An adoption study of the development of early substance use: the joint roles of genetic influences, prenatal risk, rearing environment, and pubertal maturation

项目总结/摘要 拟议的研究将阐明遗传风险以及产前和产后环境如何 与激素变化一起影响早期物质风险的发展 使用（SU）和青春期的相关问题。理解SU问题的发展 是一个重要的健康问题，因为处理SU相关伤害，疾病， 死亡、犯罪和丧失生产力。基因的途径和相互作用， 暴露，激素和关键的产后环境因素影响发育， SU没有被完全理解，部分原因是研究没有将它们放在一起考虑。的 建议的研究是创新的，通过使用和扩展 现有的前瞻性纵向 早期生长和发育研究（EGDS） 的缺乏 结合遗传、产前、激素和产后影响的研究。这项建议是 及时，直接解决PA-15-110，通过使用遗传信息的方法， 研究遗传和环境因素的相互作用，在发生和过程中. 物质使用障碍和共病状况。EGDS是一项针对儿童的纵向研究 在出生时被收养，他们的亲生父母和养父母（N = 561连锁三合会）。我们建议 收集青春期早期SU里程碑和相关行为的新数据， 发展我们将使用现有的和新的数据：（SA 1）估计的独特贡献， 遗传风险、产前和产后环境对儿童行为轨迹的影响 从婴儿期到青春期，增加SU的风险;（SA 2）检查 产前暴露传递对SU行为风险轨迹的遗传影响; (SA3)研究激素发育在遗传性、产前 和产后环境对SU行为风险轨迹的影响;以及（SA 4） 检查适度的遗传，产前，和激素的影响，由产后环境 阐明这些因素在影响儿童危险行为中可能的相互作用， 早期SU本研究将有助于提高对青少年SU发展的认识， 澄清哪些儿童在青春期早期发展SU的风险更大， 影响是最突出的SU的发展给予多种其他影响。这 使用EGDS的前瞻性、纵向、遗传学信息调查是独一无二的 为了实现这些目标，这些目标对于更准确地了解因素至关重要。 影响SU的发展过程，可用于改善预防工作。

Project Summary/Abstract The proposed research will clarify how heritable risks and prenatal and postnatal environments work together with hormonal changes to influence the development of risk for early substance use (SU) and related problems in adolescence. Understanding the development of SU problems is a vital health concern due to the economic costs of dealing with SU related injury, illness, death, crime, and lost productivity. Pathways and interactions by which genes, prenatal exposures, hormones, and key postnatal environmental factors influence the development of SU are not fully understood, in part because studies have not considered them together. The proposed research is innovative by using and expanding an existing prospective longitudinal adoption study, the Early Growth and Development Study (EGDS) to address the dearth of research combining heritable, prenatal, hormone, and postnatal influences. This proposal is timely, directly addressing PA-15-110, by using genetically informative approaches to expand research on the interplay of genetic and environmental factors in the genesis and course … of substance use disorders and comorbid conditions. The EGDS is a longitudinal study of children adopted at birth and their birth and adoptive parents (N = 561 linked triads). We propose to collect new data into early adolescence on SU milestones and related behaviors, and pubertal development. We will use existing and new data to: (SA1) estimate the unique contributions of heritable risk, prenatal, and postnatal environmental influences on trajectories of child behaviors from infancy to adolescence that increase risk for SU; (SA2) examine the mediating role of prenatal exposures for transmitting heritable influences on trajectories of behavioral risk for SU; (SA3) examine the mediating role of hormone development for transmitting heritable, prenatal and postnatal environmental influences on trajectories of behavioral risk for SU; and (SA4) Examine moderation of heritable, prenatal, and hormone influences by postnatal environments to elucidate the possible interactions among these factors in influencing child risk behaviors and early SU. This study will help to advance knowledge of the development of adolescent SU, to clarify which children are at greater risk for developing SU early in adolescence, and which influences are most salient for SU development given multiple other influences. This prospective, longitudinal, genetically-informed investigation using the EGDS is uniquely poised to achieve these aims, which are critical for gaining a more precise understanding of factors influencing the developmental course of SU that can be used to improve prevention efforts.