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, a known predictor of premature disability and death by coronary heart disease (CHD). Prior work supported by this R01 (HL089850) has characterized a network of brain systems that regulate stressor-evoked blood pressure reactions, encompassing subdivisions of the cingulate cortex, insula, and amygdala. Additional cross-sectional work showed that stressor-evoked functional activity in these brain systems is associated with preclinical carotid atherosclerosis. This continuation project extends HL089850 by testing the organizing hypothesis that stressor-evoked functional activity in the cingulate cortex, insula, and amygdala predicts the 3-year longitudinal progression of preclinical atherosclerosis. It also extends HL089850 by testing the new hypothesis that individual differences in cingulate cortex, insula, and amygdala activity during the regulation of negative emotional experiences also accounts for cross-sectional and longitudinal variation in preclinical atherosclerosis. To test specific predictions derived from these hypothesis, three specific aims will be pursued in a community sample of men and women (aged 30-50 years) who are asymptomatic for clinical cardiovascular disease and who are well characterized for known demographic, anthropometric, biological, and psychosocial cardiovascular risk factors. Participants will complete a battery of psychological stress reactivity and emotion regulation tasks in a functional magnetic resonance imaging (fMRI) session with concurrent peripheral physiological monitoring. They will also complete a non-invasive carotid artery ultrasound protocol to assess preclinical atherosclerosis, as well as protocols to assess other known and emerging CHD risk factors at a baseline time point (Time 1) and at a follow-up time point 3-years later (Time 2).
Aim 1 tests whether stressor-evoked functional connectivity between the anterior cingulate cortex, anterior insula, and amygdala predicts the progression of preclinical atherosclerosis (as measured by carotid intima-media thickness and adventitial diameter) after accounting for known cardiovascular risk factors.
Aim 2 tests whether stressor-evoked blood pressure reactivity partially mediates the associations between stressor-evoked functional connectivity and the progression of preclinical atherosclerosis.
Aim 3 tests whether the functional connectivity between the anterior cingulate cortex, anterior insula, and amygdala during the cognitive reappraisal of negative emotional stimuli associates with preclinical atherosclerosis at Time 1 and progression to Time 2.

Public Health Relevance

The human brain systems linking individual differences in stress and emotion regulation processes to risk for coronary heart disease (CHD) are uncertain. From a public health perspective, it is important to specify these brain systems to (1) understand the mechanistic pathways by which stress and emotion regulation increase or protect against CHD risk and (2) identify markers of stress- and emotion-related neural activity that could be objectively identified and possibly targeted for modification in otherwise healthy 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 #
4R01HL089850-09
Application #
9015263
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Stoney, Catherine
Project Start
2007-07-01
Project End
2018-02-28
Budget Start
2016-03-01
Budget End
2018-02-28
Support Year
9
Fiscal Year
2016
Total Cost
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
Jorgensen, Dana; White, Gretchen E; Sekikawa, Akira et al. (2018) Higher dietary inflammation is associated with increased odds of depression independent of Framingham Risk Score in the National Health and Nutrition Examination Survey. Nutr Res 54:23-32
Kragel, Philip A; Kano, Michiko; Van Oudenhove, Lukas et al. (2018) Generalizable representations of pain, cognitive control, and negative emotion in medial frontal cortex. Nat Neurosci 21:283-289
Ginty, Annie T; Kraynak, Thomas E; Fisher, James P et al. (2017) Cardiovascular and autonomic reactivity to psychological stress: Neurophysiological substrates and links to cardiovascular disease. Auton Neurosci 207:2-9
Gianaros, Peter J; Kuan, Dora C-H; Marsland, Anna L et al. (2017) Community Socioeconomic Disadvantage in Midlife Relates to Cortical Morphology via Neuroendocrine and Cardiometabolic Pathways. Cereb Cortex 27:460-473
Marsland, Anna L; Kuan, Dora C-H; Sheu, Lei K et al. (2017) Systemic inflammation and resting state connectivity of the default mode network. Brain Behav Immun 62:162-170
Taren, Adrienne A; Gianaros, Peter J; Greco, Carol M et al. (2017) Mindfulness Meditation Training and Executive Control Network Resting State Functional Connectivity: A Randomized Controlled Trial. Psychosom Med 79:674-683
Jennings, J Richard; Sheu, Lei K; Kuan, Dora C-H et al. (2016) Resting state connectivity of the medial prefrontal cortex covaries with individual differences in high-frequency heart rate variability. Psychophysiology 53:444-54
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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