Journal of Gambling Studies

, Volume 31, Issue 2, pp 513–524 | Cite as

COMT Associations with Disordered Gambling and Drinking Measures

  • Casey R. Guillot
  • Jennifer R. Fanning
  • Tiebing Liang
  • Mitchell E. Berman
Original Paper


Disordered gambling and alcohol dependence are influenced by unique and shared genetic factors. Although the evidence is mixed, some research has linked catechol-O-methyltransferase (COMT) rs4680 (or COMT Val158Met) to the development of gambling or drinking problems; however, no molecular genetic study has jointly examined gambling and drinking problems. Furthermore, the majority of past studies examined gambling or drinking problems using a case–control design. The purpose of the current study was to examine associations of COMT rs4680 with dimensionally and categorically measured gambling and drinking problems in a nonclinical sample (139 Caucasian adults). The current study found that COMT rs4680 was related to both dimensionally and categorically measured gambling and drinking problems. It appears that the COMT Met/Met genotype may be a genetic risk factor that contributes to the development of both gambling and drinking problems.


Alcohol use COMT gene Gambling South Oaks Gambling Screen Michigan Alcoholism Screening Test 



This study was supported by funding from the National Institute on Alcohol Abuse and Alcoholism to Mitchell E. Berman (Grant Number: AA14025).

