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Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression

Molecular Psychiatry volume 13, pages 813–820 (2008)Cite this article

Abstract

Impaired brain serotonin neurotransmission is a potential component of the diathesis of major depression. Tryptophan hydroxylase-2 (TPH2), is the rate limiting biosynthetic isoenzyme for serotonin that is preferentially expressed in the brain and a cause of impaired serotonin transmission. Here, we identify a novel TPH2 short isoform with truncated catalytic domain expressed in human brainstem, prefrontal cortex, hippocampus and amygdala. An exploratory study of 166 Caucasian subjects revealed association with major depression or suicide of a novel single nucleotide polymorphism (SNP) g.22879A>G located in exon 6 of this short isoform. This SNP and additional SNPs were discovered through a systematic characterization of the genetic architecture of the TPH2 gene for further genetic and functional investigations of its relationship to major depression and other psychopathology.

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Acknowledgements

This study was supported by PHS Grants MH40210, MH64168, MH63749, HG002915 and MH62185. We thank Drs A Dumas, B Mancevski and T Serafimova for contributing to collection of specimens and psychological autopsies.

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Authors and Affiliations

  1. Columbia Genome Center, Columbia University, New York, NY, USA

    F Haghighi, S Shi, H T Sheng, I Morozova, J Ju & J J Russo

  2. Department of Psychiatry, Division of Molecular Imaging and Neuropathology, Columbia University, New York, NY, USA

    F Haghighi, H Bach-Mizrachi, Y Y Huang, V Arango, A J Dwork, G Rosoklija & J J Mann

  3. Department of Pathology, Columbia University, New York, NY, USA

    A J Dwork

  4. School of Medicine, Ss Cyril and Methodius University, Skopje, Republic of Macedonia

    G Rosoklija

  5. Department of Chemical Engineering, Columbia University, New York, NY, USA

    J Ju

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  1. F Haghighi
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Correspondence to J J Mann.

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Haghighi, F., Bach-Mizrachi, H., Huang, Y. et al. Genetic architecture of the human tryptophan hydroxylase 2 Gene: existence of neural isoforms and relevance for major depression. Mol Psychiatry 13, 813–820 (2008). https://doi.org/10.1038/sj.mp.4002127

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