Skip to main content
SpringerLink
Log in

Neurodevelopmental Aspects of Suicide

  • Chapter
  • First Online:
Depression Conceptualization and Treatment

  • 999 Accesses

Abstract

In this chapter, we are going to discuss about suicide and suicidal behavior from a developmental aspect. In the beginning, we will discuss definitions of suicide and suicidal behavior and known risk factors. The stress-diathesis model of suicidal behavior is going to be presented and describe the course of the suicide process from a neurodevelopmental perspective. Known and promising biomarkers integrated to suicidal process will be analyzed. Focus is going to be on key neurobiological systems such as the hypothalamic-pituitary-adrenal (HPA) axis, the serotonin system, and the oxytocin system. The central role of childhood adversity on neurodevelopment and the impact on suicide will be presented through a genetic and an epigenetic perspective. Finally, we will close the chapter with recommendations for treatment as well as prevention. At the end of the chapter, there is a case study presentation followed by discussion to illustrate a real-life example of suicidal behavior.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 16.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 89.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Arato, M., Banki, C. M., Bissette, G., & Nemeroff, C. B. (1989). Elevated CSF CRF in suicide victims. Biological Psychiatry, 25(3), 355–359. 0006-3223(89)90183-2 [pii].

    Article  Google Scholar 

  • Asberg, M., Nordstrom, P., & Traskman-Bendz, L. (1986). Cerebrospinal fluid studies in suicide. An overview. Annals of the New York Academy of Sciences, 487, 243–255.

    Google Scholar 

  • Asberg, M., Traskman, L., & Thoren, P. (1976). 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Archives of General Psychiatry, 33(10), 1193–1197.

    Article  Google Scholar 

  • Bertsch, K., Schmidinger, I., Neumann, I. D., & Herpertz, S. C. (2013). Reduced plasma oxytocin levels in female patients with borderline personality disorder. Hormones and Behavior, 63(3), 424–429.

    Article  Google Scholar 

  • Bradley, B., Davis, T. A., Wingo, A. P., Mercer, K. B., & Ressler, K. J. (2013). Family environment and adult resilience: Contributions of positive parenting and the oxytocin receptor gene. European Journal of Psychotraumatology, 4.

    Google Scholar 

  • Brodsky, B. S. (2016). Early childhood environment and genetic interactions: The diathesis for suicidal behavior. Current Psychiatry Reports, 18(9), 86.

    Article  Google Scholar 

  • Carroll, B. J., Martin, F. I., & Davies, B. (1968). Resistance to suppression by dexamethasone of plasma 11-O.H.C.S. levels in severe depressive illness. British Medical Journal, 3(5613), 285–287.

    Article  Google Scholar 

  • Caspi, A., Sugden, K., Moffitt, T. E., Taylor, A., Craig, I. W., Harrington, H., … Poulton, R. (2003). Influence of life stress on depression: Moderation by a polymorphism in the 5-HTT gene. Science, 301(5631), 386–389.

    Article  Google Scholar 

  • Chatzittofis, A., Nordstrom, P., Hellstrom, C., Arver, S., Asberg, M., & Jokinen, J. (2013). CSF 5-HIAA, cortisol and DHEAS levels in suicide attempters. European Neuropsychopharmacology, 23(10), 1280–1287. https://doi.org/10.1016/j.euroneuro.2013.02.002

    Article  Google Scholar 

  • Chatzittofis, A., Nordstrom, P., Uvnas-Moberg, K., Asberg, M., & Jokinen, J. (2014). CSF and plasma oxytocin levels in suicide attempters, the role of childhood trauma and revictimization. Neuroendocrinology Letters, 35(3), 213–217.

    Google Scholar 

  • Cicchetti, D., Rogosch, F. A., Hecht, K. F., Crick, N. R., & Hetzel, S. (2014). Moderation of maltreatment effects on childhood borderline personality symptoms by gender and oxytocin receptor and FK506 binding protein 5 genes. Developmental Psychopathology, 26(3), 831–849.

