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Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior

Abstract

Suicidal behavior, which ranks among the top 10 causes of death worldwide, is an important public-health problem and a psychiatric disorder, which has been the subject of considerable study. Studies have shown association between the serotonin transporter (5-HTT) gene and suicidal behavior, although a proportion of alternative studies have produced contrary results both in terms of positive and negative findings, possibly reflecting inadequate statistical power and the use of different populations. Using the cumulative data from recent years in both European and, more particularly, Asian populations, this updated meta-analysis seeks to examine whether the aggregate data provide evidence of statistical significance, and to clarify the contradictory findings suggested by previous studies. It covers all published studies using multiple research methods up to January 2006. Compared with a previous meta-analysis, which found no association between the 5-HTTLPR polymorphism and suicidal behavior (P=0.38), the current results (39 studies) suggest a significant association with a P-value of 0.0068 (overall odds ratio=0.88 (0.8,0.97)), and supports the involvement of the brain 5-HTT in the pathogenesis of suicidal behavior.

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References

  1. Lecrubier Y, Ustun TB . Panic and depression: a worldwide primary care perspective. Int Clin Psychopharmacol 1998; 13 (Suppl 4): S7–S11.

    PubMed  Google Scholar 

  2. Souery D, Oswald P, Linkowski P, Mendlewicz J . Molecular genetics in the analysis of suicide. Ann Med 2003; 35: 191–196.

    Article  CAS  Google Scholar 

  3. Underwood MD, Mann JJ, Arango V . Serotonergic and noradrenergic neurobiology of alcoholic suicide. Alcohol Clin Exp Res 2004; 28: 57S–69S.

    Article  CAS  Google Scholar 

  4. Lee JH, Kim HT, Hyun DS . Possible association between serotonin transporter promoter region polymorphism and impulsivity in Koreans. Psychiatry Res 2003; 118: 19–24.

    Article  CAS  Google Scholar 

  5. Mann JJ, Brent DA, Arango V . The neurobiology and genetics of suicide and attempted suicide: a focus on the serotonergic system. Neuropsychopharmacology 2001; 24: 467–477.

    Article  CAS  Google Scholar 

  6. van Heeringen K . The neurobiology of suicide and suicidality. Can J Psychiatry 2003; 48: 292–300.

    Article  Google Scholar 

  7. 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 2003; 8: 646–653.

    Article  CAS  Google Scholar 

  8. Gerra G, Garofano L, Santoro G, Bosari S, Pellegrini C, Zaimovic A et al. Association between low-activity serotonin transporter genotype and heroin dependence: behavioral and personality correlates. Am J Med Genet B Neuropsychiatr Genet 2004; 126: 37–42.

    Article  Google Scholar 

  9. Collier DA, Stober G, Li T, Heils A, Catalano M, Di Bella D et al. A novel functional polymorphism within the promoter of the serotonin transporter gene: possible role in susceptibility to affective disorders. Mol Psychiatry 1996; 1: 453–460.

    PubMed  CAS  Google Scholar 

  10. Arango V, Huang YY, Underwood MD, Mann JJ . Genetics of the serotonergic system in suicidal behavior. J Psychiatry Res 2003; 37: 375–386.

    Article  Google Scholar 

  11. Egger M, Davey Smith G, Schneider M, Minder C . Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 629–634.

    Article  CAS  Google Scholar 

  12. 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.

    Article  CAS  Google Scholar 

  13. Du L, Faludi G, Palkovits M, Bakish D, Hrdina PD . Tryptophan hydroxylase gene 218A/C polymorphism is not associated with depressed suicide. Int J Neuropsychopharmacol 2000; 3: 215–220.

    Article  CAS  Google Scholar 

  14. 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.

    Article  CAS  Google Scholar 

  15. 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 five other serotonergic genes. Psychol Med 2003; 33: 775–783.

    Article  CAS  Google Scholar 

  16. Sakinofsky I . The International Handbook of Suicide and Attempted Suicide. John Wiley: Chichester, 2000.

    Google Scholar 

  17. Bellivier F, Szoke A, Henry C, Lacoste J, Bottos C, Nosten-Bertrand M et al. Possible association between serotonin transporter gene polymorphism and violent suicidal behavior in mood disorders. Biol Psychiatry 2000; 48: 319–322.

    Article  CAS  Google Scholar 

  18. Gorwood P, Batel P, Ades J, Hamon M, Boni C . Serotonin transporter gene polymorphisms, alcoholism, and suicidal behavior. Biol Psychiatry 2000; 48: 259–264.

    Article  CAS  Google Scholar 

  19. Russ MJ, Lachman HM, Kashdan T, Saito T, Bajmakovic-Kacila S . Analysis of catechol-O-methyltransferase and 5-hydroxytryptamine transporter polymorphisms in patients at risk for suicide. Psychiatry Res 2000; 93: 73–78.

    Article  CAS  Google Scholar 

  20. Geijer T, Frisch A, Persson ML, Wasserman D, Rockah R, Michaelovsky E et al. Search for association between suicide attempt and serotonergic polymorphisms. Psychiatry Genet 2000; 10: 19–26.

    Article  CAS  Google Scholar 

  21. 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.

