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Early-Life Adversity, Suicide Risk and Epigenetics of Trauma

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Suicide by Self-Immolation

Abstract

Understanding the neurobiology of suicide, in particular gene-environment interactions, could be relevant in the clinical assessment of suicide risk and prevention. Although there are no studies examining the neurobiology of suicide by self-immolation, we will demonstrate how general findings from suicide research may prove relevant in the care of persons at risk for self-immolation who experienced early trauma and retraumatization during young adulthood. The neurobiology and pathogenesis of suicide is complex and involves multiple neurotransmitter systems (serotonergic, noradrenergic, dopaminergic, glutamatergic) and different regions of the brain (brainstem, prefrontal cortex, anterior cingulate cortex, amygdala and hippocampus). Biomarkers of suicide include levels of CSF 5-HIAA, MHPG, quinolinic acid and kynurenic acid. The intergenerational transmission and a positive family history of suicide results from a combination of factors, including modeling and imitation, contagion, the transmission of an impulsive aggression phenotype, child rearing styles and concomitant environmental stressors, a shared genetic makeup and epigenetic changes. Adverse childhood experiences and a chaotic family environment increase suicide risk. Violent trauma during young adulthood also triggers suicidal behavior. Traumatic events, in particular during these sensitive periods of brain development, may trigger enduring epigenetic changes. We will review how epigenetics may be an important underlying mechanism for the pathogenesis of suicide. Epigenetic mechanisms associated with suicide include DNA methylation, histone modifications and non-coding RNA interference and silencing. Lastly, we will summarize data showing that psychosocial interventions, including brief psychotherapy interventions, may reverse epigenetic changes associated major depression, PTSD and stressor related disorders, decreasing suicide risk.

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References

  1. Joiner TE, Brown JS, Wingate LR. The psychology and neurobiology of suicidal behavior. Annu Rev Psychol. 2005;56:287–314.

    Article  PubMed  Google Scholar 

  2. Van Heeringen K, Mann JJ. The neurobiology of suicide. Lancet Psychiatry. 2014;1(1):63–72. https://doi.org/10.1016/S2215-0366(14)70220-2.

    Article  PubMed  Google Scholar 

  3. Asberg M, Traskman L, Thoren P. 5-HIAA in the cerebrospinal fluid: a biochemical suicide predictor? Arch Gen Psychiatry. 1976;33:1193–7.

    Article  CAS  PubMed  Google Scholar 

  4. Virkkunen M, Rawlings R, Tokola R, Poland RE. CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry. 1994;51:20–7.

    Article  CAS  PubMed  Google Scholar 

  5. Mann JJ, Malone KM, Sweeney JA, et al. Attempted suicide characteristics and cerebrospinal fluid amine metabolites in depressed inpatient. Neuropsychopharmacology. 1996;15:576–86.

    Article  CAS  PubMed  Google Scholar 

  6. Mann JJ, Arango V, Marzuk PM, et al. Evidence for the 5-HT hypothesis of suicide: a review of post-mortem studies. Br J Psychiatry. 1989;155:7–14.

    Article  Google Scholar 

  7. Arango V, Underwood M, Mann JJ. Biological alterations in the brainstem of suicides. In: Mann JJ, editor. Suicide, psychiatric clinics of North America. Philadelphia: WB Saunders; 1997.

    Google Scholar 

  8. Underwood MD, Mann JJ, Arango V. Serotonergic and noradrenergic neurobiology of alcoholic suicide. Alcohol Clin Exp Res. 2004;28:57s–69s.

    Article  CAS  PubMed  Google Scholar 

  9. Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Dwork AJ, Mann JJ, Arango V. Serotonin receptors and suicide, major depression, alcohol use disorder and reported early life adversity. Transl Psychiatry. 2018;8:279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Currier M, Mann JJ. Stress, genes and the biology of suicidal behavior. Psychiatr Clin North Am. 2008;31(2):247–69. https://doi.org/10.1016/j.psc.2008.01.005.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Lutz PE, Mechawar N, Turecki G. Neuropathology of suicide: recent findings and future directions. Mol Psychiatry. 2017;22:1395–412.

    Article  PubMed  Google Scholar 

  12. Ehrlich S, Breeze JL, Hesdorff er DC, et al. White matter hyperintensities and their association with suicidality in depressed young adults. J Affect Disord. 2005;86:281–7.

    Article  PubMed  Google Scholar 

  13. Pompili M, Innamorati M, Mann JJ, et al. Periventricular white matter hyperintensities as predictors of suicide attempts in bipolar disorders and unipolar depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32:1501–7.

    Article  Google Scholar 

  14. Monkul ES, Hatch JP, Nicoletti MA, et al. Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder. Mol Psychiatry. 2007;12:360–6.