    Article  Google Scholar 

  • Cipriano, A., Cella, S., & Cotrufo, P. (2017). Nonsuicidal self-injury: A systematic review. Frontiers in Psychology, 8, 1946. https://doi.org/10.3389/fpsyg.2017.01946

    Article  Google Scholar 

  • Coryell, W. (2012). Do serum cholesterol values and DST results comprise independent risk factors for suicide? In The neurobiological basis of suicide. Boca Raton, FL: CRC Press/Taylor & Francis. NBK107215.

    Google Scholar 

  • Coryell, W., & Schlesser, M. (2001). The dexamethasone suppression test and suicide prediction. American Journal of Psychiatry, 158(5), 748–753.

    Article  Google Scholar 

  • Dashorst, P., Mooren, T. M., Kleber, R. J., de Jong, P. J., & Huntjens, R. J. C. (2019). Intergenerational consequences of the Holocaust on offspring mental health: A systematic review of associated factors and mechanisms. European Jouranl of Psychotraumatology, 10(1), 1654065. https://doi.org/10.1080/20008198.2019.1654065

    Article  Google Scholar 

  • De Bellis, M. D., & Zisk, A. (2014). The biological effects of childhood trauma. Child and Adolescent Psychiatric Clinics, 23(2), 185–222.

    Article  Google Scholar 

  • Guillaume, S., Perroud, N., Jollant, F., Jaussent, I., Olie, E., Malafosse, A., & Courtet, P. (2013). HPA axis genes may modulate the effect of childhood adversities on decision-making in suicide attempters. Journal of Psychiatry Research, 47(2), 259–265.

    Article  Google Scholar 

  • Guintivano, J., Brown, T., Newcomer, A., Jones, M., Cox, O., Maher, B. S., … Kaminsky, Z. A. (2014). Identification and replication of a combined epigenetic and genetic biomarker predicting suicide and suicidal behaviors. American Journal of Psychiatry, 171(12), 1287–1296.

    Article  Google Scholar 

  • Hawton, K., & van Heeringen, K. (2009). Suicide. Lancet, 373(9672), 1372–1381.

    Article  Google Scholar 

  • Heim, C., Mletzko, T., Purselle, D., Musselman, D. L., & Nemeroff, C. B. (2008). The dexamethasone/corticotropin-releasing factor test in men with major depression: Role of childhood trauma. Biological Psychiatry, 63(4), 398–405.

    Article  Google Scholar 

  • Heim, C., Newport, D. J., Bonsall, R., Miller, A. H., & Nemeroff, C. B. (2001). Altered pituitary-adrenal axis responses to provocative challenge tests in adult survivors of childhood abuse. American Journal of Psychiatry, 158(4), 575–581.

    Article  Google Scholar 

  • Heim, C., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2008). The link between childhood trauma and depression: Insights from HPA axis studies in humans. Psychoneuroendocrinology, 33(6), 693–710.

    Article  Google Scholar 

  • Heim, C., Young, L. J., Newport, D. J., Mletzko, T., Miller, A. H., & Nemeroff, C. B. (2009). Lower CSF oxytocin concentrations in women with a history of childhood abuse. Molecular Psychiatry, 14(10), 954–958.

    Article  Google Scholar 

  • Heinrichs, M., Baumgartner, T., Kirschbaum, C., & Ehlert, U. (2003). Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biological Psychiatry, 54(12), 1389–1398.

    Article  Google Scholar 

  • Heinrichs, M., von Dawans, B., & Domes, G. (2009). Oxytocin, vasopressin, and human social behavior. Frontiers in Neuroendocrinology, 30(4), 548–557.

    Article  Google Scholar 

  • Herpertz, S. C., & Bertsch, K. (2015). A new perspective on the pathophysiology of borderline personality disorder: A model of the role of oxytocin. American Journal of Psychiatry, 172(9), 840–851.

    Article  Google Scholar 

  • Hollander, E., Novotny, S., Hanratty, M., Yaffe, R., DeCaria, C. M., Aronowitz, B. R., & Mosovich, S. (2003). Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology, 28(1), 193–198.

    Article  Google Scholar 

  • Insel, T. R. (2010). The challenge of translation in social neuroscience: A review of oxytocin, vasopressin, and affiliative behavior. Neuron, 65(6), 768–779.

