iBet uBet web content aggregator. Adding the entire web to your favor.
iBet uBet web content aggregator. Adding the entire web to your favor.



Link to original content: https://doi.org/10.1038/nrn1220
Neurobiology of suicidal behaviour | Nature Reviews Neuroscience
Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Neurobiology of suicidal behaviour

Nature Reviews Neuroscience volume 4, pages 819–828 (2003)Cite this article

Key Points

  • Suicidal behaviour refers to the occurrence of self-directed injurious acts with intent to end one's own life. Suicide is not simply a response to stress, but is a complication of an existing psychiatric disorder.

  • Many models of suicidal behaviour have been put forward. This article presents a stress–diathesis model in which a stressor leads to the acute worsening of a psychiatric disorder, leading to suicidal behaviour. Many factors are components of the diathesis for suicidal behaviour. They include pessimism, aggression, impulsivity, familial/genetic factors and childhood experiences.

  • Most of the neurochemical evidence, particularly evidence obtained from the brains of suicide victims, points to the involvement of the serotonergic system in suicidal behaviour. The noradrenergic and dopaminergic systems have also been implicated, but the evidence is more fragmentary.

  • As a result of the neurochemical observations, the genetic study of suicidal behaviour has centred on the study of genes that govern the function of the serotonergic system. Although different polymorphisms in the genes that encode tryptophan hydroxylase, the serotonin transporter, the different serotonin receptors and monoamine oxidase have been found, their relationship to suicidal behaviour remains unclear.

  • Neuroanatomically, people who display suicidal behaviour tend to show abnormalities in the ventromedial prefrontal cortex. These abnormalities largely correlate with the neurochemical deficits that have been reported in this population.

  • The diathesis of suicidal behaviour offers new therapeutic possibilities. However, these are still early days in the study of suicide, and it will be important to identify additional markers (genetic, anatomical and neuropsychological) for identifying people at risk of showing suicidal behaviour.

Abstract

About one million suicides and ten million suicide attempts occur worldwide each year. Suicide is not simply a response to stress, but generally a complication of a psychiatric disorder. A proposed stress–diathesis model is described in clinical and neurobiological terms. Neurobiological correlates of the diathesis for suicidal acts point to the involvement of the serotonergic and noradrenergic systems, and the ventromedial prefrontal cortex. Some treatments seem to reduce suicide risk independently of an effect on the primary psychiatric disorder, perhaps by reducing the diathesis.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Effects of genetics, head injury and childhood abuse on mood disorders and impulsivity in relation to suicidal behaviour.
Figure 2: A stress–diathesis model of suicidal behaviour.
Figure 3: Serotonin and suicidal behaviour.
Figure 4: Serotonin and suicidal behaviour.
Figure 5: Stress sensitivity and hopelessness.
Figure 6: Differences in anterior cingulate and lateral prefrontal cortex brain activity after serotonin release related to suicide attempt behaviour.

Similar content being viewed by others

References

  1. Beck, A. T., Weissman, A., Lester, D. & Trexler, L. Classification of suicidal behaviors. II. Dimensions of suicidal intent. Arch. Gen. Psychiatry 33, 835–837 (1976).

    Article  CAS  PubMed  Google Scholar 

  2. Stengel, E. Suicide and Attempted Suicide (C. Nicholls & Company Ltd., Harmondsworth, Middlesex, 1973).

    Google Scholar 

  3. Mann, J. J. et al. Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatients. Neuropsychopharmacology 15, 576–586 (1996). The serotonin index of CSF levels of 5-HIAA, the main metabolite of serotonin, correlates with more lethal suicide-attempt behaviour and is associated with higher suicidal intent.

    Article  CAS  PubMed  Google Scholar 

  4. Linehan, M. M. Suicidal people. One population or two? Ann. NY Acad. Sci. 487, 16–33 (1986).

    Article  CAS  PubMed  Google Scholar 

  5. Mann, J. J. et al. Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients. Arch. Gen. Psychiatry 49, 442–446 (1992).

    Article  CAS  PubMed  Google Scholar 

  6. Oquendo, M. A. et al. Positron emission tomography of regional brain metabolic responses to a serotonergic challenge and lethality of suicide attempts in major depression. Arch. Gen. Psychiatry 60, 14–22 (2003). Relative regional activity in areas of prefrontal cortex correlates with lethality of suicidal behaviour because of relationships to impulsiveness and to suicide intent or planning.

    Article  PubMed  Google Scholar 

  7. Beautrais, A. L. et al. Prevalence and comorbidity of mental disorders in persons making serious suicide attempts: a case-control study. Am. J. Psychiatry 153, 1009–1014 (1996).

    Article  CAS  PubMed  Google Scholar 

  8. Shaffer, D. et al. Psychiatric diagnosis in child and adolescent suicide. Arch. Gen. Psychiatry 53, 339–348 (1996).

    Article  CAS  PubMed  Google Scholar 

  9. Robins, E., Murphy, G. E., Wilkinson, R. H. Jr, Gassner, S. & Kayes, J. Some clinical considerations in the prevention of suicide based on a study of 134 successful suicides. Am. J. Public Health 49, 888–899 (1959).

    Article  CAS  Google Scholar 

  10. Murphy, G. E., Wetzel, R. D., Robins, E. & McEvoy, L. Multiple risk factors predict suicide in alcoholism. Arch. Gen. Psychiatry 49, 459–463 (1992).

    Article  CAS  PubMed  Google Scholar 

  11. Murphy, G. E. Suicide and substance abuse. Arch. Gen. Psychiatry 45, 593–594 (1988).

    Article  CAS  PubMed  Google Scholar 

  12. Henriksson, M. M. et al. Mental disorders and comorbidity in suicide. Am. J. Psychiatry 150, 935–940 (1993).

    Article  CAS  PubMed  Google Scholar 

  13. Frances, A., Fyer, M. & Clarkin, J. Personality and Suicide. Ann. NY Acad. Sci. 487, 281–293 (1986).

    Article  CAS  PubMed  Google Scholar 

  14. Jamison, K. R. Suicide and bipolar disorders. Ann. NY Acad. Sci. 487, 301–315 (1986).

    Article  CAS  PubMed  Google Scholar 

  15. Johns, C. A., Stanley, M. & Stanley, B. Suicide in schizophrenia. Ann. NY Acad. Sci. 487, 294–300 (1986).

    Article  CAS  PubMed  Google Scholar 

  16. Roy, A. & Linnoila, M. Alcoholism and suicide. Suicide Life Threat. Behav. 16, 244–273 (1986).

    Article  CAS  PubMed  Google Scholar 

  17. Murphy, G. E. & Wetzel, R. D. The lifetime risk of suicide in alcoholism. Arch. Gen. Psychiatry 47, 383–392 (1990).

    Article  CAS  PubMed  Google Scholar 

  18. Bostwick, J. M. & Pankratz, V. S. Affective disorders and suicide risk: a reexamination. Am. J. Psychiatry 157, 1925–1932 (2000). The risk of lifetime suicide is higher in subjects with a history of hospitalization compared with patients who have never hospitalized.

