Brandeis Magazine

You don’t have to be in the grip of a lion’s maw to feel stress breathing down your neck. Everybody knows ordinary life can be a stress-producing furnace. But just how psychosocial stress insinuates itself into body and mind — sometimes with devastating effects — is a hot area of research of considerable consequence to anyone facing a modern-day malady like heart disease, depression or diabetes. So when assistant professors of psychology Nicolas Rohleder and Jutta Wolf asked whether I wanted to take a psychological stress test informally in their health psychology lab a few months ago, it seemed the least I could do to understand their area of research better.

Standing before two white-coated examiners seated at a table covered with pages of handwritten notes, I felt pretty relaxed. All I had to do was talk about myself and my qualifications for an imaginary — and unnamed — job for five minutes and then follow up with some simple mathematical calculations for another five minutes. It seemed an easy enough task, especially for someone with ample work experience. I was even given several minutes to collect my thoughts with pen and paper while I sat at a small table facing into the corner.

If it hadn’t been for the examiners’ implacably blank faces — a perfect mirror of the featureless walls of the tiny, windowless room in which I was enclosed — maybe everything would have been all right. The first hint things might not go as I imagined, even though the contours of the interview had been outlined previously for me, occurred when I was told I couldn’t use the notes I had just created to keep me on message. “No biggie,” I thought to myself. “I’ve got tons to say.”

Eye contact seemed key, since I had been warned that the panel would be observing my body language. So I was just a little unsettled by the sense that the young man and woman before me were boring into my very soul with a look of bottomless ennui, not to mention barely concealed hostility. I detected an uptick in my heart rate and a burgeoning sense of unease — probably a spike in blood pressure. It was a sure sign that the primordial fight-or-flight stress response, activated by my sympathetic nervous system (SNS), was on high alert and in charge. One thing was certain: My body and brain didn’t seem to care that this was just a test, not a real job interview.

When I did break eye contact, I was drawn to the video camera attached to a tripod positioned between the panelists, recording my every syllable and nervous gesture. I could barely see myself in the video screen — just enough to know that I appeared remarkably insignificant. Somehow I managed to lurch through the allotted five minutes of uninterrupted speaking time (some subjects don’t), though I have no detailed memory of what I actually said. Then came the coup de grâce.

“Count backward by 13 starting with 1,311,” ordered the charmless young man before me as he resumed scribbling on the paper in front of him.

“OK, 1,311 minus 13 is, ah, ah, 1,298, minus 13 is, ah, ah, ah, 1,285, minus 13, is 1,273.”

“No, you made an error. Start again at 1,311 and count backward by 13,” he ordered, summoning all the gravitas of a CEO about to downsize the company by a few hundred workers.

“What, go back to the top?” I blurted, incredulous. At that moment stress — never mind that the examiners were students — simply hijacked reason, ditching mine in a confused heap in a back corner of my mind. The next few minutes were a Sisyphean struggle as I lugged boulder-sized numbers up a hill, only to watch them roll back down again because they weren’t the right ones.

The Trier Social Stress Test (TSST) is the gold standard for inducing stress responses in people under laboratory conditions. (According to my examiners, who morphed into fresh-faced and friendly kids once the test was over, I was a pretty average guinea pig.) Participants’ physiological responses to the TSST are recorded on heart monitors and measured in pre- and post-test saliva and blood samples timed to correspond with stress hormones surging and returning to normal levels. The video camera, of course, captures behavioral responses. The test always proceeds the same way — with a panel evaluating a “job applicant,” who also has to count backward in increments of some odd number, starting with a ridiculously high prime number. It doesn’t seem to matter one jot that test subjects are informed beforehand what is going to happen during the stress test.

Rohleder and Wolf deploy this test to help them document how psychosocial stress, as they put it, “gets under the skin.” As doctoral students in the 1990s at the University of Trier in Germany (the birthplace of the TSST), they were introduced to psychoneuroimmunology, the study of how psychology interacts with the immune and nervous systems. It’s a relatively new area of research that, despite its showy nomenclature, actually has a pretty straightforward goal. Says Rohleder, “It’s about how psychosocial stress states get translated into physical disease.”

After arriving at Brandeis three years ago, Rohleder, 39, and Wolf, 36, established the Health Psychology Lab to study how acute and chronic psychological stress contributes to aging, heart disease, stroke and diabetes, as well as to mood disturbances such as post-traumatic stress disorder (PTSD), depression and eating disorders.

Unlike most research on stress, which captures snapshots of a person’s stress response, the Health Psychology Lab also looks at how stress response patterns develop over a long time, potentially permanently altering a person’s immune response and paving the way for cardiovascular ailments, diabetes and other diseases linked to inflammation.

