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Genetic overlap between impulsivity and alcohol dependence: a large-scale national twin study

Published online by Cambridge University Press:  16 December 2015

L. Khemiri*
Affiliation:
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
R. Kuja-Halkola
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
H. Larsson
Affiliation:
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
N. Jayaram-Lindström
Affiliation:
Department of Clinical Neuroscience, Centre for Psychiatric Research, Karolinska Institutet, Stockholm, Sweden
*
*Address for correspondence: L. Khemiri, M.D., Centre for Psychiatry Research (CPF), Karolinska University Hospital, Norra Stationsgatan 69, 7th floor, 113 64, Stockholm, Sweden. (Email: Lotfi.khemiri@ki.se)

Abstract

Background

Alcohol dependence is associated with increased levels of impulsivity, but the genetic and environmental underpinnings of this overlap remain unclear. The purpose of the current study was to investigate the degree to which genetic and environmental factors contribute to the overlap between alcohol dependence and impulsivity.

Method

Univariate and bivariate twin model fitting was conducted for alcohol dependence and impulsivity in a national sample of 16 819 twins born in Sweden from 1959 to 1985.

Results

The heritability estimate for alcohol dependence was 44% [95% confidence interval (CI) 31–57%] for males and 62% (95% CI 52–72%) for females. For impulsivity, the heritability was 33% (95% CI 30–36%) in males and females. The bivariate twin analysis indicated a statistically significant genetic correlation between alcohol dependence and impulsivity of 0.40 (95% CI 0.23–0.58) in males and 0.20 (95% CI 0.07–0.33) in females. The phenotypic correlation between alcohol dependence and impulsivity was 0.20 and 0.17 for males and females, respectively, and the bivariate heritability was 80% (95% CI 47–117%) for males and 53% (95% CI 19–86%) for females. The remaining variance in all models was accounted for by non-shared environmental factors.

Conclusions

The association between alcohol dependence and impulsivity can be partially accounted for by shared genetic factors. The genetic correlation was greater in men compared with women, which may indicate different pathways to the development of alcohol dependence between sexes. The observed genetic overlap has clinical implications regarding treatment and prevention, and partially explains the substantial co-morbidity between alcohol dependence and psychiatric disorders characterized by impulsive behaviour.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2015 