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Abi-Dargham, A., Rodenhiser, J., Printz, D., Zea-Ponce, Y., Gil, R., Kegeles, L. S., et al. (2000). Increased baseline occupancy of D2 receptors by dopamine in schizophrenia. Proceedings of the National Academy of Sciences, 97, 8104–8109.CrossRefGoogle Scholar
  2. Agrawal, A., Verweij, K. J. H., Gillespie, N. A., Heath, A. C., Lessov-Schlagger, C. N., Martin, N. G., et al. (2012). The genetics of addiction—A translational perspective. Translational Psychiatry, 2, e140. doi: 10.1038/tp.2012.54.CrossRefPubMedCentralPubMedGoogle Scholar
  3. Berridge, K. C. (2007). The debate over dopamine’s role in reward: The case for incentive salience. Psychopharmacology, 191, 391–431.CrossRefPubMedGoogle Scholar
  4. Bierut, L. J., Agrawal, A., Bucholz, K. K., Doheny, K. F., Laurie, C., Pugh, E., et al. (2010). A genome-wide association study of alcohol dependence. Proceedings of the National Academy of Sciences of the United States of America, 107, 5082–5087.CrossRefPubMedCentralPubMedGoogle Scholar
  5. Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004). The catechol-O-methyltransferase polymorphism: Relations to the tonic–phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology, 29, 1943–1961.CrossRefPubMedGoogle Scholar
  6. Boettiger, C. A., Mitchell, J. M., Tavares, V. C., Robertson, M., Joslyn, G., D’Esposito, M., et al. (2007). Immediate reward bias in humans: Fronto-parietal networks and a role for the catechol-O-methyltransferase 158Val/Val genotype. The Journal of Neuroscience, 27, 14383–14391.CrossRefPubMedGoogle Scholar
  7. Bonke, J., & Borregaard, K. (2009). The prevalence of problematic gambling behaviour: A scandinavian comparison. Scandinavian Journal of Public Health, 37, 654–660.CrossRefPubMedGoogle Scholar
  8. Bousman, C. A., Glatt, S. J., Cherner, M., Atkinson, J. H., Grant, I., Tsuang, M. T., et al. (2010). Preliminary evidence of ethnic divergence in associations of putative genetic variants for methamphetamine dependence. Psychiatry Research, 178, 295–298.CrossRefPubMedCentralPubMedGoogle Scholar
  9. Braverman, J., LaBrie, R. A., & Shaffer, H. J. (2011). A taxometric analysis of actual internet sports gambling behavior. Psychological Assessment, 23, 234–244.CrossRefPubMedGoogle Scholar
  10. Cagniard, B., Balsam, P. D., Brunner, D., & Zhuang, X. (2006). Mice with chronically elevated dopamine exhibit enhanced motivation, but not learning, for a food reward. Neuropsychopharmacology, 31, 1362–1370.CrossRefPubMedGoogle Scholar
  11. Chen, J., Lipska, B. K., Halim, N., Ma, Q. D., Matsumoto, M., Melhem, S., et al. (2004). Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain. The American Journal of Human Genetics, 75, 807–821.CrossRefGoogle Scholar
  12. Cohen, J. (2009). Statistical power analysis for the behavioral sciences (2nd ed.). New York: Psychology Press. (Original work published 1988).Google Scholar
  13. Comings, D. E., Gade-Andavolu, R., Gonzalez, N., Wu, S., Muhleman, D., Chen, C., et al. (2001). The additive effect of neurotransmitter genes in pathological gambling. Clinical Genetics, 60, 107–116.CrossRefPubMedGoogle Scholar
  14. Diana, M. (2011). The dopamine hypothesis of drug addiction and its potential therapeutic value. Frontiers in Psychiatry, 2. doi: 10.3389/fpsyt.2011.00064.
  15. Foroud, T., Wetherill, L. F., Dick, D. M., Hesselbrock, V., Nurnberger, J. I., Kramer, J., et al. (2007). Lack of association of alcohol dependence and habitual smoking with catechol-O-methyltransferase. Alcoholism: Clinical and Experimental Research, 31, 1773–1779.CrossRefGoogle Scholar
  16. Gianotti, L. R. R., Figner, B., Ebstein, R. P., & Knoch, D. (2012). Why some people discount more than others: Baseline activation in the dorsal PFC mediates the link between COMT genotype and impatient choice. Frontiers in Neuroscience, 6. doi: 10.3389/fnins.2012.00054.
  17. Green, B. A., Ahmed, A. O., Marcus, D. K., & Walters, G. D. (2011). The latent structure of alcohol use pathology in an epidemiological sample. Journal of Psychiatric Research, 45, 225–233.CrossRefPubMedGoogle Scholar
  18. Hasin, D. S., Stinson, F. S., Ogburn, E., & Grant, B. F. (2007). Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: Results from the National Epidemiologic Survey on alcohol and related conditions. Archives of General Psychiatry, 64, 830–842.CrossRefPubMedGoogle Scholar
