The purpose of this study is to map the neural and molecular mechanisms underlying psychological stress-induced changes in inflammation which could reveal new targets for intervention to reduce the risk of cardiovascular disease.
The proposed work will conduct a mechanistic clinical trial utilizing the non-selective beta-adrenergic receptor blocker propranolol to examine the role of beta-adrenergic signaling in shaping neural and inflammatory responses to stress. The investigators will focus on beta-adrenergic signaling given seminal pre-clinical work showing that this molecular pathway is an important driver of stress-related increases in inflammation, and initial human neuroimaging work showing that beta-blockade leads to changes in neural responses to negative stimuli. Here, the investigators will bring these two previously disparate lines of work together to determine how experimentally blocking one critical stress-signaling pathway shapes neural activity and inflammatory responses to stress. In doing so, the investigators will be advancing knowledge by mapping mechanisms (i.e., beta-adrenergic signaling), offering methodological improvements (i.e., moving beyond correlation to using pharmacological manipulations to provide causal evidence), and identifying intervention targets (i.e., the neurocognitive systems that shift activity/connectivity in response to beta-blockade). In sum, the work proposed herein is significant because it will address the mechanisms by which one critical risk factor, psychological stress, may ultimately lead to cardiovascular disease via inflammation. The proposed study also offers significant methodological improvements over past work by using neuroimaging to identify neurocognitive pathways, and pharmacology to provide causal experimental evidence to move us beyond correlation. Finally, this project is significant because it could provide insight into novel targets for future interventions.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
120
Tablet encapsulated to visually look identical to the placebo.
Encapsulated sugar pill to visually look identical to the experimental condition.
Social Neuroscience and Health Laboratory
Chapel Hill, North Carolina, United States
RECRUITINGChange in levels of pro-inflammatory cytokine interleukin-6 in response to social stress
Blood plasma will be analyzed for levels of pro-inflammatory cytokine interleukin-6 (IL-6), from baseline, a baseline after drug administration, a sample 90-minutes after the stress task (T-90) measured in pg/mL. The timeline was determined on meta-analytic work showing changes in the inflammatory cytokine IL-6 are largest at 90 minutes post-stress.
Time frame: Post-drug baseline to 90-minutes post-stress task (T-90)
Change in levels of inflammatory gene expression in response to social stress
Whole blood samples will be collected in PaxGene tubes and analyzed for changes in inflammatory gene expression from baseline, a baseline after drug administration, and 30-minutes after the stress task (T-30), measured in gene transcript counts per million. The timeline is based on the Principal Investigator's work showing that changes in pro-inflammatory gene expression are observed 30-minutes post-stress.
Time frame: Post-drug baseline to 30-minutes post-stress task (T-30)
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