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An overview of the neurobiology of suicidal behaviors as one meta-system

Molecular Psychiatry volume 20, pages 56–71 (2015)Cite this article

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Abstract

Suicidal behaviors (SB) may be regarded as the outmost consequence of mental illnesses, or as a distinct entity per se. Regardless, the consequences of SB are very large to both society and affected individuals. The path leading to SB is clearly a complex one involving interactions between the subject’s biology and environmental influences throughout life. With the aim to generate a representative and diversified overview of the different neurobiological components hypothesized or shown implicated across the entire SB field up to date by any approach, we selected and compiled a list of 212 gene symbols from the literature. An increasing number of novel gene (products) have been introduced as candidates, with half being implicated in SB in only the last 4 years. These candidates represent different neurosystems and functions and might therefore be regarded as competing or redundant explanations. We then adopted a unifying approach by treating them all as parts of the same meta-system, using bioinformatic tools. We present a network of all components connected by physical protein–protein interactions (the SB interactome). We proceeded by exploring the differences between the highly connected core (~30% of the candidate genes) and its peripheral parts, observing more functional homogeneity at the core, with multiple signal transduction pathways and actin-interacting proteins connecting a subset of receptors in nerve cell compartments as well as development/morphology phenotypes and the stress-sensitive synaptic plasticity processes of long term potentiation/depression. We suggest that SB neurobiology might also be viewed as one meta-system and perhaps be explained as intrinsic unbalances acting within the core or as imbalances arising between core and specific peripheral components.

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References

  1. Isometsa ET, Lonnqvist JK . Suicide attempts preceding completed suicide. Br J Psychiatry 1998; 173: 531–535.

    Article  CAS  PubMed  Google Scholar 

  2. 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: 1035–1043.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Wasserman D, Rihmer Z, Rujescu D, Sarchiapone M, Sokolowski M, Titelman D et al. The European Psychiatric Association (EPA) guidance on suicide treatment and prevention. Eur Psychiatry 2012; 27: 129–141.

    Article  CAS  PubMed  Google Scholar 

  4. Carli V, Mandelli L, Zaninotto L, Iosue M, Hadlaczky G, Wasserman D et al. Serious suicidal behaviors: socio-demographic and clinical features in a multinational, multicenter sample. Nord J Psychiatry 2014; 68: 44–52.

    Article  PubMed  Google Scholar 

  5. Mann JJ . A current perspective of suicide and attempted suicide. Ann Intern Med 2002; 136: 302–311.

    Article  PubMed  Google Scholar 

  6. Baca-Garcia E, Perez-Rodriguez MM, Oquendo MA, Keyes KM, Hasin DS, Grant BF et al. Estimating risk for suicide attempt: are we asking the right questions? Passive suicidal ideation as a marker for suicidal behavior. J Affect Disord 2011; 134: 327–332.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Dwivedi Y (ed) The Neurobiological Basis of Suicide. CRC Press: Boca Raton, FL, USA, 2012.

  8. Wasserman D, Wasserman C (eds) Oxford Textbook of Suicidology – The Five Continents Perspective. Oxford University Press: Oxford, UK, 2009.

  9. Robins E, Murphy GE, Wilkinson RH Jr, Gassner S, Kayes J . Some clinical considerations in the prevention of suicide based on a study of 134 successful suicides. Am J Public Health Nations Health 1959; 49: 888–899.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Harris EC, Barraclough B . Suicide as an outcome for mental disorders. A meta-analysis. Br J Psychiatry 1997; 170: 205–228.

    Article  CAS  PubMed  Google Scholar 

  11. Asberg M, Traskman L, Thoren P . 5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor? Arch Gen Psychiatry 1976; 33: 1193–1197.

    Article  CAS  PubMed  Google Scholar 

  12. Goldston DB, Daniel S, Reboussin DM, Kelley A, Ievers C, Brunstetter R . First-time suicide attempters, repeat attempters, and previous attempters on an adolescent inpatient psychiatry unit. J Am Acad Child Adolesc Psychiatry 1996; 35: 631–639.

    Article  CAS  PubMed  Google Scholar 

  13. Nock MK, Hwang I, Sampson N, Kessler RC, Angermeyer M, Beautrais A et al. Cross-national analysis of the associations among mental disorders and suicidal behavior: findings from the WHO World Mental Health Surveys. PLoS Med 2009; 6: e1000123.

    Article  PubMed  PubMed Central  Google Scholar 

  14. 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: 556–563.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brent D . What family studies teach us about suicidal behavior: implications for research, treatment, and prevention. Eur Psychiatry 2010; 25: 260–263.

    Article  CAS  PubMed  Google Scholar 

  16. Courtet P, Gottesman II, Jollant F, Gould TD . The neuroscience of suicidal behaviors: what can we expect from endophenotype strategies? Transl Psychiatry 2011; 1: e7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Schumann G, Binder EB, Holte A, de Kloet ER, Oedegaard KJ, Robbins TW et al. Stratified medicine for mental disorders. Eur Neuropsychopharmacol 2014; 24: 5–50.

    Article  CAS  PubMed  Google Scholar 

  18. Richard-Devantoy S, Berlim MT, Jollant F . A meta-analysis of neuropsychological markers of vulnerability to suicidal behavior in mood disorders. Psychol Med 2013; 1–11.

  19. Keilp JG, Gorlyn M, Russell M, Oquendo MA, Burke AK, Harkavy-Friedman J et al. Neuropsychological function and suicidal behavior: attention control, memory and executive dysfunction in suicide attempt. Psychol Med 2013; 43: 539–551.

    Article  CAS  PubMed  Google Scholar 

  20. Bunney WE Jr, Fawcett JA . Possibility of a biochemical test for suicidal potential: an analysis of endocrine findings prior to three suicides. Arch Gen Psychiatry 1965; 13: 232–239.

    Article  CAS  PubMed  Google Scholar 

  21. Brezo J, Klempan T, Turecki G . The genetics of suicide: a critical review of molecular studies. Psychiatr Clin North Am 2008; 31: 179–203.

    Article  PubMed  Google Scholar 

  22. Bogdan R, Hyde LW, Hariri AR . A neurogenetics approach to understanding individual differences in brain, behavior, and risk for psychopathology. Mol Psychiatry 2013; 18: 288–299.

    Article  CAS  PubMed  Google Scholar 

  23. Mann JJ, Arango V . Integration of neurobiology and psychopathology in a unified model of suicidal behavior. J Clin Psychopharmacol 1992; 12 (Suppl 2): 2S–7S.

    CAS  PubMed  Google Scholar 

  24. Carballo JJ, Akamnonu CP, Oquendo MA . Neurobiology of suicidal behavior. An integration of biological and clinical findings. Arch Suicide Res 2008; 12: 93–110.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Turecki G, Ernst C, Jollant F, Labonte B, Mechawar N . The neurodevelopmental origins of suicidal behavior. Trends Neurosci 2012; 35: 14–23.

    Article  CAS  PubMed  Google Scholar 

  26. Wasserman D, Wasserman J, Sokolowski M . Genetics of HPA-axis, depression and suicidality. Eur Psychiatry 2010; 25: 278–280.

    Article  CAS  PubMed  Google Scholar 

  27. Mann JJ, Currier DM . Stress, genetics and epigenetic effects on the neurobiology of suicidal behavior and depression. Eur Psychiatry 2010; 25: 268–271.

    Article  CAS  PubMed  Google Scholar 

  28. Brent DA, Melhem N . Familial transmission of suicidal behavior. Psychiat Clin North Am 2008; 31: 157–177.

    Article  Google Scholar 

  29. Voracek M, Loibl LM . Genetics of suicide: a systematic review of twin studies. Wien Klin Wochenschr 2007; 119: 463–475.

    Article  CAS  PubMed  Google Scholar 

  30. Vineis P, Pearce NE . Genome-wide association studies may be misinterpreted: genes versus heritability. Carcinogenesis 2011; 32: 1295–1298.

    Article  CAS  PubMed  Google Scholar 

  31. Kendler KS . Decision making in the pathway from genes to psychiatric and substance use disorders. Mol Psychiatry 2013; 18: 640–645.

    Article  CAS  PubMed  Google Scholar 

  32. Fiori LM, Turecki G . Broadening our horizons: gene expression profiling to help better understand the neurobiology of suicide and depression. Neurobiol Dis 2012; 45: 14–22.

    Article  PubMed  Google Scholar 

  33. Rujescu D, Giegling I . The genetics of neurosystems in mental ill-health and suicidality: beyond serotonin. Eur Psychiatry 2010; 25: 272–274.

    Article  CAS  PubMed  Google Scholar 

  34. Wasserman D, Sokolowski M, Wasserman J, Rujescu D . Neurobiology and genetics of suicide. In: Wasserman D, Wasserman C (eds), Oxford Textbook of Suicidology – The Five Continents Perspective. Oxford University Press: Oxford, UK, 2009, pp 165–182.

    Chapter  Google Scholar 

  35. Antypa N, Serretti A, Rujescu D . Serotonergic genes and suicide: a systematic review. Eur Neuropsychopharmacol 2013; 23: 1125–1142.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  37. 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: 1672–1686.

    Article  CAS  PubMed  Google Scholar 

  38. Serafini G, Pompili M, Lindqvist D, Dwivedi Y, Girardi P . The role of neuropeptides in suicidal behavior: a systematic review. Biomed Res Int 2013; 2013: 687575.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Zhurov V, Stead JD, Merali Z, Palkovits M, Faludi G, Schild-Poulter C et al. Molecular pathway reconstruction and analysis of disturbed gene expression in depressed individuals who died by suicide. PLoS One 2012; 7: e47581.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Klempan TA, Sequeira A, Canetti L, Lalovic A, Ernst C, ffrench-Mullen J et al. Altered expression of genes involved in ATP biosynthesis and GABAergic neurotransmission in the ventral prefrontal cortex of suicides with and without major depression. Mol Psychiatry 2009; 14: 175–189.

    Article  CAS  PubMed  Google Scholar 

  41. Kim S, Choi KH, Baykiz AF, Gershenfeld HK . Suicide candidate genes associated with bipolar disorder and schizophrenia: an exploratory gene expression profiling analysis of post-mortem prefrontal cortex. BMC Genomics 2007; 8: 413.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Thalmeier A, Dickmann M, Giegling I, Schneider B, M Hartmann A, Maurer K et al. Gene expression profiling of post-mortem orbitofrontal cortex in violent suicide victims. Int J Neuropsychopharmacol 2008; 11: 217–228.

    Article  CAS  PubMed  Google Scholar 

  43. Fiori LM, Bureau A, Labbe A, Croteau J, Noel S, Merette C et al. Global gene expression profiling of the polyamine system in suicide completers. Int J Neuropsychopharmacol 2011; 14: 595–605.

    Article  CAS  PubMed  Google Scholar 

  44. Sequeira A, Klempan T, Canetti L, ffrench-Mullen J, Benkelfat C, Rouleau GA et al. Patterns of gene expression in the limbic system of suicides with and without major depression. Mol Psychiatry 2007; 12: 640–655.

    Article  CAS  PubMed  Google Scholar 

  45. Sequeira A, Mamdani F, Ernst C, Vawter MP, Bunney WE, Lebel V et al. Global brain gene expression analysis links glutamatergic and GABAergic alterations to suicide and major depression. PLoS One 2009; 4: e6585.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Le-Niculescu H, Levey DF, Ayalew M, Palmer L, Gavrin LM, Jain N et al. Discovery and validation of blood biomarkers for suicidality. Mol Psychiatry 2013; 18: 1249–1264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Kekesi KA, Juhasz G, Simor A, Gulyassy P, Szego EM, Hunyadi-Gulyas E et al. Altered functional protein networks in the prefrontal cortex and amygdala of victims of suicide. PLoS One 2012; 7: e50532.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Perlis RH, Huang J, Purcell S, Fava M, Rush AJ, Sullivan PF et al. Genome-wide association study of suicide attempts in mood disorder patients. Am J Psychiatry 2010; 167: 1499–1507.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Schosser A, Butler AW, Ising M, Perroud N, Uher R, Ng MY et al. Genomewide association scan of suicidal thoughts and behaviour in major depression. PLoS One 2011; 6: e20690.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Willour VL, Seifuddin F, Mahon PB, Jancic D, Pirooznia M, Steele J et al. A genome-wide association study of attempted suicide. Mol Psychiatry 2012; 17: 433–444.

    Article  CAS  PubMed  Google Scholar 

  51. Galfalvy H, Zalsman G, Huang YY, Murphy L, Rosoklija G, Dwork AJ et al. A pilot genome wide association and gene expression array study of suicide with and without major depression. World J Biol Psychiatry 2013; 14: 574–582.

    Article  PubMed  Google Scholar 

  52. Cristino AS, Williams SM, Hawi Z, An JY, Bellgrove MA, Schwartz CE et al. Neurodevelopmental and neuropsychiatric disorders represent an interconnected molecular system. Mol Psychiatry 2014; 19: 294–301.

    Article  CAS  PubMed  Google Scholar 

  53. Deo AJ, Huang YY, Hodgkinson CA, Xin Y, Oquendo MA, Dwork AJ et al. A large-scale candidate gene analysis of mood disorders: evidence of neurotrophic tyrosine kinase receptor and opioid receptor signaling dysfunction. Psychiatr Genet 2013; 23: 47–55.

    Article  CAS  PubMed  Google Scholar 

  54. Jia P, Kao CF, Kuo PH, Zhao Z . A comprehensive network and pathway analysis of candidate genes in major depressive disorder. BMC Syst Biol 2011; 5 (Suppl 3): S12.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Sun J, Jia P, Fanous AH, van den Oord E, Chen X, Riley BP et al. Schizophrenia gene networks and pathways and their applications for novel candidate gene selection. PLoS One 2010; 5: e11351.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wong ML, Dong C, Andreev V, Arcos-Burgos M, Licinio J . Prediction of susceptibility to major depression by a model of interactions of multiple functional genetic variants and environmental factors. Mol Psychiatry 2012; 17: 624–633.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Gonzalez MW, Kann MG . Chapter 4: protein interactions and disease. PLoS Comput Biol 2012; 8: e1002819.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Kendler KS . What psychiatric genetics has taught us about the nature of psychiatric illness and what is left to learn. Mol Psychiatry 2013; 18: 1058–1066.

    Article  CAS  PubMed  Google Scholar 

  59. Lehner B . Genotype to phenotype: lessons from model organisms for human genetics. Nat Rev Genet 2013; 14: 168–178.

    Article  CAS  PubMed  Google Scholar 

  60. Rossin EJ, Lage K, Raychaudhuri S, Xavier RJ, Tatar D, Benita Y et al. Proteins encoded in genomic regions associated with immune-mediated disease physically interact and suggest underlying biology. PLoS Genet 2011; 7: e1001273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Gandhi TK, Zhong J, Mathivanan S, Karthick L, Chandrika KN, Mohan SS et al. Analysis of the human protein interactome and comparison with yeast, worm and fly interaction datasets. Nat Genet 2006; 38: 285–293.

    Article  CAS  PubMed  Google Scholar 

  62. Smith MC, Gestwicki JE . Features of protein-protein interactions that translate into potent inhibitors: topology, surface area and affinity. Expert Rev Mol Med 2012; 14: e16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Chen Y, Andres AL, Frotscher M, Baram TZ . Tuning synaptic transmission in the hippocampus by stress: the CRH system. Front Cell Neurosci 2012; 6: 13.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Joels M, Baram TZ . The neuro-symphony of stress. Nat Rev Neurosci 2009; 10: 459–466.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Popoli M, Yan Z, McEwen BS, Sanacora G . The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev Neurosci 2012; 13: 22–37.

    Article  CAS  Google Scholar 

  66. Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM et al. Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 2000; 25: 25–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chen J, Bardes EE, Aronow BJ, Jegga AG . ToppGene Suite for gene list enrichment analysis and candidate gene prioritization. Nucleic Acids Res 2009; 37, Web Server issue W305–W311.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Kanehisa M, Goto S, Sato Y, Kawashima M, Furumichi M, Tanabe M . Data, information, knowledge and principle: back to metabolism in KEGG. Nucleic Acids Res 2014; 42: D199–D205.

    Article  CAS  PubMed  Google Scholar 

  69. Levy BH, Tasker JG . Synaptic regulation of the hypothalamic-pituitary-adrenal axis and its modulation by glucocorticoids and stress. Front Cell Neurosci 2012; 6: 24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Maras PM, Baram TZ . Sculpting the hippocampus from within: stress, spines, and CRH. Trends Neurosci 2012; 35: 315–324.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Roozendaal B, McEwen BS, Chattarji S . Stress, memory and the amygdala. Nat Rev Neurosci 2009; 10: 423–433.

    Article  CAS  PubMed  Google Scholar 

  72. Lage K . Protein-protein interactions and genetic diseases: the interactome. Biochim Biophys Acta 2014; S0925-4439: 00156–2.

    Google Scholar 

  73. Lage K, Hansen NT, Karlberg EO, Eklund AC, Roque FS, Donahoe PK et al. A large-scale analysis of tissue-specific pathology and gene expression of human disease genes and complexes. Proc Natl Acad Sci USA 2008; 105: 20870–20875.

    Article  PubMed  PubMed Central  Google Scholar 

  74. Franceschini A, Szklarczyk D, Frankild S, Kuhn M, Simonovic M, Roth A et al. STRING v9.1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Res 2013; 41, Database issue D808–D815.

    Article  CAS  PubMed  Google Scholar 

  75. Lehner B . Molecular mechanisms of epistasis within and between genes. Trends Genet 2011; 27: 323–331.

    Article  CAS  PubMed  Google Scholar 

  76. Pattin KA, Moore JH . Exploiting the proteome to improve the genome-wide genetic analysis of epistasis in common human diseases. Hum Genet 2008; 124: 19–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kim YA, Przytycka TM . Bridging the gap between genotype and phenotype via network approaches. Front Genet 2012; 3: 227.

    PubMed  Google Scholar 

  78. Li K, Zhou T, Liao L, Yang Z, Wong C, Henn F et al. betaCaMKII in lateral habenula mediates core symptoms of depression. Science 2013; 341: 1016–1020.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Boiso Moreno S, Zackrisson AL, Jakobsen Falk I, Karlsson L, Carlsson B, Tillmar A et al. ABCB1 gene polymorphisms are associated with suicide in forensic autopsies. Pharmacogenet Genomics 2013; 23: 463–469.

    Article  CAS  PubMed  Google Scholar 

  80. Gietl A, Giegling I, Hartmann AM, Schneider B, Schnabel A, Maurer K et al. ABCG1 gene variants in suicidal behavior and aggression-related traits. Eur Neuropsychopharmacol 2007; 17: 410–416.

    Article  CAS  PubMed  Google Scholar 

  81. Rujescu D, Giegling I, Dahmen N, Szegedi A, Anghelescu I, Gietl A et al. Association study of suicidal behavior and affective disorders with a genetic polymorphism in ABCG1, a positional candidate on chromosome 21q22.3. Neuropsychobiology 2000; 42 (Suppl 1): 22–25.

    Article  CAS  PubMed  Google Scholar 

  82. Fudalej S, Fudalej M, Kostrzewa G, Kuzniar P, Franaszczyk M, Wojnar M et al. Angiotensin-converting enzyme polymorphism and completed suicide: an association in Caucasians and evidence for a link with a method of self-injury. Neuropsychobiology 2009; 59: 151–158.

    Article  CAS  PubMed  Google Scholar 

  83. Hishimoto A, Shirakawa O, Nishiguchi N, Hashimoto T, Yanagi M, Nushida H et al. Association between a functional polymorphism in the renin-angiotensin system and completed suicide. J Neural Transm 2006; 113: 1915–1920.

