Coronary heart disease (CHD) is the most common cause of death in the United States. Traditional risk factors, such as smoking and hypertension, do not account for all of the risks in the development of heart disease. Recently, research has demonstrated that depression, which affects 16-23% of patients suffering heart attacks, is an important factor that affects the risk of death in patients with coronary heart disease. Brain regions involved in depression and stress may mediate the increased risk of cardiac mortality in depression. We have developed a model of brain areas including anterior cingulate and hippocampus, through either direct or indirect pathways through cortisol and the sympathetic system to the heart, mediating an increased risk for cardiac mortality. We have developed techniques to perform simultaneous imaging of the heart and brain, as well as measurement of the stress hormones cortisol and norepinephrine, during a stress challenge in patients with heart disease, with and without depression. Preliminary data shows decreased hippocampal and anterior cingulate activation with a stressful challenge in CHD patients with depression. Patients with CHD and depression showed a pattern of greater stress induced myocardial ischemia.
Specific Aims of this proposal are therefore to: 1) Use positron emission tomography (PET) and O-15 water to measure brain correlates of a stressful cognitive challenge in patients with heart disease, with and without depression;2) Inject [Tc-99m]sestamibi at the time of the stress challenge and image myocardial perfusion with single photon emission tomography (SPECT) in the same subjects;3) Assess the effects of stress on cortisol and norepinephrine as well as heart rate variability as mediators of the effects of the brain on myocardial function. Secondary aims are to assess the effects of early life trauma on brain and heart activation, to compare mental stress and exercise stress induced myocardial ischemia, and to assess the effects of high intensity white matter lesions on T2 weighted MRI. Hypotheses are that CHD patients with depression will show decreased hippocampal and anterior cingulate function during stress which will be associated with myocardial ischemia and decreased heart rate variability.

Public Health Relevance

Depression in CHD is associated with increased mortality;understanding mechanisms involved may lead to new treatments with the potential to reduce CHD mortality. Narrative This project uses positron emission tomography (PET) measurement of brain function and single photon emission tomography (SPECT) imaging of heart function during a stressful task to look at mechanisms by which depression increases the risk of mortality from cardiovascular disease (CVD). The project will measure changes in brain function that occur during stress and the way these may affect myocardial ischemia in patients with CVD and depression, as well neurohormonal changes that may mediate these effects. Understanding brain-based mechanisms by which depression increases mortality from CVD has the potential to lead to new treatments for this disorder.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL088726-04
Application #
8110711
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Czajkowski, Susan
Project Start
2008-09-01
Project End
2014-05-31
Budget Start
2012-06-01
Budget End
2014-05-31
Support Year
4
Fiscal Year
2012
Total Cost
$636,326
Indirect Cost
$225,793
Name
Emory University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Rooks, Cherie R; Ibeanu, Ijeoma; Shah, Amit et al. (2016) Young women post-MI have higher plasma concentrations of interleukin-6 before and after stress testing. Brain Behav Immun 51:92-8
Klebaner, Daniella; Huang, Yunfeng; Hui, Qin et al. (2016) X chromosome-wide analysis identifies DNA methylation sites influenced by cigarette smoking. Clin Epigenetics 8:20
Hammadah, Muhammad; Al Mheid, Ibhar; Wilmot, Kobina et al. (2016) Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes. Circ Res :
Saigh, Philip A; Yasik, Anastasia E; Halamandaris, Phill V et al. (2015) The parent ratings of traumatized children with or without PTSD. Psychol Trauma 7:85-92
Pimple, Pratik; Shah, Amit; Rooks, Cherie et al. (2015) Association between anger and mental stress-induced myocardial ischemia. Am Heart J 169:115-21.e2
Goetz, Margarethe; Shah, Amit; Goldberg, Jack et al. (2014) Posttraumatic stress disorder, combat exposure, and carotid intima-media thickness in male twins. Am J Epidemiol 180:989-96
Kulshreshtha, Ambar; Goyal, Abhinav; Veledar, Emir et al. (2014) Association between ideal cardiovascular health and carotid intima-media thickness: a twin study. J Am Heart Assoc 3:e000282
Wei, Jingkai; Pimple, Pratik; Shah, Amit J et al. (2014) Depressive symptoms are associated with mental stress-induced myocardial ischemia after acute myocardial infarction. PLoS One 9:e102986
Wei, Jingkai; Rooks, Cherie; Ramadan, Ronnie et al. (2014) Meta-analysis of mental stress-induced myocardial ischemia and subsequent cardiac events in patients with coronary artery disease. Am J Cardiol 114:187-92
Nye, Jonathon A; Votaw, John R; Bremner, J Douglas et al. (2014) Quantification of dopamine transporter density with [18F]FECNT PET in healthy humans. Nucl Med Biol 41:217-22

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