Specificity of Genetic and Environmental Risk Factors for Use and Abuse/Dependence of Cannabis, Cocaine, Hallucinogens, Sedatives, Stimulants, and Opiates in Male Twins
Abstract
OBJECTIVE: Data on use and misuse of six classes of illicit substances by male twin pairs were used to examine whether genetic and shared environmental risk factors for substance use disorders are substance-specific or -nonspecific in their effect. METHOD: Lifetime history of use and abuse/dependence of cannabis, cocaine, hallucinogens, sedatives, stimulants, and opiates was assessed at personal interview in both members of 1,196 male-male twin pairs ascertained by the Virginia Twin Registry. Multivariate twin modeling of substance-nonspecific (common) and substance-specific genetic, shared environmental, and unique environmental risk factors was performed by using the program Mx. RESULTS: High levels of comorbidity involving the different substance categories were observed for both use and abuse/dependence. One common genetic factor was found to have a strong influence on risk for illicit use and abuse/dependence for all six substance classes. A modest influence of substance-specific genetic factors was seen for use but not for abuse/dependence. Shared environmental factors were more important for use than for abuse/dependence and were mediated entirely through a single common factor. CONCLUSIONS: In an adult population-based sample of male twins, both the genetic and the shared environmental effects on risk for the use and misuse of six classes of illicit substances were largely or entirely nonspecific in their effect. Environmental experiences unique to the person largely determine whether predisposed individuals will use or misuse one class of psychoactive substances rather than another.
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Common genetic vulnerabilities help explain the frequent comorbidity between SUDs and ADHD as well as anxiety disorders and depression.
“These common genetic vulner abilities help explain the frequent comorbidity between SUDs and attention- deficit/hyperactivity disorder (ADHD) as well as anx iety disorders and depression 93 .”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [93]
The genetics of SUDs appears to be part of a general genetic predisposition to externalizing disorders, though common genetic predisposition has also been reported between SUDs and internalizing disorders.
“The genetics of SUDs appears to be part of a general genetic predisposition to externalizing disorders, though common genetic predisposition has also been reported between SUDs and internalizing disorders.”
From Substance use disorders: a comprehensive update of classification, epidemiology, neurobiology, clinical aspects, treatment and prevention (2023) · cites this paper as [93]
Cites
Akaike, H. (1987) · Psychometrika · doi:10.1007/bf02294359 · Cited by 5,264 · see citing works
Akaike, H. (1987) · Springer Series in Statistics · doi:10.1007/978-1-4612-1694-0_29 · Cited by 4,027 · see citing works
Methodology for Genetic Studies of Twins and Families
Neale, M. C., & Cardon, L. R. (1992) · doi:10.1007/978-94-015-8018-2 · Cited by 4,005 · see citing works
Self-citationDrug abuse: hedonic homeostatic dysregulation
Koob, G. F., & Moal, M. L. (1997) · Science · doi:10.1126/science.278.5335.52 · Cited by 2,535 · see citing works
The Structured Clinical Interview for DSM-III-R (SCID)
Williams, J. B. W. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820080038006 · Cited by 1,627 · see citing works
Familial Transmission of Substance Use Disorders
Merikangas, K. R., Stolar, M., Stevens, D. E., Goulet, J., Preisig, M. A., Fenton, B., Zhang, H., O'Malley, S. S., & Rounsaville, B. J. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.11.973 · Cited by 783 · see citing works
Tsuang, M. T., Lyons, M. J., Meyer, J. M., Doyle, T., Eisen, S. A., Goldberg, J., True, W., Lin, N., Toomey, R., & Eaves, L. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.11.967 · Cited by 710 · see citing works
The Genetic Epidemiology of Phobias in Women
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820040025003 · Cited by 551 · see citing works
Self-citationKendler, K. S., Karkowski, L. M., Neale, M. C., & Prescott, C. A. (2000) · Archives of General Psychiatry · doi:10.1001/archpsyc.57.3.261 · Cited by 503 · see citing works
Self-citationFamilial Transmission of Substance Dependence: Alcohol, Marijuana, Cocaine, and Habitual Smoking
Bierut, L. J., Dinwiddie, S. H., Begleiter, H., Crowe, R., HESSELBROCK, V. M., Nürnberger, J. I., Bernice Porjesz, A., Schuckit, M. A., & Reich, T. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.11.982 · Cited by 484 · see citing works
A Population-Based Twin Study of Major Depression in Women
Kendler, K. S. (1992) · Archives of General Psychiatry · doi:10.1001/archpsyc.1992.01820040009001 · Cited by 455 · see citing works
Self-citationA population-based twin study in women of smoking initiation and nicotine dependence
Kendler, K. S., Neale, M. C., Sullivan, P. F., Corey, L. A., GARDNER, C. O., & Prescott, C. A. (1999) · Psychological Medicine · doi:10.1017/s0033291798008022 · Cited by 438 · see citing works
Self-citationModels of comorbidity for multifactorial disorders.
