Dismantling MBRP: Identifying Critical Neuroimmune Mechanisms of Action

拆解 MBRP：识别关键的神经免疫作用机制

• 批准号: 10313471
• 负责人: KENT E. HUTCHISON
• 金额: $ 56.58万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-12-08 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10313471
• 关键词: Dismantling; MBRP; Identifying; Critical; Neuroimmune

 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（由适用提供）：最近的工作表明，多巴胺基因的表观遗传调节是奖励回路适应的重要分子机制。几项研究还表明，导致神经炎症的免疫系统中的扰动是执行控制网络连通性的重要机制。这两个因素都是育种障碍的病因和维持的基础的机制。许多研究表明，基于正念的干预措施可能会减少感染（即神经炎症）并影响表观遗传调节。最后，尽管尚不清楚MBRP的工作原理，但基于正念的预防（MBRP）最近证明了药物使用障碍的治疗效率。在拟议的研究的第一个目的中，将通过比较MBRP干预与预防救济预防（RP）干预的影响，从而隔离正念效果，从而从中继预防组件中删除MBRP的正念成分。在第二个目的中，拟议的研究将通过测试干预措施对炎性生物标志物（IL-6，IL-8和TNFα）的影响以及MBRP对关键基因（DRD2，SLC6A3，DBH）的表观遗传调节的影响，研究可能介导MBRP影响的机制。此外，拟议的工作将研究干预对奖励系统神经功能以及大脑执行控制网络中的连通性的影响。在AIM 3中，研究将确定MBRP对免疫系统功能和表观遗传调节的影响是否介导MBRP对治疗结果的影响。为此，将有226名患者被随机分为MBRP或RP治疗8周。推定的调解员将在4周和8周内分配。饮酒结果将在4、8、20（治疗结束后12周）和32周（治疗结束后24周）进行评估。预计拟议研究的成功完成将具有重大的临床和科学意义。

项目成果

Comparing the Efficacy of Mindfulness-Based Relapse Prevention Versus Relapse Prevention for Alcohol Use Disorder: A Randomized Control Trial.

比较基于正念的复发预防与酒精使用障碍复发预防的功效：随机对照试验。

• DOI: 10.15288/jsad.21-00392
• 发表时间: 2023
• 期刊: Journal of studies on alcohol and drugs
• 影响因子: 3.4
• 作者: Skrzynski,CarillonJ;Karoly,Hollis;Ellingson,JarrodM;Hagerty,SarahL;Bryan,AngelaD;Hutchison,KentE
• 通讯作者: Hutchison,KentE

Biological Systems Are a Common Link Between Alcohol Use Disorder and Co-Occurring Psychiatric and Medical Conditions.

生物系统是酒精使用障碍与同时发生的精神和医疗状况之间的常见联系。

• DOI: 10.1111/acer.13570
• 发表时间: 2018
• 期刊: Alcoholism, clinical and experimental research
• 作者: Hagerty,SarahL;Ellingson,JarrodM;Hutchison,KentE
• 通讯作者: Hutchison,KentE

Mindfulness mechanisms in alcohol use: Comparing top-down and bottom-up processes.

饮酒中的正念机制：比较自上而下和自下而上的过程。

• DOI: 10.1037/adb0000932
• 发表时间: 2024
• 期刊: Psychology of addictive behaviors : journal of the Society of Psychologists in Addictive Behaviors
• 作者: Skrzynski,CarillonJ;Bryan,AngelaD;Hutchison,KentE
• 通讯作者: Hutchison,KentE

Exploring relationships between alcohol consumption, inflammation, and brain structure in a heavy drinking sample.

• DOI: 10.1111/acer.14712
• 发表时间: 2021-11
• 期刊: Alcoholism, clinical and experimental research
• 作者: Karoly HC;Skrzynski CJ;Moe EN;Bryan AD;Hutchison KE
• 通讯作者: Hutchison KE