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

项目摘要/摘要 这项拟议的研究将阐明可遗传风险与产前和出生后环境 与荷尔蒙变化一起影响早期物质风险的发展 青春期使用(SU)及相关问题。对SU问题发展的认识 是一个至关重要的健康问题，因为处理与SU相关的伤害、疾病、 死亡、犯罪和生产力的丧失。产前基因的途径和相互作用 暴露、荷尔蒙和关键的出生后环境因素影响着 人们对苏的理解并不充分，部分原因是研究没有把它们放在一起考虑。这个 建议的研究在使用和扩展方面具有创新性 现有的前瞻性纵向 采用研究、早期成长和发育研究(EGDS)以解决 缺乏…… 结合遗传、产前、激素和后天影响的研究。这项建议是 及时、直接处理PA-15-110，使用遗传信息方法扩大 遗传和环境因素在…发生发展中的相互作用研究的 物质使用障碍和合并症。EGDS是一项针对儿童的纵向研究 出生时收养及其出生和养父母(N=561个有联系的三合会)。我们建议 在青春期早期收集有关SU里程碑和相关行为以及青春期的新数据 发展。我们将使用现有数据和新数据来：(SA1)估计以下方面的独特贡献 遗传风险、出生前和出生后环境对儿童行为轨迹的影响 从婴儿期到青春期会增加SU的风险；(SA2)检查 产前暴露传递遗传影响对SU行为风险轨迹的影响； (SA3)研究荷尔蒙发育对遗传、产前传播的中介作用 以及出生后环境对SU行为风险轨迹的影响；以及(SA4) 检查出生后环境对可遗传的、产前的和激素影响的调节 阐明影响儿童危险行为的这些因素之间可能的相互作用以及 早苏。本研究将有助于加深对青春期SU发展的认识 阐明哪些儿童在青春期早期发生SU的风险更高，哪些 考虑到其他多种影响，SU发展的影响是最突出的。这 使用EGDS进行前瞻性、纵向、基因知情的研究是独一无二的 实现这些目标，这些目标对于更准确地了解因素是至关重要的 影响SU的发展进程，可用于改进预防工作。

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.