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Cited by 100Suicide and Self-Harm StudiesNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Neuron density and serotonin receptor binding in prefrontal cortex in suicide

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Underwood, Mark D., Kassir, Suham A., Bakalian, Mihran J., Galfalvy, Hanga, Mann, J. John, Arango, Victoria·2012·The International Journal of Neuropsychopharmacology
DOI 10.1017/s1461145711000691PMC PMC4167642
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Abstract

Although serotonin receptor and cytoarchitectonic alterations are reported in prefrontal cortex (PFC) in suicide and depression, no study has considered binding relative to neuron density. Therefore, we measured neuron density and serotonin transporter (SERT), 5-HT1A and 5-HT2A binding in matched suicides and controls. Suicides and normal controls (n=15 matched pairs) were psychiatrically characterized. Neuron density and binding were determined in dorsal [Brodmann area (BA) 9] and ventral (BA 47) PFC by stereology and quantitative autoradiography in near-adjacent sections. Binding index was defined as the ratio of receptor binding to neuron density. Suicides had lower neuron density in the gyrus of both areas. The binding index was lower for SERT in BA 47 but not in BA9; the 5-HT1A binding index was higher in BA 9 but not in BA 47, while the 5-HT2A binding index was not different between groups. SERT binding was lower in suicides in BA 47 but not BA 9, while 5-HT1A binding was higher in BA 9 but not BA 47. SERT binding negatively correlated with 5-HT1A binding in BA 47 in suicides. Neuron density decreased with age. The 5-HT1A binding index was higher in females than males. We found lower neuron density and lower SERT binding index in both PFC regions in suicides. More 5-HT1A binding with less SERT binding and the negative correlation in depressed suicides suggests post-synaptic receptor up-regulation, and it is independent of the difference in neuron density. Thus, abnormalities in both cortical neurons and in their serotonergic innervation are present in suicides and future studies will need to determine whether cortical changes reflect the trophic effect of altered serotonin innervation.

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  • Synaptic dysfunctions with neuronal atrophy and reductions of glial and GABAergic interneurons in the dorsolateral prefrontal cortex are found in post-mortem analyses of brains of depressive patients and animal models of chronic unpredictable stress.

    “However, synaptic dysfunctions with neuronal atrophy and reductions of glial and GABAergic interneurons in the dorsolateral prefrontal cortex (dlPFC) are found in post-mortem analyses of brains of depressive patients (and animal models of chronic unpredictable stress; Duman and Aghajanian, 2012; Underwood et al., 2012).”

    From Serotonin and neuroplasticity – Links between molecular, functional and structural pathophysiology in depression (2017) · cites this paper as Underwood et al., 2012

    The Introduction reports reduced pyramidal-neuron size and density in prefrontal regions of patients with major depression, and the Discussion reports reduced glial density and lower prefrontal neuron density in depressed suicides (pages unavailable). But the Discussion explicitly says this study could not determine whether a particular neuronal class was lost, so it does not establish a reduction in GABAergic interneurons. It also does not report findings from animal models of chronic unpredictable stress. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • 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 [68]

  • The dentate gyrus plays a role in emotion regulation through its connection to the PFC, which also shows lower neuron density and serotonin receptor binding in suicide decedents.

    “Moreover, the dentate gyrus plays a role in emotion regulation through its connection to the PFC—which also shows lower neuron density and serotonin receptor binding in suicide decedents (68).”

    From A brain-centric model of suicidal behavior (2020) · cites this paper as [68]

  • Men and women with MDD differ in serotonin synthesis and the density of serotonin 5HT1A autoreceptors.

    “as well as differences in serotonin synthesis and the density of serotonin 5HT1A autoreceptors.161,162”

    From Epigenetic mechanisms of major depression: Targeting neuronal plasticity (2018) · cites this paper as [162]

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Research works printed but not linked: 1

  1. Pandey GN Dwivedi Y Ren X Robert RC Conley R Tamminga C 2001 Increased 5HT2A Receptors and Impaired Phosphoinositide Siginaling in the Postmortem Brain of Suicide Victims Miyoshi K Shapiro CM Gaviria M Morita Y Contemporary Neuropsychiatry 314 321 Tokyo Springer-Verlag

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Authors
Underwood, M. D., Kassir, S. A., Bakalian, M. J., Galfalvy, H., Mann, J. J., & Arango, V.
Affiliations
New York State Psychiatric Institute (US)
Corresponding author
Underwood, Mark D.
ORCID
Venue
The International Journal of Neuropsychopharmacology
Publisher
Oxford University Press (OUP)
Published
2011-05-09
Volume
15
Issue
04
Pages
435-447
ISSN
  • 1461-1457 (ISSN-L)
  • 1469-5111
DOI
10.1017/s1461145711000691
PMC
PMC4167642
OpenAlex
W2093956835
Cited by
100
References
82
Citations by year
2026: 3 · 2025: 3 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 3 · 2020: 8 · 2019: 5 · 2018: 9 · 2017: 8 · 2016: 8 · 2015: 9 · 2014: 14 · 2013: 5 · 2012: 9
FWCI
10.21
Type
journal article
Language
en
Open access
Locations
  • The International Journal of Neuropsychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Mental Health (MH 62185, MH-40210, R01MH040210, MH79439, P50MH062185, R01MH079439)
Topics
  • Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
Keywords
suicide, prefrontal cortex, neuronal density, serotonin receptor binding, serotonin transporter, 5-HT1A receptor, 5-HT2A receptor, Brodmann area 9, depression, sex differences, age effects
MeSH terms
Adolescent, Adult, Aged, Autoradiography, Major Depressive Disorder, Female, Humans, Imipramine, Ketanserin, Male, Middle Aged, Neurons, Postmortem Changes, Protein Binding, Receptors, Serotonin, Suicide, Tritium, Up-Regulation, Case-Control Studies, 8-Hydroxy-2-(di-n-propylamino)tetralin, Prefrontal Cortex, Serotonin Agents, Young Adult

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