Anxiety Disorders
EXPLORING HOW THEY RELATE TO THE MECHANICS OF THE BRAIN
Anxiety disorders are the most prevalent mental illnesses in the world. According to data from the “Global Burden of Disease Study 2019” published by Dr. Yang and colleagues in Epidemiology and Psychiatric Sciences in 2021, there was an estimated 45.82 million cases of anxiety disorders in 2019, which constituted a 50% increase in cases over 30 years.
There are disparities based on sex, with women suffering from anxiety disorders 1.6 times as often as men.
While it is well established that the prevalence of anxiety disorders is higher for women than for men, there is limited research on sex-related differences and a poor understanding of the mechanisms that underscore experiences of anxiety.
Because of this, identifying appropriate therapies for anxiety disorders continues to be challenging for health professionals, and there are only a few therapeutic targets for pharmaceuticals in treating anxiety.
WITH THE DEVELOPMENT OF SOPHISTICATED TOOLS OVER THE LAST TWO DECADES, NEUROSCIENTISTS HAVE DISCOVERED THAT THE NEURAL CIRCUITS THAT ACCOMPANY ANXIETY ARE INCREDIBLY COMPLEX AND INTERCONNECTED.
Optogenetics is a modern technique that uses light to stimulate the activity of neural pathways and can provide insights into individual neural pathways within complex circuit systems.
As more mechanistic data is gathered, we may be able to modify the activity of specific pathways, and this could be beneficial for developing new therapeutic approaches.
Dr. Bénédicte Amilhon is an assistant professor at Université de Montréal, and Principal Investigator for a project that examines sex differences in specific neural circuits – serotonergic circuits – that regulate anxiety. This project is supported by Brain Canada Foundation, the Azrieli Foundation, and Health Canada through the Future Leaders in Canadian Brain Research grant.
Mind Over Matter® (MOM) interviewed Dr. Amilhon to learn more about her project and its contributions to our knowledge of anxiety disorders.
MOM: Can you tell us more about what you are studying and the methods that you are using?
Dr. Amilhon: Generally speaking, compared to other research domains like physics and mathematics, neuroscience is quite young. One of the reasons is because in the past, we had not developed the powerful tools to be able to study the brain in a high level of detail, and precisely probe the roles of the identified circuits.
To understand intricate circuits in animal models and the differences between sexes or between individuals in relation to specific behaviours is an important first step, or preclinical step.
Our project is trying to understand the mechanics of the brain, but not the brain as a whole, a very specific population of neurons – serotonergic neurons – and their connections in the brain. We are really trying to pinpoint a subpopulation of neurons that release serotonin in a particular region of the brain, the ventral hippocampus, that we know is important for anxiety.
WE ARE USING OPTOGENETICS, BEHAVIOURAL STUDIES, AND OTHER METHODS TO STUDY HOW A SMALL GROUP OF NEURONS INFLUENCE ANXIETY LEVELS DIFFERENTLY IN MALES AND FEMALES.
Serotonergic neurons are nerve cells that use the hormone serotonin as a neurotransmitter. Serotonin plays a large role in mood in general, and anxiety states in particular. As such, many anti-anxiety and anti-depressive medications act on the serotonergic system.
Because mice and humans respond similarly and show a reduction in anxious behaviours when certain medications like anxiolytics, benzodiazepines, or SSRIs are administered, mice provide a good model for studying anxiety.
As you can’t give animals questionnaires about how anxious they feel, we get behavioural readouts of what we interpret as different anxiety levels in relation to environments that are potentially threatening.
MOM: How do you study the behaviour of mice and explore sex differences in anxiety levels?
Dr. Amilhon: Mice have a natural tendency to explore new environments. When you observe mice moving around, you’ll notice that they tend to stay in more secure areas like dark corners and will rarely wander into the open areas.
We exploit this natural tendency to explore in a lab setting where some parts of the environment are more potentially threatening than others. Darker, more confined areas are perceived as less threatening, and brighter, more exposed areas are more threatening.
One way that we assess levels of anxiety is to observe how many times during a fixed period, like ten minutes, a mouse will enter a potentially threatening area and how long it will stay there. We use this information to estimate overall levels of anxiety and use the same test for male mice and female mice.
As part of our research, we used optogenetics to manipulate the activity of a specific subpopulation of serotonergic neurons for male and female mice and observed different behaviours.
Female mice seemed to show more risk assessment and enter less into the open areas. But male mice did not change the number of times they were out in the open areas.
MOM: How can mechanistic research translate into therapeutic targets?
Dr. Amilhon: The number of drugs that we have for anxiety disorders and their efficiency is not optimal. Relative to medications for other types of disorders, development of medications for mood disorders has been very slow despite their prevalence.
What is motivating this research is that we need to understand the system and how it works precisely. We are gathering fundamental information about the mechanics of the brain.
At some point in the future, we might be able to say, “Now that we know that this brain pathway plays this role in modulating anxiety, let’s go look at patient data. Let’s go investigate specific types of receptors or markers that we could change to modulate this specific brain pathway.”
You need to start with the mechanics of the brain to then think of new therapeutical targets and new ways of approaching and pursuing treatment for anxiety disorders.
MOM: Could learning about specific brain pathways involved in anxiety disorders be helpful for other brain conditions where there are known sex differences?
Dr. Amilhon: You must be open-minded in science and neuroscience because you can find useful information in research domains that are quite different from yours. I hope that whatever we’re doing in the lab in terms of neural circuits and anxiety might spark new ideas or catch the attention of someone that is working in another field of research so that they take a new perspective on their own research.
Any information is valuable and informative outside its own field of research. Many brain diseases show sex differences in prevalence. I hope that what we’re finding in relation to anxiety might be helpful and informative for other types of neurological diseases.
Women’s health and the mechanics of the female brain have really been overlooked in the past, but women’s health is important because 50% of the world’s population is female. Society is changing, and this parallels changes in our research culture and the way we think about scientific problems.
MOM: What final thoughts would you like to share with our readers?
Dr. Amilhon: We need to remember that research takes a long time. Great discoveries do not come exactly when or where you think they will come from. Science is curiosity driven and something beautiful that can have impacts on fields that you did not think of initially.