Mild depression breeds prolonged inflammation in caregivers

October 13, 2003

COLUMBUS, Ohio -- Even mild depression can substantially unbalance the human immune system and that change can be pivotal in setting older Americans up for developing serious age-related diseases.

These findings, published today in the Archives of General Psychiatry, are the latest from a quarter-century-long body of research aimed at unraveling the link between increased stress and weakened immunity.

A key conclusion from this study is that a persons mental health really does matter, explained Janice Kiecolt-Glaser, professor of psychiatry and psychology at Ohio State University. From this work, we get a clear picture of how the body responds differently depending on whether a person is even mildly depressed or not.

The researchers looked at a group of 47 people who were either current or former caregivers at the time of the study. In the case of each of these people, their spouse either had Alzheimers disease or some other form of progressive dementia. This group was matched with a somewhat larger control group of people who were not caregivers.

Blood samples were drawn from each person in the study just before they received their annual influenza vaccination and then again approximately two weeks after the injection. In addition to analyzing the blood samples, each participant completed a survey form intended to gauge their level of depression.

Kiecolt-Glaser and colleague Ronald Glaser, a professor of molecular virology, immunology and genetics, had predicted there would be a link between a persons depressive status and the levels of a specific immune system component Interleukin-6 (IL-6) found in the blood.

The survey showed that present and former caregivers had modest levels of depression, Kiecolt-Glaser said. These people are not clinically depressed. On the other hand, clearly things are not right with their world, she said.

Caregivers felt blue and probably were suffering from some kind of sleep disturbance. They also reported having less energy than normal. All these symptoms had been there for some time.

When the blood samples were analyzed, the depressed caregivers IL-6 levels were 30 percent higher two weeks after the influenza vaccination while the non-depressed participants IL-6 levels were essentially unchanged, Glaser said.

The absence of an overall increase in IL-6 from baseline to after vaccination in the control group is consistent with what we would have expected, Glaser said.

Generally speaking, there is very little inflammatory response including the production of IL-6 in people who have already been exposed to the virus for which they are being vaccinated.

Because these were older people, most of them already had been exposed to influenza virus. Therefore, the significant increase in IL-6 that we found in the caregivers after vaccination is unexpected and important, primarily because it suggests that even low levels of depression are associated with an increased IL-6 response to an antigen, he said.

Sustained higher-than-normal levels of IL-6 have been linked long-term inflammation which, in turn, is implicated in a host of age-related illnesses. These include cardiovascular disease, osteoporosis, arthritis, type-2 diabetes, certain lymphoproliferative diseases and cancers, Alzheimers disease and periodontal disease, the researchers said.

Chronic inflammation has been suggested as one key biological mechanism that may fuel declines in physical function leading to frailty, disability and, ultimately, death, they wrote.

The immune system has to be balanced, Glaser said. If it is accelerated, that is bad and if it is weakened, that is also bad. The body is as amazingly fine-tuned as is a good watch.

The researchers used influenza vaccinations in this study as a surrogate for other pathogens and the public shouldnt interpret these results as reasons to avoid the vaccinations, Kiecolt-Glaser said.

These findings provide a good reason why people should definitely get a flu shot no matter what, she said. Earlier studies showed that if you are depressed, then you are more likely to get sick. This research shows that there are long-term changes taking place in your immune system so we should be more cautious as we age.

Along with Kiecolt-Glaser and Glaser, other researchers on the project included William Malarkey, professor of internal medicine; John Sheridan, professor of oral biology; and Theodore Robles, a doctoral student in psychology.
-end-
This research was supported by the National Institutes of Health, the National Institute of Health Clinical Research Center, Ohio State Universitys Comprehensive Cancer Center and the National Science Foundation. Contact: Ronald Glaser, 614-292-5526; Glaser.1@osu.edu.
Written by Earle Holland, 614-292-8384; Holland.8@osu.edu.

Ohio State University

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