  19. Johnson, P. S., Madden, G. J., & Stein, J. S. (2012). Effects of acute pramipexole on male rats’ preference for gambling-like rewards II. Experimental and Clinical Psychopharmacology, 20, 167–172.CrossRefPubMedCentralPubMedGoogle Scholar
  20. Joutsa, J., Johansson, J., Niemela, S., Ollikainen, A., Hirvonen, M. M., Piepponen, P., et al. (2012). Mesolimbic dopamine release is linked to symptom severity in pathological gambling. NeuroImage, 60, 1992–1999.CrossRefPubMedGoogle Scholar
  21. Kapur, S. (2003). Psychosis as a state of aberrant salience: A framework linking biology, phenomenology, and pharmacology in schizophrenia. The American Journal of Psychiatry, 160, 13–23.CrossRefPubMedGoogle Scholar
  22. Kauhanen, J., Hallikainen, T., Tuomainen, T. P., Koulu, M., Karvonen, M. K., Salonen, J. T., et al. (2000). Association between the functional polymorphism of catechol-O-methyltransferase gene and alcohol consumption among social drinkers. Alcoholism, Clinical and Experimental Research, 24, 135–139.CrossRefPubMedGoogle Scholar
  23. Keppel, G. (1991). Design and analysis: A researcher’s handbook (3rd ed.). NJ: Prentice-Hall.Google Scholar
  24. Kessler, R. C., Hwang, I., LaBrie, R., Petukhova, M., Sampson, N. A., Winters, K. C., et al. (2008). The prevalence and correlates of DSM-IV pathological gambling in the National Comorbidity Survey Replication. Psychological Medicine, 38, 1351–1360.PubMedCentralPubMedGoogle Scholar
  25. Kincaid, H., Daniels, R., Dellis, A., Hofmeyr, A., Rousseau, J., Sharp, C., et al. (2013). A taxometric analysis of problem gambling data from a South African national urban sample. Journal of Gambling Studies, 29, 377–392.CrossRefPubMedGoogle Scholar
  26. Kokotailo, P. K., Egan, J., Gangnon, R., Brown, D., Mundt, M., & Fleming, M. (2004). Validity of the alcohol use disorders identification test in college students. Alcoholism, Clinical and Experimental Research, 28, 914–920.CrossRefPubMedGoogle Scholar
  27. Lancaster, T. M., Linden, D. E., & Heerey, E. A. (2012). COMT val158met predicts reward responsiveness in humans. Genes, Brain and Behavior,. doi: 10.1111/j.1601-183X.2012.00838.x.Google Scholar
  28. Lesieur, H. R., & Blume, S. B. (1993). Revising the South Oaks Gambling Screen in different settings. Journal of Gambling Studies, 9, 213–223.CrossRefGoogle Scholar
  29. Lind, P. A., Zhu, G., Montgomery, G. W., Madden, P. A. F., Heath, A. C., Martin, N. G., et al. (2013). Genome-wide association study of a quantitative disordered gambling trait. Addiction Biology, 18, 511–522.CrossRefPubMedCentralPubMedGoogle Scholar
  30. Linnet, J., Moller, A., Peterson, E., Gjedde, A., & Doudet, D. (2011). Inverse association between dopaminergic neurotransmission and Iowa Gambling Task performance in pathological gamblers and healthy controls. Scandinavian Journal of Psychology, 52, 28–34.CrossRefPubMedGoogle Scholar
  31. Linnet, J., Peterson, E., Doudet, D. J., Gjedde, A., & Moller, A. (2010). Dopamine release in ventral striatum of pathological gamblers losing money. Acta Psychiatrica Scandinavica, 122, 326–333.CrossRefPubMedGoogle Scholar
  32. Lobo, D. S. S., & Kennedy, J. L. (2009). Genetic aspects of pathological gambling: A complex disorder with shared genetic vulnerabilities. Addiction, 104, 1454–1465.CrossRefPubMedGoogle Scholar
  33. Mannisto, P. T., & Kaakkola, S. (1999). Catechol-O-methyltransferase (COMT): Biochemistry, molecular biology, pharmacology, and clinical efficacy of the new selective COMT inhibitors. Pharmacological Reviews, 51, 593–628.PubMedGoogle Scholar
  34. Munafo, M. R., Freathy, R. M., Ring, S. M., St Pourcain, B., & Smith, G. D. (2011). Association of COMT Val108/158Met genotype and cigarette smoking in pregnant women. Nicotine & Tobacco Research, 13, 55–63.CrossRefGoogle Scholar
  35. Olfson, E., & Bierut, L. J. (2012). Convergence of genome-wide association and candidate gene studies for alcoholism. Alcoholism, Clinical and Experimental Research, 36, 2086–2094.CrossRefPubMedCentralPubMedGoogle Scholar
  36. Reid, M. C., Fiellin, D. A., & O’Connor, P. G. (1999). Hazardous and harmful alcohol consumption in primary care. Archives of Internal Medicine, 159, 1681–1689.CrossRefPubMedGoogle Scholar
  37. Robinson, T. E., & Berridge, K. C. (2008). The incentive sensitization theory of addiction: Some current issues. Philosophical Transactions of the Royal Society B, 363, 3137–3146.CrossRefGoogle Scholar
