Z.H. contributed to the study design, coordinated

the study, conducted the analyses, and was lead author. W.V. contributed to the study design, and all sections of this paper. All authors have read and approved the final manuscript. All authors declare that they have no conflicts of interest. We are grateful to our colleagues Wietze Gjaltema, Michiel Maas and Peter Janssen who helped us to transform the camper in a mobile lab and to drive safely with it. We thank Carel Peeters, Karin Monshouwer and Quinten Raaijmakers for their advice on the Navitoclax in vitro statistical analyses. We thank the bachelor and master students for helping with collection of the dataset. We are indebted to the principal and staff of the schools, the Trimbos Institute, all the participants and the confederates for their participation. “
“Persistent substance use during adolescence has been associated with various adverse outcomes, including an increased risk of developing substance use disorders and delinquent behaviors (Chabrol and Saint-Martin, 2009, Swift et al., 2008 and Toumbourou et al., 2003).

Research on the determinants of persistent substance use in this developmental PLX4032 purchase phase can improve our understanding of liability to substance use disorders. Twin studies have established that genetic influences contribute to the etiology of substance abuse and dependence (Agrawal and Lynskey, 2008). These studies have reported heritability estimates that range from 50 to 70% for alcohol abuse/dependence and from

34 to 78% for cannabis dependence. While genetic influences have generally been found to be strongest for these heavier stages of substance use (Agrawal and Lynskey, 2006), the role of genetic factors on initiation, use, and non-diagnostic problem use of substances has also been established (McGue et al., 2000 and Rhee et al., 2003). For the latter, the influence of shared environmental factors is relatively stronger. Findings from MTMR9 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 and Kendler et al., 1999). The genetic influences estimated in twin studies represent the composite variance explained by multiple genes. Two of the candidate genes implicated in substance use disorders are the dopamine D2 receptor gene (DRD2) and the dopamine D4 receptor gene (DRD4) (Agrawal and Lynskey, 2009 and Kotler et al., 1997). Individuals carrying the A1 allele of the TaqIA polymorphism, close to DRD2 (rs1800497), have a reduced number of D2 dopamine receptors in brain structures linked to reinforcement, particularly in the striatum (Jonsson et al., 1999, Pohjalainen et al., 1998 and Thompson et al.