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Dismantling MBRP: Identifying Critical Neuroimmune Mechanisms of Action

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? 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 TNF?) 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.
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