Resilience Is Associated With Larger Dentate Gyrus, While Suicide Decedents With Major Depressive Disorder Have Fewer Granule Neurons
Open accessAbstract
Background Early life adversity (ELA) increases major depressive disorder (MDD) and suicide risk and potentially affects dentate gyrus (DG) plasticity. We reported smaller DG and fewer granular neurons (GNs) in MDD. ELA effects on DG plasticity in suicide decedents with MDD (MDDSui) and resilient subjects (ELA history without MDD or suicide) are unknown. Methods We quantified neural progenitor cells (NPCs), GNs, glia, and DG volume in whole hippocampus postmortem in four groups of drug-free, neuropathology-free subjects (N = 52 total): psychological autopsy-defined MDDSui and control subjects with and without ELA (before 15 years of age). Results ELA was associated with larger DG (p < .0001) and trending fewer NPCs (p = .0190) only in control subjects in whole DG, showing no effect on NPCs and DG volume in MDDSui. ELA exposure was associated with more GNs (p = .0003) and a trend for more glia (p = .0160) in whole DG in MDDSui and control subjects. MDDSui without ELA had fewer anterior and mid DG GNs (p < .0001), fewer anterior DG NPCs (p < .0001), and smaller whole DG volume (p = .0005) compared with control subjects without ELA. In MDDSui, lower Global Assessment Scale score correlated with fewer GNs and smaller DG. Conclusions Resilience to ELA involves a larger DG, perhaps related to more neurogenesis depleting NPCs, and because mature GNs and glia numbers do not differ in the resilient group, perhaps there are effects on process extension and synaptic load that can be examined in future studies. In MDDSui without ELA, smaller DG volume, with fewer GNs and NPCs, suggests less neurogenesis and/or more apoptosis and dendrite changes.
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Resilient subjects exposed to childhood adversity but with no lifetime psychiatric diagnosis and natural death had more granule neurons and a larger dentate gyrus.
“Additionally, we found more granule neurons and a larger DG in resilient subjects who were exposed to childhood adversity but had no lifetime psychiatric diagnosis and died from natural causes63.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [63]
Neurogenesis may be blunted in major depressive disorder.
“suggesting that neurogenesis may be blunted in MDD62, 63”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [63]
In postmortem human brain, unmedicated depressed subjects had fewer neural progenitor cells and mature granular neurons selectively in anterior dentate gyrus compared with non-psychiatric sudden death controls.
“In postmortem human brain, we found fewer neural progenitor cells and mature granular neurons in unmedicated depressed subjects, selectively in anterior DG, compared with non-psychiatric sudden death controls, suggesting that neurogenesis may be blunted in MDD62, 63.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [63]
Suicide decedents have smaller gray matter volume in the dlPFC and hippocampus.
“Suicide decedents have smaller gray matter volume in the dlPFC (68) and hippocampus (69, 70), perhaps related to impaired decision making and learning/memory functions, respectively.”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [70]
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- Authors
- Boldrini, M., Galfalvy, H., Dwork, A. J., Rosoklija, G. B., Trencevska-Ivanovska, I., Pavlovski, G., Hen, R., Arango, V., & Mann, J. J.
- Affiliations
- Columbia University Irving Medical Center (US)
- New York State Psychiatric Institute (US)
- Macedonian Academy of Sciences and Arts (MK)
- Ss. Cyril and Methodius University in Skopje (MK)
- Corresponding author
- Boldrini, Maura
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 85
- Issue
- 10
- Pages
- 850-862
- ISSN
- 0006-3223 (ISSN-L)
- PMC
- PMC6830307
- OpenAlex
- W2910607342
- Cited by
- 116
- References
- 111
- Citations by year
- 2026: 11 · 2025: 14 · 2024: 21 · 2023: 14 · 2022: 22 · 2021: 14 · 2020: 12 · 2019: 7
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Foundation for Suicide Prevention (SRG-0-129-12)
- Brain and Behavior Research Foundation (56388)
- National Institutes of Health (NS090415, MH098786, MH94888, MH090964, MH64168, MH40210, MH83862)
- New York Stem Cell Foundation
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- resilience, childhood adversity, major depressive disorder, suicide, dentate gyrus, granule neurons, neural progenitor cells, hippocampal neurogenesis, glia, postmortem brain, psychological autopsy
- MeSH terms
- Adverse Childhood Experiences, Adolescent, Adult, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Neuroglia, Neurons, Suicide, Dentate Gyrus, Resilience, Psychological, Young Adult, Neural Stem Cells
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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