With an intriguing overlap of immune response-associated symptoms and depression, research in this area may lead to better understanding of the biology of depression and may potentially lead to new treatments for depression. Dr. Margaret Kemeny presented information on the effects of depression on immune function. She pointed out that it is important to realize depression is a systemic illness that adversely affects the entire body.
Depression is the most common psychological problem in the US. Minor Depression can be attributed to normal depressed feelings that arise because of a specific life situation, a side effect of medication, hormonal changes or physical illness, and does not usually require treatment. Major Depression (depressive illness) is a serious condition that result in extreme fatigue, sleep problems and eventually an inability to function. The exact cause is unknown, but it is thought to be a malfunction of brain neurotransmitters, which are chemicals that modulate moods. Major Depression is usually treated with a combination of psychotherapy and antidepressants which moderate or correct chemical imbalances in the brain. The group of antidepressants most frequently prescribed is the selective serotonin reuptake inhibitors (SSRIs) which regulate the neurotransmitter serotonin.
Depression has been associated with a decreased number of circulating lymphocytes including T cells, B cells, and particularly natural killer cells, which are involved in the detection and removal of tumor cells. A number of risk factors including age, hospitalization, melancholia, and alcoholism are associated with the altered immune function seen in depressed patients.
There is also evidence of increased production of proinflammatory cytokines in major depression, which appear to normalize during remission, indicating that these alterations may be a state marker. Elevated levels of IL-6, a potent proinflammatory cytokine, have been reported with the highest levels occurring in treatment-resistant depression. The animal literature has also suggested antidepressant treatment may reduce cytokine levels, but the human data are so far mixed (probably due to differences in which cytokines were measured, end points of the studies, drugs used, etc.) Antidepressant administration has also been shown to attenuate the occurrence of sickness following injection of IL-1, another proinflammatory cytokine. These data then lead to the very interesting question: do proinflammatory cytokines cause or contribute to depression?
Several pieces of evidence suggest that cytokines may contribute to depression, at least in some patients. Patients with inflammatory disease show an increased risk of depression, although this of course does not suggest causality. More intriguing is the ability of proinflammatory cytokines such as IL-6 to induce “sickness behavior” in animals, which is associated with sleep disorders, anorexia, and anhedonia. These symptoms mimic many of the cardinal features of depression. Sickness behavior is not inherently maladapative in response to an acute inflammatory process as it lowers energy usage and may help limit the spread of an infection.
As cytokines are predominantly released peripherally in response to inflammatory processes, one important issue is how cytokines get in the brain, which is a logical prerequisite for them to influence depression. Cytokines are detected by the vagus nerve, which then releases cytokines within the central nervous system. There is also evidence of active transport of cytokines across the blood brain barrier. Another important question is whether cytokines are activated in “normal” people without an infection. Maes and colleagues have demonstrated elevated cytokines in students prior to stressful exams, which correlated with self reported stress, but more studies are needed to investigate the involvement of cytokines in the “normal” stress response.
Although it is premature to start measuring cytokines in patients, it provides an interesting framework to aid in our understanding how medical conditions may influence depression.
Revision date: June 20, 2011
Last revised: by Janet A. Staessen, MD, PhD