Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders

Gabriella Juhasz, Darragh Downey, Neal S Hinvest, Emma Thomas, Diana Chase, Zoltan G Toth, Kathryn Lloyd-Williams, Krisztina Mekli, Hazel Platt, Antony Payton, Gyorgy Bagdy, Rebecca Elliott, J F William Deakin, Ian M Anderson

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29 Citations (Scopus)

Abstract

Decision making, choosing the best option from the possible outcomes, is impaired in many psychiatric conditions including affective disorders. We tested the hypothesis that variations in serotonergic genes (TPH2, TPH1, SLC6A4, HTR1A), which influence serotonin availability, affect choice behavior in a probabilistic gambling task. A population cohort (N=1035) completed a paper-and-pencil gambling task, filled out personality and symptom questionnaires and gave consent for the use of their DNA in a genetic association study. A subgroup of subjects (N=69) also completed a computer version of the task. The gambling task was designed to estimate an individual's tendency to take a risk when choosing between a smaller but more certain ‘win’ and a larger, less probable one. We genotyped seven haplotype tagging SNPs in the TPH2 gene, and previously reported functional polymorphisms from the other genes (rs1800532, 5HTTLPR, and rs6295). Carriers of the more prevalent TPH2 haplotype, which was previously associated with less active enzyme variant, showed reduced risk taking on both tasks compared with subjects not carrying the common haplotype. The effect of TPH2 haplotypes on risk-taking was independent of current depression and anxiety symptoms, neuroticism and impulsiveness scores. We did not find an association between functional polymorphisms in the TPH1, SLC6A4, HTR1A genes and risk-taking behavior. In conclusion, our study demonstrates the role of the TPH2 gene and the serotonin system in risk taking and suggests that TPH2 gene may contribute to the expression of psychiatric phenotypes through altered decision making.
Original languageEnglish
Pages (from-to)1109-1119
Number of pages11
JournalNeuropsychopharmacology
Volume35
Issue number5
Early online date30 Dec 2009
DOIs
Publication statusPublished - Apr 2010

Keywords

  • risk taking
  • depression
  • psychiatric disorders
  • haplotype analysis
  • TPH2

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    Juhasz, G., Downey, D., Hinvest, N. S., Thomas, E., Chase, D., Toth, Z. G., Lloyd-Williams, K., Mekli, K., Platt, H., Payton, A., Bagdy, G., Elliott, R., Deakin, J. F. W., & Anderson, I. M. (2010). Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders. Neuropsychopharmacology, 35(5), 1109-1119. https://doi.org/10.1038/npp.2009.216