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References

Acheson, A, Richard, DM, Mathias, CW, Dougherty, DM (2011). Adults with a family history of alcohol related problems are more impulsive on measures of response initiation and response inhibition. Drug and Alcohol Dependence 117, 198203.CrossRefGoogle ScholarPubMed
Akaike, H (1987). Factor analysis and AIC. Psychometrika 52, 317332.Google Scholar
Arnsten, AFT, Li, B-M (2005). Neurobiology of executive functions: catecholamine influences on prefrontal cortical functions. Biological Psychiatry 57, 13771384.Google Scholar
Bezdjian, S, Baker, LA, Tuvblad, C (2011). Genetic and environmental influences on impulsivity: a meta-analysis of twin, family and adoption studies. Clinical Psychology Review 31, 12091223.Google Scholar
Bjork, JM, Hommer, DW, Grant, SJ, Danube, C (2004). Impulsivity in abstinent alcohol-dependent patients: relation to control subjects and type 1-/type 2-like traits. Alcohol (Fayetteville, NY) 34, 133150.CrossRefGoogle ScholarPubMed
Boker, S, Neale, M, Maes, H, Wilde, M, Spiegel, M, Brick, T, Spies, J, Estabrook, R, Kenny, S, Bates, T, Mehta, P, Fox, J (2011). OpenMx: an open source extended structural equation modeling framework. Psychometrika 76, 306317.Google Scholar
Bowden-Jones, H, McPhillips, M, Rogers, R, Hutton, S, Joyce, E (2005). Risk-taking on tests sensitive to ventromedial prefrontal cortex dysfunction predicts early relapse in alcohol dependency: a pilot study. Journal of Neuropsychiatry and Clinical Neurosciences 17, 417420.CrossRefGoogle ScholarPubMed
Bush, B, Shaw, S, Cleary, P, Delbanco, TL, Aronson, MD (1987). Screening for alcohol abuse using the CAGE questionnaire. American Journal of Medicine 82, 231235.Google Scholar
Cloninger, CR (1987). Neurogenetic adaptive mechanisms in alcoholism. Science (New York, N.Y.) 236, 410416.Google Scholar
Cloninger, CR, Bohman, M, Sigvardsson, S (1981). Inheritance of alcohol abuse. Cross-fostering analysis of adopted men. Archives of General Psychiatry 38, 861868.Google Scholar
De Wilde, B, Verdejo-García, A, Sabbe, B, Hulstijn, W, Dom, G (2013). Affective decision-making is predictive of three-month relapse in polysubstance-dependent alcoholics. European Addiction Research 19, 2128.CrossRefGoogle ScholarPubMed
De Wit, H (2009). Impulsivity as a determinant and consequence of drug use: a review of underlying processes. Addiction Biology 14, 2231.CrossRefGoogle ScholarPubMed
Dick, DM, Smith, G, Olausson, P, Mitchell, SH, Leeman, RF, O'Malley, SS, Sher, K (2010). Understanding the construct of impulsivity and its relationship to alcohol use disorders. Addiction Biology 15, 217226.Google Scholar
Edwards, AC, Kendler, KS (2012). Twin study of the relationship between adolescent attention-deficit/hyperactivity disorder and adult alcohol dependence. Journal of Studies on Alcohol and Drugs 73, 185194.Google Scholar
Evren, C, Durkaya, M, Evren, B, Dalbudak, E, Cetin, R (2012). Relationship of relapse with impulsivity, novelty seeking and craving in male alcohol-dependent inpatients. Drug and Alcohol Review 31, 8190.Google Scholar
Finn, PR, Mazas, CA, Justus, AN, Steinmetz, J (2002). Early-onset alcoholism with conduct disorder: go/no go learning deficits, working memory capacity, and personality. Alcoholism, Clinical and Experimental Research 26, 186206.CrossRefGoogle ScholarPubMed
Furberg, H, Lichtenstein, P, Pedersen, NL, Thornton, L, Bulik, CM, Lerman, C, Sullivan, PF (2008). The STAGE cohort: a prospective study of tobacco use among Swedish twins. Nicotine and Tobacco Research: Official Journal of the Society for Research on Nicotine and Tobacco 10, 17271735.CrossRefGoogle ScholarPubMed
Goldstein, R, Alexoff, D, Thanos, PK, Volkow, ND, Wang, G-J, Begleiter, H, Porjesz, B, Fowler, JS, Telang, F, Wong, C, Ma, Y, Logan, J (2006). High levels of dopamine D2 receptors in unaffected members of alcoholic families: possible protective factors. Archives of General Psychiatry 63, 9991008.Google Scholar
