Book Summary - Why zebras don’t get ulcers by Sapolsky (3rd edition)

What basic principles of human functioning are important? - Chapter 1

What has changed in common disease patterns?

In recent decades, much has changed in common disease patterns. Partly due to advances in the development of pharmacy, the patterns now look very different and are no longer comparable with, for example, diseases that our ancestors died from. Nowadays , more and more people suffer from heart failure and cardio-vascular diseases than, for example , from infections and malnutrition. In connection with this change in disease patterns, the picture of how we view diseases has also undergone changes. We have discovered that there is a strong connection between emotions and the biological processes in our body. Our thoughts, feelings and personalities influence these processes in our body , which can cause that two people who get the same disease to go through a totally different course of the disease. Stress also affects our health and can even make us feel sick. However, stress can lead to adaptation of the body to certain situations in order to survive. In this way, the neurons in our brain can survive for five minutes without oxygen during a heart attack , without being permanently damaged .

In addition to differences between people of today and of the past , there are also differences between people and animals. This difference mainly concerns the area of ​​how they experience stress. Animals experience stress only in acute physical crisis situations. Consider the following example: A zebra is hunted by a tiger. The zebra will suddenly have to run , in order to bring itself to safety . The zebra can even be injured by the tiger and still keep on trying to flee. At this point, a lot of things are physically demanded of the zebra. However, their body appears to be perfectly capable of dealing with this type of stress. People, on the other hand, more often experience chronic physical stress instead of acute stress. For example, when a farmer's crops have been eaten by animals, he will have to get his food from somewhere else for a long period of time. For example, he will have to walk much further each time to get some food . Because every time, for a long time, he has to make more effort for his food, he undergoes chronic physical stress. The human body can handle this type of stress reasonably well.

In addition to acute and chronic physical stress, there is a third form of stress, which is psychological and social stress. This type of stress is typical for humans. What stands out is that this type of stress actually only exists in our heads: There is no real physical threat. So, we can experience intense emotions that are in reality just the result of our thoughts . Our bodies can give the same reactions to psychological and social stress as to physical stress. Our bodies can adapt very well to cope with acute stress that lasts for a short time . However , this is different when the stress appears to be chronic and we activate our stress system very often for a long period of time.

The body is not prepared for this kind of activity, because the physiological defense mechanisms were originally intended to enable the body to respond quickly and efficiently to a sudden threat. For a certain period of time, the body will resist the psychological stress, but exhaustion will inevitably follow. This can cause stress-related diseases.

The body is constantly working in order to reach a state of homeostasis. Homeostasis refers to the idea that the body consists of different mechanisms and that each of these mechanisms has an optimal level; a balance. Homeostasis means that the body is fully outbalanced, in other words: all mechanisms have reached their optimum level. For example, during homeostasis; the brain receives just enough oxygen and the blood is pumped through the body at a steady pace. The body is always trying to achieve this state of homeostasis. There are, however, a number of factors that can disrupt the body's homeostasis. We call these factors stressors. Stressors are all the events that take place outside the body that can take us out of the homeostatic balance. The body responds by means of a stress response, through which it will start activities to reach the state of homeostasis again.

However, a stressor does not only have to be an event that is currently taking place. People are able to look ahead and see possible threats in the future. Humans can anticipate this. Resultingly, we can elicit a stress response only by thinking about potential stressors. The stress response is therefore not only triggered by physical or psychological threats, but also already in anticipation of a threat. This was first discovered by Selye, about sixty-five years ago. Selye did a study on rats. He injected his rats on a daily basis with an extract from an ovary. But because he was a bit clumsy, the rats often fell and he had to look for them for a long period of time before he could try to inject them again. At the end of the study, it appeared that the rats were suffering from enlarged adrenal glands and stomach ulcers. To exclude that these symptoms were the result of the injections, Selye used a control group that he injected with saline. These rats also regularly fell to the ground and were hunted by Selye in an attempt to get a hold of them. The control group appeared to show the very same symptoms as the experimental group, which led Selye to conclude that these physical symptoms were caused by the stress that arose when he followed the fallen rats.

Selye came to two conclusions:

1. The body uses the same responses for multiple different stressors. Selye called this the general adaptation syndrome, and nowadays this phenomenon is called the stress response.

2. Stressors that persist for too long can lead to illness.

What is allostase?

The original concept of homeostasis was based on two ideas:

1. There is one optimum level or optimum amount for all measurable things in the body, such as the ideal blood pressure, temperature, etc.

2. You achieve this optimum level or this optimum amount through a local regulatory mechanism.

However, this concept was proved to be incorrect and has therefore been extended with the theory of allostase. With regard to the first idea, this means that there are different optimal levels, depending on what you are doing. The optimum value for heart rate is much lower when you are sleeping than when you are training for the marathon. So there is not one optimum level, but multiple different optimum levels. Considering the second idea, this means that there is not one way in which the ideal level can be achieved, but this can be done in multiple different ways. Every way will have its own outcome. Roughly speaking, the difference between homeostasis and allostase is that in the case of a deficiency, homeostasis only addresses the responsible mechanism but allostase causes the brain to direct changes in the entire body, and often in behavior too. An example : suppose your body lacks water . With homeostasis, only the kidneys would be directed to produce less urine . Allostase does this as well, but it also extracts water from other body parts and causes you to get thirsty.

The body does not have to stop all complex regulatory processes to restore a certain value. Moreover, the body is able to anticipate values ​​that will deviate from their optimum level. The brain can therefore control certain bodily functions in advance, which will ensure that a certain value will not lose its optimum level. This corresponds to the fact that the body can respond to a stressor before it actually occurs.

How to adapt to an acute stressor?

In this adapted theory, a stressor is seen as all factors that could possibly get you out of your allostatic balance. The stress response concerns your body's attempts to restore allostasis. Although it is logical to think that specific challenges for the body require specific adjustments, every stressor yields the same stress response.

In people, the key point of the stress response lies in the fact that the muscles in the body have to work much harder than normal. Firstly, glucose must be mobilized, which provides energy. The glucose is then rapidly transported through the body by increasing its heart rate, blood pressure and speed of breathing. The sympathetic system is activated, while other processes in the body are ceased . Examples of this are digestion, growth and reproduction.

The immune system will also be suppressed temporarily . The energy that is saved by this will be used to make the sympathetic system work harder. The parasympathetic system is temporarily switched off. Remember the story about the zebra running from the tiger: The perception of pain can also be switched off during acute stress. Another example, think of a soldier who does not realize that he was injured during the time that the fight is still going on. Only once the battle is over, the perception of pain returns.

During acute stress there is also a change in cognitive and sensory skills. Certain parts of the memory improve, so you can quickly remember whether you have been in a similar situation before and how you can get out of it. Moreover, your senses become sharper. During an acute stress situation you can be startled by the squeaking of a door, while normally, you would barely notice this .

Selye designed a three-phase theory about stress responses. The first phase is the alarm phase, in which the stressor is noticed. This can be compared to an alarm that goes off in your head and at that point you can tell that something is wrong. The second phase is the phase of adaptation or resistance, in which the stress response system is mobilized and the body attempts to return to its allostatic balance. With persistent stress, the third phase of exhaustion can start . However, Selye made the mistake of thinking that you became ill because the hormones that are secreted during the stress response ran out . However, this cannot be the case, because these hormones are so crucial that we can't possibly ever run out of it. The stress response can have a harmful effect on the body if it is activated sufficiently. The stress response is especially harmful if the stressor is psychological. The consequences can be enormous , especially in the case of long-term (psychological) stress or when you suffer from stress very often. Because you spend your energy in response to stress so often, the body does not have time to recover and rebuild its reserves . Because you do not build up your reserves, your body will be exhausted faster. People who are under chronic stress also often suffer from reproductive disorders. You are also more likely to suffer from diabetes and high blood pressure, because the cardiovascular system is activated chronically . In addition , the immune system is often suppressed, making you more susceptible to infectious diseases. You will also have more trouble eliminating these diseases from your body . Finally, certain brain functions can also be affected if a certain hormone that is secreted during stress is produced excessively. When you have a lot of stress and therefore often excrete stress hormones, it will always be harder to find the balance of allostase. The following problems may arise:

• It takes a lot of energy to keep on trying to find this balance. This energy can no longer be used for processes that take place in the long term, such as storing energy.

• The use of stress hormones helps to relieve the stressor, but it often gets small processes in the body out of balance. Thus, a complete allostase is still not achieved.

• Illness can also occur when the stress response is turned off too slowly , or when different components are turned off at different times . For example, the values ​​of one stress hormone may return to normal, while the values ​​of another hormone are still very high.

Having a stress response is important, which has become evident from the studies of people who do not have the stress response due to an illness. Two important hormones are secreted during stress. In Addison's disease and 'Shy-carrier syndrome' people are unable to secrete certain hormones, which results in the fact that no stress response is triggered. When people with Addison's disease are confronted with a trauma , they go into a so-called 'Adissonian' crisis, which means that blood pressure falls and they fall into shock.

Shy carrier syndrome is a disease in which the blood pressure drops sharply when the patient stands up . The amount of sweat, tear fluid and saliva diminishes, vision is poor, urination is difficult and often, there is impotence.

If you repeatedly activate your stress response or if you have difficulty turning off the stress response again when the stressful situation is over, it is possible that the stress response may ultimately be harmful to your body . However , it is not the stress or the stressor that makes you sick. Chronic stressors or recurring stressors only increase the risk of getting sick. They also increase the chance that defense mechanisms cannot win the fight against a disease. There are different steps between getting a disease and actually getting sick. This also causes individual differences.

Practice questions

1. What is allostase?

2. Which of the following is no function of the biological 'fight or flight' stress response?

A) Limiting damage 

B) Transporting oxygen to the muscles

C) Causing negative emotions

D) Saving energy by suppressing unnecessary bodily activities

3. During the stress response the sympathetic nervous system is active / deactivated and the parasympathetic nervous system is active / deactivated.

Answers to the practice questions:

1. Allostase is a balanced state of the body. Attaining the state of allostase in the body happens through the secretion of stress hormones and mediators by the brain.

2. C

3. Active, deactivated

What happens in the body during a stress response? - Chapter 2

Thoughts can end up affecting your entire body. The thought of something frightening can cause you to start sweating, even though in reality there is nothing wrong. What happens in your body is controlled by the brain.

What is the connection between stress and the nervous system?

Your brain controls the rest of your body by sending signals to the nerves that run down from the brain through the spinal cord. This can happen deliberately when, for example, you control your muscles to walk home. These actions are driven by the voluntary nervous system . But actions can also happen unconsciously. When you get cold, you often get goosebumps without consciously controlling your body to get these goosebumps. These signals are therefore automatic and are involuntary. For example, when you blush, you often do not want this at all, but you cannot help it.

The set of nerves that control this kind of automatic, involuntary processes is called the autonomic nervous system . This system is very important for the stress response . Half of this autonomic nervous system is activated during a stress response, the other half is suppressed . The half that is activated is called the sympathetic nervous system . Half that is suppressed is called the parasympathetic nervous system . Both systems start in the brain and go through the spinal cord to practically all places in your body, such as organs, blood fibers and sweat glands.

The sympathetic nervous system is activated in the case of an emergency, or when you suspect that there is an emergency. You could also say that it is activated in case of flight, fighting, fear and sex.

The sympathetic nerve cells secrete epinephrine (adrenaline) and norepinephrine (noradrenaline). Epinephrine is excreted by the glands that are just above the kidneys (the adrenal glands) . Norepinephrine is excreted by all other sympathetic nerve endings.

The parasympathetic nervous system controls the quiet, time-consuming activities in the body such as energy storage and growth. The sympathetic and the parasympathetic nervous system are therefore opposite to each other and cannot work simultaneously on the same process in the body .

How does the brain work during a stress response?

The brain controls the stress response through the nerves in the sympathetic nervous system. Yet, this is not the only way in which the brain creates a stress response. The brain also secretes hormones.

A neuron (a cell from the nervous system) can secrete a neurotransmitter. A neurotransmitter is a chemical messenger that can travel super fast to another neuron to make it do something different from what it is currently doing. For example, a sympathetic nerve endings can secrete norepinephrine into the heart, causing the heart muscle to work differently.

However, a neuron can also send a messenger that ends up in the blood instead of another neuron and can travel great distances through the body. Such a messenger is a hormone. Some hormones are activated during stress, while others are suppressed.

It used to be thought that the parts of the body that secret the hormones (peripheral glands), such as the pancreas and the testes, knew themselves when and when not to excrete hormones.

