Higher Postmortem Prefrontal 5-HT2A Receptor Binding Correlates with Lifetime Aggression in Suicide
Abstract
Background In vivo studies find altered serotonin function associated with aggressive and suicidal behaviors. Postmortem studies also reveal serotonergic alterations in suicide subjects but have not reported on the relationship between aggression and the serotonin system. We measured 5-hydroxytryptamine 2A (5-HT(2A)) receptor binding in prefrontal cortex of suicide and nonsuicide subjects and explored the relationship between 5-HT(2A) receptor binding, lifetime aggression, and suicide.Methods The 5-HT(2A) receptor binding in coronal sections of prefrontal cortex was quantified by autoradiography with [(3)H] ketanserin in 37 suicide subjects and 73 nonsuicide subjects. The relationship between [(3)H] ketanserin binding and lifetime aggression, rated on the Brown-Goodwin Aggression History Scale, was assessed controlling for age and sex.Results In suicide subjects, lifetime aggression scores correlated positively with [(3)H] ketanserin binding in all prefrontal Brodmann areas examined, after adjusting for age and sex. This was not the case in nonsuicide subjects. We found no significant differences in aggression scores or [(3)H] ketanserin binding between the suicide subjects and nonsuicide subjects.Conclusions The relationship between aggression and 5-HT(2A) receptor binding in suicide subjects, but not in nonsuicide subjects, may reflect differences in the regulation of the 5-HT(2A) receptor related to suicidal behavior and perhaps other proaggressive changes in brains of suicide subjects.
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Up-regulated postsynaptic cortical serotonin 2A receptors correlate with lifetime aggression severity.
“Other studies report up-regulated postsynaptic cortical serotonin 2A receptors that correlate with lifetime aggression severity (114).”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [114]
Cites
A Simple Sequentially Rejective Multiple Test Procedure
(1979) · Scandinavian Journal of Statistics · doi:10.2307/4615733 · Cited by 21,526 · see citing works
Pazos, Á., & Palacios, J. M. (1985) · Brain Research · doi:10.1016/0006-8993(85)90856-x · Cited by 1,855 · see citing works
Toward a clinical model of suicidal behavior in psychiatric patients
Mann, J. J., Waternaux, C., Haas, G. L., & Malone, K. M. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.2.181 · Cited by 1,791 · see citing works
Self-citationAdrenal steroid receptors and actions in the nervous system
McEwen, B. S., de Kloet, E. R., & Rostène, W. H. (1986) · Physiological Reviews · doi:10.1152/physrev.1986.66.4.1121 · Cited by 1,238 · see citing works
Aggression in humans correlates with cerebrospinal fluid amine metabolites
Brown, G. L., Goodwin, F. K., Ballenger, J. C., Goyer, P. F., & Major, L. F. (1979) · Psychiatry Research · doi:10.1016/0165-1781(79)90053-2 · Cited by 1,133 · see citing works
Pazos, Á., Cortés, R., & Palacios, J. M. (1985) · Brain Research · doi:10.1016/0006-8993(85)90857-1 · Cited by 824 · see citing works
Oquendo, M. A., Galfalvy, H., Russo, S., Ellis, S. P., Grunebaum, M. F., Burke, A., & Mann, J. J. (2004) · American Journal of Psychiatry · doi:10.1176/appi.ajp.161.8.1433 · Cited by 605 · see citing works
Self-citationIncreased Serotonin2 and β-Adrenergic Receptor Binding in the Frontal Cortices of Suicide Victims
Mann, J. J. (1986) · Archives of General Psychiatry · doi:10.1001/archpsyc.1986.01800100048007 · Cited by 549 · see citing works
Self-citationINCREASED SEROTONIN-2 BINDING SITES IN FRONTAL CORTEX OF SUICIDE VICTIMS
Stanley, M., & Mann, J. J. (1983) · The Lancet · doi:10.1016/s0140-6736(83)92590-4 · Cited by 529 · see citing works