    Article  CAS  PubMed  Google Scholar 

  19. Dulit, R. A., Fyer, M. R., Haas, G. L., Sullivan, T. & Frances, A. J. Substance use in borderline personality disorder. Am. J. Psychiatry 147, 1002–1007 (1990).

    Article  CAS  PubMed  Google Scholar 

  20. Marzuk, P. M. & Mann, J. J. Suicide and substance abuse. Psychiatr. Ann. 18, 639–645 (1988).

    Google Scholar 

  21. Brent, D. A. Overrepresentation of epileptics in a consecutive series of suicide attempters seen at a children's hospital, 1978–1983. J. Am. Acad. Child Psychiatry 25, 242–246 (1986).

    Article  CAS  PubMed  Google Scholar 

  22. Breslau, N., Davis, G. C. & Andreski, P. Migraine, psychiatric disorders, and suicide attempts: an epidemiologic study of young adults. Psychiatry Res. 37, 11–23 (1991).

    Article  CAS  PubMed  Google Scholar 

  23. Schoenfeld, M. et al. Increased rate of suicide among patients with Huntington's disease. J. Neurol. Neurosurg. Psychiatry 47, 1283–1287 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Breslau, N., Kilbey, M. M. & Andreski, P. Nicotine dependence and major depression: new evidence from a prospective investigation. Arch. Gen. Psychiatry 50, 31–35 (1993).

    Article  CAS  PubMed  Google Scholar 

  25. Mann, J. J., Waternaux, C., Haas, G. L. & Malone, K. M. Towards a clinical model of suicidal behavior in psychiatric patients. Am. J. Psychiatry 156, 181–189 (1999). Suicide attempters differ from psychiatric controls who have never attempted suicide, by reporting greater subjective depression and more lifetime aggression/impulsiveness.

    CAS  PubMed  Google Scholar 

  26. Brent, D. A. et al. Personality disorder, personality traits, impulsive violence, and completed suicide in adolescents. J. Am. Acad. Child Adolesc. Psychiatry 33, 1080–1086 (1994).

    Article  CAS  PubMed  Google Scholar 

  27. Cornelius, J. R. et al. Disproportionate suicidality in patients with comorbid major depression and alcoholism. Am. J. Psychiatry 152, 358–364 (1995).

    Article  CAS  PubMed  Google Scholar 

  28. McAllister, T. W. Neuropsychiatric sequelae of head injuries. Psychiatr. Clin. North Am. 15, 395–413 (1992).

    Article  CAS  PubMed  Google Scholar 

  29. Gorenstein, E. E. & Newman, J. P. Disinhibitory psychopathology: a new perspective and a model for research. Psychol. Rev. 87, 301–315 (1980).

    Article  CAS  PubMed  Google Scholar 

  30. Raine, A., Buchsbaum, M. & LaCasse, L. Brain abnormalities in murderers indicated by positron emission tomography. Biol. Psychiatry 42, 495–508 (1997).

    Article  CAS  PubMed  Google Scholar 

  31. Henriksson, M. M., Isometsä, E. T., Hietanen, P. S., Aro, H. M. & Lönnqvist, J. K. Mental disorders in cancer suicides. J. Affect. Disord. 36, 11–20 (1995).

    Article  CAS  PubMed  Google Scholar 

  32. Marzuk, P. M. et al. Increased risk of suicide in persons with AIDS. J. Am. Med. Assoc. 259, 1333–1337 (1988).

    Article  CAS  Google Scholar 

  33. Vauhkonen, K. Suicide among the male disabled with war injuries to the brain. Acta Psychiatr. Scand. 90–91 (1959).

  34. Maris, R. W., Berman, A. L. & Silverman, M. M. Comprehensive Textbook of Suicidology (The Guilford Press, New York, 2000).

    Google Scholar 

  35. Smith, J. C., Mercy, J. A. & Conn, J. M. Marital status and the risk of suicide. Am. J. Public Health 78, 78–80 (1988).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Beautrais, A. L., Joyce, P. R. & Mulder, R. T. Access to firearms and the risk of suicide: a case control study. Aust. NZ J. Med. 30, 741–748 (1996).

    CAS  Google Scholar 

  37. Gould, M. S. Teenage suicide clusters. J. Am. Med. Assoc. 263, 2051 (1990).

    Article  CAS  Google Scholar 

  38. Johnson, J. G., Cohen, P., Smailes, E. M., Kasen, S. & Brook, J. S. Television viewing and aggressive behavior during adolescence and adulthood. Science 295, 2468–2471 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Stanley, M., Virgilio, J. & Gershon, S. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science 216, 1337–1339 (1982).

    Article  CAS  PubMed  Google Scholar 

  40. Stanley, M. & Mann, J. J. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet 1, 214–216 (1983).

    Article  CAS  PubMed  Google Scholar 

  41. Mann, J. J. et al. Lower 3H-paroxetine binding in cerebral cortex of suicide victims is partly due to fewer high-affinity, non-transporter sites. J. Neural Transm. 103, 1337–1350 (1996).

    Article  CAS  PubMed  Google Scholar 

  42. Arango, V., Underwood, M. D., Gubbi, A. V. & Mann, J. J. Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res. 688, 121–133 (1995). Fewer serotonin transporters and more 5-HT 1A binding to the ventral prefrontal cortex characterizes suicide and indicates less serotonin input, which might underlie reduced behavioural inhibition and a greater probability of acting on suicidal feelings.

