The role of inflammation in suicidal behaviour

Acta Psychiatrica Scandinavica

Volumn 132, Issue 3, 2015, Pages 192-203

  Brundin, L ^a,b   Erhardt, S ^c   Bryleva, E Y ^b   Achtyes, E D ^a   Postolache, T T ^d,e,f  

^a MICHIGAN STATE UNIVERSITY   (United States)

^b VAN ANDEL RESEARCH INSTITUTE   (United States)

^c KAROLINSKA INSTITUTE   (Sweden)

^d UNIVERSITY OF MARYLAND SCHOOL OF MEDICINE   (United States)

^e Mental Illness Research Education and Clinical Center   (United States)

^f MIRECC   (United States)

Author keywords

Allergy; Asthma; Autoimmunity; Cytokine; Glutamate; Infection; Inflammation; Kynurenine; Neurobiology; Neuroendocrinology; Neuroimmunology; Suicide; Traumatic brain injury

Indexed keywords

CYTOKINE; KYNURENINE; VITAMIN D;

ALLERGY; ARTICLE; ASTHMA; AUTOIMMUNITY; CLINICAL PRACTICE; DISEASE ASSOCIATION; ENVIRONMENTAL FACTOR; GENETIC PREDISPOSITION; HUMAN; INFLAMMATION; MONTGOMERY ASBERG DEPRESSION RATING SCALE; NEUROTRANSMISSION; NONHUMAN; OUTCOME ASSESSMENT; PATHOPHYSIOLOGY; PRIORITY JOURNAL; RISK FACTOR; SUICIDAL BEHAVIOR; SUICIDAL IDEATION; TRAUMATIC BRAIN INJURY; IMMUNOLOGY; PSYCHOLOGY; SUICIDE;

CYTOKINES; HUMANS; INFLAMMATION; RISK FACTORS; SUICIDAL IDEATION; SUICIDE;

EID: 84938678970     PISSN: 0001690X     EISSN: 16000447     Source Type: Journal    
DOI: 10.1111/acps.12458     Document Type: Article

References (114)

