Environmental Stressors May Drive Inflammation and Alter Neurocircuitry to Promote Suicidal Behavior

  • Eve K. MościckiEmail author
  • John C. Umhau
Mood Disorders (E Baca-Garcia, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Mood Disorders


Suicide morbidity and mortality are serious public health problems, accounting for over 40,000 deaths annually and over $10 billion in combined medical and work loss costs. Suicidal behavior is the outcome of a complex causal web of distal and proximal risk processes that includes a range of interacting environmental and biological determinants. We review current understanding of risk and protective factors, including recent findings on inflammatory processes, discuss recent research on environmental risks for suicidal behaviors with a focus on economic stress, and examine potential mechanisms by which external factors and internal processes such as inflammation might contribute to pathways leading to suicidal behavior. We propose a model that links changes in the default network or resting state of brain activity with corresponding changes in brain structure and function, which in turn may be influenced by diverse inflammatory mediators, and suggest a potential framework that highlights multidisciplinary opportunities for further research.


Suicidal behavior Neuroinflammation Stress fMRI Default network Unemployment 



The editors would like to thank Drs. Maria Oquendo and Michael Grunebaum for suggesting this topic and reviewing the manuscript.

Compliance with Ethical Standards

Conflict of Interest

Eve K. Mościcki and John C. Umhau declare that they have no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Centers for Disease Control and Prevention. Suicide facts at a glance 2015. National Center for Injury Prevention and Control. Accessed 6/15/2017.
  2. 2.
    Centers for Disease Control and Prevention. Suicide facts at a glance, Summer 2010. National Center for Injury Prevention and Control. Cached. Accessed 6/15/2017.
  3. 3.
    Goldsmith SK, Pellmar TC, Kleinman AM, Bunney WE, editors. Reducing suicide: a national imperative. Washington, DC: National Academies Press; 2002.Google Scholar
  4. 4.
    Mościcki EK. Suicidal behaviors in adults. In: Nock MK, editor. Oxford handbook of suicide and self-injury. New York: Oxford University Press; 2014.Google Scholar
  5. 5.
    Crosby AE, Ortega L, Melanson C. Self-directed violence surveillance: uniform definitions and recommended data elements, version 1.0. Atlanta GA: Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2011. Accessed 6/15/2017Google Scholar
  6. 6.
    Posner K, Oquendo MA, Gould M, Stanley B, Davies M. Columbia Classification Algorithm of Suicide Assessment (C-CASA): classification of suicidal events in the FDA’s pediatric suicidal risk analysis of antidepressants. Am J Psychiatry. 2007;164:1035–43.CrossRefGoogle Scholar
  7. 7.
    World Health Organization. International Statistical Classification of Diseases and Health Related Problems (The) ICD-10. 2nd ed. 2007. Accessed 6/16/2017.
  8. 8.
    Hedegaard H, Curtin SC, Warner M. Suicide mortality in the United States, 1999–2017. NCHS data brief, no 330. Hyattsville: National Center for Health Statistics; 2018.Google Scholar
  9. 9.
    Murphy SL, Xu JQ, Kochanek KD, Arias E. Mortality in the United States, 2017. NCHS data brief, no 328. Hyattsville: National Center for Health Statistics. 2018.Google Scholar
  10. 10.
    Kochanek KD, Murphy SL, Xu JQ, Tejada-Vera B. Deaths: final data for 2014. National vital statistics reports; vol 65 no 4. Hyattsville: National Center for Health Statistics; 2016.Google Scholar
  11. 11.
    Mościcki EK, O’Carroll P, Rae DS, Locke BZ, Roy A, Regier DA. Suicide attempts in the Epidemiologic Catchment Area Study. Yale J Biol Med. 1988;61:259–68.PubMedPubMedCentralGoogle Scholar
  12. 12.
    Kessler RC, Borges G, Walters EE. Prevalence of and risk factors for lifetime suicide attempts in the National Comorbidity Survey. Arch Gen Psychiatry. 1999;56:617–26.CrossRefGoogle Scholar
  13. 13.
    Kessler RC, Berglund P, Borges G, Nock M, Wang PS. Trends in suicide ideation, plans, gestures, and attempts in the United States, 1990-1992 to 2001-2003. J Am Med Assoc. 2005;293:2487–95.CrossRefGoogle Scholar
  14. 14.
    Fortuna L, Perez D, Canino G, Sribney W, Alegría M. Prevalence and correlates of lifetime suicidal ideation and suicide attempts among Latino subgroups in the United States. J Clin Psychiatry. 2007;68:572–81.CrossRefGoogle Scholar
  15. 15.
