Structural changes in the hippocampus in major depressive disorder: contributions of disease and treatment
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BACKGROUND: Previous magnetic resonance imaging (MRI) studies of patients with major depressive disorder (MDD) have consistently shown bilateral and unilateral reductions in hippocampal volume relative to healthy controls. Recent structural MRI studies have addressed the question of whether changes in the volume of hippocampal subregions may be associated with MDD. METHODS: We used a comprehensive and reliable 3-dimensional tracing protocol that enables delineation of hippocampal subregions (head, body, tail) to study changes in the hippocampus of patients with MDD. We recruited 39 MDD patients (16 medicated, 23 unmedicated) and 34 healthy age- and sex-matched controls. We acquired images using a magnetization-prepared rapid acquisition gradient echo sequence on a 1.5-T scanner with a spatial resolution of 1.5 mm x 0.5 mm x 0.5 mm. We performed volumetric analyses, blinded to diagnosis, using the interactive software package Display. All volumes were adjusted for intracranial volume. RESULTS: We found a significant reduction in the volume of the hippocampal tail bilaterally, right hippocampal head and right total hippocampus in MDD patients. Medicated MDD patients showed increased hippocampal body volume compared with both healthy controls and unmedicated patients. LIMITATIONS: This study was cross-sectional. Further prospective studies are needed to determine the direct effect of antidepressant treatment. CONCLUSION: Our results suggest that decreased hippocampal tail and hippocampal head volumes could be trait changes, whereas hippocampal body changes may be dependent on treatment. We showed that long-term antidepressant treatment may affect hippocampal volume in patients with MDD.
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Hippocampal subfield analyses show smaller cornu ammonis 1-3, dentate gyrus/cornu ammonis 4, and subiculum volumes, plus anterior and posterior subdivisions, in major depressive disorder.
“those that have parcellated the hippocampus into different subfields have found evidence for reduced cornu ammonis 1–3, dentate gyrus/cornu ammonis 4, and subiculum volumes as well as both anterior and posterior subdivisions in MDD (e.g., 15,16).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [16]
The structure, function, and chemical composition of fronto-temporal and fronto-subcortical circuitry are implicated in the emergence of cognitive symptoms in major depressive disorder.
“The structure, function, and chemical composition of fronto-temporal and fronto-subcortical circuitry have also been implicated in the emergence of cognitive symptoms in MDD.23,24”
From Cognitive Impairment in Major Depressive Disorder (2019) · cites this paper as [23]
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Henje Blom, E., Han, L. K. M., Connolly, C. G., Ho, T. C., Lin, J., LeWinn, K. Z., Simmons, A. N., Sacchet, M. D., Mobayed, N., Luna, M. E., et al. (2015) · Translational Psychiatry · doi:10.1038/tp.2015.172 · Cited by 51 · see citing works
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How do serotonergic psychedelics treat depression: The potential role of neuroplasticity
Artin, H., Zisook, S., & Ramanathan, D. (2021) · World Journal of Psychiatry · doi:10.5498/wjp.v11.i6.201 · Cited by 33 · see citing works
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Willard, S. L., Uberseder, B., Clark, A., Daunais, J. B., Johnston, W. D., Neely, D., Massey, A., Williamson, J. D., Kraft, R. A., Bourland, J. D., et al. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.06.011 · Cited by 25 · see citing works
Zarate-Garza, P. P., Ortega-Balderas, J. A., Ontiveros-Sanchez de la Barquera, J. A., Lugo-Guillen, R. A., Marfil-Rivera, A., Quiroga-Garza, A., Guzman-Lopez, S., & Elizondo-Omaña, R. E. (2021) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2021.06.008 · Cited by 13 · see citing works
- Authors
- Malykhin, N. V., Carter, R., Seres, P., & Coupland, N. J.
- Affiliations
- University of Alberta (CA)
- Venue
- Journal of Psychiatry and Neuroscience
- Publisher
- Canadian Science Publishing
- Published
- 2010-09
- Volume
- 35
- Issue
- 5
- Pages
- 337-343
- ISSN
- 1180-4882 (ISSN-L)
- PMC
- PMC2928287
- OpenAlex
- W1974666078
- Cited by
- 212
- References
- 65
- Citations by year
- 2026: 11 · 2025: 5 · 2024: 19 · 2023: 13 · 2022: 6 · 2021: 16 · 2020: 15 · 2019: 16 · 2018: 20 · 2017: 13 · 2016: 9 · 2015: 11 · 2014: 15 · 2013: 8 · 2012: 23
- FWCI
- 9.63
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- public-domain
- Locations
- Journal of Psychiatry and Neuroscience (publishedVersion, public-domain)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondation pour la Recherche Médicale
- Canadian Institutes of Health Research (MOP 64413)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- major depressive disorder, hippocampus, hippocampal subfields, hippocampal volume, hippocampal tail, hippocampal head, antidepressant treatment, hippocampal plasticity, brain structural changes
- MeSH terms
- Analysis of Variance, Cross-Sectional Studies, Major Depressive Disorder, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Organ Size, Surveys and Questionnaires
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