Neale, M. C., & Kendler, K. S. (1995) · PubMed Central · Cited by 353 · see citing works
Self-citationNatural Histories of Conduct Problems, Delinquency, and Associated Substance Use
Loeber, R. (1988) · Springer eBooks · doi:10.1007/978-1-4613-9829-5_2 · Cited by 267 · see citing works
Cannabis Use, Abuse, and Dependence in a Population-Based Sample of Female Twins
Kendler, K. S., & Prescott, C. A. (1998) · American Journal of Psychiatry · doi:10.1176/ajp.155.8.1016 · Cited by 265 · see citing works
Self-citationParsimony‐based fit indices for multiple‐indicator models: Do they work?
Williams, L. J., & Holahan, P. J. (1994) · Structural Equation Modeling A Multidisciplinary Journal · doi:10.1080/10705519409539970 · Cited by 253 · see citing works
Uhl, G. R., Liu, Q., Walther, D. M., Hess, J., & Naiman, D. Q. (2001) · The American Journal of Human Genetics · doi:10.1086/324467 · Cited by 251 · see citing works
Genetic and environmental influences on drug use and abuse/dependence in male and female twins
van den Bree, M. B. M., Johnson, E. O., Neale, M. C., & Pickens, R. W. (1998) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(98)00101-x · Cited by 237 · see citing works
Self-citationPsychiatric Disorders in Relatives of Probands With Opiate Addiction
Rounsaville, B. J. (1991) · Archives of General Psychiatry · doi:10.1001/archpsyc.1991.01810250035004 · Cited by 195 · see citing works
Evaluation of Analyses of Univariate Discrete Twin Data
Sullivan, P. F., & Eaves, L. J. (2002) · Behavior Genetics · doi:10.1023/a:1016025229858 · Cited by 101 · see citing works
On Use of Multiple Tests of Significance in Psychological Research
Feild, H. S., & Armenakis, A. A. (1974) · Psychological Reports · doi:10.2466/pr0.1974.35.1.427 · Cited by 101 · see citing works
General and Specific Inheritance of Substance Abuse and Alcoholism
Goldman, D. A., & Bergen, A. W. (1998) · Archives of General Psychiatry · doi:10.1001/archpsyc.55.11.964 · Cited by 95 · see citing works
Genetic and Family Studies in Psychiatric Illness and Alcohol and Drug Dependence
Dinwiddie, S. H., & Reich, T. (1993) · Journal of Addictive Diseases · doi:10.1300/j069v12n03_03 · Cited by 17 · see citing works
Young (2000) · doi:10.1002/1096-8628(20001009)96:5
Flagged first, then by citations
Cited by
Sorted by citations
The genetics of addictions: uncovering the genes
Goldman, D., Oroszi, G., & Ducci, F. (2005) · Nature Reviews Genetics · doi:10.1038/nrg1635 · Cited by 1,099 · see citing works
Kreek, M. J., Nielsen, D. A., Butelman, E. R., & LaForge, K. S. (2005) · Nature Neuroscience · doi:10.1038/nn1583 · Cited by 1,024 · see citing works
The Neuroscience of Drug Reward and Addiction
Volkow, N. D., Michaelides, M., & Baler, R. (2019) · Physiological Reviews · doi:10.1152/physrev.00014.2018 · Cited by 863 · see citing works
Toward a syndrome model of addiction: Multiple expressions, common etiology
Shaffer, H. J., LaPlante, D. A., LaBrie, R. A., Kidman, R. C., Donato, A. N., & Stanton, M. V. (2004) · Harvard Review of Psychiatry · doi:10.1080/10673220490905705 · Cited by 682 · see citing works
The epidemiology of dual diagnosis
Kessler, R. C. (2004) · Biological Psychiatry · doi:10.1016/j.biopsych.2004.06.034 · Cited by 588 · see citing works
Volkow, N. D., & Blanco, C. (2023) · World psychiatry · doi:10.1002/wps.21073 · Cited by 503 · see citing works
Pharmacogenetics and Human Molecular Genetics of Opiate and Cocaine Addictions and Their Treatments
Kreek, M. J., Bart, G., Lilly, C., Laforge, K. S., & Nielsen, D. A. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.1.1 · Cited by 391 · see citing works
GRANT, J. D., SCHERRER, J. F., LYNSKEY, M. T., LYONS, M. J., EISEN, S. A., TSUANG, M. T., TRUE, W. R., & BUCHOLZ, K. K. (2006) · Psychological Medicine · doi:10.1017/s0033291705006045 · Cited by 321 · see citing works
Drugs as instruments: A new framework for non-addictive psychoactive drug use
Müller, C. P., & Schumann, G. (2011) · Behavioral and Brain Sciences · doi:10.1017/s0140525x11000057 · Cited by 286 · see citing works
Early Developmental Processes and the Continuity of Risk for Underage Drinking and Problem Drinking