    Article  CAS  Google Scholar 

  22. 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.

    Article  CAS  Google Scholar 

  23. Rujescu D, Giegling I, Sato T, Moeller HJ . A polymorphism in the promoter of the serotonin transporter gene is not associated with suicidal behavior. Psychiatry Genet 2001; 11: 169–172.

    Article  CAS  Google Scholar 

  24. Baca-Garcia E, Vaquero C, Diaz-Sastre C, Saiz-Ruiz J, Fernandez-Piqueras J, de Leon J . A gender-specific association between the serotonin transporter gene and suicide attempts. Neuropsychopharmacology 2002; 26: 692–695.

    Article  CAS  Google Scholar 

  25. Shen Y, Li H, Gu N, Tan Z, Tang J, Fan J et al. Relationship between suicidal behavior of psychotic inpatients and serotonin transporter gene in Han Chinese. Neurosci Lett 2004; 372: 94–98.

    Article  CAS  Google Scholar 

  26. Ohara K, Nagai M, Tsukamoto T, Tani K, Suzuki Y, Ohara K . Functional polymorphism in the serotonin transporter promoter at the SLC6A4 locus and mood disorders. Biol Psychiatry 1998; 44: 550–554.

    Article  CAS  Google Scholar 

  27. Bayle FJ, Leroy S, Gourion D, Millet B, Olie JP, Poirier MF et al. 5HTTLPR polymorphism in schizophrenic patients: further support for association with violent suicide attempts. Am J Med Genet B Neuropsychiatr Genet 2003; 119: 13–17.

    Article  Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

  29. Courtet P, Buresi C, Abbar M, Baud P, Boulenger JP, Castelnau D et al. No association between non-violent suicidal behavior and the serotonin transporter promoter polymorphism. Am J Med Genet B Neuropsychiatr Genet 2003; 116: 72–76.

    Article  Google Scholar 

  30. Bondy B, Erfurth A, de Jonge S, 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.

    Article  CAS  Google Scholar 

  31. 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.

    Article  CAS  Google Scholar 

  32. Hranilovic D, Stefulj J, Furac I, Kubat M, Balija M, Jernej B . Serotonin transporter gene promoter (5-HTTLPR) and intron 2 (VNTR) polymorphisms in Croatian suicide victims. Biol Psychiatry 2003; 54: 884–889.

    Article  CAS  Google Scholar 

  33. Campi-Azevedo AC, Boson W, De Marco L, Romano-Silva MA, Correa H . Association of the serotonin transporter promoter polymorphism with suicidal behavior. Mol Psychiatry 2003; 8: 899–900.

    Article  CAS  Google Scholar 

  34. Yen FC, Hong CJ, Hou SJ, Wang JK, Tsai SJ . Association study of serotonin transporter gene VNTR polymorphism and mood disorders, onset age and suicide attempts in a Chinese sample. Neuropsychobiology 2003; 48: 5–9.

    Article  CAS  Google Scholar 

  35. Fan JB, Sklar P . Meta-analysis reveals association between serotonin transporter gene STin2 VNTR polymorphism and schizophrenia. Mol Psychiatry 2005; 10: 928–938, 891.

    Article  CAS  Google Scholar 

  36. Chotai J, Serretti A, Lattuada E, Lorenzi C, Lilli R . Gene-environment interaction in psychiatric disorders as indicated by season of birth variations in tryptophan hydroxylase (TPH), serotonin transporter (5-HTTLPR) and dopamine receptor (DRD4) gene polymorphisms. Psychiatry Res 2003; 119: 99–111.

    Article  CAS  Google Scholar 

  37. Lin PY, Tsai G . Association between serotonin transporter gene promoter polymorphism and suicide: results of a meta-analysis. Biol Psychiatry 2004; 55: 1023–1030.

    Article  CAS  Google Scholar 

  38. Kessler RC, Borges G, Walters EE . Prevalence of and risk factors for lifetime suicide attempts in the National Comorbidity Survey. Arch Gen Psychiatry 1999; 56: 617–626.

    Article  CAS  Google Scholar 

  39. Cho HJ, Meira-Lima I, Cordeiro Q, Michelon L, Sham P, Vallada H et al. Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis. Mol Psychiatry 2005; 10: 771–781.

    Article  CAS  Google Scholar 

  40. Lieberman JA, Mailman RB, Duncan G, Sikich L, Chakos M, Nichols DE et al. Serotonergic basis of antipsychotic drug effects in schizophrenia. Biol Psychiatry 1998; 44: 1099–1117.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants from the Ministry of Education, PRC, the national 973 and 863 programs, the National Natural Science Foundation of China and the Shanghai Municipal Commission for Science and Technology.

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Correspondence to L He.

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Accession numbers and URLs for data in this article are as follows:

Online Mendelian Inheritance in Man, http://www.ncbi.nlm.nih.gov/Omim for 5-HTT;

Genotype data, http://www.hapmap.org/ for 5-HTT;

Genome data, http://genome.ucsc.edu/ for 5-HTT.

Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Li, D., He, L. Meta-analysis supports association between serotonin transporter (5-HTT) and suicidal behavior. Mol Psychiatry 12, 47–54 (2007). https://doi.org/10.1038/sj.mp.4001890

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