Self-citationArango, V., Underwood, M. D., Gubbi, A., & Mann, J. J. (1995) · Brain Research · doi:10.1016/0006-8993(95)00523-s · Cited by 458 · see citing works
Self-citationArango, V. (1990) · Archives of General Psychiatry · doi:10.1001/archpsyc.1990.01810230054009 · Cited by 420 · see citing works
Self-citationAggressive Behavior, Increased Accumbal Dopamine, and Decreased Cortical Serotonin in Rats
van Erp, A. M. M., & Miczek, K. A. (2000) · Journal of Neuroscience · doi:10.1523/jneurosci.20-24-09320.2000 · Cited by 380 · see citing works
Arango, V (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00310-4 · Cited by 368 · see citing works
Self-citationHrdina, P. D., Demeter, E., Vu, T. B., Sótonyi, P., & Palkovits, M. (1993) · Brain Research · doi:10.1016/0006-8993(93)91015-k · Cited by 327 · see citing works
THE BIOLOGY OF IMPULSIVITY AND SUICIDALITY
Oquendo, M. A., & Mann, J. J. (2000) · Psychiatric Clinics of North America · doi:10.1016/s0193-953x(05)70140-4 · Cited by 325 · see citing works
Self-citationArora, R. C., & Meltzer, H. Y. (1989) · American Journal of Psychiatry · doi:10.1176/ajp.146.6.730 · Cited by 313 · see citing works
Crow, T. J. (1984) · Neuropharmacology · doi:10.1016/0028-3908(84)90100-x · Cited by 308 · see citing works
The Dexamethasone Suppression Test and Suicide Prediction
Coryell, W., & Schlesser, M. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.5.748 · Cited by 304 · see citing works
Serotonin Receptors and Animal Models of Aggressive Behavior
Olivier, B., Mos, J., van Oorschot, R., & Hen, R. (1995) · Pharmacopsychiatry · doi:10.1055/s-2007-979624 · Cited by 285 · see citing works
Mann, J. J. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820060022003 · Cited by 281 · see citing works
Self-citationHigher Expression of Serotonin 5-HT2A Receptors in the Postmortem Brains of Teenage Suicide Victims
Pandey, G. N., Dwivedi, Y., Rizavi, H. S., Ren, X., Pandey, S. C., Pesold, C., Roberts, R. C., Conley, R. R., & Tamminga, C. A. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.3.419 · Cited by 281 · see citing works
Turecki, G., Brière, R., Dewar, K. M., Antonetti, T., LESAGE, A. D., Séguin, M., Chawky, N., Vanier, C., Alda, M., Joober, R., et al. (1999) · American Journal of Psychiatry · doi:10.1176/ajp.156.9.1456 · Cited by 276 · see citing works
Kelly, T. M., & Mann, J. J. (1996) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.1996.tb09869.x · Cited by 272 · see citing works
Self-citationQuantitative film autoradiography for tritium: Methodological considerations
Geary, W. A., Toga, A. W., & Wooten, G. F. (1985) · Brain Research · doi:10.1016/0006-8993(85)91613-0 · Cited by 240 · see citing works
Selective Abnormalities of Prefrontal Serotonergic Receptors in Schizophrenia
Laruelle, M. A. (1993) · Archives of General Psychiatry · doi:10.1001/archpsyc.1993.01820220066007 · Cited by 235 · see citing works
Brain 5-HT2 receptor binding sites in depressed suicide victims
Cheetham, S. C., Crompton, M. R., Katona, C., & Horton, R. W. (1988) · Brain Research · doi:10.1016/0006-8993(88)91621-6 · Cited by 223 · see citing works
Meijer, O. C., & de Kloet, E. R. (1998) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v12.i1-2.10 · Cited by 204 · see citing works
Serotonergic mechanisms in brains of suicide victims
Owen, F., Chambers, D., Cooper, S. J., Crow, T. J., Johnson, J. A., Lofthouse, R., & Poulter, M. (1986) · Brain Research · doi:10.1016/0006-8993(86)91415-0 · Cited by 160 · see citing works
Stanley, B., Molcho, A., Stanley, M., Winchel, R., Gameroff, M. J., Parsons, B., & Mann, J. J. (2000) · American Journal of Psychiatry · doi:10.1176/appi.ajp.157.4.609 · Cited by 155 · see citing works
