Skip to main content

Advertisement

SpringerLink
Log in

Interaction effect between childhood abuse and interleukin-1β levels on suicidality in depressed patients

  • Original Paper
  • Published:
European Archives of Psychiatry and Clinical Neuroscience Aims and scope Submit manuscript

Abstract

Introduction

The roles of childhood abuse and interleukin (IL)-1β levels, a representative pro-inflammatory cytokine, in suicidal behavior are unclear. This study investigated the main and interactive effects of childhood abuse and IL-1β levels on suicidal behavior in patients with a depressive disorder before and after pharmacological treatment.

Methods

At baseline, exposure to self-reported childhood abuse, including emotional, physical, and sexual abuse, before the age of 16 years, and IL-1β levels, were measured in 1,094 outpatients with a depressive disorder, 884 of whom were followed for 1 year. Suicidal behavior was evaluated, including previous suicide attempts (at baseline), suicidal ideation (at baseline and follow-up), and fatal/non-fatal suicide attempts (at follow-up). The main and interaction effects of self-reported childhood abuse and IL-1β level on the four types of suicidal behavior were analyzed using logistic regression after adjusting for covariates.

Results

Individual associations of self-reported childhood abuse were significant only with previous suicidal attempt but not with other suicidal behaviors. There was no significant association of plasma IL-1β level with any suicidal behavior. There were significant interactive associations of self-reported childhood abuse and a high IL-1β level on previous suicide attempts, baseline suicidal ideation, and fatal/non-fatal suicidal attempts during follow-up.

Conclusion

Suicidal behavior in patients with a depressive disorder could be influenced by considering the interactive effect of childhood abuse and IL-1β levels. Our study suggests that childhood trauma and biochemical factors play roles in the pathology of suicide in depressed patients.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Patel V, Flisher AJ, Hetrick S, McGorry P (2007) Mental health of young people: a global public-health challenge. Lancet 369:1302–1313

    Article  PubMed  Google Scholar 

  2. Organization for Economic Co-operation and Development. OECD health data 2019. https://data.oecd.org/healthstat/suicide-rates.htm (Accessed on Dec 2020)

  3. Phillips MR, Yang G, Zhang Y, Wang L, Ji H, Zhou M (2002) Risk factors for suicide in China: a national case-control psychological autopsy study. Lancet 360:1728–1736

    Article  PubMed  Google Scholar 

  4. Sokero TP, Melartin TK, Rytsälä HJ, Leskelä US, Lestelä-Mielonen PS, Isometsä ET (2003) Suicidal ideation and attempts among psychiatric patients with major depressive disorder. J Clin Psychiatry 64:1094–1100

    Article  PubMed  Google Scholar 

  5. de Mattos D, Souza L, Lopez Molina M, Azevedo da Silva R, Jansen K (2016) History of childhood trauma as risk factors to suicide risk in major depression. Psychiatry Res 246:612–616

    Article  Google Scholar 

  6. Goldberg X, Serra-Blasco M, Vicent-Gil M, Aguilar E, Ros L, Arias B, Courtet P, Palao D, Cardoner N (2019) Childhood maltreatment and risk for suicide attempts in major depression: a sex-specific approach. Eur J Psychotraumatol 10:1603557

    Article  PubMed  PubMed Central  Google Scholar 

  7. Nelson J, Klumparendt A, Doebler P, Ehring T (2017) Childhood maltreatment and characteristics of adult depression: meta-analysis. Br J Psychiatry 210:96–104

    Article  PubMed  Google Scholar 

  8. De Bellis MD, Zisk A (2014) The biological effects of childhood trauma. Child Adolesc Psychiatr Clin N Am 23:185–222

    Article  PubMed  PubMed Central  Google Scholar 

  9. Tafet GE, Nemeroff CB (2015) The links between stress and depression: psychoneuroendocrinological, genetic, and environmental interactions. J Neuropsychiatry Clin Neurosci 28:77–88

    Article  PubMed  Google Scholar 

  10. Schiweck C, Claes S, Van Oudenhove L, Lafit G, Vaessen T, de Beeck GO, Berghmans R, Wijkhuijs A, Müller N, Arolt V, Drexhage H, Vrieze E (2020) Childhood trauma, suicide risk and inflammatory phenotypes of depression: insights from monocyte gene expression. Transl Psychiatry 10:296

