The role of the serotonergic system in suicidal behavior

Neuropsychiatric Disease and Treatment

Volumn 9, Issue , 2013, Pages 1699-1716

  Sadkowski, Marta ^a   Dennis, Brittany ^a   Clayden, Robert C ^a   ElSheikh, Wala ^b   Rangarajan, Sumathy ^b   DeJesus, Jane ^b   Samaan, Zainab ^a,c  

^a MCMASTER UNIVERSITY   (Canada)

^b MCMASTER UNIVERSITY   (Canada)

^c MCMASTER UNIVERSITY   (Canada)

Author keywords

Genetic; Serotonin; Suicide

Indexed keywords

SEROTONIN 1A RECEPTOR; SEROTONIN 1B RECEPTOR; SEROTONIN 2A RECEPTOR;

ALLELE; DDC GENE; ETHNICITY; GENE; GENETIC ASSOCIATION; GENETIC VARIABILITY; HTR1A GENE; HTR1B GENE; HTR2A GENE; HUMAN; MAOA GENE; MAOB GENE; PATHOPHYSIOLOGY; REVIEW; SEROTONINERGIC SYSTEM; SINGLE NUCLEOTIDE POLYMORPHISM; SLC18A2 GENE; SLC6A4 GENE; SUICIDE ATTEMPT; SYSTEMATIC REVIEW; TPH1 GENE; TPH2 GENE;

EID: 84887146320     PISSN: 11766328     EISSN: 11782021     Source Type: Journal    
DOI: 10.2147/NDT.S50300     Document Type: Review

References (143)

