Risk-taking behavior in a gambling task associated with variations in the tryptophan hydroxylase 2 gene: relevance to psychiatric disorders.
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.
Juhasz
Gabriella
G
Neuroscience and Psychiatry Unit, School of Community Based Medicine, Faculty of Medical and Human Sciences, The University of Manchester, Manchester, UK. gabriella.juhasz@manchester.ac.uk
Downey
Darragh
D
Hinvest
Neal
N
Thomas
Emma
E
Chase
Diana
D
Toth
Zoltan G
ZG
Lloyd-Williams
Kathryn
K
Mekli
Krisztina
K
Platt
Hazel
H
Payton
Antony
A
Bagdy
Gyorgy
G
Elliott
Rebecca
R
Deakin
J F William
JF
Anderson
Ian M
IM
D000328:Adult; D015331:Cohort Studies; D003657:Decision Making; D005260:Female; D005715:Gambling; D056726:Genetic Association Studies; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D010556:Personality Tests; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044282:Receptor, Serotonin, 5-HT1A / Q000235:genetics; D012309:Risk-Taking; D017422:Sequence Analysis, DNA; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D011795:Surveys and Questionnaires; D014365:Tryptophan Hydroxylase / Q000235:genetics*
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D044282:Receptor, Serotonin, 5-HT1A; C497467:TPH1 protein, human; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase