Stress as a mediating factor in the association between the DRD2 TaqI polymorphism and alcoholism

Madrid, Gloria; MacMurray, James P.; Lee, Jerry; Anderson, Bonita; De, Comings

doi:10.1016/s0741-8329(00)00138-5

Cited by 84 publications

(54 citation statements)

References 18 publications

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“…This possibility, although speculative, is supported by evidence that stress exposure mediates the association between the DRD2 Taq1A polymorphism and alcoholism. 23 Future studies should use longitudinal data to investigate the potential role of gene Â environment interactions in the progression from social drinking to alcohol dependence.…”

Section: Discussionmentioning

confidence: 99%

Association between the DRD2 gene Taq1A (C32806T) polymorphism and alcohol consumption in social drinkers

Munafò

Johnstone

et al. 2005

Pharmacogenomics J

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An association between the DRD2 Taq1A (C32806T) polymorphism and social alcohol consumption in the opposite direction to that reported for alcoholism has recently been reported in a male Finnish sample. We attempted to replicate these findings in two independent samples, and extend on previous work by including female participants. The DRD2 A1 allele was significantly associated with reduced alcohol consumption in sample one (P ¼ 0.004) and sample two (P ¼ 0.015). In sample two there was a significant genotype Â sex interaction (P ¼ 0.016), with the association of the A1 allele and reduced alcohol consumption significant in men only. This interaction was marginally significant (P ¼ 0.042) in a meta-analysis of combined data from both samples, and the main effect of genotype highly significant (Po0.001). Age at time of data collection and cigarette consumption were entered as covariates in all analyses. These results replicate recent previous findings and suggest a possibility that this association may exist in men only, or be stronger in men. INTRODUCTIONThe human central dopamingeric system is widely considered to play an important role in substance use and the development of subsequent dependence. Evidence for a role for this system extends to a range of psychoactive substances, including opiates, cocaine, nicotine and alcohol.1-3 As a consequence, in attempting to elucidate the genetic determinants of substance use, a great deal of attention has been paid to the potential role of candidate genes related to individual variation in dopaminergic function. In particular, the dopamine D2 receptor (DRD2) gene on chromosome 11 (q22-q23) has been widely studied.

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Section: Discussionmentioning

confidence: 99%

Association between the DRD2 gene Taq1A (C32806T) polymorphism and alcohol consumption in social drinkers

Munafò

Johnstone

et al. 2005

Pharmacogenomics J

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“…In the past decade, various studies have examined the interaction between genetic polymorphisms and adverse environments, such as stressful events, [26][27][28] parental maltreatment, [29][30][31] negative family relationships 32 and inadequate parenting 33 on adolescent engagement in problem behaviors. Regarding adolescent alcohol use, no studies are available that have tested interactions between genes implicated in the dopaminergic system and environmental factors.…”

Section: Introductionmentioning

confidence: 99%

Interaction between dopamine D2 receptor genotype and parental rule-setting in adolescent alcohol use: evidence for a gene-parenting interaction

et al. 2009

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Association studies investigating the link between the dopamine D2 receptor gene (DRD2) and alcohol (mis)use have shown inconsistent results. This may be due to lack of attention for environmental factors. High levels of parental rule-setting are associated with lower levels of adolescent alcohol use and delay of initiation of drinking. We tested whether DRD2 TaqI A (rs1800497) genotype interacts with alcohol-specific parenting practices in predicting the uptake of regular adolescent alcohol use. Non-regular drinkers were selected from a Dutch, nationwide sample of 428 adolescents (mean age 13.4 years at baseline) and participated in a prospective, community-based study with three annual waves. Parental rule-setting was directly and inversely related to adolescent alcohol use over time. For DRD2 genotype no significant main effect was found. DRD2 genotype interacted with parental rule-setting on adolescent alcohol use over time: adolescents, with parents highly permissive toward alcohol consumption and carrying a genotype with the DRD2 A1 (rs1800497T) allele, used significantly more alcohol over time than adolescents without these characteristics. The DRD2 genotype may pose an increased risk for alcohol use and abuse, depending on the presence of environmental risk factors, such as alcohol-specific parenting.

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“…Findings from human laboratory studies have further shown that stress increases drug craving (Sinha et al, 1999(Sinha et al, , 2000(Sinha et al, , 2003 alters subjective responses to alcohol (Soderpalm and de Wit, 2002) and increases alcohol consumption (de Wit et al, 2003;Hull and Young, 1983). There is also evidence that genetic influences on stress reactivity may be associated with individual differences in risk for alcoholism (Bau et al, 2000;Dai et al, 2002a, b;King et al, 2002;Madrid et al, 2001;Ohannessian et al, 1994;Schuckit et al, 1996;Waltman et al, 1994;Wand et al, 2001Wand et al, , 1998Wand et al, , 1999a and that the dynamics of the physiological stress response may be deranged in drug dependent individuals (Errico et al, 2002;Kemper et al, 1990;Kreek and Koob, 1998).…”

Section: Introductionmentioning

confidence: 99%

Relationships Among Ventral Striatal Dopamine Release, Cortisol Secretion, and Subjective Responses to Amphetamine

Oswald

Wong

McCaul

et al. 2005

Neuropsychopharmacol

295

166

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There is evidence that stress and glucocorticoids alter drug self-administration and mesolimbic dopamine (DA) activity in preclinical models. The primary purpose of this study was to test the hypothesis that glucocorticoids are associated with psychostimulant reinforcement and DA release in humans. In total, 16 healthy adults, ages 18-27 years, underwent two consecutive 90-min PET studies with high specific activity [11 C]raclopride. The first scan was preceded by intravenous saline, and the second by intravenous amphetamine (AMPH 0.3 mg/kg). DA release was defined as the percent change in raclopride binding between the placebo and AMPH scans. Measures of subjective drug effects, plasma cortisol, and growth hormone (GH) were obtained. Findings showed that cortisol levels were positively associated with AMPH-induced DA release in the left ventral striatum (LVS) and the dorsal putamen. Subjects with higher cortisol responses to AMPH also reported more positive subjective drug effects than subjects with lower cortisol responses; no association was observed between cortisol levels and negative drug effects. Higher ratings of positive drug effects were also associated with greater DA release in the LVS, dorsal putamen, and dorsal caudate. A general lack of relationship was observed between GH responses to AMPH and DA release or subjective drug responses. Our findings provide evidence of interrelationships between glucocorticoid levels, subjective responses to IV AMPH, and brain DA release in humans. The results are consistent with those of preclinical studies, suggesting that individual differences in HPA axis function may influence vulnerability to alcohol and drug dependence in humans.

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Stress as a mediating factor in the association between the DRD2 TaqI polymorphism and alcoholism

Cited by 84 publications

References 18 publications

Association between the DRD2 gene Taq1A (C32806T) polymorphism and alcohol consumption in social drinkers

Association between the DRD2 gene Taq1A (C32806T) polymorphism and alcohol consumption in social drinkers

Interaction between dopamine D2 receptor genotype and parental rule-setting in adolescent alcohol use: evidence for a gene-parenting interaction

Relationships Among Ventral Striatal Dopamine Release, Cortisol Secretion, and Subjective Responses to Amphetamine

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