Self-citationSerotonin Receptors in Suicide Victims with Major Depression
Stockmeier, C. A. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00170-4 · Cited by 153 · see citing works
Brain 5-HT1A, 5-HT1D, and 5-HT2 Receptors in suicide victims
Arranz, B., Eriksson, A., Mellerup, E. T., Plenge, P., & Marcusson, J. O. (1994) · Biological Psychiatry · doi:10.1016/0006-3223(94)90044-2 · Cited by 120 · see citing works
Arango, V., Ernsberger, P. R., Sved, A. F., & Mann, J. J. (1993) · Brain Research · doi:10.1016/0006-8993(93)90666-b · Cited by 107 · see citing works
Self-citationAutoradiographic analysis of [3H]ketanserin binding in the human brain postmortem: effect of suicide
Gross‐Isseroff, R., Salama, D., Israeli, M., & Biegon, A. R. (1990) · Brain Research · doi:10.1016/0006-8993(90)90274-f · Cited by 106 · see citing works
Impulsive Aggression in Personality Disorder Correlates with Platelet 5-HT2A Receptor Binding
Coccaro, E. F. (1997) · Neuropsychopharmacology · doi:10.1016/s0893-133x(96)00194-7 · Cited by 100 · see citing works
Cerebrospinal Fluid Correlates of Suicide Attempts and Aggression
Brown, G. L., & Goodwin, F. K. (1986) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1986.tb27897.x · Cited by 99 · see citing works
Lowther, S., Paermentier, F. D., Crompton, M. R., Katona, C., & Horton, R. W. (1994) · Brain Research · doi:10.1016/0006-8993(94)90932-6 · Cited by 97 · see citing works
McBride, P., Brown, R. P., Michael, D. C., Keilp, J. G., Mieczkowski, T. A., & Mann, J. J. (1994) · Biological Psychiatry · doi:10.1016/0006-3223(94)90033-7 · Cited by 95 · see citing works
Self-citationKetanserin and tetrabenazine abolish aggression in mice lacking monoamine oxidase A
Shih, J. C., Ridd, M. J., Chen, K., Meehan, W. P., Kung, M., Seif, I., & Maeyer, E. D. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01478-x · Cited by 88 · see citing works
BRAIN 5-HT2 RECEPTORS AND SUICIDE
Owen, F., Cross, A. J., Crow, T. J., Deakin, J. F. W., Ferrier, I. N., Lofthouse, R., & Poulter, M. (1983) · The Lancet · doi:10.1016/s0140-6736(83)91310-7 · Cited by 86 · see citing works
Rosel, P., Arranz, B., Urretavizcaya, M., Oros, M., San, L., & Navarro, M. A. (2004) · Neuropsychobiology · doi:10.1159/000077365 · Cited by 84 · see citing works
Rosel, P., Arranz, B., San, L., Vallejo, J., Crespo, J. M., Urretavizcaya, M., & Navarro, M. A. (2000) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(00)00076-7 · Cited by 82 · see citing works
Altered Serotonin Function in Suicide
Pandey, G. N. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb52360.x · Cited by 68 · see citing works
Serotonergic and adrenergic receptors in alcohol-preferring and non-preferring rats
Wong, D. T., Lumeng, L., Threlkeld, P. G., et al. (1988) · Journal of Neural Transmission · doi:10.1007/bf01245714 · Cited by 57 · see citing works
Serotonergic and Noradrenergic Neurobiology of Alcoholic Suicide
Underwood, M. D., Mann, J. J., & Arango, V. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000127415.15000.ca · Cited by 56 · see citing works
Self-citationKuroda, Y., Mikuni, M., Nomura, N., & Takahashi, K. (1993) · Neuroscience Letters · doi:10.1016/0304-3940(93)90706-q · Cited by 39 · see citing works
McBride, W. J., Chernet, E., Russell, R., Chamberlain, J. K., Lumeng, L., & Li, T. (1997) · Alcohol · doi:10.1016/s0741-8329(97)00072-4 · Cited by 37 · see citing works
[3H]Ketanserin Labels Serotonin 5-HT2 and α1-Adrenergic Receptors in Human Brain Cortex
Hoyer, D., Vos, P., Closse, A., Palacios, J. M., Engel, G., & Davies, H. (1987) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-198706103-00012 · Cited by 24 · see citing works
