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Evidence for the 5-HT Hypothesis of Suicide A Review of Post-mortem Studies

Published online by Cambridge University Press:  06 August 2018

J. J. Mann ,
V. Arango ,
P. M. Marzuk ,
S. Theccanat  and
D. J. Reis
J. J. Mann
Affiliation:
Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, New York
V. Arango
Affiliation:
Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, New York
P. M. Marzuk
Affiliation:
Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, New York
S. Theccanat
Affiliation:
Laboratory of Psychopharmacology, Department of Psychiatry, Cornell University Medical College, New York
D. J. Reis
Affiliation:
Division of Neurobiology, Department of Neurology, Cornell University Medical College, New York
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Extract

Although suicide was traditionally considered an extreme response to stress, with the most frequent stress being depressive illness, severity of depression does not distinguish those who commit suicide from non-suicide attempters. A biological role involving the serotonergic system, possibly associated with a genetic risk factor, has been postulated. Low levels of 5-HT and 5-HIAA have been found in post-mortem examinations of brain-stem tissues of suicide victims (levels in cortical tissue were generally normal). An increased number of 5-HT2 receptors was found in the pre-frontal cortex of suicide victims, such upregulation having been demonstrated in induced 5-HT deficiency states; 5-HT1A receptors were also increased. Receptor populations may be altered by chronic psychotropic medication; e.g. 5-HT2 downregulation occurs following administration of antidepressants. There is some indication that the adrenergic system may be involved as well, but this will require further study. Antidepressant drugs may be effective in preventing suicide in patients with non-depressive syndromes who exhibit suicidal behaviour.

Type
Research Article
Information
The British Journal of Psychiatry , Volume 155 , Issue S8: SEROTONIN IN BEHAVIOURAL DISORDERS , December 1989 , pp. 7 - 14
Copyright
Copyright © Royal College of Psychiatrists, 1989 

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References

Ågren, H. (1980) Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid. II. Suicide. Psychiatry Research, 3, 225–236.Google Scholar
Allen, S. J., Benton, J. S., Goodhardt, M. J., et al (1983) Biochemical evidence of selective nerve cell changes in the normal ageing human and rat brain. Journal of Neurochemistry, 41, 256–265.CrossRefGoogle ScholarPubMed
Arató, M., Tekes, K., Tóthfalusi, L., et al (1987) Serotonergic split brain and suicide. Psychiatry Research, 21, 355–356.Google Scholar
Beck, A. T., Steer, R. A., Kovacs, M. et al (1985) Hopelessness and eventual suicide: a 10-year prospective study of patients hospitalized with suicidal ideation. American Journal of Psychiatry, 142, 559–563.Google ScholarPubMed
Beskow, J., Gottfries, C. G., Roos, B. E., et al (1976) Determination of monoamine and monoamine metabolites in the human brain: postmortem studies in a group of suicides and a control group. Acta Psychiatrica Scandinavica, 53, 7–20.CrossRefGoogle Scholar
Biegon, A. & Israeli, M. (1988) Regionally selective increases in β-adrenergic receptor density in the brains of suicide victims. Brain Research, 442, 199–203.Google ScholarPubMed
Bourne, H. R., Bunney, W. E. Jr., Colburn, R. W., et al (1968) Noradrenaline, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid in hindbrains of suicidal patients. Lancet, ii, 805–808.CrossRefGoogle Scholar
