Abstract
The different serotonin (5-HT) receptors, including the serotonin transporter (5-HTT), are excellent candidate genes for suicide and suicidal behavior, and thus, they have been investigated in a large number of allelic association studies. The individual results of these studies have been inconsistent and definite conclusions are difficult to establish. A reliable method for assessing individual studies and generating combined results is provided by systematic reviews using meta-analytical techniques. In this study, we carried out a systematic review of studies investigating 5-HT receptors and the 5-HTT in suicidal behavior. Studies were identified by means of MEDLINE database searches and by scanning reference lists. More than 190 articles were reviewed and 26 met the inclusion criteria. In all, 14 studies investigated six different 5-HT receptor loci and 12 studies investigated the 5-HTT promoter 44 bp insertion/deletion polymorphism. Two specific meta-analyses were carried out, pooling studies investigating the 5-HT2A 102 T/C and the 5-HTT promoter loci that included, respectively, a total of 1599 and 2539 subjects. The combined evidence was significant for association with the 5-HTT locus (Mantel–Haenszel weighted odds ratio (M–Hw OR)=1.17 CI : 1.04–1.32, P=0.009), but not for the 5-HT2A 102 T/C variant (M-Hw OR)=1.09 CI : 0.93–1.27, P=0.319). The 5-HTT result was robust and remained significant following sensitivity analysis, suggesting that 5-HTT may play a role in the predisposition to suicide.
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References
WHO World Health Report 2000. Health Systems: Improving Performance. WHO: Geneva, 2002.
Mann JJ . Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 1999; 21: 99S–105S.
Turecki G . Suicidal behavior: is there a genetic predisposition? Bipolar Disord 2001; 3: 335–349.
Lalovic A, Turecki G . Meta-analysis of the association between tryptophan hydroxylase and suicidal behavior. Am J Med Genet 2002; 114: 533–540.
Mulrow CD . The medical review article: state of the science. Ann Intern Med 1987; 106: 485–488.
Mulrow CD . Rationale for systematic reviews. BMJ 1994; 309: 597–599.
Olkin I . Statistical and theoretical considerations in meta-analysis. J Clin Epidemiol 1995; 48: 133–146.
Rosenthal R . Comparing and combining research results . 1984; 63–111.
Anguelova M, Benkelfat C, Turecki G . A Systematic review of association studies investigating genes coding for serotonin receptors and transporter: I. Affective disorders. Mol Psychiatry (In press).
Fleiss J . Combining evidence from fourfold tables. In: Statistical Methods for Rates and Proportions. New York 1981; pp. 160–187.
Rosenthal R . Comparing and combining research results. In Meta-analytic procedures for Social Sciences. Beverly Hills 1984: Sage Publications, pp 63–111.
Hedges LV, Olkin I . Statistical Methods for Meta-analysis. Academic Press: Orlando, 1985.
Nishiguchi N, Shirakawa O, Ono H, Nishimura A, Nushida H, Ueno Y et al. Lack of an association between 5-HT1A receptor gene structural polymorphisms and suicide victims. Am J Med Genet 2002; 114: 423–425.
Nishiguchi N, Shirakawa O, Ono H, Nishimura A, Nushida H, Ueno Y 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: 343–345.
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.
Turecki G, Briere R, Dewar K, Antonetti T, Lesage AD, Seguin M 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: 1456–1458.
Preuss UW, Koller G, Bahlmann M, Soyka M, Bondy B . No association between suicidal behavior and 5-HT2A-T102C polymorphism in alcohol dependents. Am J Med Genet 2000; 96: 877–878.
Du L, Faludi G, Palkovits M, Demeter E, Bakish D, Lapierre YD et al. Frequency of long allele in serotonin transporter gene is increased in depressed suicide victims. Biol Psychiatry 1999; 46: 196–201.
Geijer T, Frisch A, Persson ML, Wasserman D, Rockah R, Michaelovsky E et al. Search for association between suicide attempt and serotonergic polymorphisms. Psychiatr Genet 2000; 10: 19–26.
Bondy B, Kuznik J, Baghai T, Schule C, Zwanzger P, Minov C et al. Lack of association of serotonin-2A receptor gene polymorphism (T102C) with suicidal ideation and suicide. Am J Med Genet 2000; 96: 831–835.
Arias B, Gasto C, Catalan R, Gutierrez B, Pintor L, Fananas L . The 5-HT(2A) receptor gene 102T/C polymorphism is associated with suicidal behavior in depressed patients. Am J Med Genet 2001; 105: 801–804.
