Illness progression, recent stress, and morphometry of hippocampal subfields and medial prefrontal cortex in major depression
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Background Longitudinal studies of illness progression in patients with major depressive disorder (MDD) indicate that the onset of subsequent depressive episodes becomes increasingly decoupled from external stressors. A possible mechanism underlying this phenomenon is that multiple episodes induce long-lasting neurobiological changes that confer increased risk for recurrence. Prior morphometric studies have frequently reported volumetric reductions in patients with MDD--especially in medial prefrontal cortex (mPFC) and the hippocampus--but few studies have investigated whether these changes are exacerbated by prior episodes.Methods In a sample of 103 medication-free patients with depression and control subjects with no history of depression, structural magnetic resonance imaging was performed to examine relationships between number of prior episodes, current stress, hippocampal subfield volume and cortical thickness. Volumetric analyses of the hippocampus were performed using a recently validated subfield segmentation approach, and cortical thickness estimates were obtained using vertex-based methods. Participants were grouped on the basis of the number of prior depressive episodes and current depressive diagnosis.Results Number of prior episodes was associated with both lower reported stress levels and reduced volume in the dentate gyrus. Cortical thinning of the left mPFC was associated with a greater number of prior depressive episodes but not current depressive diagnosis.Conclusions Collectively, these findings are consistent with preclinical models suggesting that the dentate gyrus and mPFC are especially vulnerable to stress exposure and provide evidence for morphometric changes that are consistent with stress-sensitization models of recurrence in MDD.
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In two independent MRI hippocampal subsegmentation studies, the dentate gyrus is more affected by depression than the cornu ammonis or subiculum.
“In two independent studies MRI-based hippocampal subsegmentation demonstrated that the dentate gyrus, where neurogenesis is located, is more affected by depression than the cornu ammonis or the subiculum (Huang et al., 2013;Treadway et al., 2015).”
From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Treadway et al., 2015
The hippocampus and medial prefrontal cortex are repeatedly linked to the pathophysiology and progression of major depressive disorder.
“the hippocampus and medial prefrontal cortex (mPFC) have been repeatedly implicated in the pathophysiology and progression of this illness (2,3).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [3]
Smaller hippocampal and medial prefrontal cortex volumes are consistently linked to a more recurrent or relapsing course of major depressive disorder.
“they have been consistently associated with markers of a progressive course of MDD characterized by more recurrent episodes/relapses (3,19–25)”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [3]
People with multiple prior major depressive episodes had smaller hippocampal and medial prefrontal cortex volumes yet reported lower perceived life stress than those with fewer episodes.
“individuals with a history of multiple MDEs exhibited smaller hippocampal and mPFC volumes, yet reported less perceived life stress, compared to those with fewer episodes (3).”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [3]
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BackgroundMethodInfluentialPeripheral telomere length and hippocampal volume in adolescents with major depressive disorder
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- Authors
- Treadway, M. T., Waskom, M. L., Dillon, D. G., Holmes, A. J., Park, M. T. M., Chakravarty, M. M., Dutra, S. J., Polli, F. E., Iosifescu, D. V., Fava, M., Gabrieli, J. D. E., & Pizzagalli, D. A.
- Affiliations
- Harvard University (US)
- Stanford University (US)
- Centre for Addiction and Mental Health (CA)
- Yale University (US)
- Massachusetts Institute of Technology (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Pizzagalli, Diego A.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2015-02
- Volume
- 77
- Issue
- 3
- Pages
- 285-294
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC4277904
- OpenAlex
- W2100143444
- Cited by
- 331
- References
- 78
- Citations by year
- 2026: 11 · 2025: 16 · 2024: 15 · 2023: 22 · 2022: 42 · 2021: 48 · 2020: 41 · 2019: 38 · 2018: 20 · 2017: 30 · 2016: 25 · 2015: 20 · 2014: 2
- FWCI
- 18.65
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- PMC
- Funders
- National Institute of Mental Health (R01 MH068376)
- National Center for Complementary and Alternative Medicine (K01 MH099232, K99 MH094438, R01 AT001638, R21 AT002974)
- W. Garfield Weston Foundation
- 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, disease progression, depression recurrence, hippocampal subfields, dentate gyrus, medial prefrontal cortex, cortical thickness, cortical thinning, stress exposure, hippocampal subfield segmentation, brain structural changes
- MeSH terms
- Adult, Amygdala, Major Depressive Disorder, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Organ Size, Recurrence, Stress, Psychological, Prefrontal Cortex, Disease Progression
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