    Article  CAS  PubMed  Google Scholar 

  43. Mann, J. J. et al. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch. Gen. Psychiatry 57, 729–738 (2000).

    Article  CAS  PubMed  Google Scholar 

  44. Austin, M. C., Whitehead, R. E., Edgar, C. L., Janosky, J. E. & Lewis, D. A. Localized decrease in serotonin transporter-immunoreactive axons in the prefrontal cortex of depressed subjects committing suicide. Neuroscience 114, 807–815 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Ono, H. et al. Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls. Mol. Psychiatry 7, 1127–1132 (2002).

    Article  CAS  PubMed  Google Scholar 

  46. Mann, J. J. & Arango, V. in Suicide: An Unnecessary Death (ed. Wasserman, D.) 29–34 (Martin Dunitz Ltd, London, 2001).

    Book  Google Scholar 

  47. Pandey, G. N. et al. Higher expression of serotonin 5-HT2A receptors in the postmortem brains of teenage suicide victims. Am. J. Psychiatry 159, 419–429 (2002).

    Article  PubMed  Google Scholar 

  48. Shallice, T. & Burgess, P. The domain of supervisory processes and temporal organization of behaviour. Phil. Trans. R. Soc. Lond. B 351, 1405–1412 (1996).

    Article  CAS  Google Scholar 

  49. Damasio, H., Grabowski, T., Frank, R., Galaburda, A. M. & Damasio, A. R. The return of Phineas Gage: clues about the brain from the skull of a famous patient. Science 264, 1102–1105 (1994). Damage to the ventromedial prefrontal cortex might result in behavioural disinhibition, as illustrated by this analysis of the brain injury suffered by Phineas Gage.

    Article  CAS  PubMed  Google Scholar 

  50. Mann, J. J. in Psychopharmacology: The Fourth Generation of Progress (eds Bloom, F. E. & Kupfer, D. J.) 1919–1928 (Raven Press, New York, 1995).

    Google Scholar 

  51. Mann, J. J., Arango, V., Marzuk, P. M., Theccanat, S. & Reis, D. J. Evidence for the 5-HT hypothesis of suicide. A review of post-mortem studies. Br. J. Psychiatry Suppl. 7–14 (1989).

  52. Åsberg, M., Nordström, P. & Träskman-Bendz, L. Cerebrospinal fluid studies in suicide. An overview. Ann. NY Acad. Sci. 487, 243–255 (1986).

    Article  PubMed  Google Scholar 

  53. Underwood, M. D. et al. Morphometry of the dorsal raphe nucleus serotonergic neurons in suicide victims. Biol. Psychiatry 46, 473–483 (1999).

    Article  CAS  PubMed  Google Scholar 

  54. Boldrini, M. et al. Increased tryptophan hydroxylase concentration in the brainstem raphe nuclei of depressed suicide victims compared to controls. American College of Neuropsychopharmacology 40th Annual Meeting. 70 (2001).

    Google Scholar 

  55. Walther, D. J. et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science 299, 76 (2003).

    Article  CAS  PubMed  Google Scholar 

  56. Arango, V. et al. Serotonin 1A receptors, serotonin transporter binding and serotonin transporter mRNA expression in the brainstem of depressed suicide victims. Neuropsychopharmacology 25, 892–903 (2001).

    Article  CAS  PubMed  Google Scholar 

  57. Stockmeier, C. A. et al. Increase in serotonin-1A autoreceptors in the midbrain of suicide victims with major depression — postmortem evidence for decrease serotonin activity. J. Neurosci. 18, 7394–7401 (1998).

    Article  CAS  PubMed  Google Scholar 

  58. Cooper, S. J., Kelly, C. B. & King, D. J. 5-Hydroxyindoleacetic acid in cerebrospinal fluid and prediction of suicidal behaviour in schizophrenia. Lancet 340, 940–941 (1992).

    Article  CAS  PubMed  Google Scholar 

  59. Nordström, P. et al. CSF 5-HIAA predicts suicide risk after attempted suicide. Suicide Life Threat. Behav. 24, 1–9 (1994). Low serotonin function can predict suicide on one year follow-up after discharge from hospital.

    PubMed  Google Scholar 

  60. Mann, J. J., McBride, P. A., Malone, K. M., DeMeo, M. D. & Keilp, J. G. Blunted serotonergic responsivity in depressed patients. Neuropsychopharmacology 13, 53–64 (1995).

    Article  CAS  PubMed  Google Scholar 

  61. Coccaro, E. F. et al. Serotonergic studies in patients with affective and personality disorders. Correlates with suicidal and impulsive aggressive behavior. Arch. Gen. Psychiatry 46, 587–599 (1989).

    Article  CAS  PubMed  Google Scholar 

  62. Mann, J. J. & Malone, K. M. Cerebrospinal fluid amines and higher-lethality suicide attempts in depressed inpatients. Biol. Psychiatry 41, 162–171 (1997).

    Article  CAS  PubMed  Google Scholar 

  63. Mann, J. J., Underwood, M. D. & Arango, V. in Biology of Schizophrenia and Affective Disease (ed. Watson, S. J.) 197–220 (American Psychiatric Press Inc., Washington DC, 1996).

    Google Scholar 

  64. Arango, V., Underwood, M. D. & Mann, J. J. Fewer pigmented locus coeruleus neurons in suicide victims: preliminary results. Biol. Psychiatry 39, 112–120 (1996).

    Article  CAS  PubMed  Google Scholar 

  65. Ordway, G. A., Widdowson, P. S., Smith, K. S. & Halaris, A. Agonist binding to α2-adrenoceptors is elevated in the locus coeruleus from victims of suicide. J. Neurochem. 63, 617–624 (1994).

    Article  CAS  PubMed  Google Scholar 

  66. Ordway, G. A., Smith, K. S. & Haycock, J. W. Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims. J. Neurochem. 62, 680–685 (1994).

    Article  CAS  PubMed  Google Scholar 

  67. Biegon, A. & Fieldust, S. Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. Synapse 10, 79–82 (1992).

    Article  CAS  PubMed  Google Scholar 

  68. Weiss, J. M. et al. Depression and anxiety: role of the locus coeruleus and corticotropin-releasing factor. Brain Res. Bull. 35, 561–572 (1994).

    Article  CAS  PubMed  Google Scholar 

  69. Mann, J. J., Stanley, M., McBride, P. A. & McEwen, B. S. Increased serotonin-2 and β-adrenergic receptor binding in the frontal cortices of suicide victims. Arch. Gen. Psychiatry 43, 954–959 (1986).