    Joe S, Baser RE, Breeden G, Neighbors HW, Jackson JS. Prevalence of and risk factors for lifetime suicide attempts among blacks in the United States. J Am Med Assoc. 2006;296:2112–23.CrossRefGoogle Scholar
  16. 16.
    Ialongo N, McCreary BK, Pearson JL, Koenig AL, Wagner BM, et al. Suicidal behavior among urban, African American young adults. Suicide Life Threat Behav. 2002;32:256–71.CrossRefGoogle Scholar
  17. 17.
    Nock MK, Kessler RC. Prevalence of and risk factors for suicide attempts versus suicide gestures: analysis of the National Comorbidity Survey. J Abnorm Psychol. 2006;115:616–23.CrossRefGoogle Scholar
  18. 18.
    Piscopo K, Lipari RN, Cooney J, Glasheen C. Suicidal thoughts and behavior among adults: NSDUH Data Review. September, 2016. Retrieved 6/6/2017 from
  19. 19.
    Petronis KR, Samuels JF, Mościcki EK, Anthony JC. An epidemiologic investigation of potential risk factors for suicide attempts. Soc Psychiatry Psychiatr Epidemiol. 1990;25:193–9.PubMedGoogle Scholar
  20. 20.
    Kuo WH, Gallo JJ, Tien AY. Incidence of suicide ideation and attempts in adults: the 13-year follow-up of a community sample in Baltimore, Maryland. Psychol Med. 2001;31:1181–91.CrossRefGoogle Scholar
  21. 21.
    Hamza CA, Stewart SL, Willoughby T. Examining the link between nonsuicidal self-injury and suicidal behavior: a review of the literature and an integrated model. Clin Psychol Rev. 2012;32:482–95.CrossRefGoogle Scholar
  22. 22.
    Whitlock J, Muehlenkamp J, Eckenrode J, Purington A, Baral Abrams G, Barreira P, et al. Nonsuicidal self-injury as a gateway to suicide in young adults. J Adolesc Health. 2013;52:486–92.CrossRefGoogle Scholar
  23. 23.
    Victor SE, Klonsky ED. Correlates of suicide attempts among self-injurers: a meta-analysis. Clin Psychol Rev. 2014;34:282–97.CrossRefGoogle Scholar
  24. 24.
    Stewart JG, Esposito EC, Glenn CR, Gilman SE, Pridgen B, Gold J, et al. Adolescent self-injurers: comparing non-ideators, suicide ideators, and suicide attempters. J Psychiatr Res. 2017;84:105–12.CrossRefGoogle Scholar
  25. 25.
    Castellvi P, Lucas-Romero E, Miranda-Mendizábala A, Parés-Badella O, et al. Longitudinal association between self-injurious thoughts and behaviors and suicidal behavior in adolescents and young adults: a systematic review with meta-analysis. J Affect Disord. 2017;215:37–48.CrossRefGoogle Scholar
  26. 26.
    Mościcki EK. Gender differences in completed and attempted suicides. Ann Epidemiol. 1994;4:152–8.CrossRefGoogle Scholar
  27. 27.
    Nock MK, Borges G, Bromet EJ, Alonso J, Angermeyer M, Beautrais A, et al. Cross-national prevalence and risk factors for suicidal ideation, plans and attempts. Br J Psychiatry. 2008;192:98–105. Scholar
  28. 28.
    Verona E, Sachs-Ericsson N, Joiner TE. Suicide attempts associated with externalizing psychopathology in an epidemiological sample. Am J Psychiatry. 2004;161:444–51.CrossRefGoogle Scholar
  29. 29.
    Weissman MM. The epidemiology of suicide attempts 1960 to 1971. Arch Gen Psychiatry. 1974;30:737–46.CrossRefGoogle Scholar
  30. 30.
    Gunnell D, Harbord R, Singleton N, Jenkins R, Lewis G. Factors influencing the development and amelioration of suicidal thoughts in the general population. Br J Psychiatry. 2004;185:385–93.CrossRefGoogle Scholar
  31. 31.
    Beautrais AL, Joyce PR, Mulder RT, et al. Prevalence and comorbidity of mental disorders in persons making serious suicide attempts: a case-control study. Am J Psychiatry. 1996;153:1009–14.CrossRefGoogle Scholar
  32. 32.
    Rhodes AE, Bethell J, Spence J, Links PS, et al. Age-sex differences in medicinal self-poisonings: a population-based study of deliberate intent and medical severity. Soc Psychiatry Psychiatr Epidemiol. 2008;43:462–652.CrossRefGoogle Scholar
  33. 33.
