Stress!

STRESS!

You BOLT upright out of bed. You’re LATE! You struggle to rouse the kids. You toss some bagels in the toaster. The baby starts crying. Smoke fills the kitchen. You’ve burned the bagels. You can’t find your car keys. Little Jimmy can’t find his shoes. Your cell phone is ringing. It’s your boss. You’re late for a meeting. It starts to RAIN. You can’t find the umbrella.

Life can be stressful. And stress over a prolonged period — known as chronic stress — can be detrimental to your health … even deadly.

At his laboratory at Washington University School of Medicine in St. Louis, where he is an associate professor of anesthesiology and neuroscience, Creighton alumnus Michael Bruchas, BS’99 (biology), PhD’04 (pharmacology), is studying stress — specifically as it relates to the brain’s pathways of reward, aversion, addiction and depression. It’s something that’s interested him since his days as a graduate student working in the lab of Creighton pharmacology professor Peter Abel, Ph.D.

“We’re trying to understand, ‘What are the receptors in the brain that coordinate different types of behavioral responses?’ By understanding those receptors and understanding the pathways and circuits that mediate behavior, we might be able to uncover new therapies,” Bruchas says.

Yeah, a cure for stress.

“If we can understand it better, perhaps we can not only understand how the brain works and how we make decisions and how we engage with our environment, but also produce treatments for these diseases known to be widely impacted by stress.”

Bruchas is making, excuse the pun, headway — discovering, among other things, how calming a neural circuit in the brain can alleviate stress in laboratory mice.

That’s a big deal, because whether mouse or man, stress is a killer.

“We know that stress is a major contributor to most chronic conditions now,” says Thomas Lenz, Pharm.D., director of Creighton’s new Healthy Lifestyle Management degree program. “Upwards of 85 percent of most diseases have a connection with stress.

“I think it’s fair to say in our current society, compared to our former way of living, that we are in hyper-stress mode compared to what our bodies are genetically used to. We’re in a new era of our culture, and stress certainly has a contribution to the chronic diseases we’re seeing, like obesity and diabetes and cardiovascular disease, in a way we’ve never experienced before.”

An Epidemic

In a 2013 Gallup poll of people in 138 countries, one in three said they had experienced stress the previous day. And it’s particularly prevalent with women and Millennials. In the annual American Psychological Association (APA) Stress in America survey in 2014, 51 percent of women said they’ve lain awake at night because of stress in the past month versus 32 percent of men. Among Millennials — which includes Creighton students — 36 percent say their stress has increased the past year, more than any other generation.

The latter statistic doesn’t go unnoticed at Creighton’s Center for Health and Counseling, where staffers are seeing an increase in students seeking help for anxiety-type disorders.

“What we see commonly are the expectations that students are putting on themselves to be perfect,” says Stephanie Stockham-Ronollo, a center counselor. “Really focusing more on the future of what they’re going to be, more than realizing that it’s important who they are right now and taking care of themselves.”

The leading cause of stress away from campus isn’t likely to raise eyebrows — money.

In the APA survey, 72 percent of adults reported being stressed about money some of the time and 26 percent most or all of the time. Those are typical results since the survey began in 2007.

Other top sources of stress in the APA poll were work (60 percent), the economy (49 percent), family responsibilities (47 percent) and personal health (46 percent). Technology also gets mentioned by stress experts.

“We’re constantly being connected to something like a device or messages or just external stimulation,” Lenz says. “It might be from TV, might be from the phone or computer … those seem to make people more stressed (rather) than less.”

The odd thing about stress, though, is how subjective it is.

“Stress is something very unique to each person,” Lenz says. “It really is, for the most part, a perception.”

And how it is perceived influences its impact.

“If it’s good or bad it can have totally different affects on the brain and lead to totally different outcomes,” Bruchas says.

Consider bungee jumping, says professor Deniz Yilmazer-Hanke, M.D., Ph.D., director of Creighton’s Master’s in Clinical Anatomy Program.

“Bungee jumping might be very stressful to one person because it’s unpleasant while it’s very stimulating to another person and the reward areas in the brain are activated,” Yilmazer-Hanke says.

Or, notes, Geri Moore, director of Creighton’s Exercise Testing and Training Laboratory in the Department of Exercise Science and Pre-Health Professions, one person might thrive giving a speech while another person “breaks out in hives or vomits.”

