Immune cells in the brain – a link between inflammation and depression

One in four people in Sweden will be affected at some time in their life by a depression so serious that it requires treatment. Wouldn’t it be great if we could understand the brain circuits that determine the way we feel, and find new and better treatments? Meet Professor David Engblom of LiU. 

Professor David Engblom. Per Groth

- I have always been fascinated by the brain, even before I started working on it. The brain is intimately linked with the self and I find it an incredibly exciting organ. ‘Your brain defines you’ in a completely different manner than ‘Your liver defines you’, says Professor David Engblom.

David Engblom started his pathway into research when studying medicine at Linköping University and felt immediately at home – so much so that he chose to make research his full-time career. After a PhD and a three-year post doc in Germany, he returned to LiU 10 years ago and now leads his own research group at the Center for Social and Affective Neuroscience (CSAN) in the Department of Clinical and Experimental Medicine (IKE).

The group is studying how inflammatory diseases or active inflammations in the body influence the circuits of nerve cells in the brain that determine how we feel – optimistic or depressed. When we are healthy, these circuits are in balance, but this can be disturbed when we suffer from certain diseases.

Link between inflammation and depression

Stained immune cells.Stained immunecells (microglia) in the brain. Photo credit: David EngblomThe most recent study carried out by the group showed that certain brain cells of the immune system, microglial cells, are activated in experimental models of inflammation. This, in turn, leads to a feeling of unease and we become despondent (see box).

If you have an inflammation that causes you to feel poorly, the brain cells of the immune system will, in other words, act as a link between the cells of the immune system that have been activated in the body outside of the brain and the brain’s punishment system. You feel uneasy, retreat into your shell, and become depressed.

- We’re interested in this not simply from curiosity. Our findings showing why you feel depressed when you have, for example, influenza, are extremely clinically interesting for people with chronic inflammatory diseases such as rheumatism and multiple sclerosis, says David Engblom.

Several studies have suggested that inflammation can be a contributing factor in depression. Scientists have identified a subgroup among people with depression who show increased inflammatory activity. They have also shown that there is an increased risk of suffering from depression during chronic inflammatory diseases.

The importance of behavioural models 

It is, however, not easy to study depression. An inflammation in the body outside of the brain changes the levels of hundreds of molecules in many parts of the brain. Only a few of these are important in determining how you feel.

-There are currently no molecular or cellular changes that psychiatrists can use directly to determine whether a person is depressed or not. Ultimately, therefore, it is often behaviour and models that are important for our understanding. It remains to be seen whether the mechanisms that we have identified in slightly more acute inflammatory models are active and relevant in people with depression, says David Engblom.

Excellent conditions at LiU and RÖ

The excellent conditions that allow a coupling between basic research and clinical research at Linköping University and Region Östergötland will play a major role in further research. An ongoing clinical study, led by Professor Markus Heilig and Senior Lecturer Paul Hamilton at the Psychiatry Clinic, Linköping University Hospital, involves giving a specific anti-inflammatory treatment against a molecule known as IL-6 to people with depression and an increased inflammatory response. It is hoped that the treatment will help to alleviate the depression. If a positive effect can be shown in the clinical study, David Engblom and his research group will continue to study the system in the laboratory.

Translated by George Farrants


Brief Facts

Inflammation and depression

When an inflammation is present, the body’s defensive cells (immune cells) release small molecules (cytokines) that activate several defence mechanisms. The cytokines bind to the walls of blood vessels (the endothelium), which release a signal that activates the brain’s immune cells (microglial cells). The microglial cells in turn manufacture hormone-like fatty acids (prostaglandins), that act by binding to nerve cells in the reward circuits of the brain and weakening the “I’m fine” signal. The result is that the person feels depressed, uneasy and despondent.

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