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When good stress turns bad

Everyone experiences stress, whether it’s dealing with day-to-day annoyances, such as traffic jams or machines that just won’t work, or with truly life-altering events, such as the death of a loved one, a divorce or the loss of a job.

Whatever the trigger, the initial response by the body and the brain to a stressful event is remarkably consistent: heart rates and blood pressure increase, while a surge of adrenaline provides an exceptional source of energy.

Stress can concentrate the mind in positive ways — it’s this primitive, evolutionary response, after all, that impels us to jump out of the way of an oncoming vehicle or to flee a burning building.

But exposure to too many stressful events in too rapid a succession can lead to chronic stress, which, in turn, contributes to a number of serious mental and physical health conditions, including depression, anxiety, fatigue, memory loss and even heart disease and hypertension.

Neuroscientist Jaideep Bains and his team at the University of Calgary’s Hotchkiss Brain Institute are mapping how and why “good” stress responses can turn bad. The findings could help point the way to possible treatments to combat the worst effects of chronic stress.

Bains has been studying stress responses for nearly a decade as part of a broader effort to understand brain connections and how neurons communicate with one another.

In addition to identifying the specific protein that switches on the brain’s stress command centre, Bains’ team has recently uncovered a mechanism that primes brain cells in lab rats to be increasingly sensitive to subsequent stresses.

It’s long been known that the brain responds to stress signals by releasing circulating hormones into the bloodstream — in humans, the most important one is cortisol.

“The idea is that you want to channel all the body’s resources to deal with the immediate stressor,” says Bains. “The beauty of this response system is that it’s also self-limiting. Once the hormones help you cope with the stressor, they feed back on the brain’s command centre and shut the system down.”

But Bains’ team also discovered that stress signals arriving in the brain leave a molecular imprint on brain cells in this stress centre that lasts for about a week. Those imprinted cells then respond to new stressors in an amplified fashion, releasing even more cortisol. If this happens often enough, the command centre’s natural shutdown system is broken, essentially leaving the brain permanently primed to go into overdrive.

“If you are consistently exposed to stress at work or in your personal life,” says Bains, “your brain stays stuck in hypervigilant mode.”It’s at this point that “good” stress can transform into chronic stress.

Such findings could ultimately lead to new drug treatments that would erase the imprint left on brain cells by the initial stress response — or at least reduce its duration. The trick is to do so without inhibiting the beneficial way the brain is now programmed to help us deal with stress.

Bains believes his research could also shed new light on post-traumatic stress disorder (PTSD), a condition sometimes experienced by combat soldiers, among others.

“One of the intriguing things about PTSD is that people who have been exposed to a really intense stressor are usually fine after they leave that environment,” says Bains. “Then something triggers the memory of that event and brings back the body’s stress response. That indicates an amazing capacity to recall stressful events. We think the priming mechanism we’ve uncovered could be a step toward understanding what’s going on.”

There are plenty of other unanswered questions, including whether certain types of stressors — economic versus emotional, for example — impact the human brain more than others.

“That’s a tough one,” says Bains. “One thing we know is that regardless of the stressor, the response, in terms of hormone release is the same. Once your brain has identified a stress, whether it’s that bus rushing toward you or the fact you’ve just gone bankrupt, the same switch gets turned on and tries to protect you from the perceived threat.”

One area the team hopes to study further is why some people seem to handle stress better than others. While certain individuals are probably genetically predisposed to cope with stress, Bains would like to find out whether exposure to significant stress at an early stage of development — say, in adolescence — makes one more vulnerable or resilient to stress later in life.

“It could be that having to deal with stress at an early age helps equip you to cope with later events,” he says. “Or it could be just the opposite. The question is wide open and is one that we’re very keen to investigate.”