Bio-behavioral Developmental Origins of Adolescent Substance Abuse

 描述（由申请人提供）：本K 01的目的有两个。1)该K 01将支持候选人获得独立的跨学科研究职业所需的额外培训，对物质使用和相关表型的发展进行复杂的生物行为，纵向研究。2)本K 01将阐明（目标1）发育的生物行为途径和（目标2）生物（遗传、内分泌）X环境（产前、养育）相互作用，这些相互作用可预测青春期酒精、烟草和其他药物的使用。了解物质使用问题的发展是一个至关重要的健康问题，因为处理物质使用相关的伤害，疾病，死亡，犯罪，执法和生产力损失的个人健康和全国经济成本。基因、产前暴露、内分泌功能和养育影响物质使用发展的途径和相互作用尚未完全了解，部分原因是研究没有在同一发展模型中考虑这些影响。本提案的研究部分检验了两个中心假设：1）产前暴露和随后的内分泌发育代表了遗传和养育影响的一类重要机制。（具体来说，父母的消极态度）被内化，从而影响行为发展和随后的物质使用; 2）遗传影响可以修正产前暴露和父母消极的影响，这两种情况也可以改变内分泌发育对青少年使用药物的影响。从这些目标的结果将推进我们的知识的青少年物质使用的起源，青少年将启动和使用哪种类型的物质，以及发展的影响是最突出的物质使用的发展给予多个其他的影响。研究结果也将有影响的干预措施，确定最佳的目标，以加强保护机制和破坏机制的风险，青少年物质使用多种其他发展的影响。该K 01也将允许候选人所需的时间和培训，以建立在她现有的专业知识和开始过渡到一个独立的，跨学科的研究人员。通过与经验丰富的导师谁是在该领域的领导者的培训，候选人将获得1）在新的统计方法分析遗传数据的专业知识2）产前风险的机制知识，3）从行为风险到青少年物质使用的过渡知识，4）青春期激素功能和物质使用的神经基础的基本知识，和5）整合和翻译的技能。在这些领域和研究道德的培训是不可或缺的完成研究目标，并准备候选人的职业生涯作为NIH资助的研究人员调查青少年物质使用从发展的角度来看。

 DESCRIPTION (provided by applicant): The objectives of this K01 are twofold. 1) This K01 will support the Candidate to gain the additional training required for an independent interdisciplinary research career conducting complex biobehavioral, longitudinal research on the development of substance use and related phenotypes. 2) This K01 will clarify (aim 1) biobehavioral pathways of development and (aim 2) biological (genetic, endocrine) X environmental (prenatal, parenting) interactions that predict alcohol vs. tobacco vs. other drug use during adolescence. Understanding the development of substance use problems is a vital health concern because of the individual health and nationwide economic costs of dealing with substance use related injury, illness, death, crime, law enforcement, and lost productivity. Pathways and interactions by which genes, prenatal exposures, endocrine function, and parenting influence the development of substance use are not fully understood, in part because studies have not considered each of these influences together in the same developmental model. The research portion of this proposal tests two central hypotheses: 1) Prenatal exposures and subsequent endocrine development represent an important class of mechanisms by which genetic and parenting influences (specifically, parental negativity) are internalized, thus affecting behavioral development and subsequent substance use; and 2) Genetic influences can modify the influences of prenatal exposures and parental negativity, both of which can also modify the influence of endocrine development on adolescent substance use. Results from these aims will advance our knowledge of the origins of adolescent substance use, which adolescents will initiate and use which types of substances, and which developmental influences are most salient for substance use development given multiple other influences. Findings will also have implications for intervention by identifying optimal targets for enhancing protective mechanisms and disrupting mechanisms of risk for adolescent substance use given multiple other developmental influences. This K01 will also allow the Candidate the time and training required to build on her existing expertise and begin the transition to an independent, interdisciplinary researcher. Through training with experienced mentors who are leaders in the field, the Candidate will gain 1) expertise in novel statistical methods for analyzing genetic data 2) knowledge in mechanisms of prenatal risk, 3) knowledge of transitions from behavioral risk to adolescent substance use, 4) basic knowledge of the neural bases of adolescent hormone function and substance use, and 5) skills in integration and translation. Training in these areas and in research ethics is integral to completing the research aims, and preparing the Candidate for a career as a NIH-funded researcher investigating the adolescent substance use from a developmental perspective.