    Article  CAS  PubMed  Google Scholar 

  70. Arango, V., Ernsberger, P., Sved, A. F. & Mann, J. J. Quantitative autoradiography of α1- and α2-adrenergic receptors in the cerebral cortex of controls and suicide victims. Brain Res. 630, 271–282 (1993).

    Article  CAS  PubMed  Google Scholar 

  71. Weiss, G. K. et al. The effect of two different types of stress on locus coeruleus α-2 receptor binding. Brain Res. Bull. 33, 219–221 (1994).

    Article  PubMed  Google Scholar 

  72. Heim, C. & Nemeroff, C. B. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol. Psychiatry 49, 1023–1039 (2001).

    Article  CAS  PubMed  Google Scholar 

  73. Ågren, H. Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid. II. Suicide. Psychiatry Res. 3, 225–236 (1980).

    Article  PubMed  Google Scholar 

  74. Ågren, H. Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid. I. General patterns. Psychiatry Res. 3, 211–223 (1980).

    Article  PubMed  Google Scholar 

  75. Fawcett, J., Busch, K. A., Jacobs, D., Kravitz, H. M. & Fogg, L. Suicide: a four-pathway clinical-biochemical model. Ann. NY Acad. Sci. 836, 288–301 (1997).

    Article  CAS  PubMed  Google Scholar 

  76. Brown, R. P. et al. Adrenocortical hyperactivity in depression: effects of agitation, delusions, melancholia, and other illness variables. Psychiatry Res. 23, 167–178 (1987).

    Article  Google Scholar 

  77. Hurd, Y. L. et al. Prodynorphin mRNA expression is increased in the patch vs matrix compartment of the caudate nucleus in suicide subjects. Mol. Psychiatry 2, 495–500 (1997).

    Article  CAS  PubMed  Google Scholar 

  78. Ohmori, T., Arora, R. C. & Meltzer, H. Y. Serotonergic measures in suicide brain: the concentration of 5-HIAA, HVA, and tryptophan in frontal cortex of suicide victims. Biol. Psychiatry 32, 57–71 (1992).

    Article  CAS  PubMed  Google Scholar 

  79. Sumiyoshi, T., Stockmeier, C. A., Overholser, J. C., Thompson, P. A. & Meltzer, H. Y. Dopamine D4 receptors and effects of guanine nucleotides on [3H]raclopride binding in postmortem caudate nucleus of subjects with schizophrenia or major depression. Brain Res. 681, 109–116 (1995).

    Article  CAS  PubMed  Google Scholar 

  80. Bachus, S. E., Hyde, T. M., Herman, M. M., Egan, M. F. & Kleinman, J. E. Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics. J. Psychiat. Res. 31, 233–256 (1997).

    Article  CAS  PubMed  Google Scholar 

  81. Träskman, L., Åsberg, M., Bertilsson, L. & Sjöstrand, L. Monoamine metabolites in CSF and suicidal behavior. Arch. Gen. Psychiatry 38, 631–636 (1981).

    Article  PubMed  Google Scholar 

  82. Kapur, S. & Mann, J. J. Role of the dopaminergic system in depression. Biol. Psychiatry 32, 1–17 (1992).

    Article  CAS  PubMed  Google Scholar 

  83. Pitchot, W. et al. Reduced dopaminergic activity in depressed suicides. Psychoneuroendocrinology 26, 331–335 (2001).

    Article  CAS  PubMed  Google Scholar 

  84. Logue, A. W. et al. Cocaine decreases self-control in rats: a preliminary report. Psychopharmacology (Berl.) 109, 245–247 (1992).

    Article  CAS  Google Scholar 

  85. Evenden, J. L. & Ryan, C. N. The pharmacology of impulsive behaviour in rats: the effects of drugs on response choice with varying delays of reinforcement. Psychopharmacology (Berl.) 128, 161–170 (1996).

    Article  CAS  Google Scholar 

  86. Richards, J. B., Sabol, K. E. & de Wit, H. Effects of methamphetamine on the adjusting amount procedure, a model of impulsive behavior in rats. Psychopharmacology (Berl.) 146, 432–439 (1999).

    Article  CAS  Google Scholar 

  87. de Wit, H., Enggasser, J. L. & Richards, J. B. Acute administration of D-amphetamine decreases impulsivity in healthy volunteers. Neuropsychopharmacology 27, 813–825 (2002).

    Article  CAS  PubMed  Google Scholar 

  88. Cohen, J. D. & Servan-Schreiber, D. A theory of dopamine function and its role in cognitive deficits in schizophrenia. Schizophr. Bull. 19, 85–104 (1993).

    Article  CAS  PubMed  Google Scholar 

  89. Pandey, G. N. et al. Protein kinase C in the postmortem brain of teenage suicide victims. Neurosci. Lett. 228, 111–114 (1997).

    Article  CAS  PubMed  Google Scholar 

  90. Dwivedi, Y. et al. Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch. Gen. Psychiatry 60, 273–282 (2003).

    Article  CAS  PubMed  Google Scholar 

  91. Dwivedi, Y. et al. mRNA and protein expression of selective α-subunits of G proteins are abnormal in prefrontal cortex of suicide victims. Neuropsychopharmacology 27, 499–517 (2002).

    CAS  PubMed  Google Scholar 

  92. Arango, V., Underwood, M. D. & Mann, J. J. Serotonin brain circuits involved in major depression and suicide. Prog. Brain Res. 136, 443–453 (2002).

    Article  CAS  PubMed  Google Scholar 

  93. Dwivedi, Y. et al. Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J. Neurochem. 77, 916–928 (2001).

    Article  CAS  PubMed  Google Scholar 

  94. Higley, J. D. et al. Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in Rhesus monkeys (Macaca mulatta). Arch. Gen. Psychiatry 50, 615–623 (1993).

    Article  CAS  PubMed  Google Scholar 

  95. Carroll, B. J. et al. A specific laboratory test for the diagnosis of melancholia. Standardization, validation, and clinical utility. Arch. Gen. Psychiatry 38, 15–22 (1981).