For example, they thought that the fact that the sexual urges of men decrease with age is because the testicles excrete less testosterone. The solution to this problem would then be easy: give the men testosterone! The testosterone extracts that were used were taken from animals and injected into the men. However, this did not work. Patients were in fact injected with a water-based extract, and testosterone does not dissolve in water. But if it would have dissolved, it would also not have worked. The fact that the testes excrete less testosterone is not due to the testes, but because another organ (namely the brain) no longer tells them to do that. Scientists also came to this discovery. At first they thought that the pituitary gland controlled these peripheral glands . They only release hormones after the pituitary gland has secreted a hormone, which causes the peripheral glands to take action. When the pituitary gland is damaged, the hormone balance is disrupted.

In the 1950s it was discovered that the pituitary gland was not the 'master gland'. In a study, a pituitary gland had been removed and replaced in a kind of bottle with nutrients. The result was that certain hormones that are normally excreted were not released now, while other hormones were released in very large numbers. For example, it was discovered that the pituitary gland does not work on its own, because if this had been the case, the pituitary gland would have had to release the same amounts of hormones during the study as it normally did. It was found that the pituitary gland follows the orders of the brain. This was investigated by damaging parts of the brain that were close to the pituitary gland, with the result that the pituitary gland became disrupted and started to secrete hormones.

One question remains: how does the brain accomplish this? There are no nerves from the brain to the pituitary gland. In 1944, physiologist Geoffrey Harris came up with the idea that it could be that the brain also releases hormones, which then go to the pituitary gland and regulate the actions of this organ. Some hormones stimulate the secretion of hormones, other hormones suppress the release that hormones . Guillemin and Schally investigated this and discovered after years of research that this is indeed the case.

We now know that the brain is at the head of secreting hormones. This is based on the hypothalamus, which can secrete a large amount of different hormones. The hypothalamus can control the pituitary gland by secreting only one hormone. This hormone has an activating function and an inhibitory function. The hypothalamus can also control the pituitary gland by means of an activating and an inhibiting hormone. We then speak of dual control. Moreover, it is possible that the hypothalamus secretes several different hormones in order to control the pituitary gland.

What is the connection between hormones and stress?

Hormones are very important for stress. The two hormones that are most important in the stress response are the previously discussed epinephrine and norepinephrine ; which are both excreted by the sympathetic nervous system. Glucocorticoids are also very important for the stress response. Glucocorticoids are among the steroid hormones (including: androgen, estrogen, progestin, mineralocorticoids and glucocorticoids). They are excreted by the adrenal glands, which lie just above the kidneys.

The glucocorticoids resemble the effect on epinephrine. But epinephrine already works within a few seconds, while glucocorticoids only work after a few minutes to a few hours. It could be argued that glucocorticoids take over the activities of epinephrine.

The secretion of glucocorticoids is also controlled by the brain. When something happens that is stressful or that the person involves perceives to be stressful, the hypothalamus secretes different hormones into the pituitary gland. This is a circulating system. The most important hormone secreted by the hypothalamus is CRH (corticotropin releasing hormone). Within about fifteen seconds, the CRH stimulates the pituitary gland to secrete the hormone ACTH (corticotropin). ACTH then enters the bloodstream and reaches the adrenal glands. In the adrenal glands, ACTH ensures that glucocorticoids are excreted.

Together with the action of the sympathetic nervous system (in particular the excretion of epinephrine and norepinephrine), the glucocorticoids cause the body's most important reactions to stress.

Your pancreas is also stimulated during stress to excrete the hormone glucagon . Glucagon, glucocorticoids and the sympathetic nervous system ensure that the sugar level (glucose) in the body is increased. This provides more energy. The brain and pituitary gland also secrete endogenous, morphine-like substances, namely endorphins and enkephalin . These hormones ensure, among other things, that you hardly notice any pain. The pituitary gland also secretes an anti-diuretic hormone (vasopressin), which ensures that little urine is excreted for water conservation in the body.

In addition to the activation of certain hormones, there are also hormones that are suppressed during the stress response. This mainly concerns hormones that are related to reproduction, growth and the release of insulin, which normally causes the body to store energy for later use.

What are the possible complications?

So the aim of the stress response is to 'fight or flight'. However, researcher Taylor disputes whether this response is the same for men and women. Research has shown that the fight or flight response actually only occurs in men. Men are often much more aggressive than women. That is why men will fight a lot faster. However, women must also take their children into account, making them often unable to fight or to flee; Since in that case, they would need to leave their children behind. 'Be careful and be a friend' (tend and befriend) is therefore a more common stress response in women. This is, from an evolutionary perspective, much more useful for them than fighting or fleeing.

During stress, the pituitary gland also secretes the hormone oxytocin in women . Among other things, this hormone causes women to stay with one man and to therefore be monogamous. That is why this hormone fits much better with Taylor's theory about being careful and becoming friends. There are opponents who say that women might as well be aggressive and flee, but often women tend to be aggressive only when there is a threat to their children.

Taylor's theory is generally accepted. It is recognized that the body does not only respond to stress by preparing the body for fighting and fleeing. Moreover, it has become common knowledge that there are important sex differences in the physiology and psychology of stress.

Another complication is that some characteristics of the stress response are different for different animals: Take, for example, the difference in time of the effects of epinephrine and glucocorticoids. In humans, epinephrine works within seconds, while glucocorticoids only work after a few hours. For some animal species, however, this is not at all convenient. If you are the zebra that is being hunted, you do not have to sustain the flight response for hours. The effect of the glucocorticoids would therefore occur too late. In this type of animal, glucocorticoids appear to be more responsible for recovery after the stress response. In some cases, glucocorticoids can also act as preparation for the next stressor.

Epinephrine and glucocorticoids can each cause the other to be excreted because they are both excreted by the adrenal gland.

Because of this your stress response is often the same for all stressors. However, it has been found that not all stressors provide the same stress response. The speed and amount of the sympathetic system and the glucocorticoids vary per stressor. Moreover, not all other endocrine components of the stress response are always activated. This differs per stressor as well. Similarly, the secreted hormones and their exact amount differ per stressor. However, two different stressors may result in a secretion of exactly the same amount of the same hormones. In this case the sensitivity for the two stressors differs in different parts of the body. This means that some parts of the body will not respond to one stressor, but will respond to the other.

Practice questions

1. From an evolutionary perspective, what does one try to do in the case of a stress response?

2. True or untrue: The adrenal gland is responsible for excreting adrenalin.

3. What order of events is correct?

A) CRH > ACTH > cortisol

B) ACTH > CRH > cortisol

C) ACTH > cortisol > CRH

D) CRH > cortisol > ACTH

4. Why does the body suppress the production of insulin during a stress response?

Answers to the practice questions

1. Fight or flight.

2. True

3. A

4. In order to conserve energy and fuel needed for the fight or flight response.

How does the heart respond to stress? - Chapter 3

How does the heart respond to stress?

With the help of the sympathetic nervous system and some glucocorticoids, it is fairly easy to activate the cardiovascular system; including the heart and its vessels .

To start with, your heart starts to beat faster by the activation of the sympathetic nervous system and the inhibition of the parasympathetic nervous system. Glucocorticoids cause neurons in the brainstem to be activated. These then ensure that the sympathetic arousal is stimulated; by enhancing the effects of epinephrine and norepinephrine on the heart muscle. The sympathetic nervous system also ensures that your blood flows through your veins with more force. As a result, the blood is pumped against the heart walls with more force, so the heart starts beating with more force. In order to activate the cardiovascular system, the heartbeat and blood pressure must first be raised.

After this, it is important that the blood is spread through the body. The veins lead the muscles to relax, allowing more blood to pass through resulting in more oxygen is being delivered to the muscles. In addition, the parts of the body that are not important during the stress response, such as digestion, get less blood.

When the amount of blood in your body diminishes due to dehydration or because you are injured, it is important to get water from the rest of your body as quickly as possible. This water can then extend the rest of your blood and thus increase, so that enough blood can still go to the muscles. This water can be extracted from the urine that is still present in the kidneys. The kidneys work in two directions: water can be put in, but also taken out again.

However, this is not possible with the bladder. The bladder can only receive fluid, but cannot send it back into the body. That is why the brain sends a signal to the kidneys in such a case, not to produce urine and to absorb the water from the urine that is already made. This water then returns to the circular system in your body. Moreover, in such a case the blood supply to the kidneys is reduced. All this is achieved by the hormone vasopressin, also called antidiuretic hormone , and by related hormones, which maintain the water balance in the body.

You can also experience stress when it is crucial to be quiet and not stand out. For example, consider a zebra that sees a tiger walk by, but has not been seen by the tiger. The zebra will have to be extremely quiet in order not to stand out. In such a case, the blood flow is slower and resistance of the vascular system occurs throughout the body.

When a stressor is gone, the parasympathetic nervous system ensures that your heart starts beating more calmly by the influence of the vagus nerve. Your body then becomes calm again.

What are cardiovascular diseases?

In the event of acute stress, your heart starts beating faster, your blood flows through your veins with more force and more blood and energy goes to certain muscles. This is very useful. But when you sit quietly and only think of a certain stressor, the same system will be activated. However, you do not have to make any physical effort for this. This can be harmful in the long run.

You activate your heart and vessels during a stress response. But if you activate it regularly, they will wear out faster. In the case of chronic stress, your blood pressure also rises chronically. We speak of a raised blood pressure in this situation.

When it regularly happens that the heart rate and blood pressure go up as a result of stress, the risk of heart diseases is increased. What is the reason for this? When you have chronic stress, you also put more chronic pressure on certain blood vessels, because these blood vessels lead to important muscles. Therefore, these blood vessels often have to work harder, with the result that they develop thicker muscles around them, so that they can handle this powerful blood supply better.

However, these thicker, muscular blood vessels will have more resistance to the blood supply. This increases your blood pressure, so you end up in a vicious circle. Moreover, the blood arrives in the heart with more force, so that the heart starts to develop thicker muscles. However, this only happens on the left side of the heart, because blood enters the heart there and goes out again on the right. This is called "left ventricular hypertrophy": the mass of the left ventricle increases. Because your heart is now more developed on one side, an irregular heartbeat can occur. Moreover, it is possible that the left ventricle now needs more blood than the veins can deliver because of the extra muscle mass. This is the second best predictor of heart disease when considering age.

A characteristic of the circulatory system is that the large blood vessels branch out into smaller blood vessels at various points. These smaller blood vessels then branch into even smaller blood vessels, and so on. This process is called bifurcation . The points where the vessels come together are often very fragile and easily damaged.

If these points are damaged, the immune cells help to repair this damage. They do this by forming fatty nutrients (called foam cells) there. The sympathetic system also ensures that the blood becomes stickier with the help of epinephrine. During stress, energy also passes through the blood vessels. This energy contains fat, glucose and the type of cholesterol that is bad for your health.

Stress can therefore cause the blood to become stickier and that more and more blood vessels will be damaged. The result is that fat, glucose and cholesterol that circulate in the body will attach itself to the damaged blood vessels.

Scientists have tried for years to determine the risk of developing cardiovascular disease. To this end, they investigated in particular what kind of cholesterol level you may have without running your (increased) risk of cardiovascular disease. Cholesterol is also found in various products, such as eggs.

Cholesterol turned out not to be such an important predictor as people initially thought. Indeed, there are many peoples who suffer from cholesterol level that is too high, without having cardiovascular disease. In addition, only half of the people who die from a heart attack suffer from a high cholesterol level. That is why cholesterol is not a good predictor for a heart attack, despite the fact that it is a clear risk factor.

In recent years it has become clear that the number of damaged blood vessels is a more important predictor than, among other things, the amount of cholesterol circulating through the body. The amount of damage to the blood vessels is measured with a C-reacting protein, called CRP . CRP is produced in the liver and is only excreted when there is a signal that there is a wound somewhere. CRP moves to the injured blood vessels to help with healing. But CRP ensures, among other things, that bad cholesterol will attach itself to the blood vessels. The level of CRP in the body is a much better predictor of cardiovascular disease than cholesterol, even years before the disease develops.

All in all, stress can therefore lead to increased blood pressure and atherosclerosis. Atherosclerosis is the accumulation of - among other things - cholesterol in the damaged blood vessels.

Kaplan has done research on monkeys. He discovered that they too can suffer from atherosclerosis. When you put a group of monkeys together, the person with the lowest social position will often develop atherosclerosis. This is because he, as the lowest individual in the social ranking, not only has a physically lower weight (for example, he is the last to eat anything), but also socially-emotionally. As a result, this monkey suffers more from stress, with all its consequences. However, if you constantly change the composition of a group of monkeys, the monkey that is highest in the hierarchy will suffer from stress and often also from atherosclerosis. He is not sure of his dominant position, because a new group might have a stronger monkey again.

In short, the monkey with the greatest social stress suffered the most from atherosclerosis. This also happened when the monkeys were fed a diet that was low in fat. When the monkeys received beta blockers, no atherosclerosis occurred. From this we can therefore conclude that one can also suffer from atherosclerosis if one eats low-fat. The fat that flows through the blood vessels during stress is the fat that is already stored in the body, not the fat that was just in your food. However, if you follow a high-fat diet and moreover often suffer from stress, the effects are increased. Among other things, more blood vessels will be damaged.

When your blood vessels are clogged to such an extent that not enough blood flows to the lower half of your body, this is called claudication . There is not enough oxygen and glucose in the lower half of your body. This can cause your legs and chest to hurt. This can be remedied with a bypass operation. If the same thing happens near your heart, you can get different heart diseases.

If the blood passes through the veins with a lot of force, the chance of plaque breaking off is increased. Such a loose piece is called a thrombus . If this thrombus ends up in a smaller blood vessel, this blood vessel becomes completely clogged. If such a loose piece comes into a vein near the heart, you can get a heart attack. If it enters a vein near your brain, you may get a cerebral infarction.

When you have to deal with an acute stressor and your heart and vessels are in good condition, then everything in the body works as it should work. But when the vessels that lead to your heart are clogged, major problems can arise. The heart then receives too little oxygen and energy. As a result, the coronary arteries (the veins leading to your heart) will contract instead of expand. Your heart will then receive far too little nutrients. This is called myocordial ischemia . Because of this you get chest pain during stress.

Ambulatory electrocardiography was invented in the 1970s . This is a kind of small camera that you can tie on the chest and with which you see the heart beating and the blood flow.

It has turned out that the development of  ischemia often goes unnoticed. It can arise from all kinds of daily psychological stress, such as giving a presentation, without experiencing pain. Once your heart and vessels are damaged, you are much more sensitive to acute stressors, both physical and psychological.

If you are stressed very often, and therefore very often activate the sympathetic nervous system, you also chronically switch off the parasympathetic nervous system. This makes it more and more difficult to switch off the sympathetic nervous system after a stress response and to return to a calm state again.

The parasympathetic nervous system controls the vagus nerve to calm the heart rate. It can be measured whether the vagus nerve is doing its job. Your heartbeat is faster when you breathe in, because your sympathetic nervous system is then switched on. When you exhale, your parasympathetic nervous system is switched on and your heart rate is therefore slower. By measuring the heart rate very accurately, you can determine whether the vagus nerve is still working properly. There must be a slight difference between the heartbeat during inhalation and during the exhalation. When there is little or no difference between them, this means that the vagus nerve is not working properly: It is not properly activated by the parasympathetic nervous system. You can conclude from this,that you activate the sympathetic nervous system too often and that the parasympathetic nervous system is chronically switched off.

What causes sudden heart problems?

A strong, unfavorable emotion, such as losing a loved one, doubles the chance of a heart attack during the next two hours. It is very difficult to investigate the concrete (biological) causes of such a heart attack, because you often cannot interview the person afterwards. This way you cannot trace what someone felt at such a moment. Moreover, it is difficult to predict what will happen. Everyone reacts differently to different situations.

However, cardiologists agree that it is an extreme form of acute stress, such as a death, threat, acute sadness, loss of status or self-esteem, a birthday, triumph or enormous joy. Irritation and joy have different effects on growth, the immune system, etc., but they have about the same effects on the heart. It does not matter very much in which direction we have gotten out of our allostatic balance, it only matters to what degree we are out of balance.

A sudden death from a heart attack has to do with the sympathetic nervous system and therefore usually occurs in people whose heart tissue is already somewhat damaged and in people suffering from atherosclerosis. But often people are not aware that their heart and vessels are damaged. As long as other barrels are undamaged and take over the tasks from the damaged barrels, someone will probably not notice anything and will therefore feel perfectly healthy. That is why such a heart attack is often so sudden.

Fibrillation appears to be a very important event in a heart attack. The heart muscle of a damaged heart is in fact more electrically charged, which increases the chance of fibrillation.

The sympathetic nervous system also sends two symmetrical nerve projections to the heart. During strong emotional excitement, these two symmetrical inputs are activated in such a way that they can be disrupted.

The above can not only happen with a strong unfavorable emotion, but also with a strong favorable emotion (for example winning the lottery).

What is it like about heart disease in women?

Heart disease has been found to be less common in women, but heart disease is still the leading cause of death in women in the United States (US). The percentage of heart diseases in women is however rising, while the percentage in men is decreasing. However, it also appears that on average, women suffer from heart disease ten years later than men. Because they are older, they are also less likely to recover. Stress causes women to get more and more heart disease nowadays.

The number of people with obesity is also increasing and obesity also increases the risk of heart disease.

Although the number of people who smoke diminishes in the US, it decreases more slowly among women than among men. In addition, women tend to work outside the home more often in contemporary society. Now working outside the home does not increase the risk of cardiovascular disease, but the fact that women also have to do the household and have children at home does mean that all these different stress factors accumulate.

It has long been thought that estrogen protects against cardiovascular disease: These diseases do not occur so often in women, until the point of menopause, when estrogen levels drop. Stress causes a decrease in estrogen levels. Kaplan's stress monkeys had estrogen levels similar to those found in monkeys whose ovaries had been removed. The monkeys who were subjected to stress for years, but treated with estrogen had no increased risk on atherosclerosis. When their ovaries were removed and they were no longer protected against atherosclerosis. In 2002, a study with thousands of women was conducted. The aim was to detect the effects of eight years of 'replacement therapy' with estrogen and progestin. At one point the results were found, it turned out not to be ethical to continue the study, because estrogen plus progestin greatly increases the risk of heart disease. Why did the researchers see such a difference compared with previous statistical data? The answer lies in the fact that studies such as those by Kaplan related to estrogen, and this study was about estrogen plus progestin. Perhaps the amount of hormones makes a difference, as does the type of estrogen. In addition, the laboratory studies claim that estrogen protects against the formation of atherosclerosis, rather than reducing it when it is already present. 

Psycho-physiological death is a big mystery , also known as voodoo death. When someone in traditional non-Western cultures eats forbidden food, insults the tribal chief, sleeps with a stranger, or does something violent, the city enlists someone who makes a voodoo doll or cheats on someone. Soon after, the bewitched person dies. How can this happen? Maybe it is because already very sick people are bewitched, or the person dies because of poison, or because he / she no longer receives food. However, there are also cases that remain a mystery. There is speculation as to why this can possibily happen. Richter thought death occurred as due to too much activity in the parasympathetic nervous system. According to him, the one who is cursed gives up hope, which makes the vagus nerve very active. This slows the heart rate more and more until it finally stops. Cannon also thought that it was a consequence of too much activity of the sympathetic nervous system. The person becomes very nervous because he is cursed and therefore suffers from stress. As a result, the sympathetic nervous system will do its work for a long time. The blood vessels will contract, making the blood pressure lower and lower until the person dies. Research has shown that Cannon is probably rAight.

Practice question

1. What is the consequence of arteriosclerosis in the heart?

Answer to the practice question

1. Due to arteriosclerosis of the coronary arteries, the heart muscle receives too little oxygen, which can casue that part of the heart muscle to die (heart attack) and the pump function falls to a life-threatening level.

What is the effect of stress on diabetes and metabolism? - Chapter 4

How does energy storage work?

When you have an acute stress situation, such as the zebra when it was being hunted by the tiger, you immediately need energy. However, you do not have time to eat and get energy, or to get energy from food that is not completely digested yet. Your body then gets the required energy from fat, the liver or from muscles that are not being used.

Food that you eat is taken apart by your body to be able to store and use it. It is divided into molecules such as amino acids (the building blocks of protein), sugars, such as glucose, from which more complex sugars can later be built by the body and fatty acids and glycerol (the building blocks of fat). This is accomplished in the stomach and intestines by enzymes. These are chemicals that can decrease the more complex molecules. The building materials obtained end up in the blood stream so that they can be transported to the cells in the body that need these building materials.

For example, if you ate much food at your Christmas dinner than your body actually needs in terms of energy, the surplus nutrients are stored. Enzymes in fat cells can link fatty acids and glycerol to one another, creating triglycerides. In the meantime, our cells can also attach glucose molecules to each other. The glucose chains that are created are called glycogen. This process mainly takes place in your muscles and liver.

Enzymes in different cells in your body are in this way able to bind amino acids to each other, and in this way create proteins.

The hormone insulin, secreted by the pancreas, ensures that the nutrients end up in the right cells and in this way ensures the metabolism in the future.

If you eat very regularly, for example every day at seven o'clock in the evening, insulin will be excreted in advance (around a quarter to seven), even before the glucose level in the body has risen. This is controlled by the parasympathetic nervous system. The body's ability to secrete insulin before a person actually eats is a good example of the anticipatory quality of the allostatic balance.

How does mobilization of energy work during a stressor?

Breaking down food into small pieces is exactly what the body should do when you have eaten a lot. But it is also exactly what the body should not do in the event of a threatening stressor. Then, the energy storage must be stopped for a moment. At the time of a major stressor, the sympathetic nervous system is switched on and the parasympathetic nervous system is switched off, so that less insulin is excreted. The glucocorticoids that are then excreted ensure that no nutrients are transported to the fat cells. The effect of insulin that may still circulate through the body is prevented in this way.

By releasing the stress hormones glucocorticoids, glucagon, epinephrine and norepinephrine, the steps of storing nutrients are carried out in reverse, so that energy is released. The intention is that the body gets access to the stored energy. Triglycerides are disassembled in the fat cells, releasing acid and glycerol into the circulation. These hormones also ensure that glucogen is converted back into glucose, which then ends up in the blood stream. They also ensure that proteins in muscles that are not used are converted back to amino acids. Your body then sends these amino acids to the liver, where they are converted into glucose for energy delivery. Amino acids are not a good source of energy, while glucose is. In addition, your liver can produce new glucose. This is called gluconeogenesis .

All these processes generate a lot of energy for the muscles, which means that the zebra from the example can run away faster for the tiger.

Glucocorticoids and other stress hormones block the absorption of energy in the muscles and in fat cells during a stress response. The muscles that are used during the stress response are, however, able to break through this blockade and obtain sufficient nutrients. This only gives energy to the muscles that are used.

There are people with certain diseases, such as the chronic fatigue syndrome where the body has, among other things, too low levels of glucocorticoids and / or epinephrine and norepinephrine. The above-mentioned processes cannot then be initiated and the body then has too little energy during a stress response.

Why are we getting sick?

If we activate our stress response too often, metabolism problems may arise. Every time you save energy and then take it up again, you lose a part of the potential energy. So if you often activate your stress response, you lose a lot of your energy. After all, it takes a lot of energy to remove the building materials from the circulation and to attach and store enzymes to each other. Logically, it takes energy again to let the enzymes disassemble the building materials and the liver needs energy to make glucose. So you also get tired faster if you often activate the stress response, because you lose a lot of energy.

Moreover, it is bad for the muscles. These contain many proteins that are partially broken down during stress. However, if you often activate the stress response, the muscles only have a small chance of recovering. Thus, frequent stress affects the muscles. But every time the body has a stress response the muscles undergo a very small amount of volume reduction, so an enormous amount of stress is needed to do serious damage.

In some cases, clinicians give patients large amounts of glucocorticoids. This can cause myopathy . This means that the muscles are broken down further and further. This is also evident in patients who are bedridden for a long period of time.

Moreover, it is not a good thing when fat and glucose circulate in the blood stream very often, because it will become more likely that it will attach itself to damaged blood vessels. This increases the risk of atherosclerosis. The bad form of cholesterol (low-density lipoprotein-associated cholesterol, or LDL cholesterol) also plays a role in getting atherosclerosis. This type of cholesterol attaches itself to damaged blood vessels, while good cholesterol (high-density lipoprotein-associated cholesterol, or HDL cholesterol) is removed from the damaged blood vessels and goes to the liver to be broken down. Because there are two different types of cholesterol, the total cholesterol level in the blood stream is not that meaningful. During stress your LDL cholesterol level is increased and your HDL cholesterol level is lowered.

What is diabetes?

In some people, the immune system notices and attacks the cells in the pancreas; which secretes insulin; as if they were hostile cells. This autoimmune disease is reffered to as juvenile diabetes. Another name for this type of diabetes is type 1 diabetes, or insulin-dependent diabetes. Because this kind of person excretes too little or even no insulin at all, he is unable to absorb glucose into the cells, for which insulin is intended. As a result, cells die, there will be not enough energy and various organs do not function properly. In addition, glucose and fatty acids then continue to circulate in the blood stream, which increases the risk of developing atherosclerosis. Blood vessels can also start clogging in other organs, such as the kidneys and eyes. Small strokes can occur in these tissues and it is often accompanied by chronic pain.The kidneys can stop working or the person has the risk of blindness.

Someone with diabetes needs to make sure that insulin levels do not get too low by correcting for this by injecting insulin. When this is however the case, cells receive too little energy and the glucose level circulating in the blood becomes too high. But too much insulin is not good either. This can lead to insufficient energy for the brain, which in turn can lead to a shock, even a coma and damage to neurons. The hormones released during the stress response ensure that even more glucose and fatty acids enter the bloodstream.