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chu AL, Hickman M, Steel N, Jones PB, Davey Smith G, Khandaker GM (2021) Inflammation and depression: a public health perspective. Brain Behav Immun 95:1–3

    Article  PubMed  Google Scholar 

  12. Farooq RK, Asghar K, Kanwal S, Zulqernain A (2017) Role of inflammatory cytokines in depression: Focus on interleukin-1β. Biomed Rep 6:15–20

    Article  CAS  PubMed  Google Scholar 

  13. Benedetti F, Poletti S, Vai B, Mazza MG, Lorenzi C, Brioschi S, Aggio V, Branchi I, Colombo C, Furlan R, Zanardi R (2021) Higher baseline interleukin-1beta and TNF-alpha hamper antidepressant response in major depressive disorder. Eur Neuropsychopharmacol 42:35–44

    Article  CAS  PubMed  Google Scholar 

  14. Ellul P, Boyer L, Groc L, Leboyer M, Fond G (2016) Interleukin-1 β-targeted treatment strategies in inflammatory depression: toward personalized care. Acta Psychiatr Scand 134:469–484

    Article  CAS  PubMed  Google Scholar 

  15. Kosuge A, Kunisawa K, Arai S, Sugawara Y, Shinohara K, Iida T, Wulaer B, Kawai T, Fujigaki H, Yamamoto Y, Saito K, Nabeshima T, Mouri A (2021) Heat-sterilized Bifidobacterium breve prevents depression-like behavior and interleukin-1beta expression in mice exposed to chronic social defeat stress. Brain Behav Immun. https://doi.org/10.1016/j.bbi.2021.05.028

    Article  PubMed  Google Scholar 

  16. Pandey GN, Rizavi HS, Zhang H, Bhaumik R, Ren X (2018) Abnormal protein and mRNA expression of inflammatory cytokines in the prefrontal cortex of depressed individuals who died by suicide. J Psychiatry Neurosci 43:376–385

    Article  PubMed  PubMed Central  Google Scholar 

  17. Ganança L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME (2016) The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology 63:296–310

    Article  PubMed  Google Scholar 

  18. Marini S, Vellante F, Matarazzo I, De Berardis D, Serroni N, Gianfelice D, Olivieri L, Di Renzo F, Di Marco A, Fornaro M, Orsolini L, Valchera A, Iasevoli F, Mazza M, Perna G, Martinotti G, Di Giannantonio M (2016) Inflammatory markers and suicidal attempts in depressed patients: a review. Int J Immunopathol Pharmacol 29:583–594

    Article  PubMed  PubMed Central  Google Scholar 

  19. Ganança L, Galfalvy HC, Cisneros-Trujillo S, Basseda Z, Cooper TB, Ren X, Figueira ML, Oquendo MA, Mann JJ, Sublette ME (2021) Relationships between inflammatory markers and suicide risk status in major depression. J Psychiatr Res 134:192–199

    Article  PubMed  Google Scholar 

  20. Kang HJ, Kim JW, Kim SY, Kim SW, Shin HY, Shin MG, Kim JM (2018) The MAKE biomarker discovery for enhancing antidepressant treatment effect and response (MAKE BETTER) study: design and methodology. Psychiatry Investig 15:538–545

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sheehan DV (1998) The mini-international neuropsychiatric interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59:22–33

    PubMed  Google Scholar 

  22. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Press Inc, Washington DC

    Google Scholar 

  23. Hamilton MA (1960) Rating scale for depression. J Neurol Neurosurg Psychiatry 23:56–62

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. De Graaf R, Bijl RV, Smit F, Vollebergh WA, Spijker J (2002) Risk factors for 12-month comorbidity of mood, anxiety, and substance use disorders: findings from the Netherlands mental health survey and incidence study. Am J Psychiatry 159:620–629

    Article  PubMed  Google Scholar 

  25. Hovens JGFM, Wiersma JE, Giltay EJ, van Oppen P, Spinhoven P, Penninx BW, Zitman FG (2010) Childhood life events and childhood trauma in adult patients with depressive, anxiety and comorbid disorders vs. controls. Acta Psychiatr Scand 122:66–74

