A person's tendency to show exaggerated blood pressure reactions to acute psychological stressors is associated with an increased risk for preclinical atherosclerosis in the carotid arteries, which is a known predictor of premature disability and death by coronary heart disease. However, the neural pathways that link psychological stress to exaggerated blood pressure reactivity and risk for carotid atherosclerosis in humans are unknown. Supported by preliminary results, this project tests the central hypothesis that exaggerated blood pressure reactivity to psychological stress and greater preclinical carotid atherosclerosis are commonly associated with stress-induced hyperactivity in a network of brain systems that both process psychological stressors and regulate autonomic, neuroendocrine, and cardiovascular activity. These brain systems include functional subdivisions of the cingulate cortex, insula, and amygdala. To test specific predictions of this central hypothesis, three specific aims will be evaluated in a representative community sample of 75 men and 75 women (aged 30-50 years) who are asymptomatic for clinical cardiovascular disease and who are well characterized for known and emerging demographic, anthropometric, biological, and psychosocial cardiovascular risk factors. Participants will complete a battery of psychological stress tasks to elicit blood pressure reactivity in a functional magnetic resonance imaging (fMRI) session;they will also complete a non-invasive carotid ultrasound protocol to assess preclinical atherosclerosis.
Aim 1 tests the prediction that exaggerated blood pressure reactivity to the stressor battery will be associated with a greater activation (as revealed by greater fMRI blood oxygen level-dependent [BOLD] responses) in the perigenual, dorsal, and posterior cingulate cortex, the anterior insula, and the amygdala.
Aim 2 tests the prediction that greater activation in these brain systems to the stressor battery, but not to a non-stressor control task, will be associated with more preclinical atherosclerosis (as indicated by greater carotid intima-media thickness) after accounting for other cardiovascular risk factors.
Aim 3 tests the prediction that stressor-induced activation in these brain systems is a stable response tendency of individuals, as determined by the test-retest reliability of stressor-induced fMRI BOLD responses in 30 participants who will be tested in 2 repeat fMRI sessions separated by 8 weeks. Health-related significance: The proposed study is designed to specify the neural pathways that may link psychological stress to exaggerated cardiovascular reactivity and preclinical atherosclerosis. The information provided by this study may reveal a novel stress-related neural phenotype that could be targeted by brain-based interventions for early modification in pre-symptomatic people at high risk for coronary heart disease.

Public Health Relevance

Submitted in response to PA-07-046: Research on Mind-Body Interactions and Health. The broad objective of this project is to delineate the human brain systems that centrally link individual differences in cardiovascular reactions to stress and risk for coronary heart disease (CHD). From a public health perspective, it is important to delineate these brain systems to (1) understand the neural pathways by which psychological stress leads to cardiovascular reactions that may increase CHD risk and (2) identify markers of stress-related neural activity that could be objectively identified and possibly targeted for early modification in people at risk for future CHD.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL089850-02
Application #
7599673
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Stoney, Catherine
Project Start
2008-04-01
Project End
2012-01-31
Budget Start
2009-02-01
Budget End
2010-01-31
Support Year
2
Fiscal Year
2009
Total Cost
$452,740
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Gianaros, Peter J; Jennings, J Richard (2018) Host in the machine: A neurobiological perspective on psychological stress and cardiovascular disease. Am Psychol 73:1031-1044
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Lockwood, Kimberly G; Marsland, Anna L; Cohen, Sheldon et al. (2016) Sex differences in the association between stressor-evoked interleukin-6 reactivity and C-reactive protein. Brain Behav Immun 58:173-180
Cohen, Sheldon; Gianaros, Peter J; Manuck, Stephen B (2016) A Stage Model of Stress and Disease. Perspect Psychol Sci 11:456-63

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