    Article  CAS  PubMed  Google Scholar 

  84. Sparks DL, Hunsaker JC 3rd, Amouyel P, Malafosse A, Bellivier F, Leboyer M et al. Angiotensin I-converting enzyme I/D polymorphism and suicidal behaviors. Am J Med Genet B Neuropsychiatr Genet 2009; 150B: 290–294.

    Article  CAS  PubMed  Google Scholar 

  85. Baca-Garcia E, Vaquero-Lorenzo C, Perez-Rodriguez MM, Gratacos M, Bayes M, Santiago-Mozos R et al. Nucleotide variation in central nervous system genes among male suicide attempters. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 208–213.

    CAS  PubMed  Google Scholar 

  86. Hishimoto A, Fukutake M, Mouri K, Nagasaki Y, Asano M, Ueno Y et al. Alcohol and aldehyde dehydrogenase polymorphisms and risk for suicide: a preliminary observation in the Japanese male population. Genes Brain Behav 2010; 9: 498–502.

    CAS  PubMed  Google Scholar 

  87. Fukutake M, Hishimoto A, Nishiguchi N, Nushida H, Ueno Y, Shirakawa O et al. Association of alpha2A-adrenergic receptor gene polymorphism with susceptibility to suicide in Japanese females. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 1428–1433.

    Article  CAS  PubMed  Google Scholar 

  88. Sequeira A, Mamdani F, Lalovic A, Anguelova M, Lesage A, Seguin M et al. Alpha 2A adrenergic receptor gene and suicide. Psychiatry Res 2004; 125: 87–93.

    Article  CAS  PubMed  Google Scholar 

  89. Martin-Guerrero I, Callado LF, Saitua K, Rivero G, Garcia-Orad A, Meana JJ . The N251K functional polymorphism in the alpha(2A)-adrenoceptor gene is not associated with depression: a study in suicide completers. Psychopharmacology 2006; 184: 82–86.

    Article  CAS  PubMed  Google Scholar 

  90. Escriba PV, Ozaita A, Garcia-Sevilla JA . Increased mRNA expression of alpha2A-adrenoceptors, serotonin receptors and mu-opioid receptors in the brains of suicide victims. Neuropsychopharmacology 2004; 29: 1512–1521.

    Article  CAS  PubMed  Google Scholar 

  91. Garcia-Sevilla JA, Escriba PV, Ozaita A, La Harpe R, Walzer C, Eytan A et al. Up-regulation of immunolabeled alpha2A-adrenoceptors, Gi coupling proteins, and regulatory receptor kinases in the prefrontal cortex of depressed suicides. J Neurochem 1999; 72: 282–291.

    Article  CAS  PubMed  Google Scholar 

  92. Meana JJ, Garcia-Sevilla JA . Increased alpha 2-adrenoceptor density in the frontal cortex of depressed suicide victims. J Neural Transm 1987; 70: 377–381.

    Article  CAS  PubMed  Google Scholar 

  93. Molnar S, Mihanovic M, Grah M, Kezic S, Filakovic P, Degmecic D . Comparative study on gene tags of the neurotransmission system in schizophrenic and suicidal subjects. Coll Antropol 2010; 34: 1427–1432.

    PubMed  Google Scholar 

  94. Mann JJ, Stanley M, McBride PA, McEwen BS . Increased serotonin2 and beta-adrenergic receptor binding in the frontal cortices of suicide victims. Arch Gen Psychiatry 1986; 43: 954–959.

    Article  CAS  PubMed  Google Scholar 

  95. He Y, Zhou Y, Xi Q, Cui H, Luo T, Song H et al. Genetic variations in microRNA processing genes are associated with susceptibility in depression. DNA Cell Biol 2012; 31: 1499–1506.

    Article  CAS  PubMed  Google Scholar 

  96. Magno LA, Miranda DM, Neves FS, Pimenta GJ, Mello MP, De Marco LA et al. Association between AKT1 but not AKTIP genetic variants and increased risk for suicidal behavior in bipolar patients. Genes Brain Behav 2010; 9: 411–418.

    Article  CAS  PubMed  Google Scholar 

  97. Dwivedi Y, Rizavi HS, Zhang H, Roberts RC, Conley RR, Pandey GN . Modulation in activation and expression of phosphatase and tensin homolog on chromosome ten, Akt1, and 3-phosphoinositide-dependent kinase 1: further evidence demonstrating altered phosphoinositide 3-kinase signaling in postmortem brain of suicide subjects. Biol Psychiatry 2010; 67: 1017–1025.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Finseth PI, Sonderby IE, Djurovic S, Agartz I, Malt UF, Melle I et al. Association analysis between suicidal behaviour and candidate genes of bipolar disorder and schizophrenia. J Affect Disord 2014; 163: 110–114.

    Article  CAS  PubMed  Google Scholar 

  99. Edgar PF, Hooper AJ, Poa NR, Burnett JR . Violent behavior associated with hypocholesterolemia due to a novel APOB gene mutation. Mol Psychiatry 2007; 12 3: 221, 258–263.

    Google Scholar 

  100. Hwang JP, Yang CH, Hong CJ, Lirng JF, Yang YM, Tsai SJ . Association of APOE genetic polymorphism with cognitive function and suicide history in geriatric depression. Dement Geriatr Cogn Disord 2006; 22: 334–338.

    Article  CAS  PubMed  Google Scholar 

  101. Chojnicka I, Gajos K, Strawa K, Broda G, Fudalej S, Fudalej M et al. Possible association between suicide committed under influence of ethanol and a variant in the AUTS2 gene. PLoS One 2013; 8: e57199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Inder WJ, Donald RA, Prickett TC, Frampton CM, Sullivan PF, Mulder RT et al. Arginine vasopressin is associated with hypercortisolemia and suicide attempts in depression. Biol Psychiatry 1997; 42: 744–747.

    Article  CAS  PubMed  Google Scholar 

  103. Merali Z, Kent P, Du L, Hrdina P, Palkovits M, Faludi G et al. Corticotropin-releasing hormone, arginine vasopressin, gastrin-releasing peptide, and neuromedin B alterations in stress-relevant brain regions of suicides and control subjects. Biol Psychiatry 2006; 59: 594–602.

    Article  CAS  PubMed  Google Scholar 

  104. Ben-Efraim YJ, Wasserman D, Wasserman J, Sokolowski M . Family-based study of AVPR1B association and interaction with stressful life events on depression and anxiety in suicide attempts. Neuropsychopharmacology 2013; 38: 1504–1511.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Hong CJ, Huo SJ, Yen FC, Tung CL, Pan GM, Tsai SJ . Association study of a brain-derived neurotrophic-factor genetic polymorphism and mood disorders, age of onset and suicidal behavior. Neuropsychobiology 2003; 48: 186–189.

    Article  CAS  PubMed  Google Scholar 

  106. Sarchiapone M, Carli V, Roy A, Iacoviello L, Cuomo C, Latella MC et al. Association of polymorphism (Val66Met) of brain-derived neurotrophic factor with suicide attempts in depressed patients. Neuropsychobiology 2008; 57: 139–145.

    Article  CAS  PubMed  Google Scholar 

  107. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN . Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003; 60: 804–815.

    Article  CAS  PubMed  Google Scholar 

  108. Dwivedi Y . Brain-derived neurotrophic factor in suicide pathophysiology. In: Dwivedi Y (ed) The Neurobiological Basis of Suicide. CRC Press: Boca Raton, FL, USA, 2012.

    Chapter  Google Scholar 

  109. Zai CC, Manchia M, De Luca V, Tiwari AK, Chowdhury NI, Zai GC et al. The brain-derived neurotrophic factor gene in suicidal behaviour: a meta-analysis. Int J Neuropsychopharmacol 2012; 15: 1037–1042.

    Article  CAS  PubMed  Google Scholar 

  110. Shindo S, Yoshioka N . Polymorphisms of the cholecystokinin gene promoter region in suicide victims in Japan. Forensic Sci Int 2005; 150: 85–90.

    Article  CAS  PubMed  Google Scholar 

  111. Bachus SE, Hyde TM, Herman MM, Egan MF, Kleinman JE . Abnormal cholecystokinin mRNA levels in entorhinal cortex of schizophrenics. J Psychiatr Res 1997; 31: 233–256.

    Article  CAS  PubMed  Google Scholar 

  112. Lofberg C, Agren H, Harro J, Oreland L . Cholecystokinin in CSF from depressed patients: possible relations to severity of depression and suicidal behaviour. Eur Neuropsychopharmacol 1998; 8: 153–157.

    Article  CAS  PubMed  Google Scholar 

  113. Sears C, Wilson J, Fitches A . Investigating the role of BDNF and CCK system genes in suicidality in a familial bipolar cohort. J Affect Disord 2013; 151: 611–617.

    Article  CAS  PubMed  Google Scholar 

  114. Sherrin T, Heng KY, Zhu YZ, Tang YM, Lau G, Tan CH . Cholecystokinin-B receptor gene expression in cerebellum, pre-frontal cortex and cingulate gyrus and its association with suicide. Neurosci Lett 2004; 357: 107–110.

    Article  CAS  PubMed  Google Scholar 

  115. Harro J, Marcusson J, Oreland L . Alterations in brain cholecystokinin receptors in suicide victims. Eur Neuropsychopharmacol 1992; 2: 57–63.

    Article  CAS  PubMed  Google Scholar 

  116. Chojnicka I, Strawa K, Fudalej S, Fudalej M, Pawlak A, Kostrzewa G et al. Analysis of four genes involved in the neurodevelopment shows association of rs4307059 polymorphism in the cadherin 9/10 region with completed suicide. Neuropsychobiology 2012; 66: 134–140.

    Article  CAS  PubMed  Google Scholar 

  117. Hungund BL, Vinod KY, Kassir SA, Basavarajappa BS, Yalamanchili R, Cooper TB et al. Upregulation of CB1 receptors and agonist-stimulated [35S]GTPgammaS binding in the prefrontal cortex of depressed suicide victims. Mol Psychiatry 2004; 9: 184–190.