    Article  Google Scholar 

  • Jokinen, J., Boström, A. E., Dadfar, A., Ciuculete, D. M., Chatzittofis, A., Ã…sberg, M., & Schiöth, H. B. (2018). Epigenetic changes in the CRH gene are related to severity of suicide attempt and a general psychiatric risk score in adolescents. eBioMedicine, 27, 123–133.

    Article  Google Scholar 

  • Jokinen, J., Carlborg, A., Martensson, B., Forslund, K., Nordstrom, A. L., & Nordstrom, P. (2007). DST non-suppression predicts suicide after attempted suicide. Psychiatry Research, 150(3), 297–303.

    Article  Google Scholar 

  • Jokinen, J., Chatzittofis, A., Hellström, C., Nordström, P., Uvnäs-Moberg, K., & Ã…sberg, M. (2012). Low CSF oxytocin reflects high intent in suicide attempters. Psychoneuroendocrinology, 37(4), 482–490.

    Article  Google Scholar 

  • Jokinen, J., Nordstrom, A. L., & Nordstrom, P. (2009). CSF 5-HIAA and DST non-suppression--orthogonal biologic risk factors for suicide in male mood disorder inpatients. Psychiatry Research, 165(1–2), 96–102.

    Article  Google Scholar 

  • Jollant, F., Lawrence, N. S., Olie, E., O’Daly, O., Malafosse, A., Courtet, P., & Phillips, M. L. (2010). Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior. NeuroImage, 51(3), 1275–1281.

    Article  Google Scholar 

  • Kaminsky, Z., Jones, I., Verma, R., Saleh, L., Trivedi, H., Guintivano, J., … Potash, J. B. (2015). DNA methylation and expression of KCNQ3 in bipolar disorder. Bipolar Disorders, 17(2), 150–159.

    Article  Google Scholar 

  • Labonté, B., Suderman, M., Maussion, G., Lopez, J. P., Navarro-Sánchez, L., Yerko, V., … Turecki, G. (2013). Genome-wide methylation changes in the brains of suicide completers. American Journal of Psychiatry, 170(5), 511–520.

    Article  Google Scholar 

  • Labonte, B., Yerko, V., Gross, J., Mechawar, N., Meaney, M. J., Szyf, M., & Turecki, G. (2012). Differential glucocorticoid receptor exon 1(B), 1(C), and 1(H) expression and methylation in suicide completers with a history of childhood abuse. Biological Psychiatry, 72(1), 41–48.

    Article  Google Scholar 

  • Lee, R., Ferris, C., Van de Kar, L. D., & Coccaro, E. F. (2009). Cerebrospinal fluid oxytocin, life history of aggression, and personality disorder. Psychoneuroendocrinology, 34(10), 1567–1573.

    Article  Google Scholar 

  • Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. (2009). Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nature Reviews Neuroscience, 10(6), 434–445.

    Article  Google Scholar 

  • Mann, J. J. (2003). Neurobiology of suicidal behaviour. Nature Reviews Neuroscience, 4(10), 819–828.

    Article  Google Scholar 

  • Mann, J. J., & Currier, D. (2007). A review of prospective studies of biologic predictors of suicidal behavior in mood disorders. Archives of Suicide Research, 11(1), 3–16.

    Article  Google Scholar 

  • McGowan, P. O., Sasaki, A., D’Alessio, A. C., Dymov, S., Labonte, B., Szyf, M., … Meaney, M. J. (2009). Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nature Neuroscience, 12(3), 342–348.

    Article  Google Scholar 

  • Nemeroff, C. B., Owens, M. J., Bissette, G., Andorn, A. C., & Stanley, M. (1988). Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Archives of General Psychiatry, 45(6), 577–579.

    Article  Google Scholar 

  • Neumann, I. D. (2009). The advantage of social living: Brain neuropeptides mediate the beneficial consequences of sex and motherhood. Frontiers in Neuroendocrinology, 30(4), 483–496.

    Article  Google Scholar 

  • Neumann, I. D., Krömer, S. A., Toschi, N., & Ebner, K. (2000). Brain oxytocin inhibits the (re) activity of the hypothalamo–pituitary–adrenal axis in male rats: Involvement of hypothalamic and limbic brain regions. Regulatory Peptides, 96(1–2), 31–38.