1. Rapport MM, Geen AA, Page IH. Serum vasoconstrictor, serotonin; isolation and characterization. J Biol Chem. 1948;176(3):1243-1251.
2. Erspramer V, Asero B. Identifcation of enteramine, the specifc hormone of the enterochromaffn cell system, as 5-hydroxytryptamine. Nature. 1952;169(4306):800-801.
3. Twarog BM, Page IH. Serotonin content of some mammalian tissues and urine and a method for its determination. Am J Physiol. 1953; 175(1):157-161.
4. Sullivan PF, Neale MC, Kendler KS. Genetic epidemiology of major depression: review and meta-analysis. Am J Psychiatry.2000;157(10):1552-1562.
5. Côté F, Fligny C, Fromes Y, Mallet J, Vodjdani G. Recent advances in understanding serotonin regulation of cardiovascular function. Trends Mol Med. 2004;10(5):232-238.
6. Walther DJ, Peter JU, Bashammakh S, et al. Synthesis of serotonin by a second tryptophan hydroxylase isoform. Science. 2003;299(5603):76.
7. Nilsson T, Longmore J, Shaw D, et al. Characterisation of 5-HT receptors in human coronary arteries by molecular and pharmacological techniques. Eur J Pharmacol. 1999;372(1):49-56.
8. Yildiz O, Smith JR, Purdy RE. Serotonin and vasoconstrictor synergism. Life Sci. 1998;62(19):1723-1732.
9. Yusuf S, Al-Saady N, Camm AJ. 5-hydroxytryptamine and atrial fbrillation: how signifcant is this piece in the puzzle? J Cardiovasc Electrophysiol. 2003;14(2):209-214.
10. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterolog y. 2007;132(1):397-414.
11. Kirchgessner AL, Liu MT, Gershon MD. In situ identifcation and visualization of neurons that mediate enteric and enteropancreatic refexes. J Comp Neurol. 1996;371(2):270-286.
12. Kirchgessner AL, Tamir H, Gershon MD. Identifcation and stimulation by serotonin of intrinsic sensory neurons of the submucosal plexus of the guinea pig gut: activity-induced expression of Fos immunoreactivity. J Neurosci. 1992;12(1):235-248.
13. Cooke HJ, Sidhu M, Wang YZ. 5-HT activates neural refexes regulating secretion in the guinea-pig colon. Neurogastroenterol Motil. 1997;9(3):181-186.
14. Kim M, Cooke HJ, Javed NH, Carey H V, Christof F, Raybould HE. D-glucose releases 5-hydroxytryptamine from human BON cells as a model of enterochromaffn cells. Gastroenterology. 2001;121(6): 1400-1406.
15. Sidhu M, Cooke HJ. Role for 5-HT and ACh in submucosal refexes mediating colonic secretion. Am J Physiol. 1995;269(3 Pt 1): G346-G351.
16. Pan H, Gershon MD. Activation of intrinsic afferent pathways in submucosal ganglia of the guinea pig small intestine. J Neurosci. 2000;20(9):3295-3309.
17. Bulbring E, Crema A. Observations concerning the action of 5- hydroxytryptamine on the peristaltic reflex. Br J Pharmacol Chemother. 1958;13(4):444-457.
18. Törk I. Anatomy of the serotonergic system. Ann N Y Acad Sci. 1990;600:9-34; discussion 34-35.
19. Lesch KP, Araragi N, Waider J, van den Hove D, Gutknecht L. Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour. Philos Trans R Soc Lond, B, Biol Sci. 2012;367(1601):2426-2443.
20. Andrade C, Sandarsh S, Chethan KB, Nagesh KS. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry. 2010;71(12):1565-1575.
21. World Health Organization. Suicide prevention (SUPRE). Vol 2012 2012.
22. Ministry of Health Promotion. Prevention of Injury: Guidance Document. Toronto, ON: Standards, Programs and Community Development Branch, Ministry of Health Promotion; 2010.
23. Mann JJ. Neurobiology of suicidal behavior. Nat Rev Neurosci. 2003;4(10):819-828.
24. Practice guideline for the assessment and treatment of patients with suicidal behaviors. Am J Psychiatry. 2003;160(Suppl 11):1-60.
25. Fowler JC. Suicide risk assessment in clinical practice: pragmatic guidelines for imperfect assessments. Psychotherapy (Chic). 2012;49(1): 81-90.
26. Guze SB, Robins E. Suicide and primary affective disorders. Br J Psychiatry. 1970;117(539):437-438.
27. Runeson B. Mental disorder in youth suicide. DSM-III-R Axes I and II. Acta Psychiatr Scand. 1989;79(5):490-497.
