Genetic and environmental influences on drug use and abuse/dependence in male and female twins

Bree, Marianne Bernadette van den; Johnson, Eric O.; Neale, Michael C.; Pickens, Roy W.

doi:10.1016/s0376-8716(98)00101-x

Cited by 214 publications

(143 citation statements)

References 52 publications

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“…5 The heritability of abuse/dependence was relatively low for sedatives and opiates, but for psychostimulants such as amphetamines, it was as high as cocaine. 6 The primary site of biological activity of methamphetamine (METH) is the dopamine transporters in the brain. METH is taken into cytosol by dopamine transporters on the synaptic terminals of dopamine neurons, and endogenous dopamine is concurrently released through the transporters by carrier-exchange mechanisms, which results in a robust increase in the dopamine concentration in the synaptic clefts.…”

Section: Introductionmentioning

confidence: 99%

Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis

et al. 2003

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Susceptibility to drug dependence and drug-induced psychoses is influenced not only by the pharmacological effects of the drug but also by the genetic factors of the individual. To clarify the latter, we investigated the association between methamphetamine (METH) dependence/psychosis and the hDAT1 gene (SLC6A3) encoding the dopamine transporter, which is the primary site of METH activity in the brain. Four exonic polymorphisms of the hDAT1 gene, 242C/T (exon 2), 1342A/G (exon 9), 2319G/A (3 0 UTR), and VNTR (3 0 UTR) were examined. Although there was no significant difference in genotypic and allelic distribution of the four polymorphisms between all METH dependence/psychosis patients (N ¼ 124) and controls (N ¼ 160), the patients with METH psychosis lasting for 1 month or more after discontinuance of METH consumption showed a significant excess of nine-or fewer repeat alleles of the VNTR in 3 0 UTR of the hDAT1 gene (P ¼ 0.0054, OR ¼ 4.24, 95% CI ¼ 2. 46-7.31). The present study demonstrated that the presence of nineor fewer repeat alleles of hDAT1 is a strong risk factor for a worse prognosis of METH psychosis.

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Section: Introductionmentioning

confidence: 99%

Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis

et al. 2003

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“…15 No entanto, esse único estudo utilizou e pequena amostragem (31 MZ e 24 DZ), não podendo concluir se os resultados foram devidos a viés de seleção. Os estudos para dependência de outras drogas encontraram diversos valores para a herdabilidade entre elas, [16][17][18][19][20][21][22] tendo nos extremos a menor herdabilidade específica para sedativos em mulheres (30%) 20 e a maior para abuso de cocaína em mulheres (79%). 21 De uma maneira geral, pode-se afirmar a presença de componente genético em todas as dependências de drogas.…”

Section: Estudos Em Gêmeosunclassified

A participação da genética nas dependências químicas

Messas¹

1999

Rev. Bras. Psiquiatr.

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ResumoEste artigo procura examinar a questão da herdabilidade nas dependências químicas. Através da revisão de estudos em famílias, em gêmeos e de adoção, encontramos evidências para afirmar a importância dos fatores genéticos na transmissão da vulnerabilidade às dependências. Essa transmissão pode ser melhor compreendida através de um modelo epigenético de desenvolvimento do transtorno onde condições biológicas hereditárias associem-se a situações ambientais ao longo da vida para a produção da dependência. Neste artigo apresentamos essas condições biológicas intermediárias vinculadas ao alto risco para dependência, focadas no caso do álcool e da cocaína. Por fim, descrevemos os estudos moleculares que vêm estabelecendo associações entre polimorfismos e as dependências, com relevo para o sistema dopaminérgico. DescritoresDependência de drogas; genética epidemiológica; genética molecular, álcool; cocaína; modelo epigenético AbstractWe examined in this article the herdability of drug addiction. Family, twin and adoption sudies reviewed allow us to support the thesis of an important genetic component in drug addiction. The trasmission of this herdability occurs through a biological vulnerability associated to environmental factors, in a model called epigenetic. We also discuss the relationship between biological vulnerability and high-risk phenotypes, focusing on alcohol and cocaine. At the end, we present molecular genetic studies associated with these disorders.

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“…Studies based on twin (e.g., Grove et al, 1990;Kendler, Karkowski, Corey, Prescott, & Neale, 1999;Kendler, Karkowski, Neale, & Prescott, 2000;Tsuang et al, 1996;van den Bree, Johnson, Neale, & Pickens, 1998) and adoptive (e.g., Cadoret, Winokur et al, 1996;Cadoret, Yates, Troughton, Woodworth, & Stewart, 1996;Yates, Cadoret, Troughton, & Stewart, 1996) samples have confirmed that while shared environmental factors may play a role in the initiation of substance use, genetic factors are the primary source of familial resemblance for illicit SUDs such as dependence, abuse, or a combination of abuse/ dependence. Univariate estimates of the heritability of illicit substance abuse and dependence did vary across substance, ranging from 25% to 79%, with most in the 55-75% range.…”

Section: Genetic Influences On Illicit Substance Use Abuse and Depementioning

confidence: 99%

Is there heterogeneity among syndromes of substance use disorder for illicit drugs?

Beseler¹,

Jacobson

Kremen³

et al. 2006

Addictive Behaviors

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The use of DSM criteria to evaluate liability to substance use disorders (SUDs) and to identify SUD phenotypes may not provide the sensitivity required to identify genes associated with vulnerability to SUDs. The purpose of this study is to evaluate a number of basic aspects of substance use that may be more proximal than full SUDs to risk genes, some of which may thus have greater potential utility as phenotypes in subsequent molecular genetic analyses. In this paper we present results from the first stage of our planned analyses, focusing on how individual symptoms of abuse and dependence may be used to create alternate phenotypes for SUDs. Specifically, we used factor analysis and biometrical modeling on each symptom of illicit substance abuse and dependence within different types of substances, and compared and contrasted factor patterns and heritabilities across the different substances. These analyses were carried out using a population-based sample of 3372 male-male twin pairs from the Vietnam Era Twin Registry who participated in the Harvard Twin Study of Substance Abuse. We obtained extensive data from these participants on substance use and SUDs via telephone interview in 1992, including data on the illicit substances: opiates, cocaine, cannabis, sedatives, stimulants, and psychedelics. The results indicate that: A) although a one-factor model assuming a single underlying liability for abuse and dependence symptoms and behaviors can be rejected for most substances, there is no uniform support for a two-factor model differentiating between abuse versus dependence; B) patterns of symptoms or behaviors reported by substance users vary across substances; C) not all symptoms or behaviors contribute equally to the presentation of an SUD; and D) the heritability of symptoms or behaviors of substance users varies both within and between substances. These results represent important first steps in facilitating the search for SUD-risk genes in subsequent high-throughput molecular genetic analyses by providing alternate phenotypes that may have both optimal validity and increased heritability.

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Genetic and environmental influences on drug use and abuse/dependence in male and female twins

Cited by 214 publications

References 52 publications

Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis

Nine- or fewer repeat alleles in VNTR polymorphism of the dopamine transporter gene is a strong risk factor for prolonged methamphetamine psychosis

A participação da genética nas dependências químicas

Is there heterogeneity among syndromes of substance use disorder for illicit drugs?

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