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

Xuanqiang Chen1, Pengfeng Xu1, Shaoyong Ye1

  • 1Department of Psychiatry, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, China; Zhejiang Key Laboratory of Precision Psychiatry, Hangzhou, 310003, China.

Journal of Psychiatric Research
|March 14, 2026
PubMed
Abstract

Insights

Major Depressive Disorder with Mixed Features (MDDMF) shows distinct hippocampal abnormalities. MDDMF patients exhibit reduced hippocampal volumes and altered functional connectivity, offering new insights into its pathophysiology.

Area of Science:

  • Neuroimaging
  • Psychiatry
  • Neuroscience

Background:

  • The pathophysiology of Major Depressive Disorder with Mixed Features (MDDMF) remains unclear.
  • This study investigates hippocampal structural and functional differences in MDDMF versus Major Depressive Disorder without Mixed Features (MDDnonMF).

Purpose of the Study:

  • To identify specific alterations in hippocampal subregional structure and function in MDDMF patients.
  • To compare these findings with MDDnonMF patients and healthy controls.

Main Methods:

  • Utilized 3.0-T MRI to assess hippocampal subfield volumes and resting-state functional connectivity (RSFC) in 73 participants (20 MDDMF, 29 MDDnonMF, 24 controls).
  • Seed-based RSFC analysis was performed on subfields exhibiting group differences.

Main Results:

  • MDDMF group showed significantly smaller volumes in the right cornu ammonis 1 (CA1) and right cornu ammonis 3 (CA3) bodies compared to MDDnonMF.
  • MDDMF patients exhibited lower RSFC between the right CA1 body and right inferior temporal gyrus (ITG), and higher RSFC between the left hippocampal fissure and right pallidum.
  • Correlations were found between CUDOS-M scores and RSFC in the pooled MDD cohort.

Conclusions:

  • Structural and functional hippocampal abnormalities are suggested in MDDMF.
  • These findings contribute novel insights into the underlying pathophysiology of MDDMF.
Keywords:
HippocampusMRIMajor depressive disorderMixed featuresResting-state functional activity

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