Richard J. Servatius, PhD, associate professor of neurology and neurosciences at New Jersey Medical School
Does Stress
Change the Brain?
by Maryann Brinley
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The brain in the glass jar belonged to a researcher across the hall. And though neuro- scientist Richard J. Servatius, PhD, was busy trying to multi-task his way through a to-do list at the end of a long, busy day, he was unstressed when asked to stop everything, stand in the hallway, get ready for a photograph, smile and hold it. The brain, that is.
t’s a little sticky,” he said, laughing.
Why a brain? Well, the brain is where the effects of stress can become neuro-chemically stamped to grow into full-fledged anxiety disorders, mental illness, phobias, sleep problems and/or depression. “They’ve changed the names in the coding manual but the complaints of anxiety and depression are still the same,” Servatius explains. And if the sales’ figures for popular mood- altering pharmaceuticals and the epidemiological studies are true indicators, these are mental states many baby boomers know well.
An associate professor in the Department of Neurology and Neurosciences at UMDNJ-New Jersey Medical School (NJMS), Servatius has assembled a multidisciplinary team of researchers and theorists who are tackling problems related to “stress and coping.” Building a foundation for translational research — “even before the term was popular” — the lab studies the effects of stress using behavioral assessment techniques translating the results from mice and rats to humans. A common theme is how does stress affect coping and when does coping (avoidance) become psychopathological? Director of the Neurobehavioral Research Laboratory at the Department of Veterans Affairs-New Jersey Health Care System, he is also involved in training projects and creative solutions to homeland security issues with the support of a Defense Department task order agreement worth up to $3,300,000. As head of the UMDNJ Stress and Motivated Behavior Institute (SMBI) and a baby boomer himself, he’s an optimist even though studying a topic like stress nonstop might provide perfect fuel for pessimism.
“Humans are rather resilient,” he says. Take the 9-11 terrorists’ attacks for example. In the wake of that horrific event, the predicted epidemic of post traumatic stress disorder (PTSD) didn’t materialize. “Eighty percent of the people who went through that horrendous offense actually came out on the other side just fine without psychopathology.”
Yet, what about the other 20 percent? SMBI’s welcome online screen, written by this neuroscientist — who was, by the way, the first to graduate in 1993 from what was a new NJMS neuroscience doctoral program — addresses this question. “For some, life is a series of challenges to be met with verve. Striving, yearning and perseverance are second nature. For others, the challenges quickly overwhelm the capacity to cope; challenges bring inaction, trepidation and worry. The actual events or episodes comprising the challenge can be the same. Why are stressors a battle cry for some, but a confirmation of the difficulty of life for others?”
The answer lies in the way we learn signals in the environment under stress or in its aftermath. For the SMBI research subjects, the stress is nothing more than a tone delivered with an airpuff to the eye but by observing and assessing learning styles in mice, rats and humans, it’s not difficult to start to separate the fearful from the fearless. Meanwhile, the biochemical cascade of stress starts with a flood to the brain of corticotrophin-releasing hormone (CRH), activating the pituitary and adrenal glands. “CRH is all over the brain, including the cerebellum and is probably associated with the kind of learning that gets stamped in.” Even grasping that eye-blink response comes easier when the ventricles of the brain are infused with CRH. The team is just making “forays in adapting the work into humans,” Servatius explains. The airpuff sensation is not even as strong as a patient might
experience during an ophthalmologist’s checkup but the studies show how individuals soon blink to a warning tone even before the puff is delivered. Surprisingly, the group has found that women taking oral contraceptives learn faster than women who do not.
Learning the signals of impending stress can be beneficial because we can predict and avoid it. However, Servatius asks, “When does this learning become maladaptive and contribute to mental illness? It’s early on and I think it’s there during the development of almost perfect avoidance.” Newer work at SMBI involves a stress sensitive strain of rats, the Wistar-Kyoto (WKY). “We expected WKY rats to cower or freeze in the face of stress, but surprisingly, they learned to avoid the distress perfectly and quickly.” Even when the stress was gone, the WKYs were resistant to change or what Servatius calls “extinction.” They were unable to let go of their anxiety-ridden response, pressing little escape bars long after the shocks were gone. Like their emotionally vulnerable counterparts in the human race, male and female WKYs stuck right with their adaptive behavior. And this is the point, a possible neurobiological key, which keenly interests these researchers.
Understanding the disparate effects of stress on human biology and behavior begins in the lab for Servatius for good reasons. While he’s not a clinician, he says, “We want to understand how anxiety disorders develop.” Servatius believes that “it’s important for us to come up with an animal behavioral model that is very specific and applicable to humans.” Otherwise, drug treatments for many mental illnesses will remain little more than a guessing game for experts. “There are so many pharmacotherapies for anxiety and depression, but how to choose?” he asks.