With a diabetic person it is important that the metabolism is in balance. The better the metabolism, the smaller the chance of complications and the higher the life expectancy.

Glucocorticoids ensure that fat cells become less sensitive to insulin. These fat cells produce certain hormones that cause other tissues, such as muscles and the liver, to become less sensitive to insulin. So, stress causes more resistance to insulin. This resistance to insulin is especially bad for people who have childhood diabetes (type 1 diabetes). When these people experience chronic stress, they start to feel ill, until they find out it is because their insulin levels are too low. They then have to inject more insulin, which means the cells can offer even more resistance. When the stressor is over, it is very difficult for these people to estimate when they will have to inject smaller amounts of insulin again, because different parts of the body regain their normal insulin sensitivity at different times. Stress therefore disrupts the balance for these people.

Stress, including psychological stress, can cause damage to the metabolism of someone who has childhood diabetes. Several studies have shown that diabetic people encountered significantly more major stressors in the three years prior to the onset of childhood diabetes than other people. Regular stress and / or major stress responses may increase the risk of developing childhood diabetes, accelerate the development of childhood diabetes and may cause major complications once the disease has fully developed.

What if diabetes develops at a later age?

Diabetes can also develop later in one's life. The problem that occurs then does not have to deal with a shortage of insulin, but with a fault in the cells to respond to insulin. This type of diabetes is therefore also called insulin-resistant diabetes. Another name for this, is type 2 diabetes.

When someone gets older, one often gains weight a little, and at the same time, one becomes a little less active. This increases the risk of getting this type of diabetes. It has to do with phenomena that often go hand in hand with aging in the Western world, yet it is unrelated to aging itself. People who are old but not fat, therefore, have no increased risk of this type of diabetes.

When you are an adult, the number of fat cells in your body is a fixed number. These fat cells can become 'full'. If this is the case, excess fatty acids can no longer be stored and will circulate throughout the body's blood system, with all its consequences (such as an increased risk on atherosclerosis). The fat cells will become less responsive to insulin and less glucose will be absorbed by the fatt cells. Glucose is in fact necessary to store fat as triglycerides.

The overfull fat cells also secrete hormones that ensure that other fat cells and muscles become resistant to insulin. If this type of diabetes lasts for too long, your body becomes insulin resistant. Your pancreas responds to this by secreting more and more insulin until the cells that secrete the insulin are destroyed. In this case, you have had childhood diabetes. This is irreversible, while you can restore insulin resistance diabetes by losing weight and therefore having less fat stored in your fat cells.

So, stress has an adverse effect on this type of diabetes, because it makes your fat cells less responsive to insulin and, causing fatty acids and glucose to keep on circulating through the blood stream.

In the western world and especially in America, more and more people suffer from obesity and more and more people suffer from this type of adult diabetes. Moreover, the people who contract this type of diabetes are getting younger and younger. Even among children, this type is more common than childhood diabetes. The main reason for this is that more food is eaten that is bad for your health, and especially more 'junk food'. People also tend to be less active nowadays.

What is a metabolic syndrome?

The metabolic system and the system of heart and vessels are closely linked to one another. The metabolic syndrome (a metabolic disease, also called 'syndrome X'), has to do with the connection between these two systems. This connection is not that new, but very much 'in fashion' in recent years.

There are several things that can go wrong in the body, such as an increased insulin level, an increased glucose level, increased (systolic and diastolic) blood pressure, insulin resistance, too much LDL cholesterol, too little HDL cholesterol and too much fat or cholesterol in the blood. If you suffer from several of these things, you suffer from metabolic syndrome. Moreover, if you have a few of these things, the chances are greater on the other things. The metabolic syndrome also predicts the chance of other major diseases, such as heart attacks and strokes, and moreover, predicts death rates. This has emerged from a study by Seeman.

It can happen, especially with older people, that all the above levels are just within medical limits, but that several levels are very high at the same time. These people then have a high risk of metabolic syndrome and also serious diseases such as heart attacks. The same happens in the case of stress. Stress has an effect on many different levels and affects them all a bit.

Practice questions

1. What is the difference between type 1 and type 2 diabetes?

2. Why is the combination of diabetes and stress so bad for health?

Answers to the practice questions

1. Type 2 is acquired diabetes, diabetes because of old age, obesity or diabetes through excessive stress.

Type 1 diabetes is juvenile diabetes. 

2. Cells receive too little glucose, fatty acids and glycerol. Under stressful conditions, more and more of these types of substances are made. There is an increased risk on atherosclerosis.

What is the relationship between stress, appetite and stomach ulcers? - Chapter 5

What is the connection between stress and food consumption?

Not having enough to eat or to drink is a stressor. If you are not sure when you will get your next meal, this is also a stressor. Also, consciously choosing not to eat, such as eating disorders such as anorexia, is a stressor. Stress can change eating patterns. Stress leads two thirds of people to eat more (hyperphagic) and one third to eat less (hypophagic).

Various hormones are excreted during stress. One of them, CRH, stimulates the secretion of ACTH, it regulates other characteristics of the stress response in the brain, it helps to activate the sympathetic nervous system, and it increases vigilance and excitement during stress and suppresses appetite.

The glucocorticoids that are excreted during stress also stimulate appetite. This has been demonstrated in rats: glucocorticoids cause them to look for food more often and stimulates them to be more willing to press a lever to get their food. The unusual thing is that glucocorticoids do not only increase appetite, but especially the appetite for food that contains a lot of starch, sugars and fat. Glucocorticoids cause the brain to become less sensitive to the hormone leptin (which causes a loss of appetite), so that your appetite is not reduced when you eat. That means you will probably eat more.

During stress, CRH is excreted in just a few seconds. ATCH is then excreted within 15 seconds. It takes a little longer for glucocorticoids to be excreted. If your CRH level is high and your glucocorticoid level is low, you are probably in the situaiton of the first few minutes after the stressor has occured. You will have little appetite. When both the CRH level and the glucocorticoid level are high, there is probably a persistent stressor. Even in this case, you will probably have little appetite. If your glucocorticoid content is high and your CRH content is low, you are probably recovering from the stressor and you will regain your appetite, so that the energy and nutrients that are used during the stress response can be replenished. Glucocorticoids ensure the recovery of the stress response.

If there is a short-term stressor (for example for ten minutes), the CRH level will be very high for a short period of time (about twelve minutes). The glucocorticoid level in this example will be very high for two hours. These two hours are calculated as follows: the 8 minutes of excretion during the stressor plus the time required for the glucocorticoids to disappear from the body takes about two hours. In this situation the appetite is increased.

However, when a stressor persists for days, the CRH level and the glucocorticoid level are also very high during this period, followed by a high glucocorticoid level and a low CRH level for several hours. Your appetite is then suppressed.

The type of stressor therefore determines whether the eventual result is hyper- or hypophagia.

Imagine someone sleeping through the alarm clock and getting completely panicked when realizing this after waking up. Then, he or she becomes calm again, but gets stressed again because he is in a traffic jam. When he arrived at work, he calmed down again, suspecting that the boss was absent, and therefore did not see that he was late. He gets panicked again when he notices that the boss is there and has seen it. The life of such a person consists of frequent, periodic stressors.

These periodic stressors cause the CRH level to rise frequently. This makes glucocorticoids disappear from the bloodstream less quickly, resulting in a chronically high glucocorticoid level. By the time this level goes down, there is already a new stressor in this person's life, which keeps the level high. These people therefore get a strong appetite and become hyperphagic. Frequent psychological stressors during the day is an important reason why many of Westerners become hyperphagic due to stress.

Another variable that predicts hyperphagia or hypophagia is how the body reacts to a particular stressor. For example, the glucocorticoid level decreases faster in some people than in others. Such differences can be caused by psychological factors (for example, the way in which someone interprets a particular stressor) and physiological factors (for example, the functioning of the liver of different people). The people who excrete a lot of glucocorticoids during stress are often also the people who become hyperphagic. Moreover, there are many people who eat from an emotional need.

People who are normally reluctant to eat and do their best not to overeat, become hyperphagic faster than others during a period of stress. This is because they are normally being very strict to themselves so they believe they can 'spoil' themselves a bit during periods of stress. Furthermore, people also differ in the way their body stores the nutrients from the food after a stressor; how quickly they store it and where in the body they store it.

How does nutrient storage work?

During stress, the stored energy is used to give your muscles enough energy for the stress response. After the stressor, it is necessary to replenish these stocks. Glucocorticoids cause fat cells to produce enzymes that convert the circulating nutrients back into their stored forms.

Glucocorticoids are responsible for storing fat, and this process mainly happens in the (lower) abdomen. Some types of people will get a round figure faster (apple-shaped) and their belly size becomes larger then for other people. Glucocorticoids only have this effect if the insulin level is also high. A high level of glucocorticoids and insulin occurs in the recovery phase after stress (see Chapter 8). People who suffer from high fat storage, especially in the lower abdomen, have a greater risk of metabolic syndrome than people who store fat primarily in their buttocks (and will get more of a pear-shaped figure). 'Apples' have a belly that is larger than their hips (so a WHR (waist-hip ratio) that is greater than 1) and with 'pears' the hips are bigger than the belly.

So, if you excrete more glucocorticoids during a certain stressor than most other people do with that kind of stressor, you may have a greater appetite during the recovery of this stress response, and you may store your fat more in your (lower) abdomen, and you are more likely to contract metabolic syndrome or cardiovascular diseases.

What role do intestines play in the digestive process?

When you eat food, it first enters your gastrointestinal tract. Your food is broken down chemically, by certain hormones, and mechanically by the muscles, then converted into nutrients. Your stomach walls contract, causing the food to be thrown back and forth with force causing it to fall apart into acids and enzymes. Your small intestine makes peristaltic movements, which reduces the ground food.

At the beginning and at the end of each organ there are circular muscles, called sphincters, that can open and close, so that the food can only sink down when the previous phase is entirely completed. In addition, water must be added to the process regularly to ensure that your body doesn't create a dry mash in your gut. This happens in the mouth, stomach and small intestine. Then it goes to your large intestine, where the water is extracted again and ends up in your blood stream. This entire process takes a lot of your body's energy. That is why it is quickly stopped during a stress response. You do not make new saliva and you get a dry mouth, your stomach stops its activities, enzymes and acids are no longer excreted, your small intestine stops its peristaltic movements and less blood flows to your stomach and intestines.

After the stress response, the parasympathetic nervous system is reactivated and the process of digestion continues. Before the food reaches the small intestine, the other organs have already ensured that the food is divided into compound parts, so that the small intestine only has to remove the nutrients and bring them into the blood stream. The remaining parts are converted by the colon into faeces and eventually excreted.

During a stress response, the sympathetic nervous system ensures that the activities of the stomach and the small intestine are stopped, while those of the large intestine are stimulated. Because of this you lose some extra weight, which is very beneficial for the zebra that has to flee from the tiger. Because the food remains are pushed through the small intestine very quickly, there is not enough time to remove all the water that was added earlier in the process. As a result, you often get diarrhea with a major stressor.

What is the connection between stress and gastrointestinal disorders?

There are two types of gastrointestinal disorders; organic gastrointestinal disorders and functional gastrointestinal disorders. With organic gastrointestinal disorders, doctors can find something that does not function well and which makes you ill, such as in the case of ulcers in the digestive tract.

With functional gastrointestinal disorders, something does not work well and you feel sick as well, but the doctors cannot find anything organic that is causing it. These disorders are often very sensitive to stress. An example of such a disorder is the irritable bowel syndrome (IBS). The patient suffers from abdominal pain (especially after eating), which disappears mainly through the excretion of faeces. Common symptoms are diarrhea and constipation, mucous passage and abdominal swelling. This is due to the intestines contracting too often. The syndrome is also called a 'spastic bowel'.

Studies have shown that large, chronic stressors increase the risk of the first symptoms of IBS occurring and exacerbate the symptoms of pre-existing IBS. People with IBS are likely to experience more stressors. But the disorder can also be related to stomach and intestinal hypersensitivity to stress. Stress can also cause you to feel less pain in your skin and muscles, yet more in your gut. This is also the case with people who have IBS. Furthermore, the sympathetic nervous system is also overactive in people with IBS. The nervous system causes these intestinal contractions during stress. Moreover, the pain coming from the intestines can activate the sympathetic nervous system to have even more pain, creating a vicious circle.

Traumatic stress at a young age increases the risk of getting IBS in adulthood. However, there are also opponents of the link between stress and IBS. They blame IBS on personality types and explain it with the anal phase from psychoanalysis. There have also been several studies that showed no connection between stress and IBS. This may be due to the fact that the intensity of the symptoms and the intensity of the stressors decrease and increase over time. It is difficult to find a connection between such fluctuating patterns. In addition, most studies are retrospective and it is very difficult to accurately recall information about the stressors and symptoms afterwards.

