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Cited by 93Suicide and Self-Harm StudiesNeurotransmitter Receptor Influence on BehaviorTreatment of Major Depression

Positron Emission Tomographic Imaging of the Serotonergic System and Prediction of Risk and Lethality of Future Suicidal Behavior

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Oquendo, Maria A., Galfalvy, Hanga, Sullivan, Gregory M., Miller, Jeffrey M., Milak, Matthew M., Sublette, M. Elizabeth, Cisneros-Trujillo, Sebastian, Burke, Ainsley K. +2 more·2016·JAMA Psychiatry
DOI 10.1001/jamapsychiatry.2016.1478PMC PMC6552665
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Abstract

IMPORTANCE: Biomarkers that predict suicidal behavior, especially highly lethal behavior, are urgently needed. In cross-sectional studies, individuals with depression who attempt suicide have lower midbrain serotonin transporter binding potential compared with those who do not attempt suicide, and higher serotonin1A binding potential in the raphe nuclei (RN) is associated with greater lethality of past suicide attempts and suicidal intent and ideation. OBJECTIVES: To determine whether serotonin transporter binding potential in the lower midbrain predicts future suicide attempts and whether higher RN serotonin1A binding potential predicts future suicidal ideation and intent and lethality of future suicide attempts. DESIGN, SETTING, AND PARTICIPANTS: In this prospective 2-year observational study, a well-characterized cohort of 100 patients presenting for treatment of a major depressive episode of at least moderate severity underwent positron emission tomography using carbon 11-labeled N-(2-(1-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl))-N-(2-pyridyl)-cyclohexanecarboxamide ([11C]WAY-100635), a serotonin1A antagonist; a subset of 50 patients also underwent imaging with carbon 11-labeled 3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)- benzonitrile ([11C]DASB), a serotonin transporter radioligand. Imaging was performed at Columbia University Medical Center from May 3, 1999, to March 11, 2008. Follow-up was completed on May 28, 2010, and data were analyzed from August 1, 2013, to March 1, 2016. EXPOSURES: Patients were treated naturalistically in the community and followed up for 2 years with documentation of suicidal behavior, its lethality, and suicidal ideation and intent. MAIN OUTCOMES AND MEASURES: Suicide attempt or suicide. RESULTS: Of the 100 patients undergoing follow-up for more than 2 years (39 men; 61 women; mean [SD] age, 40.2 [11.2] years), 15 made suicide attempts, including 2 who died by suicide. Higher RN serotonin1A binding potential predicted more suicidal ideation at 3 (b = 0.02; t = 3.45; P = .001) and 12 (b = 0.02; t = 3.63; P = .001) months and greater lethality of subsequent suicidal behavior (b = 0.08; t = 2.89; P = .01). Exploratory analyses suggest that the serotonin1A binding potential of the insula (t = 2.41; P = .04), anterior cingulate (t = 2.27; P = .04), and dorsolateral prefrontal cortex (t = 2.44; P = .03) were also predictive of lethality. Contrary to our hypotheses, suicidal intent was not predicted by serotonin1A binding potential in any brain region (F1,10 = 0.83; P = .38), and midbrain serotonin transporter binding potential did not predict future attempts (log-rank χ21 = 0.4; P = .54), possibly owing to low power. CONCLUSIONS AND RELEVANCE: Greater RN serotonin1A binding potential predicted higher suicidal ideation and more lethal suicidal behavior during a 2-year period. This effect may be mediated through less serotonin neuron firing and release, which affects mood and suicidal ideation and thereby decision making.

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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 [119]

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  1. [17]First MB Sr, 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
Oquendo, M. A., Galfalvy, H., Sullivan, G. M., Miller, J. M., Milak, M. M., Sublette, M. E., Cisneros-Trujillo, S., Burke, A. K., Parsey, R. V., & Mann, J. J.
Affiliations
  • New York State Psychiatric Institute, New York2Department of Psychiatry, Columbia University, New York, New York
  • New York State Psychiatric Institute (US)
  • Tonix Pharmaceuticals (United States) (US)
  • Stony Brook School (US)
ORCID
Venue
JAMA Psychiatry
Publisher
American Medical Association (AMA)
Published
2016-10-01
Volume
73
Issue
10
Pages
1048
ISSN
2168-622X (ISSN-L)
DOI
10.1001/jamapsychiatry.2016.1478
PMC
PMC6552665
OpenAlex
W2486312578
Cited by
93
References
68
Citations by year
2026: 4 · 2025: 4 · 2024: 11 · 2023: 3 · 2022: 8 · 2021: 5 · 2020: 8 · 2019: 9 · 2018: 26 · 2017: 14 · 2016: 1
FWCI
22.28
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 (P50MH090964, R01-MH074813, R01MH040695, R01MH048514, 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
raphe nuclei, midbrain, suicide attempts, suicide lethality, suicidal ideation, suicidal intent, major depressive episode, depression, [11C]WAY-100635, [11C]DASB, serotonergic system, suicide risk prediction, follow-up
MeSH terms
Adult, Benzylamines, Brain, Brain Mapping, Carbon Radioisotopes, Major Depressive Disorder, Female, Follow-Up Studies, Humans, Male, Middle Aged, Piperazines, Prospective Studies, Pyridines, Suicide, Suicide, Attempted, Receptor, Serotonin, 5-HT1A, Positron-Emission Tomography, Serotonin Plasma Membrane Transport Proteins, Suicidal Ideation

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