Beta-Blocker Influences on Inflammatory and Neural Responses to Stress

Beta-Blocker Influences on Inflammatory and Neural Responses to Stress

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.

Inclusion Criteria:

• Ages 18-30 years
• Right-handed
• Fluent in English reading, writing, and speaking at least at a 10th grade level
• Body mass index (BMI) less than or equal to 35 kg/m^2

Exclusion Criteria:

Assessed as screening, reassessed at Session I:

• Non-removeable metal devices/implants/objects in the body
• Severe claustrophobia (assessed by self-report)
• Currently pregnant
• Left-handed
• Body mass index (BMI) greater than 35 kg/m^2
• History of fainting spells or any heart condition
• History of or present low resting heart rate (< 60 BPM) and/or low blood pressure (systolic blood pressure < 80mmHg)
• Self-reported physical illnesses: diabetes, cardiovascular diseases, high blood pressure, inflammatory bowel diseases, rheumatoid arthritis, asthma, autoimmune disease, Crohn's disease, ulcerative colitis, lupus
• Any self-reported diagnosed mental illness
• Current use of prescription medications (except hormonal contraceptives)
• Current or recent regular nicotine/tobacco use (cigarettes, e-cigarettes, vape, chewing tobacco, nicotine gum)
• Current regular (daily or almost daily) recreational drug use = 4 or more times per week

Instructed against during Session I, reassessed at Session II:

• Received any vaccine within the past two weeks
• Severe sleep disturbance (3-4 hours of sleep loss) the night before Session II
• Vigorous physical activity on the day of Session II
• Acute illness or allergy symptoms on the day of Session II
• Usage of over-the-counter medications on the day of Session II
• Usage of recreational drugs within 48 hours of Session II
• Usage of alcohol on the day of Session II