Brain on fire: inflammation and mental health

SIU Images (Lucie Pessel Vivares) 

SIU Images (Lucie Pessel Vivares) 

Author: Layal Liverpool Edited by: Isabel Wassing

Depression, or major depressive disorder, is a mental disorder that is characterised by persistent low mood. Whereas most people go through periods where they feel down, people who suffer from depression can feel continuously down for weeks, months or longer periods of time. Depression is a leading cause of disability worldwide and only two thirds of patients respond to treatment with conventional anti-depressants. There is an urgent need for more effective treatments.

Depression has been associated with signs of inflammation, which is usually the body’s response to harm, for example to an infection. Recent research explores the link between depression and inflammation to determine whether this could be an important avenue for the development of new treatments.

Some individuals with major depressive disorder have increased levels of molecules called cytokines in their circulation. Cytokines can be thought of as the messenger molecules of the immune system, alerting the body to danger. In the case of an infection, this activates immune responses that eliminate the infection. However, in the case of depression, these cytokines can cause unwanted inflammation in the brain.

Inflammation in the brain activates immune cells called microglia, which interfere with the normal production of the mood-influencing molecule serotonin. Serotonin is well known for contributing to feelings of happiness and well-being and so it is perhaps unsurprising that these disruptions to serotonin production can lead to depression.

One recent study further investigated this contribution of microglia - the brain’s immune cells – to inflammation in patients suffering from major depressive disorder. The researchers looked for markers of inflammation in the brains of patients using positron emission tomography (PET) scans, which can produce detailed 3D images of the inside of the body. They found increased levels of a key inflammatory marker on microglia in the brains of patients experiencing suicidal thoughts, which adds to mounting evidence of a link between inflammation and suicide.

Although this study had relatively few participants, this finding warrants further investigation, particularly into the potential of inflammatory mediators as new therapeutic targets. Indeed, anti-inflammatory agents are already being trialled in patients with major depressive disorder who also have heightened inflammation.

This is not the only study linking mental health and the immune system. Inflammation has long been thought to play a central role in chronic fatigue syndrome, a debilitating condition characterised by unexplained fatigue. In a recent study comparing chronic fatigue syndrome patients to healthy counterparts, scientists found that cytokine levels did in fact differ between these two groups. Higher cytokine levels were associated with more severe disease.

While the underlying cause behind the ‘overactivation’ of the immune system in these conditions is not yet fully understood, these recent findings highlight an important area for future research in order to improve treatment of psychological conditions.


1.      Holmes, S. E. et al. Elevated Translocator Protein in Anterior Cingulate in Major Depression and a Role for Inflammation in Suicidal Thinking: A Positron Emission Tomography Study. Biological Psychiatry 83, 61–69 (2018).

2.      Montoya, J. G. et al. Cytokine signature associated with disease severity in chronic fatigue syndrome patients. Proceedings of the National Academy of Sciences of the United States of America 114, E7150–E7158 (2017).