Depression, Antidepressants, and HIV-Infectivity Abstract The medical burden of depression is increasing and the World Health Organization projects that by the year 2020, depression will be the second leading cause of disability worldwide. An increasing number of studies have implicated depression as a potential risk factor in the morbidity and mortality for a wide range of human diseases, including HIV/AIDS. Although the underlying immune mechanisms by which depression influences HIV disease progression and mortality remain to be determined, considerable evidence suggests that killer lymphocytes play key roles in regulating HIV infection and are altered in depression. In our studies of individuals who are depressed, but otherwise medically healthy, we have found depression-associated decreases in natural killer (NK) cytolytic activity. In studies of HIV-infected individuals, we have shown that depression is associated with a reduction in NK cytolytic activity and an increase in HIV disease progression. We have recently demonstrated that resolution of depression is associated with restoration of NK cytotoxicity in HIV, and we have found that ex vivo treatment of lymphocytes with an SSRI enhances NK cytolytic activity. We have also observed that an SSRI and a glucocorticoid antagonist inhibit HIV infectivity of macrophages in HIV. The proposed study of depressed, HIV-seronegative individuals is designed to test whether depression is associated with non-cytolytic, chemokine and cytokine, functional alterations of killer lymphocytes, as well as chemokine receptor sensitivity of macrophages and T-cells that are relevant to HIV- infectivity. We will study the role of serotonin and glucocorticoids (GCs) by comparing killer lymphocyte function in macrophage and T-cell HIV receptor response before and after exposure to an SSRI and a GC antagonist. Previous studies of depression and HIV have focused on cytolytic function of killer lymphocytes. A unique strength of the proposed study is the emphasis on the non-cytolytic functions and the effects of depression and anti- depressants on these factors which have HIV suppressive activity. Thus, the proposed study is designed to determine if depression increases the susceptibility to HIV-infectivity, to determine if anti-depressants decrease the susceptibility to HIV-infectivity, and to determine specific HIV suppressive factors that may underlie susceptibility to HIV-infectivity in depression. This study also may help determine if anti-depressant clinical trials are warranted in depressed HIV-infected individuals in order to enhance clinical management and improve morbidity and mortality of HIV infection. -1a- The medical burden of depression is increasing and the World Health Organization projects that by the year 2020, depression will be the second leading cause of disability worldwide. An increasing number of studies have implicated depression as a potential risk factor in the morbidity and mortality for a wide range of human diseases, including HIV/AIDS. The proposed study is designed to determine if depression increases the susceptibility to HIV-infectivity, to determine if anti-depressants decrease the susceptibility to HIV-infectivity, and to determine specific HIV suppressive factors that may underlie susceptibility to HIV-infectivity in depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH082670-05
Application #
8242066
Study Section
Behavioral and Social Consequences of HIV/AIDS Study Section (BSCH)
Program Officer
Stoff, David M
Project Start
2008-04-24
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2014-03-31
Support Year
5
Fiscal Year
2012
Total Cost
$634,288
Indirect Cost
$148,731
Name
University of Pennsylvania
Department
Psychiatry
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Blume, Joshua; Douglas, Steven D; Evans, Dwight L (2011) Immune suppression and immune activation in depression. Brain Behav Immun 25:221-9