Steven Schleifer, MD, professor of psychiatry at New Jersey Medical School
Simply trying out a range of different drugs or approaches on patients who don’t respond to the initial treatment until something finally works has been inefficient but, in actuality, often the norm. Even the American Medical Association (AMA) has acknowledged what mental health experts already knew: while the practitioner can narrow down the choice of potentially effective treatments, in many cases, there are no easy answers or rules for recommending a particular pharmaceutical, cognitive behavioral therapy or any other psychiatric approach to fixing embedded neurobiological abnormalities or temporary aberrations in brain chemistry. Finding the right remedy is, at times, a matter of trial and error with long, sometimes personally costly, pharmaceutical journeys down dark mental alleys.
NJMS psychiatrist Steven Schleifer, MD, would agree. Schleifer, who has spent years studying how behavioral factors influence the immune system, notes that the rates of depression in recent decades have, if anything, increased while expectations that depression is always treatable are often disappointed. Many baby boomers, both physicians and patients, have grown disillusioned. “What we are looking at now in medicine are areas where we once thought we had all the answers, but we don’t” — not for infectious disease, depression, or other diseases once thought to be curable using pharmaceuticals. The field of psychoneuroimmunology (PNI) itself can be seen as a paradigm for this. The excitement coming from studies implicating mental states in the onset and course of diseases including infections, cancer and autoimmune disorders led to a variety of behavioral “treatments.” However, these preventions and cures have turned out to be elusive. Such mind-body links are still highly variable and scientifically out of reach. More research in the field of brain-behavior-immune interactions is needed before we can really understand how these connections contribute to why and how we get sick. And, according to Schleifer, even more investigation must be done before we can use that knowledge to craft specific therapeutic interventions.
Meanwhile, Schleifer points out that, as a generation, baby boomers once thrived on feelings of being in control. “Perhaps we’re spoiled because we always thought life was going to get better. Even in medicine, we are realizing that we don’t have as much control as we believed. We can’t always predict the emergence and course of diseases. And a key feature of stress is that its effects become more pervasive and pronounced when you’re feeling out of control. We’ve also learned that disorders such as depression are often best treated as chronic diseases.” It has taken years for psychiatrists like Schleifer to realize that even when a prescription works to lift the cloud of depression, many people with recurrent episodes need to stay on drugs indefinitely. In the past, patients would be weaned off medication as soon as they were feeling better. In the real world, mental health experts see what Servatius has found in the laboratory: Some biologically hyper-sensitive individuals have a greater susceptibility to mental health problems.
“Fortunately, most of us are well equipped to handle stress throughout life, and brain function itself is now known to remain much more plastic than we used to think,” Schleifer says. Furthermore, we’ve come to recognize that a person’s ability to cope with stress is often more important than the sheer accumulation of stressful experiences. Early approaches to measure the effects of stress, like the Holmes-Rahe Life Stress Scale, introduced back in 1967, were found to be far too simplistic. This widely used barometer of stress would list numerous life events, from a death in the family to a minor violation of the law, and assign values to each. Individuals would then check off their stressful experiences and add up the scores to find out whether or not they were in danger of getting sick. Studies calculated that if you racked up more than 300 points, you had a 90 percent chance of coming down with a serious illness! Meanwhile, experience has taught us that not everyone reacts similarly to the same event, Schleifer explains. Your personality, feeling in control, coping style, social supports, not to mention your current physical and mental state, will all play a major role in how you weather a stressful storm, both mentally and physically.
“There is no external objective measure for stress,” Servatius adds. Like the pain scale now used in patient care, stress “is simply what the patient complains about. Take relatives coming for the holidays. What might be a stressful event for one person can be a stress alleviator for someone else.” It’s a matter of interpretation and personal brain chemistry. The good news is that instead of falling victim to epidemics of stress-related illness caused by our fast-paced society, the best statistical evidence, according to Servatius, is that in general “medical science is helping baby boomers live longer and healthier.”
Steven Dinsmore, MD, associate professor, New Jersey Institute for Successful Aging, School of Osteopathic Medicine
Want to Build a Better Memory?
One answer: Become a neurologist.
“This occupation does push the limits and squeeze the brain as far as staying mentally sharp,” says boomer Steven Dinsmore, MD, a clinical neurologist and associate professor at the New Jersey Institute for Successful Aging (NJISA), UMDNJ-School of Osteopathic Medicine. Dinsmore, with his regular stream of patients, students, medical and research puzzles, points out that one of the keys to good brain hygiene is stimulating cognitive activity.