However, it can also be difficult to determine a relationship in prospective studies, because the stressor sometimes only works at a later age. This can be observed, among other things, in the effect of childhood trauma on the development of IBS as an adult. Moreover, IBS is probably caused by various things, and stress only affects a part of it. This makes it even more difficult to interpret possible results of a research as a separate series of results instead of noise in the data.

How does one develop ulcers?

An ulcer is a hole in the wall of an organ. Ulcers that origin in the stomach or related organs are called peptic ulcers. Ulcers in the stomach itself are gastric ulcers. The ulcers that are slightly above the stomach are called esophageal ulcers and the ulcers located on the edge of the stomach and the small intestine are duodenal ulcers. These ulcers are viewed as the diseases that are most related to stress. Most clinicians agree that there is a specific subtype of these ulcers that can be formed very quickly (even in a few days) in people who are exposed to a very large stressor, such as an accidental trauma.

A century ago, however, it was thought that all stomach ulcers were the result of having a particular diet, experiencing stress or genes. A revolutionary development came in 1983; with the discovery of a bacterium called "heliobacter pylori." It was discovered by the Australian pathologist Warren, who caused his colleague Marshall to become interested in this. Marshall discovered that the bacteria occurred in the stomach of people with duodenum and gastritis.

When Marshall was laughed at for this finding, he showed that the bacterium causes gastritis and ulcers in mice. When people still did not believe him, he swallowed the bacteria himself and demonstrated that he had gastritis. Marshall and Warren have also shown that microbial drugs can remove the ulcers almost completely.

85 to 100% of the stomach ulcers in Western populations are probably caused by these bacteria. However, ulcers cannot only be the result of the heliobacter, because only 10% of people infected with this bacterium get stomach ulcers! A risk factor that is related to lifestyle, such as the consumption of alcohol, could increase the risk of developing an ulcer. But stress also contributes to getting them. Numerous studies have shown that duodenal ulcers (dudenal ulcers) are more common in people who are anxious, depressed or exposed to many stressors that have had a major impact in their lives.

How do stomach acids arise?

There are hydrochloric acids in your stomach. Together with the stomach contractions, they ensure that the foods you eat are broken down into smaller pieces. To protect the stomach against these aggressive acids, the stomach wall has many layers that are covered with mucus. Bicarbonate, a type of baking soda, is also excreted to neutralize the stomach acids.

During a stress response, fewer acids are excreted and the protective layer of the stomach wall becomes somewhat thinner. This will do no harm, because your parasympathetic system is stopped during the stress response and you hardly have to digest anything. That energy then goes to other places in your body.

When after a major stressor you are rewarded or reward yourself with food, you have a greater risk of getting ulcers; because there are not enough of your own acids and your stomach wall is thinner. Your defense mechanisms are therefore not yet properly activated to properly prevent the formation of ulcers.

The recovery period after stress can therefore become very harmful. Therefore, for the development of ulcers, it is more risky to have many short periods of stress than a long period of stress, because the parasympathetic system is constantly switched off during the long period. No food is digested in the latter case.

A stressor can cause small infarctions in the stomach, resulting in dead tissue, which is the building material of ulcers. There are two possible causes of this infarctions:

1. Less blood flows to the intestines during a stressor. If less blood flows, fewer acids that normally accumulate are now washed away.

2. In addition to normal oxygen, dangerous oxygen radicals are formed in the body, albeit to a lesser extent. Under normal circumstances, your intestines produce "waste eaters" that protect you against these oxygen radicals. During a period of chronic stress, your intestines stop creating these waste eaters. After the stressor has passed, so during the recovery period, the blood flow to the intestines returns to normal, while the intestines still have too few waste eaters. This causes the oxygen radicals to destroy cells in the stomach wall. This increases the chance of getting ulcers.

You become less immune during periods of stress. As a result, the helicobacter bacterium is able to multiply faster. Normally, small ulcers occur in the body, which the body cleans up through chemical prostate glands (prostaglandin). However, during periods of stress, the excretion of these prostate glands is stopped, allowing these small ulcers to grow further, becoming larger stomach ulcers.

For reasons that are unknown, stress causes the stomach to contract in a slow rhythm (approximately once a minute). It is also unknown why this increases the chance of stomach ulcers. A possible cause is that the blood supply to the stomach is disrupted during the contractions, causing a shortage of blood here. However, there is not much evidence for this. Another idea is that the contractions damage the stomach wall.

Practice questions:

1. What is the IBS syndrome?

2. What is the Helicobacter pylori and is it harmful?

3. Weiss and Brady used gastric ulcers as dependent variables in their stress experiments with monkeys and rats. These ulcers would occur as the result of stress; due to overactivation of the autonomic nervous system and hormones. However, it has been known for a number of years that a bacterium (the Helicobacter Pylori) is responsible for stomach ulcers. Does this make a stress theory about the development of stomach ulcers untenable?

Answers to the practice questions:

1. It is the Irritable Bowel Syndrome; a disorder that can be reversible.

2. It is a type of bacteria that is located in the stomach; harmless, until it interacts with stress or bad health behaviors such as the consumption of alcohol.

3. No, since this particular bacterium is only harmful in the case of prolonged stress or bad health behaviors.

How does stress affect growth? - Chapter 6

People grow by taking in nutrients. Cells divide, become larger and produce new proteins. Bones get longer because cartilage cells at the end of the bone migrate to the shaft and become hard bone there. Fat is replaced by muscle mass, the voice becomes lower, hair grows in various places of the body, breasts develop and testes grow.

However, this does not happen automatically. Calcium is needed for the bones, amino acids for the production of proteins and fatty acids make cell walls. All these processes run on the energy that is made by glucose. These processes are driven by a growth hormone. Sometimes growth hormones act directly on the cells in the body. Sometimes, growth hormones work in an indirect way and cause the secretion of the hormone type somatomedines. In this case, they do the job. Thyroid hormones stimulate growth by secreting hormones, which make bones more susceptible to somatomedines.

The reproductive hormones (estrogen and testosterone) are activated during puberty. Among other things, they ensure that the longer bones in our body grow. When the ends of the long bones fuse together, growth stops.

Because testosterone accelerates the growth of these bones, it can cause the growth to stop faster. A shortage of testosterone will then ensure that you continue to grow for longer. This happens, for example, with boys who are neutered before puberty. They usually become very long.

What does prenatal stress entail?

During the development of a child, that starts as a fetus, the body learns about the natural processes of the world. For example, a child will learn that something hidden under a blanket is still there and that when something falls, it falls down instead of upwards. Or, when Mama leaves, she will come back, because she has always come back so far. These learning processes are important for the rest of life. For example, a child whose mother dies when he or she is still very young will learn that terrible things can happen in life that you cannot control. These children are more at risk of developing depression. In this way, children also learn how to respond to the outside world. Moreover, the child learns to make decisions regarding how he or she will react to the world around them from now on.

When certain stressors occur during the child's development, he or she may develop certain typical routes of stress responses that increase its risk on certain diseases.

A child who has not been given enough food during pregnancy will also learn that there is very little food in the outside world and that it must store everything it can get hold of. This shifts the metabolic system. This is called metabolic imprinting or metabolic programming. This type of child has a greater risk of developing hypertension, obesity, diabetes in later life and cardiovascular disease.

The lower the birth weight of a child, after a correction for height, the greater the chance of it developing the symptoms of metabolic syndrome. This is especially the case when the child has enough food available after its birth. The most dramatic example of this is the Dutch hunger winter at the end of the Second World War. The Nazis were pushed back on all fronts and the Dutch tried to help the Allies who came to liberate them. As a punishment for this, the Nazis ensured that all food transport was cut off. People ate less than 1000 calories a day and had food that consisted mainly of flower bulbs. Fetuses learned lessons about food during this time. The result was that half a century later there was a group that had a greatly increased risk of metabolic syndrome.

The link between fetal nutrition and the lifelong risk of metabolic and cardiovascular disease was first described by Barker, and is now known as 'Fetal Origins of Adult Disease' (FOAD). Other stressors that have nothing to do with nutrients can also lead to FOAD. For example, when a mother is stressed, her heightened levels of glucocorticoids will also go to her fetus. In this way, he or she learns that the outside world is very stressful, so that his glucocorticoid content will be raised for the rest of his life. Prenatal stress therefore also increases the elimination of glucocorticoids during the rest of life. This again leads to a greater chance of getting the metabolic syndrome.

Stress also reduces the excretion of testosterone. When pregnant women get stressed, this also has an effect on the male fetuses. These will be less sexually active and have smaller genitals when they are adults. A high level of glucocorticoids in the fetus can block the testosterone receptors.

In rats, it has also been shown that if you expose a pregnant rat to severe stressors, her young will become anxious. The amygdala of this type of boy becomes more sensitive to glucocorticoids and a neurotransmitter that mediates anxiety and the amygdala has fewer receptors for CRH, the hormone that reduces anxiety. Whether this also happens to people is unclear, because people do not yet have the technology to investigate this properly.

The aptitude for developing FOAD can be passed on to subsequent generations. This is not done through the passing of genes, but through a shared environment. For example, someone who has been malnourished as a fetus can develop a different metabolic system and store as many nutrients as possible. If this type of person becomes pregnant and eats enough, the fetus will nevertheless consume less nutrients, because the mother's metabolic system has stored them. As a result, this fetus is also mildly malnourished. This can continue for generations.

What does postnatal stress entail?

Postnatal stress can also have a major impact on the development of children. Plotsky has done research on rats that demonstrated that if you separate them from the mother (causing a major stressor), the young rats develop the same symptoms as with prenatal stress. They have higher glucocorticoid levels during stress and recover more slowly after the stress response, they are more anxious and the amygdala has changed (see chapter 10), and a part of the brain that is related to learning and remembering is less well developed.

Studies with rats also showed that they show similar symptoms, albeit in a milder form, if the mother is present but is inattentive and only gives the young rat little attention and care.

It is very difficult to do these types of studies on people. However, postnatal stress seems to be related to the development of various diseases, such as metabolic and cardiovascular diseases. Research involving Romanian orphanages showed that the longer the child stayed in the orphanage, the higher its glucocorticoid level.

How can stress affect bone growth?

Your bones (and therefore also the rest of your body) grow best during your childhood (for around the first ten years), especially when you have eaten well and then lie asleep.

During stress, it is convenient to use the energy it takes to grow for the stress response. You don't grow at the moment of a stress response. A child who experiences something very stressful in his life, such as neglect, therefore has little energy left to grow and remains very small. This sometimes leads to being a lilliputter. This condition is called "stress dwarfism" or "psychogenic dwarfism." However, this syndrome is very rare and only occurs under very extreme conditions. An example of this is a child who has been terrorized by a stepfather for years, or has been locked up in the toilet for months. If the stressor is removed before the child is develops to puberty, the child can catch up on part of the missed growth, but it will always remain a little smaller than average, and the personality and intellect will lag behind a bit. After a certain age, the chance of recovery is greatly reduced.

For optimum growth and development, not only enough food and warm clothing are necessary factors, but don't forget about positive contact with others (playing with other children, experiencing maternal love). This has been shown by an investigation by King Frederick II of Sicily. He locked up different children in different rooms. They got the best food and the best clothes, but hardly had any contact with people and nobody talked to them. Frederick II wanted to discover the language these children would speak. However, none of these children survived the experiment.

After the Second World War there were two different orphanages in Germany. Mrs. Grun worked in orphanage A. She was like a loving mother who dealt with the children a lot. Mrs. Schwartz worked in orphanage B. She met the demands of her profession, but did not concern herself much with the children. The children received little love from her. The children in orphanage A grew much faster than the children in orphanage B. Later on, Mrs. Grun was moved to another job and Mrs. Schwartz ended up at orphanage A. The growth of these children decreased from that moment on. The children in orphanage B grew a lot faster now that Mrs. Schwartz was gone and someone else was in charge. This shows that social interaction and receiving attention and love is very important for the growth of children.

'Stress dwarfism' has a lot to do with a low level of growth hormones that circulate in the body. These growth hormones are also very sensitive to the psychological state of the person. This was very clear from the report of a boy who was admitted to the hospital with 'stress dwarfism'. His level of growth hormones was very low at the time. In the hospital he started to attach himself to a certain sister. This doubled the level of his growth hormones, while he ate less than before. However, when the sister in question was on vacation for three weeks, the level dropped considerably again. When she came back it rose again to almost three times as much as in the beginning, when the boy was admitted to the hospital. Apparently what goes on in our head affects every cell in our body.

The growth hormone is secreted by the pituitary gland, which is controlled by the hypothalamus. The hypothalamus controls the secretion of growth hormone by excreting activating and inhibiting hormones. It seems that with 'stress dwarfism', too many inhibiting hormones are excreted.

