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.
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Acknowledgements
We are grateful to Heaton Mersey Medical Practice and Cheadle Medical Practice for their assistance in the recruitment and to Dr Xiayi Ke for statistical advices. This study was supported by the Sixth Framework Program of the EU, NewMood, LSHM-CT-2004–503474 and ETT 318-0412009. This work was presented in preliminary form at the BAP 2007 Summer Meeting of the British Association for Psychopharmacology, Harrogate, UK, 22–25 July 2007, and at the 20th ECNP Congress, Vienna, Austria, 13–17 October 2007.
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Juhasz, G., Downey, D., Hinvest, N. et al. Risk-Taking Behavior in a Gambling Task Associated with Variations in the Tryptophan Hydroxylase 2 Gene: Relevance to Psychiatric Disorders. Neuropsychopharmacol 35, 1109–1119 (2010). https://doi.org/10.1038/npp.2009.216
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DOI: https://doi.org/10.1038/npp.2009.216
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