Ethanol does not affect serotonin receptor binding in rodent brain
Buckholtz, N. S., Zhou, D., & Tabakoff, B. (1989) · Alcohol · doi:10.1016/0741-8329(89)90083-9 · Cited by 22 · see citing works
Autoradiographic Mapping of Brain 5-HT2A Binding Sites in P and in AA Alcohol-Preferring Rats
Ciccocioppo, R., Ge, J., Barnes, N. M., et al. (1997) · Brain Research Bulletin · doi:10.1016/s0361-9230(96)00379-6 · Cited by 17 · see citing works
Mixed models and multiple comparisons in analysis of human neurochemical maps
Ellis, S. P., Underwood, M. D., Arango, V., & Mann, J. J. (2000) · Psychiatry Research Neuroimaging · doi:10.1016/s0925-4927(00)00051-2 · Cited by 13 · see citing works
Self-citation
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Siever, L. J. (2008) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2008.07111774 · Cited by 984 · see citing works
Elevated Cytokine Expression in the Orbitofrontal Cortex of Victims of Suicide
Tonelli, L. H., Stiller, J., Rujescu, D., Giegling, I., Schneider, B., Maurer, K., Schnabel, A., Möller, H. ‐., Chen, H. H., & Postolache, T. T. (2008) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2007.01128.x · Cited by 252 · see citing works
A brain-centric model of suicidal behavior
Mann, J. J., & Rizk, M. M. (2020) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2020.20081224 · Cited by 214 · see citing works
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Huot, P., Fox, S. H., & Brotchie, J. M. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.08.004 · Cited by 195 · see citing works
Huot, P., Johnston, T. H., Darr, T., Hazrati, L., Visanji, N. P., Pires, D., Brotchie, J. M., & Fox, S. H. (2010) · Movement Disorders · doi:10.1002/mds.23083 · Cited by 153 · see citing works
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Antypa, N., Serretti, A., & Rujescu, D. (2013) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2013.03.013 · Cited by 150 · see citing works
Underwood, M. D., Kassir, S. A., Bakalian, M. J., Galfalvy, H., Dwork, A. J., Mann, J. J., & Arango, V. (2018) · Translational Psychiatry · doi:10.1038/s41398-018-0309-1 · Cited by 128 · see citing works
Self-citationNeuron density and serotonin receptor binding in prefrontal cortex in suicide
Underwood, M. D., Kassir, S. A., Bakalian, M. J., Galfalvy, H., Mann, J. J., & Arango, V. (2012) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711000691 · Cited by 100 · see citing works
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- Authors
- Oquendo, M. A., Russo, S. A., Underwood, M. D., Kassir, S. A., Ellis, S. P., Mann, J. J., & Arango, V.
- Affiliations
- New York State Psychiatric Institute (US)
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 59
- Issue
- 3
- Pages
- 235-243
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2068475798
- Cited by
- 96
- References
- 50
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 3 · 2022: 5 · 2021: 1 · 2020: 6 · 2019: 3 · 2018: 5 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 5 · 2013: 6 · 2012: 7
- FWCI
- 5.78
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA11293, R01AA011293, AA09004, R01AA009004)
- National Institute of Mental Health (MH 62185, MH-40210, R01MH040210, P50MH062185)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- suicide, 5-HT2A receptor, serotonin, prefrontal cortex, postmortem brain, ketanserin binding, aggression, serotonergic system
- MeSH terms
- Adolescent, Adult, Aged, Aged, 80 and over, Aggression, Major Depressive Disorder, Female, Humans, Ketanserin, Male, Middle Aged, Radioligand Assay, Statistics as Topic, Suicide, Prefrontal Cortex, Receptor, Serotonin, 5-HT2A
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