Taking a closer look at our ‘blue spot’ – A breakthrough in neuroimaging and PTSD research 

Recent findings published by a research team at The Royal are opening the door a little wider to personalized treatment for people who struggle with post-traumatic stress disorder (PTSD). 

“Evidence for locus coeruleus-norepinephrine system abnormality in military PTSD revealed by neuromelanin-sensitive MRI,” was published in the January 2024 issue of Biological Psychiatry, one of the most selective and highly cited journals in the field of psychiatric neuroscience.

This research showed that people with PTSD have increased activity in an area of the brain called the locus coeruleus (LC), commonly known as the 'blue spot' because of its pigmentation, and that is linked to hyper-arousal causing intense feelings of anxiety and distress. Understanding this linkage can help scientists and clinicians develop better diagnostics and treatments for PTSD.

“This publication highlights the power of our interdisciplinary approach and talent and The Royal’s Brain Imaging Centre,” says Dr. Florence Dzierszinski, president of the University of Ottawa Institute of Mental Health Research (IMHR) at The Royal and vice-president of research, The Royal. 

"Thoughtful integration of care and research paves the way to innovations and a brighter future. Our interprofessional team, with its diverse expertise and complementary skills, serves as a lens to illuminate the complexities of our most challenging problems and allows us to navigate new terrain with precision and compassion."  

Dr. Clifford Cassidy, a scientist affiliated with the IMHR, is the primary author of the paper. (Co-authors affiliated with The Royal include, Adelina McCall, Reihaneh Forouhandehpour, Seyda Celebi, Claude Richard-Malenfant, Rami Hamati, Dr. Synthia Guimond, Dr. Lauri Tuominen, Dr. Natalia Jaworska, Dr. Robyn J. McQuaid, Dr. Jakov Shlik, Dr. Rébecca Robillard, and Dr. Zachary Kaminsky.) 

Cassidy had long suspected that the locus coeruleus (LC), an “understudied” area of the brain could hold some answers to the complex biology of PTSD. 

The LC is a small area deep in the brainstem that affects our thoughts and actions in many different ways. It contains neurons ­(brain cells) that are responsible for the production of a brain chemical called norepinephrine which is targeted by some psychiatric medications. 

“The locus coeruleus-norepinephrine (LC-NE) system is involved in many functions,” explains Dr. Jakov Shlik, a psychiatrist in the Operational Stress Injury (OSI) Clinic at The Royal. “It regulates the sympathetic nervous system, the ‘fight or flight’ reaction in the body. In respect to PTSD, it's involved in the processing of emotions, and in attention and arousal – including sleep-wake cycles and concentration.” 

Dr. Clifford Cassidy, Dr. Florence Dzierszinski and Dr. Jakov Shlik
Dr. Clifford Cassidy, Dr. Florence Dzierszinski and Dr. Jakov Shlik

Recent advances in neuroscience have given us new tools to study this part of the brain, allowing us to uncover its secrets like never before. 

Cassidy optimized an innovative imaging technique called neuromelanin-sensitive MRI (NM-MRI), a non-invasive brain scan that enables researchers to see the dark pigment created from the breakdown of norepinephrine, called neuromelanin. NM-MRI offers a unique window into understanding conditions like PTSD and Alzheimer’s disease, where changes in neuromelanin levels are linked to the progression of the condition.

Using NM-MRI, Cassidy and his team have shown that people with PTSD have more activity in their LC-NE system compared to people who do not have PTSD. (Study participants were Canadian Armed Forces veterans with PTSD related to deployment to combat zones.)

This elevated level of activity in the LC-NE system is linked to hyper-arousal. In the context of PTSD, hyper-arousal refers to a heightened state of physiological and psychological vigilance that can manifest itself in various ways, including increased heart rate, exaggerated startle response, difficulty sleeping, irritability, and difficulty concentrating.

Hyper-arousal is often described as a feeling that the body's internal alarm system is constantly on high alert, even if there is no immediate danger. It can be triggered by reminders of a traumatic event and lead to intense feelings of anxiety and distress. It’s a common symptom for veterans and members of the Canadian military who have PTSD, says Shlik, who describes it as “enhanced reactivity to the environment” that greatly reduces quality of life.  

“People have a hard time sleeping, they are more irritated. They are always on guard, uncontrollably so, and therefore it's very hard to relate to any day-to-day situation – [such as] being in traffic – any situation outside of a very confined environment might be experienced as a threat by the brain,” he explains.  

Treatment for PTSD, like many mental health conditions, often involves a combination of therapy and medication but treatment is not universally effective. What’s more, many medications take weeks to gauge their effectiveness and often come with unwanted side effects. 

While there is more work to be done in this area, the new findings represent a positive step forward in the race to find personalized treatment for serious mental health conditions. As part of a larger interdisciplinary clinical research project called Multi-Dimensional Assessment of PTSD Subtypes (MAPS), MAPS aims to improve understanding of PTSD so it can be more easily diagnosed and more effectively treated and is funded by the Government of Canada’s Innovation for Defence Excellence and Security (IDEaS) project. Click here to read more about MAPS.