OJPsych  Vol.3 No.1 , January 2013
Variation in the DRD2 gene affects impulsivity in intertemporal choice
Abstract: Introduction: Impulsivity in intertemporal choice has been operationalized as “delay discounting,” referring to the preference for a sooner, smaller reward in neuroeconomics. It is reportedly associated with the dopaminergic systems. Dopamine receptor D2 (DRD2) is the D2 subtype of the dopamine receptor of the G-protein coupled receptor family. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in DRD2 gene on delay discounting. Methods: The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9 ± 6.9 years). Each participant completed the Kirby’s monetary choice questionnaire (MCQ) for delayed gain and donated a whole blood sample. Two SNPs (C957T (rs6277) and TaqI A (rs1800497)) in DRD2 were genotyped by using the DigiTag2 assay. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate (k). Results: The SNP C957T showed a significant association; participants with more minor alleles (T) were more impulsive in intertemporal choice for delayed gain (multiplicity-corrected P = 0.041 with a small effect size). Conclusion: The variation in the DRD2 gene is associated with impulsive decision-making. This is the first study to demonstrate an association between DRD2 and impulsivity in intertemporal choice with a multiplicity-corrected significance.
Cite this paper: Kawamura, Y. , Takahashi, T. , Liu, X. , Nishida, N. , Noda, Y. , Yoshikawa, A. , Umekage, T. and Sasaki, T. (2013) Variation in the DRD2 gene affects impulsivity in intertemporal choice. Open Journal of Psychiatry, 3, 26-31. doi: 10.4236/ojpsych.2013.31005.

[1]   Glimcher, P.W. and Rustichini, A. (2004) Neuroeconomics: The consilience of brain and decision. Science, 306, 447-452. doi:10.1126/science.1102566

[2]   Camerer, C., Loewenstein, G.F. and Prelec D. (2005) Neuroeconomics: How neuroscience can inform economics. Journal of Economic Literature, 43, 9-64. doi:10.1257/0022051053737843

[3]   Takahashi, T. (2009) Theoretical frameworks for neuroeconomics of intertemporal choice. Journal of Neuroscience, Psychology, and Economics, 2, 75-90. doi:10.1037/a0015463

[4]   Hasler, G. (2012) Can the neuroeconomics revolution revolutionize psychiatry? Neuroscience and Biobehavioral Reviews, 36, 64-78. doi:10.1016/j.neubiorev.2011.04.011

[5]   Kable, J.W. and Glimcher, P.W. (2007) The neural correlates of subjective value during intertemporal choice. Nature Neuroscience, 10, 1625-1633. doi:10.1038/nn2007

[6]   McClure, S.M., Laibson, D.I., Loewenstein, G. and Cohen, J.D. (2004) Separate neural systems value immediate and delayed monetary rewards. Science, 306, 503-507. doi:10.1126/science.1100907

[7]   McClure, S.M., Ericson, K.M., Laibson, D.I., Loewenstein, G. and Cohen, J.D. (2007) Time discounting for primary rewards. Journal of Neuroscience, 27, 5796-5804. doi:10.1523/JNEUROSCI.4246-06.2007

[8]   Yu, R. (2012) Regional white matter volumes correlate with delay discounting. PLoS One, 7, e32595. doi:10.1371/journal.pone.0032595

[9]   Mazur, J.E. (1987) An adjusting procedure for studying delayed reinforcement. In: Commons, M. L., Mazur, J. E., Nevin, J. A. and Rachlin, H., Eds., The Effect of Delay and of Intervening Events on Reinforcement Value, Quantitative Analyses of Behavior, Erlbaum, Hillsdale, New Jersey, 55-73.

