Over-Reactive Immune System May Play Role in Depression

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Treatments for depression have focused on the brain, replacing deficient neurotransmitters, such as serotonin, that control mood. But scientists think they may have been overlooking another part of the body – the immune system. Could an over-reactive immune system – aka, an allergy to stress – be responsible for some forms of depression?

Researchers at the Mount Sinai Medical Center in New York tested the theory on young mice. During the experiment, the team “stressed out” the animals by exposing them to larger, meaner and older male mice (who often pinned down and bit the younger mice) after measuring inflammatory compounds in the immune system. After a 10-day exposure to “social defeat stress,” the researchers again measured the immune system response.

Mice whose immune systems responded by overproducing an inflammatory compound called Interleukin-6 were more likely to become depressed (expressed by the mouse socially withdrawing) than mice with non-overactive systems. The same compound, a cytokine used for cell-to-cell communication, is elevated in depressed humans, says study researcher Georgia Hodes, a postdoctoral researcher at Mount Sinai.

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IL-6 acts as both a pro-inflammatory and an anti-inflammatory cytokine. It is capable of crossing the blood-brain barrier and initiating responses in the hypothalamus. The hypothalamus controls body temperature, hunger, thirst, fatigue, sleep and circadian cycles, which may be disturbed in depressed patients. This part of the brain also plays a role in social defeat.

The researchers then used a drug that blocks the action of IL-6 in the stressed mice and found that the mice began to act normally. They became resilient and did not show susceptibility to the stressor, notes Hodes.

"There's probably a subset of people with depression who have this over-sensitive inflammatory response to stress and that this is leading to the symptoms of depression," said Hodes. "In some ways, it is an analogy to an allergy. You have something that is not really dangerous, but your body thinks it is, so you have this massive immune response. In this case, the stressor is what they're having this massive immune response to."

The research into the immune system’s role in depression is still very new. The researchers will present their findings at the annual meeting of the Society for Neuroscience in New Orleans today. However, if the results can be replicated, new types of medicines may be produced that may more effectively treat depression.

Source: “Innate Immune System Influences Vulnerability to Anxiety or Depression in Animal Model” Presented at Neuroscience 2012, the annual meeting of the Society for Neuroscience at 330 on October 16, 2012.

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