Excessive activity of the sympathetic nervous system due to stress can also play a role. Moreover, the body becomes less responsive to the bit of growth hormone that is secreted. As a result, children sometimes do not respond to artificial growth hormones.

Children with 'stress dwarfism' also suffer from stomach and intestinal problems because they are less able to absorb nutrients from the small intestine. This is probably due to the strong activity of the sympathetic nervous system. This stops the secretion of enzymes, and also the contractions of the stomach, and it blocks the intake of food.

Studies by Kuhn and Schanberg and also by Hofer have shown that active contact is the most important thing for rats to grow. Especially the licking of the mother stimulates the production of their growth hormone. Even when this licking was artificially simulated, the growth was almost completely normal.

A study by Field, Schanberg, Kuhn and others showed that this also applies to people. Babies that are born prematurely usually lie in an incubator and are hardly touched. They stroked some of these babies for 15 minutes three times a day and moved the limbs. These babies grew fifty percent faster than babies that were rarely touched. Touch appears to be very important for children and missing touch is therefore a major stressor.

What is the connection between stress and the secretion of growth hormones?

The pattern of secretion of growth hormones during stress is very different in humans than in rodents. When a rat is stressed for the first time, the level of circulating growth hormones drops almost immediately. If the stressor persists, the secretion of growth hormones remains suppressed.

In humans, the secretion of growth hormones in a long-term stressor is also suppressed, but immediately after the stressor has disappeared, the level of growth hormones in humans and some other animal species rises. Short-term stress stimulates the secretion of growth hormones for a while.

Growth hormone not only stimulates bone growth and cell division, but also ensures that fat storage in fat cells is broken down and enters the blood stream as energy. That is exactly the same as what glucocorticoids, epinephrine and norepinephrine do in the body of a zebra when it flees from a lion. This energy is normally used for the growth process. During periods of stress, a short-term secretion of growth hormones can therefore cause extra energy to be released. During a stressor it is good if the body secretes growth hormones, as far as these help with mobilizing energy. However, when they are used for 'long-term projects' such as growth, that is not veyr useful.

During stress, the excretion of somatomedines is stopped, so that the excretion of growth hormones is ceased and the body becomes less sensitive to this hormone. However, the separation is not completely stopped. The reduction is necessary, because if the body would continue to excrete growth hormones for too long, the growth processes would eventually start again. Therefore, the secretion of growth hormones is eventually stopped during a stress response.

Landauer and Whiting did a study in the 1960s on the effect of stressful rituals in different tribes on growth.

A number of examples of these rituals are: circumcision, placing piercings, vaccination, tying up limbs, exposure to hot or cold baths, fire, intense sunlight, snow or cold air. They classified the cultures according to whether and at what age they exposed their children to these rituals. They also linked cultures that were the same in terms of their posture and eating habits. In the cultures where children between the ages of six and fifteen were exposed to these rituals, growth was somewhat slowed down. These children were on average 3.81 centimeters smaller than adults from other comparable cultures without these stressful rituals. For children between the ages of two and six, there appeared to be no difference in growth between cultures with and without stressful rituals.However, children exposed to such stressful rituals before their second year of life were found to be 6.35 larger than adults, compared to adults from similar cultures without stressful rituals.

The cause of the growth in children exposed to a stressful ritual before the age of two is not clear. During these rituals, the levels of growth hormones and somatomedines have never been measured, as a result of which it is not known with certainty whether they have anything to do with it, or whether there are totally different causes, such as different food intake. A possible explanation of this phenomenon could be that it makes stressful children who do not die from the rituals grow bigger and stronger.

Artificial glucocorticoids are often prescribed. During pregnancy, they are often prescribed to women with certain endocrinological disorders and women who are at risk of giving birth prematurely. However, when these women take many artificial glucocorticoids during pregnancy, their children have a smaller head size, emotional and behavioral problems, and developmental milestones are achieved later. Nobody knows yet whether these effects are permanent.

Because a high dose of artificial glucocorticoids is only prescribed for more serious diseases, this effect is probably less serious than the effect of the disease. Furthermore, it appears that even the normal distribution in birth weight can predict glucocorticoid levels as adults and the risk of metabolic diseases.

Stress and trauma at a young age appear to play a major role in increasing the risk of various psychiatric disorders years later. Furthermore, the effects do not seem to be irreversible. This has also been demonstrated at the orphanages where Mrs. Grun and Mrs. Schwartz worked. A different environment has a different effect on the child.

How do growth and growth hormones develop in adults?

When you are an adult, you still excrete growth hormones, but this happens too a smaller degree than when you are young. When you are fully grown, the growth hormones mainly ensure that things in the body are rebuilt and (re)shaped. Things that are not completely right or in complete balance in the body are restored. Most of this work takes place in the bones. The bones contain many blood vessels and small channels that are filled with fluid and different cells that constantly grow and divide. New bone is constantly being formed and old bone is being dissolved by enzymes, this is called resorption. New calcium is removed from the bloodstream and old is taken away into it. These processes are driven by growth hormones, somatomedines, parathyroid hormones and vitamin D. Bones therefore distribute calcium. One part goes to the organs of the body, another part is for the bones themselves. It is important that there is a good balance: Because, if the bones excrete too little calcium, various other body parts will no longer work. However, if they excrete too much, the bones themselves become porous and the risk of bone fractures is greater.

Stress and especially glucocorticoids influence the balance of calcium. Less new bone is then produced, less calcium comes to the bones, the intestines absorb less calcium, the excretion of calcium by the kidneys is increased and the resorption of the bone is accelerated. Extreme excretion of glucocorticoids therefore increases the risk of bone problems. This is especially the case in people with Cushing's syndrome and in people being treated with glucocorticoids to suppress a certain disease. People with Cushing's syndrome have an exceptionally high glucocorticoid content due to a tumor.

A higher level of glucocorticoids is especially problematic for older people, because there is already a lot of bone resorption in older people. This is especially true for older women, because estrogen blocks the resorption of the bones. After the menopause, women have much less estrogen and therefore a greater chance of osteoporosis, and the bones becoming softer and weaker. Chronic stress could then lead to osteoporosis and bone atrophy.

Furthermore, love is also very important for growth. A lack of love is one of the biggest stressors that someone can suffer from. Harlow did a research on monkeys. A young monkey could choose between two artificial mothers. Both had a head made of wood that looked like the head of a monkey. One mother consisted mainly of steel and had a bottle of milk in the middle for the monkey to drink on. The other mother was covered with fabric, so that it looked more like the fur of a real monkey, but this mother had no milk bottle and therefore could not feed the monkey. Behaviorists at the time thought that nutrition alone is important and that the monkey would therefore opt for the steel artificial mother. However, the monkey chose the upholstered artificial mother. This showed that love and something soft to hold on to is very important. This also applies to people.

Practice question

1. Romanian orphans are often smaller than average. What could be the reason for this?

Answer to the practice question

1. Children in Romanian orphanages often receive less touch and love, causing diminished growth.

How does stress affect reproduction? - Chapter 7

How can stress affect the excretion of testosterone?

In men, the brain secretes the hormone releasing hormone (LHRH), which stimulates the pituitary gland to excrete the hormones LH (luteinizing hormone) and FSH (follicle-stimulating hormone). LH then stimulates the testes to excrete testosterone. In men, the follicle-stimulating hormone logically does not have the task of stimulating follicles, but it does produce sperm.

When a stress response starts, the amount of LHRH in the blood decreases. Subsequently, LH and FSH levels also decrease and the testes stop shedding testosterone.

This mainly happens during physical stress, such as with injuries, illness, hunger or surgery. Anthropologists have even shown that in human societies where there is constant physical stress (such as Nepalese townspeople), there are significantly lower testosterone levels than in people from, for example, Boston.

In addition to physical stress, psychological stress also disrupts hormone management in men. For example, when a primate drops in rank, its testosterone level also drops. And when a person or monkey has a stressful task to do, the same happens.

At the start of the stress response, the hormones endorphins and enkephalin are secreted, blocking the excretion of LHRH from the hypothalamus. Endorphins play a role in blocking the perception of pain and are excreted during exercise. Men who engage in extreme physical activity, such as top athletes, have less LHRH, LH and testosterone in their bloodstream, smaller testes and less functioning sperm. They also have a higher level of glucocorticoids in their bloodstream, even when there is no stress. Glucocorticoids block the testes response to LH.

To get an erection a large amount of blood goes to the penis. This is done through stimulation of the parasympathetic system. However, during intercourse the sympathetic system is activated more and more. Your heart rate and breathing speed up, among other things. The moment your sympathetic nervous system is fully activated and the parasympathetic nervous system is switched off, the ejaculation takes place.

Sufficient stress can damage and cause clogs in your blood vessels, which can cause vascular diseases and disrupt blood flow. Stress during intercourse can also have adverse effects. If you are nervous or anxious during intercourse, your sympathetic nervous system is activated. This makes it more difficult to get an erection: impotence. However, when you have an erection, but you worry about something during intercourse, you switch faster from the parasympathetic nervous system to the sympathetic nervous system, causing you to ejaculate early.

Studies have shown that more than half of the problems of men who go to a doctor with complaints about the dysfunction of the reproductive system suffer from psychological impotence instead of organic impotence. Since erection problems are a stressor in themselves, men quickly end up in a vicious circle.

To find out if the impotence is due to psychological factors, you can let a particular individual sleep at night with a certain device on his penis. This device measures whether it has ejaculated. Men ejaculate during REM sleep. If the man has ejaculated during REM sleep, there is a good chance that his problems are of a psychological nature rather than of an organic nature.

In many animal species, the stressors related to mating behavior or the competitions prior to mating behavior do not suppress the reproductive system. These stressors stimulate the reproductive system. This is due to some animal species because these stressors do not lead to the secretion of stress hormones. In other animal species, stress hormones are secreted, but the human reproductive system is not sensitive to these hormones.

Dysfunction of the reproductive system also occurs in women. In women, too, it is partly due to the excretion of endorphins during physical exertion. Female athletes often have disrupted periods and athletic girls often arrive late in puberty.

In physiology, too much of something can be just as bad for the body as too little. Extreme physical activity can cause damage to the physiological systems. Regular exercise, for example, increases bone mass. But a thirty-year-old who runs about 65 to 80 kilometers a week has bones that are similar to those of a seventy-year-old.

Why do hyenas get erections during stress?

Among the hyenas, the females are socially dominant. They are more muscular and aggressive than men and, moreover, have more of the male sex hormone androstenedione in their bloodstream than males.

In the time of Aristotle it was thought that hyenas were hermaphrodites, that they were therefore both male and female. Hyenas, however, are in fact pseudo-hermaphrodites. This means that it looks like they belong to both sexes, but in reality they are not. The females have an enlarged clitoris that can also be erected, making it look like they have a penis.

Among many social animal species, it is normal for males to get an erection during competitive situations, as a sign of their dominance. With hyenas, however, an erection is a sign of subordination. Both male and female hyenas indicate that the other is above them in the social order. So they get erections when they are stressed. The autonomous system must then be opposite to that of other animal species, because other animal species can usually no longer get an erection during stress. Further research is being done into how exactly this works.

What effect does stress have on the reproductive system in women?

The basis of the reproductive system is the same for women as it is for men. The brain secretes LHRH, causing the pituitary gland to secrete LH and FSH. FSH stimulates the ovaries to release egg cells. LH stimulates the ovaries to produce the hormone estrogen.

During the first half of the menstrual cycle, the follicular phase, the levels of LHRH, LH and FSH continue to increase, until the climax: ovulation. The second phase is called the 'luteal' phase. Progesterone, which is made in the corpus luteum in the ovaries, is the dominant hormone in this phase and this causes the walls of the uterus to mature, so that a fertilized egg can nest and develop into an embryo.

The part of the hypothalamus that regulates the secretion of these hormones is slightly more complicated in women than in men, because a cycle must be taken into account in women. Women also have a small amount of male sex hormones in their bodies (about five percent of the amount in men). These hormones are excreted by the adrenal glands. These male hormones are usually converted into estrogen by enzymes in a women's fat cells.

During a famine there are fewer fat cells, so that fewer male hormones are converted into estrogen. The level of these male hormones therefore rises, while the level of estrogen falls. This inhibits various steps in the reproductive system. The same happens when a woman voluntarily starves herself, such as in the case of anorexia nervosa, but also with women who are extremely physically active, like athletes. It often happens that puberty starts very delayed in young girls who are dancers. And women who exercise very often, more often have irregular cycles, or even the absence of menstruation.

Stress can also lead to the inhibition of various processes in the reproductive system. This happens roughly in the same way as with men. Endorphins and enkephalin inhibit the excretion of LHRH. Prolactin and glucocorticoids inhibit the sensitivity of the pituitary gland to LHRH. Glucocorticoids also cause the ovaries to become less sensitive to LH.

