The overall aim of this proposal is to determine the relation of severity of depressive symptoms to the inflammatory process implicated in atherogenesis. Epidemiological studies indicate that severity of depressive symptoms is a significant predictor of cardiovascular disease risk. At this time, pathophysiological mechanisms underlying this link are incompletely defined. A central characteristic of the pathogenesis of atherosclerosis is the proinflammatory response of blood monocytes. This response is characterized by the increased expression of various inflammatory cytokines and cell adhesion molecules. We hypothesized that severity of depressive symptoms is associated with greater basal expression of cytokines and cell adhesion molecules on blood monocytes. We also hypothesized that, in persons with depressive symptoms, stress-induced changes in monocyte markers are positively associated with arousal of negative affects, stress-induced-neuroendocrine responses, and fasting lipids. To test these hypotheses, we propose to conduct a study in 300 healthy, non-smoking individuals, 150 men and 150 premenopausal women. We propose the following specific aims: 1) To investigate the degree to which severity of depressive symptoms is associated with greater basal expression of cytokines and adhesion molecules on blood monocytes; 2) To investigate the degree to which stress-induced changes in the expression of monocyte cytokines and cell adhesion molecules are associated with stress-induced emotional arousal as a function of severity of depressive symptoms; 3) To investigate the degree to which stress-induced changes in the expression of monocyte cytokines and cell adhesion molecules are associated with stress-induced catecholamine and cortisol responses as a function of severity of depressive symptoms; and 4) To investigate the degree to which stress-induced changes in the expression of monocyte cytokines and cell adhesion molecules are associated with fasting lipids as a function of severity of depressive symptoms. In accomplishing these aims, we will also explore the potential moderating effects of gender, as well as ovarian hormones, on the above relationships. If we are successful, we will provide empirical evidence to support the hypothesis that severity of depressive symptoms is associated with proinflammatory cellular activities linked to human atherosclerosis.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL067459-04
Application #
6763129
Study Section
Special Emphasis Panel (ZRG1-BBBP-2 (01))
Program Officer
Czajkowski, Susan
Project Start
2001-07-01
Project End
2006-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
4
Fiscal Year
2004
Total Cost
$486,201
Indirect Cost
Name
Duke University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
Suarez, Edward C; Sundy, John S (2017) The cortisol:C-reactive protein ratio and negative affect reactivity in depressed adults. Health Psychol 36:852-862
Suarez, Edward C; Beckham, Jean C; Green, Kimberly T (2017) The Relation of Light-to-Moderate Alcohol Consumption to Glucose Metabolism and Insulin Resistance in Nondiabetic Adults: the Moderating Effects of Depressive Symptom Severity, Adiposity, and Sex. Int J Behav Med 24:927-936
Suarez, Edward C; Sundy, John S; Erkanli, Alaattin (2015) Depressogenic vulnerability and gender-specific patterns of neuro-immune dysregulation: What the ratio of cortisol to C-reactive protein can tell us about loss of normal regulatory control. Brain Behav Immun 44:137-47
Suarez, Edward C; Schramm-Sapyta, Nicole L (2014) Race differences in the relation of vitamins A, C, E, and ?-carotene to metabolic and inflammatory biomarkers. Nutr Res 34:1-10
Suarez, Edward C; Schramm-Sapyta, Nicole L; Vann Hawkins, Tracey et al. (2013) Depression inhibits the anti-inflammatory effects of leisure time physical activity and light to moderate alcohol consumption. Brain Behav Immun 32:144-52
Greeson, Jeffrey M; Lewis, James G; Achanzar, Karen et al. (2009) Stress-induced changes in the expression of monocytic beta2-integrins: the impact of arousal of negative affect and adrenergic responses to the Anger Recall Interview. Brain Behav Immun 23:251-6
Darnall, Beth D; Suarez, Edward C (2009) Sex and gender in psychoneuroimmunology research: past, present and future. Brain Behav Immun 23:595-604
Suarez, Edward C (2008) Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: evidence for gender disparity. Brain Behav Immun 22:960-8
Boyle, Stephen H; Jackson, William G; Suarez, Edward C (2007) Hostility, anger, and depression predict increases in C3 over a 10-year period. Brain Behav Immun 21:816-23
Boyle, Stephen H; Michalek, Joel E; Suarez, Edward C (2006) Covariation of psychological attributes and incident coronary heart disease in U.S. Air Force veterans of the Vietnam war. Psychosom Med 68:844-50

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