Tsai SJ, Hong CJ, Hsu CC, Cheng CY, Liao WY, Song HL et al. Serotonin-2A receptor polymorphism (102T/C) in mood disorders. Psychiatry Res 1999; 87: 233–237.
Zhang HY, Ishigaki T, Tani K, Chen K, Shih JC, Miyasato K et al. Serotonin2A receptor gene polymorphism in mood disorders. Biol Psychiatry 1997; 41: 768–773.
Crawford J, Sutherland GR, Goldney RD . No evidence for association of 5-HT2A receptor polymorphism with suicide. Am J Med Genet 2000; 96: 879–880.
Ono H, Shirakawa O, Nishiguchi N, Nishimura A, Nushida H, Ueno Y et al. Serotonin 2A receptor gene polymorphism is not associated with completed suicide. J Psychiatr Res 35: 173–176.
Ohara K, Nagai M, Tsukamoto T, Tani K, Suzuki Y, Ohara K . 5-HT2A receptor gene promoter polymorphism—1438G/A and mood disorders. Neuroreport 1998; 9: 1139–1141.
Faludi G, Du L, Palkovits M, Antal B, Sotonyi P, Hrdina PD . Serotonin transporter, serotonin-2A receptor and tryptophan hydroxylase gene polymorphisms in depressed suicide victims. Neurobiology (Bp) 2000; 8: 269–271.
Fitch D, Lesage A, Seguin M, Trousignant M, Bankelfat C, Rouleau GA et al. Suicide and the serotonin transporter gene. Mol Psychiatry 2001; 6: 127–128.
Bondy B, Erfurth A, de J, Kruger M, Meyer H . Possible association of the short allele of the serotonin transporter promoter gene polymorphism (5-HTTLPR) with violent suicide. Mol Psychiatry 2000; 5: 193–195.
Rujescu D, Giegling I, Sato T, Moeller HJ . A polymorphism in the promoter of the serotonin transporter gene is not associated with suicidal behavior. Psychiatr Genet 2001; 11: 169–172.
Baca G, Vaquero C, Diaz S, Saiz R, Fernandez P, de L . A gender-specific association between the serotonin transporter gene and suicide attempts. Neuropsychopharmacology 2002; 26: 692–695.
Courtet P, Baud P, Abbar M, Boulenger JP, Castelnau D, Mouthon D et al. Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene. Mol Psychiatry 2001; 6: 338–341.
Bellivier F, Szoke A, Henry C, Lacoste J, Bottos C, Nosten B et al. Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders. Biol Psychiatry 2000; 48: 319–322.
Russ MJ, Lachman HM, Kashdan T, Saito T, Bajmakovic K . Analysis of catechol-O-methyltransferase and 5-hydroxytryptamine transporter polymorphisms in patients at risk for suicide. Psychiatry Res 2000; 93: 73–78.
Preuss UW, Koller G, Soyka M, Bondy B . Association between suicide attempts and 5-HTTLPR-S-allele in alcohol-dependent and control subjects: further evidence from a German alcohol-dependent inpatient sample. Biol Psychiatry 2001; 50: 636–639.
Gorwood P, Batel P, Ades J, Hamon M, Boni C . Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior. Biol Psychiatry 2000; 48: 259–264.
Chong SA, Lee WL, Tan CH, Tay AH, Chan AO, Tan EC . Attempted suicide and polymorphism of the serotonin transporter gene in Chinese patients with schizophrenia. Psychiatry Res 2000; 97: 101–106.
Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM et al. A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry 2000; 57: 729–738.
Lesch KP, Bengel D, Heils A, Sabol SZ, Greenberg BD, Petri S et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science 1996; 274: 1527–1531.
Mann JJ . Role of the serotonergic system in the pathogenesis of major depression and suicidal behavior. Neuropsychopharmacology 1999; 21: 99S–105S.
Acknowledgements
We thank Alexandra Lalovic, Caroline Kim, Adolfo Sequeira, Iris Groisman, and Firoza Mamdani for their expert academic assistance. This study was partly funded by CIHR Grant MOP-38078 and an AFSP grant.
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Anguelova, M., Benkelfat, C. & Turecki, G. A systematic review of association studies investigating genes coding for serotonin receptors and the serotonin transporter: II. Suicidal behavior. Mol Psychiatry 8, 646–653 (2003). https://doi.org/10.1038/sj.mp.4001336
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DOI: https://doi.org/10.1038/sj.mp.4001336
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