People suffering from clinical depression have marked levels of inflammation in their brains, a new study reveals. The findings, published today in JAMA Psychiatry, provide key insight into the biological causes of depressive disorders and could have important implications for developing new treatments for depression.
Major depressive disorder (MDD) remains a highly prevalent disease, with an estimated 15 to 20 percent of the population experiencing MDD at some point in their lifetime. Recurrence rates are high — 50 percent for first-episode patients and 80 percent for second-episode patients — and pharmacological therapy, the most common approach to treatment, often proves insufficient. Due in large part to its chronicity, MDD is now the leading cause of disability in the U.S. and the second-leading cause of disability worldwide.
While we know that depression and other mental health problems arise when something goes wrong with brain function, what causes that malfunction remains unknown. Now, scientists have found a major new clue that points to brain inflammation as a contributing factor.
“This finding provides the most compelling evidence to date of brain inflammation during a major depressive episode,” says senior author Dr. Jeffrey Meyer of the Center for Addiction and Mental Health (CAMH). “Previous studies have looked at markers of inflammation in blood, but this is the first definitive evidence found in the brain.”
Specifically, Dr. Meyer’s research team was able to measure the activation of immune cells, known as microglia, that play a key role in the brain’s inflammatory response.
To investigate whether brain inflammation was increased in people during clinical depression, Dr. Meyer and his team conducted brain scans on 20 patients with depression but who were otherwise healthy and 20 healthy control participants using a brain imaging technique called positron emission tomography (PET). Results showed a significant elevation of brain inflammation in participants with depression. Rates of inflammation were also highest among those with the most severe depression.
Although the process of inflammation is one way that the brain protects itself — similar to the inflammation of a sprained ankle — too much inflammation may not be helpful and can be damaging. A growing body of evidence suggests that inflammation may play a key role in generating the symptoms of a major depressive episode such as low mood, loss of appetite, and inability to sleep. But what was previously unclear was whether inflammation played a role in clinical depression independent of any other physical illness.
“This discovery has important implications for developing new treatments for a significant group of people who suffer from depression,” says Dr. Meyer, who also holds a Canada Research Chair in the neurochemistry of major depression. “It provides a potential new target to either reverse the brain inflammation or shift to a more positive repair role, with the idea that it would alleviate symptoms.”
The drive to uncover new ways to target and treat depression is fueled by the reality that more than half of people with major depression do not respond to antidepressant medications. Current treatments do not target inflammation, but Dr. Meyer says treating depression with anti-inflammatories is one avenue for future research.
“Depression is a complex illness and we know that it takes more than one biological change to tip someone into an episode,” says Dr. Meyer. “But we now believe that inflammation in the brain is one of these changes and that’s an important step forward.”