Stress and Your Brain

As we gain greater insight into the effects of stress on the brain, the picture that emerges is not a pretty one. Once thought to be temporary, the stress-response is now proving to have permanent repercussions.

Those irritating things that go wrong in the day and those aggravating things that go bump in the night — disrupting routines and interrupting sleep — all have a cumulative effect on your brain, especially its ability to remember and learn. Why? Because when your brain perceives a threat, it produces a chemical that actually eats away at that part of itself which is largely responsible for memory.

As research reveals the role stress plays in deteriorating mental function, renewed importance is being placed on the many techniques used to activate the relaxation response and counteract the very real consequences of stress.

A Tiger on Your Tail
That "saber-toothed tiger" stalking you today is more likely to be a tailgating SUV or an approaching final exam. No matter. Whether the threat is real, remembered, or imagined, your brain quickly responds with powerful chemicals that initiate dramatic metabolic changes throughout your body.

Your heart pounds, chest heaves, muscles tighten. Senses sharpen and time slips into slow motion. You become impervious to pain, and butterflies emerge from their cocoons in your stomach. Under certain conditions, this would be an appropriate healthy reaction, because now you are exquisitely prepared to do battle. The trouble, however, is that you're probably still sitting in your car or at your desk — stewing in your juices.

When the danger finally passes or the perceived threat is over, your brain initiates a reverse course. This releases a different bevy of biochemicals throughout your body to slowly bring you back into balance, as your brain seeks the holy grail of "homeostasis," that elusive state of metabolic equilibrium between the stimulating and the tranquilizing chemical forces in your body.

If one of these forces dominates the other without relief, then you will experience an on-going state of internal imbalance. This condition is known as stress. And it can have serious consequences for your brain cells.

The Internal Tug of War
The term "stress" is short for distress, a word evolved from Latin that means "to draw or pull apart." The Romans even used the term districtia for "a being torn asunder." When stressed-out, most of us can probably relate to this description, but it also suggests the biochemistry of stress.

The primary area of your brain that deals with stress is its limbic system. Because of its enormous influence on emotions and memory, it is often called the emotional brain, or the mammalian brain, because it evolved with our warm-blooded relatives and marked the beginning of social cooperation in the animal kingdom. Whenever you perceive a threat, imminent or imagined, the limbic system immediately responds via your autonomic nervous system — the complex network of endocrine glands that automatically regulates your metabolism. It has two branches, each pulling in opposite directions.

Your sympathetic nervous system (SNS) turns on the "fight or flight" response, while your parasympathetic nervous system (PNS) promotes the "relaxation response." Like two tug of war teams skillfully supporting their rope with a minimum of tension, the SNS and PNS carefully maintain your metabolic equilibrium by making necessary adjustments whenever something disturbs this balance.

The strongmen on these teams are hormones, the chemical messengers produced by your endocrine glands. Named after a Greek word meaning "to set in motion," hormones travel through your bloodstream to accelerate or suppress metabolic functions. The trouble is that certain stress hormones don't know when to quit pulling. They remain active in your brain for too long, injuring and even killing the brain cells you need for memory and learning.

But all is not lost. There are ways that you can learn to overcome evolution and survive this eternal internal tug of war. These techniques are introduced in Brain.com's relaxation section.

Distress Signals from Your Brain
Your sympathetic nervous system does an excellent job of rapidly preparing you to deal with what you perceive as a threat to your safety. Its hormones initiate several metabolic processes that best allow you to cope with sudden danger.

Your adrenal glands release adrenaline (also known as epinephrine) and other hormones that increase breathing, heart rate, and blood pressure. This moves more oxygen-rich blood faster to the brain and to the muscles needed for fighting or fleeing. And you have plenty of energy to do either, because adrenaline causes a rapid release of glucose and fatty acids into your bloodstream. Also, your senses become keener, your memory sharper, and you are less sensitive to pain.