Zucker, R. A., Donovan, J. E., Masten, A. S., Mattson, M. E., & Moss, H. B. (2008) · Pediatrics · doi:10.1542/peds.2007-2243b · Cited by 276 · see citing works
Sleep problems in early childhood and early onset of alcohol and other drug use in adolescence
Wong, M. M., Brower, K. J., Fitzgerald, H. E., & Zucker, R. A. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000121651.75952.39 · Cited by 271 · see citing works
Ersche, K. D., Turton, A. J., Chamberlain, S. R., Müller, U., Bullmore, E. T., & Robbins, T. W. (2012) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2012.11091421 · Cited by 252 · see citing works
Hasin, D., Hatzenbuehler, M. L., Keyes, K., & Ogburn, E. (2006) · Addiction · doi:10.1111/j.1360-0443.2006.01584.x · Cited by 213 · see citing works
Liability to substance use disorders: 1. Common mechanisms and manifestations
Vanyukov, M. M., Tarter, R. E., Kirisci, L., Kirillova, G. P., Maher, B. S., & Clark, D. B. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2003.08.002 · Cited by 205 · see citing works
Agrawal, A., Edenberg, H. J., Foroud, T., Bierut, L. J., Dunne, G., Hinrichs, A. L., Nurnberger, J. I., Crowe, R., Kuperman, S., Schuckit, M. A., et al. (2006) · Behavior Genetics · doi:10.1007/s10519-006-9069-4 · Cited by 189 · see citing works
Genetic factors influencing alcohol dependence
Mayfield, R. D., Harris, R. A., & Schuckit, M. A. (2008) · British Journal of Pharmacology · doi:10.1038/bjp.2008.88 · Cited by 186 · see citing works
Biospecimens and the ABCD study: Rationale, methods of collection, measurement and early data
Uban, K. A., Horton, M. K., Jacobus, J., Heyser, C., Thompson, W. K., Tapert, S. F., Madden, P. A. F., & Sowell, E. R. (2018) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2018.03.005 · Cited by 175 · see citing works
Recent advances in the genetic epidemiology and molecular genetics of substance use disorders
Kendler, K. S., Chen, X., Dick, D., Maes, H., Gillespie, N., Neale, M. C., & Riley, B. (2012) · Nature Neuroscience · doi:10.1038/nn.3018 · Cited by 179 · see citing works
Self-citationImaging brain response to reward in addictive disorders
Hommer, D. W., Bjork, J. M., & Gilman, J. M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2010.05898.x · Cited by 163 · see citing works
A Risk Allele for Nicotine Dependence in CHRNA5 Is a Protective Allele for Cocaine Dependence
Grucza, R. A., Wang, J. C., Stitzel, J. A., Hinrichs, A. L., Saccone, S. F., Saccone, N. L., Bucholz, K. K., Cloninger, C. R., Neuman, R. J., Budde, J. P., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.04.018 · Cited by 152 · see citing works
Evidence of CNIH3 involvement in opioid dependence
Nelson, E. C., Agrawal, A., Heath, A. C., Bogdan, R., Sherva, R., Zhang, B., Al-Hasani, R., Bruchas, M. R., Chou, Y.-L., Demers, C. H., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2015.102 · Cited by 131 · see citing works
The relationship between crystalline methamphetamine use and methamphetamine dependence
McKetin, R., Kelly, E., & McLaren, J. (2006) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2006.04.007 · Cited by 145 · see citing works
Novelty Seeking and Drug Addiction in Humans and Animals: From Behavior to Molecules
Wingo, T., Nesil, T., Choi, J.-S., & Li, M. D. (2016) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-015-9636-7 · Cited by 144 · see citing works
Elevated levels of DNA methylation at the OPRM1 promoter in blood and sperm from male opioid addicts
Chorbov, P., Todorov, P., Lynskey, P., & Cicero, P. (2018) · Journal of Opioid Management · doi:10.5055/jom.2011.0067 · Cited by 135 · see citing works
Enoch, M.-A., Hodgkinson, C. A., Yuan, Q., Shen, P.-H., Goldman, D., & Roy, A. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.08.019 · Cited by 130 · see citing works
Sloboda, Z., Glantz, M. D., & Tarter, R. E. (2012) · Substance Use & Misuse · doi:10.3109/10826084.2012.663280 · Cited by 94 · see citing works
Vanyukov, M. M., Kirisci, L., Moss, L., Tarter, R. E., Reynolds, M. D., Maher, B. S., Kirillova, G. P., Ridenour, T., & Clark, D. B. (2009) · Behavior Genetics · doi:10.1007/s10519-009-9269-9 · Cited by 88 · see citing works
Executive functions and substance use: Relations in late adolescence and early adulthood.
