The Stressful Storm of Adolescence: Implications for Autism Spectrum Disorder

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It’s a gloomy day. You’re waiting for your son to return from their first day of high school when thunder strikes and the front door swings open. Your son drops everything at the door and comes running to you. They start telling you about the terrible day they’ve had and how much their peers bullied them. You notice remnants of the washed off marker on their arm. A couple days go by and you get a call from their guidance counselor about how reserved they are in their classes, always choosing the backmost seat, away from anyone and everyone. At home, they now go straight to their room, only coming out to grab two pieces of bread and some milk for dinner. Refusing to eat anything else, you worry about their nutrition. 

A couple of years go by and despite your best efforts your son continues to be reserved. They refuse to sit with you. They say the hissing of the light bulbs coupled with the sound of your voice is too much for them to handle. You decide to take them to a doctor and get referred to a psychologist. A month later, your son gets diagnosed with anxiety and the psychologist notices sensory changes akin to autism spectrum disorder (ASD).

While it is not the case that someone will develop ASD after a stressful event, adolescence is a time when psychological and/or physiological stressors can impact health outcomes. For this reason, researchers like Deanne Wah chose to study behaviours associated with ASD and how stressors can impact these behaviours in the lab of Dr. Peter Ossenkopp and Dr. Martin Kavaliers at Western University.

Activating a rat’s stress response by introducing psychological and/or physiological stress leads to similar outcomes in comparison to that seen in humans after a stressful event. As such, rodent models have been crucial for understanding ASD. When Wah and her colleagues performed their experiment in 2019, they exposed rats to predator (cat) odor in early adolescence. This exposure activated the rats’ stress response, mimicking a psychologically stressful event. In later adolescence and adulthood, she tested these effects on ASD-related behaviours such as anxiety. In humans, 10% of kids with ASD develop anxiety, compared to only 2% of typically developing kids. In a rodent model, this can be measured using a light-dark test. Rats prefer dark enclosures over brightly lit ones because brightly lit areas are reminiscent of predatory risk. In these, rats are more likely to avoid the light compartment when they are anxious. In line with this, Wah found that the rats exposed to predator odor were less likely to explore the “dangerous” light chamber and when they did, they were much more likely to try to escape. In other words, they were showing signs of increased anxiety. 

Wah went a step further and exposed the rats to propionic acid (PPA). PPA is a molecule that is naturally occurring in our guts and is required for healthy functioning. PPA is also used as a food preservative, and elevated PPA can be found in the guts of individuals who overconsume produced that use breads and dairy products that contain PPA as a preservative. Interestingly, elevated levels of PPA in the body have been found to bring about or worsen symptoms of ASD. In her study, Wah used a paradigm called the prepulse inhibition of the acoustic startle response. Prepulse inhibition is a measure of an individual’s ability to reduce sensory overload. When Wah exposed her rats to PPA at high doses, she found that it triggered sensory overload reminiscent of the story of our teen in high school! This was not found in the rats that were not exposed to PPA. 

Some of the important caveats to point out in Wah’s research are that she only studied male rats. This was an appropriate sex to focus on however as ASD is 4 times more likely to be diagnosed in males than in females. Additionally, it is important to note that it is not the case that someone will develop ASD or that ASD symptoms will worsen after being exposed to psychological or physiological stressors. Studies looking at the impacts of adolescent stress exposure and ASD behaviours are relatively new and currently ongoing. 

These studies give us an indication that psychological stress like bullying and physiological stress like poor nutrition may have health outcomes. By understanding the mechanisms through which these psychological and physiological risk factors lead to behavioural changes, we can better understand how to prevent or manage these changes. This is perhaps even more important identifying these individual stressful events. With the advent of more research linking gut health to neuroscience and behaviour, researchers can continue to learn more about what triggers anxiety and sensory changes.

Original journal article: https://pubmed.ncbi.nlm.nih.gov/30408471/