Early-Life Adversity, but Not Suicide, Is Associated With Less Prefrontal Cortex Gray Matter in Adulthood
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Abstract
BACKGROUND: Suicide and major depression are prevalent in individuals reporting early-life adversity. Prefrontal cortex volume is reduced by stress acutely and progressively, and changes in neuron and glia density are reported in depressed suicide decedents. We previously found reduced neurotrophic factor brain-derived neurotrophic factor in suicide decedents and with early-life adversity, and we sought to determine whether cortex thickness or neuron or glia density in the dorsolateral prefrontal and anterior cingulate cortex are associated with early-life adversity or suicide. METHODS: A total of 52 brains, constituting 13 quadruplets of nonpsychiatric controls and major depressive disorder suicide decedents with and without early-life adversity, were matched for age, sex, race, and postmortem interval. Brains were collected at autopsy and frozen, and dorsolateral prefrontal cortex and anterior cingulate cortex were later dissected, postfixed, and sectioned. Sections were immunostained for neuron-specific nuclear protein (NeuN) to label neurons and counterstained with thionin to stain glial cell nuclei. Cortex thickness, neuron and glial density, and neuron volume were measured by stereology. RESULTS: Cortical thickness was 6% less with early-life adversity in dorsolateral prefrontal cortex and 12% less in anterior cingulate cortex (P < .05), but not in depressed suicide decedents in either region. Neuron density was not different in early-life adversity or with suicide, but glial density was 17% greater with early-life adversity in dorsolateral prefrontal cortex and 15% greater in anterior cingulate cortex, but not in suicides. Neuron volume was not different with early-life adversity or suicide. CONCLUSIONS: Reported early-life adversity, but not the stress associated with suicide, is associated with thinner prefrontal cortex and greater glia density in adulthood. Early-life adversity may alter normal neurodevelopment and contribute to suicide risk.
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Reduced mPFC volume has repeatedly been demonstrated in adults reporting childhood emotional maltreatment and/or early life adversity.
“Reduced mPFC volume has repeatedly been demonstrated in adults reporting childhood emotional maltreatment and/or early life adversity (120, 121).”
From Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis (2022) · cites this paper as [121]
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Childhood Trauma, the HPA Axis and Psychiatric Illnesses: A Targeted Literature Synthesis
Murphy, F., Nasa, A., Cullinane, D., Raajakesary, K., Gazzaz, A., Sooknarine, V., Haines, M., Roman, E., Kelly, L., O'Neill, A., et al. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.748372 · Cited by 181 · see citing works
“Reduced mPFC volume has repeatedly been demonstrated in adults reporting childhood emotional maltreatment and/or early life adversity (120, 121).”
BackgroundBiological bases of suicidal behaviours: a narrative review
Lengvenyte, A., Conejero, I., Courtet, P., & Olié, E. (2021) · European Journal of Neuroscience · doi:10.1111/ejn.14635 · Cited by 87 · see citing works
Kalia, V., & Knauft, K. (2020) · PLOS ONE · doi:10.1371/journal.pone.0235412 · Cited by 86 · see citing works
- Authors
- Underwood, M. D., Bakalian, M. J., Escobar, T., Kassir, S., Mann, J. J., & Arango, V.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Underwood, Mark D
- Venue
- International Journal of Neuropsychopharmacology
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-03-26
- Volume
- 22
- Issue
- 5
- Pages
- 349-357
- ISSN
- 1461-1457 (ISSN-L)
- 1469-5111
- PMC
- PMC6499245
- OpenAlex
- W2913571576
- Cited by
- 40
- References
- 15
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 6 · 2023: 7 · 2022: 9 · 2021: 6 · 2020: 3 · 2019: 3
- FWCI
- 6.13
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- The International Journal of Neuropsychopharmacology (publishedVersion, cc-by-nc)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH40210, MH62185)
- Diane Goldberg Foundation (MH90964, MH64168)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- childhood adversity, suicide, major depressive disorder, prefrontal cortex, anterior cingulate cortex, cortical thickness, glial density, neuronal density, brain development, suicide risk, brain-derived neurotrophic factor
- MeSH terms
- Adult Survivors of Child Adverse Events, Adult, Depressive Disorder, Female, Gyrus Cinguli, Humans, Male, Neuroglia, Neurons, Organ Size, Stress, Psychological, Suicide, Prefrontal Cortex, Gray Matter
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