Other hormones shut down functions unnecessary during the emergency. Growth, reproduction, and the immune system all go on hold. Blood flow to the skin is reduced. That's why chronic stress leads to sexual dysfunction, increases your chance of getting sick, and often manifests in skin ailments.

With your body and mind in this temporary state of metabolic overdrive, you are now prepared to respond to a life-threatening situation. After you have done so and the danger has passed, your body then tries to return to normal. But this may not happen so easily and becomes even more difficult as you get older.

Although the hyperactivating sympathetic nervous system jumps into action immediately, it's very slow to turn off and allow the tranquilizing parasympathetic nervous system to take over and calm you down. Once the stress response has been activated, the system wisely keeps you in a state of readiness. (That saber-toothed tiger or SUV might be preparing for another pass at you.) Because of this hierarchical dominance of the SNS over the PNS, it often requires an intentional technique to activate the relaxation response and to reestablish homeostasis.

It's All in Your Head
The irony of the stress response is that it evolved in physical environments very different from the social and psychological ones today. We experience many problems, or stressors, that our brain perceives as life-threatening, although they are not.

The thought of a late menstrual period or mortgage payment does not need an intense physical response, but we get one anyway. A chronic overreaction to stressors overloads us with powerful hormones that were only intended for short-term duty in emergency situations. Their cumulative effect damages and kills brain cells.

For example, too many stress hormones can prevent the brain from laying down a new memory or accessing already existing memories. And, in a nasty irony, stress hormones can damage the very part of the brain that's supposed to signal when to shut-off their production — creating a vicious cycle that degenerates the brain and diminishes the quality of life.

The Cortisol Conspiracy
The renowned brain researcher, Robert M. Sapolsky, has shown that sustained stress can damage the hippocampus, the part of our limbic brain which is central to learning and memory. The culprits are "glucocorticoids," a class of steroid hormones secreted from the adrenal glands during stress. They are more commonly know as corticosteroids or cortisol.

During a perceived threat, your adrenal glands immediately release adrenalin. After a couple of minutes, if the threat is severe or still persists, the adrenals then release cortisol. Once in the brain, cortisol remains much longer than adrenalin and continues to affect brain cells.

Chronic over secretion of cortisol adversely affects brain function, especially memory. Human studies show a correlation between high cortisol levels and decreased memory and cognitive functions like concentration and creativity.

How Cortisol Affects Brain Function
First, because stress hormones divert blood glucose to exercising muscles, the amount of glucose — hence energy — that reaches the hippocampus is diminished. This creates an energy crisis in the hippocampus which makes it unable to create new memories. That's why some people can't remember a very traumatic event, and why short-term memory is usually the first casualty of age-related memory loss resulting from a lifetime of stress.

Cortisol also interferes with the function of neurotransmitters, the chemicals that brain cells use to communicate with each other. This makes it difficult to think or access long-term memories. That's why people get befuddled and confused in a severe crisis. Their mind goes blank because "the lines are down."

Stress Hormones Short-Circuit Memory Retrieval
Thirty minutes after rats were stressed by an electrical shock, they were unable to remember their way around a maze. When the shock was given two minutes or four hours before going through the maze, the rats had no problem. This time-dependent effect on memory performance correlates with the levels of circulating glucocorticoids, which are highest at 30 minutes. The same thing happened when non-stressed rats were injected with glucocorticoids. When glucocorticoid production was chemically suppressed, there were no stress-induced effects on memory retrieval.

According to James McGaugh, director of the Center for the Neurobiology of Learning and Memory at the University of California at Irvine, "This effect only lasts for a couple of hours, so that the impairing effect in this case is a temporary impairment of retrieval. The memory is not lost. It is just inaccessible or less accessible for a period of time." (Nature, Aug 20, 1998)

Degeneration Why
Cortisol also causes excess amounts of calcium to enter brain cells, which eventually leads to the production of free radicals, the reactive molecules that injure and kill cells.

