Parent-adolescent interactions, gender, and substance use: Brain mechanisms.

摘要（30行） 青少年物质使用是一个重要的公共卫生问题，预测未来的物质使用 成年期的疾病需要对风险因素有准确的了解，以制定和有针对性地进行预防。一 大量研究表明，养育环境是青少年的一个重要风险因素 物质使用。然而，父母对物质使用的影响的大脑机制尚不清楚。在 我们目前的NIDA资助的R 01研究，我们发现，在我们的小说中测量的适应不良的父母行为， 实验室亲子互动任务（PAIT）对当前和未来（1年后）有显著预测作用 245名青少年使用药物。作为下一步，在R 01更新申请中，我们建议团队 与神经科学家（合作PI汤普森）研究情绪和奖励相关的大脑机制的影响， 对青少年药物使用的影响我们对72名青少年进行了一项初步的fMRI研究， R 01研究，并发现初步证据表明，在实验室PAIT任务中观察到的父母行为 预测改变额边缘纹状体激活消极情绪和奖励，这些大脑 回答预测未来青少年物质使用。此外，我们发现这些大脑通路的不同之处在于， 性别，女孩表现出以额边缘激活为特征的负面情绪途径 而男孩则表现出一种以额-纹状体激活增强为特征的奖励途径。拟议 更新研究将正式研究从父母到青少年的性别差异大脑通路 物质使用在一个大样本与更大范围的养育行为。 我们将招募326名11-12岁的未接触过药物的儿童及其父母，其中40%的儿童被过度抽样， 不适应的父母在实验室中，我们将测量观察到的养育行为和青少年 生理反应在我们的PAIT任务，在目前的R 01研究验证。青少年将完成fMRI 在标准化情绪中检查大脑功能激活（以及功能连接）的会议 处理，奖励处理，以及我们在当前R 01样本中试用的静息状态任务。我们将 收集详细的行为和生物措施的物质使用和问题使用，情绪和奖励 敏感性，并在基线和1，2，3年随访到青春期中期报告养育。 我们将研究：1. PAIT中的父母行为预测青少年情绪和奖励相关的大脑 性别功能; 2。青少年脑功能预测物质使用增加超过三个月 年，按性别。这项研究将是第一个将实验室评估与神经系统评估相结合的研究。 成像以了解父母对物质使用影响的大脑机制。通过识别大脑 育儿影响的机制以及其中的性别差异，我们可以更好地针对和加强 以父母为重点的预防方案，并制定对性别问题有敏感认识的预防措施。

Abstract (30 lines) Adolescent substance use is a significant public health problem that predicts future substance use disorders in adulthood. Precise understanding of risk factors is needed to develop and target preventions. A large body of research has identified the parenting environment as a strong risk factor for adolescent substance use. However, the brain mechanisms for effects of parenting on substance use are not known. In our current NIDA-funded R01 study, we found that maladaptive parenting behaviors measured in our novel laboratory parent-adolescent interaction task (PAIT) significantly predicted current and future (1 year later) substance use in 245 early adolescents. As a next step, in this R01 renewal application, we propose to team with a neuroscientist (co-PI Thompson) to investigate emotion- and reward-related brain mechanisms of effects of parenting on adolescent substance use. We conducted a pilot fMRI study with 72 of the adolescents from the R01 study and found initial evidence that observed parenting behaviors in the laboratory PAIT task predicted altered fronto-limbic-striatal activation to negative emotion and reward and that these brain responses predicted future adolescent substance use. Further, we found that these brain pathways differed by gender, with girls showing a pathway characterized by heightened fronto-limbic activation to negative emotion and boys showing a pathway characterized by heightened fronto-striatal activation to reward. The proposed renewal study will formally examine gender-differentiated brain pathways from parenting to adolescent substance use in a large sample with a greater range of parenting behavior. We will recruit 326 substance-naive 11-12 year olds and their parents, with 40% oversampled for maladaptive parenting. In a laboratory session, we will measure observed parenting behaviors and adolescent physiological responses in our PAIT task, validated in the current R01 study. Adolescents will complete fMRI sessions to examine brain functional activation (and also functional connectivity) in standardized emotion processing, reward processing, and resting-state tasks which we piloted in the current R01 sample. We will collect detailed behavioral and biological measures of substance use and problem use, emotion and reward sensitivity, and reported parenting at baseline and 1, 2, and 3 year follow-ups into middle adolescence. We will examine: 1. Parenting in PAIT predicting adolescent emotion- and reward-related brain function by gender and 2. Adolescent brain function predicting increases in substance use over three years, by gender. The study will be the first to integrate laboratory assessment of parenting with neuro- imaging to understand brain-based mechanisms of parenting effects on substance use. By identifying brain mechanisms of parenting effects, and gender differences in these, we can better target and strengthen parenting-focused prevention programs and develop gender-sensitive preventions.