    Article  CAS  PubMed  Google Scholar 

  96. Bunney, W. E., Jr., Fawcett, J. A., Davis, J. M. & Gifford, S. Further evaluation of urinary 17-hydrocorticosteroids in suicidal patients. Arch. Gen. Psychiatry 21, 138–150 (1969).

    Article  PubMed  Google Scholar 

  97. Nemeroff, C. B., Owens, M. J., Bissette, G., Andorn, A. C. & Stanley, M. Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch. Gen. Psychiatry 45, 577–579 (1988).

    Article  CAS  PubMed  Google Scholar 

  98. Brent, D. A. et al. Familial pathways to early-onset suicide attempt: risk for suicidal behavior in offspring of mood-disordered suicide attempters. Arch. Gen. Psychiatry 59, 801–807 (2002).

    Article  PubMed  Google Scholar 

  99. Viau, V., Sharma, S. & Meaney, M. J. Changes in plasma adrenocorticotropin, corticosterone, corticosteroid-binding globulin, and hippocampal glucocorticoid receptor occupancy/translocation in rat pups in response to stress. J. Neuroendocrinol. 8, 1–8 (1996).

    Article  CAS  PubMed  Google Scholar 

  100. Hofer, M. A. On the nature and consequences of early loss. Psychosom. Med. 58, 570–581 (1996).

    Article  CAS  PubMed  Google Scholar 

  101. Husum, H. & Mathe, A. A. Early life stress changes concentrations of neuropeptide Y and corticotropin-releasing hormone in adult rat brain. Lithium treatment modifies these changes. Neuropsychopharmacology 27, 756–764 (2002).

    Article  CAS  PubMed  Google Scholar 

  102. Davidson, J. R., Hughes, D., Blazer, D. G. & George, L. K. Post-traumatic stress disorder in the community: an epidemiological study. Psychol. Med. 21, 713–721 (1991).

    Article  CAS  PubMed  Google Scholar 

  103. Yehuda, R., Teicher, M. H., Trestman, R. L., Levengood, R. A. & Siever, L. J. Cortisol regulation in posttraumatic stress disorder and major depression: a chronobiological analysis. Biol. Psychiatry 40, 79–88 (1996).

    Article  CAS  PubMed  Google Scholar 

  104. Halbreich, U. et al. Hypothalamo-pituitary-adrenal activity in endogenously depressed post-traumatic stress disorder patients. Psychoneuroendocrinology 14, 365–370 (1989).

    Article  CAS  PubMed  Google Scholar 

  105. Yehuda, R. et al. Low cortisol and risk for PTSD in adult offspring of holocaust survivors. Am. J. Psychiatry 157, 1252–1259 (2000).

    Article  CAS  PubMed  Google Scholar 

  106. Kanter, E. D. et al. Glucocorticoid feedback sensitivity and adrenocortical responsiveness in posttraumatic stress disorder. Biol. Psychiatry 50, 238–245 (2001).

    Article  CAS  PubMed  Google Scholar 

  107. Yehuda, R. Sensitization of the hypothalamic-pituitary-adrenal axis in posttraumatic stress disorder. Ann. NY Acad. Sci. 821, 57–75 (1997).

    Article  CAS  PubMed  Google Scholar 

  108. Stein, M. B., Yehuda, R., Koverola, C. & Hanna, C. Enhanced dexamethasone suppression of plasma cortisol in adult women traumatized by childhood sexual abuse. Biol. Psychiatry 42, 680–686 (1997).

    Article  CAS  PubMed  Google Scholar 

  109. Heim, C., Newport, D. J., Bonsall, R., Miller, A. H. & Nemeroff, C. B. Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. Am. J. Psychiatry 158, 575–581 (2001).

    Article  CAS  PubMed  Google Scholar 

  110. Westrin, A., Ekman, R. & Traskman-Bendz, L. Alterations of corticotropin releasing hormone (CRH) and neuropeptide Y (NPY) plasma levels in mood disorder patients with a recent suicide attempt. Eur. Neuropsychopharmacol. 9, 205–211 (1999).

    Article  CAS  PubMed  Google Scholar 

  111. Oquendo, M. A. et al. Lower cortisol levels in depressed patients with comorbid post-traumatic stress disorder. Neuropsychopharmacology 28, 591–598 (2003).

    Article  CAS  PubMed  Google Scholar 

  112. Coryell, W. & Schlesser, M. The dexamethasone suppression test and suicide prediction. Am. J. Psychiatry 158, 748–753 (2001). Hypothalamic–pituitary axis dysfunction as demonstrated by dexamethasone resistance, can predict future suicide in depressed subjects.

    Article  CAS  PubMed  Google Scholar 

  113. Meijer, O. C. & de Kloet, E. R. Corticosterone and serotonergic neurotransmission in the hippocampus: functional implications of central corticosteriod receptor diversity. Crit. Rev. Neurobiol. 12, 1–20 (1998).

    Article  CAS  PubMed  Google Scholar 

  114. Azmitia, E. C., Liao, B. & Chen, Y. S. Increase of tryptophan hydroxylase enzyme protein by dexamethasone in adrenalectomized rat midbrain. J. Neurosci. 13, 5041–5055 (1993).

    Article  CAS  PubMed  Google Scholar 

  115. Chamas, F., Serova, L. & Sabban, E. L. Tryptophan hydroxylase mRNA levels are elevated by repeated immobilization stress in rat raphe nuclei but not in pineal gland. Neurosci. Lett. 267, 157–160 (1999).

    Article  CAS  PubMed  Google Scholar 

  116. Lopez, J. F., Chalmers, D. T., Little, K. Y. & Watson, S. J. A. E. Bennett Research Award. Regulation of serotonin1A, glucocorticoid, and mineralocorticoid receptor in rat and human hippocampus: implications for the neurobiology of depression. Biol. Psychiatry 43, 547–573 (1998).

    Article  CAS  PubMed  Google Scholar 

  117. Roy, A. Family history of suicide. Arch. Gen. Psychiatry 40, 971–974 (1983).

    Article  CAS  PubMed  Google Scholar 

  118. Roy, A., Segal, N. L., Centerwall, B. S. & Robinette, C. D. Suicide in twins. Arch. Gen. Psychiatry 48, 29–32 (1991).

    Article  CAS  PubMed  Google Scholar 

  119. Roy, A., Segal, N. L. & Sarchiapone, M. Attempted suicide among living co-twins of twin suicide victims. Am. J. Psychiatry 152, 1075–1076 (1995).

