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Cited by 118Suicide and Self-Harm StudiesNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Positron Emission Tomography Quantification of Serotonin1AReceptor Binding in Suicide Attempters With Major Depressive Disorder

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Sullivan, Gregory M., Oquendo, Maria A., Milak, Matthew, Miller, Jeffrey M., Burke, Ainsley, Ogden, R. Todd, Parsey, Ramin V., Mann, J. John·2015·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2014.2406PMC PMC4329977
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Abstract

IMPORTANCE: Serotonergic system dysfunction has been associated with increased lethal suicide attempts and suicide. Dysfunction includes higher binding of serotonin(1A) autoreceptor in the brainstem raphe of individuals who die by suicide. OBJECTIVES: To determine the relationships between brain serotonin(1A) binding and suicidal behavior in vivo in major depressive disorder (MDD) using positron emission tomography and the serotonin(1A) antagonist radiotracer carbon C 11 [11C]-labeled WAY-100635. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional positron emission tomography study at an academic medical center from 1999 through 2009. We compared serotonin(1A) binding between individuals with MDD who did not attempt suicide (nonattempters) (n = 62) and those who attempted suicide (attempters) (n = 29). We subdivided the attempters into those with lower (n = 16) and higher (n = 13) levels of lethality. MAIN OUTCOMES AND MEASURES: The binding potential (BPF) of [11C]WAY-100635 (calculated as the number of receptors available divided by affinity) in the prefrontal cortex (PFC) and brainstem, estimated by kinetic modeling with an arterial input function; the severity of suicidal behaviors, including lethality and intent of suicide attempts; and suicidal ideation. RESULTS: Using a linear mixed-effects model, we found no difference between attempters and nonattempters with MDD in serotonin(1A) BPF in the PFC regions (F1,88 = 0.03; P = .87) or in the raphe nuclei (F1,88 = 0.29; P = .59). Raphe nuclei serotonin(1A) BPF was 45.1% greater in higher-lethality attempters compared with lower-lethality attempters (F1,25 = 7.33; P = .01), whereas no difference was observed in the PFC regions (F1,25 = 0.12; P = .73). Serotonin(1A )BPF in the raphe nuclei of suicide attempters was positively correlated with the lethality rating (F1,25 = 10.56; P = .003) and the subjective lethal intent factor (F1,25 = 10.63; P = .003; R2 = 0.32) based on the most recent suicide attempt. Suicide ideation in participants with MDD was positively correlated with serotonin(1A) BPF in the PFC regions (F1,88 = 5.19; P = .03) and in the raphe nuclei (F1,87 = 7.38; P = .008; R2 = 0.12). CONCLUSIONS AND RELEVANCE: Higher brainstem raphe serotonin(1A)BPF observed in higher-lethality suicide attempters with MDD is in agreement with findings in suicide studies and also with the finding of low cerebrospinal fluid levels of 5-hydroxyindoleacetic acid in higher-lethality suicide attempters. Higher brainstem raphe serotonin(1A) BPF would be consistent with lower levels of serotonin neuron firing and release and supports a model of impaired serotonin signaling in suicide and higher-lethality suicidal behavior. Severity of suicidal ideation in MDD is related to brainstem and prefrontal serotonin(1A) BPF, suggesting a role for both regions in suicidal ideation. Lower levels of serotonin release at key brain projection sites, such as the prefrontal regions, may favor more severe suicidal ideation and higher-lethality suicide attempts.

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  • Greater raphe nucleus serotonin 1A receptor binding correlates with prior and future higher-lethality suicidal behavior.

    “Greater raphe nucleus serotonin 1A receptor binding correlates with prior and future higher-lethality suicidal behavior (112, 119).”

    From A brain-centric model of suicidal behavior (2020) · cites this paper as [112]

  • 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.

    “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 [112]

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  1. [27]First MB Spitzer RL Gibbon M Williams JBW Structured Clinical Interview for DSM-IV Axis I Disorders, Patient Edition (SCID-I/P), Version 2.0 New York Biometrics Research, New York State Psychiatric Institute 1994

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Authors
Sullivan, G. M., Oquendo, M. A., Milak, M., Miller, J. M., Burke, A., Ogden, R. T., Parsey, R. V., & Mann, J. J.
Affiliations
  • New York State Psychiatric Institute (US)
  • Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York2Department of Psychiatry, Columbia University, New York, New York
  • Stony Brook School (US)
Corresponding author
Mann, J. John
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2015-02-01
Volume
72
Issue
2
Pages
169
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2014.2406
PMC
PMC4329977
OpenAlex
W2099043751
Cited by
118
References
77
Citations by year
2026: 4 · 2025: 9 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 12 · 2020: 11 · 2019: 6 · 2018: 23 · 2017: 12 · 2016: 12 · 2015: 7
FWCI
12.19
Type
journal article
Language
en
Open access
Locations
  • JAMA Psychiatry (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (5r01mh074813-05)
  • National Institute of Mental Health (MH 62185, R01-MH074813, R01MH040695, MH 40695, MH074813, P50MH062185)
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
5-HT1A receptor, serotonin autoreceptors, suicide attempts, major depressive disorder, [11C]WAY-100635, raphe nuclei, prefrontal cortex, suicide lethality, suicidal ideation, brain receptor binding, suicide risk assessment, suicide prevention, neuroimaging biomarkers
MeSH terms
Adult, Major Depressive Disorder, Female, Humans, Male, Middle Aged, Piperazines, Pyridines, Raphe Nuclei, Serotonin Antagonists, Severity of Illness Index, Suicide, Attempted, Prefrontal Cortex, Receptor, Serotonin, 5-HT1A, Positron-Emission Tomography, Suicidal Ideation

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