Hippocampal subregional structure and function alterations in patients with major depressive disorder with mixed...

The pathophysiological mechanism of major depressive disorder with mixed features (MDDMF) is not fully understood. This study aimed to identify alterations in hippocampal subregional structure and function in patients with MDDMF compared with patients with major depressive disorder without mixed features (MDDnonMF).

Seventy-three participants (20 MDDMF, 29 MDDnonMF, and 24 healthy controls) underwent 3.0-T MRI. Hippocampal subfield volumes were quantified, and seed-based RSFC was examined for subfields showing group differences.

Compared with MDDnonMF, the MDDMF group showed smaller volumes in the right cornu ammonis 1 (CA1) body and right cornu ammonis 3 (CA3) body (FDR-corrected), whereas the left hippocampal fissure reduction was exploratory (not surviving FDR correction). Additionally, MDDMF patients displayed lower RSFC between right CA1 body and right inferior temporal gyrus (ITG), higher RSFC between left hippocampal fissure and right pallidum. In the pooled MDD cohort, there were positive correlations between the Clinically Useful Depression Outcome Scale supplemented with questions for the DSM-5 mixed features specifier (CUDOS-M) scores and RSFC between left hippocampal fissure and right pallidum, and negative correlations between CUDOS-M scores and RSFC between right CA1 body and right ITG.

The relatively small sample size of each subgroup.

Our data suggest structural and functional abnormalities of the hippocampus in MDDMF, which provides new insights into the pathophysiology of MDDMF.