Interactions between Genetic, Prenatal, Cortisol, and Parenting Influences on Adolescent Substance Use and Frequency: A TRAILS Study

Abstract

<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.

The genetic aetiology of cannabis use: from twin models to genome-wide association studies and beyond

“…Other environmental factors such as frequency of religious service attendance, organised sports, school activities, church activities and peer deviance were not or not consistently significant in these studies. The three other studies (exploring moderating roles for neighbourhood environment [134], peer cannabis use [101], prenatal stress, warm parenting, and cortisol reactivity [135]) did not find G × E interactions for cannabis use outcomes.…”