Rohleder and Wolf tend to run research studies in parallel rather than collaboratively. But they share equipment, experimental techniques, ideas and considerable enthusiasm for their line of research, creating a notably friendly and unstressful environment for the postdoctoral, graduate and undergraduate students who help run the lab and collect and analyze data.

The stress hormone known as cortisol is the linchpin of their research.

“Cortisol controls inflammation, which plays a key role in aging, disease, cognitive declines and affective disorders,” says Rohleder. Specifically, cortisol drives a host of physiological processes, among them counteracting insulin, suppressing the immune system and helping create memories of emotional events.

What most interests Rohleder actually happens after the TSST is finished — typically about 20 minutes after the SNS is activated. The ancient fight-or-flight response can mean the difference between life and death if you’re at risk of becoming a lion’s lunch and need the adrenaline rush to make a hasty escape. And because the SNS also ramps up the immune response, if you don’t manage to flee before losing a limb to the lion, you’ll still be in a better position to fight the resulting infection.

But another stress system, a complex cascade of physiological events, unfolds once you’re out of mortal danger. That’s when the hypothalamic-pituitary-adrenal (HPA) axis kicks in. Cortisol takes center stage in this intricate choreography of biochemical messages and feedback loops among the endocrine, immune and central nervous systems, and it has the potential to reach nearly every cell in the body. Released by the adrenal glands into the bloodstream, cortisol shuts down the SNS-revved immune system once the threat has passed.

As Wolf says, “You don’t want an overactive immune system if you’re not being chased by a lion.”

A healthy stress response to either physical or psychological stress occurs when cortisol surges as needed but returns to normal levels when the thorny situation abates, keeping the inflammatory response in check. But what happens biologically and psychologically when cortisol doesn’t return to baseline levels and the inflammatory response goes awry? What are the effects on age-related disease and mental function?

To answer these questions, Rohleder is deploying the TSST to study the prevalence of healthy and unhealthy stress response patterns in adults 50 to 65 years old. Funded by the American Federation for Aging Research, the study has a long-term goal of figuring out which stress response patterns turn out to predict biological and psychological age-related declines.

“Your genetic makeup plays a role in how you respond to stress, but so does your life history; if you get stressed too much or too often, or if your immune response pattern doesn’t adapt well to repeated stress, you are probably compromising your health,” says Rohleder. “There is strong evidence that inflammation in older people is associated with all causes of mortality and functional declines.”

Rohleder hopes to shed light on what kind of stress response patterns can increase the risk of heart attack, dementia and depression, a necessary first step to counteracting those patterns — for example, through counseling, aerobic exercise or meditation. While the aging study targets garden-variety stress in older people — such as the kind Alzheimer’s caregivers experience — Wolf is recruiting 60 men and women from the ranks of off-duty National Guard members to participate in a sleep deprivation study probing the effects of extreme stress on mental ability and its role in the development of PTSD.

“If you are sleep-deprived, and then stressed on top of that, how do you respond — on the immune level, on the endocrine level, on the cognitive level?” says Wolf, outlining 
the major research question. “Honestly, I feel a little bad about the sleep deprivation,” she confides, “but we do take good care of them.”

The results of the study will be useful to Wolf’s collaborator, the U.S. Army Research Institute of Environmental Medicine (USARIEM). Based in Natick, Mass., the facility is a center for “warfighter performance science,” according to the USARIEM website. Wolf says the participants, aged 20 to 40, will take the TSST after being deprived of sleep for 36 hours. Her task is to tease apart the sleep deprivation stress from the acute psychosocial stress induced by the TSST. The data, says Wolf, will help the Army create sophisticated computer models incorporating electroencephalography data as well as functional near-infrared imaging, which measures neuronal activity in the brain linked to metabolic activity.

“Ultimately, the computer models will be sensitive enough to detect stress-related disorders, most importantly PTSD, giving the Army an invaluable tool to help keep vets healthy,” explains Wolf.

Although research links depression and inflammation, it is dogged by a chicken-and-egg problem: Does depression tend to beget inflammation, or is it the other way around? Further complicating matters, while inflammation (as measured by blood tests of inflammatory responses) is characteristic of depression, PTSD and eating disorders, intriguingly, cortisol levels are elevated in depressed people and depressed in PTSD sufferers. Wolf believes answers to these conundrums exist deep inside the signaling transduction pathways of the endocrine system — the chain of events that begins with a signal to a cortisol receptor in an immune cell and ends with a change in the immune cell’s function.

The sophisticated laboratory tests Rohleder and Wolf perform on their study subjects are helping to bring psychological research to the molecular and cellular levels. Still, they have their work cut out for them decoding the effects of psychosocial stress in humans. Unlike the antediluvian fight-or-flight stress response, psychosocial stress permeates potentially every aspect of modern life. Just think about your first date, your boss, your job interview, your kids, your college debt or your spouse. If you still aren’t stressed out, consider signing up for the TSST in the Health Psychology Lab.