Indiana University Research & Creative Activity


Volume 30 Number 2
Spring 2008

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Cara Wellman
Cara Wellman
Photo © Tyagan Miller

Brain neurons showing the effects of stress
Photo courtesy Cara Wellman

Stressing Out, Outing Stress

by Ryan Piurek

Cara Wellman is killing me.

Sitting in a noisy coffee shop on a Monday morning, nervously tapping my foot as I wolf down a fat-filled pumpkin cream-cheese muffin (eating is my preferred way of coping with stress), I wonder why, once again, I have put myself in this position. It's my fault I'm now staring at a blank screen and what feels like a hopeless deadline, and all I can think about is the Indiana University Bloomington psychology professor I've agreed to profile for this magazine and how she's got my brain tied in knots.

Just a few weeks earlier, I listened intently as Wellman discussed her research on the effects of stress on the brain, how stress hormones target our prefrontal cortex (the part of our brain involved in planning complex cognitive behaviors), and how those hormones reorganize things (until my own brain unlocks, we'll call them things) in the brain's frontal lobe.

As Wellman has discovered, even minor stressors--such as deadlines, family squabbles, and traffic--can affect the brain's ability to process information. Fortunately, it turns out that our brains are pretty adaptable. Most of us get stressed now and again, and then we get over it. Our brains may bend a little, but don't actually break.

But what about those who struggle with chronic stress? What effect does chronic stress have on their brains? What about those who suffer from schizophrenia, depression, obsessive-compulsive disorder, post-traumatic stress disorder, or relapse of substance abuse? How much does stress exacerbate--or precipitate--these conditions? Over the years, researchers have shown a link between stress and various psychological disorders--Wellman's work is beginning to uncover some of the changes in the brain that may be responsible for the link between stress and mental illness.

"Stress has profound implications for all psychological disorders," Wellman says. By further understanding the effects of stress on the prefrontal cortex, she adds, we might "shed light" on how to treat--and possibly prevent--these disorders.

In other words, to get to the bottom of how stressing out affects our brains, Wellman is, essentially, outing stress.

Hooked on neuroscience

Wellman was born in Indianapolis, but grew up in Jerusalem, Ohio (population 250), just across the Ohio River from West Virginia. After reading a book about the brain in high school, she became interested in psychology.

During her freshmen year at Ohio Wesleyan University, she was one of several students given the opportunity to engage in a one-on-one tutorial with a professor. For a course on learning and memory, Wellman was paired with renowned Ohio Wesleyan psychology professor Harry Bahrick. "We spent the semester sitting in his office with him teaching me intro psychology and human memory by basically having a conversation with me and drawing diagrams of concepts on a yellow legal pad," she says.

Over time, Wellman developed a keen interest in learning more about the brain and its role in various psychological disorders. She ended up majoring in psychology and minoring in chemistry at Ohio Wesleyan, while continuing to do research in Bahrick's laboratory.

After graduating in 1986, she came to IU Bloomington to pursue a graduate degree in clinical science, with a minor in behavioral neuroscience. While at IU, she enrolled in "The Cellular Basis of …," a graduate seminar designed to expose graduate students to the biological basis of behavior. The course was different from others she had completed--the instructor allowed the students to create their own syllabus based on topics that most interested them. Wellman and her graduate student classmates designed and executed a study examining cellular changes in Alzheimer's disease. By the end of the semester, Wellman was "hooked" on neuroscience.

"This small neuroanatomical project gave me a glimpse of the powerful ways in which neuroscience techniques could address questions about the mechanisms underlying psychopathology," she says. After completing the project, Wellman refocused her research on the neurobiology of behavioral disorders. She also added a second major in neural science.

Wellman earned a Ph.D. from IU in 1993. As a professional, she initially focused her research on age-related changes in the brain's frontal cortex. She sought to better understand neural changes that result from aging, as well as the causes and treatment of age-related dementias such as Alzheimer's. Her study of the effects of aging led her into research on the neurobiology of stress. Today, she focuses most of her energies on this area.

A brain reorg

Over the last decade, the role of psychobiology in understanding abnormal behaviors has become increasingly important, Wellman says. There has been a significant amount of research, she adds, into the effects of stress, particularly chronic stress, on the brain.

The vast majority of this scientific study, though, is on how stress affects the part of the brain called the hippocampus. Located inside the medial temporal (generally, lower middle) lobe of the brain, the hippocampus plays an essential role in the complex processes of forming, sorting, and storing memories. Humans and other mammals have two hippocampi, one in each side of the brain, and studies have shown that this region of the brain, part of the limbic system, is one of the first to suffer damage from Alzheimer's disease.

While not dismissing the impact of stress hormones on the hippocampus, Wellman has focused on another region of the brain--the prefrontal cortex. The prefrontal cortex (in the forward part of the brain), she explains, has been implicated in even more disorders than the hippocampus. Until recently, though, few had "bothered to look" at this area, which is "critically important to how we process information," she says.

"I figured we ought to look," she continues. "The hippocampus is loaded with receptors for stress hormones--possibly the highest concentration in the brain. For many years, it was thought that the hippocampus was especially plastic and able to change with experience more than other neurons do. It was much more likely then that there would be structural changes in the hippocampus. But we now know that the neurons in the prefrontal cortex are changing as a result of stress."

As Wellman explains it, when someone experiences some form of stress--someone under a writing deadline, for example--his or her brain neurons are reorganized.

By conducting research on lab rats, Wellman has demonstrated that both chronic stress and exposure to the stress hormone corticosterone reorganize dendrites of neurons in the brain's prefrontal cortex. These branch-like extensions of neurons specialize in receiving information from other nerve cells (the brain is made of approximately 100 billion nerve cells) and allowing nerve impulses to be transmitted.

These branches can grow--with rest and exercise, and by stimulating the brain through such activities as reading, doing crossword puzzles, and, yes, writing. They can also retract for many reasons, including when we are exposed to stress. Wellman has learned that dendritic shrinking in the prefrontal cortex can result in significant behavioral changes. Repeated exposure to stress can result in longer term damage to the brain's frontal lobe.

"My research has shown that exposure to stress--either over the long term, such as three weeks or even one week or just one day--can produce structural changes in the neurons of the prefrontal cortex," she says. "A neuron's shape is critically important to the way it processes information. We have seen profound changes as a result of stress and changes in behavior that the prefrontal cortex is directly responsible for."

Fortunately, our brains have the ability to "extinguish" or "unlearn" a conditioned response to a stressful situation. If you've ever had a car accident, for example, the next time you drive past the site of the crash, you might feel nervous and scared and slow down. You've formed a conditioned fear response to a cue associated with the traumatic experience. If you drive past that same site every day on your way to work, eventually, you stop responding to this cue.

"That's normal, and it keeps you from being afraid of everything," Wellman says.

"We are all exposed to stress over time," she adds. "There is always this process of growing and retraction, but for most of us, stress goes away. There are little breaks, but our neurons go back to normal."

A problem occurs when "something bad happens before we have a chance to go back to normal," Wellman says. Her work with lab rats has indicated that previous exposure to stress can interfere with the brain's ability to extinguish a fear response. This inability to extinguish a conditioned response might have significant implications for those who suffer, as many war veterans do, from post-traumatic stress disorder.

It suggests that the problem with extinction might be because of stress-induced abnormalities in the frontal lobe, Wellman says, adding that this finding is not all bad, because it also suggests that it might be possible to strengthen standard behavioral treatments for PTSD by combining them with a drug treatment that promotes better functioning of the brain's frontal lobe.

"A major treatment for post-traumatic stress disorder is extinction treatment. My research suggests we may need to do something more to address the malfunction of the prefrontal cortex," she says.

Wellman is eager to take the next step in her research toward a greater understanding of the mechanisms behind changes that occur within the brain. She believes that learning more about how different types of stress affect brain neurons could lead to potential treatments--as well as possible prevention measures--for disorders such as PTSD. She is also interested in uncovering markers that could determine which individuals are more vulnerable to stress.

"Stress doesn't produce depression or post-traumatic stress disorder in everyone, so there must be something else that combines with stress," she says. "One risk factor for depression is having a particular gene that influences the amount of serotonin produced. Maybe having this gene and being in a stressful situation increases your risk for depression. I'm interested in finding a marker for who is more affected by stress."

Stress relief

At the time of our interview, Wellman was responsible for teaching an introductory course on neuroscience, an advanced course on how stress affects our brain and behavior, a new course on advanced neurobiology, and a high-level course on health psychology. She is also instructing two graduate students and five undergraduate students who are receiving hands-on experience in her laboratory in reconstructing neurons. Though she possesses what seems to be a relaxed attitude toward her teaching and research duties, she acknowledges that she has assumed a workload that, at times, can feel quite taxing.

Which begs the obvious question. After studying the subject so intently, what coping mechanisms has she discovered for beating back stress?

Gardening, baking, horseback riding, yoga, and a couple of simple rules, she says. In general, it's useful to know when to expect a stressor--and to feel like you can do something about it. If you can't control it, find a distraction--something to take your mind off what you are doing.

Of course, the latter is easier said than done. Even Wellman admits as much. "Lately," she says, "I've been running around so much that I think, ‘What must I be doing to my prefrontal cortex?'"

Ryan Piurek is assistant director of University Communications at Indiana University.