Serotonin-1A autoreceptor binding in the dorsal raphe nucleus of depressed suicides
Open accessAbstract
Serotonergic dysfunction is present in mood disorders and suicide. Brainstem 5-HT1A somatodendritic autoreceptors regulate serotonin neuron firing but studies of autoreceptor binding in the dorsal raphe nucleus (DRN) in depressed suicides report conflicting results. We sought to determine: (1) the anatomical distribution of 5-HT1A receptor binding in the DRN in depressed suicides and psychiatrically normal controls; and (2) whether sex differences in 5-HT1A binding in the DRN contribute to differences between depressed suicides and controls. Previously collected quantitative receptor autoradiograms of [3H]8-hydroxy-2-(di-n-propyl)aminotetralin (3H-8-OH-DPAT) in postmortem tissue sections containing the DRN from drug-free suicide victims (n=10) and matched controls (n=10) were analyzed. Less total receptor binding (fmol/mg tissuexmm3) was observed in the entire DRN in depressed suicides compared with controls (p<0.05). Group differences along the rostrocaudal extent of the DRN were observed for cross-sectional 5-HT(1A) binding (fmol/mg tissue) and receptor binding (fmol/mgxmm3, p<0.05). Cross-sectional 5-HT1A DRN binding in depressed suicides compared with controls was higher rostrally and lower caudally. The differences between depressed suicides and controls were present in males and females, although females had more binding than males. Less autoreceptor binding in the DRN of depressed suicides may represent a homeostatic response to less serotonin release, increasing serotonin neuron firing. More autoreceptor binding in rostral DRN might contribute to deficient serotonin release in ventromedial prefrontal cortex by lower neuronal firing.
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Abnormalities in dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems have been implicated in suicide.
“Abnormalities in dopaminergic, glutamatergic, GABAergic, and endocannabinoid systems have also been implicated in suicide.”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [34]
The Background (section 1.1) discusses serotonergic abnormalities in suicide, not the four systems named in the claim. A reference mentions GABA and glutamate receptors in the control of serotonergic neurons, but does not link their abnormalities to suicide; searches for the four systems and endocannabinoids found no passage making that link. (LLM, conf=0.76)
Experimental — accuracy not yet measuredAlterations in CB1 receptor expression in the dorsolateral prefrontal cortex of suicide victims, particularly among those with comorbid substance use, implicate the endocannabinoid system in emotional regulation and stress response.
“Alterations in CB1 receptor expression in the dorsolateral prefrontal cortex (PFC) of suicide victims, particularly among those with comorbid substance use, further implicate the endocannabinoid system in emotional regulation and stress response (32–34).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [34]
The Abstract reports serotonin-1A receptor binding in the dorsal raphe nucleus, while section 4.1 discusses serotonergic projections to the prefrontal cortex. Neither passage addresses CB1 receptor expression, comorbid substance use, or an endocannabinoid role in emotional regulation and stress response; searches for those terms found no supporting passage in our copy. Page numbers were not available. (LLM, conf=0.78)
Experimental — accuracy not yet measuredThe serotonin deficit likely involves less serotonin neuron firing and less release, because fatal and nonfatal suicide attempts are associated with up-regulated serotonin 1A autoreceptors.
“The serotonin deficit likely involves less serotonin neuron firing and less release, because fatal and nonfatal suicide attempts are associated with up-regulated serotonin 1A autoreceptors that are located on serotonin neuron cell bodies and proximal dendrites (111, 112).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [111]
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References 54 · Cited by 190
Research works printed but not linked: 1
- Leander P, Vrang N, Moller M. Neuronal projections from the mesencephalic raphe nuclear complex to the suprachiasmatic nucleus and the deep pineal gland of the golden hamster (Mesocricetus auratus). Journal of Computational Neurology 1998;399:73-93.
- Authors
- Boldrini, M., Underwood, M. D., Mann, J. J., & Arango, V.
- Affiliations
- New York State Psychiatric Institute (US)
- Corresponding author
- Arango, Victoria
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 42
- Issue
- 6
- Pages
- 433-442
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC2268626
- OpenAlex
- W1970840237
- Cited by
- 190
- References
- 54
- Citations by year
- 2026: 2 · 2025: 10 · 2024: 8 · 2023: 6 · 2022: 8 · 2021: 12 · 2020: 7 · 2019: 11 · 2018: 14 · 2017: 7 · 2016: 11 · 2015: 13 · 2014: 14 · 2013: 12 · 2012: 18
- FWCI
- 3.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Florence Research (University of Florence) (submittedVersion, other-oa)
- Funders
- American Foundation for Suicide Prevention
- National Alliance for Research on Schizophrenia and Depression
- National Institute on Alcohol Abuse and Alcoholism (R01AA009004)
- National Institute of Mental Health (MH62105, P30MH046745, MH-40210, R01MH040210, P50MH062185)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- dorsal raphe nucleus, suicide, depression, 5-HT1A receptor binding, sex differences, serotonin release, postmortem brain, ventromedial prefrontal cortex
- MeSH terms
- Autoradiography, Binding Sites, Carrier Proteins, Depression, Female, Humans, Male, Middle Aged, Raphe Nuclei, Suicide, 8-Hydroxy-2-(di-n-propylamino)tetralin, Autoreceptors, Receptor, Serotonin, 5-HT1A
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