Goodwin, DW, Schulsinger, F, Hermansen, L, Guze, SB, Winokur, G (1973). Alcohol problems in adoptees raised apart from alcoholic biological parents. Archives of General Psychiatry 28, 238243.CrossRefGoogle ScholarPubMed
Goudriaan, AE, Oosterlaan, J, de Beurs, E, van den Brink, W (2006). Neurocognitive functions in pathological gambling: a comparison with alcohol dependence, Tourette syndrome and normal controls. Addiction (Abingdon, England) 101, 534547.Google Scholar
Gustavsson, JP, Bergman, H, Edman, G, Ekselius, L, von Knorring, L, Linder, J (2000). Swedish universities Scales of Personality (SSP): construction, internal consistency and normative data. Acta Psychiatrica Scandinavica 102, 217225.CrossRefGoogle ScholarPubMed
Haberstick, BC, Young, SE, Zeiger, JS, Lessem, JM, Hewitt, JK, Hopfer, CJ (2014). Prevalence and correlates of alcohol and cannabis use disorders in the United States: results from the National Longitudinal Study of Adolescent Health. Drug and Alcohol Dependence 136, 158161.CrossRefGoogle ScholarPubMed
Heath, AC, Bucholz, KK, Madden, PA, Dinwiddie, SH, Slutske, WS, Bierut, LJ, Statham, DJ, Dunne, MP, Whitfield, JB, Martin, NG (1997). Genetic and environmental contributions to alcohol dependence risk in a national twin sample: consistency of findings in women and men. Psychological Medicine 27, 13811396.CrossRefGoogle Scholar
Hrubec, Z, Omenn, GS (1981). Evidence of genetic predisposition to alcoholic cirrhosis and psychosis: twin concordances for alcoholism and its biological end points by zygosity among male veterans. Alcoholism, Clinical and Experimental Research 5, 207215.Google Scholar
Joos, L, Goudriaan, AE, Schmaal, L, Fransen, E, van den Brink, W, Sabbe, BGC, Dom, G (2013). Effect of modafinil on impulsivity and relapse in alcohol dependent patients: a randomized, placebo-controlled trial. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology 23, 948955.CrossRefGoogle ScholarPubMed
Kareken, DA, Dzemidzic, M, Wetherill, L, Eiler, W II, Oberlin, BG, Harezlak, J, Wang, Y, O'Connor, SJ (2013). Family history of alcoholism interacts with alcohol to affect brain regions involved in behavioral inhibition. Psychopharmacology 228, 335345.Google Scholar
Kendler, KS, Heath, AC, Neale, MC, Kessler, RC, Eaves, LJ (1992). A population-based twin study of alcoholism in women. JAMA: The Journal of the American Medical Association 268, 18771882.Google Scholar
Kendler, KS, Prescott, CA, Myers, J, Neale, MC (2003). The structure of genetic and environmental risk factors for common psychiatric and substance use disorders in men and women. Archives of General Psychiatry 60, 929937.CrossRefGoogle ScholarPubMed
Kendler, KS, Prescott, CA, Neale, MC, Pedersen, NL (1997). Temperance board registration for alcohol abuse in a national sample of Swedish male twins, born 1902 to 1949. Archives of General Psychiatry 54, 178184.Google Scholar
Ketzenberger, KE, Forrest, L (2000). Impulsiveness and compulsiveness in alcoholics and nonalcoholics. Addictive Behaviors 25, 791795.Google Scholar
Khan, S, Okuda, M, Hasin, DS, Secades-Villa, R, Keyes, K, Lin, K-H, Grant, B, Blanco, C (2013). Gender differences in lifetime alcohol dependence: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Alcoholism, Clinical and Experimental Research 37, 16961705.CrossRefGoogle ScholarPubMed
Khemiri, L, Steensland, P, Guterstam, J, Beck, O, Carlsson, A, Franck, J, Jayaram-Lindström, N (2015). The effects of the monoamine stabilizer (-)-OSU6162 on craving in alcohol dependent individuals: a human laboratory study. European Neuropsychopharmacology. Published online 8 October 2015. doi:10.1016/j.euroneuro.2015.09.018.Google Scholar
