Structural changes in hippocampal subfields in major depressive disorder: a high-field magnetic resonance imaging study
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Updated: May 14, 2026
High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging
Published on: November 10, 2015
Yushan Huang1, Nicholas J Coupland, R Marc Lebel
1Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada.
Background:
Magnetic resonance imaging (MRI) has shown lower hippocampal volume in major depressive disorder (MDD). Preclinical and postmortem studies show that chronic stress and MDD may affect hippocampal subfields differently, but MRI spatial resolution has previously been insufficient to measure subfield volumes.
Methods:
Twenty MDD participants (9 unmedicated and 11 medicated, both > 6 months) and 27 healthy control subjects were studied. We used T2-weighted two-dimensional fast spin echo and T1-weighted three-dimensional magnetization prepared rapid acquisition gradient-echo sequences at 4.7 T to compare hippocampal subfield volumes at .09 μL voxel volume.
Results:
Unmedicated MDD participants had a lower dentate gyrus volume than control subjects or medicated MDD participants and a lower cornu ammonis (CA1-3) volume in the hippocampal body subregion than control subjects.
Conclusions:
Hippocampal volumes in unmedicated MDD showed evidence of localization to specific subfields and subregions, findings that appear, on the surface, consistent with preclinical evidence for localized mechanisms of hippocampal neuroplasticity. Strengths include in vivo measurement of entire hippocampal subfields and separation between unmedicated and medicated MDD. Limitations include power to control for multiple comparisons and that MRI landmarks approximate the subfields defined by cellular microstructure.
Insights
Unmedicated major depressive disorder (MDD) patients show reduced volume in specific hippocampal subfields, particularly the dentate gyrus and CA1-3 regions. These findings suggest localized neuroplasticity mechanisms in MDD.
Area of Science:
- Neuroimaging
- Neuroscience
- Psychiatry
Background:
- Major depressive disorder (MDD) is associated with reduced hippocampal volume.
- Previous MRI studies lacked resolution to examine hippocampal subfields.
- Chronic stress and MDD may impact hippocampal subfields distinctly.
Purpose of the Study:
- To investigate hippocampal subfield volumes in unmedicated and medicated MDD patients.
- To compare subfield volumes between MDD patients and healthy controls.
- To explore localized changes in hippocampal subfields related to MDD.
Main Methods:
- Utilized high-resolution MRI (4.7 T) with specific sequences (T2-weighted 2D FSE, T1-weighted 3D MRA)
- Measured hippocampal subfield volumes at 0.09 μL voxel resolution.
- Studied 20 MDD participants (9 unmedicated, 11 medicated) and 27 healthy controls.
Main Results:
- Unmedicated MDD participants exhibited lower dentate gyrus volume compared to controls and medicated MDD.
- Unmedicated MDD patients showed reduced cornu ammonis (CA1-3) volume in the hippocampal body.
- Medicated MDD participants did not show these specific subfield volume reductions compared to controls.
Conclusions:
- Hippocampal volume reductions in unmedicated MDD are localized to specific subfields and subregions.
- Findings align with preclinical evidence of localized hippocampal neuroplasticity mechanisms.
- In vivo measurement of entire hippocampal subfields and differentiation between medicated/unmedicated MDD are key strengths.
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