[10]   Bickel, W.K. and Marsch, L.A. (2001) Toward a behavioral economic understanding of drug dependence: Delay discounting processes. Addiction, 96, 73-86. doi:10.1046/j.1360-0443.2001.961736.x

[11]   Frederick, S., Loewenstein, G. and O’Donoghue, T. (2002) Time discounting and time preference: A critical review. Journal of Economic Literature, 40, 351-401. doi:10.1257/002205102320161311

[12]   Prelec, D. (2004) Decreasing impatience: A criterion for non-stationary time preference and “Hyperbolic” discounting. Scandinavian Journal of Economics, 106, 511-532. doi:10.1111/j.0347-0520.2004.00375.x

[13]   Ainslie, G. (2005) Precis of breakdown of will. Behavioral and Brain Sciences, 28, 635-650. doi:10.1017/S0140525X05000117

[14]   Takahashi, T. (2005) Loss of self-control in intertemporal choice may be attributable to logarithmic time-perception. Medical Hypotheses, 65, 691-693. doi:10.1016/j.mehy.2005.04.040

[15]   Bickel, W.K., Miller, M.L., Yi, R., Kowal, B.P., Lindquist, D.M. and Pitcock, J.A. (2006) Behavioral and neuroeconomics of drug addiction: Competing neural systems and temporal discounting processes. Drug and Alcohol Dependence, 90, S85-S91.

[16]   Reynolds, B. (2006) A review of delay-discounting research with humans: Relations to drug use and gambling. Behavioural Pharmacology, 17, 651-667. doi:10.1097/FBP.0b013e3280115f99

[17]   Petry, N.M. (2002) Discounting of delayed rewards in substance abusers: Relationship to antisocial personality disorder. Psychopharmacology, 162, 425-432. doi:10.1007/s00213-002-1115-1

[18]   Bickel, W.K., Odum, A.L. and Madden, G.J. (1999) Impulsivity and cigarette smoking: Delay discounting in current, never, and ex-smokers. Psychopharmacology, 146, 447-454. doi:10.1007/PL00005490

[19]   Kirby, K.N., Petry, N.M. and Bickel, W.K. (1999) Heroin addicts have higher discount rates for delayed rewards than non-drug-using controls. Journal of Experimental Psychology. General, 128, 78-87. doi:10.1037/0096-3445.128.1.78

[20]   Coffey, S.F., Gudleski, G.D., Saladin, M.E. and Brady, K.T. (2003) Impulsivity and rapid discounting of delayed hypothetical rewards in cocaine-dependent individuals. Experimental and Clinical Psychopharmacology, 11, 18-25. doi:10.1037/1064-1297.11.1.18

[21]   MacKillop, J., Anderson, E.J., Castelda, B.A., Mattson, R.E. and Donovick, P.J. (2006) Divergent validity of measures of cognitive distortions, impulsivity, and time perspective in pathological gambling. Journal of Gambling Studies, 22, 339-354. doi:10.1007/s10899-006-9021-9

[22]   Petry, N.M., Kirby, K.N. and Kranzler, H.R. (2002) Effects of gender and family history of alcohol dependence on a behavioral task of impulsivity in healthy subjects. Journal of Studies on Alcohol, 63, 83-90.

[23]   Sozou, P.D. (1998) On hyperbolic discounting and uncertain hazard rates. Proceedings of the Royal Society of London. Series B, 265, 2015-2020. doi:10.1098/rspb.1998.0534

[24]   Crean, J., Richards, J.B. and de Wit, H. (2002) Effect of tryptophan depletion on impulsive behavior in men with or without a family history of alcoholism. Behavioural Brain Research, 136, 349-357. doi:10.1016/S0166-4328(02)00132-8

[25]   Reynolds, B., Karraker, K., Horn, K. and Richards, J.B. (2003) Delay and probability discounting as related to different stages of adolescent smoking and non-smoking. Behavioural Processes, 64, 333-344. doi:10.1016/S0376-6357(03)00168-2

[26]   Reynolds, B. and Schiffbauer, R. (2004) Measuring state changes in human delay discounting: An experiential discounting task. Behavioural Processes, 67, 343-356.