Unfortunately, there's a final insult. The hippocampus is extremely sensitive to cortisol. Sapolsky's studies showed that lots of exposure to cortisol or lots of stress itself accelerated the degeneration of the aging hippocampus. And because the hippocampus is part of the feedback mechanism that signals when to stop cortisol production, a damaged hippocampus causes cortisol levels to get out of control — further compromising memory and cognitive function. The cycle of degeneration then continues.

Sleeplessness Kills
Researchers at Harvard Medical School found that cheating on sleep for only a few nights increased brain levels of cortisol. Inadequate sleep also deprived the brain of the time it needs to reestablish its energy. A survey by the National Sleep Foundation revealed that almost two-thirds of Americans fail to get enough sleep. Not only does this lead to impairment and death of hippocampal cells, but also to injury and death from the 100,000 accidents caused by sleepy drivers each year. (Spectrum, Sep/Oct 1998)

Sleep Less in School
A study of 500 children, under five years of age, found that those who slept less than 10 hours a day, including naps, were 25% more likely to misbehave (throw temper tantrums, act aggressively, etc.,) than children who slept 12 or more hours a day. (J Dev and Behavioral Pediatrics 1999;20:28-33)

Depression Shrinks Hippocampus
The size of the hippocampus averaged 14% smaller in a group of septuagenarians who showed high and rising cortisol levels, compared to a group with moderate and decreasing levels. They also did worse at remembering a path through a human maze and pictures they'd seen 24 hours earlier and — two tasks that use the hippocampus. A third of the 60 volunteers, who were between ages 60 and 85, had chronically high cortisol levels, a problem that seems to be fairly common in older people. This study, titled "Cortisol levels during human aging predict hippocampal atrophy and memory deficits," was reported in Nature Neuroscience, May 1998.

Dr. Sapolsky discovered that general SNS arousal is a relative indication of anxiety and vigilance — the individual is trying to deal with the challenge. On the other hand, a heavy secretion of glucocorticoids is more a marker of depression — the individual has given up on trying to cope. This burned-out feeling of depression represents the exhaustion stage of chronic stress, where a person feels worthless and has no energy to do anything about it.

New research suggests that the hippocampus is needed temporarily to bind together the various sites that represent a whole memory — sites that are distributed elsewhere in the brain. (Psychol Rev, July 1999)

Spawn and Die
Salmon amaze us with their spectacular leaps up waterfalls and over dams, in their single-minded quest to return and lay eggs in the freshwater stream of their birth. After that, they die. But why? Dr. Sapolsky explains in his book, Why Zebras Don't Get Ulcers:

"If you catch salmon right after they spawn, just when they are looking a little green abound the gills, you find they have huge adrenal glands, peptic ulcers, and kidney lesions; their immune systems have collapsed, and they are teeming with parasites and infections. . . . Moreover, the salmon have stupendously high glucocorticoid concentrations in their bloodstreams. When salmon spawn, regulation of their glucocorticoid secretion breaks down. Basically, the brain loses its ability to measure accurately the quantities of circulating hormones and keeps sending a signal to the adrenals to secrete more of them. Lots of glucocorticoids can certainly bring about all those diseases with which the salmon are festering. Is this glucocorticoid excess really responsible for their death? Yep. Take a salmon right after spawning, remove its adrenals, and it will live for a year afterward."

The Biochemistry of the Cortisol Feedback Mechanism
In his book, Brain Longevity, Dharma Singh Khalsa, M.D., describes the system:

"Normally, in response to stress, the hypothalamus secretes a substance called 'corticotropin-releasing factor,' which then causes the pituitary gland to secrete a hormone called 'corticotropin' (or ACTH). ACTH then causes the adrenals to secrete cortisol. When levels of cortisol rise to a certain degree — a 'setpoint' — several areas of the brain tell the hypothalamus to turn off the cortisol-producing mechanism. This is the proper 'feedback' response.

"However, one of the areas of the brain that is most responsible for telling the hypothalamus to turn off cortisol production is the hippocampus . . . the area most damaged by cortisol. The hippocampus is often so damaged in older people — who may have lost about 20 to 25 percent of their hippocampus cells — that it is unable to give the proper feedback to the hypothalamus.