    Article  CAS  PubMed  Google Scholar 

  118. Vinod KY, Arango V, Xie S, Kassir SA, Mann JJ, Cooper TB et al. Elevated levels of endocannabinoids and CB1 receptor-mediated G-protein signaling in the prefrontal cortex of alcoholic suicide victims. Biol Psychiatry 2005; 57: 480–486.

    Article  CAS  PubMed  Google Scholar 

  119. Vinod KY . Role of the endocannabinoid system in the neurobiology of suicide. In: Dwivedi Y (ed) The Neurobiological Basis of Suicide. CRC Press: Boca Raton, FL, USA, 2012.

    Google Scholar 

  120. Nolan KA, Volavka J, Czobor P, Cseh A, Lachman H, Saito T et al. Suicidal behavior in patients with schizophrenia is related to COMT polymorphism. Psychiatr Genet 2000; 10: 117–124.

    Article  CAS  PubMed  Google Scholar 

  121. Zalsman G, Huang YY, Oquendo MA, Brent DA, Giner L, Haghighi F et al. No association of COMT Val158Met polymorphism with suicidal behavior or CSF monoamine metabolites in mood disorders. Arch Suicide Res 2008; 12: 327–335.

    Article  PubMed  PubMed Central  Google Scholar 

  122. Abdolmaleky HM, Cheng KH, Faraone SV, Wilcox M, Glatt SJ, Gao F et al. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder. Hum Mol Genet 2006; 15: 3132–3145.

    Article  CAS  PubMed  Google Scholar 

  123. Du L, Merali Z, Poulter MO, Palkovits M, Faludi G, Anisman H . Catechol-O-methyltransferase Val158Met polymorphism and altered COMT gene expression in the prefrontal cortex of suicide brains. Prog Neuropsychopharmacol Biol Psychiatry 2014; 50C: 178–183.

    Article  CAS  Google Scholar 

  124. Calati R, Porcelli S, Giegling I, Hartmann AM, Moller HJ, De Ronchi D et al. Catechol-o-methyltransferase gene modulation on suicidal behavior and personality traits: review, meta-analysis and association study. J Psychiatr Res 2011; 45: 309–321.

    Article  PubMed  Google Scholar 

  125. Kia-Keating BM, Glatt SJ, Tsuang MT . Meta-analyses suggest association between COMT, but not HTR1B, alleles, and suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 2007; 144B: 1048–1053.

    Article  PubMed  Google Scholar 

  126. Tovilla-Zarate C, Juarez-Rojop I, Ramon-Frias T, Villar-Soto M, Pool-Garcia S, Medellin BC et al. No association between COMT val158met polymorphism and suicidal behavior: meta-analysis and new data. BMC Psychiatry 2011; 11: 151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  127. Dwivedi Y, Rao JS, Rizavi HS, Kotowski J, Conley RR, Roberts RC et al. Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch Gen Psychiatry 2003; 60: 273–282.

    Article  CAS  PubMed  Google Scholar 

  128. Dowlatshahi D, MacQueen GM, Wang JF, Reiach JS, Young LT . G Protein-coupled cyclic AMP signaling in postmortem brain of subjects with mood disorders: effects of diagnosis, suicide, and treatment at the time of death. J Neurochem 1999; 73: 1121–1126.

    Article  CAS  PubMed  Google Scholar 

  129. Arato M, Banki CM, Bissette G, Nemeroff CB . Elevated CSF CRF in suicide victims. Biol Psychiatry 1989; 25: 355–359.

    Article  CAS  PubMed  Google Scholar 

  130. De Luca V, Tharmalingam S, Zai C, Potapova N, Strauss J, Vincent J et al. Association of HPA axis genes with suicidal behaviour in schizophrenia. J Psychopharmacol 2010; 24: 677–682.

    Article  CAS  PubMed  Google Scholar 

  131. 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: 72–79.

    Article  PubMed  Google Scholar 

  132. Merali Z, Du L, Hrdina P, Palkovits M, Faludi G, Poulter MO et al. Dysregulation in the suicide brain: mRNA expression of corticotropin-releasing hormone receptors and GABA(A) receptor subunits in frontal cortical brain region. J Neurosci 2004; 24: 1478–1485.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  133. Wasserman D, Sokolowski M, Rozanov V, Wasserman J . The CRHR1 gene: a marker for suicidality in depressed males exposed to low stress. Genes Brain Behav 2008; 7: 14–19.

    CAS  PubMed  Google Scholar 

  134. Wasserman D, Wasserman J, Rozanov V, Sokolowski M . Depression in suicidal males: genetic risk variants in the CRHR1 gene. Genes Brain Behav 2009; 8: 72–79.

    Article  CAS  PubMed  Google Scholar 

  135. Hiroi N, Wong ML, Licinio J, Park C, Young M, Gold PW et al. Expression of corticotropin releasing hormone receptors type I and type II mRNA in suicide victims and controls. Mol Psychiatry 2001; 6: 540–546.

    Article  CAS  PubMed  Google Scholar 

  136. Nemeroff CB, Owens MJ, Bissette G, Andorn AC, Stanley M . Reduced corticotropin releasing factor binding sites in the frontal cortex of suicide victims. Arch Gen Psychiatry 1988; 45: 577–579.

    Article  CAS  PubMed  Google Scholar 

  137. Mandelli L, Serretti A . Gene environment interaction studies in depression and suicidal behavior: An update. Neurosci Biobehav Rev 2013; 37: 2375–2397.

    Article  PubMed  Google Scholar 

  138. De Luca V, Tharmalingam S, Kennedy JL . Association study between the corticotropin-releasing hormone receptor 2 gene and suicidality in bipolar disorder. Eur Psychiatry 2007; 22: 282–287.

    Article  PubMed  Google Scholar 

  139. Suchankova P, Holm G, Traskman-Bendz L, Brundin L, Ekman A . The +1444C>T polymorphism in the CRP gene: a study on personality traits and suicidal behaviour. Psychiatr Genet 2013; 23: 70–76.

    Article  CAS  PubMed  Google Scholar 

  140. Hofer P, Schosser A, Calati R, Serretti A, Massat I, Kocabas NA et al. The impact of Cytochrome P450 CYP1A2, CYP2C9, CYP2C19 and CYP2D6 genes on suicide attempt and suicide risk-a European multicentre study on treatment-resistant major depressive disorder. Eur Arch Psychiatry Clin Neurosci 2013; 263: 385–391.

    Article  PubMed  Google Scholar 

  141. Penas-Lledo EM, Blasco-Fontecilla H, Dorado P, Vaquero-Lorenzo C, Baca-Garcia E, Llerena A . CYP2D6 and the severity of suicide attempts. Pharmacogenomics 2012; 13: 179–184.

    Article  CAS  PubMed  Google Scholar 

  142. Zackrisson AL, Lindblom B, Ahlner J . High frequency of occurrence of CYP2D6 gene duplication/multiduplication indicating ultrarapid metabolism among suicide cases. Clin Pharmacol Ther 2010; 88: 354–359.

    Article  CAS  PubMed  Google Scholar 

  143. Preuss UW, Wurst FM, Ridinger M, Rujescu D, Fehr C, Koller G et al. Association of functional DBH genetic variants with alcohol dependence risk and related depression and suicide attempt phenotypes: results from a large multicenter association study. Drug Alcohol Depend 2013; 133: 459–467.

    Article  CAS  PubMed  Google Scholar 

  144. Fernandez-Navarro P, Vaquero-Lorenzo C, Blasco-Fontecilla H, Diaz-Hernandez M, Gratacos M, Estivill X et al. Genetic epistasis in female suicide attempters. Prog Neuropsychopharmacol Biol Psychiatry 2012; 38: 294–301.

    Article  PubMed  Google Scholar 

  145. Rochet T, Tonon MC, Kopp N, Vaudry H, Miachon S . Evaluation of endozepine-like immunoreactivity in the frontal cortex of suicide victims. Neuroreport 1998; 9: 53–56.

    Article  CAS  PubMed  Google Scholar 

  146. Giegling I, Moreno-De-Luca D, Rujescu D, Schneider B, Hartmann AM, Schnabel A et al. Dopa decarboxylase and tyrosine hydroxylase gene variants in suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 2008; 147: 308–315.

    Article  PubMed  Google Scholar 

  147. Roy A, Karoum F, Pollack S . Marked reduction in indexes of dopamine metabolism among patients with depression who attempt suicide. Arch Gen Psychiatry 1992; 49: 447–450.

    Article  CAS  PubMed  Google Scholar 

  148. Lalovic A, Sequeira A, DeGuzman R, Chawky N, Lesage A, Seguin M et al. Investigation of completed suicide and genes involved in cholesterol metabolism. J Affect Disord 2004; 79: 25–32.

    Article  CAS  PubMed  Google Scholar 

  149. Lalovic A, Merkens L, Russell L, Arsenault-Lapierre G, Nowaczyk MJ, Porter FD et al. Cholesterol metabolism and suicidality in Smith-Lemli-Opitz syndrome carriers. Am J Psychiatry 2004; 161: 2123–2126.

    Article  PubMed  Google Scholar 

  150. Ratta-apha W, Hishimoto A, Mouri K, Shiroiwa K, Sasada T, Yoshida M et al. Haplotype analysis of the DISC1 Ser704Cys variant in Japanese suicide completers. Psychiatry Res 2014; 215: 249–251.

    Article  CAS  PubMed  Google Scholar 

  151. Monsalve EM, Garcia-Gutierrez MS, Navarrete F, Giner S, Laborda J, Manzanares J . Abnormal expression pattern of Notch receptors, ligands, and downstream effectors in the dorsolateral prefrontal cortex and amygdala of suicidal victims. Mol Neurobiol 2013; 49: 957–965.

    Article  CAS  PubMed  Google Scholar 

  152. Murphy TM, Mullins N, Ryan M, Foster T, Kelly C, McClelland R et al. Genetic variation in DNMT3B and increased global DNA methylation is associated with suicide attempts in psychiatric patients. Genes Brain Behav 2013; 12: 125–132.