Knopik, VS, Heath, AC, Jacob, T, Slutske, WS, Bucholz, KK, Madden, PAF, Waldron, M, Martin, NG (2006). Maternal alcohol use disorder and offspring ADHD: disentangling genetic and environmental effects using a children-of-twins design. Psychological Medicine 36, 14611471.Google Scholar
Knopik, VS, Heath, AC, Madden, PAF, Bucholz, KK, Slutske, WS, Nelson, EC, Statham, D, Whitfield, JB, Martin, NG (2004). Genetic effects on alcohol dependence risk: re-evaluating the importance of psychiatric and other heritable risk factors. Psychological Medicine 34, 15191530.CrossRefGoogle ScholarPubMed
Lawrence, AJ, Luty, J, Bogdan, NA, Sahakian, BJ, Clark, L (2009). Problem gamblers share deficits in impulsive decision-making with alcohol-dependent individuals. Addiction (Abingdon, England) 104, 10061015.CrossRefGoogle ScholarPubMed
Leeman, RF, Ralevski, E, Limoncelli, D, Pittman, B, O'Malley, SS, Petrakis, IL (2014). Relationships between impulsivity and subjective response in an IV ethanol paradigm. Psychopharmacology 231, 28672876.Google Scholar
Lejuez, CW, Magidson, JF, Mitchell, SH, Sinha, R, Stevens, MC, de Wit, H (2010). Behavioral and biological indicators of impulsivity in the development of alcohol use, problems, and disorders. Alcoholism, Clinical and Experimental Research 34, 13341345.Google Scholar
Lichtenstein, P, De Faire, U, Floderus, B, Svartengren, M, Svedberg, P, Pedersen, NL (2002). The Swedish Twin Registry: a unique resource for clinical, epidemiological and genetic studies. Journal of Internal Medicine 252, 184205.Google Scholar
Lichtenstein, P, Sullivan, PF, Cnattingius, S, Gatz, M, Johansson, S, Carlström, E, Björk, C, Svartengren, M, Wolk, A, Klareskog, L, de Faire, U, Schalling, M, Palmgren, J, Pedersen, NL (2006). The Swedish Twin Registry in the third millennium: an update. Twin Research and Human Genetics: The Official Journal of the International Society for Twin Studies 9, 875882.Google Scholar
Mayfield, D, McLeod, G, Hall, P (1974). The CAGE questionnaire: validation of a new alcoholism screening instrument. American Journal of Psychiatry 131, 11211123.Google Scholar
Merikangas, KR, Stolar, M, Stevens, DE, Goulet, J, Preisig, MA, Fenton, B, Zhang, H, O'Malley, SS, Rounsaville, BJ (1998). Familial transmission of substance use disorders. Archives of General Psychiatry 55, 973979.Google Scholar
Moeller, FG, Barratt, ES, Dougherty, DM, Schmitz, JM, Swann, AC (2001). Psychiatric aspects of impulsivity. American Journal of Psychiatry 158, 17831793.Google Scholar
Neale, M, Cardon, L, North Atlantic Treaty Organization & Scientific Affairs Division (1992). Methodology for Genetic Studies of Twins and Families. Kluwer Academic Publishers: Dordrecht, Boston.Google Scholar
Neale, MC, Røysamb, E, Jacobson, K (2006) Multivariate genetic analysis of sex limitation and G x E interaction. Twin Research and Human Genetics: The Official Journal of the International Society for Twin Studies 9, 481489.Google Scholar
Papachristou, H, Nederkoorn, C, Havermans, R, Bongers, P, Beunen, S, Jansen, A (2013). Higher levels of trait impulsiveness and a less effective response inhibition are linked to more intense cue-elicited craving for alcohol in alcohol-dependent patients. Psychopharmacology 228, 641649.Google Scholar
Pattij, T, Vanderschuren, LJMJ (2008). The neuropharmacology of impulsive behaviour. Trends in Pharmacological Sciences 29, 192199.Google Scholar
Petry, NM (2001). Delay discounting of money and alcohol in actively using alcoholics, currently abstinent alcoholics, and controls. Psychopharmacology 154, 243250.Google Scholar
Ray, LA, Mackillop, J, Monti, PM (2010). Subjective responses to alcohol consumption as endophenotypes: advancing behavioral genetics in etiological and treatment models of alcoholism. Substance Use and Misuse 45, 17421765.CrossRefGoogle ScholarPubMed
R Development Core Team (2010). R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna.Google Scholar
