Study: Inflammation Causes Depression in Many Cases

Luke MacGregor / Reuters

Depression is one of the most common mental health problems, affecting about one in 10 Americans every year. And it remains difficult to treat; As many as 50 percent of people don't respond to typical medications.

It used to be widely thought that depression was caused by a "chemical imbalance," and antidepressant drugs still primarily target the neurotransmitter serotonin, seeking to increase its activity in the brain. But new research in the past two decades has uncovered more and more information linking the illness with inflammation, the process the body goes through to fight infection or heal trauma. But inflammation may be present in excessive or harmful levels in depressed people, perhaps triggered by an illness, stress or for some other unknown biochemical reason.

For example, many studies have shown that depressed patients have higher blood levels of cytokines, compounds created by the immune system to promote inflammation and kill pathogens. Another example: When cancer patients take a drug called interferon-alpha, which increases cytokine levels, depressive symptoms often emerge.

But these studies have mostly looked for signs of inflammation in the blood, and not necessarily at the time of a depressive episode. A new study, published Wednesday in the journal JAMA Psychiatry, found significant increases of inflammation within the brains of people who were depressed at the time.

Using a PET scanner, the researchers looked at levels of a protein that is produced by glial cells during neurological inflammation. These cells help support neurons, providing them nourishment and protection from infection, by secreting cytokines and other chemicals that lead to an immune response and inflammation.

The scientists found that the 20 depressed study participants had a 30 percent increase in inflammation in multiple areas of the brain, compared with the 20 participants who didn't suffer from depression, says co-author Jeffrey Meyer, an expert in the neurochemistry of depression at Canada's Centre for Addiction and Mental Health.

This is "really a breakthrough" when it comes to identifying brain inflammation in depressed patients, says Yogesh Dwivedi, a professor of psychiatry at the University of Alabama at Birmingham who wasn't involved in the study. And it definitely shows that "inflammation is the cause of depression in a certain subset of the population," he adds.

What to do now? Meyer's previous work suggests that between 30 and 40 percent of people with depression have increased levels of inflammation, and that these people are unlikely to directly benefit from typical antidepressants, such as selective serotonin reuptake inhibitors like Prozac, that don't have anti-inflammatory properties, he says. So they may benefit from something that directly treats inflammation.

It isn't currently known for sure what existing drugs may treat this type of neurological inflammation, Meyer says, though many groups are looking into it. He and his collaborators plan to test the effects of minocycline, an antibiotic that has the secondary effect of reducing glial inflammation, at least in rodents. And other researchers are looking at other anti-inflammatory agents, such as a chemical called celecoxib.

Unfortunately, it wouldn't be feasible to scan every depressed patient for inflammation, since PET scanning devices aren't available at many hospitals. Meyer hopes that an equivalent blood test could be developed, which might be faster and cheaper than a PET scan.