As a result, less LH, FSH and estrogen are excreted, reducing the chance of women ovulating. This extends the follicular phase and disrupts the menstrual cycle. In extreme cases, the ovulation system is not inhibited, but stopped. There is then anovulatory amenorrhea.

Also, the level of progesterone often drops during stress, causing the uterine wall not to mature properly. Moreover, during stress, prolactin is excreted, which interferes with the action of progesterone. As a result, a fertilized egg cannot implant itself properly in the womb wall and there is a greater chance of a miscarriage.

A lower level of estrogen during the stress response also has another effect. It normally protects the bones against osteoporosis. With a reduced level of estrogen, the bones therefore become less strong.

Breastfeeding is a good form of birth control. By stimulating the nipples, a direct signal is sent to the hypothalamus to excrete prolactin (this occurs in both men and women). However, breastfeeding must be very structured if it is to be effective as a contraceptive. This has emerged from a study among the hunters and gatherers of the Bushmen tribe. The women breastfeed their children for the first three years. They feed them for two minutes every fifteen minutes. At night the babies sleep next to their mother, so that they can also be fed every 15 minutes at night. The babies do this themselves and do not have to wake the mother up.

The prolactin level increases from the first feeding. Because the nipples of these women are stimulated for three years, the prolactin level remains high for a number of years. Estrogen and progesterone levels are suppressed, so these women do not ovulate. This also happens with most animal species.

What is the effect of stress on sex drive?

Stress makes women less inclined to get sexually aroused and make love. The behavior of females of different animal species may differ. This concerns behaviors such as how willingly a female responds to the approaches of a male (receptivity) and how actively she approaches males (prospectivity). The fluctuations between these behaviors are due to various behaviors, such as the point in the menstrual cycle on which it is timed, the recentness of intercourse, the time of year and subjective matters, such as who the male is.

Stress generally suppresses both 'receptivity' and 'prospectivity' behaviors. This is probably due to the suppression of various stress hormones during a stress response.

Estrogen seems to be the stimulating hormone of the sex drive. Because the estrogen level is highest around the time of ovulation, most sexual behavior is limited to this period. This is especially the case with rodents. In humans, estrogen also plays a role in sex drive, but social and interpersonal factors are more important. Estrogen only exerts these effects in the brain and peripheral tissues. Genitalia and other body parts contain many estrogen receptors and these become more sensitive to touch by the hormone estrogen.

The sex drive is reduced by the removal of a male's hormones. The sex drive can be increased again by administering artificial male hormones. This is even more the case with humans and similar animal species, such as monkeys, than with rodents. Since stress suppresses the elimination of estrogen, it also reduces sex drive.

What are different ways of fertilization?

With regard to psychological factors, there are a number of things that can cause infertility, such as the disruption of daily activities, a reduction in the ability to concentrate on work, alienation from friends and family, and depression. For people who are infertile for physical reasons, various techniques have been developed in the past decades that allow women to still get pregnant. There is artificial insemination, or in vitro fertilization, a process by which an egg is fertilized by sperm outside the womb. The fertilized eggs are then placed in the woman's womb. Another possibility to become artificially pregnant is through donor eggs or sperm cells. Also, pre-implantation screening is a possible method, whereby genetic diseases are first checked before the placement of the fertilized egg in the womb. Only embryos that do not carry the genetic disease are implanted.

However, there are two problems with artificial insemination. To begin with, it is very stressful for the people who undergo it and it is very expensive. Often it is not reimbursed by insurance companies. In addition, the clinics are generally located in large medical centers, which means that people have to spend weeks in a hotel without a social network. Often there is also a very long waiting list, because there are few places available. This is another major stressor that is being added. But the process itself also causes a lot of stress. You are given hormones every day and you are examined. Moreover, every day there is the tension whether there will be good or bad news.

Secondly, artificial insemination rarely works. Based on the rest of this chapter you might think that it rarely works, because it involves so much stress. Studies also seem to show this connection. Women who have a greater stress response (measured among other things by the glucocorticoid level) appear to have lower chance of success. However, it is not entirely clear which direction the relationship between stress and failure has. It is also possible that a woman becomes stressed because it is almost impossible for them to have children, as a result of which artificial insemination often fails. Further research towards this relationship is still needed to be done.

What causes miscarriages, psychological abortion and early birth?

Stress can lead to miscarriages. This phenomenon was already known in the time of Hippocrates. He warned pregnant women that they should avoid unnecessary emotional events. Having a job with high task requirements and little control, for example, increases the risk of getting a miscarriage.

Stress can also lead to miscarriages in animals. This can happen, for example, when pregnant animals are captured or transported in the wild.

Various studies also show that in some animal species with a social hierarchy, a new dominant male kills the young male of the previous male. For example, when the dominant male of a group of lions is chased away by another male, the new dominant male will kill the young male of the previous male, so that those genes are not passed on.

Because the females no longer have to feed their young, they become fertile again and the new male can pass on their genes.

In other animal species, such as wild horses, the new male systematically harasses the pregnant females, causing them to have a miscarriage. This is done for the same purpose. It is remarkable that the male does not necessarily have to bother these pregnant females physically, they will already become stressed by his scent. It is also useful for them to have a miscarriage, because otherwise their young will be killed anyway. This saves the energy that otherwise would be used for the pregnancy.

In reality, however, these types of miscarriages due to stress are not so common. It almost never happens to people. Miscarriages are often blamed on a certain stressor, yet only afterwards. But in many cases these stressors only occurred shortly before the miscarriage. Most miscarriages are the result of an existing dead fetus that is sent out of the body. A causative stressor must therefore have taken place a few days or weeks before the miscarriage.

When stress is the cause of a miscarriage, this has to do with the blood supply. The fetus is very sensitive to the blood flow of the mother. If less blood reaches the uterus, it is harmful to the blood supply of the fetus. Stimuli that slow or speed up the mother's heart rate also cause the same response in the fetus.

More epinephrine and norepinephrine are excreted during a stress response. Large studies conducted with various animal species have shown that these hormones reduce blood flow to the uterus. Because the fetus receives less blood, it also receives less oxygen. This phenomenon is called hypoxia.

However, it is generally assumed that several moments of hypoxia are needed for a miscarriage to occur. Severe stressors therefore increase the chance of a miscarriage.

When a women is at a later stage of delivery, stress increases the chance of an early delivery. This is probably due to an increased glucocorticoid level.

How harmful is stress for female reproduction?

From the foregoing, it seems that even the mildest stressor can completely switch off the reproductive system. However, this is not the case. The mechanisms mentioned (including the excretion of endorphin, prolactin and glucocorticoids) are not nearly as effective.

Farmers in Kenya have an average family of eight children. These people experience some chronic stress due to, among other things, parasites and seasonal malaria.

The Hutterites, another strain of un-mechanized farmers, do not experience chronic stressors. They do not use contraceptives and every woman has an average family of nine children there. So this is roughly equal to the number that Kenyan women get, even though their lifestyles are very different.

A study in a concentration camp in Theresiënstadt during the Second World War showed that fifty-four percent of the women who were about to reproduce no longer menstruated. This was due to the many stressors to which they were exposed, such as hunger, slave labor and psychological horrors. During the first month, the amount of fat these women still had in their bodies was not so low yet that they could no longer menstruate. Many researchers see this as a demonstration of the effect of psychological stress on the reproductive system.

However, it is strange that almost half of the women still menstruated, despite the many (physical) stressors. Both physical and psychological factors are important for the reproductive system.

Practice question:

1. What is the influence of stress on successfully getting pregnant through IVF (in vitro fertilization)?

Answer to the practice question:

1. Few women will get successfully pregnant by the influence of stress.

What is the relationship between stress, the immune system and diseases? - Chapter 8

It used to be thought that the brain and the immune system were two different systems that worked independently of each other. It was thought that the immune system was responsible for killing bacteria, making antibodies and the like, and that the brain causes you to invent the wheel, for example. However, this idea of independence turned out to be untrue for the immune system. Your brain can affect your immune system.

The autonomic nervous system leads nerves in the tissue that is responsible for the production and storage of the cells of the immune system; so that they can enter the blood circulation. Moreover, the tissues of the immune system appear to be sensitive to all important hormones secreted by the pituitary gland, which is controlled by the brain.

The evidence that the brain influences the immune system was provided about a hundred years ago. A well-known example is holding a fake rose in front of someone who was allergic to roses, while this person thought it was a true rose. This resulted in an allergic reaction in that person, directed from the brain. It also turned out that professional actors who had to play a depressive scene all day long had reduced immune responsiveness, while those who had to play a happy scene had increased responsiveness.

Another study revealed the conditioned immune suppression paradigm. This paradigm displays that the immune system can be conditioned. When an animal receives a drug that suppresses the immune system at the same time as a drink with a certain taste, conditioning will occur. When the animal later only receives the drink, the immune system is also automatically suppressed.

It is not surprising that when a fake rose and an artificial drink can influence the immune system, stress can.

What is the basis of the immune system?

The task of the immune system is to protect the body against viruses, bacteria, fungi and parasites. The immune system must be able to distinguish between the cells of the body itself and cells that do not belong there (the invaders). Your immune system is able to remember exactly what every cell in your body looks like. When it encounters a cell that is not exactly the same as your cells, it will be attacked. In addition, the immune system is capable enough to remember the exact structure of hostile cells (such as bacteria and viruses), so that they can be attacked more quickly in the future. The idea of ​​vaccination is based on this assumption. You then get a small amount of cells injected, so that the body can recognize them in the future if it is actually attacked.

The defense of the immune system is based on white blood cells. These consist of lymphocytes and monocytes ("cyte" is another word for cell). There are two types of lymphocytes, namely the T cells and the B cells. They are both produced in the bone marrow, but the T cells continue to grow in the thymus gland, while B cells remain in the bone marrow and grow there. The B cells produce antibodies. There are different types of T cells.

When there is an hostile cell in the body, it is first observed by a kind of monocyte; namely a macrophage. This macrophage presents the hostile cell to a T helper cell and secretes interleukin-1, which triggers the T helper cell. The T helper cell then secretes interleukin-2, causing it to multiply (interleukin-2 stimulates T-cell growth). This causes a cytotoxic cell to multiply, which then destroys the hostile cell.

In people with AIDS, the T cells no longer work.

When the T helper cells are activated by the macrophage, they stimulate the B cells to multiply. The B cells must produce an antidote, in the form of large proteins, which can recognize a certain characteristic of the hostile cell and attach to it. The proteins will fit perfectly on the hostile cell, just like a key fits in the lock. This will immobilize the enemy cell so that it can then be destroyed.

However, the immune system does not work in just that one particular place where the enemy cell is. To alert the entire body, cytokines are released into the bloodstream.

In general, the immune system works very well. But sometimes it can happen that the immune system overlooks a hostile cell or attacks a cell that is not hostile. In the latter case, we speak of an allergy. It is also possible that the immune system attacks the body's own cells. This is among other things, what happens in the case of autoimmune diseases. With multiple sclerosis, for example, a part of the body's own nervous system is attacked. In childhood diabetes, the cells in the pancreas are attacked, which should normally produce insulin.

The above issues are about acquired immunity. This form of immunity only exists in vertebrate animals.

Acquired immunity has three characteristics:

• You learn to specifically target germ X, with antibodies and cell immunity that specifically recognize that germ.

• It takes a while for the immunity to build resistance, when you are exposed for the first time to germ X. The immune system must first find an antibody that fits best, and then it will make many copies of it.

• After repeated exposure to germ X, the defenses will be strengthened more and more.

However, we also have another type of immunity that we share with almost all species, namely innate immunity. With this system, the enemy cell is not first viewed, so that a specific antidote can be created, but this system is immediately activated as soon as an enemy cell is signaled. This immune response is triggered at the place where the hostile cell enters the body.

Your saliva also contains an antidote to every microbe. At the site of the infection these are released into the capillaries, so that the cells of the innate immunity can immediately go to the infected site. These cells contain macrophages, neutrophils and natural killer cells. They then attack the microbe.

Because the capillaries come loose, there can also be a liquid that contains proteins. These also attack the microbe and also cause the area to swell, causing edema. This means that the innate immune system comes into action, causing inflammation.

What is the influence of stress on the immune system?

It has been around 60 years since Selye discovered the first evidence of stress-related immunosuppression: rats that were exposed to something unpleasant got atrophy in immune tissues such as the thymus gland.

For example, it has been found that a period of stress can disrupt various functions of the immune system. For example, stress will suppress the formation of new lymphocytes and their release into the bloodstream and, moreover, shorten the time that existing lymphocytes remain in the bloodstream. Stress also stops the production of new antidotes in response to a hostile cell and disrupts the communication between the lymphocytes by releasing relevant messengers. Moreover, stress stops the innate immunity. This is caused by all kinds of stress: physical, psychological, in primates, rats, birds, fish and people.

