New research led by UCLA Health has found that specific genes may be linked to the recovery trajectory of stroke survivors, providing doctors with useful information for developing targeted therapies.
Published in the magazine Stroke This month, the findings were part of an exploratory study that sought to find out whether candidate genes could predict a higher likelihood of stroke outcomes related to depression, post-traumatic stress disorder and cognitive decline.
Dr. Steven C. Cramer, MD, senior author of the study and a professor of neurology at UCLA, said that while there are some predictors doctors can use to anticipate stroke recovery, such as a patient’s age or initial health status, they only tell part of the story.
“In general, the problem we face is that when someone has a stroke, it’s hard to anticipate what’s going to happen next,” Cramer said. “People look at us from the emergency room gurney and say, ‘What’s next? What’s going to happen to me?’ People want to understand what their trajectory is going to be, they want to have an idea of how they’re going to fare or not and what treatments are available to them.”
Similarly, doctors treating stroke patients need improved methods to understand how the patient will fare in order to develop a personalized medical approach for each individual, Cramer said.
Previous studies have provided evidence that genetic differences are related to the stroke recovery process, but few studies have been conducted on the specific outcomes with which these genes are associated. For example, most previous genetic studies related to stroke have relied on the modified Rankin Scale, which is a global disability measure that combines recovery data from all behaviors into a single-digit score.
However, Cramer said this scoring system doesn’t account for granular differences in stroke patient outcomes — such as a patient who has improved movement but still suffers from severe depression, or who has persistent anxiety but shows good recovery of arm movement. As a result, Dr. Cramer, in collaboration with Dr. E. Alison Holman of UC Irvine, sought to determine whether there was a method to more accurately measure various behavioral outcomes among stroke survivors.
To do so, Cramer and his team measured details of a group of candidate genes to examine in more than 700 patients enrolled across the United States. In addition, the researchers conducted detailed behavioral assessments of the participants’ cognitive health, depression, PTSD symptoms and other deficits for one year after their stroke.
The study found significant associations between certain genes and these behavioral health outcomes. Specifically, the rs6265 gene variant was associated with poor cognition. This genetic variant is linked to brain-derived neurotrophic factor, or BDNF, which is the most common growth factor in the brain and is strongly associated with learning. An estimated 20 to 30 percent of people have this genetic variant, which slows the release of BDNF.
“The brain releases BDNF when you learn new things,” Cramer said. “You’d expect the brain to be releasing BDNF right now. People who have this genetic variant had worse cognitive status a year later.”
Environmental factors, such as stressors, also influenced gene expression among stroke patients. Patients with the rs4291 and rs324420 genetic variants were at increased risk of developing more severe depression and PTSD symptoms one year after stroke.
“The more stress they reported, the more the genetic variant was associated with worse outcomes,” Cramer said.
Another variant, rs4680, was associated with lower symptoms of depression and PTSD.
While the results still require independent verification, Cramer said these insights could help doctors and other allied health professionals tailor treatment options for patients based on a simple genetic test.
“If these findings are confirmed to be true, you could look at a person on the day they have a stroke and say, ‘I know that, on average, they’re at higher risk for a worse outcome in terms of cognitive function a year from now,'” Cramer said. “Maybe those are the people who need additional cognitive rehabilitation, or maybe one day we’ll have a drug that targets certain genetic receptors. The idea is that you can divide people into different groups and use that knowledge not only to make predictions but also, hopefully, one day to improve individualized treatment.”