Rehm, J, Room, R, van den Brink, W, Jacobi, F (2005). Alcohol use disorders in EU countries and Norway: an overview of the epidemiology. European Neuropsychopharmacology: The Journal of the European College of Neuropsychopharmacology 15, 377388.Google Scholar
Saunders, B, Farag, N, Vincent, AS, Collins, FL Jr., Sorocco, KH, Lovallo, WR (2008). Impulsive errors on a Go-NoGo reaction time task: disinhibitory traits in relation to a family history of alcoholism. Alcoholism, Clinical and Experimental Research 32, 888894.CrossRefGoogle ScholarPubMed
Schmaal, L, Joos, L, Koeleman, M, Veltman, DJ, van den Brink, W, Goudriaan, AE (2013). Effects of modafinil on neural correlates of response inhibition in alcohol-dependent patients. Biological Psychiatry 73, 211218.Google Scholar
Schuckit, MA (2009). An overview of genetic influences in alcoholism. Journal of Substance Abuse Treatment 36, S5S14.Google Scholar
Schuckit, MA, Smith, TL (1996). An 8-year follow-up of 450 sons of alcoholic and control subjects. Archives of General Psychiatry 53, 202210.Google Scholar
Setiawan, E, Pihl, RO, Dagher, A, Schlagintweit, H, Casey, KF, Benkelfat, C, Leyton, M (2014). Differential striatal dopamine responses following oral alcohol in individuals at varying risk for dependence. Alcoholism, Clinical and Experimental Research 38, 126134.Google Scholar
Sher, KJ, Walitzer, KS, Wood, PK, Brent, EE (1991). Characteristics of children of alcoholics: putative risk factors, substance use and abuse, and psychopathology. Journal of Abnormal Psychology 100, 427448.CrossRefGoogle ScholarPubMed
Slutske, WS, Ellingson, JM, Richmond-Rakerd, LS, Zhu, G, Martin, NG (2013). Shared genetic vulnerability for disordered gambling and alcohol use disorder in men and women: evidence from a national community-based Australian Twin Study. Twin Research and Human Genetics: The Official Journal of the International Society for Twin Studies 16, 525534.Google Scholar
Slutske, WS, Heath, AC, Dinwiddie, SH, Madden, PA, Bucholz, KK, Dunne, MP, Statham, DJ, Martin, NG (1998). Common genetic risk factors for conduct disorder and alcohol dependence. Journal of Abnormal Psychology 107, 363374.Google Scholar
Slutske, WS, Heath, AC, Madden, PAF, Bucholz, KK, Statham, DJ, Martin, NG (2002). Personality and the genetic risk for alcohol dependence. Journal of Abnormal Psychology 111, 124133.CrossRefGoogle ScholarPubMed
True, WR, Xian, H, Scherrer, JF, Madden, PA, Bucholz, KK, Heath, AC, Eisen, SA, Lyons, MJ, Goldberg, J, Tsuang, M (1999). Common genetic vulnerability for nicotine and alcohol dependence in men. Archives of General Psychiatry 56, 655661.CrossRefGoogle ScholarPubMed
Tupala, E, Tiihonen, J (2004). Dopamine and alcoholism: neurobiological basis of ethanol abuse. Progress in Neuro-Psychopharmacology and Biological Psychiatry 28, 12211247.Google Scholar
Verdejo-García, A, Lawrence, AJ, Clark, L (2008). Impulsivity as a vulnerability marker for substance-use disorders: review of findings from high-risk research, problem gamblers and genetic association studies. Neuroscience and Biobehavioral Reviews 32, 777810.Google Scholar
Voronin, K, Randall, P, Myrick, H, Anton, R (2008). Aripiprazole effects on alcohol consumption and subjective reports in a clinical laboratory paradigm – possible influence of self-control. Alcoholism, Clinical and Experimental Research 32, 19541961.Google Scholar
Vrieze, SI, Vaidyanathan, U, Hicks, BM, Iacono, WG, McGue, M (2014). The role of constraint in the development of nicotine, marijuana, and alcohol dependence in young adulthood. Behavior Genetics 44, 1424.Google Scholar
Weinshenker, D, Schroeder, JP (2007). There and back again: a tale of norepinephrine and drug addiction. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology 32, 14331451.Google Scholar
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