1. Mortality GBD, Causes OF, Death C. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;385:117-171.
2. World Health Organization. Preventing suicide: a global imperative. Geneva, 2014 [updated 2014; cited April 30, 2015]; Available from: http://apps.who.int/iris/bitstream/10665/131056/1/9789241564779_eng.pdf.
3. Varnik P. Suicide in the world. Int J Environ Res Public Health 2012;9:760-771.
4. Bertolote JM, Fleischmann A. Suicide and psychiatric diagnosis: a worldwide perspective. World Psychiatry 2002;1:181-185.
5. da Cruz D, Pearson A, Saini P et al. Emergency department contact prior to suicide in mental health patients. Emerg Med J 2011;28:467-471.
6. Wasserman D, Rihmer Z, Rujescu D et al. The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. Eur Psychiatry 2012;27:129-141.
7. Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry 2006;63:332-339.
8. Zarate C, Duman RS, Liu G, Sartori S, Quiroz J, Murck H. New paradigms for treatment-resistant depression. Ann N Y Acad Sci 2013;1292:21-31.
9. Fond G, Loundou A, Rabu C et al. Ketamine administration in depressive disorders: a systematic review and meta-analysis. Psychopharmacology 2014;231:3663-3676.
10. Roy A, Sarchiopone M, Carli V. Gene-environment interaction and suicidal behavior. J Psychiatr Pract 2009;15:282-288.
11. Harris EC, Barraclough B. Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry 1997;170:205-228.
12. Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry 2001;58:844-850.
13. Hawton K, van Heeringen K. Suicide. Lancet 2009;373:1372-1381.
14. Dumais A, Lesage AD, Alda 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;162:2116-2124.
15. Perroud N, Baud P, Mouthon D, Courtet P, Malafosse A. Impulsivity, aggression and suicidal behavior in unipolar and bipolar disorders. J Affect Disord 2011;134:112-118.
16. David Klonsky E, Kotov R, Bakst S, Rabinowitz J, Bromet EJ. Hopelessness as a predictor of attempted suicide among first admission patients with psychosis: a 10-year cohort study. Suicide Life Threat Behav 2012;42:1-10.
17. McGuffin P, Perroud N, Uher R et al. The genetics of affective disorder and suicide. Eur Psychiatry 2010;25:275-277.
18. Bach H, Arango V. Neuroanatomy of serotonergic abnormalities in suicide, Chapter 2. In: Dwivedi Y, ed. The neurobiological basis of suicide. Boca Raton, FL: CRC Press, 2012.
19. Mann JJ. Neurobiology of suicidal behaviour. Nat Rev Neurosci 2003;4:819-828.
20. Raison CL, Borisov AS, Broadwell SD et al. Depression during pegylated interferon-alpha plus ribavirin therapy: prevalence and prediction. J Clin Psychiatry 2005;66:41-48.
21. Raison CL, Borisov AS, Majer M et al. Activation of central nervous system inflammatory pathways by interferon-alpha: relationship to monoamines and depression. Biol Psychiatry 2009;65:296-303.
22. Raison CL, Dantzer R, Kelley KW et al. CSF concentrations of brain tryptophan and kynurenines during immune stimulation with IFN-alpha: relationship to CNS immune responses and depression. Mol Psychiatry 2010;15:393-403.
23. Dieperink E, Ho SB, Tetrick L, Thuras P, Dua K, Willenbring ML. Suicidal ideation during interferon-alpha2b and ribavirin treatment of patients with chronic hepatitis C. Gen Hosp Psychiatry 2004;26:237-240.
24. Janssen HL, Brouwer JT, van der Mast RC, Schalm SW. Suicide associated with alfa-interferon therapy for chronic viral hepatitis. J Hepatol 1994;21:241-243.
25. Fragoso YD, Frota ER, Lopes JS et al. Severe depression, suicide attempts, and ideation during the use of interferon beta by patients with multiple sclerosis. Clin Neuropharmacol 2010;33:312-316.
26. Reichenberg A, Yirmiya R, Schuld A et al. Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 2001;58:445-452.
27. Nassberger L, Traskman-Bendz L. Increased soluble interleukin-2 receptor concentrations in suicide attempters. Acta Psychiatr Scand 1993;88:48-52.
28. Steiner J, Bielau H, Brisch R et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res 2008;42:151-157.
29. Tonelli LH, Stiller J, Rujescu D et al. Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Acta Psychiatr Scand 2008;117:198-206.
30. Lindqvist D, Janelidze S, Hagell P et al. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol Psychiatry 2009;66:287-292.
31. Pandey GN, Rizavi HS, Ren X et al. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 2012;46:57-63.
32. Janelidze S, Mattei D, Westrin A, Traskman-Bendz L, Brundin L. Cytokine levels in the blood may distinguish suicide attempters from depressed patients. Brain Behav Immun 2011;25:335-339.
33. Kim YK, Lee SW, Kim SH et al. Differences in cytokines between non-suicidal patients and suicidal patients in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:356-361.
34. Falcone T, Fazio V, Lee C et al. Serum S100B: a potential biomarker for suicidality in adolescents? PLoS One 2010;5:e11089.
35. O'Donovan A, Rush G, Hoatam G et al. Suicidal ideation is associated with elevated inflammation in patients with major depressive disorder. Depress Anxiety 2013;30:307-314.
36. Black C, Miller BJ. Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol Psychiatry 2015;78:28-37.
37. Serafini G, Pompili M, Elena Seretti M et al. The role of inflammatory cytokines in suicidal behavior: a systematic review. Eur Neuropsychopharmacol 2013;23:1672-1686.
38. Le-Niculescu H, Levey DF, Ayalew M et al. Discovery and validation of blood biomarkers for suicidality. Mol Psychiatry 2013;18:1249-1264.
39. Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9:46-56.
40. Miller AH, Maletic V, Raison CL. Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009;65:732-741.
41. Borsini A, Zunszain PA, Thuret S, Pariante CM. The role of inflammatory cytokines as key modulators of neurogenesis. Trends Neurosci 2015;38:145-157.
42. Schobitz B, de Kloet ER, Sutanto W, Holsboer F. Cellular localization of interleukin 6 mRNA and interleukin 6 receptor mRNA in rat brain. Eur J Neuorsci 1993;5:1426-1435.
43. Schele E, Fekete C, Egri P et al. Interleukin-6 receptor alpha is co-localised with melanin-concentrating hormone in human and mouse hypothalamus. J Neuroendocrinol 2012;24:930-943.
44. Ericsson A, Liu C, Hart RP, Sawchenko PE. Type 1 interleukin-1 receptor in the rat brain: distribution, regulation, and relationship to sites of IL-1-induced cellular activation. J Comp Neurol 1995;361:681-698.
45. Kawasaki Y, Zhang L, Cheng JK, Ji RR. Cytokine mechanisms of central sensitization: distinct and overlapping role of interleukin-1beta, interleukin-6, and tumor necrosis factor-alpha in regulating synaptic and neuronal activity in the superficial spinal cord. J Neurosci 2008;28:5189-5194.
46. Garcia-Oscos F, Salgado H, Hall S et al. The stress-induced cytokine interleukin-6 decreases the inhibition/excitation ratio in the rat temporal cortex via trans-signaling. Biol Psychiatry 2012;71:574-582.
47. Dunn AJ. Effects of cytokines and infections on brain neurochemistry. Clin Neurosci Res 2006;6:52-68.
48. Malkesman O, Pine DS, Tragon T et al. Animal models of suicide-trait-related behaviors. Trends Pharmacol Sci 2009;30:165-173.
49. Hassanain M, Zalcman S, Bhatt S, Siegel A. Interleukin-1 beta in the hypothalamus potentiates feline defensive rage: role of serotonin-2 receptors. Neuroscience 2003;120:227-233.
50. Bhatt S, Bhatt R, Zalcman SS, Siegel A. Role of IL-1 beta and 5-HT2 receptors in midbrain periaqueductal gray (PAG) in potentiating defensive rage behavior in cat. Brain Behav Immun 2008;22:224-233.
51. Bhatt S, Siegel A. Potentiating role of interleukin 2 (IL-2) receptors in the midbrain periaqueductal gray (PAG) upon defensive rage behavior in the cat: role of neurokinin NK(1) receptors. Behav Brain Res 2006;167:251-260.
52. Patel A, Siegel A, Zalcman SS. Lack of aggression and anxiolytic-like behavior in TNF receptor (TNF-R1 and TNF-R2) deficient mice. Brain Behav Immun 2010;24:1276-1280.
53. Carroll JE, Low CA, Prather AA et al. Negative affective responses to a speech task predict changes in interleukin (IL)-6. Brain Behav Immun 2011;25:232-238.
54. Westling S, Ahren B, Traskman-Bendz L, Brundin L. Increased IL-1beta reactivity upon a glucose challenge in patients with deliberate self-harm. Acta Psychiatr Scand 2011;124:301-306.
55. Bezemer G, van Gool AR, Fekkes D et al. Psychiatric side effects and fluctuations in serotonergic parameters in the treatment of chronic hepatitis C infection. Neuropsychobiology 2012;65:126-132.
56. Lotrich FE, Ferrell RE, Rabinovitz M, Pollock BG. Labile anger during interferon alfa treatment is associated with a polymorphism in tumor necrosis factor alpha. Clin Neuropharmacol 2010;33:191-197.
57. Miller AH. Conceptual confluence: the kynurenine pathway as a common target for ketamine and the convergence of the inflammation and glutamate hypotheses of depression. Neuropsychopharmacology 2013;38:1607-1608.
58. Schwarcz R, Bruno JP, Muchowski PJ, Wu HQ. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci 2012;13:465-477.
59. Schwieler L, Larsson MK, Skogh E et al. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia-significance for activation of the kynurenine pathway. J Psychiatry Neurosci 2015;40:126-133.
60. Urata Y, Koga K, Hirota Y et al. IL-1beta increases expression of tryptophan 2, 3-dioxygenase and stimulates tryptophan catabolism in endometrioma stromal cells. Am J Reprod Immunol 2014;72:496-503.
61. Maes M, Leonard BE, Myint AM, Kubera M, Verkerk R. The new '5-HT' hypothesis of depression: cell-mediated immune activation induces indoleamine 2, 3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:702-721.
62. Asberg M, Traskman L, Thoren P. 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry 1976;33:1193-1197.
63. Leklem JE. Quantitative aspects of tryptophan metabolism in humans and other species: a review. Am J Clin Nutr 1971;24:659-672.
64. Guillemin GJ, Kerr SJ, Smythe GA et al. Kynurenine pathway metabolism in human astrocytes: a paradox for neuronal protection. J Neurochem 2001;78:842-853.
65. Stone TW. Neuropharmacology of quinolinic and kynurenic acids. Pharmacol Rev 1993;45:309-379.
66. de Carvalho LP, Bochet P, Rossier J. The endogenous agonist quinolinic acid and the non endogenous homoquinolinic acid discriminate between NMDAR2 receptor subunits. Neurochem Int 1996;28:445-452.
67. Hilmas C, Pereira EF, Alkondon M, Rassoulpour A, Schwarcz R, Albuquerque EX. The brain metabolite kynurenic acid inhibits alpha7 nicotinic receptor activity and increases non-alpha7 nicotinic receptor expression: physiopathological implications. J Neurosci 2001;21:7463-7473.
68. Guillemin GJ. Quinolinic acid, the inescapable neurotoxin. FEBS J 2012;279:1356-1365.
69. Erhardt S, Olsson SK, Engberg G. Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders. CNS Drugs 2009;23:91-101.
70. Linderholm KR, Skogh E, Olsson SK et al. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull 2012;38:426-432.
71. Sublette ME, Galfalvy HC, Fuchs D et al. Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav Immun 2011;25:1272-1278.
72. Erhardt S, Lim CK, Linderholm KR et al. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology 2013;38:743-752.
73. Bay-Richter C, Linderholm KR, Lim CK et al. A role for inflammatory metabolites as modulators of the glutamate N-methyl-D-aspartate receptor in depression and suicidality. Brain Behav Immun 2015;43:110-117.
74. Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B. Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 2007;98:143-151.
75. Dahl J, Andreassen OA, Verkerk R et al. Ongoing episode of major depressive disorder is not associated with elevated plasma levels of kynurenine pathway markers. Psychoneuroendocrinology 2015;56:12-22.
76. 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.
77. Steiner J, Walter M, Gos T et al. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission? J Neuroinflammation 2011;8:94.
78. Price RB, Nock MK, Charney DS, Mathew SJ. Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 2009;66:522-526.
79. Diazgranados N, Ibrahim LA, Brutsche NE et al. Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 2010;71:1605-1611.
80. Claes S, Myint AM, Domschke K et al. The kynurenine pathway in major depression: haplotype analysis of three related functional candidate genes. Psychiatry Res 2011;188:355-360.
81. Holt PG, Sly PD. Viral infections and atopy in asthma pathogenesis: new rationales for asthma prevention and treatment. Nat Med 2012;18:726-735.
82. Goodwin RD. Asthma and suicide: current knowledge and future directions. Curr Psychiatry Rep 2012;14:30-35.
83. Kuo CJ, Chen VC, Lee WC et al. Asthma and suicide mortality in young people: a 12-year follow-up study. Am J Psychiatry 2010;167:1092-1099.
84. Goodwin RD, Demmer RT, Galea S, Lemeshow AR, Ortega AN, Beautrais A. Asthma and suicide behaviors: results from the Third National Health and Nutrition Examination Survey (NHANES III). J Psychiatr Res 2012;46:1002-1007.
85. Christodoulou C, Douzenis A, Papadopoulos FC et al. Suicide and seasonality. Acta Psychiatr Scand 2012;125:127-146.
86. Postolache TT, Stiller JW, Herrell R et al. Tree pollen peaks are associated with increased nonviolent suicide in women. Mol Psychiatry 2005;10:232-235.
87. Woo JM, Gibbons RD, Rogers CA et al. Pollen counts and suicide rates. Association not replicated. Acta Psychiatr Scand 2012;125:168-175.
88. Qin P, Waltoft BL, Mortensen PB, Postolache TT. Suicide risk in relation to air pollen counts: a study based on data from Danish registers. BMJ Open 2013;3:e002462.
89. Woo JM, Gibbons RD, Qin P et al. Suicide and prescription rates of intranasal corticosteroids and nonsedating antihistamines for allergic rhinitis: an ecological study. J Clin Psychiatry 2011;72:1423-1428.
90. McCue RE, Charles RA, Orendain GC, Joseph MD, Abanishe JO. Vitamin D deficiency among psychiatric inpatients. Prim Care Companion CNS Disord 2012;14:pcc.11m01230.
91. Kjaergaard M, Joakimsen R, Jorde R. Low serum 25-hydroxyvitamin D levels are associated with depression in an adult Norwegian population. Psychiatry Res 2011;190:221-225.
92. Umhau JC, George DT, Heaney RP et al. Low vitamin D status and suicide: a case-control study of active duty military service members. PLoS One 2013;8:e51543.
93. Grudet C, Malm J, Westrin A, Brundin L. Suicidal patients are deficient in vitamin D, associated with a pro-inflammatory status in the blood. Psychoneuroendocrinology 2014;50:210-219.
94. Meszaros ZS, Perl A, Faraone SV. Psychiatric symptoms in systemic lupus erythematosus: a systematic review. J Clin Psychiatry 2012;73:993-1001.
95. Chwastiak L, Ehde DM, Gibbons LE, Sullivan M, Bowen JD, Kraft GH. Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample. Am J Psychiatry 2002;159:1862-1868.
96. Lauvsnes MB, Omdal R. Systemic lupus erythematosus, the brain, and anti-NR2 antibodies. J Neurol 2012;259:622-629.
97. Xie LF, Chen PL, Pan HF et al. Prevalence and correlates of suicidal ideation in SLE inpatients: Chinese experience. Rheumatol Int 2012;32:2707-2714.
98. Fredrikson S, Cheng Q, Jiang GX, Wasserman D. Elevated suicide risk among patients with multiple sclerosis in Sweden. Neuroepidemiology 2003;22:146-152.
99. Bronnum-Hansen H, Stenager E, Nylev Stenager E, Koch-Henriksen N. Suicide among Danes with multiple sclerosis. J Neurol Neurosurg Psychiatry 2005;76:1457-1459.
100. Ludvigsson JF, Sellgren C, Runeson B, Langstrom N, Lichtenstein P. Increased suicide risk in coeliac disease-a Swedish nationwide cohort study. Dig Liver Dis 2011;43:616-622.
101. Kumar A, Loane DJ. Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav Immun 2012;26:1191-1201.
102. Coughlin JM, Wang Y, Munro CA et al. Neuroinflammation and brain atrophy in former NFL players: an in vivo multimodal imaging pilot study. Neurobiol Dis 2015;74:58-65.
103. Fazel S, Wolf A, Pillas D, Lichtenstein P, Langstrom N. Suicide, fatal injuries, and other causes of premature mortality in patients with traumatic brain injury: a 41-year Swedish population study. JAMA Psychiatry 2014;71:326-333.
104. Juengst SB, Kumar RG, Arenth PM, Wagner AK. Exploratory associations with Tumor Necrosis Factor-alpha, disinhibition and suicidal endorsement after traumatic brain injury. Brain Behav Immun 2014;41:134-143.
105. Mackelprang JL, Bombardier CH, Fann JR, Temkin NR, Barber JK, Dikmen SS. Rates and predictors of suicidal ideation during the first year after traumatic brain injury. Am J Public Health 2014;104:e100-e107.
106. Heyes MP, Saito K, Crowley JS et al. Quinolinic acid and kynurenine pathway metabolism in inflammatory and non-inflammatory neurological disease. Brain 1992;115(Pt 5):1249-1273.
107. Arling TA, Yolken RH, Lapidus M et al. Toxoplasma gondii antibody titers and history of suicide attempts in patients with recurrent mood disorders. J Nerv Ment Dis 2009;197:905-908.
108. Okusaga O, Langenberg P, Sleemi A et al. Toxoplasma gondii antibody titers and history of suicide attempts in patients with schizophrenia. Schizophr Res 2011;133:150-155.
109. Zhang Y, Traskman-Bendz L, Janelidze S et al. Toxoplasma gondii immunoglobulin G antibodies and nonfatal suicidal self-directed violence. J Clin Psychiatry 2012;73:1069-1076.
110. Pedersen MG, Mortensen PB, Norgaard-Pedersen B, Postolache TT. Toxoplasma gondii infection and self-directed violence in mothers. Arch Gen Psychiatry 2012;69:1123-1130.
111. Notarangelo FM, Wilson EH, Horning KJ et al. Evaluation of kynurenine pathway metabolism in Toxoplasma gondii-infected mice: implications for schizophrenia. Schizophr Res 2014;152:261-267.
112. Gaskell EA, Smith JE, Pinney JW, Westhead DR, McConkey GA. A unique dual activity amino acid hydroxylase in Toxoplasma gondii. PLoS One 2009;4:e4801.
113. Cook TB, Brenner LA, Cloninger CR et al. 'Latent' infection with Toxoplasma gondii: association with trait aggression and impulsivity in healthy adults. J Psychiatr Res 2015;60:87-94.
114. Miller AH, Raison CL. Are anti-inflammatory therapies viable treatments for psychiatric disorders?: Where the rubber meets the road. JAMA Psychiatry. 2015;72:527-528.