28. Beautrais AL, Joyce PR, Mulder RT, Fergusson DM, Deavoll BJ, Nightingale SK. Prevalence and comorbidity of mental disorders in persons making serious suicide attempts: a case-control study. Am J Psychiatry. 1996;153(8):1009-1014.
29. Sareen J, Cox BJ, Aff TO, et al. Anxiety disorders and risk for suicidal ideation and suicide attempts: a population-based longitudinal study of adults. Arch Gen Psychiatry. 2005;62(11):1249-1257.
30. Clements C, Morriss R, Jones S, Peters S, Roberts C, Kapur N. Suicide in bipolar disorder in a national English sample, 1996-2009: frequency, trends and characteristics. Psychol Med. 2013:1-10.
31. Diaconu G, Turecki G. Obsessive-compulsive personality disorder and suicidal behavior: evidence for a positive association in a sample of depressed patients. J Clin Psychiatry. 2009;70(11):1551-1556.
32. Mandelli L, Serretti A. Gene environment interaction studies in depression and suicidal behavior: an update. Neurosci Biobehav Rev. Epub July 22, 2013.
33. Paykel ES. Life stress, depression and attempted suicide. J Human Stress. 1976;2(3):3-12.
34. World Health Organization. Prevention of Mental Disorders: Effective Interventions and Policy Options, Summary Report. Geneva, Switzerland: World Health Organization; 2004.
35. Linkowska K, Daca P, Sykutera M, Pufal E, Bloch-Bogusławska E, Grzybowski T. Search for association between suicide and 5-HTT, MAOA and DAT polymorphism in Polish males. Arch Med Sadowej Kryminol. 2010;60(2-3):112-117.
36. Roy A. Family history of suicide. Arch Gen Psychiatry. 1983;40(9): 971-974.
37. Roy A, Segal NL, Sarchiapone M. Attempted suicide among living co-twins of twin suicide victims. Am J Psychiatry. 1995;152(7):1075-1076.
38. Gould MS, Fisher P, Parides M, Flory M, Shaffer D. Psychosocial risk factors of child and adolescent completed suicide. Arch Gen Psychiatry. 1996;53(12):1155-1162.
39. Brent DA, Mann JJ. Family genetic studies, suicide, and suicidal behavior. Am J Med Genet C Semin Med Genet. 2005;133C(1):13-24.
40. Mann JJ, Brent DA, Arango V (2001) The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system. Neuropsychopharmacolog y 24:467-477.
41. Stanley M, Mann JJ. Suicide and serotonin receptors. Lancet. 1984; 1(8372):349.
42. Stanley M, Mann JJ. Increased serotonin-2 binding sites in frontal cortex of suicide victims. Lancet. 1983;1(8318):214-216.
43. Stanley M, Virgilio J, Gershon S. Tritiated imipramine binding sites are decreased in the frontal cortex of suicides. Science. 1982;216(4552): 1337-1339.
44. Hughes JH, Dunne F, Young AH. Effects of acute tryptophan depletion on mood and suicidal ideation in bipolar patients symptomatically stable on lithium. Br J Psychiatry. 2000;177:447-451.
45. McCloskey MS, Ben-Zeev D, Lee R, Berman ME, Coccaro EF. Acute tryptophan depletion and self-injurious behavior in aggressive patients and healthy volunteers. Psychopharmacology (Berl). 2009;203(1):53-61.
46. Sublette ME, Galfalvy HC, Fuchs D, et al. Plasma kynurenine levels are elevated in suicide attempters with major depressive disorder. Brain Behav Immun. 2011;25(6):1272-1278.
47. De Ponti F, Tonini M. Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-332.
48. Wong DT, Bymaster FP. Development of antidepressant drugs. Fluoxetine (Prozac) and other selective serotonin uptake inhibitors. Adv Exp Med Biol. 1995;363:77-95.
49. Hammad TA, Laughren T, Racoosin J. Suicidality in pediatric patients treated with antidepressant drugs. Arch Gen Psychiatry. 2006;63(3):332-339.
50. Gunnell D, Saperia J, Ashby D. Selective serotonin reuptake inhibitors (SSRIs) and suicide in adults: meta-analysis of drug company data from placebo controlled, randomised controlled trials submitted to the MHRA's safety review. BMJ. 2005;330(7488):385.
51. Hetrick SE, McKenzie JE, Cox GR, Simmons MB, Merry SN. Newer generation antidepressants for depressive disorders in children and adolescents. Cochrane Database Syst Rev. 2012;11:CD004851.
52. Tondo L, Baldessarini RJ. Long-term lithium treatment in the prevention of suicidal behavior in bipolar disorder patients. Epidemiol Psichiatr Soc. 2009;18(3):179-183.
