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Antidepressants may enhance anti-HIV activity.

SAN JUAN, P.R. -- A selective serotonin reuptake inhibitor can enhance killer lymphocyte activity against HIV infection, according to preliminary study findings.

Depression may raise the risk of morbidity and mortality in patients with many medical conditions, including HIV infection. In addition, depression has been linked to immune function deficits, such as decreased natural killer cell activity, according to a presentation at the annual meeting of the American College of Psychiatrists.

In normal physiology, natural killer cells defend against viral infections and eliminate neoplastic cells. Natural killer cells are a focus of the ongoing HIV in Women: Depression and Immunity study, funded by the National Institute of Mental Health.

In this study of 40 women, a blood sample was obtained from each subject, and the researchers then treated the sample with citalopram and/or

a substance P antagonist (an experimental agent); they then measured natural killer cell activity in vitro. They found that such treatment could reverse the detrimental effect of HIV on natural killer cell activity.

These preliminary data are "hot off the press," Dr. Dwight L. Evans said. "Next we need to look at this in a real in vivo situation."

"These findings ... suggest that killer lymphocyte antiviral activity is enhanced by an SSRI and the substance P antagonist," said Dr. Evans, the Ruth Meltzer Professor and chair of psychiatry at the University of Pennsylvania in Philadelphia.

"The reason we focused on natural killer cells--or killer lymphocytes as they are now known--is they kill or lyse HIV-1 infected cells and secrete chemokines and cytokines," Dr. Evans said.

Cytotoxic T lymphocytes also lyse HIV-infected cells and secrete HIV-suppressive factors. Severe life stress decreases both these natural killer cells and cytotoxic T lymphocytes, he added.

In another study, Dr. Evans and his associates found that resolution of major depression was associated with increased natural killer cell activity in HIV-seropositive women (Am. J. Psychiatry 2005; 162:2125-30).

The investigators assessed 57 women over 2 years and found that variations in natural killer cell levels corresponded to changes in depression status and ratings on the 17-item Hamilton Depression Rating Scale. Major depression in 11 participants resolved over time, with a simultaneous and significant increase in natural killer cell activity, which returned to normal levels.

"This study suggests that depression may impair certain aspects of innate cellular immunity relevant to delaying the progression of HIV disease and that these alterations are reversible with the resolution of a depressive episode," the investigators wrote.

"We don't know if this is a resolution of depression or if it's a direct effect of the treatment on the immune system," Dr. Evans added.

Researchers are assessing other potential mechanisms that may influence immunity and HIV disease progression, including hyperactivity of the hypothalamic-pituitary-adrenal axis and increases in substance P. Studies have shown that HIV-positive men have elevated substance P levels, compared with HIV-negative men, Dr. Evans said.

"Depression is really bad for the brain, bad for the body," Dr. Evans said. The physiologic changes that have been associated with depression include suppression of cell-mediated immunity, decreased neurogenesis in the brain, decreased heart rate variability, increased platelets, hyperactivity of the hypothalamic-pituitary-adrenal axis, and increased insulin resistance.

Dr. Evans has published an article on the topic titled, "Mood Disorders in the Medically Ill: Scientific Review and Recommendations" (Biol. Psychiatry 2005;58:175-89). "We're trying to get this issue in front of our other colleagues in medicine," he said.


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Title Annotation:drug use
Author:McNamara, Damian
Publication:Clinical Psychiatry News
Geographic Code:1U0PR
Date:May 1, 2006
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