Illicit drug use and abuse/dependence: modeling of two-stage variables using the CCC approach. Addict Behav

Department of Human Genetics, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Box# 980003 Suite 1-154, Richmond, VA 23298-0003, USA.
Addictive Behaviors (Impact Factor: 2.76). 07/2005; 30(5):1043-8. DOI: 10.1016/j.addbeh.2004.09.007
Source: PubMed


Drug use and abuse/dependence are stages of a complex drug habit. Most genetically informative models that are fit to twin data examine drug use and abuse/dependence independent of each other. This poses an interesting question: for a multistage process, how can we partition the factors influencing each stage specifically from the factors that are common to both stages? We used a causal-common-contingent (CCC) model to partition the common and specific influences on drug use and abuse/dependence. Data on use and abuse/dependence of cannabis, cocaine, sedatives, stimulants and any illicit drug was obtained from male and female twin pairs. CCC models were tested individually for each sex and in a sex-equal model. Our results suggest that there is evidence for additive genetic, shared environmental and unique environmental influences that are common to illicit drug use and abuse/dependence. Furthermore, we found substantial evidence for factors that were specific to abuse/dependence. Finally, sexes could be equated for all illicit drugs. The findings of this study emphasize the need for models that can partition the sources of individual differences into common and stage-specific influences.

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    • "However, given that SUD is contingent on use, and that use of all illicit substances was influenced by a C c factor, it is puzzling that we did not find a C c factor for SUD. Agrawal et al. (2005) found use and SUD of any illicit drug to be correlated 0.67 in males (Agrawal et al. 2005). This implicates that the C c factor for illicit substance use would in average explain 18 % of the variance in SUD. "
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    ABSTRACT: The specificity of genetic and environmental risk factors for illicit substance use and substance use disorders (SUD) was investigated by utilizing self and co-twin reports in 1,791 male twins. There was a high rate of comorbidity between both use of, and SUD from, different classes of illicit substances. For substance use, the model that included one common genetic, one shared environmental, and one individual-specific (i.e., unique) environmental factor, along with substance-specific effects that were attributed entirely to genetic factors fit the data best. For illicit SUD, one common genetic and one common unique environmental risk factor, and substance specific shared environmental and unique environmental risk factors were identified. Risk factors for illicit substance use and SUD are mainly non-specific to substance class. Co-twin rating of illicit substance use and SUD was a reliable source of information, and by taking account of random and systematic measurement error, environmental exposures unique to the individual were of lesser importance than found in earlier studies.
    Behavior Genetics 11/2013; 44(1). DOI:10.1007/s10519-013-9626-6 · 3.21 Impact Factor
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    • "For the latter, the influence of shared environmental factors is relatively stronger. Findings from twin studies assessing multiple stages of substance involvement suggest, at least partly, common genetic and environmental risk factors for substance use and misuse among adolescents and adults (Agrawal et al., 2005; Fowler et al., 2007; Kendler et al., 1999). "
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    ABSTRACT: The aims of the present study were to determine the direct effect of DRD2 and DRD4, as well as their interaction with parenting (i.e. rejection, overprotection and emotional warmth), on the development of regular alcohol and cannabis use in 1192 Dutch adolescents from the general population. Information was obtained by self-report questionnaires. Perceived rejection, overprotection and emotional warmth were assessed at age 10-12. Regular alcohol and cannabis use were determined at age 15-18 and defined as the consumption of alcohol on 10 or more occasions in the past four weeks, and the use of cannabis on 4 or more occasions in the past four weeks. Models were adjusted for age, sex, parental alcohol or cannabis use, and externalizing behavior. Carrying the A1 allele of the DRD2 TaqIA polymorphism, or the 7 repeat DRD4, was not directly related to regular alcohol or cannabis use. In addition, adolescent carriers of these genetic risk markers were not more susceptible to the influence of less optimal parenting. Main effects for parenting indicated that overprotection increased the risk of regular alcohol use, whereas the risk of cannabis use was enhanced by parental rejection and buffered by emotional warmth. Our findings do not support an association between DRD2/DRD4 and regular alcohol and cannabis use in adolescents. Given the substance-specific influences of rejection, overprotection and emotional warmth, these parenting factors might be promising candidates for prevention work.
    Drug and alcohol dependence 11/2010; 115(1-2):35-42. DOI:10.1016/j.drugalcdep.2010.10.008 · 3.42 Impact Factor
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    • "A CCC model was used for analyses, which allows substance use to be conceptualized as a two-stage process incorporating initiation of substance use and progression to heavier use [23–25]. This model allows the estimation of the magnitude of the relationship between initiation and progression (by means of a beta pathway between these two stages [see Fig. 1]). "
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    ABSTRACT: To examine the genetic and environmental contributions to the initiation of use and progression to more serious use of alcohol, cigarettes and marijuana during adolescence, and to examine the relationship between initiation and progression of substance use. The study used a twin-based design and a new theoretical model, the causal-common-contingent (CCC) model. This allows modelling of the relationship between initiation of use and progression to heavier use as a two-stage model and the examination of genetic and environmental influences on both stages, while taking into account their relationship. The participants consisted of 1214 twin pairs (69% response rate) aged 11-19 years sampled from the UK population-based Cardiff Study of All Wales and North-west of England Twins (CaStANET). Data on adolescent initiation and progression to more serious use of alcohol, cigarettes and marijuana were obtained using self-report questionnaires. Initiation of alcohol and progression to heavier alcohol use had separate but related underlying aetiologies. For cigarette and marijuana use the relation between initiation and progression to heavier use was stronger, suggesting greater overlap in aetiologies. For all three substances, environmental influences that make twins more similar (common environment) tended to be greater for initiation, while genetic influences were stronger for heavier use. These findings have implications for policy decisions aimed at an adolescent and early adult age group. Specifically, these findings suggest that it may be more efficacious to focus alcohol interventions on risk factors for the development of heavier use rather than initiation of use. In contrast, interventions aimed at reducing the initiation of cigarettes and marijuana use may be more appropriate.
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