    Article  CAS  PubMed  Google Scholar 

  26. Zigmond AS, Snaith RP (1983) The hospital anxiety and depression scale. Acta Psychiatr Scand 67:361–370

    Article  CAS  PubMed  Google Scholar 

  27. Saunders JB, Aasland OG, Babor TF, de la Fuente JR, Grant M (1993) Development of the alcohol use disorders indentification test (AUDIT): WHO collaborative project on early detection of persons with harmful alcohol consumption 1. Addiction 88:791–804

    Article  CAS  PubMed  Google Scholar 

  28. Kim JM, Stewart R, Kang HJ, Kim JW, Lee HJ, Jhon M, Lee JY, Kim SW, Shin IS (2020) Short and long-term treatment outcomes of stepwise psychopharmacotherapy based on early clinical decision in patients with depressive disorders. J Affect Disord 274:315–325

    Article  PubMed  Google Scholar 

  29. Anderson IM, Ferrier IN, Baldwin RC, Cowen PJ, Howard L, Lewis G, Matthews K, McAllister-Williams RH, Peveler RC, Scott J, Tylee A (2008) Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2000 british association for psychopharmacology guidelines. J Psychopharmacol 22:343–396

    Article  CAS  PubMed  Google Scholar 

  30. Bauer M, Pfennig A, Severus E, Whybrow PC, Angst J, Möller HJ; World Federation of Societies of Biological Psychiatry. Task Force on Unipolar Depressive Disorders (2013) World Federation of Societies of Biological Psychiatry (WFSBP) Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders. World J Biol Psychiatry 14:334–385

  31. Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Müller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R; CANMAT Depression Work Group (2016) Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry 61:540–560

  32. Malhi GS, Bassett D, Boyce P, Bryant R, Fitzgerald PB, Fritz K, Hopwood M, Lyndon B, Mulder R, Murray G, Porter R, Singh AB (2015) Royal Australian and New Zealand college of psychiatrists clinical practice guidelines for mood disorders. Aust N Z J Psychiatry 49:1087–1206

    Article  PubMed  Google Scholar 

  33. Swift JK, Callahan JL (2009) The impact of client treatment preferences on outcome: a meta-analysis. J Clin Psychol 65:368–381

    Article  PubMed  Google Scholar 

  34. Posner K, Oquendo MA, Gould M, Stanley B, Davies M (2007) 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 164:1035–1043

    Article  PubMed  PubMed Central  Google Scholar 

  35. Overall JE, Gorham DR (1962) The brief psychiatric rating scale. Psychol Rep 10:799–812

    Article  Google Scholar 

  36. Jackson AM, Deye K (2015) Aspects of abuse: consequences of childhood victimization. Curr Probl Pediatr Adolesc Health Care 45:86–93

    Article  PubMed  Google Scholar 

  37. Salloum A, Johnco C, Zepeda-Burgos RM, Cepeda SL, Guttfreund D, Novoa JC, Schneider SC, Lastra A, Hurtado A, Katz C, Storch EA (2019) Parents’ knowledge, attitudes, and experiences in child sexual abuse prevention in EL Salvador. Child Psychiatry Hum Dev 51:343–354

    Article  Google Scholar 

  38. LeCroy CW, Milligan-LeCroy S (2020) Public perceptions of child maltreatment: a national convenience sample. Child Youth Serv Rev 119:105677

    Article  Google Scholar 

  39. Liu J, Fang Y, Gong J, Cui X, Meng T, Xiao B, He Y, Shen Y, Luo X (2017) Associations between suicidal behavior and childhood abuse and neglect: a meta-analysis. J Affect Disord 220:147–155

    Article  PubMed  Google Scholar 

  40. Brown GR, McBride L, Bauer MS, Williford WO.; Cooperative Studies Program 430 Study Team (2005) Impact of childhood abuse on the course of bipolar disorder: a replication study in U.S. veterans. J Affect Disord 89:57–67

  41. Rabinovitch SM, Kerr DC, Leve LD, Chamberlain P (2015) Suicidal behavior outcomes of childhood sexual abuse: longitudinal study of adjudicated girls. Suicide Life Threat Behav 45:431–447