Brown, G. L., Ebert, M. H., Goyer, P. F., et al (1982a) Aggression, suicide and serotonin: relationships to CSF amine metabolites. American Journal of Psychiatry, 139, 741–746.Google Scholar
Brown, G. L., Goodwin, F. K. & Bunney, W. E. Jr. (1982b) Human aggression and suicide: their relationship to neuropsychiatric diagnoses and serotonin metabolism. In Serotonin in Biological Psychiatry (eds Ho, B. T., Schoolar, J. C. & Usdin, E.). New York: Raven Press.Google Scholar
Brunello, N., Chuang, D. M. & Costa, E. (1982) Different synaptic location of mianserin and imipramine binding sites. Science, 215, 1112–1115.CrossRefGoogle ScholarPubMed
Carlsson, A., Adolfsson, R., Aquilonius, S.-M., et al (1980) Biogenic amines in human brain in normal aging, senile dementia, and chronic alcoholism. In Ergot Compounds and Brain Function: Neuroendocrine and Neuropsychiatric Aspects (ed Goldstein, M.). New York: Raven Press.Google Scholar
Cheetham, S. C., Crompton, M. R., Katona, C. L. E., et al (1988) Brain 5-HT2 receptor binding sites in depressed suicide victims. Brain Research, 443, 272–280.Google Scholar
Cheetham, S. C., Cross, J. A., Crompton, M. R., Czudek, C. Z., et al (in press) Neurotransmitters and neurotransmitter receptors in depressed suicide victims. In New Directions in Affective Disorders (eds Lerer, B. & Gershon, S.). New York: Springer-Verlag.Google Scholar
Cochran, E., Robins, E. & Grote, S. (1976) Regional serotonin levels in brain: a comparison of depressive suicides and alcoholic suicides with controls. Biological Psychiatry, 11, 283–294.Google Scholar
Creese, I., Burt, D. R. & Snyder, S. H. (1976) Dopamine receptor binding predicts clinical and pharmacological potencies of antischizophrenic drugs. Science, 192, 481–483.CrossRefGoogle ScholarPubMed
Crow, T. J., Cross, A. J., Cooper, S. J., et al (1984) Neurotransmitter receptors and monoamine metabolites in the brains of patients with Alzheimer-type dementia and depression, and suicides. Neuropharmacology, 23, 1561–1569.CrossRefGoogle ScholarPubMed
Ferrier, I. N., McKeith, I. G., Cross, A. J., et al (1986) Postmortem neurochemical studies in depression. Annals of the New York Academy of Sciences, 487, 128–142.CrossRefGoogle ScholarPubMed
Gillin, J. C., Kelsoe, J. R. Jr., Kaufman, C. A., et al (1986) Muscarinic receptor density in skin fibroblasts and autopsied brain tissue in affective disorder. Annals of the New York Academy of Sciences, 487, 143–149.Google Scholar
Gross-Isseroff, R., Israeli, M. & Biegon, A. (1988) Autoradiographic analysis of serotonergic markers in brains of suicide victims. Presented at the symposium, Neurochemical Correlates of Affective Disorders and their Treatment, Copenhagen.Google Scholar
Gross-Isseroff, R., Israeli & Biegon, A. (1989) Autoradiographic analysis of tritiated imipramine binding in the human brain postmortem: effects of suicide. Archives of General Psychiatry, 46, 237–241.CrossRefGoogle ScholarPubMed
Grote, S. S., Moses, S. G., Robins, E., et al (1974) A study of selected catecholamine metabolizing enzymes: a comparison of depressive suicides and alcoholic suicides with controls. Journal of Neurochemistry, 23, 791–802.Google Scholar
Korpi, E. R., Kleinman, J. E., Goodman, S. I., et al (1986) Serotonin and 5-hydroxyindoleacetic acid in brains of suicide victims: comparison in chronic schizophrenic patients with suicide as cause of death. Archives of General Psychiatry, 43, 594–600.Google Scholar