    Kraemer HC, Kazdin AE, Offord DR, et al. Coming to terms with the terms of risk. Arch Gen Psychiatry. 1997 Apr;54(4):337–43.CrossRefGoogle Scholar
  34. 34.
    Mościcki EK. Epidemiology of completed and attempted suicide: toward a framework for prevention. Clin Neurosci Res. 2001;1:310–23.CrossRefGoogle Scholar
  35. 35.
    Rich CL, Young D, Fowler RC. San Diego suicide study. I: Young vs old subjects. Arch Gen Psychiatry. 1986;43:577–82.CrossRefGoogle Scholar
  36. 36.
    Mann JJ, Arango VA, Avenevoli S, Brent DA, Champagne FA, Clayton P, et al. Candidate endophenotypes for genetic studies of suicidal behavior. Biol Psychiatry. 2009;65:556–63.CrossRefGoogle Scholar
  37. 37.
    Brent DA, Mann JJ. Family genetic studies, suicide, and suicidal behavior. Am J Med Gen Part C (Sem Med Genet). 2005;133C:13–24.CrossRefGoogle Scholar
  38. 38.
    Brent DA, Melhem NM. Familial transmission of suicidal behavior. Psychiatr Clin N Am. 2008;31(2):157–77.CrossRefGoogle Scholar
  39. 39.
    Gottesman II, Gould TD. The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry. 2003;160:636–45.CrossRefGoogle Scholar
  40. 40.
    • Haw C, Hawton K, Gunnell D, Platt S. Economic recession and suicidal behaviour: Possible mechanisms and ameliorating factors. Int J Social Psychiatry. 2015;61(1):73–81. Although causality cannot be demonstrated in study designs that use aggregate data, a review of findings from ecological studies in middle- and high-income countries shows consistent correlation of increase in suicide rates with occurrence of economic recession. CrossRefGoogle Scholar
  41. 41.
    Chang S-S, Stuckler D, Yip P, Gunnell D. Impact of 2008 global economic crisis on suicide: time trend study in 54 countries. BMJ. 2013;347:f5239.CrossRefGoogle Scholar
  42. 42.
    Peterson C, Stone DM, Marsh SM, Schumacher PK, Tiesman HM, McIntosh WLKW, et al. Suicide rates by major occupational group—17 states, 2012 and 2015. MMWR Morb Mortal Wkly Rep. 2018;67(45):1253–60.CrossRefGoogle Scholar
  43. 43.
    • Defina R, Hannon L. The changing relationship between unemployment and suicide. Suicide Life Threat Behav. 2015;45(2):217–29. Unemployment rates over time had a highly significant effect during the recession of the early 2000s; men and people in blue-collar jobs were particularly affected. CrossRefPubMedGoogle Scholar
  44. 44.
    Blakely TA, Collings SCD, Atkinson J. Unemployment and suicide: evidence for a causal association? J Epidemiol Community Health. 2003;57:594–600.CrossRefGoogle Scholar
  45. 45.
    Agerbo A. Effect of psychiatric illness and labour market status on suicide: a healthy worker effect? J Epidemiol Commun Health. 2005;59:598–602.CrossRefGoogle Scholar
  46. 46.
    Beautrais AL, Joyce PR, Mulder RT. Unemployment and serious suicide attempts. Psychol Med. 1998;28:209–18.CrossRefGoogle Scholar
  47. 47.
    •• Milner A, Page A, LaMontagne AD. Cause and effect in studies on unemployment, mental health and suicide: a meta-analytic and conceptual review. Psychological Med. 2014;44:909–17. A meta-analysis of five population-based cohort studies of unemployment and suicide showed that controlling for a history of mental disorders substantially reduced the relative risk between unemployment and suicide. CrossRefGoogle Scholar
  48. 48.
    Mann JJ. Neurobiology of suicidal behaviour. Nat Rev Neurosci. 2003;4:819–28.CrossRefGoogle Scholar
  49. 49.
    Oquendo MA, Galfalby H, Russo S, Ellis SP, Grunebaum MF, Burke A, et al. Prospective study of clinical predictors of suicidal acts after a major depressive episode in patients with major depressive disorder or bipolar disorder. Am Psychiatry. 2004;161:1433–41.CrossRefGoogle Scholar
  50. 50.
    Dumais A, Lesage AD, Alda M, Roleau G, Dumont M, et al. Risk factors for suicide completion in major depression: a case-control study of impulsive and aggressive behaviors in men. Am J Psychiatry. 2005;162:2116–24.CrossRefGoogle Scholar
  51. 51.