53. Gibbons R, Mann JJ. Proper studies of selective serotonin reuptake inhibitors are needed for youth with depression. CMAJ. 2009;180(3): 270-271.
54. Nakagawa A, Grunebaum MF, Ellis SP, et al. Association of suicide and antidepressant prescription rates in Japan, 1999-2003. J Clin Psychiatry. 2007;68(6):908-916.
55. Castelpietra G, Morsanutto A, Pascolo-Fabrici E, Isacsson G. Antidepressant use and suicide prevention: a prescription database study in the region Friuli Venezia Giulia, Italy. Acta Psychiatr Scand. 2008;118(5):382-388.
56. Bach H, Arango V. Chapter 2: Neuroanatomy of serotonergic abnormalities in suicide. In: Dwivedi Y, editor. The Neurobiological Basis of Suicide. Boca Raton, FL: CRC Press; 2012. Available online: http://www.ncbi.nlm.nih.gov.libaccess.lib.mcmaster.ca/books/NBK107204/.
57. Yoon HK, Kim YK. TPH2-703G/T SNP may have important effect on susceptibility to suicidal behavior in major depression. Prog Neuropsychopharmacol Biol Psychiatry. 2009;33(3):403-409.
58. Patel PD, Pontrello C, Burke S. Robust and tissue-specifc expression of TPH2 versus TPH1 in rat raphe and pineal gland. Biol Psychiatry. 2004;55(4):428-433.
59. Katzung BG. Basic and Clinical Pharmacology. New York, NY: McGraw-Hill Medical; 2007.
60. Nielsen DA, Jenkins GL, Stefanisko KM, Jefferson KK, Goldman D. Sequence, splice site and population frequency distribution analyses of the polymorphic human tryptophan hydroxylase intron 7. Brain Res Mol Brain Res. 1997;45(1):145-148.
61. 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(1):34-38.
62. Bennett PJ, McMahon WM, Watabe J, et al. Tryptophan hydroxylase polymorphisms in suicide victims. Psychiatr Genet. 2000;10(1):13-17.
63. Geijer T, Frisch A, Persson ML, et al. Search for association between suicide attempt and serotonergic polymorphisms. Psychiatr Genet. 2000;10(1):19-26.
64. Koller G, Engel RR, Preuss UW, et al. Tryptophan hydroxylase gene 1 polymorphisms are not associated with suicide attempts in alcohol-dependent individuals. Addict Biol. 2005;10(3):269-273.
65. Saetre P, Lundmark P, Wang A et al. (2010) The tryptophan hydroxylase 1 (TPH1) gene, schizophrenia susceptibility, and suicidal behavior: a multi-centre case-control study and meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 153B: 387-396.
66. Courtet P, Jollant F, Castelnau D, Astruc B, Buresi C, Malafosse A. Implication of genes of the serotonergic system on vulnerability to suicidal behavior. J Psychiatry Neurosci. 2004;29(5):350-359. French.
67. Yoon HK, Kim YK. Association between serotonin-related gene polymorphisms and suicidal behavior in depressive patients. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(5):1293-1297.
68. Tsai SJ, Hong CJ, Wang YC. Tryptophan hydroxylase gene polymorphism (A218C) and suicidal behaviors. Neuroreport. 1999;10(18): 3773-3775.
69. Rujescu D, Giegling I, Sato T, Hartmann AM, Möller HJ. Genetic variations in tryptophan hydroxylase in suicidal behavior: analysis and meta-analysis. Biol Psychiatry. 2003;54(4):465-473.
70. Bellivier F, Chaste P, Malafosse A. Association between the TPH gene A218C polymorphism and suicidal behavior: a meta-analysis. Am J Med Genet B Neuropsychiatr Genet. 2004;124B(1):87-91.
71. Du L, Faludi G, Palkovits M, Bakish D, Hrdina PD. Serotonergic genes and suicidality. Crisis. 2001;22(2):54-60.
72. Rotondo A, Schuebel K, Bergen A, et al. Identifcation of four variants in the tryptophan hydroxylase promoter and association to behavior. Mol Psychiatry. 1999;4(4):360-368.
73. Turecki G, Zhu Z, Tzenova J, et al. TPH and suicidal behavior: a study in suicide completers. Mol Psychiatry. 2001;6(1):98-102.
74. Brun L, Ngu LH, Keng WT, et al. Clinical and biochemical features of aromatic L-amino acid decarboxylase defciency. Neurology. 2010; 75(1):64-71.
75. Sumi-Ichinose C, Ichinose H, Takahashi E, Hori T, Nagatsu T. Molecular cloning of genomic DNA and chromosomal assignment of the gene for human aromatic L-amino acid decarboxylase, the enzyme for catecholamine and serotonin biosynthesis. Biochemistry. 1992;31(8):2229-2238.
