Hostname: page-component-8448b6f56d-t5pn6 Total loading time: 0 Render date: 2024-04-24T00:55:05.065Z Has data issue: false hasContentIssue false

Genetic vulnerability to drug abuse

Published online by Cambridge University Press:  16 April 2020

E. Duaux
Affiliation:
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Hôpital Sainte-Anne, 75014, Paris, France
M.O. Krebs
Affiliation:
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Hôpital Sainte-Anne, 75014, Paris, France
H. Loo
Affiliation:
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Hôpital Sainte-Anne, 75014, Paris, France
M.F. Poirier
Affiliation:
Service Hospitalo-Universitaire de Santé Mentale et Thérapeutique, Hôpital Sainte-Anne, 75014, Paris, France
Get access

Summary

Addiction to various substances, including drugs and alcohol, probably arises from a combination of environmental and genetic factors. The genetic vulnerability to drug addiction is supported by several familial, adoption and twin studies. However, as in other mental disorders, the genetic vulnerability to drug addiction appears complex: these disorders do not follow the rules of Mendelian inheritance. Instead, they are probably influenced by multiple susceptibility genes, each of which contributes to the disorder. The more genes necessary for a disorder, the harder it is to detect any of them. This difficulty is magnified by the role of environmental factors. Association studies using the candidate gene approach can identify susceptibility genes for drug abuse supported by the pathophysiological hypothesis of the illness. This review will focus on the clinical and molecular genetic studies in drug abuse.

