Inflammatory Markers Altered in Depression and Suicide

Inflammation is a hot topic in medical research, with studies showing links to heart disease, dementia and longevity. Depression is a relatively new addition to the list of inflammation-associated diseases, with two recent publications demonstrating altered levels of inflammatory molecules in the blood of patients with major depressive disorder (MDD). Both studies evaluated the levels of cytokines in patient’s blood.

Cytokines are proteins produced by a variety of different cell types, most commonly cells of the immune system. They can circulate in the blood stream or stay localized in certain tissues, and serve as communication signals between cells. Both pro- and anti-inflammatory cytokines are recognized and the effects of different cytokine molecules are wide-ranging.

In the first study, depressed patients who did not respond to pharmacological treatment with escitalopram (Lexapro) had increased levels of tumor necrosis factor-alpha (TNF-alpha). TNF-alpha is a potent cytokine with a variety of cellular activities, including effects on cell death and reproduction, systemic inflammation and control of viral replication. TNF-alpha has proinflammatory effects throughout the body. When release during acute inflammation, it causes fever, loss of appetite, activation of immune cells and release of cortisol, a major stress hormone.

A second study compared levels of cytokines produced in the laboratory by blood cells from non-suicidal and suicidal MDD patients and normal controls. Non-suicidal MDD patients had increased levels of interleukin-6 (IL-6), another cytokine associated with acute inflammation and fever. Levels of IL-6 correlated directly with depression severity. Suicidal MDD patients did not have increased levels of IL-6, but instead showed markedly decreased levels of interleukin-2 (IL-2). IL-2 is another proinflammatory cytokine that acts primarily by increasing the activity of the cells of the immune system, in order to fight off infection.

What the increased levels of inflammatory cytokines actually means in depressed patients is uncertain. Prior to these two reports, numerous other investigators have reported aberrant levels of inflammatory cytokines in patients with MDD. The immune system is affected by stress hormones, which are often elevated with depression. It is also possible that these cytokines possess as yet undetermined functions, in addition to their role in inflammation, that directly links them to brain function and the development of depression.

The fact that cytokine levels differed not only from normal controls, but also between suicidal and non-suicidal patients and between responders and nonresponders to pharmacological therapy, further confuses the issue. The relationship is far from clear. However, it is possible that future research will provide more substantial evidence as to the serum cytokine profile in MDD and allow physicians to prescribe directed therapy, based on predicted response to specific medications or risk of suicidal behavior.

References

Eller, T. et al. (2008). Pro-inflammatory cytokines and treatment response to escitalopram in major depressive disorder. Progress in Neuro-psychopharmacology and Biological Psychiatry, 32(2), 445-450.

Kim, Y. et al. (2008). Differences in cytokines between non-suicidal patients and suicidal patients in major depression. Progress in Neuro-psychopharmacology and Biological Psychiatry, 32(2), 356-361.