Research Project 1: Neuroimmune Mechanisms, Addictive Behaviors, and Cardiometabolic Health among African American Emerging Adults: A Prospective Study

项目概要：研究项目1 格鲁吉亚大学（UGA）转化和预防科学中心（CTAPS; P20 MH 068666， P30 DA 027827）自2003年以来一直得到资助，以推动下一代基本和预防性 调查生活在资源贫乏地区的非洲裔美国年轻人的风险，弹性和药物使用情况 社区. CTAPS P50提案是基于这样一种假设，即预防药物滥用的进展 非裔美国人的滥用和心脏代谢疾病需要考虑的过程， 这种长期的、多代人的贫困和社会逆境， 系统的方式赋予高度的脆弱性成瘾行为。从概念上讲，中心的 该研究计划基于由中心科学家撰写的神经免疫网络（NIN）模型， 强调了成瘾的病理生理学中大脑和免疫系统之间的双向信号传导 行为。NIN模型提出，慢性应激源放大了外周炎症之间的串扰， 以及帮助情绪产生和调节的神经回路。这种串扰导致慢性低级别 炎症，一旦进入大脑，就会加重皮质杏仁核回路中的威胁处理， 减弱皮质-纹状体环路中的奖赏处理，并抑制前额叶执行控制。NIN 失调被假设为使个体易于物质滥用和高脂肪饮食，部分地，自我调节， 消除与神经信号中断有关的负面情绪。这些行为产生 额外的炎症，以及奖励回路的神经适应性变化，进一步增加了 滥用药物在研究项目（RP）1中，我们提出了第一个前瞻性研究来测试NIN 225名非裔美国青年的样本预测。受试者在研究入组时年龄为18-19岁， 在这段时间里，非裔美国人的物质使用和不健康饮食迅速升级。在 时间1（T1）和T2（2.5年后），参与者将完成抽血，以量化低级别 炎症，威胁，奖励和执行控制神经活动的fMRI扫描，以及 压力暴露、成瘾行为和心脏代谢风险。RP 1整合了多器官研究 系统（即，大脑和免疫系统）来推进成瘾行为的风险和恢复力科学 及其对心脏代谢健康的影响，特别是在低收入的非洲裔美国人社区中， 和其他暴露在慢性压力下的美国人群。

PROJECT SUMMARY: Research Project 1 The University of Georgia’s (UGA) Center for Translational and Prevention Science (CTAPS; P20 MH068666, P30 DA027827) has been funded continuously since 2003 to advance next-generation basic and preventive investigations of risk, resilience, and drug use among African American young people living in resource poor communities. The CTAPS P50 proposal is based on the hypothesis that progress in the prevention of drug abuse and cardiometabolic disease among African Americans requires consideration of the processes through which chronic, multigenerational poverty and social adversity become embedded in biological and behavioral systems in ways that confer heightened vulnerability to addictive behaviors. Conceptually, the Center’s research program is grounded in a neuroimmune network (NIN) model authored by Center scientists that highlights bidirectional signaling between the brain and immune system in the pathophysiology of addictive behaviors. The NIN model proposes that chronic stressors amplify crosstalk between peripheral inflammation and neural circuitries subserving emotion generation and regulation. This crosstalk results in chronic low-grade inflammation, which upon accessing the brain, accentuates threat processing in cortico-amygdala circuity, attenuates reward processing in cortico-striatal circuity, and dampens prefrontal executive control. NIN dysregulation is hypothesized to predispose individuals to substance misuse and high fat diets, in part, to self- medicate the negative emotions associated with disrupted neural signaling. These behaviors generate additional inflammation, as well as neuroadaptive changes in reward circuitry, further elevating risk for substance misuse. In Research Project (RP) 1, we propose one of the first prospective studies to test NIN predictions from a sample of 225 African American youth. Participants will be ages 18-19 at study enrollment, a period of time in which substance use and unhealthy eating rapidly escalate among African Americans. At Time 1 (T1) and T2 (2.5 years later), participants will complete a blood draw to quantify low-grade inflammation, fMRI scanning of threat-, reward-, and executive control neural activity, and assessments of stress exposure, addictive behaviors, and cardiometabolic risk. RP1 integrates research on multiple organ systems (i.e., brain and immune system) to advance the science of risk and resilience for addictive behaviors and their cardiometabolic health consequences, especially among low income African American communities and other US populations exposed to chronic stress.