TY - JOUR
T1 - Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders.
AU - Juhasz, Gabriella
AU - Downey, Darragh
AU - Hinvest, Neal
AU - Thomas, Emma
AU - Chase, Diana
AU - Toth, Zoltan G
AU - Lloyd-Williams, Kathryn
AU - Mekli, Krisztina
AU - Platt, Hazel
AU - Payton, Antony
AU - Bagdy, Gyorgy
AU - Elliott, Rebecca
AU - Deakin, J F William
AU - Anderson, Ian M
N1 - G9828266, Medical Research Council, United KingdomNF-SI-0509-10229, Department of Health, United Kingdom
PY - 2010/4
Y1 - 2010/4
N2 - 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.
AB - 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.
KW - Depression
KW - Haplotype analysis
KW - Psychiatric disorders
KW - Risk taking
KW - TPH2
U2 - 10.1038/npp.2009.216
DO - 10.1038/npp.2009.216
M3 - Article
C2 - 20043001
VL - 35
SP - 1109
EP - 1119
JO - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
IS - 5
ER -