    Article  CAS  PubMed  Google Scholar 

  120. Schulsinger, F., Kety, S. S., Rosenthal, D. & Wender, P. H. in Origin, Prevention and Treatment of Affective Disorders (eds Schou, M. & Stromgren, E.) 277–287 (Academic Press, New York, 1979).

    Google Scholar 

  121. Brent, D. A., Bridge, J., Johnson, B. A. & Connolly, J. Suicidal behavior runs in families. A controlled family study of adolescent suicide victims. Arch. Gen. Psychiatry 53, 1145–1152 (1996).

    Article  CAS  PubMed  Google Scholar 

  122. Statham, D. J. et al. Suicidal behaviour: an epidemiological and genetic study. Psychol. Med. 28, 839–855 (1998). Twin study showing that suicide, suicide attempts and suicidal ideation are heritable.

    Article  CAS  PubMed  Google Scholar 

  123. Manuck, S. B. et al. Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene. Biol. Psychiatry 45, 603–614 (1999).

    Article  CAS  PubMed  Google Scholar 

  124. Jönsson, E. G. et al. Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers. Eur. Arch. Psychiatry Clin. Neurosci. 247, 297–302 (1997).

    Article  PubMed  Google Scholar 

  125. Lalovic, A. & Turecki, G. Meta-analysis of the association between tryptophan hydroxylase and suicidal behavior. Am. J. Med. Genet. 114, 533–540 (2002).

    Article  CAS  PubMed  Google Scholar 

  126. Lesch, K.-P. et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 274, 1527–1531 (1996).

    Article  CAS  Google Scholar 

  127. Gorwood, P., Batel, P., Ades, J., Hamon, M. & Boni, C. Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior. Biol. Psychiatry 48, 259–264 (2000).

    Article  CAS  PubMed  Google Scholar 

  128. Bellivier, F. et al. Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders. Biol. Psychiatry 48, 319–322 (2000).

    Article  CAS  PubMed  Google Scholar 

  129. Bondy, B., Erfurth, A., de Jonge, S., Kruger, M. & Meyer, H. Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide. Mol. Psychiatry 5, 193–195 (2000).

    Article  CAS  PubMed  Google Scholar 

  130. Du, L. et al. Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol. Psychiatry 46, 196–201 (1999).

    Article  CAS  PubMed  Google Scholar 

  131. Mann, J. J., Brent, D. A. & Arango, V. The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system. Neuropsychopharmacology 24, 467–477 (2001). A review of serotonin-related candidate gene studies in suicidal behaviour.

    Article  CAS  PubMed  Google Scholar 

  132. Ramboz, S. et al. Serotonin receptor 1A knockout: an animal model of anxiety-related disorder. Proc. Natl Acad. Sci. USA 95, 14476–14481 (1998).

    Article  CAS  PubMed  Google Scholar 

  133. Nakhai, B., Nielsen, D. A., Linnoila, M. & Goldman, D. Two naturally occurring amino acid substitutions in the human 5-HT1A receptor: glycine 22 to serine 22 and isoleucine 28 to valine 28. Biochem. Biophys. Res. Commun. 210, 530–536 (1995).

    Article  CAS  PubMed  Google Scholar 

  134. Huang, Y. et al. Human 5-HT1A receptor C1019G polymorphism and psychopathology. Soc. Neurosci. Abstr. 706.20 (2002).

  135. Tsai, S.-J. et al. Serotonin-2A receptor polymorphism (102T/C) in mood disorders. Psychiatry Res. 87, 233–237 (1999).

    Article  CAS  PubMed  Google Scholar 

  136. Du, L., Bakish, D., Lapierre, Y. D., Ravindran, A. V. & Hrdina, P. D. Association of polymorphism of serotonin 2A receptor gene with suicidal ideation in major depressive disorder. Am. J. Med. Genet. 96, 56–60 (2000).

    Article  CAS  PubMed  Google Scholar 

  137. Turecki, G. et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am. J. Psychiatry 156, 1456–1458 (1999).

    CAS  PubMed  Google Scholar 

  138. Geijer, T. et al. Search for association between suicide attempt and serotonergic polymorphisms. Psychiatr. Genet. 10, 19–26 (2000).

    Article  CAS  PubMed  Google Scholar 

  139. Zhang, H.-Y. et al. Serotonin2A receptor gene polymorphism in mood disorders. Biol. Psychiatry 41, 768–773 (1997).

    Article  CAS  PubMed  Google Scholar 

  140. Ramboz, S. et al. 5-HT1B receptor knock out — behavioral consequences. Behav. Brain Res. 73, 305–312 (1996).

    Article  CAS  PubMed  Google Scholar 

  141. Rocha, B. A. et al. Increased vulnerability to cocaine in mice lacking the serotonin-1B receptor. Nature 393, 176–178 (1998).

    Article  Google Scholar 

  142. de Almeida, R. M. & Miczek, K. A. Aggression escalated by social instigation or by discontinuation of reinforcement ('frustration') in mice: inhibition by anpirtoline: a 5-HT1B receptor agonist. Neuropsychopharmacology 27, 171–181 (2002).

    Article  CAS  PubMed  Google Scholar 

  143. Parsons, L. H., Weiss, F. & Koob, G. F. Serotonin 1B receptor stimulation enhances cocaine reinforcement. J. Neurosci. 18, 10078–10089 (1998).

    Article  CAS  PubMed  Google Scholar 

  144. Huang, Y., Grailhe, R., Arango, V., Hen, R. & Mann, J. J. Relationship of psychopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue. Neuropsychopharmacology 21, 238–246 (1999).

    Article  CAS  PubMed  Google Scholar 

  145. Lappalainen, J. et al. Linkage of antisocial alcoholism to the serotonin 5-HT1B receptor gene in 2 populations. Arch. Gen. Psychiatry 55, 989–994 (1998).

    Article  CAS  PubMed  Google Scholar 

  146. Huang, Y. Y. et al. Substance abuse disorder and major depression are associated with the human 5-HT1B receptor gene (HTR1B) G861C polymorphism. Neuropsychopharmacology 28, 163–169 (2003).

