Mechanisms underlying the lifetime co-occurrence of tobacco and cannabis use in adolescent and young adult twins
Introduction
Over 70% of those aged 12 years and older, in the United States, report a lifetime history of tobacco use, primarily cigarettes (Substance Abuse and Mental Health Services Administration (SAMHSA, 2005). Globally, the rates of youth tobacco use vary greatly, being highest in Central and Eastern Europe, India and some of the Pacific Islands (Mackay et al., 2006). Lifetime use of cannabis, the most common illicit psychoactive substance in developed nations, shows marked variations in prevalence across countries, 40% in the United States and New Zealand being highest in the world in this age group (Degenhardt et al., 2008). While there is epidemiological evidence in favor of a robust association between tobacco and cannabis use (Degenhardt et al., 2001, Kandel and Yamaguchi, 1993, Korhonen et al., 2008, Lynskey et al., 1998, Mathers et al., 2006, Patton et al., 2006), the potential genetic underpinnings of their co-occurrence are largely unknown. Adolescent twin studies have demonstrated that both tobacco (heritability ranging from 0.45 to 0.84) (Maes et al., 1999, McGue et al., 2000, Rose et al., 2009) and cannabis use (heritability ranging from 0.40 to 0.65) (Agrawal and Lynskey, 2006, Rhee et al., 2003) are heritable and there is some suggestion that common genetic factors mould the lifetime co-occurrence of tobacco and cannabis use (Young et al., 2006). However, common genetic influences are but one of several mechanisms by which the relationship between tobacco and cannabis can be explained.
There are two important considerations related to the genetic and environmental underpinnings of substance use. First, the etiology of substance use changes significantly across developmental stages. For instance, McGue et al. (2000) report substance shared environmental influences on both cannabis and tobacco use (Fowler et al., 2007, Maes et al., 1999, Rhee et al., 2003) during adolescence while adult samples often find that heritable factors explain twin similarity in substance use (Agrawal and Lynskey, 2006, Heath et al., 1993, Kendler et al., 1999, Kendler et al., 2003a, Kendler et al., 2008, Lynskey et al., 2002, Maes et al., 2004). Kendler and colleagues also show decay in the relative role of shared environment with increasing respondent age (Kendler et al., 2008). A second related consideration is that the mechanisms that induce the observed correlations between tobacco and cannabis use may also vary across development. In the case of alcohol and illicit drug dependence, Rhee et al. (2006) found that in adolescents, a model where a single liability underlying both alcohol and illicit drug dependence fit significantly better than the traditional correlated risks model, which has been shown to be a reasonable fit to data on adult twins (Kendler et al., 2003b, Kendler et al., 2007).
We are not aware of any systematic hypothesis-testing for the relationship between tobacco and cannabis use. In the present study, we use data from the Virginia Twin Study of Adolescent Behavioral Development (VTSABD, ages 8–17 years) and the Young Adult Follow-up (YAFU, aged 18–27 years) to contrast 13 genetically informative mechanisms, established for twin data by Neale and Kendler (1995) and subsequently modified to allow for covariates by Rhee et al. (2007) that may govern the association between cannabis and tobacco use in a longitudinal sample that assessed twin pairs during childhood/adolescence and young adulthood.
Section snippets
Sample
Data for this study are drawn from the VTSABD (Eaves et al., 1997, Hewitt et al., 1997, Silberg et al., 1996, Simonoff et al., 1997), a longitudinal study of 1412 juvenile twin pairs, and the YAFU (Silberg et al., 2007), a follow-up to the VTSABD, which re-interviewed 2289 twins at 18 years or older. The sampling design, ascertainment strategy and recruitment have been extensively described in related publications. In brief, the VTSABD used a cohort – sequential design to recruit twins aged
Association between cannabis and tobacco use
When they were assessed at childhood/adolescence, the sample (VTSABD) consisted of 1412 pairs of twins aged 8–17 years. Of the boys, 35.1% and 13.9% reported tobacco and cannabis use respectively with the odds of cannabis use in boys with tobacco use being 20.6 [95% C.I. 12.8–33.8]. In girls as well, the association between tobacco and cannabis use was high [O.R. 50.5, 95% C.I. 25.7–89.1], with 24.9 and 10.7% of the girls reporting tobacco and cannabis use respectively. In the young adult
Discussion
In 1975, Kandel (Kandel, 1975) proposed that underlying patterns of licit and illicit drug use was a gateway effect, which was characterized by sequence (i.e. a gateway drug is always initiated before other drugs), association (i.e. use of a gateway drug independently increases risk for use of other drugs) and causation (i.e. use of a gateway drug asserts a causal influence on use of other drugs) (Kandel, 2003). Research by her (Chen and Kandel, 1995, Kandel and Yamaguchi, 1993, Kandel, 2002,
Conflict of interest
None.
Role of funding source
This work was supported by grants MH-55557 & MH-62368 (JLS), MH068521 (LJE), DA023668 (AA), DA18660 & DA18267 (MTL), DA16977 & DA18673 (HHM). The funding sources had no further role in study design; in the collection, analysis and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
Contributors
Arpana Agrawal formulated hypotheses, analyzed data and wrote the first draft and all revisions of this study; Judy Silberg collected data, supervised data analysis and reviewed all versions of the manuscript. Michael Lynskey developed phenotypes, interpreted results and revised the manuscript; Hermine Maes analyzed data and revised the manuscript; Lindon Eaves collected data, formulated hypotheses and reviewed results and all drafts of the manuscript.
Acknowledgements
We acknowledge the work of Theresa Martin, Sandra Lee Muzik, Susan Williams and Bonnie Dedeian in the collection of these data.
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