    Article  CAS  PubMed  Google Scholar 

  153. Poulter MO, Du L, Weaver IC, Palkovits M, Faludi G, Merali Z et al. GABAA receptor promoter hypermethylation in suicide brain: implications for the involvement of epigenetic processes. Biol Psychiatry 2008; 64: 645–652.

    Article  CAS  PubMed  Google Scholar 

  154. Johann M, Putzhammer A, Eichhammer P, Wodarz N . Association of the -141C Del variant of the dopamine D2 receptor (DRD2) with positive family history and suicidality in German alcoholics. Am J Med Genet B Neuropsychiatr Genet 2005; 132B: 46–49.

    Article  PubMed  Google Scholar 

  155. Suda A, Kawanishi C, Kishida I, Sato R, Yamada T, Nakagawa M et al. Dopamine D2 receptor gene polymorphisms are associated with suicide attempt in the Japanese population. Neuropsychobiology 2009; 59: 130–134.

    Article  CAS  PubMed  Google Scholar 

  156. Bowden C, Cheetham SC, Lowther S, Katona CL, Crompton MR, Horton RW . Reduced dopamine turnover in the basal ganglia of depressed suicides. Brain Res 1997; 769: 135–140.

    Article  CAS  PubMed  Google Scholar 

  157. Tsai SJ, Wang YC, Hong CJ, Chiu HJ . Association study of oestrogen receptor alpha gene polymorphism and suicidal behaviours in major depressive disorder. Psychiatr Genet 2003; 13: 19–22.

    Article  PubMed  Google Scholar 

  158. Giegling I, Chiesa A, Calati R, Hartmann AM, Moller HJ, De Ronchi D et al. Do the estrogen receptors 1 gene variants influence the temperament and character inventory scores in suicidal attempters and healthy subjects? Am J Med Genet B Neuropsychiatr Genet 2009; 150B: 434–438.

    Article  CAS  PubMed  Google Scholar 

  159. Baca-Garcia E, Diaz-Sastre C, Ceverino A, Perez-Rodriguez MM, Navarro-Jimenez R, Lopez-Castroman J et al. Suicide attempts among women during low estradiol/low progesterone states. J Psychiatr Res 2010; 44: 209–214.

    Article  PubMed  Google Scholar 

  160. Ostlund H, Keller E, Hurd YL . Estrogen receptor gene expression in relation to neuropsychiatric disorders. Ann NY Acad Sci 2003; 1007: 54–63.

    Article  CAS  PubMed  Google Scholar 

  161. Must A, Koks S, Vasar E, Tasa G, Lang A, Maron E et al. Common variations in 4p locus are related to male completed suicide. Neuromolecular Med 2009; 11: 13–19.

    Article  CAS  PubMed  Google Scholar 

  162. Monteleone P, Bifulco M, Maina G, Tortorella A, Gazzerro P, Proto MC et al. Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression. Pharmacol Res 2010; 61: 400–404.

    Article  CAS  PubMed  Google Scholar 

  163. Vinod KY, Kassir SA, Hungund BL, Cooper TB, Mann JJ, Arango V . Selective alterations of the CB1 receptors and the fatty acid amide hydrolase in the ventral striatum of alcoholics and suicides. J Psychiatr Res 2010; 44: 591–597.

    Article  PubMed  Google Scholar 

  164. Lalovic A, Klempan T, Sequeira A, Luheshi G, Turecki G . Altered expression of lipid metabolism and immune response genes in the frontal cortex of suicide completers. J Affect Disord 2010; 120: 24–31.

    Article  CAS  PubMed  Google Scholar 

  165. 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: 261–268.

    Article  CAS  PubMed  Google Scholar 

  166. 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: 1674–1683.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  167. Perez-Ortiz JM, Garcia-Gutierrez MS, Navarrete F, Giner S, Manzanares J . Gene and protein alterations of FKBP5 and glucocorticoid receptor in the amygdala of suicide victims. Psychoneuroendocrinology 2013; 38: 1251–1258.

    Article  CAS  PubMed  Google Scholar 

  168. Minoretti P, Arra M, Emanuele E, Olivieri V, Aldeghi A, Politi P et al. A W148R mutation in the human FOXD4 gene segregating with dilated cardiomyopathy, obsessive-compulsive disorder, and suicidality. Int J Mol Med 2007; 19: 369–372.

    CAS  PubMed  Google Scholar 

  169. 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: 985–992.

    Article  CAS  PubMed  Google Scholar 

  170. Poulter MO, Du L, Zhurov V, Palkovits M, Faludi G, Merali Z et al. Altered organization of GABA(A) receptor mRNA expression in the depressed suicide brain. Front Mol Neurosci 2010; 3: 3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  171. Cheetham SC, Crompton MR, Katona CL, Parker SJ, Horton RW . Brain GABAA/benzodiazepine binding sites and glutamic acid decarboxylase activity in depressed suicide victims. Brain Res 1988; 460: 114–123.

    Article  CAS  PubMed  Google Scholar 

  172. Rochet T, Kopp N, Vedrinne J, Deluermoz S, Debilly G, Miachon S . Benzodiazepine binding sites and their modulators in hippocampus of violent suicide victims. Biol Psychiatry 1992; 32: 922–931.

    Article  CAS  PubMed  Google Scholar 

  173. Bernstein HG, Tausch A, Wagner R, Steiner J, Seeleke P, Walter M et al. Disruption of glutamate-glutamine-GABA cycle significantly impacts on suicidal behaviour: survey of the literature and own findings on glutamine synthetase. CNS Neurol Disord Drug Targets 2013; 12: 900–913.

    Article  CAS  PubMed  Google Scholar 

  174. Jancic D, Seifuddin F, Zandi PP, Potash JB, Willour VL . Association study of X chromosome SNPs in attempted suicide. Psychiatry Res 2012; 200: 1044–1046.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  175. Nagy C, Suderman M, Yang J, Szyf M, Mechawar N, Ernst C et al. Astrocytic abnormalities and global DNA methylation patterns in depression and suicide. Mol Psychiatry advance online publication, 25 March 2014; doi:10.1038/mp.2014.21 (e-pub ahead of print).

  176. Jimenez E, Arias B, Mitjans M, Goikolea JM, Roda E, Saiz PA et al. Genetic variability at IMPA2, INPP1 and GSK3beta increases the risk of suicidal behavior in bipolar patients. Eur Neuropsychopharmacol 2013; 23: 1452–1462.

    Article  CAS  PubMed  Google Scholar 

  177. Yoon HK, Kim YK . Association between glycogen synthase kinase-3beta gene polymorphisms and major depression and suicidal behavior in a Korean population. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 331–334.

    Article  CAS  PubMed  Google Scholar 

  178. Pandey GN, Dwivedi Y, Rizavi HS, Teppen T, Gaszner GL, Roberts RC et al. GSK-3beta gene expression in human postmortem brain: regional distribution, effects of age and suicide. Neurochem Res 2009; 34: 274–285.

    Article  CAS  PubMed  Google Scholar 

  179. Strauss J, McGregor S, Freeman N, Tiwari A, George CJ, Kovacs M et al. Association study of early-immediate genes in childhood-onset mood disorders and suicide attempt. Psychiatry Res 2012; 197: 49–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  180. Lemonde S, Turecki G, Bakish D, Du L, Hrdina PD, Bown CD et al. Impaired repression at a 5-hydroxytryptamine 1A receptor gene polymorphism associated with major depression and suicide. J Neurosci 2003; 23: 8788–8799.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  181. Huang YY, Battistuzzi C, Oquendo MA, Harkavy-Friedman J, Greenhill L, Zalsman G et al. Human 5-HT1A receptor C(-1019)G polymorphism and psychopathology. Int J Neuropsychopharmacol 2004; 7: 441–451.

    Article  CAS  PubMed  Google Scholar 

  182. Arango V, Underwood MD, Gubbi AV, Mann JJ . Localized alterations in pre- and postsynaptic serotonin binding sites in the ventrolateral prefrontal cortex of suicide victims. Brain Res 1995; 688: 121–133.

    Article  CAS  PubMed  Google Scholar 

  183. Gonzalez-Castro TB, Tovilla-Zarate CA, Juarez-Rojop I, Pool Garcia S, Genis A, Nicolini H et al. Association of 5HTR1A gene variants with suicidal behavior: case-control study and updated meta-analysis. J Psychiatr Res 2013; 47: 1665–1672.

    Article  PubMed  Google Scholar 

  184. New AS, Gelernter J, Goodman M, Mitropoulou V, Koenigsberg H, Silverman J et al. Suicide, impulsive aggression, and HTR1B genotype. Biol Psychiatry 2001; 50: 62–65.

    Article  CAS  PubMed  Google Scholar 

  185. Rujescu D, Giegling I, Sato T, Moller HJ . Lack of association between serotonin 5-HT1B receptor gene polymorphism and suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 2003; 116B: 69–71.

    Article  PubMed  Google Scholar 

  186. Murphy TM, Ryan M, Foster T, Kelly C, McClelland R, O'Grady J et al. Risk and protective genetic variants in suicidal behaviour: association with SLC1A2, SLC1A3, 5-HTR1B &NTRK2 polymorphisms. Behav Brain Funct 2011; 7: 22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Turecki G, Sequeira A, Gingras Y, Seguin M, Lesage A, Tousignant M et al. Suicide and serotonin: study of variation at seven serotonin receptor genes in suicide completers. Am J Med Genet B Neuropsychiatr Genet 2003; 118B: 36–40.

    Article  CAS  PubMed  Google Scholar 

  188. Huang YY, Grailhe R, Arango V, Hen R, Mann JJ . Relationship of psychopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue. Neuropsychopharmacology 1999; 21: 238–246.

    Article  CAS  PubMed  Google Scholar 

  189. Zhang L, Su TP, Choi K, Maree W, Li CT, Chung MY et al. P11 (S100A10) as a potential biomarker of psychiatric patients at risk of suicide. J Psychiatr Res 2011; 45: 435–441.