Gustavson, D. E., Stallings, M. C., Corley, R. P., Miyake, A., Hewitt, J. K., & Friedman, N. P. (2017) · Journal of Abnormal Psychology · doi:10.1037/abn0000250 · Cited by 84 · see citing works
Psychopathological aspects of dopaminergic gene polymorphisms in adolescence and young adulthood
Nemoda, Z., Szekely, A., & Sasvari-Szekely, M. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.04.002 · Cited by 78 · see citing works
Adolescent drinking and brain morphometry: A co-twin control analysis
Wilson, S., Malone, S. M., Thomas, K. M., & Iacono, W. G. (2015) · Developmental Cognitive Neuroscience · doi:10.1016/j.dcn.2015.07.005 · Cited by 64 · see citing works
Levran, O., Randesi, M., Li, Y., Rotrosen, J., Ott, J., Adelson, M., & Jeanne Kreek, M. (2014) · Annals of Human Genetics · doi:10.1111/ahg.12064 · Cited by 62 · see citing works
Genetic association analyses of PDYN polymorphisms with heroin and cocaine addiction
Clarke, T. ‐., Ambrose‐Lanci, L., Ferraro, T. N., Berrettini, W. H., Kampman, K. M., Dackis, C. A., Pettinati, H. M., O’Brien, C. P., Oslin, D. W., & Lohoff, F. W. (2012) · Genes, Brain and Behavior · doi:10.1111/j.1601-183x.2012.00785.x · Cited by 55 · see citing works
Blanco, C., Okuda, M., Wang, S., Liu, S.-M., & Olfson, M. (2014) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2014.1206 · Cited by 49 · see citing works
Family Transmission and Heritability of Externalizing Disorders: A Twin-Family Study
Hicks, B. M., Krueger, R. F., Iacono, W. G., McGue, M., & Patrick, C. J. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.9.922 · Cited by 46 · see citing works
Serra-Pinheiro, M. A., Coutinho, E. S. F., Souza, I. S., Pinna, C., Fortes, D., Araújo, C., Szobot, C. M., Rohde, L. A., & Mattos, P. (2013) · Journal of Attention Disorders · doi:10.1177/1087054711435362 · Cited by 43 · see citing works
Integrated Treatment of Adolescents with Co-occurring Depression and Substance Use Disorder
Hinckley, J. D., & Riggs, P. (2019) · Child and Adolescent Psychiatric Clinics of North America · doi:10.1016/j.chc.2019.02.006 · Cited by 27 · see citing works
Kirisci, L., Tarter, R., Ridenour, T., Reynolds, M., Horner, M., & Vanyukov, M. (2015) · Addictive Behaviors · doi:10.1016/j.addbeh.2014.10.028 · Cited by 19 · see citing works
Cadoni, C., De Felice, M., Corongiu, S., Dessì, C., Espa, E., Melis, M., & Fenu, S. (2020) · Addiction Biology · doi:10.1111/adb.12803 · Cited by 10 · see citing works
Hendy, K. (2024) · Public Understanding of Science · doi:10.1177/09636625231190743 · Cited by 4 · see citing works
- Authors
- Kendler, K. S., Jacobson, K. C., Prescott, C. A., & Neale, M. C.
- Venue
- American Journal of Psychiatry
- Published
- 2003-04-01
- Volume
- 160
- Issue
- 4
- Pages
- 687-695
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- OpenAlex
- W2124484771
- Cited by
- 693
- References
- 24
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 19 · 2023: 24 · 2022: 26 · 2021: 24 · 2020: 92 · 2019: 24 · 2018: 28 · 2017: 22 · 2016: 25 · 2015: 39 · 2014: 32 · 2013: 37 · 2012: 47
- FWCI
- 19.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (AA-00236)
- National Institute of Mental Health (K02MH001458, MH-01458, MH/AA/DA-49492)
- National Institute on Drug Abuse (DA11287, R01DA011287)
- Topics
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- substance use disorders, cannabis use, cocaine dependence, hallucinogen use, sedative use, stimulant use, opioid use disorder, genetic risk factors, unique environmental factors, twin brothers
- MeSH terms
- Adult, Marijuana Abuse, Diseases in Twins, Humans, Male, Middle Aged, Opioid-Related Disorders, Phenotype, Registries, Risk Factors, Sex Factors, Twins, Dizygotic, Twins, Monozygotic, Virginia, Comorbidity, Prevalence, Multivariate Analysis, Substance-Related Disorders, Cocaine-Related Disorders, Genetic Predisposition to Disease
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