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Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls

Molecular Psychiatry volume 7, pages 1127–1132 (2002)Cite this article

Abstract

Several lines of evidence suggest that a partly genetically controlled serotonergic dysfunction is involved in the biological pathogenesis of suicide. In this study, we measured tryptophan hydroxylase (TPH) immunoreactivity as a pre-synaptic marker, and serotonin receptor 2A (5HT2A receptor) density as a post-synaptic marker in the serotonergic system in 10 postmortem brains of suicide victims. We also examined whether TPH gene polymorphisms (A218C and A-6526G polymorphisms) could affect TPH immunoreactivity and 5HT2A receptor gene polymorphism (A-1438G polymorphism) could affect 5HT2A receptor density in 28 postmortem brain samples. No significant differences were found in TPH immunoreactivity or 5HT2A receptor density between suicide victims and controls. The AA genotype of the A218C polymorphism of the TPH gene showed higher TPH immunoreactivity along with lower 5HT2A receptor density than did any other genotypes in the postmortem brains of both suicide victims and controls. Our findings suggest that the A218C polymorphism of the TPH gene can be expected to provide new insights not only for neurobiological studies of suicide, but also for research into the behavioral characteristics that may be associated with serotonergic dysfunction.

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Acknowledgements

This research was supported by a Research Grant for Nervous and Mental Disorders from the Ministry of Health and Welfare Japan, and by Health Sciences Research Grants from the Ministry of Health and Welfare Japan.

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Authors and Affiliations

  1. Division of Psychiatry and Neurology, Department of Environmental Health and Safety, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan

    H Ono, O Shirakawa, T Hashimoto, N Nishiguchi & K Maeda

  2. Department of Psychiatry and Neurology, Kobe General City Hospital, Kobe, Japan

    N Kitamura

  3. Department of Legal Medicine, Yokohama City University School of Medicine, Yokohama, Japan

    A Nishimura

  4. Division of Legal Medicine, Department of Environmental Health and Safety, Faculty of Medical Sciences, Kobe University Graduate School of Medicine, Kobe, Japan

    H Nushida & Y Ueno

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  1. H Ono
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Correspondence to O Shirakawa.

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Ono, H., Shirakawa, O., Kitamura, N. et al. Tryptophan hydroxylase immunoreactivity is altered by the genetic variation in postmortem brain samples of both suicide victims and controls. Mol Psychiatry 7, 1127–1132 (2002). https://doi.org/10.1038/sj.mp.4001150

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