    Article  PubMed  Google Scholar 

  190. Schild AH, Pietschnig J, Tran US, Voracek M . Genetic association studies between SNPs and suicidal behavior: a meta-analytical field synopsis. Prog Neuropsychopharmacol Biol Psychiatry 2013; 46: 36–42.

    Article  CAS  PubMed  Google Scholar 

  191. Lowther S, Katona CL, Crompton MR, Horton RW . 5-HT1D and 5-HT1E/1F binding sites in depressed suicides: increased 5-HT1D binding in globus pallidus but not cortex. Mol Psychiatry 1997; 2: 314–321.

    Article  CAS  PubMed  Google Scholar 

  192. Gonzalez-Castro TB, Tovilla-Zarate C, Juarez-Rojop I, Pool Garcia S, Velazquez-Sanchez MP, Genis A et al. Association of the 5HTR2A gene with suicidal behavior: case-control study and updated meta-analysis. BMC Psychiatry 2013; 13: 25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  193. Garbett K, Gal-Chis R, Gaszner G, Lewis DA, Mirnics K . Transcriptome alterations in the prefrontal cortex of subjects with schizophrenia who committed suicide. Neuropsychopharmacol Hung 2008; 10: 9–14.

    PubMed  Google Scholar 

  194. Sequeira A, Morgan L, Walsh DM, Cartagena PM, Choudary P, Li J et al. Gene expression changes in the prefrontal cortex, anterior cingulate cortex and nucleus accumbens of mood disorders subjects that committed suicide. PLoS One 2012; 7: e35367.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  195. Bevilacqua L, Doly S, Kaprio J, Yuan Q, Tikkanen R, Paunio T et al. A population-specific HTR2B stop codon predisposes to severe impulsivity. Nature 2010; 468: 1061–1066.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. Videtic A, Peternelj TT, Zupanc T, Balazic J, Komel R . Promoter and functional polymorphisms of HTR2C and suicide victims. Genes Brain Behav 2009; 8: 541–545.

    Article  CAS  PubMed  Google Scholar 

  197. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Faludi G, Sarosi A et al. Regional distribution and relative abundance of serotonin(2c) receptors in human brain: effect of suicide. Neurochem Res 2006; 31: 167–176.

    Article  PubMed  Google Scholar 

  198. Polsinelli G, Zai CC, Strauss J, Kennedy JL, De Luca V . Association and CpG SNP analysis of HTR4 polymorphisms with suicidal behavior in subjects with schizophrenia. J Neural Transm 2013; 120: 253–258.

    Article  CAS  PubMed  Google Scholar 

  199. Azenha D, Alves M, Matos R, Santa JF, Silva B, Cordeiro C et al. Male specific association between the 5-HTR6 gene 267C/T SNP and suicide in the Portuguese population. Neurosci Lett 2009; 466: 128–130.

    Article  CAS  PubMed  Google Scholar 

  200. Omrani MD, Bushehri B, Bagheri M, Salari-Lak S, Alipour A, Anoshae MR et al. Role of IL-10 -1082, IFN-gamma +874, and TNF-alpha -308 genes polymorphisms in suicidal behavior. Arch Suicide Res 2009; 13: 330–339.

    Article  PubMed  Google Scholar 

  201. Pandey GN, Rizavi HS, Ren X, Fareed J, Hoppensteadt DA, Roberts RC et al. Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims. J Psychiatr Res 2012; 46: 57–63.

    Article  PubMed  Google Scholar 

  202. Freemantle E, Mechawar N, Turecki G . Cholesterol and phospholipids in frontal cortex and synaptosomes of suicide completers: relationship with endosomal lipid trafficking genes. J Psychiatr Res 2013; 47: 272–279.

    Article  PubMed  Google Scholar 

  203. Must A, Tasa G, Lang A, Vasar E, Koks S, Maron E et al. Association of limbic system-associated membrane protein (LSAMP) to male completed suicide. BMC Med Genet 2008; 9: 34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  204. Perlis RH, Ruderfer D, Hamilton SP, Ernst C . Copy number variation in subjects with major depressive disorder who attempted suicide. PLoS One 2012; 7: e46315.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  205. Du L, Faludi G, Palkovits M, Sotonyi P, Bakish D, Hrdina PD . High activity-related allele of MAO-A gene associated with depressed suicide in males. Neuroreport 2002; 13: 1195–1198.

    Article  CAS  PubMed  Google Scholar 

  206. Hung CF, Lung FW, Hung TH, Chong MY, Wu CK, Wen JK et al. Monoamine oxidase A gene polymorphism and suicide: an association study and meta-analysis. J Affect Disord 2012; 136: 643–649.

    Article  CAS  PubMed  Google Scholar 

  207. Gottfries CG, Oreland L, Wiberg A, Winblad B . Lowered monoamine oxidase activity in brains from alcoholic suicides. J Neurochem 1975; 25: 667–673.

    Article  CAS  PubMed  Google Scholar 

  208. Mann JJ, Stanley M . Postmortem monoamine oxidase enzyme kinetics in the frontal cortex of suicide victims and controls. Acta Psychiatr Scand 1984; 69: 135–139.

    Article  CAS  PubMed  Google Scholar 

  209. Brunner HG, Nelen MR, van Zandvoort P, Abeling NG, van Gennip AH, Wolters EC et al. X-linked borderline mental retardation with prominent behavioral disturbance: phenotype, genetic localization, and evidence for disturbed monoamine metabolism. Am J Hum Genet 1993; 52: 1032–1039.

    CAS  PubMed  PubMed Central  Google Scholar 

  210. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Roberts RC, Conley RR et al. Altered expression and phosphorylation of myristoylated alanine-rich C kinase substrate (MARCKS) in postmortem brain of suicide victims with or without depression. J Psychiatr Res 2003; 37: 421–432.

    Article  PubMed  Google Scholar 

  211. Chojnicka I, Sobczyk-Kopciol A, Fudalej M, Fudalej S, Wojnar M, Waskiewicz A et al. No association between MTHFR C677T polymorphism and completed suicide. Gene 2012; 511: 118–121.

    Article  CAS  PubMed  Google Scholar 

  212. Giegling I, Calati R, Porcelli S, Hartmann AM, Moller HJ, De Ronchi D et al. NCAM1, TACR1 and NOS genes and temperament: a study on suicide attempters and controls. Neuropsychobiology 2011; 64: 32–37.

    Article  CAS  PubMed  Google Scholar 

  213. Giegling I, Chiesa A, Mandelli L, Gibiino S, Hartmann AM, Moller HJ et al. Influence of neuronal cell adhesion molecule (NCAM1) variants on suicidal behaviour and correlated traits. Psychiatry Res 2010; 179: 222–225.

    Article  CAS  PubMed  Google Scholar 

  214. Maheu ME, Davoli MA, Turecki G, Mechawar N . Amygdalar expression of proteins associated with neuroplasticity in major depression and suicide. J Psychiatr Res 2013; 47: 384–390.

    Article  PubMed  Google Scholar 

  215. Dwivedi Y, Mondal AC, Rizavi HS, Conley RR . Suicide brain is associated with decreased expression of neurotrophins. Biol Psychiatry 2005; 58: 315–324.

    Article  CAS  PubMed  Google Scholar 

  216. Banerjee R, Ghosh AK, Ghosh B, Bhattacharyya S, Mondal AC . Decreased mRNA and protein expression of BDNF, NGF, and their receptors in the hippocampus from suicide: an analysis in human postmortem brain. Clin Med Insights Pathol 2013; 6: 1–11.

    Article  PubMed  PubMed Central  Google Scholar 

  217. McGregor S, Strauss J, Bulgin N, De Luca V, George CJ, Kovacs M et al. p75(NTR) gene and suicide attempts in young adults with a history of childhood-onset mood disorder. Am J Med Genet B Neuropsychiatr Genet 2007; 144B: 696–700.

    Article  CAS  PubMed  Google Scholar 

  218. Cui H, Supriyanto I, Asano M, Ueno Y, Nagasaki Y, Nishiguchi N et al. A common polymorphism in the 3'-UTR of the NOS1 gene was associated with completed suicides in Japanese male population. Prog Neuropsychopharmacol Biol Psychiatry 2010; 34: 992–996.

    Article  CAS  PubMed  Google Scholar 

  219. Rujescu D, Giegling I, Mandelli L, Schneider B, Hartmann AM, Schnabel A et al. NOS-I and -III gene variants are differentially associated with facets of suicidal behavior and aggression-related traits. Am J Med Genet B Neuropsychiatr Genet 2008; 147B: 42–48.

    Article  CAS  PubMed  Google Scholar 

  220. Wang AG, Koefoed P, Jacoby AS, Woldbye D, Rasmussen HB, Timm S et al. Neuropeptide Y genes and suicidal behaviour among schizophrenic patients. Psychiatr Genet 2013; 23: 139–140.

    Article  PubMed  Google Scholar 

  221. Traskman-Bendz L, Ekman R, Regnell G, Ohman R . HPA-related CSF neuropeptides in suicide attempters. Eur Neuropsychopharmacol 1992; 2: 99–106.

    Article  CAS  PubMed  Google Scholar 

  222. Widdowson PS, Ordway GA, Halaris AE . Reduced neuropeptide Y concentrations in suicide brain. J Neurochem 1992; 59: 73–80.

    Article  CAS  PubMed  Google Scholar 

  223. Caberlotto L, Hurd YL . Neuropeptide Y Y(1) and Y(2) receptor mRNA expression in the prefrontal cortex of psychiatric subjects. Relationship of Y(2) subtype to suicidal behavior. Neuropsychopharmacology 2001; 25: 91–97.

    Article  CAS  PubMed  Google Scholar 

  224. Lopez JF, Palkovits M, Arato M, Mansour A, Akil H, Watson SJ . Localization and quantification of pro-opiomelanocortin mRNA and glucocorticoid receptor mRNA in pituitaries of suicide victims. Neuroendocrinology 1992; 56: 491–501.