  38. Rodriguez, S., Gaunt, T. R., & Day, I. N. M. (2009). Hardy–Weinberg equilibrium testing of biological ascertainment for Mendelian randomization studies. American Journal of Epidemiology, 169, 505–514.CrossRefPubMedCentralPubMedGoogle Scholar
  39. Schellekens, A. F. A., Franke, B., Ellenbrock, B., Cools, A., de Jong, C. A. J., Buitelaar, J. K., et al. (2012). Reduced dopamine receptor sensitivity as an intermediate phenotype in alcohol dependence and the role of the COMT Val158Met and DRD2 Taq1A genotypes. Archives of General Psychiatry, 69, 339–348.CrossRefPubMedGoogle Scholar
  40. Selzer, M. L., Vinokur, A., & van Rooijen, L. (1975). A self-administered Short Michigan Alcoholism Screening Test (SMAST). Journal of Studies on Alcohol, 36, 117–126.CrossRefPubMedGoogle Scholar
  41. Singer, B. F., Scott-Railton, J., & Vezina, P. (2012). Unpredictable saccharin reinforcement enhances locomotor responding to amphetamine. Behavioural Brain Research, 226, 340–344.CrossRefPubMedCentralPubMedGoogle Scholar
  42. Steeves, T. D. L., Miyasaki, J., Zurowski, M., Lang, A. E., Pellecchia, G., van Eimeren, T., et al. (2009). Increased striatal dopamine release in Parkinsonian patients with pathological gambling: A [11C] raclopride PET study. Brain, 132, 1376–1385.CrossRefPubMedCentralPubMedGoogle Scholar
  43. Tiihonen, J., Hallikainen, T., Lachman, H., Saito, T., Volavka, J., Kauhanen, J., et al. (1999). Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism. Molecular Psychiatry, 4, 286–289.CrossRefPubMedGoogle Scholar
  44. Truett, G. E., Heeger, P., Mynatt, R. L., Truett, A. A., Walker, J. A., & Warman, M. L. (2000). Preparation of PCR-quality mouse genomic DNA with hot sodium hydroxide and tris (HotSHOT). BioTechniques, 29, 52–54.PubMedGoogle Scholar
  45. Urban, N. B. L., Kegeles, L. S., Slifstein, M., Xu, X., Martinez, D., Sakr, E., et al. (2010). Sex differences in striatal dopamine release in young adults after oral alcohol challenge: A positron emission tomography imaging study with [11C]raclopride. Biological Psychiatry, 68, 689–696.CrossRefPubMedCentralPubMedGoogle Scholar
  46. van den Bos, R., Homberg, J., Gijsbers, E., den Heijer, E., & Cuppen, E. (2009). The effect of COMT Val158 Met genotype on decision-making and preliminary findings on its interaction with the 5-HTTLPR in healthy females. Neuropharmacology, 56, 493–498.CrossRefPubMedGoogle Scholar
  47. Vandenbergh, D. J., Rodriguez, L. A., Miller, I. T., Uhl, G. R., & Lachman, H. M. (1997). High-activity catechol-O-methyltransferase allele is more prevalent in polysubstance abusers. American Journal of Medical Genetics, 74, 439–442.CrossRefPubMedGoogle Scholar
  48. Voon, V., Reynolds, B., Brezing, C., Gallea, C., Skaljic, M., Ekanayake, V., et al. (2010). Impulsive choice and response dopamine agonist-related impulse control behaviors. Psychopharmacology, 207, 645–659.CrossRefPubMedCentralPubMedGoogle Scholar
  49. Wang, T., Franke, P., Neidt, H., Cichon, S., Knapp, M., Lichtermann, D., et al. (2001). Association study of the low-activity allele of catechol-O-methyltransferase and alcoholism using a family-based approach. Molecular Psychiatry, 6, 109–111.CrossRefPubMedGoogle Scholar
  50. Weintraub, D., Koester, J., Potenza, M. N., Siderowf, A. D., Stacy, M., Voon, V., et al. (2010). Impulse control disorders in Parkinson disease: A cross-sectional study of 3090 patients. Archives of Neurology, 67, 589–595.CrossRefPubMedGoogle Scholar
  51. Wise, R. A. (2004). Dopamine, learning and motivation. Nature Reviews Neuroscience, 5, 483–494.CrossRefPubMedGoogle Scholar
  52. Zack, M., & Poulos, C. X. (2004). Amphetamine primes motivation to gamble and gambling-related semantic networks in problem gamblers. Neuropsychopharmacology, 29, 195–207.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Casey R. Guillot
    • 1
  • Jennifer R. Fanning
    • 2
  • Tiebing Liang
    • 3
  • Mitchell E. Berman
    • 4
  1. 1.University of Southern California Keck School of MedicineLos AngelesUSA
  2. 2.Department of Psychiatry and Behavioral NeuroscienceUniversity of ChicagoChicagoUSA
  3. 3.Indiana University School of MedicineIndianapolisUSA
  4. 4.Department of PsychologyMississippi State UniversityStarkvilleUSA

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