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Cited by 40Suicide and Self-Harm StudiesChild Abuse and TraumaStress Responses and Cortisol

Early-Life Adversity, but Not Suicide, Is Associated With Less Prefrontal Cortex Gray Matter in Adulthood

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Underwood, Mark D, Bakalian, Mihran J, Escobar, Teresa, Kassir, Suham, Mann, J John, Arango, Victoria·2019·International Journal of Neuropsychopharmacology
DOI 10.1093/ijnp/pyz013PMC PMC6499245

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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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Cited by

Sorted by citations

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
ORCID
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
DOI
10.1093/ijnp/pyz013
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
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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