    Article  CAS  PubMed  Google Scholar 

  225. McGowan PO, Sasaki A, D'Alessio AC, Dymov S, Labonte B, Szyf M et al. Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci 2009; 12: 342–348.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  226. Pandey GN, Rizavi HS, Ren X, Dwivedi Y, Palkovits M . Region-specific alterations in glucocorticoid receptor expression in the postmortem brain of teenage suicide victims. Psychoneuroendocrinology 2013; 38: 2628–2639.

    Article  CAS  PubMed  Google Scholar 

  227. Coryell W, Schlesser M . Combined biological tests for suicide prediction. Psychiatry Res 2007; 150: 187–191.

    Article  PubMed  PubMed Central  Google Scholar 

  228. Jokinen J, Nordstrom AL, Nordstrom P . ROC analysis of dexamethasone suppression test threshold in suicide prediction after attempted suicide. J Affect Disord 2008; 106: 145–152.

    Article  CAS  PubMed  Google Scholar 

  229. Mann JJ, Currier D, Stanley B, Oquendo MA, Amsel LV, Ellis SP . Can biological tests assist prediction of suicide in mood disorders? Int J Neuropsychopharmacol 2006; 9: 465–474.

    Article  PubMed  Google Scholar 

  230. Kohli MA, Salyakina D, Pfennig A, Lucae S, Horstmann S, Menke A et al. Association of genetic variants in the neurotrophic receptor-encoding gene NTRK2 and a lifetime history of suicide attempts in depressed patients. Arch Gen Psychiatry 2010; 67: 348–359.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  231. Chen GG, Fiori LM, Moquin L, Gratton A, Mamer O, Mechawar N et al. Evidence of altered polyamine concentrations in cerebral cortex of suicide completers. Neuropsychopharmacology 2010; 35: 1477–1484.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  232. Fiori LM, Gross JA, Turecki G . Effects of histone modifications on increased expression of polyamine biosynthetic genes in suicide. Int J Neuropsychopharmacol 2012; 15: 1161–1166.

    Article  CAS  PubMed  Google Scholar 

  233. Gross JA, Turecki G . Suicide and the polyamine system. CNS Neurol Disord Drug Targets 2013; 12: 980–988.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  234. Arias AJ, Chan G, Gelernter J, Farrer L, Kranzler HR . Variation in OPRM1 and risk of suicidal behavior in drug-dependent individuals. Am J Addict 2012; 21: 5–10.

    Article  PubMed  Google Scholar 

  235. Hishimoto A, Cui H, Mouri K, Nushida H, Ueno Y, Maeda K et al. A functional polymorphism of the micro-opioid receptor gene is associated with completed suicides. J Neural Transm 2008; 115: 531–536.

    Article  CAS  PubMed  Google Scholar 

  236. Gross-Isseroff R, Dillon KA, Israeli M, Biegon A . Regionally selective increases in mu opioid receptor density in the brains of suicide victims. Brain Res 1990; 530: 312–316.

    Article  CAS  PubMed  Google Scholar 

  237. Deisenhammer EA, Hofer S, Schwitzer O, Defrancesco M, Kemmler G, Wildt L et al. Oxytocin plasma levels in psychiatric patients with and without recent suicide attempt. Psychiatry Res 2012; 200: 59–62.

    Article  CAS  PubMed  Google Scholar 

  238. Jokinen J, Chatzittofis A, Hellstrom C, Nordstrom P, Uvnas-Moberg K, Asberg M . Low CSF oxytocin reflects high intent in suicide attempters. Psychoneuroendocrinology 2012; 37: 482–490.

    Article  CAS  PubMed  Google Scholar 

  239. Dwivedi Y, Rizavi HS, Teppen T, Zhang H, Mondal A, Roberts RC et al. Lower phosphoinositide 3-kinase (PI 3-kinase) activity and differential expression levels of selective catalytic and regulatory PI 3-kinase subunit isoforms in prefrontal cortex and hippocampus of suicide subjects. Neuropsychopharmacology 2008; 33: 2324–2340.

    Article  CAS  PubMed  Google Scholar 

  240. Pandey GN, Dwivedi Y, Pandey SC, Teas SS, Conley RR, Roberts RC et al. Low phosphoinositide-specific phospholipase C activity and expression of phospholipase C beta1 protein in the prefrontal cortex of teenage suicide subjects. Am J Psychiatry 1999; 156: 1895–1901.

    CAS  PubMed  Google Scholar 

  241. Feldcamp LA, Souza RP, Romano-Silva M, Kennedy JL, Wong AH . Reduced prefrontal cortex DARPP-32 mRNA in completed suicide victims with schizophrenia. Schizophr Res 2008; 103: 192–200.

    Article  PubMed  Google Scholar 

  242. Dwivedi Y, Rizavi HS, Shukla PK, Lyons J, Faludi G, Palkovits M et al. Protein kinase A in postmortem brain of depressed suicide victims: altered expression of specific regulatory and catalytic subunits. Biol Psychiatry 2004; 55: 234–243.

    Article  CAS  PubMed  Google Scholar 

  243. Pandey GN, Dwivedi Y, Ren X, Rizavi HS, Mondal AC, Shukla PK et al. Brain region specific alterations in the protein and mRNA levels of protein kinase A subunits in the post-mortem brain of teenage suicide victims. Neuropsychopharmacology 2005; 30: 1548–1556.

    Article  CAS  PubMed  Google Scholar 

  244. Pandey GN, Dwivedi Y, Rizavi HS, Ren X, Conley RR . Decreased catalytic activity and expression of protein kinase C isozymes in teenage suicide victims: a postmortem brain study. Arch Gen Psychiatry 2004; 61: 685–693.

    Article  CAS  PubMed  Google Scholar 

  245. Pandey GN, Dwivedi Y, Pandey SC, Conley RR, Roberts RC, Tamminga CA . Protein kinase C in the postmortem brain of teenage suicide victims. Neurosci Lett 1997; 228: 111–114.

    Article  CAS  PubMed  Google Scholar 

  246. Klempan TA, Ernst C, Deleva V, Labonte B, Turecki G . Characterization of QKI gene expression, genetics, and epigenetics in suicide victims with major depressive disorder. Biol Psychiatry 2009; 66: 824–831.

    Article  CAS  PubMed  Google Scholar 

  247. Cui H, Nishiguchi N, Ivleva E, Yanagi M, Fukutake M, Nushida H et al. Association of RGS2 gene polymorphisms with suicide and increased RGS2 immunoreactivity in the postmortem brain of suicide victims. Neuropsychopharmacology 2008; 33: 1537–1544.

    Article  CAS  PubMed  Google Scholar 

  248. Bani-Fatemi A, Goncalves VF, Zai C, de Souza R, Le Foll B, Kennedy JL et al. Analysis of CpG SNPs in 34 genes: association test with suicide attempt in schizophrenia. Schizophr Res 2013; 147: 262–268.

    Article  PubMed  Google Scholar 

  249. Fiori LM, Wanner B, Jomphe V, Croteau J, Vitaro F, Tremblay RE et al. Association of polyaminergic loci with anxiety, mood disorders, and attempted suicide. PLoS One 2010; 5: e15146.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  250. Sequeira A, Gwadry FG, Ffrench-Mullen JM, Canetti L, Gingras Y, Casero RA Jr et al. Implication of SSAT by gene expression and genetic variation in suicide and major depression. Arch Gen Psychiatry 2006; 63: 35–48.

    Article  CAS  PubMed  Google Scholar 

  251. Fiori LM, Mechawar N, Turecki G . Identification and characterization of spermidine/spermine N1-acetyltransferase promoter variants in suicide completers. Biol Psychiatry 2009; 66: 460–467.

    Article  CAS  PubMed  Google Scholar 

  252. Wasserman D, Geijer T, Rozanov V, Wasserman J . Suicide attempt and basic mechanisms in neural conduction: relationships to the SCN8A and VAMP4 genes. Am J Med Genet B Neuropsychiatr Genet 2005; 133B: 116–119.

    Article  CAS  PubMed  Google Scholar 

  253. Papale LA, Paul KN, Sawyer NT, Manns JR, Tufik S, Escayg A . Dysfunction of the Scn8a voltage-gated sodium channel alters sleep architecture, reduces diurnal corticosterone levels, and enhances spatial memory. J Biol Chem 2010; 285: 16553–16561.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  254. Sundman-Eriksson I, Allard P . [(3)H]Tiagabine binding to GABA transporter-1 (GAT-1) in suicidal depression. J Affect Disord 2002; 71: 29–33.

    Article  CAS  PubMed  Google Scholar 

  255. Bowden C, Cheetham SC, Lowther S, Katona CL, Crompton MR, Horton RW . Dopamine uptake sites, labelled with [3H]GBR12935, in brain samples from depressed suicides and controls. Eur Neuropsychopharmacol 1997; 7: 247–252.

    Article  CAS  PubMed  Google Scholar 

  256. Ryding E, Ahnlide JA, Lindstrom M, Rosen I, Traskman-Bendz L . Regional brain serotonin and dopamine transporter binding capacity in suicide attempters relate to impulsiveness and mental energy. Psychiatry Res 2006; 148: 195–203.

    Article  CAS  PubMed  Google Scholar 

  257. Caspi A, Sugden K, Moffitt TE, Taylor A, Craig IW, Harrington H et al. Influence of life stress on depression: moderation by a polymorphism in the 5-HTT gene. Science 2003; 301: 386–389.

    Article  CAS  PubMed  Google Scholar 

  258. Zalsman G, Frisch A, Bromberg M, Gelernter J, Michaelovsky E, Campino A et al. Family-based association study of serotonin transporter promoter in suicidal adolescents: no association with suicidality but possible role in violence traits. Am J Med Genet 2001; 105: 239–245.

    Article  CAS  PubMed  Google Scholar 

  259. Little KY, McLauglin DP, Ranc J, Gilmore J, Lopez JF, Watson SJ et al. Serotonin transporter binding sites and mRNA levels in depressed persons committing suicide. Biol Psychiatry 1997; 41: 1156–1164.