Type
Original Article
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Benjamin, JLi, LPatterson, CGreenberg, B.GMurphy, D.LHamer, D.HPopulation and familial association between the D4 dopamine receptor gene and measures of novelty seeking. Nat Gen 12 1996 81–84CrossRefGoogle ScholarPubMed
Berrettini, W.HPersico, A.MDopamine D2 receptor gene polymorphisms and vulnerability to substance abuse in African Americans. Biol Psychiatry 40 1996 144–147CrossRefGoogle ScholarPubMed
Blum, KSheridan, PWood, RBracermann, EChen, TComings, DDopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. Pharmacogenetics 5 1995 121–141CrossRefGoogle ScholarPubMed
Bond, CLaforge, KTian, MMelia, DZhang, SBorg, L et al. Single-nucleotide polymorphism in the human mu opiod receptor gene alters betaendorphin binding and activity: possible implications for opiate addiction. Proc Natl Acad Sci USA 95 1998 9608–9613CrossRefGoogle Scholar
Cadoret, R.JTroughton, EO'Gorman, T.WHeywood, EAn adoption study of genetic and environmental factors in drug abuse. Arch Gen Psychiatry 43 1986 1131–1136CrossRefGoogle ScholarPubMed
Cadoret, R.JYates, W.RTroughton, EWoodworth, GStewart, M.AAdoption studies demonstrating two genetic pathways to drug abuse. Arch Gen Psychiatry 52 1995 42–52CrossRefGoogle ScholarPubMed
Chaudry, HArria, ATarter, RChaudhry, SChaudhry, NFamilial history of opium use and reported problems among opium addicts in Pakistan. Br J Addicts 86 1991 785–788CrossRefGoogle Scholar
Comings, D.EGade, RMuhleman, DChiu, CWu, STo, M et al. Exon and intron variants in the human tryptophan 2, 3 dioxygenase gene: potential association with Tourette's syndrome, substance abuse and other disorders. Pharmacogenetics 4 1996 307–318CrossRefGoogle Scholar
Comings, D.EGade, RWu, SChiu, CDietz, GMuhleman, D et al. Studies of the potential role of the dopamine D1 receptor gene in addictive behaviors. Mol Psychiatry 2 1997 44–56CrossRefGoogle ScholarPubMed
Comings, D.EMuhleman, DAhn, CGysin, RFlanagan, SThe dopamine D2 receptor gene: a genetic risk factor in substance abuse. Drug Alcohol Depend 34 1994 175–180CrossRefGoogle ScholarPubMed
Comings, D.EMuhleman, DGade, RJohnson, PVerde, RSaucier, G et al. Cannabinoid receptor gene (CNR1): association with IV drug use. Mol Psychiatry 2 1997 161–168CrossRefGoogle Scholar
Duaux, EGorwood, PGriffon, NBourdel, M.CSautel, FSokoloff, P et al. Homozygosity at the dopamine D3 receptor gene is associated with opiate dependence. Mol Psychiatry 3 1998 333–336CrossRefGoogle ScholarPubMed
Duaux, ELaplanche, PGorwood, PBourdel, M.CLaunay, J.MPoirier, M.FRole of the serotonin transporter promoter polymorphism, opiate dependence and suicide attempts. Communication at the IBANGS Meeting, Key Largo Oct 1999Google Scholar
Ebstein, R.PGritsenko, INemanov, LFrish, AOsher, YBelmaker, R.HNo association between the serotonin transporter gene regulatory region polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament of harm avoidance. Mol Psychiatry 2 1997 224–226CrossRefGoogle ScholarPubMed
Ebstein, R.PNovick, OUmansky, RPriel, BOsher, YBlaine, D et al. Dopamine D4 receptor exon III polymorphism associated with the human personality trait of novelty seeking. Nat Gen 12 1996 78–84CrossRefGoogle ScholarPubMed
Edenberg, H.JReynolds, JKoller, D.LBegleiter, HBucholz, K.KConneally, P.M et al. A family-ased analysis of whether the functional promoter alleles of the serotonin transporter gene 5-HTT affect the risk for alcohol dependence. Alcohol Clin Exp Res 22 1998 1080–1085CrossRefGoogle Scholar
Freimer, MKranzler, HSatel, SLacobelle, JSkipsey, KCharney, D et al. No association between D3 dopamine receptor (DRD3) alleles and cocaine dependence. Addict Biol 1 1996 281–287CrossRefGoogle ScholarPubMed
Gebhardt, CFüreder, TFuchs, KUrmann, AStompe, TFathi, N et al. No association of novelty seeking with DRD2 and DRD3 receptor gene polymorphims [abstract]. Am J Med Gen 81 1998 497Google Scholar
Gelernter, JKranzler, HCubells, JGenetic of two opiod receptor gene (OPRM1) exon I polymorphisms: population studies, and allele frequencies in alcohol- and drug-dependence subjects. Mol Psychiatry 4 1999 476–483CrossRefGoogle Scholar
Gelernter, JKranzler, HSatel, S.LNo association between D2 dopamine receptor (DRD2) alleles or haplotypes and cocaine dependence or severity of coccaine dependence in European- and African-Americans. Biol Psychiatry 45 1999 340–345CrossRefGoogle ScholarPubMed
Golberg, JLyons, M.JEisen, S.ATrue, W.RTsuang, MGenetic influence on drug use: a preliminary analysis of 2, 674 Vietnam-era veteran twins [abstract]. Behav Genet 552 1993Google Scholar
Gorwood, PBatel, PAdes, JHamon, MBoni, C Serotonin transporter gene polymorphisms, alcoholism and suicidal behaviour. Biol Psychiatry in pressGoogle Scholar
Grove, W.MEckert, E.DHeston, LBouchard, T.JSegal, NLykken, D.THeritability of substance abuse and antisocial behavior: a study of monozygotic twins reared apart. Biol Psychiatry 27 1990 1293–1304CrossRefGoogle ScholarPubMed
Hallikainen, TSaito, TLachman, H.MVolavka, JPohjalainen, TRyynänen, et al. Association between low activity serototnin transporter promoter genotype and early onset alcoholism with habitual impulsive violent behavior. Mol Psychiatry 4 1999 385–388CrossRefGoogle ScholarPubMed
Helzer, J.EBurman, AMcEvoy, L.TAlcohol abuse and dependence.Regier, A.DRobins, L.NPsychiatric disorders in America. The Epidemiolog Catchment Area Study. 1991 Free Press; New York81–115Google Scholar
