Serotonin 1A Receptors, Serotonin Transporter Binding and Serotonin Transporter mRNA Expression in the Brainstem of Depressed Suicide Victims
Open accessAbstract
Suicide and depression are associated with reduced serotonergic neurotransmission. In suicides, there is a reduction in serotonin transporter (SERT) sites and an increase in postsynaptic 5-HT(1A) receptors in localized regions of the prefrontal cortex. In depression, there is a diffuse decrease in SERT binding throughout the dorsoventral extent of the prefrontal cortex. Serotonergic innervation of the prefrontal cortex arises predominantly from neurons in the brainstem dorsal raphe nucleus (DRN). We, therefore, examined postmortem SERT binding and mRNA expression, as well as 5-HT(1A) autoreceptor binding in the DRN of 10 matched pairs of controls and depressed suicide victims. The concentration of SERT sites, SERT mRNA, and 5-HT(1A) binding was not different between controls and suicides (p >.05). In the DRN of suicides, the volume of tissue defined by 5-HT(1A) binding was 40% smaller than controls. An index of the total number of 5-HT(1A) receptors (receptor binding x volume of receptor distribution) was 43.3% lower in the DRN of suicides, compared with controls. The suicide group had 54% fewer DRN neurons expressing SERT mRNA compared with controls. In the serotonin neurons that expressed the SERT gene, expression per neuron was greater in suicides. Less total 5-HT(1A) and SERT binding is consistent with results of in vivo studies in depression. Less feedback inhibition of serotonin DRN firing via 5-HT(1A) autoreceptors and enhancement of serotonin action due to less uptake of serotonin, is consistent with compensatory changes in response to hypofunction in depressed suicides.
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Early-life trauma impairs stress-coping capacity, promoting chronic inflammation that disrupts stress regulation, neuroplasticity, and neurotransmission.
“Additionally, early-life trauma impairs stress-coping capacity, promoting chronic inflammation that disrupts stress regulation, neuroplasticity, and neurotransmission (10).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [10]
The paper’s opening section and Discussion describe altered serotonergic neurotransmission in depressed suicide victims, but do not link it to early-life trauma or inflammation. Searches for early-life trauma, stress coping, inflammation, and neuroplasticity found no passage addressing the claimed causal chain. Page numbers were unavailable in our copy. (LLM, conf=0.76)
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Salehi, M., Saeidi, M., Amanat, M., Barias, T., Anyeji, U., Alzein, O., & Gunturu, S. (2026) · Frontiers in Pediatrics · doi:10.3389/fped.2026.1738009
- Authors
- Arango, V
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Arango, V
- ORCID
- Arango, V
- Venue
- Neuropsychopharmacology
- Published
- 2001-12
- Volume
- 25
- Issue
- 6
- Pages
- 892-903
- ISSN
- 0893-133X (ISSN-L)
- OpenAlex
- W2169374157
- Cited by
- 368
- References
- 56
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 12 · 2023: 3 · 2022: 8 · 2021: 4 · 2020: 13 · 2019: 9 · 2018: 13 · 2017: 18 · 2016: 13 · 2015: 20 · 2014: 20 · 2013: 20 · 2012: 14
- FWCI
- 4.93
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- Florence Research (University of Florence) (submittedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (MH46745, MH-40210, R01MH040210)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Keywords
- 5-HT1A receptor, serotonin transporter, dorsal raphe nucleus, suicide, depression, serotonergic neurotransmission, brainstem, receptor binding, mRNA expression, autoreceptors, postmortem brain
- MeSH terms
- Adult, Aged, Aged, 80 and over, Autoradiography, Brain Stem, Carrier Proteins, Depressive Disorder, Female, Humans, Hydrogen-Ion Concentration, Imipramine, Male, Membrane Glycoproteins, Middle Aged, Nerve Tissue Proteins, Raphe Nuclei, Receptors, Serotonin, RNA, Messenger, Serotonin Antagonists, Sex Characteristics, Suicide, Serotonin Receptor Agonists, 8-Hydroxy-2-(di-n-propylamino)tetralin, In Situ Hybridization, Membrane Transport Proteins, Receptors, Serotonin, 5-HT1, Serotonin Plasma Membrane Transport Proteins
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