"When that happens, the hypothalamus keeps pumping out the chemicals that cause cortisol oversecretion. This, in turn, causes even more to the hippocampus. And this, of course, causes even more cortisol production. Thus, a catch-22, 'degenerative cascade' begins. And this cascade can be very difficult to stop."

What Blood-Brain Barrier?
To protect themselves from chemical and biological weapons during the Gulf War, Israeli soldiers were given a drug called pyridostigmine. Nearly one-quarter of them complained of headaches, nausea, and dizziness — symptoms which occur only if the drug reaches the brain. Pyridostigmine molecules generally can't get into the brain, so why had the side-effects increased during combat?

An Israeli biochemist and physician wondered whether the stress of war might somehow have increased the permeability of the blood-brain barrier. The two researchers took a group of mice and stressed some by dunking them in water. They then injected the rodents with a dye and measured its intensity in the autopsied brains. They found that the dye had passed much more readily into the brains of the stressed animals.

The fact that stress can dramatically increase the ability of chemicals to pass through the blood-brain barrier has enormous implications, since many drugs are developed under the assumption that they will stay in the periphery. (Discover, May 1997)

It's Not All in Your Head
Dr. Sapolsky's research with animals also showed that glucocorticoid excess brings about many problems, including "fatigue, thinning muscles, adult-onset diabetes, hypertension, osteoporosis, reproductive decline, and immune suppression — all conditions more common among the elderly." Dr. Sapolsky concludes that "Aged organisms not only have trouble turning off the stress-response after the end of stress, they also secrete more stress-related hormones even in their normal, nonstressed state. . . . Old individuals of all sorts tend to have the stress-response turned on even when nothing stressful is happening."

Table of Discontents
As youngsters, we were all told to settle down at the dinner table. Fine dining is synonymous with an atmosphere conducive to relaxation. All for good reason. We shouldn't eat while in a state of anxiety. The stress response diverts blood away from the digestive tract, which inhibits the absorption of nutrients from food.

In a study at Temple University in Philadelphia, stress was shown to inhibit the production of alpha-amylase, an enzyme in saliva that digests carbohydrates. Test subjects either meditated or did math problems in their head five minutes before eating cereal. When their alpha-amylase production was measured, those who concentrated on the math had 22% less enzyme than the meditators. (American Health, Dec. 1997)

Ideally, we should be content before as well as after a meal.

Why Stress Slows Healing
The wound healing process depends on the activity of two key healing compounds, but stress from emotional upset appears to reduce their activity. Interleukin-1 and interleukin-8 help protect against infection and prepare injured tissue for repair. In a study of women who were healing from blisters, researchers at Ohio State University found interleukin compounds at significantly lower levels in the women with the highest levels of cortisol. As stress and cortisol levels rise, interleukin levels fall — triggering a slowdown in the healing process. (Archives of General Psychiatry 1999;56:450-456)

Stress Adds Injury to Insult
Athletes are two to five times more likely to get injured if they're experiencing recent life stress, compared to less stressed counterparts — according to at least 18 different studies. (Spectrum, Sep/Oct 1997)

A Prescription for Dementia?
At Neuroscience 2000, a worldwide gathering of neurologists sponsored by the Society for Neuroscience, Robert Sapolsky of Stanford University expressed concern about the use of certain steroid hormones to treat arthritis. He noted that hydrocortisone may damage the hippocampus and has been linked to cases of "steroid dementia."

Stress is Not All Bad
Bear in mind that an appropriate stress response is a healthy and necessary part of life. One of the things it does is to release norepinephrine, one of the principal excitatory neurotransmitters. Norepinephrine is needed to create new memories. It improves mood. Problems feel more like challenges, which encourages creative thinking that stimulates your brain to grow new connections within itself.

The challenge in this day and age is to not let your sympathetic nervous system stay chronically aroused, but this takes a conscious effort and requires knowledge of techniques that work to activate your relaxation response.