    Article  CAS  PubMed  Google Scholar 

  260. Clayden RC, Zaruk A, Meyre D, Thabane L, Samaan Z . The association of attempted suicide with genetic variants in the SLC6A4 and TPH genes depends on the definition of suicidal behavior: a systematic review and meta-analysis. Transl Psychiatry 2012; 2: e166.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  261. Sokolowski M, Wasserman J, Wasserman D . Association of polymorphisms in the SLIT2 axonal guidance gene with anger in suicide attempters. Mol Psychiatry 2010; 15: 10–11.

    Article  CAS  PubMed  Google Scholar 

  262. Fiori LM, Turecki G . Genetic and epigenetic influences on expression of spermine synthase and spermine oxidase in suicide completers. Int J Neuropsychopharmacol 2010; 13: 725–736.

    Article  CAS  PubMed  Google Scholar 

  263. Olsson A, Regnell G, Traskman-Bendz L, Ekman R, Westrin A . Cerebrospinal neuropeptide Y and substance P in suicide attempters during long-term antidepressant treatment. Eur Neuropsychopharmacol 2004; 14: 479–485.

    Article  CAS  PubMed  Google Scholar 

  264. Giegling I, Rujescu D, Mandelli L, Schneider B, Hartmann AM, Schnabel A et al. Tachykinin receptor 1 variants associated with aggression in suicidal behavior. Am J Med Genet B Neuropsychiatr Genet 2007; 144B: 757–761.

    Article  CAS  PubMed  Google Scholar 

  265. Burnet PW, Harrison PJ . Substance P (NK1) receptors in the cingulate cortex in unipolar and bipolar mood disorder and schizophrenia. Biol Psychiatry 2000; 47: 80–83.

    Article  CAS  PubMed  Google Scholar 

  266. Stockmeier CA, Shi X, Konick L, Overholser JC, Jurjus G, Meltzer HY et al. Neurokinin-1 receptors are decreased in major depressive disorder. Neuroreport 2002; 13: 1223–1227.

    Article  CAS  PubMed  Google Scholar 

  267. Wasserman D, Geijer T, Sokolowski M, Rozanov V, Wasserman J . Genetic variation in the hypothalamic-pituitary-adrenocortical axis regulatory factor, T-box 19, and the angry/hostility personality trait. Genes Brain Behav 2007; 6: 321–328.

    Article  CAS  PubMed  Google Scholar 

  268. Omrani MD, Bagheri M, Bushehri B, Azizi F, Anoshae MR . The association of TGF-beta1 codon 10 polymorphism with suicide behavior. Am J Med Genet B Neuropsychiatr Genet 2012; 159B: 772–775.

    Article  CAS  PubMed  Google Scholar 

  269. Kim YK, Lee SW, Kim SH, Shim SH, Han SW, Choi SH et al. Differences in cytokines between non-suicidal patients and suicidal patients in major depression. Prog Neuropsychopharmacol Biol Psychiatry 2008; 32: 356–361.

    Article  CAS  PubMed  Google Scholar 

  270. Mahon PB, Stutz AM, Seifuddin F, Huo Y, Goes FS, Jancic D et al. Case-control association study of TGOLN2 in attempted suicide. Am J Med Genet B Neuropsychiatr Genet 2010; 153B: 1016–1023.

    CAS  PubMed  Google Scholar 

  271. Persson ML, Wasserman D, Geijer T, Jonsson EG, Terenius L . Tyrosine hydroxylase allelic distribution in suicide attempters. Psychiatry Res 1997; 72: 73–80.

    Article  CAS  PubMed  Google Scholar 

  272. Baumann B, Danos P, Diekmann S, Krell D, Bielau H, Geretsegger C et al. Tyrosine hydroxylase immunoreactivity in the locus coeruleus is reduced in depressed non-suicidal patients but normal in depressed suicide patients. Eur Arch Psychiatry Clin Neurosci 1999; 249: 212–219.

    Article  CAS  PubMed  Google Scholar 

  273. Ordway GA, Smith KS, Haycock JW . Elevated tyrosine hydroxylase in the locus coeruleus of suicide victims. J Neurochem 1994; 62: 680–685.

    Article  CAS  PubMed  Google Scholar 

  274. Biegon A, Fieldust S . Reduced tyrosine hydroxylase immunoreactivity in locus coeruleus of suicide victims. Synapse 1992; 10: 79–82.

    Article  CAS  PubMed  Google Scholar 

  275. Gos T, Krell D, Bielau H, Brisch R, Trubner K, Steiner J et al. Tyrosine hydroxylase immunoreactivity in the locus coeruleus is elevated in violent suicidal depressive patients. Eur Arch Psychiatry Clin Neurosci 2008; 258: 513–520.

    Article  PubMed  Google Scholar 

  276. Tonelli LH, Stiller J, Rujescu D, Giegling I, Schneider B, Maurer K et al. Elevated cytokine expression in the orbitofrontal cortex of victims of suicide. Acta Psychiatr Scand 2008; 117: 198–206.

    Article  CAS  PubMed  Google Scholar 

  277. Nielsen DA, Goldman D, Virkkunen M, Tokola R, Rawlings R, Linnoila M . Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Arch Gen Psychiatry 1994; 51: 34–38.

    Article  CAS  PubMed  Google Scholar 

  278. Zill P, Buttner A, Eisenmenger W, Muller J, Moller HJ, Bondy B . Predominant expression of tryptophan hydroxylase 1 mRNA in the pituitary: a postmortem study in human brain. Neuroscience 2009; 159: 1274–1282.

    Article  CAS  PubMed  Google Scholar 

  279. Boldrini M, Underwood MD, Mann JJ, Arango V . More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides. Brain Res 2005; 1041: 19–28.

    Article  CAS  PubMed  Google Scholar 

  280. Bonkale WL, Murdock S, Janosky JE, Austin MC . Normal levels of tryptophan hydroxylase immunoreactivity in the dorsal raphe of depressed suicide victims. J Neurochem 2004; 88: 958–964.

    Article  CAS  PubMed  Google Scholar 

  281. Zill P, Buttner A, Eisenmenger W, Moller HJ, Bondy B, Ackenheil M . Single nucleotide polymorphism and haplotype analysis of a novel tryptophan hydroxylase isoform (TPH2) gene in suicide victims. Biol Psychiatry 2004; 56: 581–586.

    Article  CAS  PubMed  Google Scholar 

  282. De Luca V, Mueller DJ, Tharmalingam S, King N, Kennedy JL . Analysis of the novel TPH2 gene in bipolar disorder and suicidality. Mol Psychiatry 2004; 9: 896–897.

    Article  CAS  PubMed  Google Scholar 

  283. Bach-Mizrachi H, Underwood MD, Kassir SA, Bakalian MJ, Sibille E, Tamir H et al. Neuronal tryptophan hydroxylase mRNA expression in the human dorsal and median raphe nuclei: major depression and suicide. Neuropsychopharmacology 2006; 31: 814–824.

    Article  CAS  PubMed  Google Scholar 

  284. Isung J, Aeinehband S, Mobarrez F, Martensson B, Nordstrom P, Asberg M et al. Low vascular endothelial growth factor and interleukin-8 in cerebrospinal fluid of suicide attempters. Transl Psychiatry 2012; 2: e196.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  285. Isung J, Mobarrez F, Nordstrom P, Asberg M, Jokinen J . Low plasma vascular endothelial growth factor (VEGF) associated with completed suicide. World J Biol Psychiatry 2012; 13: 468–473.

    Article  PubMed  Google Scholar 

  286. Sequeira A, Kim C, Seguin M, Lesage A, Chawky N, Desautels A et al. Wolfram syndrome and suicide: evidence for a role of WFS1 in suicidal and impulsive behavior. Am J Med Genet B Neuropsychiatr Genet 2003; 119B: 108–113.

    Article  PubMed  Google Scholar 

  287. Zalsman G, Mann MJ, Huang YY, Oquendo MA, Brent DA, Burke AK et al. Wolframin gene H611R polymorphism: no direct association with suicidal behavior but possible link to mood disorders. Prog Neuropsychopharmacol Biol Psychiatry 2009; 33: 707–710.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  288. Thakker-Varia S, Alder J . Neuropeptides in depression: role of VGF. Behav Brain Res 2009; 197: 262–278.

    Article  CAS  PubMed  Google Scholar 

  289. Yanagi M, Shirakawa O, Kitamura N, Okamura K, Sakurai K, Nishiguchi N et al. Association of 14-3-3 epsilon gene haplotype with completed suicide in Japanese. J Hum Genet 2005; 50: 210–216.

    Article  PubMed  Google Scholar 

  290. Lett TA, Zai CC, Tiwari AK, Shaikh SA, Likhodi O, Kennedy JL et al. ANK3, CACNA1C and ZNF804A gene variants in bipolar disorders and psychosis subphenotype. World J Biol Psychiatry 2011; 12: 392–397.

    Article  PubMed  Google Scholar 

  291. Hess JL, Glatt SJ . How might ZNF804A variants influence risk for schizophrenia and bipolar disorder? A literature review, synthesis, and bioinformatic analysis. Am J Med Genet B Neuropsychiatr Genet 2014; 165: 28–40.

    Article  CAS  Google Scholar 

  292. Kin T, Ono Y . Idiographica: a general-purpose web application to build idiograms on-demand for human, mouse and rat. Bioinformatics 2007; 23: 2945–2946.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The study was funded by the Marianne and Marcus Wallenberg Foundation, the American Foundation for Suicide Prevention, and Knut and Alice Wallenberg Foundation.

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  1. National Centre for Suicide Research and Prevention of Mental Ill-Health (NASP), Karolinska Institute (KI), Stockholm, Sweden

    M Sokolowski, J Wasserman & D Wasserman

  2. WHO Collaborating Centre for Research, Methods Development and Training in Suicide Prevention, Stockholm, Sweden

    D Wasserman

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Correspondence to M Sokolowski.

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Sokolowski, M., Wasserman, J. & Wasserman, D. An overview of the neurobiology of suicidal behaviors as one meta-system. Mol Psychiatry 20, 56–71 (2015). https://doi.org/10.1038/mp.2014.101

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