    Roy B, Dwivedi Y. Understanding epigenetic architecture of suicide neurobiology: a critical perspective. Neurosci Biobehav Rev. 2017;72:10–27.CrossRefGoogle Scholar
  52. 52.
    Melhem NM, Keilp JG, Porta G, Oquendo MA, Burke A, Stanley B, et al. Blunted HPA axis activity in suicide attempters compared to those at high risk for suicidal behavior. Neuropsychopharmacology. 2016;41(6):1447–56.Google Scholar
  53. 53.
    •• Brundin L, Erhardt S, Bryleva EY, Achtyes ED, Postolache TT. The role of inflammation in suicidal behaviour. Acta Psychiatr Scand. 2015;132:192–203. A review of studies of how inflammation might contribute to the pathophysiology of suicide identified potential biomarkers for novel therapeutic approaches. CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Johnson VE, Stewart JE, Begbie FD, Trojanowski JQ, et al. Inflammation and white matter degeneration persist for years after a single traumatic brain injury. Brain. 2013;136.1:28–42.CrossRefGoogle Scholar
  55. 55.
    Umhau JC, George DT, Heaney RP, Lewis MD, Ursano RJ, Heilig M, et al. Low vitamin D status and suicide: a case-control study of active duty military service members. PLoS One. 2013;8(1):e51543. Scholar
  56. 56.
    Grosso G, Galvano F, Marventano S, Malaguarnera M, Bucolo C, Drago F, et al. Omega-3 fatty acids and depression: scientific evidence and biological mechanisms. Oxidative Med Cell Longev. 2014;2014:1–16.CrossRefGoogle Scholar
  57. 57.
    Janelidze S, Mattei D, Westrin Å, Träskman-Bendz L, Brundin L. Cytokine levels in the blood may distinguish suicide attempters from depressed patients. Brain Behav Immun. 2011;25(2):335–9.CrossRefGoogle Scholar
  58. 58.
    Myint AM, Kim YK. Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses. 2003;61(5):519–25.CrossRefGoogle Scholar
  59. 59.
    Feinstein A. An examination of suicidal intent in patients with multiple sclerosis. Neurology. 2002;59(5):674–8.CrossRefGoogle Scholar
  60. 60.
    Rosenberg GA. Neurological diseases in relation to the blood-brain barrier. J Cereb Blood Flow Metab. 2012;32(7):1139–51.CrossRefGoogle Scholar
  61. 61.
    Yang Y, Rosenberg GA. Matrix metalloproteinases as therapeutic targets for stroke. Brain Res. 1623;2015:30–8.Google Scholar
  62. 62.
    Rosenberg GA. Matrix metalloproteinases and their multiple roles in neurodegenerative diseases. Lancet Neurol. 2009;8(2):205–16.CrossRefGoogle Scholar
  63. 63.
    • Umhau JC, Schwandt M, Solomon MG, Yuan P, et al. Cerebrospinal fluid monocyte chemoattractant protein-1 in alcoholics: support for a neuroinflammatory model of chronic alcoholism. Alcohol Clin Exp Res. 2014;38(5):1301–6. This report describes current thinking regarding the role of inflammation in alcoholism. CrossRefGoogle Scholar
  64. 64.
    •• Sudol K, Mann JJ. Biomarkers of suicide attempt behavior: towards a biological model of risk. Curr Psychiatry Rep. 2017;19(6):31. This review of recent findings on potential biomarkers for suicide risk identifies serotonergic function, inflammation, neuronal plasticity, and lipids as being the most promising. CrossRefGoogle Scholar
  65. 65.
    Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry. 2009;65(9):732–41.CrossRefGoogle Scholar
  66. 66.
    •• Rogers GB, Keating DJ, Young RL, Wong ML, et al. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016;21(6):738–48. This review provides a thoughtful overview of novel mechanisms for the development of mental illness. CrossRefGoogle Scholar
  67. 67.
    Kim Y-K, Na K-S, Myint A-M, Leonard B. The role of pro-inflammatory cytokines in neuroinflammation, neurogenesis and the neuroendocrine system in major depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2016;64:277–84.CrossRefGoogle Scholar
  68. 68.
    Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD. Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness. Psychopharmacology. 2016;233(9):1637–50.CrossRefGoogle Scholar
  69. 69.
    Serafini G, Pardini M, Pompili M, et al. Understanding suicidal behavior: the contribution of recent resting-state fMRI techniques. Front Psychiatry. 2016;7:69. Scholar
  70. 70.
