Cytokines Play Crucial Role In Depression-Cardiac Link
People with depression are at greater risk of developing heart failure, and people with heart failure are prone to develop depression, which exacerbates heart disease.
The pathophysiologic link between the two has been attributed to elevated levels of cytokines, the proinflammatory proteins secreted by the immune system after injury or infection. Cytokines are known to damage the myocardium, are elevated in heart failure, and have been associated with major depressive disorders.
Now a study at the Ohio State University School of Public Health provides a clearer picture of how cytokines are associated with depression and how their elevation could provide the basis for the additive effect of depression on adverse outcomes in heart failure. The study was published in the July American Heart Journal.
“Patients with heart disease are prone to developing depression. Physicians need to pay more attention to this.”
Not only does depression raise the level of cytokines, but also one cytokine in particular may speed the progress of heart failure, according to Amy Ferketich, Ph.D., lead author
“People with heart failure typically have much higher levels of tissue necrosis factor alpha [TNFα] than those without the disease, but depression seems to make the levels of this cytokine go even higher, which is bad for heart patients,” said Ferketich, an assistant professor of public health at Ohio State.
In their study, Ferketich and coworkers compared the levels of proinflammatory cytokines in heart failure patients with and without depression.
Symptoms of depression in 32 patients recruited from the heart failure clinic at Ohio State University were measured using the 21-question Beck Depression Inventory (BDI). Blood samples were tested for TNFα, interleukin-6 (IL-6), and interleukin-1beta (IL-1β), all of which are known to cause inflammation and are elevated in heart failure patients.
Does Depression Trigger TNFα Production?
Subjects with a BDI score of 10 or higher had levels of TNFα nearly twice that of those with a score of less than 10 (4.9 pg/ml vs 2.7 pg/ml; pg is the abbreviation of picogram, a trillionth of a gram).
“Depression clearly raises the levels of one cytokine that plays a role in increasing inflammation,” Ferketich said. “What we don't know for sure is if depression causes the inflammation that may lead to heart failure or if heart failure causes depression that accelerates inflammation.”
All patients had higher-than-normal levels of each cytokine. But TNFα was markedly higher in patients who reported feeling depressed on a regular basis.
Levels of the other two cytokines were similar for depressed and nondepressed patients: 5.9 pg/ml vs. 5.1 pg/ml for IL-6 and 4.4 pg/ml and 3.6 pg/ml for IL-1β, respectively.
“We were surprised to find that this was not the case for the other two cytokines, suggesting that something about depression may trigger the production of TNFα,” she said.
Ferketich believes this is an important finding because the total BDI score may be influenced by both an intrinsic cognitive-affective disorder and the physical symptoms of heart failure. The relationship was still present when the physical symptoms of depression were removed from the BDI total score, suggesting there might be a true association between depression and TNFα in heart failure patients.
Study Paves Way for Prevention
Despite the promising results in her study, many questions remain, Ferketich said. As stated previously, it is not known whether depression causes the inflammation that may lead to heart failure or heart failure causes depression that accelerates inflammation. Also, it is not clear why similar relations between elevated symptoms of depression and levels of IL-6 and IL-1β were not found. The patients without symptoms of depression had higher levels of IL-6 than other studies have reported. She believes some of the discrepancies might be due to the small sample size in her study.
“Patients with heart disease are prone to developing depression,” Ferketich said. “Physicians need to pay more attention to this. But research still needs to be done to find out if treating patients with antidepressants would help to actually slow the progression of heart disease.”
Commenting on the study, Radu Saveanu, M.D., chair of the Department of Psychiatry at Ohio State, told Psychiatric News that “this line of investigation is extremely important and timely. It is relevant to psychiatrists in that it better identifies the link between the immune system and stress and the role stress has on immunity and depression, as well as the effect that stress and depression have on the cardiac system.
“It's only been in the last few years that we've begun to understand the [effect] that stress and now depression causes on the endocrine system and the effect the endocrine system has on the immune system and the changes in cytokines. I think a lot more work needs to be done to further [Ferketich's] investigations. Ultimately, the impact it has on psychiatry has to do with our ability to know when to provide early detection of patients who may be under a lot of stress or suffering from minor or severe depression, and who among those patients should be treated early to prevent any cardiac events or to prevent recurrence of cardiac events. The other thing that we need to understand is what kind of treatment is best for those patients who have cardiac disease.”
The study was supported by the National Institutes of Health's National Heart, Lung, and Blood Institute.
An abstract of “Depressive Symptoms and Inflammation Among Heart Failure Patients” is posted at<www.ahjonline.com/article/PIIS0002870304005770/abstract>.▪
