People with depression are at greater risk of developing heart failure, and
people with heart failure are prone to develop depression, which exacerbates
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
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.
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
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.
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
All patients had higher-than-normal levels of each cytokine. But TNFα
was markedly higher in patients who reported feeling depressed on a regular
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.
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
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
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>.▪