Researchers Awarded $8M Grant to Study Depression, Cardiovascular Disease

PHOENIX — Researchers are trying to better understand the sex differences of the co-occurrence of major depression and cardiovascular disease, one of the primary causes of disability worldwide. Prior research shows major depression can affect up to 40% of patients who suffer a cardiac event.

Researchers at Massachusetts General Hospital, the Harvard School of Public Health, Colorado State University and the University of Arizona College of Medicine – Phoenix will use an $8 million specialized center grant for research on sex differences (SCORE) from the National Institutes of Health (NIH) Office for Research on Women’s Health and the National Institute of Mental Health to examine the sex differences of depression and heart disease.

“Heart disease is the leading cause of death in women, many of whom also have unrecognized or untreated major depressive disorder, or MDD,” said Taben Hale, PhD, an associate professor in the UArizona College of Medicine – Phoenix’s Department of Basic Medical Sciences who is leading the UArizona team. “MDD is among the top two, along with heart disease, primary causes of disability worldwide, and women have twice the risk of the co-occurrence of MDD with cardiovascular disease compared to men. Identifying a novel therapeutic strategy for these conditions would have significant impact on both lifespan and quality of life.”

The grant will fund three integrated studies that include:

• A population-level clinical neuroscience study relating prenatal stress and immune biomarkers to sex differences in brain circuitry and physiologic deficits in response to stress in MDD in early midlife.
• Testing a novel therapeutic device to target the central nervous system’s control of mood, the autonomic nervous system, which regulates bodily functions such as heart rate, and associated physiology to reduce sex-dependent deficits in MDD.
• Experimental studies that will identify the mechanistic pathways in the brain that are involved in projects one and two. 

The first two projects will be performed at Massachusetts General Hospital under the leadership of co-principal investigator Jill Goldstein, PhD, a professor of psychiatry and medicine and executive director of the Innovation Center on Sex Differences in Medicine at Massachusetts General Hospital and Harvard Medical School, along with Ronald Garcia, MD, PhD, and Vitaly Napadow, PhD.

“The goal of this SCORE is to enhance our understanding of sex on MDD and translate this knowledge into sex-selective treatment strategies,” Dr. Goldstein said. 

The third project is directed by co-principal investigator Robert Handa, PhD, a professor of basic medical sciences at the College of Medicine – Phoenix and biomedical sciences at Colorado State University. The work will be performed at Colorado State University and in Dr. Hale’s laboratory at the College of Medicine – Phoenix.

Drs. Hale and Handa will evaluate the impact of prenatal stress on the regulation of blood pressure and heart rate, as well as the effect of prenatal glucocorticoid exposure on behaviors that are suggestive of anxiety and depression. Glucocorticoids, including cortisol, are hormones that are increased in response to stress.

“These studies are focusing on changes that may be occurring during fetal development that may set the stage for future disease in adulthood,” Dr. Hale said. “Understanding the long-term consequences of prenatal stress is particularly important right now given the increased stress that everyone is experiencing.”

UArizona researchers also will study transcutaneous vagal nerve stimulation as a potential therapy to reverse the effects of prenatal stress. Transcutaneous vagal nerve stimulation is a non-invasive therapy that sends mild pulses of electrical energy to the brain via a branch of the vagus nerve that is accessible in the outer ear.

MDD is associated with abnormalities in the stress response areas of the brain. These brain regions also regulate the autonomic nervous system, which is involved in the short-term regulation of blood pressure and heart rate. Dysregulation of the autonomic nervous system is associated with cardiovascular disease. Women are twice as likely as men to have a co-occurrence of MDD, autonomic dysregulation and heart disease, resulting in up to a fivefold greater risk of death from heart disease, often with unrecognized and untreated MDD.

“This funding is critical to perform studies to advance our knowledge of the relationships between disorders of the brain and the heart and to identify novel treatment strategies to specifically target cardiovascular disease and MDD,” Dr. Hale said.

This research is supported by the National Institute of Mental Health, a unit of the National Institutes of Health (U54MH118919).

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A version of this article originally appeared on the College of Medicine – Phoenix website.

NOTE: Photos available upon request.

About the UArizona College of Medicine – Phoenix
Founded in 2007, the University of Arizona College of Medicine – Phoenix inspires and trains exemplary physicians, scientists and leaders to optimize health and health care in Arizona and beyond. By cultivating collaborative research locally and globally, the college accelerates discovery in a number of critical areas — including cancer, stroke, traumatic brain injury and cardiovascular disease. Championed as a student-centric campus, the college has graduated 500 physicians, all of whom received exceptional training from nine clinical partners and 1,800 diverse faculty members. As the anchor to the Phoenix Biomedical Campus, which is projected to have an economic impact of $3.1 billion by 2025, the college prides itself on engaging with the community, fostering education, inclusion, access and advocacy. For more information, please visit phoenixmed.arizona.edu (Follow us: Facebook | Twitter | YouTube | LinkedIn | Instagram).

About the UArizona Health Sciences
The University of Arizona Health Sciences is the statewide leader in biomedical research and health professions training. UArizona Health Sciences includes the Colleges of Medicine (Tucson and Phoenix), Nursing, Pharmacy, and the Mel and Enid Zuckerman College of Public Health, with main campus locations in Tucson and the Phoenix Biomedical Campus in downtown Phoenix. From these vantage points, Health Sciences reaches across the state of Arizona, the greater Southwest and around the world to provide next-generation education, research and outreach. A major economic engine, Health Sciences employs nearly 5,000 people, has approximately 4,000 students and 900 faculty members, and garners $200 million in research grants and contracts annually. For more information: uahs.arizona.edu (Follow us: Facebook | Twitter | YouTube | LinkedIn | Instagram).