76. Speight G, Turic D, Austin J, et al. Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder. Mol Psychiatry. 2000;5(3):327-331.
77. Giegling I, Moreno-De-Luca D, Rujescu D, et al. Dopa decarboxylase and tyrosine hydroxylase gene variants in suicidal behavior. Am J Med Genet B Neuropsychiatr Genet. 2008;147(3):308-315.
78. Surratt CK, Persico AM, Yang XD, et al. A human synaptic vesicle monoamine transporter cDNA predicts posttranslational modifcations, reveals chromosome 10 gene localization and identifes TaqI RFLPs. FEBS Lett. 1993;318(3):325-330.
79. Peter D, Finn JP, Klisak I, et al. Chromosomal localization of the human vesicular amine transporter genes. Genomics. 1993;18(3):720-723.
80. Glatt CE, DeYoung JA, Delgado S, et al. Screening a large reference sample to identify very low frequency sequence variants: comparisons between two genes. Nat Genet. 2001;27(4):435-438.
81. Burman J, Tran CH, Glatt C, Freimer NB, Edwards RH. The effect of rare human sequence variants on the function of vesicular monoamine transporter 2. Pharmacogenetics. 2004;14(9):587-594.
82. Trowbridge S, Narboux-Nême N, Gaspar P. Genetic models of serotonin (5-HT) depletion: what do they tell us about the developmental role of 5-HT? Anat Rec (Hoboken). 2011;294(10):1615-1623.
83. Ozelius L, Hsu YP, Bruns G, et al. Human monoamine oxidase gene (MAOA): chromosome position (Xp21-p11) and DNA polymorphism. Genomics. 1988;3(1):53-58.
84. 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 defnition of suicidal behavior: a systematic review and meta-analysis. Transl Psychiatry. 2012;2:e166.
85. Hung CF, Lung F W, Hung TH, et al. Monoamine oxidase A gene polymorphism and suicide: an association study and meta-analysis. J Affect Disord. 2012;136(3):643-649.
86. Mann JJ, Stanley M. Postmortem monoamine oxidase enzyme kinetics in the frontal cortex of suicide victims and controls. Acta Psychiatr Scand. 1984;69(2):135-139.
87. Sherif F, Marcusson J, Oreland L. Brain gamma-aminobutyrate transami-nase and monoamine oxidase activities in suicide victims. Eur Arch Psychiatry Clin Neurosci. 1991;241(3):139-144.
88. Lan NC, Heinzmann C, Gal A, et al. Human monoamine oxidase A and B genes map to Xp 11.23 and are deleted in a patient with Norrie disease. Genomics. 1989;4(4):552-559.
89. Sabol SZ, Hu S, Hamer D. A functional polymorphism in the monoamine oxidase A gene promoter. Hum Genet. 1998;103(3): 273-279.
90. Lung FW, Tzeng DS, Huang MF, Lee MB. Association of the MAOA promoter uVNTR polymorphism with suicide attempts in patients with major depressive disorder. BMC Med Genet. 2011;12:74.
91. Ono H, Shirakawa O, Nishiguchi N, et al. No evidence of an association between a functional monoamine oxidase a gene polymorphism and completed suicides. Am J Med Genet. 2002;114(3):340-342.
92. Asberg M. Neurotransmitters and suicidal behavior. The evidence from cerebrospinal fluid studies. Ann N Y Acad Sci. 1997;836: 158-181.
93. Asberg M, Träskman L, Thorén P. 5-HIAA in the cerebrospinal fuid. A biochemical suicide predictor? Arch Gen Psychiatry. 1976; 33(10):1193-1197.
94. Mann JJ, Currier D. A review of prospective studies of biologic predictors of suicidal behavior in mood disorders. Arch Suicide Res. 2007;11(1):3-16.
95. Jokinen J, Nordström AL, Nordström P. Cerebrospinal fuid mono-amine metabolites and suicide. Nord J Psychiatry. 2009;63(4): 276-279.
96. Samuelsson M, Jokinen J, Nordström AL, Nordström P. CSF 5-HIAA, suicide intent and hopelessness in the prediction of early suicide in male high-risk suicide attempters. Acta Psychiatr Scand. 2006; 113(1):44-47.
97. Träskman L, Asberg M, Bertilsson L, Sjöstrand L. Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry. 1981;38(6):631-636.
98. Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK. Low cerebrospinal fuid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci. 1983;33(26):2609-2614.