    Article  CAS  PubMed  Google Scholar 

  15. Dombrovski AY, Siegle GJ, Szanto K, Clark L, Reynolds CF, Aizenstein H. The temptation of suicide: striatal gray matter, discounting of delayed rewards, and suicide attempts in late-life depression. Psychol Med. 2012;42:1203–15.

    Article  CAS  PubMed  Google Scholar 

  16. Cyprien F, Courtet P, Malafosse A, et al. Suicidal behavior is associated with reduced corpus callosum area. Biol Psychiatry. 2011;70:320–6.

    Article  PubMed  Google Scholar 

  17. Vang FJ, Ryding E, Trskman-Bendz L, van Westen D, Lindstrom MB. Size of basal ganglia in suicide attempters, and its association with temperament and serotonin transporter density. Psychiatry Res. 2010;183:177–9.

    Article  PubMed  Google Scholar 

  18. Oquendo MA, Placidi GP, Malone KM, 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. 2003;60:14–22.

    Article  PubMed  Google Scholar 

  19. Steiner J, Bielau H, Brisch R, Danos P, Ullrich O, Mawrin C, et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res. 2008;42:151–7.

    Article  PubMed  Google Scholar 

  20. Wu S, Ding Y, Wu F, **e G, Hou J, Mao P. Serum lipid levels and suicidality: a meta-analysis of 65 epidemiological studies. J Psychiatry Neurosci. 2016;41:56–69.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Deisenhammer EA, Kramer-Reinstadler K, Liensberger D, Kemmler G, Hinterhuber H, Fleischhacker WW. No evidence for an association between serum cholesterol and the course of depression and suicidality. Psychiatry Res. 2004;121:253–61.

    Article  CAS  PubMed  Google Scholar 

  22. Roy A, Roy M. No relationship between serum cholesterol and suicidal ideation and depression in African American diabetics. Arch Suicide Res. 2006;10:11–4.

    Article  PubMed  Google Scholar 

  23. Mann JJ. Neurobiology of suicidal behavior. Nat Rev Neurosci. 2003;4:819–28.

    Article  CAS  PubMed  Google Scholar 

  24. Stanley B, Michel CA, Galfalvy HC, Kelp JG, Rizk MM, Richardson-Vejlgaard R, Oquendo MA, Mann JJ. Suicidal subtypes, stress responsivity and impulsive aggression. Psychiatry Res. 2019;280:112486. https://doi.org/10.1016/j.psychres.2019.112486.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Mann JJ. A current perspective of suicide and attempted suicide. Ann Intern Med. 2002;136:302–11.

    Article  PubMed  Google Scholar 

  26. Brent DA, Melhem N. Familial Transmission of Suicidal Behavior. Psychiatr Clin North Am. 2008;31(2):157–77.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Felitti VJ, Anda RF, Nordenberg D, et al. Relationship of childhood abuse and household dysfunction to many of the leading causes of death in adults: the adverse childhood experiences (ACE) study. Am J Prev Med. 1998;14:245–58.

    Article  CAS  PubMed  Google Scholar 

  28. Merrick MT, Ford DC, Ports KA, et al. Vital signs: estimated Proportion of Adult Health Problems Attributable to Adverse Childhood Experiences and Implications for Prevention—25 States, 2015–2017. MMWR Morb Mortal Wkly Rep. 2019;68:999–1005.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Slopen N, Koenen KC, Kubzansky LD. Cumulative adversity in childhood and emergent risk factors for long-term health. J Pediatr. 2014;164:631–8.

    Article  PubMed  Google Scholar 

  30. Hughes K, Bellis MA, Hardcastle KA, et al. The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis. Lancet Public Health. 2017;2:e356–66.

    Article  PubMed  Google Scholar 

  31. Katz DA, Sprang G, Cooke C. The cost of chronic stress in childhood: understanding and applying the concept of allostatic load. Psychodyn Psychiatry. 2012;40(3):469–80.

    Article  PubMed  Google Scholar 

  32. Alfonso CA, Friedman RC, Downey JI. Advances in psychodynamic psychiatry. New York: Guilford Press; 2018.

    Google Scholar 

  33. Lagomasino IT, Stern TA. The suicidal patient. In: MGH guide to primary care psychiatry. New York: McGraw-Hill; 2004.

    Google Scholar 

  34. Yu M, Linna KA, Shinohara RT, Oathes DJ, Cook PA, Duprata R, Mooree TM, Oquendo MA, Phillips ML, McInnis M, Fava M, Trivedi MH, McGrath P, Parseyk R, Weissman MM, Sheline YI. Childhood trauma history is linked to abnormal brain connectivity in major depression. PNAS. 2019;116(17):8582–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Marshall RD, Olfson M, Hellman F, Blanco C, Guardiano M, Struering EL. Comorbidity, impairment, and suicidality in subthreshold PTSD. Am J Psychiatry. 2001;158:1467–73.