    Article  PubMed  Google Scholar 

  42. Williams LM, Debattista C, Duchemin AM, Schatzberg AF, Nemeroff CB (2016) Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression. Transl Psychiatry 6:e799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Asarnow JR, Emslie G, Clarke G, Wagner KD, Spirito A, Vitiello B, Iyengar S, Shamseddeen W, Ritz L, Birmaher B, Ryan N, Kennard B, Mayes T, DeBar L, McCracken J, Strober M, Suddath R, Leonard H, Porta G, Keller M, Brent D (2009) Treatment of selective serotonin reuptake inhibitor-resistant depression in adolescents: predictors and moderators of treatment response. J Am Acad Child Adolesc Psychiatry 48:330–339

    PubMed  PubMed Central  Google Scholar 

  44. Lewis CC, Simons AD, Nguyen LJ, Murakami JL, Reid MW, Silva SG, March JS (2010) Impact of childhood trauma on treatment outcome in the Treatment for Adolescents with Depression Study (TADS). J Am Acad Child Adolesc Psychiatry 49:132–140

    PubMed  Google Scholar 

  45. Schiweck C, Valles-Colomer M, Arolt V, Müller N, Raes J, Wijkhuijs A, Claes S, Drexhage H, Vrieze E (2020) Depression and suicidality: A link to premature T helper cell aging and increased Th17 cells. Brain Behav Immun 87:603–609

    Article  CAS  PubMed  Google Scholar 

  46. Black C, Miller BJ (2015) Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol Psychiatry 78:28–37

    Article  CAS  PubMed  Google Scholar 

  47. Martinez JM, Garakani A, Yehuda R, Gorman JM (2012) Proinflammatory and “resiliency” proteins in the CSF of patients with major depression. Depress Anxiety 29:32–38

    Article  CAS  PubMed  Google Scholar 

  48. Pandey GN, Rizavi HS, Ren X, Fareed J, Hoppensteadt DA, Roberts RC, Conley RR, Dwivedi Y (2012) Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 46:57–63

    Article  PubMed  Google Scholar 

  49. Levine J, Barak Y, Chengappa KN, Rapoport A, Rebey M, Barak V (1999) Cerebrospinal cytokine levels in patients with acute depression. Neuropsychobiology 40:171–176

    Article  CAS  PubMed  Google Scholar 

  50. Coryell W, Wilcox H, Evans SJ, Pandey GN, Jones-Brando L, Dickerson F, Yolken R (2018) Aggression, impulsivity and inflammatory markers as risk factors for suicidal behavior. J Psychiatr Res 106:38–42

    Article  PubMed  Google Scholar 

  51. Lu J, Li S, Li H, Mou T, Zhou L, Huang B, Huang M, Xu Y (2019) Changes in plasma NPY, IL-1β and hypocretin in people who died by suicide. Neuropsychiatric Dis Treat 15:2893–2900

    Article  CAS  Google Scholar 

  52. Angelakis I, Gillespie EL, Panagioti M (2019) Childhood maltreatment and adult suicidality: a comprehensive systemic review with meta-analysis. Psychol Med 49:107–1078

    Article  Google Scholar 

  53. Renna ME, Peng J, Shrout MR, Madison AA, Andridge R, Alfano CM, Povoski SP, Lipari AM, Malarkey WB, Kiecolt-Glaser JK (2021) Childhood abuse histories predict steeper inflammatory trajectories across time. Brain Behav Immun 91:541–545

    Article  CAS  PubMed  Google Scholar 

  54. O’Brien SM, Scott LV, Dinan TG (2004) Cytokines: abnormalities in major depression and implications for pharmacological treatment. Hum Psychopharmacol 19:397–403

    Article  PubMed  Google Scholar 

  55. Pirnia B, Khosravani V, Maleki F, Kalbasi R, Pirnia K, Malekanmehr P, Zahiroddin A (2020) The role of childhood maltreatment in cortisol in the hypothalamic-pituitary-adrenal (HPA) axis in methamphetamine-dependent individuals with and without depression comorbidity and suicide attempts. J Affect Disord 263:274–281

    Article  CAS  PubMed  Google Scholar 

  56. Träskman-Bendz L, Alling C, Oreland L, Regnéll G, Vinge E, Ohman R (1992) Prediction of suicidal behavior from biologic tests. J Clin Psychopharmacol 12:21S-26S