Langer, S. Z., Galzin, A. M., Poirier, M. F., et al (1987) Association of [3H]-imipramine and [3H]-paroxetine binding with the 5HT transporter in brain and platelets: relevance to studies in depression. Journal of Receptor Research, 7, 499–521.Google Scholar
Laruelle, M., Vanisberg, M.-A. & Maloteaux, J.-M. (1988) Regional and subcellular localization in human brain of [3H]paroxetine binding, a marker of serotonin uptake sites. Biological Psychiatry, 24, 299–309.Google Scholar
Lloyd, K. G., Farley, I. J., Deck, J. H. N., et al (1974) Serotonin and 5-hydroxyindoleacetic acid in discrete areas of the brainstem of suicide victims and control patients. Advances in Biochemical Psychopharmacology, 11, 387–397.Google ScholarPubMed
Manchon, M., Kopp, N., Rouzioux, J.J., et al (1987) Benzodiazepine receptor and neurotransmitter studies in the brain of suicides. Life Sciences, 41, 2623–2630.Google Scholar
Mann, J. J. & Stanley, M. (1984) Postmortem monoamine oxidase enzyme kinetics in the frontal cortex of suicide victims and controls. Acta Psychiatrica Scandinavica, 69, 135–139.CrossRefGoogle ScholarPubMed
Mann, J. J. & Stanley, M. (eds) (1986) Annals of the New York Academy of Sciences. Vol. 487. New York: New York Academy of Sciences.Google Scholar
Mann, J. J., Petito, C., McBride, P. A., et al (1984) Age and gender effects upon amine receptors and MAO in postmortem human brain tissue. In Clinical and Pharmacological Studies in Psychiatric Disorders (eds Burrows, G. D. & Norman, T. R.). London: John Libbey & Company.Google Scholar
Mann, J. J., Stanley, M., McBride, P. A., et al (1986) Increased serotonin2 and β-adrenergic receptor binding in the frontal cortex of suicide victims. Archives of General Psychiatry, 43, 954–959.Google Scholar
Meltzer, H. Y. (1988) Role of serotonin in depression. Psychopharmacology, 96 (Suppl.), 134.Google Scholar
Meltzer, H. Y., Perline, R., Tricou, B. J., et al (1984) Effect of 5-hydroxytryptophan on serum cortisol levels in major affective disorders. II. Relation to suicide, psychosis, and depressive symptoms. Archives of General Psychiatry, 41, 379–387.Google Scholar
Meltzer, H. Y., Nash, J. F., Ohmari, T. (1987) Neuroendocrine and biochemical studies of serotonin and dopamine in depression and suicide. Presented at the International Conference on New Directions in Affective Disorders, Jerusalem, Israel.Google Scholar
Meyerson, L. R., Wennogle, L. P., Abel, M. S., et al (1982) Human brain receptor alterations in suicide victims. Pharmacology, Biochemistry and Behavior, 17, 159–163.Google Scholar
Nemeroff, C. B., Owens, M. J., Bissette, G., et al (1988) Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Archives of General Psychiatry, 45, 577–579.CrossRefGoogle ScholarPubMed
Ninan, P. T., van Kammen, D. P., Scheinin, M., et al (1984) CSF 5-hydroxyindoleacetic acid levels in suicidal schizophrenic patients. American Journal of Psychiatry, 141, 566–569.Google Scholar
Owen, F., Cross, A. J., Crow, T. J., et al (1983) Brain 5-HT2 receptors and suicide. Lancet, ii, 1256.Google Scholar
Owen, F., Chambers, D. R., Cooper, S. J., et al (1986) Serotonergic mechanisms in brains of suicide victims. Brain Research, 362, 185–188.Google Scholar
Pare, C. M. B., Young, D. P. H., Price, K., et al (1969) 5-Hydroxytryptamine, noradrenaline, and dopamine in brainstem, hypothalamus, and caudate nucleus of controls and of patients committing suicide by coal-gas poisoning. Lancet, ii, 133–135.Google Scholar
Paul, S. M., Rehavi, M., Skolnik, P., et al (1984) High affinity binding of antidepressants to biogenic amine transport sites in human brain and platelet: studies in depression. In Neurobiology of Mood Disorders (eds Post, R. M. & Ballenger, J. C.). Baltimore, London: Williams & Wilkins.Google Scholar