    Article  CAS  PubMed  Google Scholar 

  147. Manuck, S. B., Flory, J. D., Ferrell, R. E., Mann, J. J. & Muldoon, M. F. A regulatory polymorphism of the monoamine oxidase-A gene maybe associated with variability in aggression, impulsivity and central nervous system serotonergic responsivity. Psychiatry Res. 95, 9–23 (2000).

    Article  CAS  PubMed  Google Scholar 

  148. Brunner, H. G., Nelen, M., Breakefield, X. O., Ropers, H. H. & van Oost, B. A. Abnormal behavior associated with a point mutation in the structural gene for monoamine oxidase A. Science 262, 578–580 (1993).

    Article  CAS  PubMed  Google Scholar 

  149. Caspi, A. et al. Role of genotype in the cycle of violence in maltreated children. Science 297, 851–854 (2002).

    Article  CAS  PubMed  Google Scholar 

  150. Terwilliger, J. D. & Göring, H. H. Gene mapping in the 20th and 21st centuries: statistical methods, data analysis, and experimental design. Hum. Biol. 72, 63–132 (2000).

    CAS  PubMed  Google Scholar 

  151. Bechara, A., Damasio, H. & Damasio, A. R. Emotion, decision making and the orbitofrontal cortex. Cereb. Cortex 10, 295–307 (2000).

    Article  CAS  PubMed  Google Scholar 

  152. Ingvar, D. H. The will of the brain: cerebral correlates of willful acts. J. Theor. Biol. 171, 7–12 (1994).

    Article  CAS  PubMed  Google Scholar 

  153. Bechara, A., Damasio, A. R., Damasio, H. & Anderson, S. W. Insensitivity to future consequences following damage to human prefrontal cortex. Cognition 50, 7–15 (1994).

    Article  CAS  PubMed  Google Scholar 

  154. Miller, L. A. Impulsivity, risk-taking, and the ability to synthesize fragmented information after frontal lobectomy. Neuropsychologia 30, 69–79 (1992).

    Article  CAS  PubMed  Google Scholar 

  155. Rogers, R. D. et al. Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. Neuropsychopharmacology 20, 322–339 (1999).

    Article  CAS  PubMed  Google Scholar 

  156. Frith, C. D., Friston, K. J., Liddle, P. F. & Frackowiak, R. S. J. Willed action and the prefrontal cortex in man: a study with PET. Proc. R. Soc. Lond. B 244, 241–246 (1991).

    Article  CAS  Google Scholar 

  157. Davidson, R. J., Putnam, K. M. & Larson, C. L. Dysfunction in the neural circuitry of emotion regulation — a possible prelude to violence. Science 289, 591–594 (2000).

    Article  CAS  PubMed  Google Scholar 

  158. Blair, R. J., Morris, J. S., Frith, C. D., Perrett, D. I. & Dolan, R. J. Dissociable neural responses to facial expressions of sadness and anger. Brain 122, 883–893 (1999).

    Article  PubMed  Google Scholar 

  159. Morgan, M. A., Romanski, L. M. & LeDoux, J. E. Extinction of emotional learning: contribution of medial prefrontal cortex. Neurosci. Lett. 163, 109–113 (1993).

    Article  CAS  PubMed  Google Scholar 

  160. Gewirtz, J. C. & Falls, W. A. Normal conditioned inhibition and extinction of freezing and fear-potentiated startle following electrolytic lesions of medical prefrontal cortex in rats. Behav. Neurosci. 111, 712–726 (1997).

    Article  CAS  PubMed  Google Scholar 

  161. Drevets, W. C. et al. A functional anatomical study of unipolar depression. J. Neurosci. 12, 3628–3641 (1992).

    Article  CAS  PubMed  Google Scholar 

  162. Mann, J. J. et al. Demonstration in vivo of reduced serotonin responsivity in the brain of untreated depressed patients. Am. J. Psychiatry 153, 174–182 (1996).

    Article  CAS  PubMed  Google Scholar 

  163. Siever, L. J. et al. d,1-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography. Neuropsychopharmacology 20, 413–423 (1999).

    Article  CAS  PubMed  Google Scholar 

  164. Raine, A. et al. Reduced prefrontal and increased subcortical brain functioning assessed using positron emission tomography in predatory and affective murderers. Behav. Sci. Law 16, 319–332 (1998).

    Article  CAS  PubMed  Google Scholar 

  165. Hoptman, M. J. et al. Frontal white matter microstructure, aggression, and impulsivity in men with schizophrenia: a preliminary study. Biol. Psychiatry 52, 9–14 (2002).

    Article  PubMed  Google Scholar 

  166. Mann, J. J. Neurobiology of Suicide and Aggression. ACNP Fourth Generation of Progress, <http://www.acnp.org/citations/GN401000185/> (2000).

    Google Scholar 

  167. Dalley, J. W., Theobald, D. E., Pereira, E. A., Li, P. M. & Robbins, T. W. Specific abnormalities in serotonin release in the prefrontal cortex of isolation-reared rats measured during behavioural performance of a task assessing visuospatial attention and impulsivity. Psychopharmacology (Berl.) 164, 329–340 (2002).

    Article  CAS  Google Scholar 

  168. Heidbreder, C. A. et al. Behavioral, neurochemical and endocrinological characterization of the early social isolation syndrome. Neuroscience 100, 749–768 (2000).

    Article  CAS  PubMed  Google Scholar 

  169. Sahakian, B. J., Robbins, T. W., Morgan, M. J. & Iversen, S. D. The effects of psychomotor stimulants on stereotypy and locomotor activity in socially-deprived and control rats. Brain Res. 84, 195–205 (1975).

    Article  CAS  PubMed  Google Scholar 

  170. Dias, R., Robbins, T. W. & Roberts, A. C. Dissociation in prefrontal cortex of affective and attentional shifts. Nature 380, 69–72 (1996).

    Article  CAS  PubMed  Google Scholar 

  171. Jaskiw, G. E. et al. Effect of ibotenic acid lesions of the medial prefrontal cortex on amphetamine-induced locomotion and regional brain catecholamine concentrations in the rat. Brain Res. 534, 263–272 (1990).

    Article  CAS  PubMed  Google Scholar 

  172. Womack, S. et al. Medial frontal cortex lesions: deficits and treatment with nimodipine. Exp. Neurol. 124, 387–389 (1993).