[27]   Ohmura, Y., Takahashi, T. and Kitamura, N. (2005) Discounting delayed and probabilistic monetary gains and losses by smokers of cigarettes. Psychopharmacology, 182, 508-515. doi:10.1007/s00213-005-0110-8

[28]   Ohmura, Y., Takahashi, T., Kitamura, N. and Wehr, P. (2006) Three-month stability of delay and probability discounting measures. Experimental and Clinical Psychopharmacology, 14, 318-328. doi:10.1037/1064-1297.14.3.318

[29]   Estle, S.J., Green, L., Myerson, J. and Holt, D.D. (2007) Discounting of monetary and directly consumable rewards. Psychological Science, 18, 58-63. doi:10.1111/j.1467-9280.2007.01849.x

[30]   Takahashi, T., Oono, H. and Radford, M.H.B. (2007) Empirical estimation of consistency parameter in intertemporal choice based on Tsallis’ statistics. Physica A, 381, 338-342. doi:10.1016/j.physa.2007.03.038

[31]   Sellitto, M., Ciaramelli, E. and di Pellegrino, G. (2011) The neurobiology of intertemporal choice: Insight from imaging and lesion studies. Reviews in the Neurosciences, 22, 565-574. doi:10.1515/RNS.2011.046

[32]   Dayan, P. and Abbott, L.F. (2001) Theoretical Neuroscience. MIT Press, Cambridge.

[33]   Schultz, W. (2004) Neural coding of basic reward terms of animal learning theory, game theory, microeconomics and behavioural ecology. Current Opinion in Neurobiology, 14, 139-147. doi:10.1016/j.conb.2004.03.017

[34]   Takahashi, T., Ikeda, K. and Hasegawa, T. (2007) A hyperbolic decay of subjective probability of obtaining delayed rewards. Behavioral and Brain Functions, 25, 3-52.

[35]   Simon, N.W., Montgomery, K.S., Beas, B.S., Mitchell, M.R., LaSarge, C.L., Mendez, I.A., Banuelos, C., Vokes, C.M., Taylor, A.B., Haberman, R.P., Bizon, J.L. and Setlow, B. (2011) Dopaminergic modulation of risky decision-making. Journal of Neuroscience, 31, 17460-17470. doi:10.1523/JNEUROSCI.3772-11.2011

[36]   Heerey, E.A., Robinson, B.M., McMahon, R.P. and Gold, J.M. (2007) Delay discounting in schizophrenia. Cognitive Neuropsychiatry, 12, 213-221. doi:10.1080/13546800601005900

[37]   Colzato, L.S., van den Wildenberg, W.P., Van der Does, A.J. and Hommel, B. (2010) Genetic markers of striatal dopamine predict individual differences in dysfunctional, but not functional impulsivity. Neuroscience, 170, 782-788. doi:10.1016/j.neuroscience.2010.07.050

[38]   Eisenberg, D.T.A., MacKillop, J., Modi, M., Beauchemin, J., Dang, D., Lisman, S.A., Lum, J.K. and Wilson, D.S. (2007) Examining impulsivity as an endophenotype using a behavioral approach: A DRD2 TaqI A and DRD4 48-bp VNTR association study. Behavioral and Brain Functions, 3, 2. doi:10.1186/1744-9081-3-2

[39]   Young, R.M., Lawford, B.R., Nutting, A. and Noble, E.P. (2004) Advances in molecular genetics and the prevention and treatment of substance misuse: Implications of association studies of the A1 allele of the D2 dopamine receptor gene. Addictive Behaviours, 29, 1275-1294. doi:10.1016/j.addbeh.2004.06.012

[40]   Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., Hergueta, T., Baker, R. and Dunbar, G.C. (1998) The Mini-International Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59, 22-57.

[41]   American Psychiatric Association, (2000) Diagnostic and statistical manual of mental disorders, 4th Edition, text revision: DSM-IV-TR. American Psychiatric Press, Washington DC.