99. Nordstöm P, Asgård U. Suicide risk by age and birth cohort in Sweden. Crisis. 1986;7(2):75-80.
100. Oquendo MA, Placidi GP, Malone KM, 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.
101. Milak MS, Parsey RV, Keilp J, Oquendo MA, Malone KM, Mann JJ. Neuroanatomic correlates of psychopathologic components of major depressive disorder. Arch Gen Psychiatry. 2005;62(4): 397-408.
102. Raymond JR, Mukhin YV, Gelasco A, et al. Multiplicity of mechanisms of serotonin receptor signal transduction. Pharmacol Ther. 2001;92(2-3):179-212.
103. Blier P, Lista A, De Montigny C. Differential properties of pre- and postsynaptic 5-hydroxytryptamine1A receptors in the dorsal raphe and hippocampus: I. Effect of spiperone. J Pharmacol Exp Ther. 1993;265(1):7-15.
104. Kobilka BK, Frielle T, Collins S, et al. An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature. 1987;329(6134):75-79.
105. David SP, Murthy N V, Rabiner EA, et al. A functional genetic variation of the serotonin (5-HT) transporter affects 5-HT1A receptor binding in humans. J Neurosci. 2005;25(10):2586-2590.
106. Hettema JM, An SS, van den Oord EJ, Neale MC, Kendler KS, Chen X. Association study between the serotonin 1A receptor (HTR1A) gene and neuroticism, major depression, and anxiety disorders. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(5): 661-666.
107. Göthert M, Propping P, Bönisch H, Brüss M, Nöthen MM. Genetic variation in human 5-HT receptors: potential pathogenetic and pharmacological role. Ann N Y Acad Sci. 1998;861:26-30.
108. Wasserman D, Geijer T, Sokolowski M, Rozanov V, Wasserman J. The serotonin 1A receptor C(-1019)G polymorphism in relation to suicide attempt. Behav Brain Funct. 2006;2:14.
109. Serretti A, Mandelli L, Giegling I, et al. HTR2C and HTR1A gene variants in German and Italian suicide attempters and completers. Am J Med Genet B Neuropsychiatr Genet. 2007;144B(3):291-299.
110. Videtic A, Zupanc T, Pregelj P, Balazic J, Tomori M, Komel R. Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C.G in Slovenian suicide victims. Eur Arch Psychiatry Clin Neurosci. 2009;259(4):234-238.
111. Jin H, Oksenberg D, Ashkenazi, et al. Characterization of the human 5-hydroxytryptamine 1B receptor. J Biol Chem. 1992;267(9): 5735-5738.
112. Sanders AR, Cao Q, Taylor J, et al. Genetic diversity of the human serotonin receptor 1B (HTR1B) gene. Genomics. 2001;72(1): 1-14.
113. Kiel S, Brüss M, Bönisch H, Göthert M. Pharmacological properties of the naturally occurring Phe-124-Cys variant of the human 5-HT1B receptor: changes in ligand binding, G-protein coupling and second messenger formation. Pharmacogenetics. 2000;10(7): 655-666.
114. Sanders AR, Duan J, Gejman PV. DNA variation and psychopharma-cology of the human serotonin receptor 1B (HTR1B) gene. Pharma-cogenomics. 2002;3(6):745-762.
115. Huang YY, Grailhe R, Arango V, Hen R, Mann JJ. Relationship of psy-chopathology to the human serotonin1B genotype and receptor binding kinetics in postmortem brain tissue. Neuropsychopharmacology. 1999;21(2):238-246.
116. Stefulj J, Büttner A, Skavic J, et al. Serotonin 1B (5HT-1B) receptor polymorphism (G861C) in suicide victims: association studies in German and Slavic population. Am J Med Genet B Neuropsychiatr Genet. 2004;127B(1):48-50.
117. Rujescu D, Giegling I, Sato T, Möller HJ. Lack of association between serotonin 5-HT1B receptor gene polymorphism and suicidal behavior. Am J Med Genet B Neuropsychiatr Genet. 2003;116B(1): 69-71.
118. Nishiguchi N, Shirakawa O, Ono H, et al. No evidence of an association between 5HT1B receptor gene polymorphism and suicide victims in a Japanese population. Am J Med Genet. 2001;105(4):343-345.
119. Cornea-Hébert V, Riad M, Wu C, Singh SK, Descarries L. Cellular and subcellular distribution of the serotonin 5-HT2A receptor in the central nervous system of adult rat. J Comp Neurol. 1999;409(2): 187-209.
120. Barnes NM, Sharp T. A review of central 5-HT receptors and their function. Neuropharmacology. 1999;38(8):1083-1152.