    Article  Google Scholar 

  • Neuringer, C. (1964). Rigid thinking in suicidal individuals. Journal of Consulting Psychology, 28, 54–58.

    Article  Google Scholar 

  • Niculescu, A. B., Levey, D. F., Phalen, P. L., Le-Niculescu, H., Dainton, H. D., Jain, N., … Salomon, D. R. (2015). Understanding and predicting suicidality using a combined genomic and clinical risk assessment approach. Molecular Psychiatry, 20(11), 1266–1285.

    Article  Google Scholar 

  • Nock, M. K., Borges, G., Bromet, E. J., Cha, C. B., Kessler, R. C., & Lee, S. (2008). Suicide and suicidal behavior. Epidemiologic Reviews, 30, 133–154.

    Article  Google Scholar 

  • Olff, M. (2012). Bonding after trauma: On the role of social support and the oxytocin system in traumatic stress. European Journal of Psychotraumatology, 3(1), 18597. https://doi.org/10.3402/ejpt.v3i0.18597

    Article  Google Scholar 

  • Opacka-Juffry, J., & Mohiyeddini, C. (2012). Experience of stress in childhood negatively correlates with plasma oxytocin concentration in adult men. Stress, 15(1), 1–10.

    Article  Google Scholar 

  • Oquendo, M. A., Sullivan, G. M., Sudol, K., Baca-Garcia, E., Stanley, B. H., Sublette, M. E., & Mann, J. J. (2014). Toward a biosignature for suicide. The American Journal of Psychiatry, 171(12), 1259–1277.

    Article  Google Scholar 

  • Perroud, N., Rutembesa, E., Paoloni-Giacobino, A., Mutabaruka, J., Mutesa, L., Stenz, L., … Karege, F. (2014). The Tutsi genocide and transgenerational transmission of maternal stress: Epigenetics and biology of the HPA axis. The World Journal of Biological Psychiatry, 15, 334.

    Article  Google Scholar 

  • Petersson, M., Hulting, A. L., & Uvnas-Moberg, K. (1999). Oxytocin causes a sustained decrease in plasma levels of corticosterone in rats. Neuroscience Letters, 264(1–3), 41–44.

    Article  Google Scholar 

  • Pfennig, A., Kunzel, H. E., Kern, N., Ising, M., Majer, M., Fuchs, B., … Binder, E. B. (2005). Hypothalamus-pituitary-adrenal system regulation and suicidal behavior in depression. Biological Psychiatry, 57(4), 336–342.

    Article  Google Scholar 

  • Pierrehumbert, B., Torrisi, R., Laufer, D., Halfon, O., Ansermet, F., & Beck Popovic, M. (2010). Oxytocin response to an experimental psychosocial challenge in adults exposed to traumatic experiences during childhood or adolescence. Neuroscience, 166(1), 168–177.

    Article  Google Scholar 

  • Policicchio, S., Washer, S., Viana, J., Iatrou, A., Burrage, J., Hannon, E., … Murphy, T. M. (2020). Genome-wide DNA methylation meta-analysis in the brains of suicide completers. Translational Psychiatry, 10(1), 1–13.

    Article  Google Scholar 

  • Rosell, D. R., & Siever, L. J. (2015). The neurobiology of aggression and violence. CNS Spectrums, 20(3), 254–279.

    Article  Google Scholar 

  • Roy, A., Gorodetsky, E., Yuan, Q., Goldman, D., & Enoch, M. A. (2010). Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology, 35(8), 1674–1683.

    Article  Google Scholar 

  • Roy, B., Shelton, R. C., & Dwivedi, Y. (2017). DNA methylation and expression of stress related genes in PBMC of MDD patients with and without serious suicidal ideation. Journal of Psychiatry Research, 89, 115–124.

    Article  Google Scholar 

  • Seltzer, L. J., Ziegler, T., Connolly, M. J., Prososki, A. R., & Pollak, S. D. (2014). Stress-induced elevation of oxytocin in maltreated children: Evolution, neurodevelopment, and social behavior. Child Development, 85(2), 501–512.

