Posted by jrbecker on August 20, 2004, at 14:41:27
8/19/2004 - Scientists build on case connecting inflammatory disease and depression - Depression
2004 AUG 18 - -- Feeling sick can be "all in the head" for people with inflammatory disorders or for those receiving immunotherapy, say Robert Dantzer and Keith Kelley, professors in the department of animal sciences at the University of Illinois at Urbana-Champaign.
NewsRxImmunotherapy via NewsEdge Corporation : 2004 AUG 18 - (NewsRx.com & NewsRx.net) -- Feeling sick can be "all in the head" for people with inflammatory disorders or for those receiving immunotherapy, say Robert Dantzer and Keith Kelley, professors in the department of animal sciences at the University of Illinois at Urbana-Champaign."For the first time, we have evidence of a strong relationship between a molecular event and the development of psychopathology," Dantzer said.
The two scientists, who have collaborated for 25 years, have identified how a molecular pathway in the brain may explain why some patients suffering from inflammatory diseases develop depression. "The goal of our research is to understand the mechanisms that are responsible for causing depression in patients with inflammatory diseases," Dantzer said.
Depressive disorders occur in 12-30% of patients who suffer from various diseases with an inflammatory component, including coronary heart disease and autoimmune diseases such as rheumatoid arthritis and inflammatory bowels. These mood disorders usually are attributed to psychological problems encountered by patients having to deal with the suffering and disability brought about by their diseases.
However, Dantzer and Kelley explained, research on patients whose immune systems are boosted by immunotherapy challenge this view and suggest that depression may originate in the immune system. Immunotherapy is used to treat patients who suffer either from kidney cancer or melanoma with metastasis, or from viral infections such as hepatitis C and AIDS.
"A few thousand cancer patients and several hundreds of thousands of hepatitis C patients are treated each year with immunotherapy," Dantzer said.
Immunotherapy involves the injections of cytokines, which are chemicals normally made by immune cells that boost the immune system to fight infectious pathogens and kill cancer cells. Unfortunately, immunotherapy also causes depression in 33% of patients, as reported by Dantzer in 2002.
Symptoms of depression begin within days to weeks of beginning treatment and vanish once it ends. "The occurrence of depression in cytokine-treated patients indicates that treatment must be discontinued since depressed patients can commit suicide," he said.
For about 30 years, depression has been linked to low levels of serotonin, a brain chemical that regulates mood. Drugs called selective serotonin reuptake inhibitors (SSRIs) such as Prozac ease depression by elevating serotonin levels.
"Although SSRIs can be used to treat immunotherapy-induced depression, they are not 100% effective and will not prevent suicide in patients with suicidal thoughts," Dantzer said. "Clinical studies are investigating whether SSRI treatment could be used in a preventative manner if it were possible to identify in advance those vulnerable patients."
Since the 1980s, medical professionals have observed that patients treated with cytokines experience a greater occurrence of depression. Until recently, the mechanisms of depression during cytokine therapy have remained unclear. By exploring potential mechanisms, Dantzer and Kelley hope to help patients avoid depression while benefiting from the immune-boosting effects of cytokine treatments.
This summer, they started a series of experiments on mice, whose immune responses are similar to those in humans, to show how cytokine treatment causes serotonin depletion. The work is funded by a newly awarded $1.7 million 5-year grant from the U.S. National Institute of Mental Health.
Dantzer and Kelley hypothesize that cytokines suppress serotonin by activating an enzyme called indoleamine-2,3-dioxygenase (IDO) that catabolizes tryptophan, an essential amino acid provided by ingested food. In the brain, IDO prevents tryptophan from being turned into serotonin, which causes decreased levels of serotonin and leads to the symptoms of depression.
Dantzer and Kelley will seek to identify specific brain areas where cytokines activate IDO and where serotonin levels differ. They theorize that the same brain areas related to depression will show increased IDO activation and decreased serotonin levels.
They also will evaluate potential treatments that may ease cytokine-caused depression. Oxidizing agents and free radicals activate IDO. Antioxidants will be used in an effort to decrease the free radicals, which may decrease the IDO activation. By suppressing the IDO activity, tryptophan should be available to be converted to serotonin, the researchers believe. If antioxidant treatment proves effective in the mice, then human patients eventually may benefit from the approach.
This article was prepared by Immunotherapy Weekly editors from staff and other reports. Copyright 2004, Immunotherapy Weekly via NewsRx.com & NewsRx.net. .end (paragraph)<>
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