A possible answer to saving a broken heart

The phrase “to die of a broken heart” has often been used in the metaphorical sense, but new research shows it could be literal, too.

Researchers at The University of Texas Health Science Center at Houston have found a link between depression and higher levels of an inflammatory protein in the blood that can put people at risk for heart disease and stroke.

Common sense tells us that those who suffer from depression are less likely to maintain healthy eating habits, exercise regimens and social engagements. That depression-induced lethargy can set off a domino effect that leads to health issues, but the clinical explanation for the connection between depression and comorbid diseases was unclear to scientists.

“We know that stress is associated with cardiovascular disease, but it’s really unclear what translates the impact of the psychosocial stress to the body such that the body is at risk for coronary artery syndromes, including heart attack or unstable angina,” said Alan Prossin, M.B.B.S., assistant professor in the Department of Psychiatry and Behavioral Sciences at John P. and Kathrine G. McGovern Medical School, who led one of the studies.

Prossin said he was inspired by his mentor’s research in PET studies that looked at the brain’s opioid receptors. The opioid system helps modulate pleasure, pain and reward sensations, as well as anxiety symptoms.

“I thought this would be a really good neurotransmitter system to investigate mind-body interactions because the opioid system in the brain is very tightly connected with pain syndromes in the body,” Prossin said. “We know that if people feel depressed, they get stronger pain sensations in their lower back, etc.”

He and his team added an immune component to his mentor’s research and quantified the levels of an inflammatory cytokine associated with cardiovascular disease called interleukin-18. When he and his team noticed that psychosocial stress was impacting peripheral inflammatory markers, he said he went on to further test whether the stress-induced immune changes in the blood were related to the brain’s opioid system response to the same stress.

They evaluated a total of 28 people, 15 with a major depressive disorder and 13 healthy controls, all of whom completed PET scans. When researchers triggered a depressive emotional reaction by instructing test subjects to focus on a sad memory, Prossin discovered that those who suffered from depression exhibited both higher levels of opioids released in the brain and greater increase in IL-18 concentration in the blood. The increase in opioids and Il-18 were much more prominent in the depressed individuals than in the healthy controls.

“These effects were observed during sadness in both groups, but were much greater in people with major depression as compared to non-depressed, otherwise healthy people,” Prossin said.

When researchers asked depressed individuals to focus on neutral thoughts, their levels of IL-18 were reduced even after researchers triggered sad emotional reactions.

“This is potentially a new pathway associated with stress-related affective changes that could explain why treatments based on classic stress hormones may not be as effective in depressed people with stress-related mood changes,” Prossin said.

Prossin said his findings, which were published in the August 2015 issue of Molecular Psychiatry, are initial data that still need to be studied further. Although he and his team will need to replicate and validate his findings with larger studies to accurately see how the data translates to the general population, these initial findings could open the door to more focused studies in the future that could more definitively prove whether treating depression can reverse some of the risk for heart disease.

In a similar ongoing research project, Lorraine Frazier, Ph.D., dean of the UTHealth School of Nursing, also studied the correlation between depression and heart disease. In her nearly decade-long study, titled “Depressive Symptoms and Genetic Influences on Cardiac Outcomes,” she focuses on the impact of behavior and genetics on patients diagnosed with acute coronary syndromes. While Prossin studied concentration of IL-18, Frazier looked at those of five other proteins, including IL-6, another interleukin in the inflammatory response system, and tumor necrosis factor alpha (TNFα), a cell signaling protein involved with systemic inflammation.

“We looked to see if there could be a genetic component or mutation in [patients’] inflammatory markers that causes that spike in inflammation as it relates to depression,” Frazier said. “We don’t know the answer to that yet, but we do know that, in patients with depression, their outcomes are worse.”

Frazier said women who suffered from depression reported different depressive symptoms than men, namely somatic symptoms such as appetite and sleep disturbances. Because of the increase in those types of symptoms, Frazier said doctors should take a more holistic approach in evaluating patients by screening women for depression if they complain about symptoms such as loss of appetite or trouble sleeping — a test that could play an important role in her coronary health going forward.

“The symptoms of heart disease can be caused by many pathways and we know that it’s the clinical symptom of the heart attack that brings people to the hospital. We’re trying to understand if there is a population whose depression is really critical in their coronary outcomes, and we should look at people who have major depression,” she said.

While Frazier and Prossin continue to explore the link between depression and heart disease, one thing remains clear: A happy heart is a healthy heart.

“At this point, from a general health maintenance perspective, if people improve their overall mental health, particularly those who are depressed, then it’s much more likely they’ll exercise, start interacting with people and be able to deal with stress in a more efficient, healthy manner — all of which we believe will have an impact on reducing risk for heart disease,” Prossin said.