Here it’s important to note that stress … is good.

Or at least can be.

Back when lions and other scary things roamed free, stress kicked in hormones prompting a fight or flight response whenever our life was in danger.

“We’re grateful we had that because if we didn’t, we might not be around,” says Tom Guck, Ph.D., director of behavior sciences in the Department of Family Medicine.

Good stress still comes in handy today. Guck, who has given campus presentations about stress and its effect on the heart, points to athletes: “You hear about teams, for example, that come out flat. Their stress level and motivation are not where they need to be, at their peak. You have to have a certain amount of stress, or anxiety, for being up for something.”

It can even be good for students. Yilmazer-Hanke cites studies that show how the right amount of stress hormones can improve learning. But too much stress, and learning begins to deteriorate. Or a team’s performance suffers.

“Look at stress and performance and it’s a U-curve,” Guck says. “Typically if you have some moderate level of stress, you maximize your performance. If you’re under or over, your performance is a little bit less.”

The real problem is when stress comes to stay. With chronic stress, bad performance on the field or on a test becomes the least of worries.

“When it goes on for a long time, it can even elicit some sort of physiological damage,” Guck says.

Beginning in the Brain

The damage starts in the brain, something we’ve only recently begun to understand, says Sanjay Singh, M.D., chair of Creighton’s Department of Neurology. “We didn’t know much about it until the last 10, 15 years.”

Tools such as functional MRIs have helped. Researchers can look at the brain as it’s solving a mathematical problem or getting angry and see what parts are firing.

With stress, the hormones adrenaline and cortisol are released throughout the body. With chronic stress — stress that doesn’t go away — cortisol floods the body in large amounts, killing brain cells and restructuring areas like the hippocampus, our memory and learning center. Cognition begins to suffer. Singh says the amygdala, the fear center of the brain, “actually increases in size, physically.”

Not good. “Some of the new, late-breaking information is the kind of stuff which really puts a physiological perspective to how dangerous this can be,” Singh adds.

Some of the most recent and cutting-edge research on stress is being done by Bruchas in his Washington University lab. There, he explores how stress can lead to anxiety disorders, panic attacks, depression, addiction and more.

He’s found a way to shut off the bad effects of stress — in mice, at least.

Bruchas did so in mice genetically engineered with brain cells that have special receptors that can be activated by light (optogenetics) or synthetic chemicals (chemogenetics) to trigger or block neuronal activity. He and other researchers targeted a small structure in the brain called the locus coeruleus (LC). There, neurons secrete the hormone norepinephrine, which surges under stress.

Bruchas and other researchers observed mice moving through mazes and roaming freely in an open box. “Mice usually move toward the wall and try to stay out of the open area, just like a mouse in your house,” Bruchas says.

When his team selectively controlled the firing of LC neurons in stressed mice, lowering norepinephrine levels, the animals were more likely to venture into the middle even when stressed. They also discovered that by activating LC neurons with light, mice in the mazes behaved as if they were stressed, even when they had not been exposed to a stressful event.

Bruchas also has studied the brain region called the dorsal raphe nucleus. There, he discovered that after stress exposure, mouse brains activate a protein called p38α MAPK, lowering serotonin levels and triggering depression-like or drug-seeking behaviors. Stressed animals stopped interacting with other mice. In animals previously given cocaine injections while in specific places, stress made them more likely to seek out those locations.

When that protein was disabled only in cells of the brain’s serotonin system, stress-exposed mice no longer withdrew from social interactions, displayed depression-like behavior or sought drugs.

Body Blows

As the brain goes, so goes the body.

“We used to think that the mind and the body are separate,” Guck says. “Now we’re seeing it’s more integrated with reciprocal interactions among the environment, thoughts, emotions, physiology and behavior.”

With chronic stress, that can be devastating below the neck.

Creighton students observe this firsthand during Moore’s senior capstone course Laboratory Methods and Procedures. Students stress fellow students by giving them time-sensitive tasks or mathematical equations to solve. Then they measure what happens to the body. Often they see heart rate and blood pressure rise. Respiration increases, and skin temperature dips as blood flow is diverted to the heart.

Stress can be particularly devastating on the cardiovascular system. Over time, blood vessels harden and arteries are blocked.

