Suchergebnisse

<b><i>Introduction:</i></b> Dynamic relations between genetic, hormone, and pre- and postnatal environments are theorized as critically important for adolescent substance use but are rarely tested in multifactorial models. This study assessed the impact of interactions of genetic risk and cortisol reactivity with prenatal and parenting influences on both any and frequency of adolescent substance use. <b><i>Methods:</i></b> Data are from the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective longitudinal, multi-rater study of 2,230 Dutch adolescents. Genetic risk was assessed via 3 substance-specific polygenic scores. Mothers retrospectively reported prenatal risk when adolescents were 11 years old. Adolescents rated their parents' warmth and hostility at age 11. Salivary cortisol reactivity was measured in response to a social stress task at age 16. Adolescents' self-reported cigarette, alcohol, and cannabis use frequency at age 16. <b><i>Results:</i></b> A multivariate hurdle regression model showed that polygenic risk for smoking, alcohol, and cannabis predicted any use of each substance, respectively, but predicted more frequent use only for smoking. Blunted cortisol reactivity predicted any use and more frequent use for all 3 outcomes. There were 2 interactions: blunted cortisol reactivity exacerbated the association of polygenic risk with any smoking and the association of prenatal risk with any alcohol use. <b><i>Conclusion:</i></b> Polygenic risk seems of importance for early use but less so for frequency of use, whereas blunted cortisol reactivity was correlated with both. Blunted cortisol reactivity may also catalyze early risks for substance use, though to a limited degree. Gene-environment interactions play no role in the context of this multifactorial model.

BACKGROUND: Tobacco, alcohol, and cannabis use are prevalent behaviors that pose considerable health risks. Genetic vulnerability and characteristics of the neighborhood of residence form important risk factors for substance use. Possibly, these factors do not act in isolation. This study tested the interaction between neighborhood characteristics and genetic risk (gene-environment interaction, GxE) and the association between these classes of risk factors (gene-environment correlation, rGE) in substance use. METHODS: Two polygenic scores (PGS) each (based on different discovery datasets) were created for smoking initiation, cigarettes per day, and glasses of alcohol per week based on summary statistics of different genome-wide association studies (GWAS). For cannabis initiation one PGS was created. These PGS were used to predict their respective phenotype in a large population-based sample from the Netherlands Twin Register (N = 6,567). Neighborhood characteristics as retrieved from governmental registration systems were factor analyzed and resulting measures of socioeconomic status (SES) and metropolitanism were used as predictors. RESULTS: There were (small) main effects of neighborhood characteristics and PGS on substance use. One of the 14 tested GxE effects was significant, such that the PGS was more strongly associated with alcohol use in individuals with high SES. This was effect was only significant for one out of two PGS. There were weak indications of rGE, mainly with age and cohort covariates. CONCLUSION: We conclude that both genetic and neighborhood-level factors are predictors for substance use. More research is needed to establish the robustness of the findings on the interplay between these factors.