Introduction: 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. Methods: 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. Results: 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. Conclusion: 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.
Eur Addict Res

中文翻译：

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遗传、产前、皮质醇和育儿对青少年物质使用和频率的影响之间的相互作用：一项 TRAILS 研究

简介：理论上，遗传、激素和产前和产后环境之间的动态关系对于青少年物质使用至关重要，但很少在多因素模型中进行测试。本研究评估了遗传风险和皮质醇反应与产前和养育子女的相互作用对青少年物质使用的任何和频率的影响。方法：数据来自追踪青少年个人生活调查 (TRAILS)，这是一项针对 2,230 名荷兰青少年的前瞻性纵向、多评估者研究。通过 3 个物质特异性多基因评分评估遗传风险。母亲们回顾性地报告了青少年 11 岁时的产前风险。青少年在 11 岁时评估父母的热情和敌意。在 16 岁时测量唾液皮质醇反应以应对社会压力任务。青少年在 16 岁时自我报告使用香烟、酒精和大麻的频率。结果：多变量障碍回归模型表明，吸烟、饮酒和大麻的多基因风险分别预测了每种物质的任何使用，但仅预测了吸烟的更频繁使用。减弱的皮质醇反应性预测了所有 3 种结果的任何使用和更频繁的使用。有两种相互作用：减弱的皮质醇反应加剧了多基因风险与任何吸烟的关联，以及产前风险与任何酒精使用的关联。结论：多基因风险似乎对早期使用很重要，但对使用频率不太重要，而皮质醇反应性减弱与两者相关。皮质醇反应迟钝也可能催化物质使用的早期风险，尽管程度有限。在这种多因素模型的背景下，基因-环境相互作用没有任何作用。
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