Provencal%2C%20Nadine%20-%20Preferred%20Photo.jpgCan stress early in life – or even in the womb – make us susceptible to health problems as teens or adults? Mental health conditions like anxiety and depression often run in families, but typically aren’t the result of a single genetic mutation. So what causes them? If we understood how emotional trauma affects our biology could we develop new therapies to help kids recover from tragedy, abuse and adversity? 

These questions lie at the heart of BC Children’s Hospital investigator Dr. Nadine Provencal’s research, and she’s using an emerging area of study called epigenetics to search for the answers. 

Epigenetics is the study of the environmental and biological factors that affect how genes are expressed. It has the potential help scientists understand the origins of many serious health conditions from autism to cancer to schizophrenia. However, it requires researchers to analyze a vast amount of genomic information from many people and to isolate many different variables in order to locate the changes in gene expression that contribute to disease. This requires a large investment of time, staff and money, which can slow the pace of research.  

A new method for analyzing targeted regions of the genome developed by Dr. Provençal and her colleagues is now making it faster and easier to do leading-edge epigenetic research by giving scientists a more accurate and efficient way to measure DNA methylation, a chemical tag on genes related to whether they’re turned “on” or “off.”

This method, which is outlined in a recent study in Epigenetics & Chromatin, is called high-accuracy methylation measurement targeted bisulfite sequencing (HAM-TBS). HAM-TBS makes it possible to analyze targeted regions of the genome in samples from more than 300 people at the same time. It uses high resolution, which enables scientists to find small changes in methylation more accurately. Simply, it’s more precise and allows researchers to analyze more samples, in less time at a lower cost.

Dr. Provençal is currently using this new method to study the effects of stress early in life on the development of behavioral and psychiatric illnesses, research that may one day inform interventions’ efficacy and lead to new treatments and preventative measures for mental health conditions.

Together with her colleagues, Dr. Provençal is studying DNA methylation on a gene called FKBP5 that is involved in the regulation of stress systems in the body. FKBP5 is more highly expressed in the body when a person experiences stress. Previous research has found a link between childhood trauma and the expression of FKBP5. Research has also shown a connection between the way FKBP5 is expressed and a number of psychiatric disorders, including post-traumatic stress disorder, depression, anxiety and psychosis.

“We know that stress and trauma early in life can contribute to mental health conditions, but there are still so many unknowns,” says Dr. Provençal.

“Some children can go through extremely stressful experiences and never develop mental illness, while others suffer from serious psychiatric disorders after one traumatic event. Why are some children more susceptible than others? Does the timing or length of the stressful experience make a difference? Our research could help answer these questions.”

By understanding the biological processes that contribute to mental health conditions, Dr. Provençal hopes to eventually develop new tools to better assess the long-term impacts of our current intervention and preventive programs as well as contribute to new therapies that could interrupt these processes to treat mental illnesses or prevent them from developing.

“Imagine if we could give all children who’d experienced traumatic events an intervention that would prevent them from developing psychiatric illness in the future,” says Dr. Provençal. “If we can understand the molecular processes that lead to these conditions, we can better assess the long-term impact of our interventions as well as opens the door to new preventative measures and therapies.”

Additionally, understanding more about how stress affects the expression of our genes, such as FKBP5, could ultimately lead to the creation of an accurate test that measures how stress affects the body. Right now, researchers must rely on reports from parents or caregivers to determine how much stress a child has experienced. These reports are subjective and may not be entirely accurate. Being able to test for stress exposure could improve both care and research.

“If there was an accurate way to assess how much stress a child had experienced, we could more easily identify high-risk children and intervene to reduce the negative effects of any trauma they’d experienced,” says Dr. Provençal. “This test could also help us study stress in large groups of children and better understand how and why traumatic experiences affect development.”

In addition to facilitating Dr. Provençal’s research on mental health, the HAM-TBS method has the potential to help scientists around the world learn more about epigenetic processes involved in disease development.

“Epigenetics has great promise to advance the diagnosis, prevention and treatment of many serious diseases,” says Dr. Provençal. “The HAM-TBS method is a valuable new tool for the scientists undertaking this important research. I’m looking forward to seeing how my colleagues in the scientific community use HAM-TBS to make new discoveries about human health.”

Dr. Provençal is also an Assistant Professor in the Faculty of Health Sciences at Simon Fraser University. She receives support from the Canadian Institutes of Health Research and BC Children’s Hospital Foundation.