Abstract
An association between the gene that codes for tryptophan hydroxylase (TPH)—the rate-limiting enzyme in the synthesis of serotonin—and suicidal behavior has been investigated with some detail in samples of living subjects who attempted suicide. In this study, we investigated TPH and suicide completion, the most severe form of suicidal behavior. A relatively large sample of suicide completers (n = 101) was genotyped at three TPH loci (two polymorphisms in the promoter region, A-6526G and G-5806T, and one in intron 7, A218C) and compared to psychiatrically normal living controls (n = 129). Although no significant differences were found between groups for genetic variation at single loci, haplotype analysis revealed that one haplotype (-6526G -5806T 218C) was significantly more frequent among suicide cases than in normal controls (χ2 = 11.30, df = 2, P = 0.0008; OR = 2.0 CI: 1.30–3.6). Further analyses suggested that this haplotype is particularly more frequent among subjects who committed suicide using violent methods. Similar results were observed in recent haplotype analyses in suicide attempters, which found that the equivalent of haplotype -6526G -5806T 218C was more frequent in impulsive attempters (Rotondo et al, Mol Psychiatry 1999; 4: 360–368). Our results replicate in suicide completers previous data observed in suicide attempters. These and other results continue to point to the substantial role that the gene that codes for TPH may play in the neurobiology of suicidal behavior
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Diekstra RFW . The epidemiology of suicide and parasuicide Acta Psychiatr Scand 1993 371: 9–20
Brent DA, Bridge J, Johnson BA, Connolly J . Suicidal behavior runs in families. A controlled family study of adolescent suicide victims Arch Gen Psychiatry 1996 53: 1145–1152
Tsuang M . Risk of suicide in the relatives of schizophrenics, manics, depressives, and controls J Clin Psychiatry 1983 44: 396–400
Roy A, Segal NL, Sarchiapone M . Attempted suicide among living co-twins of twin suicide victims Am J Psychiatry 1995 152: 1075–1076
Roy A, Segal NL, Centerwall BS, Robinette CD . Suicide in twins Arch Gen Psychiatry 1991 48: 29–32X
Wender PH, Seymour SK, Rosenthal D, Schulsinger F, Ortmann J, Lunde I . Psychiatric disorders in the biological and adoptive families of adopted individuals with affective disorders Arch Gen Psychiatry 1986 43: 923–929
Statham DJ, Heath AC, Madden PA et al. Suicidal behaviour: an epidemiological and genetic study Psychol Med 1998 28: 839–855
Mann JJ . The neurobiology of suicide Nature Med 1998 4: 25–30
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: 34–38X
Nielsen DA, Virkkunen M, Lappalainen J et al. A tryptophan hydroxylase gene marker for suicidality and alcoholism Arch Gen Psychiatry 1998 55: 593–602
Mann JJ, Malone KM, Nielsen DA, Goldman D, Erdos J, Gelernter J . Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients Am J Psychiatry 1997 154: 1451–1453
Tsai SJ, Hong CJ, Wang YC . Tryptophan hydroxylase gene polymorphism (A218C) and suicidal behaviors Neuroreport 1999 10: 3773–3775
Lesage AD, Boyer R, Grunberg F et al. Suicide and mental disorders: a case-control study of young men Am J Psychiatry 1994 151: 1063–1068
Conwell Y, Duberstein PR, Cox C, Herrmann JH, Forbes NT, Caine ED . Relationships of age and axis I diagnoses in victims of completed suicide: a psychological autopsy study Am J Psychiatry 1996 153: 1001–1008
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: 1009–1014
Barner-Rasmussen P, Dupont A, Bille H . Suicide in psychiatric patients in Denmark, 1971–81. I. Demographic and diagnostic description Acta Psychiatr Scand 1986 73: 441–448
Barraclough B, Bunch J, Nelson B, Sainsbury P . A hundred cases of suicide: clinical aspects Br J Psychiatry 1974 125: 355–373
Strategie quebecoise d'action face au suicide . S'entraider pour la vie. Gouvernament du Quebec Ministere de la sante et des services sociaux 1998
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: 145–148
Rotondo A, Schuebel K, Bergen A et al. Identification of four variants in the tryptophan hydroxylase promoter and association to behavior Mol Psychiatry 1999 4: 360–368
Long JC, Williams RC, Urbanek M . An E-M algorithm and testing strategy for multiple-locus haplotypes Am J Hum Genet 1995 56: 799–810
Mann JJ, Waternaux C, Haas GL, Malone KM . Toward a clinical model of suicidal behavior in psychiatric patients Am J Psychiatry 1999 156: 181–189
Devlin B, Risch N . A comparison of linkage disequilibrium measures for fine-scale mapping Genomics 1995 29: 311–322
Manuck SB, Flory JD, Ferrell RE, Dent KM, Mann JJ, Muldoon MF . Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene Biol Psychiatry 1999 45: 603–614
Acknowledgements
This study was funded in part by the Réseau de Santé Méntale du Québec—Suicide Axis and the Canadian Medical Research Council grant 38078.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Turecki, G., Zhu, Z., Tzenova, J. et al. TPH and suicidal behavior: a study in suicide completers. Mol Psychiatry 6, 98–102 (2001). https://doi.org/10.1038/sj.mp.4000816
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.mp.4000816
Keywords
This article is cited by
-
Association of TPH-1 and TPH-2 gene polymorphisms with suicidal behavior: a systematic review and meta-analysis
BMC Psychiatry (2014)
-
Endophenotypes as a measure of suicidality
Journal of Applied Genetics (2012)
-
Neuronal Tryptophan Hydroxylase mRNA Expression in the Human Dorsal and Median Raphe Nuclei: Major Depression and Suicide
Neuropsychopharmacology (2006)
-
Genetics of suicide
Molecular Psychiatry (2006)
-
Further clarification of the contribution of the tryptophan hydroxylase (TPH) gene to suicidal behavior using systematic allelic and genotypic meta-analyses
Human Genetics (2006)