    Article  Google Scholar 

  • Teicher, M. H., & Samson, J. A. (2013). Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. American Journal of Psychiatry, 170(10), 1114–1133.

    Article  Google Scholar 

  • Thompson, R. J., Parker, K. J., Hallmayer, J. F., Waugh, C. E., & Gotlib, I. H. (2011). Oxytocin receptor gene polymorphism (rs2254298) interacts with familial risk for psychopathology to predict symptoms of depression and anxiety in adolescent girls. Psychoneuroendocrinology, 36(1), 144–147.

    Article  Google Scholar 

  • Turecki, G. (2014). The molecular bases of the suicidal brain. Nature Reviews Neuroscience, 15(12), 802–816.

    Article  Google Scholar 

  • Turecki, G., & Brent, D. A. (2016). Suicide and suicidal behaviour. Lancet, 387, 1227. S0140-6736(15)00234-2.

    Article  Google Scholar 

  • Turecki, G., Ernst, C., Jollant, F., Labonte, B., & Mechawar, N. (2012). The neurodevelopmental origins of suicidal behavior. Trends in Neurosciences, 35(1), 14–23.

    Article  Google Scholar 

  • Turecki, G., Ota, V. K., Belangero, S. I., Jackowski, A., & Kaufman, J. (2014). Early life adversity, genomic plasticity, and psychopathology. Lancet Psychiatry, 1(6), 461–466.

    Article  Google Scholar 

  • van Heeringen, K., & Mann, J. J. (2014). The neurobiology of suicide. Lancet Psychiatry, 1(1), 63–72.

    Article  Google Scholar 

  • Veening, J. G., de Jong, T., & Barendregt, H. P. (2010). Oxytocin-messages via the cerebrospinal fluid: Behavioral effects; A review. Physiology & Behavior, 101(2), 193–210.

    Article  Google Scholar 

  • WHO. (2019). Suicide. Retrieved from https://www.who.int/news-room/fact-sheets/detail/suicide

  • Widom, C. S., Czaja, S. J., & Dutton, M. A. (2008). Childhood victimization and lifetime revictimization. Child Abuse and Neglect, 32(8), 785–796.

    Article  Google Scholar 

  • Windle, R. J., Kershaw, Y. M., Shanks, N., Wood, S. A., Lightman, S. L., & Ingram, C. D. (2004). Oxytocin attenuates stress-induced c-fos mRNA expression in specific forebrain regions associated with modulation of hypothalamo-pituitary-adrenal activity. Journal of Neurosciece, 24(12), 2974–2982.

    Article  Google Scholar 

  • Windle, R. J., Shanks, N., Lightman, S. L., & Ingram, C. D. (1997). Central oxytocin administration reduces stress-induced corticosterone release and anxiety behavior in rats. Endocrinology, 138(7), 2829–2834.

    Article  Google Scholar 

  • Yehuda, R., Daskalakis, N. P., Bierer, L. M., Bader, H. N., Klengel, T., Holsboer, F., & Binder, E. B. (2016). Holocaust exposure induced intergenerational effects on FKBP5 methylation. Biological Psychiatry, 80(5), 372–380.

    Article  Google Scholar 

  • Yrigollen, C. M., Han, S. S., Kochetkova, A., Babitz, T., Chang, J. T., Volkmar, F. R., … Grigorenko, E. L. (2008). Genes controlling affiliative behavior as candidate genes for autism. Biological Psychiatry, 63(10), 911–916.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, University of Cyprus, Nicosia, Cyprus

    Andreas Chatzittofis

Authors
  1. Andreas Chatzittofis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Chatzittofis .

Editor information

Editors and Affiliations

  1. Private Practice, Dillenburg, Germany

    Christos Charis

  2. Department of Psychology and Center of Applied Neuroscience, University of Cyprus, Nicosia, Cyprus

    Georgia Panayiotou

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Chatzittofis, A. (2021). Neurodevelopmental Aspects of Suicide. In: Charis, C., Panayiotou, G. (eds) Depression Conceptualization and Treatment. Springer, Cham. https://doi.org/10.1007/978-3-030-68932-2_1

Download citation

Publish with us

Policies and ethics

Search

Navigation