    Article  CAS  PubMed  Google Scholar 

  36. Plakun EM. What psychotherapists should understand about DNA methylation. J Psychiatr Pract. 2019;25(3):212–4.

    Article  PubMed  Google Scholar 

  37. Chambers J. The neurobiology of attachment: from infancy to clinical outcomes. Psychodyn Psychiatr. 2017;45(4):542–63.

    Article  Google Scholar 

  38. Labonte B, Turecki G. The epigenetics of suicide: explaining the biological effects of early life environmental adversity. Archiv Suicide Res. 2010;14:291–310.

    Article  Google Scholar 

  39. Bani-Fatemi A, Howe S, De Luca V. Epigenetic studies of suicidal behavior. Neurocase. 2015;21(2):134–43. https://doi.org/10.1080/13554794.2013.826679.

    Article  PubMed  Google Scholar 

  40. McGowan PO, Sasaki A, Huang TC, Unterberger A, Suderman M, Ernst C, Szyf M. Promoter wide hypermethylation of the ribosomal RNA gene promoter in the suicide brain. PLoS One. 2008;3(5):e2085.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Abdolmaleky HM, Yaqubi S, Papageorgis P, Lambert AW, Ozturk S, Sivaraman V, Thiagalingam S. Epigenetic dysregulation of 5-HTR2A in the brain of patients with schizophrenia and bipolar disorder. Schizophr Res. 2011;129(2–3):183–90.

    Article  PubMed  Google Scholar 

  42. Keller S, Sarchiapone M, Zarrilli F, Videtic A, Ferraro A, Carli V, Chiariotti L. Increased BDNF promoter methylation in the Wernicke area of suicide subjects. Archiv Gen Psychiatr. 2010;67(3):258–67.

    Article  CAS  Google Scholar 

  43. Poulter MO, et al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry. 2008;64(8):645–52.

    Article  CAS  PubMed  Google Scholar 

  44. Ernst C, Chen ES, Turecki G. Histone methylation and decreased expression of TrkB.T1 in orbital frontal cortex of suicide completers. Molecul Psychiatr. 2009;14(9):830–2.

    Article  CAS  Google Scholar 

  45. Fiori LM, Turecki G. Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers. Int J Neuropsychopharmacol. 2010;13(6):725–36.

    Article  CAS  PubMed  Google Scholar 

  46. Maussion G, Yang J, Yerko V, Barker P, Mechawar N, Ernst C, Turecki G. Regulation of a truncated form of tropomyosin-related kinase B (TrkB) by Hsa-miR-185* in frontal cortex of suicide completers. PLoS One. 2012;7(6):e39301.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Dunn EC, et al. Sensitive periods for the effect of childhood adversity on DNA methylation: results from a prospective, longitudinal study. Biol Psychiatry. 2019;85:838–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Jiménez JP, Botto A, Herrera L, Leighton C, Rossi JL, Quevedo Y, Luyten P. Psychotherapy and genetic neuroscience: an emerging dialog. Front Genet. 2018;9(257):1–19.

    Google Scholar 

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Author information

Authors and Affiliations

  1. World Psychiatric Association Psychotherapy Section, Geneva, Switzerland

    César A. Alfonso

  2. Columbia University Medical Center, New York, NY, USA

    César A. Alfonso

  3. Universitas Indonesia, Jakarta, Indonesia

    César A. Alfonso

  4. National University of Malaysia, Kuala Lumpur, Malaysia

    César A. Alfonso

  5. World Psychiatric Association Secretary for Scientific Sections, Geneva, Switzerland

    Thomas G. Schulze

  6. Institute of Psychiatric Phenomics and Genomics (IPPG), University Hospital, LMU, Munich, Germany

    Thomas G. Schulze

  7. Department of Psychiatry and Behavioral Sciences, SUNY Upstate Medical University, Syracuse, NY, USA

    Thomas G. Schulze

Authors
  1. César A. Alfonso
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  2. Thomas G. Schulze
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Correspondence to César A. Alfonso .

Editor information

Editors and Affiliations

  1. Department of Psychiatry, Columbia University Medical Center, New York, NY, USA

    César A. Alfonso

  2. Department of Psychiatry, National Institute of Mental Health, Bengaluru, India

    Prabha S. Chandra

  3. IPPG, Klinikum der Universität München, Munich, Germany

    Thomas G. Schulze

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Alfonso, C.A., Schulze, T.G. (2021). Early-Life Adversity, Suicide Risk and Epigenetics of Trauma. In: Alfonso, C.A., Chandra, P.S., Schulze, T.G. (eds) Suicide by Self-Immolation. Springer, Cham. https://doi.org/10.1007/978-3-030-62613-6_12

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  • DOI: https://doi.org/10.1007/978-3-030-62613-6_12

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  • Online ISBN: 978-3-030-62613-6

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