Neurocardiac Interactions Evaluated by Anatomic and Physiologic MRI Assessment

The purpose of project is to answer fundamental questions about the mechanisms underlying mental stress ischemia in patients with coronary artery disease, mood disorders, or both, and to identify potential biomarkers and psychosocial risk factors associated with this condition.

To achieve this goal, investigators will use cutting-edge cardiovascular and functional neuroimaging tools to study mental stress ischemia in a carefully controlled laboratory setting in subjects recruited from four patient populations: 1) patients who recently sustained a myocardial infarction; 2) patients undergoing non-emergent invasive coronary angiography (with and without known coronary artery disease); 3) patients with a diagnosis of major depressive disorder; and 4) patients with a diagnosis of bipolar 1 or bipolar 2 disorder.

Mental stress ischemia occurs when a psychosocial or mental stressor triggers an imbalance between the supply and demand for oxygen by cardiac myocytes. Epidemiological studies indicate that mental stress ischemia is common, occurring in 20-25% of patients with coronary artery disease (CAD) and portends a poor prognosis. The underlying mechanisms are thought to involve stress-induced activation of the sympathetic nervous system and associated effects on cardiovascular function. But how neurobiological and cardiovascular factors interact to generate mental stress ischemia is unknown. Furthermore, patients with major depressive disorder, bipolar disorder, and other stress-related psychiatric conditions have elevated rates of cardiovascular co-morbidities, including sudden cardiac death, yet mental stress ischemia has not been studied extensively in these psychiatric populations. The purpose of project is to answer fundamental questions about the mechanisms underlying mental stress ischemia in patients with coronary artery disease, mood disorders, or both, and to identify potential biomarkers and psychosocial risk factors associated with this condition.

To achieve this goal, investigators will use cutting-edge cardiovascular and functional neuroimaging tools to study mental stress ischemia in a carefully controlled laboratory setting in subjects recruited from four patient populations: 1) patients who recently sustained a myocardial infarction; 2) patients undergoing non-emergent invasive coronary angiography (with and without known coronary artery disease); 3) patients with a diagnosis of major depressive disorder; and 4) patients with a diagnosis of bipolar 1 or bipolar 2 disorder.

Eligibility Criteria:
Inclusion Criteria for Cardiac Subjects:

1. Male and female subjects, ages 50 years or more
2. Able to provide informed consent. Must be fluent english speakers.
3. Known coronary artery disease (CAD) as defined by prior PCI, CABG, prior MI, prior abnormal stress test or invasive coronary angiography (ICA)
4. Patients that are hemodynamically stable

Exclusion Criteria for Cardiac subjects:

1. Evidence of ongoing myocardial infarction or homonymic instability
2. Positive pregnancy test or unknown pregnant state at the time of enrollment for all women of child-bearing potential
3. Known contraindications to cardiovascular CT angiography with intravenous contrast (A) Known allergies (B) Renal dysfunction (GFR \< 30ml/min) (C) Contraindications to beta-blockers or nitroglycerin or adenosine (D) Irregular heart rate not controlled by administration of beta-blockers
4. Patients with contraindications to MRI scans (A) Non-MR compatible device or material implant (B) Known allergies to gadolinium containing contrast agent (C) Renal dysfunction (GFR \< 30 ml/min)

Inclusion Criteria for Psychiatric Subjects

1. Male and female subjects, ages 50 years or more
2. Must be fluent English-speakers due to the design of the mental stress tasks. Able to provide informed consent.
3. Subjects who are stable and meet DSM-V criteria for a diagnosis of major depressive disorder, bipolar 1 disorder, or bipolar 2 disorder, as assessed in an initial screening interview by phone and confirmed by a structured clinical interview on the first day of the study.

Exclusion Criteria for Psychiatric Subjects:

1. Subjects with a history of seizure disorder, stroke, Parkinson's disease, any form of dementia, or head injury resulting in loss of consciousness will be excluded from this study.
2. Contraindications to MRI be assessed during the screening interview and again using the NY-Presbyterian Hospital MRI Checklist prior to scanning and will also serve as exclusion criteria. They include claustrophobia; a history of metal implants (including braces, orthopedic implant, cochlear implant, implanted cardiac pacemaker, implanted cardioverter defibrillator, and ocular implant); weight over 250 pounds (owing to the size of the MR scanner bore); and women who are currently pregnant or breastfeeding.
3. Subjects who indicate that there is a chance that they may be pregnant will be asked to take a pregnancy test. They will be informed of the potential for false positive results due to diet, vitamins, and supplements, or over-the-counter medications. A positive pregnancy test will necessitate exclusion from the study, and the results will be disclosed to the participant.
4. Patients who are currently being treated with a beta blocker or daily (standing) benzodiazepines will be excluded, unless, in the judgment of the prescribing physician, the dose can be withheld on the morning of the each study session, due to the potential for these medications to mask neurobiological and cardiovascular responses to mental stress.
5. Investigators will also assess for additional psychiatric exclusion criteria during the screening interview and structured clinical interview: patients with bipolar 1 disorder who are currently manic; patients with any mood disorder currently complicated by hallucinations, delusions, or other psychotic features; patients with active suicidal ideation; and patients meeting DSM-V criteria for a co-morbid substance abuse disorder within the last 12 months will all be excluded. Other psychiatric co-morbidities will be permitted.

Subjects who meet both the psychiatric and cardiac inclusion criteria will also be enrolled in the study.