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The Effect of Interferon-Alpha Treatment on Emotional and Physical Functioning in Patients with Chronic Hepatitis C
Study Details
The overall objective of this study is to identify biological contributions to depression in patients who are medically ill. Depression in the medically ill is a serious public health problem given that it is common (~10-50% of patients depending on the illness) and has been shown to have a significant impact on morbidity and mortality as well as quality of life. Recent developments in our understanding of the impact of innate immune cytokines on the brain have revolutionized our conceptualization of depression in the medically ill. We previously assumed behavioral complications during medical illness were largely psychological in nature. However, we are becoming increasingly aware that these complications have a significant biological component. Innate immune cytokines released by the immune system have been shown to cause neurobiological changes that mimic changes seen in depression including depletion of relevant neurotransmitters and activation of the neuroendocrine system including corticotropin releasing factor. In addition, innate immune cytokines have been shown to induce a syndrome called “sickness behavior” which has many overlapping symptoms with major depression. To study the impact of cytokines on behavior in humans (and depression in the medically ill), clinical studies have focused on individuals receiving the innate immune cytokine, interferon (IFN)-alpha. IFN-alpha is an important early cytokine in viral infection, and although IFN-alpha can be an effective therapy for cancer or infectious diseases such as hepatitis C, patients receiving IFN-alpha exhibit a high rate of central nervous system side effects including depression and fatigue. Following acute administration of IFN-alpha, patients show marked activation of interleukin (IL)-6 (and to a lesser extent TNF-alpha and IL-1) and the hypothalamic pituitary adrenal axis (with the resultant release of glucocorticoids), which in turn correlates with the development of depression.
To further understand the mechanisms by which IFN-alpha causes changes in behavior, in this study we are obtaining behavioral measures (including continuous measures of sleep, body temperature and metabolism), as well as plasma, peripheral blood mononuclear cells and cerebrospinal fluid from patients undergoing IFN-alpha therapy for the treatment of hepatitis C. We are also studying patients who have hepatitis C who are not undergoing IFN-alpha treatment as control subjects. If you are interested in participating in this study, please call (404) 727-8229 or click here for more information.
Miller, A.H., Capuron, L., Raison, C.L. Immunologic influences on emotion regulation. Clin. Neurosci. Res, 4:325-333, 2005.
Capuron, L., Miller, A.H. Cytokines and psychopathology: lessons from interferon alpha. Biological Psychiatry, 56(11):819-24, 2004. |
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