Problems arise elsewhere in the body. The risk of developing diabetes increases. Energy dips, weight rises. Inflammation courses throughout the body. The immune and reproductive systems can be suppressed. The stomach can take a hit. “GI (gastrointestinal) disorders are on a huge rise,” Lenz says. “There’s a direct connection with stress and the GI system.”

De-Stressing

So what to do with all this stress wreaking havoc on our brains and bodies?

There’s good news. First, “stress reduction techniques are almost all free,” Singh says.

The bad news: “When people are stressed or feeling an intense pressure, anxiety,” Stockham-Ronollo says, “they tend to stop doing all the things that help them decrease anxiety.”

Two remedies for stress are mentioned most frequently — exercise and sleep.

Of the two, Lenz says, he’d start with exercise. “Because exercise helps promote better sleep,” Lenz says. “Stress is unique in its relationship with sleep. If you’re stressed, you can’t sleep. And if you can’t sleep, your body induces a stress response. It’s a pretty bad cycle.”

Exercise looks like it helps with stress in two ways, he says. “One, it helps you rest more comfortably and get better sleep in better quality and quantity. But it also induces stress, physical stress, and research points to it in helping your body deal with stress. You are putting yourself in a controlled stress environment for a period of time — 15, 30, 45 minutes. Whatever your body physically gets, it is more able to deal with emotional stress.”

If exercise doesn’t induce sleep, another stress-busting technique might do so — meditation.

Lenz says it’s a “very Ignatian” approach. Every day, he practices the Jesuit Examen, a technique of prayerful reflection on the events of the day. Others mention meditation alongside “mindfulness,” or being aware of the events of a day. Lenz asks clients he sees to journal about their days.

“Sometimes people have to learn how to do that, how to be mindful,” Lenz says. “This is really a way for them to stop what they’re doing and think about where it comes from and how they are coping with it and get to the source of what the stress is.”

Even counting your blessings — being grateful — can help.

The impact of such approaches is real and can be rather dramatic. Singh cites a study on people with multiple sclerosis who were asked to practice regular meditation/mindfulness. Cortisol and adrenaline levels dropped and MRIs showed a decrease in harmful brain lesions by the end of the 24-week study. When the meditation ceased, the lesions returned.

“This, we didn’t know could happen,” Singh says. “A biological thing in a major neurological disorder. How does that happen? Now we have good data, especially in the last three to six years, which tells us that meditation leads to long-term changes in brain structure.”

Creighton students can practice mindfulness without leaving home thanks to the Virtual Mindfulness Clinic Stockham-Ronollo established last August. It’s an online resource available any time of day and offers students numerous ways to de-stress via guided meditation, breathing exercises, movement practices and even apps (like Fluid Monkey, which gets users to interact with smooth, responsive pools of liquid).

But just as what stresses individuals can be subjective, so is what calms us.

“What works for me might not work for you or someone else or could even have the reverse effect,” Moore says. Yoga might relax one person but spike anxiety in another.

A few other ways to bust stress, as cited by Creighton sources include:

  • Eat Better — “Some foods you eat can actually induce a stress response,” Lenz says. Especially foods high in refined sugar or flour. “It can almost immediately, within a very short time after eating it, give the stress response where you have a shorter fuse,” he says. Avoiding drugs, alcohol and tobacco also helps.
  • Socialize — While being around some people might induce stress, being with others — especially friends — can calm us. In the APA survey, 43 percent of those who say they have no emotional support report their overall stress has increased in the past year, compared with 26 percent of those who say they have emotional support. And those connections are best in person rather than over the phone or online. “Partly because of the physical presence,” Lenz says. “When we do a lot of connecting without that physical presence, we’re not getting the same effect.”
  • Relax Your Body — At Creighton, Moore teaches a stress management technique called “Jacobson’s Progressive Relaxation.”  Students in the class are asked to tense then relax parts of the body, starting at one end and working toward the other. “It’s the idea of becoming aware of our body’s tension,” Moore says. 
  • Have a Good Laugh — It really is the best medicine, says Singh, who often tunes into “The Big Bang Theory” for his dose of chuckles. “I like the comedy shows,” he says. “That does decrease your stress.”
  • Take a Day Off — From technology, that is.

Again, most of this is free.

If Bruchas succeeds, though, blocking stress might be as easy as popping a pill. He mentions pharmaceutical clinical trials looking to place a blocker in the stress system that could benefit not just stress sufferers, but addicts, too.

“It’s very exciting,” Bruchas says.