Research Project 2: Can Family-Centered Prevention Programming Reduce Neuroimmune Vulnerabilities for Drug Use and Health Risk among African American Adolescents?: A Randomized Prevention Trial

项目概要：研究项目2 拟议的研究项目（RP）2和更广泛的P50中心的非裔美国人群体 焦点不成比例地暴露在社会逆境中，这些逆境会对个人的生物， 神经认知和行为系统。在向成年人过渡的过程中，这种损失表现为 成瘾行为的发生率，包括吸毒和不健康饮食。一个科学共识正在形成， 在童年和青春期暴露于社会逆境和其他压力因素， 和心脏代谢的脆弱性，通过累积效应“皮下”，包括失调， 神经免疫网络（NIN）。然而，尽管长期处于压力之下，许多非洲裔美国青年和 年轻人不会表现出NIN调节失调以及容易吸毒和其他形式的成瘾 行为在我们的P30中心赞助的一系列原理验证研究中，我们调查了 在11岁时参加强大的非裔美国人家庭（SAAF）计划对个人的影响， 他们正在向成年人过渡（19-25岁）。参与的一些额外好处成为 显然，其中许多涉及修改与NIN框架中指定的那些过程相关联的过程（即， 前额叶-边缘连接、边缘区域结构、炎症和心脏代谢健康）。虽然 挑衅性的发现，关于炎症和神经活动的数据是事后收集的，这些发现必须 在进行更严格的研究之前，应将其视为初步研究。建议的RP 2旨在满足 通过对SAAF计划（N = 300个低收入家庭）进行随机对照试验， 哪些青少年将参与功能磁共振成像评估和抽血，以索引NIN相关的神经系统， 基线和长期随访（2年）时的外周炎症。父母的心理社会措施 还将在基线、1年和2年随访时对青年进行研究。我们的具体目标是测试 假设：（1）参与SAAF对NIN相关风险标志物变化的影响 （神经回路subserving威胁，奖励和执行控制，以及外周炎症）在2 （2）父母保护在联系SAAF参与与NIN相关风险中的中介作用 （3）SAAF对与情绪相关的成瘾行为脆弱性变化的影响 监管、风险决策、早发性物质使用、不健康饮食和心脏代谢风险 标记;（4）通过改变SAAF与成瘾行为脆弱性之间的中介链， 父母养育和NIN相关的风险标志物。测试SAAF对NIN指定的实验效果 通过预测和随访功能磁共振成像和炎症评估的脆弱性因素， 我们希望RP 2能为未来的药物研究提供一个模板， 使用预防方案。

PROJECT SUMMARY: Research Project 2 The African American populations on whom the proposed Research Project (RP) 2 and broader P50 Center focus are disproportionately exposed to social adversities, hardships that take a toll on individuals’ biological, neurocognitive, and behavioral systems. During the transition to adulthood, this toll manifests in escalating rates of addictive behavior, including drug use and unhealthy eating. A scientific consensus is emerging that exposure to social adversity and other stressors during childhood and adolescence can promote both drug use and cardiometabolic vulnerabilities through cumulative effects “under the skin”, including dysregulation of the neuroimmune network (NIN). Despite exposure to chronic stress, however, many African American youth and young adults do not evince NIN dysregulation and vulnerability to drug use and other forms of addictive behavior. In a series of proof-of-principle studies sponsored by our P30 Center, we investigated the long-term effects of participation at age 11 in the Strong African American Families (SAAF) program on individuals when they were transitioning to adulthood (ages 19-25). A number of additional benefits from participation became apparent, many of which involved modifying processes linked to those specified in the NIN framework (i.e., prefrontal-limbic connectivity, limbic region structures, inflammation, and cardiometabolic health). Although provocative findings, data on inflammation and neural activity were collected post hoc, and these findings must be regarded as preliminary until a more rigorous study is performed. The proposed RP2 is designed to meet this need by conducting a randomized controlled trial of the SAAF program (N = 300 low-income families) in which youth will participate in an fMRI assessment and blood draw to index NIN-related neural systems and peripheral inflammation at baseline and a long-term follow-up (2 years). Psychosocial measures from parents and youth will also be conducted at baseline, 1-year, and 2-year follow-up. Our specific aims are to test hypotheses regarding: (1) the influence of participation in SAAF on change in NIN-associated risk markers (neural circuitry subserving threat, reward, and executive control, as well as peripheral inflammation) across 2 years; (2) the mediating role of protective parenting in linking SAAF participation to NIN-associated risk markers; (3) the influence of SAAF on change in addictive behavior vulnerabilities associated with emotion regulation, risky decision making, early-onset substance use, unhealthy eating, and cardiometabolic risk markers; and (4) the mediational chain linking SAAF to addictive behavior vulnerabilities via changes in parenting and NIN-associated risk markers. Testing the experimental effects of SAAF on NIN-specified vulnerability factors with pretest and follow-up fMRI and inflammation assessments represents a dramatic step forward in prevention science, and we hope that RP2 will provide a template for future investigations of drug use prevention programs.