    Chase HW, Segreti AM, Keller TA, Cherkassky VL, Just MA, Pan LA, et al. Alterations of functional connectivity and intrinsic activity within the cingulate cortex of suicidal ideators. J Affect Disord. 2017;212:78–85.CrossRefGoogle Scholar
  71. 71.
    Smith AJ, Blumenfeld H, Behar KL, Rothman DL, Shulman RG, Hyder F. Cerebral energetics and spiking frequency: the neurophysiological basis of fMRI. Proc Natl Acad Sci U S A. 2002;99(16):10765–70.CrossRefGoogle Scholar
  72. 72.
    Lippard ETC, Johnston JA, Blumberg HP. Neurobiological risk factors for suicide: insights from brain imaging. Am J Prev Med. 2014;47(3):S152–62.CrossRefGoogle Scholar
  73. 73.
    van Heeringen K, Bijttebier S, Desmyter S, Vervaet M, Baeken C. Is there a neuroanatomical basis of the vulnerability to suicidal behavior? A coordinate-based meta-analysis of structural and functional MRI studies. Front Hum Neurosci. 2014;8:824. Scholar
  74. 74.
    Miranda R, Valderrama J, Tsypes A, Gadol E, Gallagher M. Cognitive inflexibility and suicidal ideation: mediating role of brooding and hopelessness. Psychiatry Res. 2013;210(1):174–81.CrossRefGoogle Scholar
  75. 75.
    Scheidegger M, Walter M, Lehmann M, Metzger C, Grimm S, Boeker H, et al. Ketamine decreases resting state functional network connectivity in healthy subjects: implications for antidepressant drug action. PLoS One. 2012;7(9):e44799. Scholar
  76. 76.
    Postolache TT, Komarow H, Tonelli LH. Allergy: a risk factor for suicide? Curr Treat Options Neurol. 2008;10(5):363–76.CrossRefGoogle Scholar
  77. 77.
    Pompili M, Innamorati M, Trovarelli S, Narcisi A, et al. Psychiatric comorbidity and suicide risk in patients with psoriasis. Eur Psychiatry. 2016;33:S487–8.Google Scholar
  78. 78.
    Klemens CM, Berman DR, Mozurkewich EL. The effect of perinatal omega-3 fatty acid supplementation on inflammatory markers and allergic diseases: a systematic review. BJOG Int J Obstet Gynaecol. 2011;118(8):916–25.CrossRefGoogle Scholar
  79. 79.
    Calder PC. Marine omega-3 fatty acids and inflammatory processes: effects, mechanisms and clinical relevance. Biochim Biophys Acta. 2015;1851(4):469–84.CrossRefGoogle Scholar
  80. 80.
    • Hibbeln JR, Gow RV. The potential for military diets to reduce depression, suicide, and impulsive aggression: a review of current evidence for omega-3 and omega-6 fatty acids. Mil Med. 2014;179(11S):117–28. This review presents the background for a promising biologically based suicide prevention initiative. CrossRefGoogle Scholar
  81. 81.
    Lewis MD, Hibbeln JR, Johnson JE, Lin YH, Hyun DY, Loewke JD. Suicide deaths of active duty US military and omega-3 fatty acid status: a case control comparison. J Clin Psychiatry. 2011;72(12):1585–90.CrossRefGoogle Scholar
  82. 82.
    McNamara RK. Mitigation of inflammation-induced mood dysregulation by long-chain omega-3 fatty acids. J Am Coll Nutr. 2015;34(sup1):48–55.CrossRefGoogle Scholar
  83. 83.
    Vaz JS, Kac G, Nardi AE, Hibbeln JR. Omega-6 fatty acids and greater likelihood of suicide risk and major depression in early pregnancy. J Affect Disord. 2014;152:76–82.CrossRefGoogle Scholar
  84. 84.
    Young AJ, Marriott BP, Champagne CM, Hawes MR, et al. Blood fatty acid changes in healthy young Americans in response to a 10-week diet that increased n-3 and reduced n-6 fatty acid consumption: a randomised controlled trial. Br J Nutrition. 2017;1–13.Google Scholar
  85. 85.
    Pandey GN. Biological basis of suicide and suicidal behavior. Bipolar Disord. 2013;15(5):524–41.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.WashingtonUSA
  2. 2.Office of New Drugs, Division of Psychiatry ProductsCenter for Drug Evaluation and Research, Food and Drug AdministrationSilver SpringUSA
  3. 3.Fort Belvoir Community HospitalFort BelvoirUSA

Personalised recommendations