Dismantling MBRP: Identifying Critical Neuroimmune Mechanisms of Action

拆解 MBRP：识别关键的神经免疫作用机制

基本信息

批准号：
9036740
负责人：
KENT E. HUTCHISON
金额：
$ 62.28万
依托单位：
UNIVERSITY OF COLORADO
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-03-10 至 2021-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9036740
关键词：
Abstinence Alcohol consumption Alcohol dependence Biological Assay Biological Markers Brain Clinical Corpus striatum structure Cues DRD2 gene Data Disease Dopamine Dopamine D2 Receptor Dopamine Receptor Effectiveness Epigenetic Process Equation Equilibrium Etiology Genes Heavy Drinking Human IL8 gene Immune system Individual Inflammatory Interleukin-4 Interleukin-6 Knowledge Left Link Liver Function Tests Maintenance Malignant Neoplasms Mediating Mediator of activation protein Methylation Modality Modeling Modification Molecular Molecular Target Mood Disorders Neuroimmunomodulation Neurophysiology - biologic function Outcome Pathway interactions Patients Pharmacotherapy Population Preventive Intervention Public Health Randomized Regulator Genes Research Research Design Rewards Route Stress Substance Use Disorder System TLR4 gene TLR6 gene TNF gene Testing Therapeutic Toll-like receptors Treatment outcome Work alcohol effect alcohol use disorder base blood oxygenation level dependent response compare effectiveness cytokine disorder later incidence prevention drinking effective therapy epigenetic regulation executive function inflammatory marker innovation intervention effect mindfulness mindfulness intervention neuroadaptation neuroinflammation novel programs psychosocial public health relevance socioeconomics success

项目摘要

DESCRIPTION (provided by applicant): Recent work suggests that the epigenetic regulation of dopamine genes is an important molecular mechanism underlying adaptations in reward circuits. Several studies have also indicated that perturbations in the immune system leading to neuroinflammation is an important mechanism underlying changes in the connectivity of executive control networks. Both of these factors are mechanisms that putatively underlie the etiology and maintenance of alcohol use disorders. A number of studies indicate that mindfulness based interventions may reduce inflammation (i.e., neuroinflammation) and influence epigenetic regulation. Finally, Mindfulness Based Relapse Prevention (MBRP) has recently demonstrated efficacy in the treatment of substance use disorders, although it is not clear how MBRP works. In the first aim of the proposed research, the mindfulness components of MBRP will be dismantled from the relapse prevention components by comparing the effects of an MBRP intervention to a relapse prevention (RP) intervention, thereby isolating the mindfulness effects. In the second aim, the proposed research will examine the mechanisms that may mediate the effects of MBRP by testing the effects of the intervention on inflammatory biomarkers (IL-6, IL-8, and TNFα) as well as the effect of MBRP on epigenetic regulation of key genes (DRD2, SLC6A3, DBH). Further, the proposed work will examine the effects of the intervention on the neural function of the reward system as well as connectivity in executive control networks in the brain. In Aim 3, the research will determine whether the effects of MBRP on immune system function and epigenetic regulation mediate the effects of MBRP on treatment outcomes. To that end, 226 patients will be randomized to 8 weeks of treatment with MBRP or RP. Putative mediators will be assayed at 4 and 8 weeks. Drinking outcomes will be assessed at 4, 8, 20 (12 weeks after the end of treatment), and 32 weeks (24 weeks after the end of treatment). The successful completion of the proposed research is expected to have significant clinical and scientific implications.

描述（由申请人提供）：最近的工作表明，多巴胺基因的表观遗传调控是奖励回路适应的重要分子机制，一些研究还表明，导致神经炎症的免疫系统扰动是导致神经炎症变化的重要机制。这两个因素被认为是酒精使用障碍的病因和维持的机制。许多研究表明，基于正念的干预措施可以减少炎症（即，最后，基于正念的复发预防 (MBRP) 最近已证明在治疗药物滥用障碍方面有效，尽管目前尚不清楚 MBRP 的作用原理。通过比较 MBRP 干预与复发预防 (RP) 干预的效果，将 MBRP 从复发预防部分中拆除，从而分离出正念效果。在第二个目标中，拟议的研究将检查可能的机制。通过测试干预对炎症生物标志物（IL-6、IL-8 和 TNFα）的影响以及 MBRP 对关键基因（DRD2、SLC6A3、DBH）表观遗传调控的影响来介导 MBRP 的影响。拟议的工作将检查干预对奖励系统神经功能以及大脑执行控制网络连接的影响。在目标 3 中，该研究将确定 MBRP 是否对免疫系统产生影响。为此，226 名患者将被随机分配接受 8 周的 MBRP 或 RP 治疗，并在第 4 周评估假定的调节因子。、8、20（治疗结束后12周）和32周（治疗结束后24周）的成功完成预计将具有重大的临床和科学意义。影响。