Peroutka, S. J. & Snyder, S. H. (1980) Long-term antidepressant treatment decreases spiroperidol-labeled serotonin receptor binding. Science, 210, 88–90.Google Scholar
Perry, E. K., Marshall, E. F., Blessed, G., et al (1983) Decreased imipramine binding in the brains of patients with depressive illness. British Journal of Psychiatry, 142, 188–192.CrossRefGoogle ScholarPubMed
Pokorny, A. D. (1983) Prediction of suicide in psychiatric patients: report of a prospective study. Archives of General Psychiatry, 40, 249–257.Google Scholar
Reis, D. J., Ross, R. A. & Joh, T. H. (1977) Changes in the activity and amounts of enzymes synthesizing catecholamines and acetylcholine in brain, adrenal medulla, and sympathetic ganglia of aged rat and mouse. Brain Research, 136, 465–474.CrossRefGoogle ScholarPubMed
Roth, B. L., McLean, S., Zhu, X.-Z., et al (1987) Characterization of two [3H]ketanserin recognition sites in rat striatum. Journal of Neurochemistry, 49, 1833–1838.Google Scholar
Roy, A. (1986) Genetics of suicide. Annals of the New York Academy of Sciences, 487, 97–105.Google Scholar
Shaw, D. M., Camps, E. F. & Eccleston, E. G. (1967) 5-Hydroxytryptamine in the hindbrain of depressive suicides. British Journal of Psychiatry, 113, 1407–1411.Google Scholar
Spokes, E. G. S. (1979) An analysis of factors influencing measurements of dopamine, noradrenaline, glutamate decarboxylase and choline acetylase in human post-mortem brain tissue. Brain, 102, 333–346.CrossRefGoogle ScholarPubMed
Stanley, M. (1984) Cholinergic receptor binding in the frontal cortex of suicide victims. American Journal of Psychiatry, 141, 1432–1436.Google Scholar
Stanley, M. & Mann, J. J. (1983) Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet, i, 214–216.Google Scholar
Stanley, M. & Mann, J. J. (1984) Suicide and serotonin receptors. Lancet, i, 349.CrossRefGoogle Scholar
Stanley, M., Virgilio, J. & Gershon, S. (1982) Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science, 216, 1337–1339.Google Scholar
Stanley, M., Mann, J. J., Cohen, L. S. (1986) Serotonin and serotonergic receptors in suicide. Annals of the New York Academy of Sciences, 487, 122–127.Google Scholar
Takahashi, R., Tateishi, T., Yoshida, H., et al (1982) Effects of chronic treatment with antidepressant drugs on serotonergic receptor binding activity in normal and tetrabenazine depression rat. In New Vistas in Depression (eds Langer, S. Z., Takahashi, R., Segawa, T., et al). Oxford: Pergamon Press.Google Scholar
Träskman, L., Åsberg, M., Bertilsson, L., et al (1981) Monoamine metabolites in CSF and suicidal behaviour. Archives of General Psychiatry, 38, 631–636.Google Scholar
Träskman-Bendz, L., Åsberg, M. & Schalling, D. (1986) Serotonergic function and suicidal behaviour in personality disorders. Annals of the New York Academy of Sciences, 487, 168–174.Google Scholar
van Praag, H. M. (1983) CSF 5-HIAA and suicide in non-depressed schizophrenics. Lancet, ii, 977–978.Google Scholar
Wirz-Justice, A., Krauchi, K., Lichtsteiner, M., et al (1978) Is it possible to modify serotonin receptor sensitivity? Life Sciences, 23, 1249–1254.CrossRefGoogle ScholarPubMed
Yates, M., Leake, A., Fairbairn, A., et al (1988) Postmortem investigation of serotonergic and peptidergic hypotheses of depression. Presented at the symposium, Neurochemical Correlates of Affective Disorders and their Treatment, 1988.Google Scholar
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