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Some depression might have roots in immune-generated inflammation

This article was published in Scientific American’s former blog network and reflects the views of the author, not necessarily those of Scientific American


NEW YORK—The immune system works hard to keep us well physically, but might it also be partly to blame for some mental illnesses?

"The immune system may play a significant role in the development of depression," Andrew Miller, a professor of psychiatry and behavioral sciences at Emory University School of Medicine, said Tuesday at a symposium on neuroscience and immunology at the New York Academy of Sciences. Evidence for this link has been mounting in recent years, and he described this research, which falls in the jauntily named field of psychoneuroimmunology, one of the most exciting recent developments in psychiatry.


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Research has shown that depressed or stressed-out people tend to be more susceptible to medical ailments, such as infectious diseases and perhaps even cancer. But the correlation might also work in the opposite direction, Miller explained. People who are critically ill have about five to 10 times higher rates of depression, and that might not just be due to battling their illness, he noted. It could be stemming from underlying inflammation—a common bodily response to illness or injury.

Studies have shown that people with depression or bipolar disorder, both those who had a physical illness and those who were medically healthy, had higher levels of inflammation. And as the depression faded, so, too, did the evidence of inflammation. Similarly, a 2009 study showed that mice that with chronic inflammation showed depressive symptoms, but blocking a key inflammatory enzyme alleviated the downer behavior in the mice.

The big discovery has been that depressed patients who have proved most resistant to traditional treatments (such as therapy or selective serotonin re-uptake inhibitor drugs) seem to have particularly high rates of inflammation. And in studies from the last few years, inhibiting inflammatory cytokines (signaling cells found in both the immune and nervous systems) seems to help alleviate depressive symptoms. Miller said that these results suggest that "cytokines might have an effect on fundamental dopamine synthesis," an important chemical process that, if thrown out of whack, can have big impacts on mood, energy and motivation.

If this association holds, keeping inflammatory cytokines in check could also help treat conditions beyond classic depression, such as cancer-related fatigue or even chronic fatigue syndrome, Miller noted. And because much of the inflammation in question seems to be coming from outside of the brain—the periphery, as the neuroscientists like to call it—new depression-targeting drugs might not even have to cross the blood-brain barrier to have palliative effects.

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