Jorm, A.FHenderson, A.SJacomb, P.AChristensen, HKorten, A.ERodgers, B et al. An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms. Mol Psychiatry 3 1998 449–451CrossRefGoogle ScholarPubMed
Kendler, K.SKarkowski, LPrescott, C.AHallucinogen, opiate, sedative and stimulant use and abuse in a population-based sample of female twins. Acta Psychiatr Scand 5 1999 368–376Google Scholar
Kessler, R.CCrum, R.MWarner, L.ANelson, C.BSchulemberg, JAnthony, J.C et al. Lifetime co-occurence of DSM-III-R alcohol abuse and dependence with other psychiatric disorders in the National Comorbidity Survey. Arch Gen Psychiatry 54 1997 313–321CrossRefGoogle Scholar
Kotler, MCohen, HKremer, IMel, HHorowitz, ROhel, N et al. No association between the serotonin transporter promoter region (5-HTTLPR) and the dopamine D3 receptor (Bal I D3DR) polymorphisms and heroin addiction. Mol Psychiatry 4 1999 313–316CrossRefGoogle Scholar
Kotler, MCohen, HSegman, RGritsenko, INemanov, LLere, B et al. Excess dopamine D4 receptor (D4DR) exon III seven repeat allele in opioid-dependent subjects. Mol Psychiatry 2 1997 251–254CrossRefGoogle ScholarPubMed
Kranzler, HGelernter, JO'Malley, Hernandezavila, CKaufman, DAssociation of alcohol or other drug dependence with alleles of the mu opiod receptor gene (OPMR1). Alcohol Clin Exp Res 22 1998 1359–1362Google Scholar
Li, TXu, KDeng, HCai, GLiu, JWang, R et al. Association analysis of the dopamine D4 gene exon III VNTR and heroin abuse in Chinese subjects. Mol Psychiatry 2 1997 413–416CrossRefGoogle ScholarPubMed
Luthar, S.SAnton, S.FMerikangas, K.RRounsaville, B.JVulnerability to substance abuse and psychopathology among siblings of opioid abusers. J Nerv Ment Dis 180 1992 153–161CrossRefGoogle ScholarPubMed
Malhotra, A.KVirkkunen, MRooney, WEggert, MLinnoila, MGoldman, DThe association between the dopamine D4 receptor (D4DR) 16 amino acid repeat polymorphism and novelty seeking. Mol Psychiatry 1 1996 388–391Google ScholarPubMed
Mayer, PRochlitz, HRauch, ERommelsacher, HHasse, H.ESchmidt, SHollt, VAssociation between a delta opioid receptor gene polymorphism and heroin dependence in man. Neuroreport 8 1997 2547–2550CrossRefGoogle ScholarPubMed
Merikangas, K.RStolar, MStevens, D.EGoulet, JPreisig, M.AFenton, B et al. Familial transmission of substance use disorders. Arch Gen Psychiatry 55 1998 973–979CrossRefGoogle ScholarPubMed
Miller, N.SGold, M.SBelkin, B.MKlahr, A.LThe diagnosis of alcohol and cannabis dependence in cocaine dependents and alcohol dependence in their families. Br J Addict 84 1993 1491–1498CrossRefGoogle Scholar
Mirin, S.MWeiss, R.DGriffin, M.LMichael, J.LPsychopathology in drugs abusers and their families. Compr Psychiatry 32 1991 36–51CrossRefGoogle Scholar
Noble, E.PBlum, KKhalsa, M.ERitchie, TMontgomery, AWood, R.C et al. Allelic association of the D2 dopamine receptor gene with cocaine dependence. Drug Alcohol Depend 33 1993 271–285CrossRefGoogle ScholarPubMed
O'Hara, B.FSmith, S.SBird, GPersico, A.MSuarez, B.KCutting, G.R et al. Dopamine D2 receptor RFLPs, haplotypes and their association with substance use in black and Caucasian research volunteers. Hum Her 43 1993 209–218CrossRefGoogle ScholarPubMed
Ono, YManki, HYoshimura, KMuramatsu, TMizushima, HHiguchi, S et al. Association between dopamine D4 receptor (DRD4) exon III polymorphism and novelty seeking in Japanese subjects. Am J Med Gen 74 1997 501–5033.0.CO;2-Q>CrossRefGoogle ScholarPubMed
Pickens, R.WSvikis, D.SGenetic influences in human substance abuse. Arch Gen Psychiatry 10 1991 202–213Google ScholarPubMed
Regier, D.AFarmer, M.ERae, D.SLocke, B.ZKeith, S.JJudd, L.L et al. Comorbidity of mental disorders with alcohol and other drug abuse. Results from the Epidemiologic Catchment Area (ECA) study. JAMA 264 1990 2511–2518CrossRefGoogle ScholarPubMed
Rounsaville, B.JKosten, T.RWeissman, M.M.PPauls, DAnton, S.FMerikangas, KPsychiatric disorders in the relatives of probands with opiate addiction. Arch Gen Psychiatry 488 1991 33–42CrossRefGoogle Scholar
Sander, THarms, HDufeu, PKuhn, SHoehe, MLesh, K.P et al. Serotonin transporter gene variants in alcohol-dependent subjects with dissocial personality disorder. Biol Psychiatry 43 1998 908–912CrossRefGoogle ScholarPubMed
Smith, S.SO'Hara, B.FPersico, A.MGorelick, M.ANewlin, D.BVlahov, D et al. Genetic vulnerability to drug abuse, the D2 dopamine receptor Taq 1 B1 restriction fragment length polymorphism appears more frequently in polysubstance abusers. Arch Gen Psychiatry 49 1992 723–727CrossRefGoogle Scholar
Tsuang, M.TLyons, M.JMeyer, J.MDoyle, TEisen, S.AGoldberg, J et al. Co-occurence of abuse of different drugs in men, the role of drug-specific and shared vulnerabilities. Arch Gen Psychiatry 55 1998 967–972CrossRefGoogle Scholar
Vandenbergh, D.JZonderman, A.BWang, JUhl, G.RCosta, P.TNo association between novelty seeking and dopamine D4 receptor (D4DR) exon III seven repeat alleles in Baltimore Longitudinal Study of Aging participants. Mol Psychiatry 2 1997 417–419CrossRefGoogle ScholarPubMed
Warner, L.AKessler, R.CHughes, MAnthony, J.CNelson, C.BPrevalence and correlates of drug use and dependence in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 52 1995 219–229CrossRefGoogle ScholarPubMed
Submit a response

Comments

No Comments have been published for this article.