    Article  CAS  PubMed  Google Scholar 

  173. Hirschfeld, R. M. & Russell, J. M. Assessment and treatment of suicidal patients. N. Engl. J. Med. 337, 910–915 (1997). A review of current clinical approaches to evaluating and treating the suicidal patient.

    Article  CAS  PubMed  Google Scholar 

  174. Baldessarini, R. J., Tondo, L. & Hennen, J. Effects of lithium treatment and its discontinuation on suicidal behavior in bipolar manic-depressive disorders. J. Clin. Psychiatry 60, 77–84 (1999).

    Article  CAS  PubMed  Google Scholar 

  175. Nilsson, A. Lithium therapy and suicide risk. J. Clin. Psychiatry 60, 85–88 (1999).

    CAS  PubMed  Google Scholar 

  176. Meltzer, H. Y. & Okayli, G. Reduction of suicidality during clozapine treatment of neuroleptic-resistant schizophrenia: impact on risk-benefit assessment. Am. J. Psychiatry 152, 183–190 (1995).

    Article  CAS  PubMed  Google Scholar 

  177. Walker, A. M., Lanza, L. L., Arellano, F. & Rothman, K. J. Mortality in current and former users of clozapine. Epidemiology 8, 671–677 (1997).

    Article  CAS  PubMed  Google Scholar 

  178. Reid, W. H., Mason, M. & Hogan, T. Suicide prevention effects associated with clozapine therapy in schizophrenia and schizoaffective disorder. Psychiatric Services 49, 1029–1033 (1998).

    Article  CAS  PubMed  Google Scholar 

  179. Oquendo, M. A. et al. Postmortem frontal cortex 5HT2A binding is higher in suicide victims with elevated lifetime aggression. American College of Neuropsycopharmacology 39th Annual Meeting, 85 (2000).

    Google Scholar 

  180. Muldoon, M. F., Manuck, S. B. & Matthews, K. A. Lowering cholesterol concentrations and mortality: a quantitative review of primary prevention trials. Br. Med. J. 301, 309–314 (1990).

    Article  CAS  Google Scholar 

  181. Muldoon, M. F. et al. Low or lowered cholesterol and risk of death from suicide and trauma. Metabolism 42, 45–56 (1993).

    Article  CAS  PubMed  Google Scholar 

  182. Golomb, B. A. Cholesterol and violence: is there a connection? Ann. Intern. Med. 128, 478–487 (1998).

    Article  CAS  PubMed  Google Scholar 

  183. Kaplan, J. R. et al. Demonstration of an association among dietary cholesterol, central serotonergic activity, and social behavior in monkeys. Psychosom. Med. 56, 479–484 (1994).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Thanks to V. Arango, M. Underwood, D. Brent and M. Oquendo for ideas and suggestions. Supported by grants from the National Institute of Mental Health.

Author information

Authors and Affiliations

  1. Department of Neuroscience, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, 10032, New York, USA

    J. John Mann

Authors
  1. J. John Mann
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASES

LocusLink

5-HT1A

5-HT2A

HTR1A

HTR1B

HTR2A

MAOA

SERT

TPH1

TPH2

FURTHER INFORMATION

Encyclopedia of Life Sciences

mood disorders

National Center for Injury Prevention and Control

World Health Organization Statistical Information System

Glossary

BORDERLINE PERSONALITY DISORDER

According to the Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV), this is a pervasive pattern of instability of interpersonal relationships, self-image, affects and marked impulsivity, which begins by early adulthood and is present in various contexts.

ANTISOCIAL PERSONALITY DISORDER

According to the DSM-IV, this is a pervasive pattern of disregard for and violation of the rights of others, occurring from the age of 15 years.

DIATHESIS

In the medical literature, it is a constitution of the body that makes it react in specific ways to extrinsic stimuli, thereby tending to make the person more susceptible than normal to certain diseases.

STATINS

Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A, which are commonly used to reduce the amount of low-density lipoprotein cholesterol.

PSYCHOLOGICAL AUTOPSY

Interviews with friends and next-of-kin of a subject who committed suicide, trying to establish the reasons for suicidal behaviour.

AUTORADIOGRAPHIC STUDIES

Technique in which a specimen that has been labelled with a radioactive molecule (usually the ligand of a receptor) is placed on a photographic emulsion. Its subsequent development reveals the localization of radioactivity, and therefore the localization of the molecule of interest, as a pattern of silver grains.

BRODMANN AREAS

Korbinian Brodmann (1868–1918) was an anatomist who divided the cerebral cortex into numbered subdivisions on the basis of cell arrangements, types and staining properties. Modern derivatives of his maps are commonly used as the reference system for discussion of brain-imaging findings.

CONCORDANCE

The occurrence of a trait in two related individuals, such as twins or siblings.

HERITABILITY

The proportion of variability in a particular characteristic that can be attributed to genetic influences. This is a statistical description that applies to a specific population and might change if the environment is altered.

POLYMORPHISM

The simultaneous existence in the same population of two or more genotypes in frequencies that cannot be explained by recurrent mutations.

LINKAGE DISEQUILIBRIUM

A condition in which the frequency of a particular haplotype for two loci is significantly greater than that expected from the product of the observed allelic frequencies at each locus.

ENDOPHENOTYPES

The physiological traits that are related to a disease; for example, blood pressure, angiotensin levels or salt sensitivity are endophenotypes of hypertension.

ANISOTROPY

When the physical properties of a given medium have different values, when measured along axes orientated in different directions, it is said to be anisotropic.

REVERSAL LEARNING

A situation in which a subject is trained to respond differentially to two stimuli, and is subsequently trained under reversed reward values.

PERSEVERATION

The persistent use of a specific strategy to solve a problem, despite the fact that the strategy is wrong or the rule of the task has changed.

DIALECTICAL BEHAVIOUR THERAPY

A cognitive–behavioural approach that was originally developed to treat people with borderline personality disorder, especially those with chronic patterns of suicidal behaviour. As people with this disorder lack interpersonal skills and have an impaired self-image, the dialectical strategy aims to help the patients accept the way they are while simultaneously helping them to change.

HAPLOTYPE

A combination of alleles at different sites on a single chromosome.

MODIFIER GENE

A gene that influences the phenotypic expression of another gene.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mann, J. Neurobiology of suicidal behaviour. Nat Rev Neurosci 4, 819–828 (2003). https://doi.org/10.1038/nrn1220

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrn1220

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing