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Biomarkers of Suicide Attempt Behavior: Towards a Biological Model of Risk

  • Mood Disorders (MA Oquendo and MF Grunebaum, Section Editors)
  • Published:
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Abstract

Purpose of Review

The rising suicide rate in the USA will not be reversed without improved risk assessment and prevention practices. To date, the best method for clinicians to assess a patient’s risk for suicide is screening for past suicide attempts in the patient and their family. However, neuroimaging, genomic, and biochemical studies have generated a body of findings that allow description of an initial heuristic biological model for suicidal behavior that may have predictive value.

Recent Findings

We review studies from the past 3 years examining potential biological predictors of suicide attempt behavior. We divide findings into two major categories: (1) structural and functional brain imaging findings and (2) biochemical and genomic findings encompassing several systems, including major neurotransmitters (serotonin, catecholamines, GABA, and glutamate), the hypothalamic pituitary adrenal (HPA) axis, the inflammasome, lipids, and neuroplasticity.

Summary

The biomarkers that appear promising for assessing suicide risk in clinical settings include indices of serotonergic function, inflammation, neuronal plasticity, and lipids.

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References

Papers of Particular Interest, Published Recently, Have Been Highlighted as: • Of Importance •• Of Major Importance

  1. World Health Organization. Preventing suicide: A global imperative: World Health Organization; 2014. Available from: http://apps.who.int/iris/bitstream/10665/131056/1/9789241564779_eng.pdf?ua=1&ua=1.

  2. Centers for Disease Control and Prevention. Web-based injury statistics query and reporting system (WISQARS). National Center for Injury Prevention and Control, Centers for Disease Control and Prevention (2014) Retrieved from: http://www.cdc.gov/injury/wisqars/index.html.

  3. Murphy S, Kochanek K, Xu J, Arias E. Mortality in the United States, 2014. NCHS data brief, no 229. Hyattsville, MD: National Center for Health Statistics; 2015.

  4. Centers for Disease Control and Prevention. Suicide: Facts at a Glance 2015. May 28, 2016. Available from: http://www.cdc.gov/violenceprevention/pdf/suicide-datasheet-a.pdf.

  5. • Oquendo MA, Sullivan GM, Sudol K, Baca-Garcia E, Stanley BH, Sublette ME, et al. Toward a biosignature for suicide. Am J Psychiatry. 2014;171(12):1259–77. A review of literature examining biomarkers associated with death by suicide

    Article  PubMed  PubMed Central  Google Scholar 

  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(7):1035–43.

  7. Busch KA, Fawcett J, Jacobs DG. Clinical correlates of inpatient suicide. J Clin Psychiatry. 2003;64(1):14–9.

    Article  PubMed  Google Scholar 

  8. Aguilar EJ, Garcia-Marti G, Marti-Bonmati L, Lull JJ, Moratal D, Escarti MJ, et al. Left orbitofrontal and superior temporal gyrus structural changes associated to suicidal behavior in patients with schizophrenia. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32(7):1673–6.

    Article  CAS  Google Scholar 

  9. Benedetti F, Radaelli D, Poletti S, Locatelli C, Falini A, Colombo C, et al. Opposite effects of suicidality and lithium on gray matter volumes in bipolar depression. J Affect Disord. 2011;135(1–3):139–47.

    Article  CAS  PubMed  Google Scholar 

  10. Hwang JP, Lee TW, Tsai SJ, Chen TJ, Yang CH, Lirng JF, et al. Cortical and subcortical abnormalities in late-onset depression with history of suicide attempts investigated with MRI and voxel-based morphometry. J Geriatr Psychiatry Neurol. 2010;23(3):171–84.

    Article  PubMed  Google Scholar 

  11. 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(6):1203–15.

    Article  CAS  PubMed  Google Scholar 

  12. Soloff PH, Pruitt P, Sharma M, Radwan J, White R, Diwadkar VA. Structural brain abnormalities and suicidal behavior in borderline personality disorder. J Psychiatr Res. 2012;46(4):516–25.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Rusch N, Spoletini I, Wilke M, Martinotti G, Bria P, Trequattrini A, et al. Inferior frontal white matter volume and suicidality in schizophrenia. Psychiatry Res. 2008;164(3):206–14.

    Article  PubMed  Google Scholar 

  14. Cyprien F, Courtet P, Malafosse A, Maller J, Meslin C, Bonafe A, et al. Suicidal behavior is associated with reduced corpus callosum area. Biol Psychiatry. 2011;70(4):320–6.

    Article  PubMed  Google Scholar 

  15. Spoletini I, Piras F, Fagioli S, Rubino IA, Martinotti G, Siracusano A, et al. Suicidal attempts and increased right amygdala volume in schizophrenia. Schizophr Res. 2011;125(1):30–40.

    Article  PubMed  Google Scholar 

  16. Monkul ES, Hatch JP, Nicoletti MA, Spence S, Brambilla P, Lacerda AL, et al. Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder. Mol Psychiatry. 2007;12(4):360–6.

    Article  CAS  PubMed  Google Scholar 

  17. Ahearn EP, Jamison KR, Steffens DC, Cassidy F, Provenzale JM, Lehman A, et al. MRI correlates of suicide attempt history in unipolar depression. Biol Psychiatry. 2001;50(4):266–70.

    Article  CAS  PubMed  Google Scholar 

  18. Ehrlich S, Breeze JL, Hesdorffer DC, Noam GG, Hong X, Alban RL, et al. White matter hyperintensities and their association with suicidality in depressed young adults. J Affect Disord. 2005;86(2–3):281–7.

    Article  PubMed  Google Scholar 

  19. Ehrlich S, Noam GG, Lyoo IK, Kwon BJ, Clark MA, Renshaw PF. White matter hyperintensities and their associations with suicidality in psychiatrically hospitalized children and adolescents. J Am Acad Child Adolesc Psychiatry. 2004;43(6):770–6.

    Article  PubMed  Google Scholar 

  20. Pompili M, Ehrlich S, De Pisa E, Mann JJ, Innamorati M, Cittadini A, et al. White matter hyperintensities and their associations with suicidality in patients with major affective disorders. Eur Arch Psychiatry Clin Neurosci. 2007;257(8):494–9.

    Article  PubMed  Google Scholar 

  21. Pompili M, Innamorati M, Mann JJ, Oquendo MA, Lester D, Del Casale A, et al. Periventricular white matter hyperintensities as predictors of suicide attempts in bipolar disorders and unipolar depression. Prog Neuro-Psychopharmacol Biol Psychiatry. 2008;32(6):1501–7.

    Article  Google Scholar 

  22. Pan LA, Ramos L, Segreti A, Brent DA, Phillips ML. Right superior temporal gyrus volume in adolescents with a history of suicide attempt. Br J Psychiatry. 2015;206(4):339–40.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Lee YJ, Kim S, Gwak AR, Kim SJ, Kang S-G, Na K-S, et al. Decreased regional gray matter volume in suicide attempters compared to suicide non-attempters with major depressive disorders. Compr Psychiatry. 2016;67:59–65.

    Article  PubMed  Google Scholar 

  24. Peng H, Wu K, Li J, Qi H, Guo S, Chi M, et al. Increased suicide attempts in young depressed patients with abnormal temporal-parietal-limbic gray matter volume. J Affect Disord. 2014;165:69–73.

    Article  PubMed  Google Scholar 

  25. Colle R, Chupin M, Cury C, Vandendrie C, Gressier F, Hardy P, et al. Depressed suicide attempters have smaller hippocampus than depressed patients without suicide attempts. J Psychiatr Res. 2015;61:13–8.

    Article  PubMed  Google Scholar 

  26. Ding Y, Lawrence N, Olie E, Cyprien F, le Bars E, Bonafe A, et al. Prefrontal cortex markers of suicidal vulnerability in mood disorders: a model-based structural neuroimaging study with a translational perspective. Transl Psychiatry. 2015;5(2):e516.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Giakoumatos CI, Tandon N, Shah J, Mathew IT, Brady RO, Clementz BA, et al. Are structural brain abnormalities associated with suicidal behavior in patients with psychotic disorders? J Psychiatr Res. 2013;47(10):1389–95.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Besteher B, Wagner G, Koch K, Schachtzabel C, Reichenbach JR, Schlosser R, et al. Pronounced prefronto-temporal cortical thinning in schizophrenia: neuroanatomical correlate of suicidal behavior? Schizophr Res. 2016;176(2):151–7.

    Article  PubMed  Google Scholar 

  29. Gifuni AJ, Ding Y, Olié E, Lawrence N, Cyprien F, Le Bars E, et al. Subcortical nuclei volumes in suicidal behavior: nucleus accumbens may modulate the lethality of acts. Brain Imaging Behav. 2016;10(1):96–104.

    Article  PubMed  Google Scholar 

  30. Soloff P, White R, Diwadkar VA. Impulsivity, aggression and brain structure in high and low lethality suicide attempters with borderline personality disorder. Psychiatry Res. 2014;222(3):131–9.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lijffijt M, Rourke ED, Swann AC, Zunta-Soares GB, Soares JC. Illness-course modulates suicidality-related prefrontal gray matter reduction in women with bipolar disorder. Acta Psychiatr Scand. 2014;130(5):374–87.

    Article  CAS  PubMed  Google Scholar 

  32. Mahon K, Burdick KE, Wu J, Ardekani BA, Szeszko PR. Relationship between suicidality and impulsivity in bipolar I disorder: a diffusion tensor imaging study. Bipolar Disord. 2012;14(1):80–9.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Jia Z, Huang X, Wu Q, Zhang T, Lui S, Zhang J, et al. High-field magnetic resonance imaging of suicidality in patients with major depressive disorder. Am J Psychiatry. 2010;167(11):1381–90.

    Article  PubMed  Google Scholar 

  34. • Olvet DM, Peruzzo D, Thapa-Chhetry B, Sublette ME, Sullivan GM, Oquendo MA, et al. A diffusion tensor imaging study of suicide attempters. J Psychiatr Res. 2014;51:60–7. This imaging study of brain white matter tracts identified the dorsomedial PFC as a potential region of interest for understanding the diathesis of suicidal behavior

    Article  PubMed  PubMed Central  Google Scholar 

  35. • Jia Z, Wang Y, Huang X, Kuang W, Wu Q, Lui S, et al. Impaired frontothalamic circuitry in suicidal patients with depression revealed by diffusion tensor imaging at 3.0 T. J Psychiatry Neurosci. 2014;39(3):170–7. This imaging study of brain white matter tracts found abnormalities in the frontothalamic pathways of depressed patients and that these abnormalities are more pronounced in suicide attemtpers compared to non-attempters

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cyprien F, de Champfleur NM, Deverdun J, Olie E, Le Bars E, Bonafe A, et al. Corpus Callosum integrity is affected by mood disorders and also by the suicide attempt history: a diffusion tensor imaging study. J Affect Disord. 2016;206:115–24.

    Article  PubMed  Google Scholar 

  37. Kim B, Oh J, Kim MK, Lee S, Tae WS, Kim CM, et al. White matter alterations are associated with suicide attempt in patients with panic disorder. J Affect Disord. 2015;175:139–46.

    Article  PubMed  Google Scholar 

  38. Lee SJ, Kim B, Oh D, Kim MK, Kim KH, Bang SY, et al. White matter alterations associated with suicide in patients with schizophrenia or schizophreniform disorder. Psychiatry Res. 2016;248:23–9.

    Article  PubMed  Google Scholar 

  39. • Sachs-Ericsson N, Hames JL, Joiner TE, Corsentino E, Rushing NC, Palmer E, et al. Differences between suicide attempters and nonattempters in depressed older patients: depression severity, white-matter lesions, and cognitive functioning. Am J Geriatr Psychiatry. 2014;22(1):75–85. This study showed that white matter lesions differentiated older depressed suicide attempters from non-attempters

    Article  PubMed  Google Scholar 

  40. Jollant F, Lawrence NS, Giampietro V, Brammer MJ, Fullana MA, Drapier D, et al. Orbitofrontal cortex response to angry faces in men with histories of suicide attempts. Am J Psychiatry. 2008;165(6):740–8.

    Article  PubMed  Google Scholar 

  41. Jollant F, Lawrence NS, Olie E, O'Daly O, Malafosse A, Courtet P, et al. Decreased activation of lateral orbitofrontal cortex during risky choices under uncertainty is associated with disadvantageous decision-making and suicidal behavior. NeuroImage. 2010;51(3):1275–81.

    Article  PubMed  Google Scholar 

  42. Pan LA, Batezati-Alves SC, Almeida JR, Segreti A, Akkal D, Hassel S, et al. Dissociable patterns of neural activity during response inhibition in depressed adolescents with and without suicidal behavior. J Am Acad Child Adolesc Psychiatry. 2011;50(6):602–11.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Olie E, Ding Y, Le Bars E, de Champfleur NM, Mura T, Bonafe A, et al. Processing of decision-making and social threat in patients with history of suicidal attempt: a neuroimaging replication study. Psychiatry Res. 2015;234(3):369–77.

    Article  PubMed  Google Scholar 

  44. Pan L, Segreti A, Almeida J, Jollant F, Lawrence N, Brent D, et al. Preserved hippocampal function during learning in the context of risk in adolescent suicide attempt. Psychiatry Res. 2013;211(2):112–8.

    Article  PubMed  Google Scholar 

  45. Pan LA, Hassel S, Segreti AM, Nau SA, Brent DA, Phillips ML. Differential patterns of activity and functional connectivity in emotion processing neural circuitry to angry and happy faces in adolescents with and without suicide attempt. Psychol Med. 2013;43(10):2129–42.

    Article  CAS  PubMed  Google Scholar 

  46. Dombrovski AY, Szanto K, Clark L, Reynolds CF, Siegle GJ. Reward signals, attempted suicide, and impulsivity in late-life depression. JAMA Psychiatry. 2013;70(10):1020–30.

    Article  Google Scholar 

  47. Vanyukov PM, Szanto K, Siegle GJ, Hallquist MN, Reynolds 3rd CF, Aizenstein HJ, et al. Impulsive traits and unplanned suicide attempts predict exaggerated prefrontal response to angry faces in the elderly. Am J Geriatr Psychiatry. 2015;23(8):829–39.

    Article  PubMed  Google Scholar 

  48. Vanyukov PM, Szanto K, Hallquist MN, Siegle GJ, Reynolds 3rd CF, Forman SD, et al. Paralimbic and lateral prefrontal encoding of reward value during intertemporal choice in attempted suicide. Psychol Med. 2016;46(2):381–91.

    Article  CAS  PubMed  Google Scholar 

  49. Richard-Devantoy S, Ding Y, Lepage M, Turecki G, Jollant F. Cognitive inhibition in depression and suicidal behavior: a neuroimaging study. Psychol Med. 2016;46(5):933–44.

    Article  CAS  PubMed  Google Scholar 

  50. Cannon DM, Ichise M, Fromm SJ, Nugent AC, Rollis D, Gandhi SK, et al. Serotonin transporter binding in bipolar disorder assessed using [11C]DASB and positron emission tomography. Biol Psychiatry. 2006;60(3):207–17.

    Article  CAS  PubMed  Google Scholar 

  51. Oquendo MA, Placidi GP, Malone KM, Campbell C, Keilp J, Brodsky B, 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(1):14–22.

    Article  PubMed  Google Scholar 

  52. Miller JM, Hesselgrave N, Ogden RT, Sullivan GM, Oquendo MA, Mann JJ, et al. Positron emission tomography quantification of serotonin transporter in suicide attempters with major depressive disorder. Biol Psychiatry. 2013;74(4):287–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Yeh Y-W, Ho P-S, Chen C-Y, Kuo S-C, Liang C-S, Ma K-H, et al. Incongruent reduction of serotonin transporter associated with suicide attempts in patients with major depressive disorder: a positron emission tomography study with 4-[18F]-ADAM. Int J Neuropsychopharmacol. 2015;18(3):pyu065.

    Article  PubMed Central  Google Scholar 

  54. Nye JA, Purselle D, Plisson C, Voll RJ, Stehouwer JS, Votaw JR, et al. Decreased brainstem and putamen SERT binding potential in depressed suicide attempters using [11C]-zient PET imaging. Depress Anxiety. 2013;30(10):902–7.

    CAS  PubMed  Google Scholar 

  55. Sublette ME, Milak MS, Galfalvy HC, Oquendo MA, Malone KM, Mann JJ. Regional brain glucose uptake distinguishes suicide attempters from non-attempters in major depression. Arch Suicide Res. 2013;17(4):434–47.

    Article  PubMed  Google Scholar 

  56. Sullivan GM, Oquendo MA, Milak M, Miller JM, Burke A, Ogden RT, et al. Positron emission tomography quantification of serotonin(1A) receptor binding in suicide attempters with major depressive disorder. JAMA Psychiatry. 2015;72(2):169–78.

    Article  PubMed  PubMed Central  Google Scholar 

  57. • Oquendo MA, Galfalvy H, Sullivan GM, Miller JM, Milak MM, Sublette ME, et al. Positron emission tomographic imaging of the serotonergic system and prediction of risk and lethality of future suicidal behavior. JAMA Psychiatry. 2016;73(10):1048–55. This longitudinal prospective observational study of moderately depressed patients showed that higher serotonin 1A autoreceptor binding, which results in less serotonin being released, predicted more severe suicidal ideation up to one year after the brain scan and the lethality of suicide attempts up to two years following the brain scan .

    Article  PubMed  Google Scholar 

  58. Currier D, Mann JJ. Stress, genes and the biology of suicidal behavior. Psychiatr Clin North Am. 2008;31(2):247–69.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Keilp JG, Stanley BH, Beers SR, Melhem NM, Burke AK, Cooper TB, et al. Further evidence of low baseline cortisol levels in suicide attempters. J Affect Disord. 2016;190:187–92.

    Article  CAS  PubMed  Google Scholar 

  60. • 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. This study was able to distinguish suicide attempters from individuals with suicide-related behaviors (but no attempts) using indices of HPA-axis activity. Other studies have reported that HPA axis abnormalities also predict risk of dying by suicide

    Article  PubMed  Google Scholar 

  61. Chatzittofis A, Nordstrom P, Hellstrom C, Arver S, Asberg M, Jokinen J. CSF 5-HIAA, cortisol and DHEAS levels in suicide attempters. Eur Neuropsychopharmacol. 2013;23(10):1280–7.

    Article  CAS  PubMed  Google Scholar 

  62. Yin H, Galfalvy H, Pantazatos SP, Huang YY, Rosoklija GB, Dwork AJ, et al. Glucocorticoid receptor-related genes: genotype and brain gene expression relationships to suicide and major depressive disorder. Depress Anxiety. 2016;33(6):531–40.

    Article  CAS  PubMed  Google Scholar 

  63. Brent D, Melhem N, Ferrell R, Emslie G, Wagner KD, Ryan N, et al. Association of FKBP5 polymorphisms with suicidal events in the treatment of resistant depression in adolescents (TORDIA) study. Am J Psychiatry. 2009;167(2):190–7.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Roy A, Gorodetsky E, Yuan Q, Goldman D, Enoch MA. Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology. 2010;35(8):1674–83.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Roy A, Hodgkinson CA, DeLuca V, Goldman D, Enoch MA. Two HPA axis genes, CRHBP and FKBP5, interact with childhood trauma to increase the risk for suicidal behavior. J Psychiatr Res. 2012;46(1):72–9.

    Article  PubMed  Google Scholar 

  66. Willour VL, Chen H, Toolan J, Belmonte P, Cutler DJ, Goes FS, et al. Family-based association of FKBP5 in bipolar disorder. Mol Psychiatry. 2009;14(3):261–8.

    Article  CAS  PubMed  Google Scholar 

  67. Mann JJ. The serotonergic system in mood disorders and suicidal behaviour. Philos Trans R Soc Lond Ser B Biol Sci. 2013;368(1615):20120537.

    Article  Google Scholar 

  68. Karanovic J, Ivkovic M, Jovanovic VM, Pantovic M, Pavlovic-Jankovic N, Damjanovic A, et al. Tryptophan hydroxylase 1 variant rs1800532 is associated with suicide attempt in Serbian psychiatric patients but does not moderate the effect of recent stressful life events. Suicide Life Threat Behav. 2016;46(6):664–8.

    Article  PubMed  Google Scholar 

  69. Lopez-Narvaez ML, Tovilla-Zarate CA, Gonzalez-Castro TB, Juarez-Rojop I, Pool-Garcia S, Genis A, et al. Association analysis of TPH-1 and TPH-2 genes with suicidal behavior in patients with attempted suicide in Mexican population. Compr Psychiatry. 2015;61:72–7.

    Article  PubMed  Google Scholar 

  70. Zhang Y, Chang Z, Chen J, Ling Y, Liu X, Feng Z, et al. Methylation of the tryptophan hydroxylase2 gene is associated with mRNA expression in patients with major depression with suicide attempts. Mol Med Rep. 2015;12(2):3184–90.

    CAS  PubMed  Google Scholar 

  71. Donaldson ZR, le Francois B, Santos TL, Almli LM, Boldrini M, Champagne FA, et al. The functional serotonin 1a receptor promoter polymorphism, rs6295, is associated with psychiatric illness and differences in transcription. Transl Psychiatry. 2016;6(3):e746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Karanovic J, Svikovic S, Pantovic M, Durica S, Brajuskovic G, Damjanovic A, et al. Joint effect of ADARB1 gene, HTR2C gene and stressful life events on suicide attempt risk in patients with major psychiatric disorders. World J Biol Psychiatry. 2015;16(4):261–71.

    Article  PubMed  Google Scholar 

  73. • Perroud N, Zewdie S, Stenz L, Adouan W, Bavamian S, Prada P, et al. Methylation of serotonin receptor 3a in ADHD, borderline personality, and bipolar disorders: link with severity of the disorders and childhood maltreatment. Depress Anxiety. 2016;33(1):45–55. This study shows a link between early childhood maltreatment, epigenetic changes in the serotonin receptor 3A, and suicidal behavior

    Article  CAS  PubMed  Google Scholar 

  74. Benedetti F, Riccaboni R, Poletti S, Radaelli D, Locatelli C, Lorenzi C, et al. The serotonin transporter genotype modulates the relationship between early stress and adult suicidality in bipolar disorder. Bipolar Disord. 2014;16(8):857–66.

    Article  PubMed  Google Scholar 

  75. Enoch MA, Hodgkinson CA, Gorodetsky E, Goldman D, Roy A. Independent effects of 5′ and 3′ functional variants in the serotonin transporter gene on suicidal behavior in the context of childhood trauma. J Psychiatr Res. 2013;47(7):900–7.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Lee HY, Hong JP, Hwang JA, Lee HJ, Yoon HK, Lee BH, et al. Possible association between serotonin transporter gene polymorphism and suicide behavior in major depressive disorder. Psychiatry Investig. 2015;12(1):136–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kim DH, Park YM. The association between suicidality and serotonergic dysfunction in depressed patients. J Affect Disord. 2013;148(1):72–6.

    Article  CAS  PubMed  Google Scholar 

  78. Hu J, Chan LF, Souza RP, Tampakeras M, Kennedy JL, Zai C, et al. The role of tyrosine hydroxylase gene variants in suicide attempt in schizophrenia. Neurosci Lett. 2014;559:39–43.

    Article  CAS  PubMed  Google Scholar 

  79. Kim YK, Hwang JA, Lee HJ, Yoon HK, Ko YH, Lee BH, et al. Association between norepinephrine transporter gene (SLC6A2) polymorphisms and suicide in patients with major depressive disorder. J Affect Disord. 2014;158:127–32.

    Article  CAS  PubMed  Google Scholar 

  80. Zai CC, Manchia M, Sonderby IE, Yilmaz Z, De Luca V, Tiwari AK, et al. Investigation of the genetic interaction between BDNF and DRD3 genes in suicidical behaviour in psychiatric disorders. World J Biol Psychiatry. 2015;16(3):171–9.

    Article  PubMed  Google Scholar 

  81. Sokolowski M, Ben-Efraim YJ, Wasserman J, Wasserman D. Glutamatergic GRIN2B and polyaminergic ODC1 genes in suicide attempts: associations and gene-environment interactions with childhood/adolescent physical assault. Mol Psychiatry. 2013;18(9):985–92.

    Article  CAS  PubMed  Google Scholar 

  82. Mann JJ, Oquendo MA, Watson KT, Boldrini M, Malone KM, Ellis SP, et al. Anxiety in major depression and cerebrospinal fluid free gamma-aminobutyric acid. Depress Anxiety. 2014;31(10):814–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Yin H, Pantazatos SP, Galfalvy H, Huang YY, Rosoklija GB, Dwork AJ, et al. A pilot integrative genomics study of GABA and glutamate neurotransmitter systems in suicide, suicidal behavior, and major depressive disorder. Am J Med Genet B Neuropsychiatr Genet. 2016;171B(3):414–26.

    Article  PubMed  CAS  Google Scholar 

  84. Zai CC, Zai GC, Tiwari AK, Manchia M, de Luca V, Shaikh SA, et al. Association study of GABRG2 polymorphisms with suicidal behaviour in schizophrenia patients with alcohol use disorder. Neuropsychobiology. 2014;69(3):154–8.

    Article  CAS  PubMed  Google Scholar 

  85. •• Black C, Miller BJ. Meta-analysis of cytokines and chemokines in suicidality: distinguishing suicidal versus nonsuicidal patients. Biol Psychiatry. 2015;78(1):28–37. This meta-analysis showed that certain cytokines may distinguish suicidal patients from nonsuicidal patients across different diagnoses

    Article  CAS  PubMed  Google Scholar 

  86. •• Gananca L, Oquendo MA, Tyrka AR, Cisneros-Trujillo S, Mann JJ, Sublette ME. The role of cytokines in the pathophysiology of suicidal behavior. Psychoneuroendocrinology. 2016;63:296–310. An extensive meta-analysis of the role of cytokines in suicidal behavior

    Article  CAS  PubMed  Google Scholar 

  87. Serafini G, Pompili M, Elena Seretti M, Stefani H, Palermo M, Coryell W, et al. The role of inflammatory cytokines in suicidal behavior: a systematic review. Eur Neuropsychopharmacol. 2013;23(12):1672–86.

    Article  CAS  PubMed  Google Scholar 

  88. •• Bay-Richter C, Linderholm KR, Lim CK, Samuelsson M, Traskman-Bendz L, Guillemin GJ, 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;43:110–7. This study provides longitudinal data demonstrating increased inflammation and abnormal functioning of the kynurenine pathway in the brain of suicide attempters

    Article  CAS  PubMed  Google Scholar 

  89. Erhardt S, Lim CK, Linderholm KR, Janelidze S, Lindqvist D, Samuelsson M, et al. Connecting inflammation with glutamate agonism in suicidality. Neuropsychopharmacology. 2013;38(5):743–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Brundin L, Sellgren CM, Lim CK, Grit J, Palsson E, Landen M, et al. An enzyme in the kynurenine pathway that governs vulnerability to suicidal behavior by regulating excitotoxicity and neuroinflammation. Transl Psychiatry. 2016;6(8):e865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Bradley KA, Case JA, Khan O, Ricart T, Hanna A, Alonso CM, et al. The role of the kynurenine pathway in suicidality in adolescent major depressive disorder. Psychiatry Res. 2015;227(2–3):206–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Isung J, Aeinehband S, Mobarrez F, Nordstrom P, Runeson B, Asberg M, et al. High interleukin-6 and impulsivity: determining the role of endophenotypes in attempted suicide. Transl Psychiatry. 2014;4:e470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Gibbs HM, Davis L, Han X, Clothier J, Eads LA, Caceda R. Association between C-reactive protein and suicidal behavior in an adult inpatient population. J Psychiatr Res. 2016;79:28–33.

    Article  PubMed  Google Scholar 

  94. Courtet P, Jaussent I, Genty C, Dupuy AM, Guillaume S, Ducasse D, et al. Increased CRP levels may be a trait marker of suicidal attempt. Eur Neuropsychopharmacol. 2015;25(10):1824–31.

    Article  CAS  PubMed  Google Scholar 

  95. Ventorp F, Gustafsson A, Traskman-Bendz L, Westrin A, Ljunggren L. Increased soluble urokinase-type plasminogen activator receptor (suPAR) levels in plasma of suicide attempters. PLoS One. 2015;10(10):e0140052.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. Vargas HO, Nunes SO, Pizzo de Castro M, Bortolasci CC, Sabbatini Barbosa D, Kaminami Morimoto H, et al. Oxidative stress and lowered total antioxidant status are associated with a history of suicide attempts. J Affect Disord. 2013;150(3):923–30.

    Article  PubMed  CAS  Google Scholar 

  97. Kim YK, Hong JP, Hwang JA, Lee HJ, Yoon HK, Lee BH, et al. TNF-alpha -308G>a polymorphism is associated with suicide attempts in major depressive disorder. J Affect Disord. 2013;150(2):668–72.

    Article  CAS  PubMed  Google Scholar 

  98. •• Wu S, Ding Y, Wu F, Xie G, Hou J, Mao P. Serum lipid levels and suicidality: a meta-analysis of 65 epidemiological studies. J Psychiatry Neurosci. 2016;41(1):56–69. A meta-analysis emcomassing a large sample, examining the association between suicidal behavior and serum lipid levels .

    Article  PubMed  PubMed Central  Google Scholar 

  99. da Graca CM, Nardin P, Buffon A, Eidt MC, Antonio Godoy L, Fernandes BS, et al. Serum triglycerides, but not cholesterol or leptin, are decreased in suicide attempters with mood disorders. J Affect Disord. 2015;172:403–9.

    Article  CAS  Google Scholar 

  100. Baek JH, Kang ES, Fava M, Mischoulon D, Nierenberg AA, Yu BH, et al. Serum lipids, recent suicide attempt and recent suicide status in patients with major depressive disorder. Prog Neuro-Psychopharmacol Biol Psychiatry. 2014;51:113–8.

    Article  CAS  Google Scholar 

  101. Papadopoulou A, Markianos M, Christodoulou C, Lykouras L. Plasma total cholesterol in psychiatric patients after a suicide attempt and in follow-up. J Affect Disord. 2013;148(2–3):440–3.

    Article  CAS  PubMed  Google Scholar 

  102. Sublette ME, Hibbeln JR, Galfalvy H, Oquendo MA, Mann JJ. Omega-3 polyunsaturated essential fatty acid status as a predictor of future suicide risk. Am J Psychiatry. 2006;163(6):1100–2.

    Article  PubMed  Google Scholar 

  103. Asellus P, Nordstrom P, Nordstrom AL, Jokinen J. Plasma apolipoprotein E and severity of suicidal behaviour. J Affect Disord. 2016;190:137–42.

    Article  CAS  PubMed  Google Scholar 

  104. Beier AM, Lauritzen L, Galfalvy HC, Cooper TB, Oquendo MA, Grunebaum MF, et al. Low plasma eicosapentaenoic acid levels are associated with elevated trait aggression and impulsivity in major depressive disorder with a history of comorbid substance use disorder. J Psychiatr Res. 2014;57:133–40.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Haghighi F, Galfalvy H, Chen S, Huang YY, Cooper TB, Burke AK, et al. DNA methylation perturbations in genes involved in polyunsaturated fatty acid biosynthesis associated with depression and suicide risk. Front Neurol. 2015;6:92.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Sublette ME, Vaquero C, Baca-Garcia E, Pachano G, Huang YY, Oquendo MA, et al. Lack of association of SNPs from the FADS1-FADS2 gene cluster with major depression or suicidal behavior. Psychiatr Genet. 2016;26(2):81–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Perera S, Eisen RB, Dennis BB, Bawor M, Bhatt M, Bhatnagar N, et al. Body mass index is an important predictor for suicide: results from a systematic review and meta-analysis. Suicide Life Threat Behav. 2016;46(6):697–736.

    Article  PubMed  Google Scholar 

  108. Klinitzke G, Steinig J, Bluher M, Kersting A, Wagner B. Obesity and suicide risk in adults--a systematic review. J Affect Disord. 2013;145(3):277–84.

    Article  CAS  PubMed  Google Scholar 

  109. Bhatti JA, Nathens AB, Thiruchelvam D, Grantcharov T, Goldstein BI, Redelmeier DA. Self-harm emergencies after bariatric surgery: a population-based cohort study. JAMA Surg. 2016;151(3):226–32.

    Article  PubMed  Google Scholar 

  110. Kovacs Z, Valentin JB, Nielsen RE. Risk of psychiatric disorders, self-harm behaviour and service use associated with bariatric surgery. Acta Psychiatr Scand. 2017;135(2):149–58.

    Article  CAS  PubMed  Google Scholar 

  111. Huang EJ, Reichardt LF. Neurotrophins: roles in neuronal development and function. Annu Rev Neurosci. 2001;24:677–736.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  112. Dwivedi Y. Brain-derived neurotrophic factor in suicide pathophysiology. In: Dwivedi Y, editor. The neurobiological basis of suicide. Frontiers in neuroscience. 1st ed. Boca Raton, FL: CRC Press; 2012. p. 139–58.

    Chapter  Google Scholar 

  113. Bresin K, Sima Finy M, Verona E. Childhood emotional environment and self-injurious behaviors: the moderating role of the BDNF Val66Met polymorphism. J Affect Disord. 2013;150(2):594–600.

    Article  CAS  PubMed  Google Scholar 

  114. Gonzalez-Castro TB, Nicolini H, Lanzagorta N, Lopez-Narvaez L, Genis A, Pool Garcia S, et al. The role of brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism in bipolar disorder: a case-control study, comorbidities, and meta-analysis of 16,786 subjects. Bipolar Disord. 2015;17(1):27–38.

    Article  CAS  PubMed  Google Scholar 

  115. Kang HJ, Kim JM, Lee JY, Kim SY, Bae KY, Kim SW, et al. BDNF promoter methylation and suicidal behavior in depressive patients. J Affect Disord. 2013;151(2):679–85.

    Article  CAS  PubMed  Google Scholar 

  116. Grah M, Mihanovic M, Ruljancic N, Restek-Petrovic B, Molnar S, Jelavic S. Brain-derived neurotrophic factor as a suicide factor in mental disorders. Acta Neuropsychiatr. 2014;26(6):356–63.

    Article  PubMed  Google Scholar 

  117. Eisen RB, Perera S, Bawor M, Dennis BB, El-Sheikh W, DeJesus J, et al. Exploring the association between serum BDNF and attempted suicide. Sci Rep. 2016;6:25229.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by NIMH PHS grant P50MH090964.

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Authors and Affiliations

  1. Frank H. Netter MD School of Medicine, Quinnipiac University, 370 Bassett Road, North Haven, CT, 06473, USA

    Katherin Sudol

  2. Department of Psychiatry, Columbia University College of Physicians and Surgeons, Molecular Imaging and Neuropathology Division, New York State Psychiatric Institute, 1051 Riverside Drive, Box 42, New York, NY, 10032, USA

    J. John Mann

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  1. Katherin Sudol
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Correspondence to J. John Mann.

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Katherin Sudol declares that she has no conflict of interest.

J. John Mann has received royalties from the Research Foundation for Mental Hygiene for commercial use of the C-SSRS.

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This article is part of the Topical Collection on Mood Disorders

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Sudol, K., Mann, J.J. Biomarkers of Suicide Attempt Behavior: Towards a Biological Model of Risk. Curr Psychiatry Rep 19, 31 (2017). https://doi.org/10.1007/s11920-017-0781-y

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