Generation Scotland


Long-term inflammation may hold a key to understanding depression

Researchers, based at the University of Edinburgh, found that longer-term inflammation was related to changes in brain structure, which may help shed light on causes of depression.

Graph showing the changes in brain structure as described in text
The dotted line indicates the threshold above which results become significant. Each dot represents one observable chracterisic. Each colour represents different types of imaging technology. The diamonds represent observable chracteristics that are also significant after correction.

Depression is the most common mental health condition in adults worldwide, yet we still don’t understand what might lead to people experiencing it.  One leading theory is that inflammation in the body adds to depressive symptoms through effects on the brain.  This leads to symptoms such as tiredness and low mood.  

Earlier research measured inflammation in the blood from a single point in time. This approach is not ideal.  Inflammation levels can change often, like when you have a cold. It also doesn’t capture longer-term (chronic) inflammation.

Long-term inflammation is thought to be more important in understanding changes in brain structure and in depression.  In this study, researchers used Generation Scotland data to study changes that reflect longer-term inflammation. They did so by looking at a biological process called DNA methylation. This process adds chemical groups to DNA, which change the activity of genes. We can use these longer-term changes to study the signature that long-term inflammation leaves on DNA.

We found that the signature of longer-term inflammation was related to changes in the brain. Changes included differences in grey matter and changes to structural connections.  By comparison, the single timepoint blood measure of inflammation was related to current depression symptoms but was not strongly related to brain features.

This research shows that having a long term measure or ‘signature’ of chronic inflammation over a person’s lifetime is related to brain structure. Research using single time point measures are not able to show this. However, more research is needed to find out if targeting medical care at inflammation will be a useful treatment for people with depression.

This work was led by researchers based at the Division of Psychiatry, University of Edinburgh. The publication can be found in the Brain, Behavior, and Immunity journal, linked below.

Structural brain correlates of serum and epigenetic markers of inflammation in major depressive disorder