Positron Emission Tomography of Regional Brain Metabolic Responses to a Serotonergic Challenge and Lethality of Suicide Attempts in Major Depression
Abstract
BACKGROUND: Lower serotonergic activity correlates with high-lethality suicide attempts in major depression. Postmortem studies of serotonin receptors in suicides localize changes to the ventral prefrontal cortex (PFC). We studied serotonergic response in ventral PFC in depressed patients surviving a high-lethality suicide attempt. METHODS: Depressed patients with a history of a high-lethality suicide attempt (n = 16) were compared with those with low-lethality attempts (n = 9) for level of depression, suicidal intent and ideation, impulsivity, aggression, and neuropsychological test performance. Subjects were scanned while medication free after a single-blind placebo and after fenfluramine hydrochloride administration on a second day. Brain responses were measured by positron emission tomography imaging of fludeoxyglucose F 18 and serial prolactin levels. Scans were compared by means of statistical parametric mapping. Correlations of changes in relative regional cerebral uptake (rCMRglu) with clinical and neuropsychological measures were assessed. RESULTS: Depressed high-lethality suicide attempters had lower rCMRglu in ventral, medial, and lateral PFC compared with low-lethality attempters. This difference was more pronounced after fenfluramine administration. Lower ventromedial PFC activity was associated with lower lifetime impulsivity, higher suicidal intent (planning), and higher-lethality suicide attempts. Higher verbal fluency was positively correlated with rCMRglu in the same regions. CONCLUSIONS: Prefrontal localized hypofunction and impaired serotonergic responsivity are proportional to the lethality of the suicide attempt and may mediate the effects of suicide intent and impulsivity on lethality. Positron emission tomographic neuroreceptor studies are needed to determine whether postmortem serotonin receptor findings are also present in vivo and contribute to the abnormal rCMRglu responses.
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Serotonergic release deficits in the ventral PFC and ACC are more prominent in high-lethality suicidal behavior and suicide death.
“4) serotonergic release deficits in the ventral PFC and ACC that are more prominent in high-lethality suicidal behavior and suicide death;”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [118]
Serotonin dysfunction is more prominent in higher-lethality suicidal behavior, indicating localized PFC hypofunction.
“Serotonin dysfunction is more prominent in higher-lethality suicidal behavior (117), indicating localized PFC hypofunction (118).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [118]
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Gray matter volumetric study of major depression and suicidal behavior
Rizk, M. M., Rubin-Falcone, H., Lin, X., Keilp, J. G., Miller, J. M., Milak, M. S., Sublette, M. E., Oquendo, M. A., Ogden, R. T., Abdelfadeel, N. A., et al. (2019) · Psychiatry Research: Neuroimaging · doi:10.1016/j.pscychresns.2018.11.007 · Cited by 35 · see citing works
Self-citationSilvers, J. A., Hubbard, A. D., Chaudhury, S., Biggs, E., Shu, J., Grunebaum, M. F., Fertuck, E., Weber, J., Kober, H., Carson-Wong, A., et al. (2016) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2016.06.020 · Cited by 30 · see citing works
Self-citationImpulsivity, Mental Disorder, and Suicide in Rural China
Lin, L., & Zhang, J. (2017) · Archives of Suicide Research · doi:10.1080/13811118.2015.1004478 · Cited by 21 · see citing works
Cognitive Control as a 5-HT1A-Based Domain That Is Disrupted in Major Depressive Disorder
Langenecker, S. A., Mickey, B. J., Eichhammer, P., Sen, S., Elverman, K. H., Kennedy, S. E., Heitzeg, M. M., Ribeiro, S. M., Love, T. M., Hsu, D. T., et al. (2019) · Frontiers in Psychology · doi:10.3389/fpsyg.2019.00691 · Cited by 18 · see citing works
- Authors
- Oquendo, M. A., Placidi, G. P. A., Malone, K. M., Campbell, C., Keilp, J., Brodsky, B., Kegeles, L. S., Cooper, T. B., Parsey, R. V., Van Heertum, R. L., & Mann, J. J.
- Affiliations
- Columbia University (US)
- Columbia University Irving Medical Center (US)
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2003-01-01
- Volume
- 60
- Issue
- 1
- Pages
- 14
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W1966647036
- Cited by
- 313
- References
- 37
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 6 · 2023: 6 · 2022: 6 · 2021: 12 · 2020: 9 · 2019: 8 · 2018: 33 · 2017: 10 · 2016: 19 · 2015: 22 · 2014: 25 · 2013: 13 · 2012: 9
- FWCI
- 16.92
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (MH 62185, R01MH040695, MH 40695, P50MH062185)
- National Center for Research Resources (RR 00645, M01RR000645)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- major depressive disorder, suicide attempts, suicide lethality, fenfluramine, ventral prefrontal cortex, regional cerebral glucose metabolism, impulsivity, suicidal intent, verbal fluency, prolactin, serotonin receptors
- MeSH terms
- Adult, Age Factors, Brain, Depressive Disorder, Female, Fenfluramine, Glucose, Humans, Hydroxyindoleacetic Acid, Impulsive Behavior, Male, Prolactin, Receptors, Serotonin, Serotonin, Suicide, Attempted, Tissue Distribution, Tomography, Emission-Computed, Selective Serotonin Reuptake Inhibitors, Prefrontal Cortex, Fluorodeoxyglucose F18
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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