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Analysis of the novel TPH2 gene in bipolar disorder and suicidality

Molecular Psychiatry volume 9, pages 896–897 (2004)Cite this article

SIR—Genetic factors have been generally implicated in the etiology of suicide, although the precise mechanism and amount of the genetic contribution are not yet well established.1 The serotonergic system is thought to be trait dependent and associated with disturbances in the regulation of anxiety, impulsivity, and aggression.2 Furthermore, serotonergic dysfunction has been suggested in suicide based on several observations. For example, low concentration of the metabolite of serotonin (5-HIAA), in CSF has been associated with suicide attempts and completed suicide,3 and low levels of 5-HT or 5-HIAA were also observed in suicide victims.4 5-HT is synthesized in two steps, with tryptophan hydroxylase (TPH) as the rate-limiting enzyme.5

Thus far, two TPH genes have been identified. The TPH1 gene is located on chromosome 11p15 and has been the focus of a number of genetic studies of suicidality. A recent meta-analysis concluded that the TPH1 intron 7 A218 polymorphism is associated with suicide-related behavior.6 Interestingly, a new TPH gene (TPH2) located on chromosome 12q21 has recently been described. In mice brain stem, expression of TPH1 appears to be 150 times lower than TPH2, suggesting that TPH2 may play a much more important role in serotonin synthesis in the brain than TPH1.7 Therefore, we were interested in investigating the putative role of the TPH2 gene in suicide attempters using a large and well-characterized sample of patients with bipolar disorder. TPH2 has three highly polymorphic single-nucleotide polymorphisms (SNPs): hCV245410 (C/T), hCV8376173 (A/G), rs1487280 (A/G). These SNPs are located in introns 1, 5, and 8, respectively.

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Author notes

  1. V De Luca: Dr V De Luca is supported by a Postdoctoral Research Fellowship from the American Foundation for Suicide Prevention.

Authors and Affiliations

  1. Department of Psychiatry, Neurogenetics Section, Clarke Site, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada

    V De Luca, D J Mueller, S Tharmalingam, N King & J L Kennedy

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  1. V De Luca
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  2. D J Mueller
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  3. S Tharmalingam
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  4. N King
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  5. J L Kennedy
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Correspondence to J L Kennedy.

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De Luca, V., Mueller, D., Tharmalingam, S. et al. Analysis of the novel TPH2 gene in bipolar disorder and suicidality. Mol Psychiatry 9, 896–897 (2004). https://doi.org/10.1038/sj.mp.4001531

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