in hippocampal formation are linked to major depressive disorder (MDD). However, the resting-state functional connectivity (RSFC) of hippocampal subfields in MDD remains unclear. This cross-sectional study aimed to investigate the RSFC of hippocampal subfields in a large sample of MDD patients. The results revealed that patients with MDD showed lower RSFC between the right anterior hippocampus and the insula, and the RSFC was inversely correlated with anxiety symptoms of depression. Depressed patients also showed decreased RSFC between the bilateral intermediate hippocampus and left nucleus accumbens (NAcc), and the hippocampus-NAcc circuit was negatively correlated with core symptoms of depression. The functional connectivity between the right anterior hippocampus and left postcentral gyrus increased with ageing in MDD patients compared with healthy controls. These findings suggest that the functional network of hippocampal subfields may underlie anxiety and core depression symptoms.