Research conducted by Elaine Setiawan, Ph.D., a 2013 NARSAD Young Investigator grantee, and her colleagues provides the first evidence of a link between inflammation of brain cells––neuroinflammation––and major depressive disorder (MDD). The team’s results were reported January 28th in JAMA Psychiatry.

Although some scientists have suspected that neuroinflammation can play a causal role in MDD, it has been difficult to prove. Inflammation often occurs when the immune system is active. It is known that activation of the immune system causes behaviors that are present during major depressive episodes, including low mood, inability to experience pleasure, weight loss, and even anorexia.

Yet until now, neuroinflammation has not actually been observed in a living patient during a major depressive episode. There has been some evidence of the link between inflammation and depression in the analysis of postmortem brain tissue. Dr. Setiawan and her colleagues used a new dye that is visible on brain scans of patients, which led them to correlate neuroinflammation with the severity of depression symptoms.

The team of scientists was led by Jeffrey Meyer, M.D., Ph.D., of the University of Toronto and included five other past NARSAD grant recipients.* They performed PET scans on 20 adults with MDD and 20 adults who did not have MDD. The team wanted to see whether the biological marker of neuroinflammation (called translocator protein) that is visible with the new dye would be elevated in regions of the brain that regulate mood. They also wanted to see whether higher levels of the marker corresponded with more severe symptoms. They were able to show that both of these hypotheses were correct.

The team said its findings “provide the most compelling evidence to date of brain inflammation” in major depression. Specifically, this study is the first to see activation of immune cells called microglia that live in the brain and central nervous system. Activation of these cells indicates the immune system is active, in response to a threat.

Finding active microglia in the brains of people with MDD “is important for improving treatment,” Dr. Setiawan says, “because it implies that therapeutics that reduce microglial activation should be promising for treating major depression.”

The team cautions that linking inflammation and depression does not necessarily mean that one causes the other. In theory, both can be caused by separate things, or one can make the other more likely. None of these relationships can be demonstrated in this study. But Dr. Setiawan and colleagues say they “favor a causal mechanism of neuroinflammation contributing to depressive symptoms.”  

* Other NARSAD grantees involved in this research:

• Romina Mizrahi, M.D., Ph.D. - 2014 Independent Investigator (II), 2010 Young Investigator (YI)
• Grazyna Rajkowska, Ph.D. - 1995 YI, 1999 II
• James L. Kennedy, M.D. - 1988, 1989, 1990 YI, 1995 II, 2013 Distinguished Investigator, Scientific Council Member
• Paraskevi Vivien Rekkas, Ph.D. - 1998, 2000, 2013 YI
• Jeffrey H. Meyer, M.D., Ph.D. - 2000 YI

Read the abstract.