Beyond mind-bending pursuits, there are other concrete ways to keep your memory — that sometimes frustrating, and often fearful topic for middle-agers — in thoughtful, resilient shape. In fact, the NJISA staff has been taking “BAM!” (Brain and Memory), an innovative community program, on the roads in New Jersey to have Claire DiVito, education coordinator and nutritionist, teach “everyday strategies that can help individuals retain information. It’s not just tricks and tips,” she explains.
There are definitely physical changes in the brain after age 40, according to Dinsmore. “We lose weight there, and in scans, you can see an increase in the size of the deep ventricles as well as the gyri and the sulci, which are the folds in the brain.” Biochemically, there is also depletion in the neurochemicals needed for cell to cell communication. The brain responds to all sorts of inherited as well as environmental events, DiVito explains, which can enhance or diminish the capacity to think and remember. A decrease in blood supply, hearing loss and fading eyesight make it more difficult to learn but multi-tasking and an onslaught of high stress (which floods the brain with the hormone cortisol) aren’t going to help you encode, or get the information into your memory bank.
“Memory isn’t just one function. It’s actually a complex interaction of learning, storing and retrieving information.” Scientific models for how all this works are still in flux, says Dinsmore. “The best way to break it down from a clinical standpoint and the real issues are: new learning versus stored information.” Grasping something new requires a different range of neural and biochemical functions from retaining and retrieving old knowledge. Like film left sitting in an old fashioned still photographic camera, new learning is stored at first in a flimsy state and will eventually decay or deteriorate if it’s never used.
“That original, initial capture of the information by the brain is fragile and time
dependent,” he explains. Experts call this first step encoding. Undeveloped, such film images can turn blank white. Only at the next stage, is the memory developed further and fixed in your mind. Then memories become stable and retrievable. When you do this, you are actually reinforcing the synapses between the neurons in your brain, which are protein based and have real physical structure. “Think about it. Even long established ideas and thoughts are bolstered as people recall events, laying them down deeper into the brain and probably more redundantly in a physical sense.” An emotionally charged atmosphere, where many senses are engaged, will also increase the likelihood of a memory lasting a long time. “The higher the emotional content, the more likely a memory is to stick. Simply being interested in a topic is a quality of emotion.”
Brain damaging factors include everything from head injury, uncontrolled diabetes, high blood pressure, smoking, and drinking alcohol excessively to poor cardiovascular health. “You might question whether having your brain
banged around playing football or soccer is such a good idea. Also, the heart used to get all the attention, especially in the 70s,” Dinsmore says, but the concept that has now emerged is that the same cardio and arterial risk factors apply to the brain. “High lipids, high cholesterol, poor diet, lack of exercise…these are the same significant parameters for brain health.” At 40, your mind is still fairly robust and plastic, “especially if you haven’t been behaving badly, but by 50, you really need to hammer at those issues within your control because they will contribute to mental decline.” Even Alzheimer’s is now being seen as a disease process somehow related to low blood flow. Small blood vessel damage in the brain was once thought of as separate from Alzheimer’s but “there is a lot of synergistic overlap,” Dinsmore explains. “Perhaps the cerebrovascular disease precipitates Alzheimer’s.”
There is an oft-repeated list of good health habits for a long happy life and regular aerobic activity always tops this chart because of the oxygen, endorphins and other good things it delivers everywhere in your body. However, even one of Dinsmore’s old rules for brain health — eating a balanced diet — received a recent new twist. A study published in November in Neurology followed more than 3,000 aging Chicago residents for six years and found that those who consumed 2.8
servings of vegetables each day had a slower rate of cognitive decline, by 40 percent, than people who didn’t. “Green leafy vegetables had the strongest association,” Dinsmore reports.
Though he admits that he’s a carbohydrate kind of guy who walks at least three times a week, this neurologist wonders, “The relationship between mental health and food makes me want to ask: how do we really know what to eat? Our eating habits and food preferences have emerged through trial and error through the millennia.” And while the evidence is empirical, Dinsmore explains, even fruits didn’t have the same powerful effect as the brightly colored vegetables with certain botanical plant pigments and antioxidant qualities. “Eat more vegetables,” he suggests. And as a nutritionist, DiVito also recommends folate, B vitamins, vitamin C, riboflavin, thiamin, niacin, zinc, iron and plain old water.
“The brain is very dynamic,” Dinsmore explains, “and doesn’t have the perfection we’d like. In fact, it has glaring variabilities in its functioning from day to day.” But theoretically, it is always capable of being remodeled. “Even with stroke and head injury victims, the brain has been shown to rebound.”