    PubMed  Google Scholar 

  57. Placidi GP, Oquendo MA, Malone KM, Huang YY, Ellis SP, Mann JJ (2001) Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels. Biol Psychiatry 50:783–791

    Article  CAS  PubMed  Google Scholar 

  58. O’Connor DB, Branley-Bell D, Green JA, Ferguson E, O’Carroll RE, O’Connor RC (2020) Effects of childhood trauma, daily stress, and emotions on daily cortisol levels in individuals vulnerable to suicide. J Abnorm Psychol 129:92–107

    Article  PubMed  Google Scholar 

  59. Alia-Klein N, Goldstein RZ, Kriplani A, Logan J, Tomasi D, Williams B, Telang F, Shumay E, Biegon A, Craig IW, Henn F, Wang GJ, Volkow ND, Fowler JS (2008) Brain monoamine oxidase A activity predicts trait aggression. J Neurosci 28:5099–5104

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Mello MF, Mello AF, Ruiz JE, Fiks JP, Andreoli SB, Bressan RA, Costa MCP, Mari JJ, Suchecki D, Juruena M (2013) The effect of comorbid depression and sexual abuse during childhood on glucocorticoid and mineralocorticoid receptor sensitivity of patients with post-traumatic stress disorder. J Depress Anxiety S 4:004

    Google Scholar 

  61. Heim CM, Mayberg HS, Mletzko T, Nemeroff CB, Pruessner JC (2013) Decreased cortical representation of genital somatosensory field after childhood sexual abuse. Am J Psychiatry 170:616–623

    Article  PubMed  Google Scholar 

  62. Wang AK, Miller BJ (2018) Meta-analysis of cerebrospinal fluid cytokine and tryptophan catabolite alterations in psychiatric patients: comparisons between schizophrenia, bipolar disorder, and depression. Schizophr Bull 44:75–83

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The study was funded by a grant of National Research Foundation of Korea Grant [NRF-2020R1A2C2003472 and NRF-2020M3E5D9080733] to Jae-Min Kim.

Author information

Authors and Affiliations

  1. Department of Psychiatry, Chonnam National University Medical School, 160 Baekseoro, 12 Dong-gu, Gwangju, 61469, Republic of Korea

    Ju-Yeon Lee, Min Jhon, Ju-Wan Kim, Hee-Ju Kang, Sung-Wan Kim, Il-Seon Shin & Jae-Min Kim

  2. Department of Pediatrics, Chonnam National University Children’s Hospital and Medical School, Gwangju, Korea

    Hwa Jin Cho

  3. Department of Emergency Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea

    Byeong Jo Chun

Authors
  1. Ju-Yeon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Min Jhon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ju-Wan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hee-Ju Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Sung-Wan Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Il-Seon Shin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hwa Jin Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Byeong Jo Chun
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Jae-Min Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JMK, and JYJ were involved in the conception and design of the study. JMK, JYJ, MJ, JWK, HJK, SWK, and ISS were responsible for the acquisition of data. JMK, JYJ, and SWK, were involved in the analysis and interpretation of data. JYJ and JMK drafted the manuscript. MJ, JWK, HJK, SWK, ISS, HJC, and BJC revised the manuscript critically for important intellectual content. JMK and JYJ performed the statistical analysis. JWK, HJK, SWK, and ISS contributed to administrative, technical, or material support. SWK, ISS, and HJC supervised the study. All authors read and approved the final paper.

Corresponding author

Correspondence to Jae-Min Kim.

Ethics declarations

Conflict of interest

Prof. Jae-Min Kim declares research support in the last 5 years from Janssen and Lundbeck. Sung-Wan Kim declares research support in the last 5 years from Janssen, Boehringer Ingelheim, Allergan, and Otsuka.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (DOCX 1210 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, JY., Jhon, M., Kim, JW. et al. Interaction effect between childhood abuse and interleukin-1β levels on suicidality in depressed patients. Eur Arch Psychiatry Clin Neurosci 272, 1535–1546 (2022). https://doi.org/10.1007/s00406-022-01408-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00406-022-01408-6

Keywords

Search

Navigation