121. Zhang J, Shen Y, He G, et al. Lack of association between three serotonin genes and suicidal behavior in Chinese psychiatric patients. Prog Neuropsychopharmacol Biol Psychiatry. 2008;32(2):467-471.
122. Ertugrul A, Kennedy JL, Masellis M, Basile VS, Jayathilake K, Meltzer HY. No association of the T102C polymorphism of the serotonin 2A receptor gene (HTR2A) with suicidality in schizophrenia. Schizophr Res. 2004;69(2-3):301-305.
123. Pooley EC, Houston K, Hawton K, Harrison PJ. Deliberate self-harm is associated with allelic variation in the tryptophan hydroxylase gene (TPH A779C), but not with polymorphisms in fve other serotonergic genes. Psychol Med. 2003;33(5):775-783.
124. Ramamoorthy S, Leibach FH, Mahesh VB, Ganapathy V. Partial purifcation and characterization of the human placental serotonin transporter. Placenta. 1993;14(4):449-461.
125. Heils A, Teufel A, Petri S, et al. Allelic variation of human serotonin transporter gene expression. J Neurochem. 1996;66(6):2621-2624.
126. Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996;274(5292):1527-1531.
127. Mergen H, Demirel B, Akar T, Senol E. Lack of association between the serotonin transporter and tryptophan hydroxylase gene polymorphisms and completed suicide. Psychiatr Genet. 2006;16(2):53.
128. Owens MJ, Nemeroff CB. Role of serotonin in the pathophysiol-ogy of depression: focus on the serotonin transporter. Clin Chem. 1994;40(2):288-295.
129. Ressler KJ, Nemeroff CB. Role of serotonergic and noradrenergic systems in the pathophysiology of depression and anxiety disorders. Depress Anxiety. 2000;12 Suppl 1:2-19.
130. Asberg M, Nordström P, Träskman-Bendz L. Cerebrospinal fuid studies in suicide. An overview. Ann N Y Acad Sci. 1986;487:243-255.
131. Hrdina PD, Demeter E, Vu TB, Sótónyi P, Palkovits M. 5-HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5-HT2 sites in cortex and amygdala. Brain Res. 1993;614(1-2):37-44.
132. Turecki G, Brière R, Dewar K, et al. Prediction of level of serotonin 2A receptor binding by serotonin receptor 2A genetic variation in postmortem brain samples from subjects who did or did not commit suicide. Am J Psychiatry. 1999;156(9):1456-1458.
133. Arango V, Ernsberger P, Marzuk PM, et al. Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry. 1990;47(11):1038-1047.
134. Gonzalez-Castro TB, Tovilla-Zarate CA, Juarez-Rojop I, Pool Garcia S, Genis A, et al. (2013) Association of 5HTR1A gene variants with suicidal behavior: Case-control study and updated meta-analysis. J Psychiatr Res.
135. Anguelova M, Benkelfat C, Turecki G (2003) A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior. Mol Psychiatry 8:646-653.
136. Mann JJ, Arango VA, Avenevoli S, et al. Candidate endopheno-types for genetic studies of suicidal behavior. Biol Psychiatry. 2009;65(7):556-563.
137. Brezo J, Klempan T, Turecki G. The genetics of suicide: a critical review of molecular studies. Psychiatr Clin North Am. 2008;31(2): 179-203.
138. Perason TA, Manolio TA. How to interpret a genome-wide association study. JAMA. 2008;299(11):1335-1344.
139. Du L, Faludi G, Palkovits M, Bakish D, Hrdina PD. Tryptophan hydrox-ylase gene 218A/C polymorphism is not associated with depressed suicide. Int J Neuropsychopharmacol. 2000;3(3):215-220.
140. Zalsman G, Frisch A, King RA, et al. Case control and family-based studies of tryptophan hydroxylase gene A218C polymorphism and suicidality in adolescents. Am J Med Genet. 2001;105(5):451-457.
141. Serretti A, Calati R, Giegling I, Hartmann AM, Möller HJ, Rujescu D. Serotonin receptor HTR1A and HTR2C variants and personality traits in suicide attempters and controls. J Psychiatr Res. 2009;43(5):519-525.
142. Stefulj J, Kubat M, Balija M, Skavic J, Jernej B. Variability of the tryptophan hydroxylase gene: study in victims of violent suicide. Psychiatry Res. 2005;134(1):67-73.
143. Videtic A, Zupanc T, Pregelj P, Balazic J, Tomori M, et al. (2009) Suicide, stress and serotonin receptor 1A promoter polymorphism -1019C.G in Slovenian suicide victims. Eur Arch Psychiatry Clin Neurosci 259:234-238.