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Genetic and Inflammatory Biomarkers for Post-Stroke Depression

 Originally written for The Centre for Stroke Recovery, The Centre at Work

Post-stroke depression is very common – and very dangerous. As many as 30 per cent of stroke survivors experience at least one episode of depression. These individuals tend to recover more slowly than people without depression and they have a higher risk of recurrence and mortality.  

Researchers at The Heart and Stroke Foundation Centre for Stroke Recovery (HSFCSR) are working to gain a better understanding of post-stroke depression – what causes it, how it differs from ‘typical’ depression, and whether the presence of certain brain chemicals or biomarkers, combined with a genetic predisposition, can predict it. From their research may come better ways to identify people at high risk for this condition, as well as to initiate improved treatments.  

A collaborative effort
The study is a collaborative effort between teams led by Dr. Paul Albert, Senior Scientist in the Neuroscience Program at the Ottawa Hospital Research Institute and by Dr. Krista Lanctôt, Scientist with the Brain Sciences Program at Sunnybrook Health Sciences Centre. Dr. Albert is working to identify genetic markers associated with depression and suicide. By contrast, Dr. Lanctot is looking for markers in the immune system which may play a role in depression. Her team is also responsible for recruiting subjects for this study.  

“Post-stroke depression seems to be different from what we see in the general population,” explains Dr. Lanctôt. “Not surprisingly, right after their stroke, many people have ‘reactive’ depression – but this usually passes. The post-stroke depression we are studying doesn’t go away, and current treatments don’t seem to work very well. We’re trying to find out why this is.”

Inflammatory response linked to depression
Severe post-stroke depression may be linked to an inflammatory response to stroke, according to Dr. Lanctôt. This in turn produces neurotoxic metabolites – naturally produced substances activated by stroke and inflammation – that contribute to early brain aging and deplete an important brain chemical called serotonin. “We actually think we’ve found a substance that is contributing to post-stroke depression,” says Dr. Lanctôt. “We’re looking at levels of this substance in different people, and trying to determine whether people with higher levels do more poorly. We’re also looking at brain scans to relate levels of this substance to loss of neural tissue. Using advanced imaging techniques, we can find very subtle changes in brain tissue and determine when it is not functioning properly.”  

Genetic markers may predict post-stroke depression
“We have already identified genetic markers in the serotonin system that are associated with depression and suicide,” explains Dr. Albert. “Evidence suggests these markers are linked to major depression. The hypothesis is that they’ll also predict post-stroke depression.”  

“We also believe the immune system is playing a role in depression. We’re looking to see if there is a link between abnormal immune function and post-stroke depression by studying changes in specific proteins and lipids which help regulate the immune system. Deregulation of this system may be more severe in people at risk for post-stroke depression.”  

So far, about 100 patients have volunteered for the study and given blood samples. These are analyzed then stored for possible future use. If all goes well, preliminary results may be available in a year or so. “On the other hand, many factors contribute to depression, so the likelihood is that we might need to increase the patient population before publishing results,” says Dr. Albert.  

Early treatment for high risk individuals?
If serious post-stroke depression can be predicted, then high-risk individuals can be treated at an early stage, and treatment could potentially be tailored to their specific needs.  

“These biomarkers will not only help us identify people at high risk,” says Dr. Albert. “They might also be able to tell us whether they would respond better to drugs or other treatments like psychosocial therapy. We already suspect one of our biomarkers is linked to a specific drug response. One of our long-term goals is to learn what drugs are most effective in treating this form of depression.”  

“If we show a link between depression and a neurotoxic metabolite, we want to develop a drug that will target this substance, so that we can interfere with the process that ultimately results in severe post-stroke depression,” adds Dr. Lanctôt. “The drugs we have now may not target this cascade. This may be why we have such a large proportion of patients not responding to standard therapy when they get seriously depressed after their stroke. If so, finding the biomarkers for severe post-stroke depression might ultimately lead us to new agents to treat this disorder.”