[42]   Hirsh, J.B., Morisano, D. and Peterson, J.B. (2008) Delay discounting: Interactions between personality and cognitive ability. Journal of Research in Personality, 42, 1646-1650. doi:10.1016/j.jrp.2008.07.005

[43]   Kirby, K.N. (2009). One-year temporal stability of delaydiscount rates. Psychonomic Bulletin & Review, 16, 457-462. doi:10.3758/PBR.16.3.457

[44]   Takahashi, T., Sakaguchi, K., Oki, M., Homma, S. and Hasegawa, T. (2006) Testosterone levels and discounting delayed monetary gains and losses in male humans. Neuro Endocrinology Letters, 27, 439-444.

[45]   Takahashi, T., Ikeda, K., Fukushima, H. and Hasegawa, T. (2007) Salivary-alpha amylase levels and hyperbolic discounting in male human. Neuro Endocrinology Letters, 28, 101-104.

[46]   Takahashi, T., Shinada, M., Inukai, K., Tanida, S., Takahashi, C., Mifune, N., Takagishi, H., Horita, Y., Hashimoto, H., Yokota, K., Kameda, T. and Yamagishi, T. (2010) Stress hormones predict hyperbolic time-discount rates six months later in adults. Neuro Endocrinology Letters, 31, 616-621.

[47]   Kawamura, Y., Takahashi, T., Liu, X., Nishida, N., Tokunaga, K., Ukawa, K., Noda, Y., Yoshikawa, A., Shimada, T., Umekage, T. and Sasaki, T. (In Press) DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice. Asia-Pacific Psychiatry. doi:10.1111/appy.12009

[48]   Promega Corp. (2005) Technical manual: Wizard genomic DNA purification kit: Instructions for use of products A1120, A1123, A1125 and A1620. Promega Corp., Madison.

[49]   Nishida, N., Tanabe, T., Hashido, K., Hirayasu, K., Takasu, M., Suyama, A. and Tokunaga, K. (2005) DigiTag assay for multiplex single nucleotide polymorphism typing with high success rate. Analytical Biochemistry, 346, 281-288. doi:10.1016/j.ab.2005.08.007

[50]   Nishida, N., Tanabe, T., Takasu, M., Suyama, A. and Tokunaga, K. (2007) Further development of multiplex single nucleotide polymorphism typing method, the DigiTag2 assay. Analytical Biochemistry, 364, 78-85. doi:10.1016/j.ab.2007.02.005

[51]   Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M.A., Bender, D., Maller, J., Sklar, P., de Bakker, P.I., Daly, M.J. and Sham, P.C. (2007) PLINK: A tool set for whole-genome association and populationbased linkage analyses. American Journal of Human Genetics, 81, 559-575. doi:10.1086/519795

[52]   Good, P. (2000) Permutation tests: A practical guide to resampling methods for testing hypothesis. Second Edition, Springer-Verlag, New York.

[53]   Hochberg, Y. and Tamhane, A.C. (1987) Multiple comparison procedures: Probability and mathematical statistics. Wiley-Interscience, New York. doi:10.1002/9780470316672

[54]   Cohen, J. (1988) Statistical power analysis for the behaviorral sciences. Second Edition, Lawrence Erlbaum, Hillsdale.

[55]   Field, A. (2005) Discovering statistics using SPSS. Second Edition, Sage Publications, London.

[56]   Gauderman, W.J. (2002) Sample size requirements for matched case-control studies of gene-environment interaction. Statistics in Medicine, 21, 35-50. doi:10.1002/sim.973

[57]   SPSS Inc. (2007) SPSS base 16.0 user’s guide. SPSS Inc., Chicago.

[58]   DeVona, J. (2005) Delay discounting task. Binghamton, New York.

[59]   Tachibana, Y. and Hikosaka O. (2012) The primate ventral pallidum encodes expected reward value and regulates motor action. Neuron, 76, 826-837. doi:10.1016/j.neuron.2012.09.030