Genetic, hormone, and family environmental influences on adolescent substance use

描述(由申请人提供)：了解药物使用问题的发展是一个至关重要的健康问题，因为处理与药物使用有关的伤害、疾病、死亡、犯罪、执法和生产力损失的个人健康和国家经济成本1。本申请中描述的研究旨在检查青少年药物使用的发展机制，目的是确定预防药物使用的目标。基因、荷尔蒙和家庭环境对物质使用发展的作用途径尚未被完全理解，部分原因是研究没有在同一概念模型中同时考虑这些影响。推动我的研究计划的中心假设是，父母的消极是一种机制，它改变了青春期药物使用问题的遗传、激素和行为风险的影响。具体地说，拟议的研究将澄清(目标1)父母的消极态度与青少年物质使用之间的联系是因为父母对青少年遗传影响的物质使用的反应方式增加了父母的消极情绪，还是因为父母传递了影响物质使用的基因和负面养育方式而产生了物质使用，还是通过直接的环境影响产生了物质使用。这项研究还将显示(目标2)父母的消极态度是否缓和了激素反应性和物质使用风险(外化精神病理学)之间的联系。结合我之前的研究，这些研究将阐明父母教养、激素和遗传风险在物质使用发展中是如何相关的，并研究亲子关系如何改变对物质使用问题风险的生物学影响。通过研究目的中的发现，我将提炼一个概念模型，考虑遗传、激素和家庭环境对青少年物质使用的交易性、发展性影响。这笔赠款的产品将是三份手稿：两份介绍每个研究目标的发现，一份介绍精炼的概念模型和支持证据。我的职业目标是进行跨学科研究，目的是了解物质使用的发展。本论文的研究是我迈向职业目标的第一步。为了更好地为我的职业生涯做准备，我正在进行纵向研究，探讨基因-环境相互作用和激素在家庭环境中对物质使用发展的作用，我正在寻求额外的培训，以1)进一步发展将物质使用作为一种表型来概念化和理解的技能，2)加强我对行为内分泌学在青春期物质使用风险方面的作用的理解，以及3)将家庭环境影响与遗传和激素影响充分整合到青少年物质使用发展的交易性发展模型中。物质使用、行为内分泌学、家庭流程和研究伦理方面的培训是完成研究目标和为我的职业生涯做好准备不可或缺的一部分，我是NIH资助的研究人员，研究青少年物质使用的发展。

DESCRIPTION (provided by applicant): Understanding the development of substance use problems is a vital health concern because of individual health and nationwide economic costs of dealing with substance use related injury, illness, death, crime, law enforcement, and lost productivity1. The research described in this application is designed to examine mechanisms of development of adolescent substance use, with the aim of identifying targets for prevention of substance use. Pathways by which genes, hormones, and family environments operate for the development of substance use are not fully understood, in part because studies have not considered each of these influences together in the same conceptual model. The central hypothesis driving my program of research is that parental negativity is a mechanism modifying the influence of genetic, hormonal, and behavioral risk for substance use problems during adolescence. Specifically, the proposed research will clarify (aim 1) whether the association between parental negativity and adolescent substance use arises because parents respond to adolescents' genetically influenced substance use in such a way that increases parental negativity, or if substance use arises because parents pass on genes and negative parenting, both influencing substance use, or through direct environmental influences. This research will also show (aim 2) whether parental negativity moderates the association between hormone reactivity and risk for substance use (externalizing psychopathology). Together, these studies combined with my previous research will clarify how parenting, hormone, and genetic risk are related in the development of substance use, and examine how parent-child relationships can modify biological influences on risk for substance use problems. Through findings in the research aims, I will refine a conceptual model considering the transactional, developmental nature of genetic, hormone, and family environmental influences on adolescent substance use. The product of this grant will be three manuscripts: two presenting findings from each research aim, and one presenting the refined conceptual model and supporting evidence. My career goal is to conduct interdisciplinary research with the aim to understand the development of substance use. This dissertation research is a first step toward my career goal. To better prepare myself for my career conducting longitudinal research that addresses gene-environment interplay and hormone functioning in the family context for the development of substance use, I am seeking additional training to 1) further develop skills at conceptualizing and understanding substance use as a phenotype, 2) strengthen my understanding of the role of behavioral endocrinology on risk for substance use during adolescence, and 3) fully integrate family environmental influences with genetic and hormone influences in the transactional developmental model of the development of adolescent substance use. Training in substance use, behavioral endocrinology, family processes, and research ethics are integral to completing the research aims, and preparing me for a career in which I am a NIH funded researcher investigating the development of adolescent substance use.