This suppression of the immune system is mainly regulated by glucocorticoids. They cause the thymus gland to become smaller. They do this by preventing the formation of new lymphocytes in the thymus. And lymphocytes are the most important components from which the thymus is made.

Glucocorticoids also stop the release of interleukins and intererons, making the lymphocytes less responsive to an alarm. Glucocorticoids simultaneously lead the lymphocytes to be removed from the bloodstream and stored again in the tissues of the immune system. In addition, glucocorticoids can destroy the lymphocytes. Furthermore, most of the effects of glucocorticoids are directed at T cells rather than B cells.

Beta-endorphins and CRH, hormones of the sympathetic nervous system also play a role in suppressing immunity during stress.

What is a reason for the suppression of the immune system?

It is useful to know how it can happen that the immune system is suppressed during stress. In the chapter on the basic principles of human functioning it was explained that during a stress period the immune system is switched off, so that no energy goes to long-term projects; but all energy can be used immediately. This would make sense if the immune system can be switched off completely at any time. However, this is not the case. The immune system is actually broken down during stress. The tissue shrinks and cells are broken down. It takes energy to do this.

The response of the immune system is divided into 3 phases:

• Phase A, in which the stress begins,

• Phase B, in which the stress persists,

• Phase C, in which there is chronic stress.

During an infection, the immune system secretes interleukin-1. Among other things, this activates the hypothalamus to excrete CRH. CRH then stimulates the pituitary gland to secrete ACTH, causing the adrenal gland to release glucocorticoids. These suppress the immune system. In other words: under some circumstances the immune system asks the body to release hormones that suppress the immune system.

During the first half hour after the start of the stressor, the immune system is not immediately switched off, but strengthened. This applies in particular to the innate immunity, but also to the other types of immunity. There will be more immune cells in the bloodstream and if you have a wound, more inflammatory cells will go to the site of this wound. The lymphocytes are therefore better at excreting and responding to the messengers of the immune system. More antibodies are also released in the saliva. This short, enhanced activity of the immune system occurs both with infections and with physical and psychological stressors.

From the moment that the stressor persists for about an hour, glucocorticoids and the sympathetic system suppress the immune system. When the stressor ends soon after that, the immune system is reactivated relatively quickly and restored to the usual level. However, if the stressor lasts longer or if very many glucocorticoids are released, the immune system can remain suppressed to forty to seventy percent below the standard level. This was discovered rather late, since most techniques were previously unable to detect small, rapid differences in the immune system. For decades, researchers thought they were measuring the "immune response" to stress, while they were actually only measuring its recovery. Moreover, most researchers mainly investigated major stressors and large amounts of glucocorticoids that remained for a longer period of time.

Later discoveries were mainly made by Munck. He also predicted why the level of the immune system does not always remain at that higher level (the first half hour after a stressor), but falls back to a basic level. This is because the costs are otherwise too high and if the system would always be too alert, it is more likely that it will attack its own good cells. This happens with immune systems that are chronically activated, which can lead to autoimmune diseases.

As a result, Munck also predicted that without phase B, the phase in which the immune system is brought back to baseline after strong activation, the chance of an autoimmune disease is greater. This result has been verified in at least two areas. First, when you cease glucocorticoid levels in rats and cause them to become stressed, the animals do have phase A, which is mainly controlled by epinephrine, but they do not have an increase in glucocorticoids, so they cannot enter phase B. Now the rat has a greater risk of an autoimmune disease. Secondly, sometimes doctors are forced to remove one of the two adrenal glands because they contain a tumor. Immediately afterwards the glucocorticoid content is halved for a while, until the other adrenal gland has become so large, that it can perform the function of the two adrenals. Until this situation arises, patients are more susceptible to an autoimmune disease or inflammation.

During stress, the immune system is therefore first activated, but then the stress response ensures that the immune system is suppressed again, so that no autoimmune diseases arise.

When stress lasts long enough to suppress the immune system, there are aspects that have been seen as aspects of immune suppression in the past, which are actually subtle features of immune system's activation. First, give a person large amounts of glucocorticoids or a major stressor that lasts for several hours. The hormones will kill lymphocytes without discrimination. If you have a subtle rise in glucocorticoid levels for a short time, the hormones only kill part of the lymphocytes: the part that is old, that no longer works as well. In this way glucocorticoids help the 'immune response' by getting rid of lymphocytes that are not ideal in an emergency. In addition, Dhabbar has shown that glucocorticoids do not only destroy lymphocytes, but that they store part of them in the thymus. Another part of the lymphocytes is brought to the site of infection, so that wounds heal faster.

When autoimmune diseases are the result of over-activation of the immune system, stress hormones such as steroids can be administered so that many glucocorticoids enter the body. These reduce the damage caused by the autoimmune disease. The logic behind this is: by dramatically suppressing the immune system, it can no longer attack the pancreas or nervous system.

It was also found in rats that prolonged, severe stress has the same consequences as administering stress hormones. However, stress can also aggravate autoimmune diseases. This is apparent from retrospective studies in patients. Many researchers who knew that stress hormones help reduce an autoimmune disease ignored this.

The risk of autoimmune diseases is increased by being exposed to many short-term stressors and by the absence of phase B. So when you are exposed to large, persistent stressors, it is best to activate phase C (dramatic immune suppression). This reduces the symptoms of autoimmunity. Also in rats with the autoimmune disease multiple sclerosis it has been found that chronic stress reduces the symptoms of the disease.

What factors cause chronic stress?

Various evidence suggests that stress can affect the immune system and increase the risk of disease. However, it is unclear how much chronic stress is needed to make you more vulnerable to diseases that your immune system would normally ward off.

Investigations towards this always involve four steps that together form the psycho-neuro-immune route:

1. Individuals have been stressed. Whoever studies the effects of stressors on the immune system will always have to struggle with the problem of whether the alleged stressor is actually a stressor for the person. Moreover, it is not always clear whether people are actually exposed to the stressor to which they claim to be exposed. For example, people who have a stomach ulcer will often be able to give up stressors, but the question is whether the stomach ulcer is really caused by this.

2. There was a stress response (the release of glucocorticoids, epinephrine, etc.).

3. The stress response was long and strong enough to suppress the immune system.

4. This would increase the chance that these people would get a disease and that they would be less able to defend themselves against such a disease.

However, immunologists do not yet know how often a change in the immune profile changes the disease patterns. Opposite this is via the lifestyle route. In this route stress is related to the lifestyle of the person, but it also refers to the protective and risk factors the individual encounters.

When a certain disease is more common in people with a lot of stress, you first have to check whether the above steps apply. You must then check whether there are any other explanations that may have put these people under stress and have contracted this disease.

For animals it appears that steps two to four always follow after sufficient stress. But the stressors to which animals are exposed in experiments are worse than the various stressors that people experience. Moreover, people differ in what they experience as stressful. It may therefore be that someone is actually at step one, while he does not experience it that way. It is also possible that someone thinks that he is at step one, but that this is not the case. When a doctor asks if the patient has been suffering from a lot of stress lately, the patient will often decide that there was indeed stress, which could be the cause of the disease. This also happens if there had actually been no excessive stress. Retrospective investigations therefore often lead to a wrong relationship between stress and illness.

In the case of more subtle stressors, the stress responses are also more subtle (step two), so that they are noticed less quickly. And moderate stressors stimulate the immune system more (step three).

Regarding step four, strong suppression of the immune system does indeed lead to a greater risk of disease. But with subtle differences in immunity, the implications are not so clear. In addition, the various steps have been manipulated in studies with rats. It is too expensive and too time-consuming to keep a rat in the laboratory for the rest of its life to observe. In this way, no research is done into the spontaneous development of diseases.

What is the relationship between stress and illness?

Research shows that the fewer social relationships a person has, the shorter the life expectancy and the worse the effects of various infectious diseases are. This applies to both men and women of all races. Protective relationships can take various forms: marriage, contact with friends and family or church membership. The impact of these factors is very large, about the same as the effect of smoking on health, high blood pressure, obesity, physical activity and life expectancy. This could be because people with fewer social relationships experience more loneliness, which causes them to experience more stress. Step one (see section 7.4) is then initiated, which could increase the chance of the following steps to occur. However, little is known about step two. Step three has been proved to exist. In one study, socially isolated individuals produced less antidotes during vaccination than is normal. The evidence for step four is very weak.

However, it is also possible that a shorter life expectancy and stronger effects of infectious diseases are not due to steps one to four, but to entirely different things. For example, it may be that lonely people do not take their medication properly because there is no one who reminds them or encourages them to take them.

Many studies have been conducted in which factors of a risky lifestyle, such as smoking, extreme sports and the like, were controlled. Then there was still a strong link between social isolation and poor health.

Another factor is the loss of a loved one. In one study, the parents of all Israeli soldiers who died in the war against Lebanon were followed for ten years. The loss of a child was generally found to have no effect on death rates, but there were significantly higher rates among those who were already widowed or divorced. A higher risk of death therefore seemed to be mainly associated with the risk of less social support. People who lost a child were more likely to die if they were single than if they were married. This seems to go together with the psycho-neuro-immune route, although the lifestyle route cannot be turned off.

The risk of a cold is also greater during stress. During exams, for example, many students often have a cold. Studies where stress increased the risk of a cold showed that these people had fewer antibodies against a cold in their saliva and nasal passages. Here too it is not clear whether it has to do with the psycho-neuro-immune route or the lifestyle route. Stress changes the lifestyle and a different lifestyle causes a different exposure to viruses that can cause a cold. However, a large-scale study has also been carried out focusing on lifestyle control. This showed that more stress made the chance three times as high that someone got a cold after being exposed to the virus that causes a cold.

Stress can also have an impact on AIDS. This has been investigated by putting human lymphocytes in a petri dish and exposing them to the HIV virus. If the lymphocytes were also exposed to glucocorticoids, they were more likely to get the virus. Norepinephrine also made it easier for the virus to invade the lymphocyte and copy itself. People with HIV also have a greater risk of deterioration and death if they have a negative coping style, if they have little social support, if their temperament is inhibited by the social environment and if they experience multiple stressors, in particular the loss of a person / a loved one. This could be seen as step one in the psychoneuroimmune route.

They also appeared to have an increased activation of the sympathetic nervous system (step two). Steps three and four also seem to be satisfied. The psychoneuroimmune route could therefore contribute to the link between stress and the deterioration of aspects of AIDS. However, more research is needed into how much stress affects people, to what extent they adhere to their treatment and to what extent this treatment works.

Why are there hidden viruses?

There are viruses that are not immediately active once they enter your body. They crawl into a few cells of your body and wait there, until they are set in motion later by something else. These are hidden or latent viruses. When the virus is activated, it copies itself and then hides itself again. An example of such a virus is the herpes virus. Some viruses hide themselves until the immune system has become 'lazy'. Then they copy themselves quickly. The immune system is 'lazy' during physical and psychological stressors.

There have been several explanations on how these viruses know that the immune system is temporarily less active. It could be that the virus is always trying to break out, but the immune system is normally there before the virus has had a chance. It is also possible that the virus can measure the state of the immune system. In recent years it has become clear how these viruses know when they can break out, namely by measuring the glucocorticoid content. When the glucocorticoid level is high, a DNA sensor activates the genes involved in 'waking up' from the latency. Herpes is also able to excrete the CRH hypothalamus. CRH then stimulates the secretion of ACTH, which causes the glucocorticoid level to rise.

What is the connection between stress and cancer?

Studies with animals have shown that stress can influence the course of some types of cancer. For example, tumors grow faster in mice when they are in a stressful environment, with many sounds around them, for example. If you transplant some tumors into a rat and you expose the rat to electrical shock from which it can eventually escape, the rat will reject the tumors. However, if such a rat cannot escape the shocks, it is unable to repel the tumors. This research also showed that when mice are placed on a rotating platform, there is a connection between the number of spins and the extent of tumor growth.

In these studies, stress seems to work at least partially via the psycho-neuro-immune route. The amount of glucocorticoids is namely higher. Glucocorticoids directly affect the biology of the tumor. This is done both through the immune system and through other systems. The immune system contains natural killer cells that prevent the spread of tumors. Stress suppresses the number of natural killer cells, making tumors more likely to grow. If a tumor then starts to grow, it requires a lot of energy from the body. That is why he sends a signal to the nearest blood vessel to grow capillaries into the tumor. This is called angiogenesis and ensures that blood and nutrients reach the tumor. Glucocorticoids support this process. A tumor also needs a lot of glucose. It is therefore very capable of extracting a lot of glucose from the blood and various storage sites in the body, even before this glucose reaches the muscles for which it was intended. And in a stress situation, energy storage is stopped, and the glucose level circulating in the blood is increased so that it can be transported to the muscles. However, the tumor receives the glucose before it reaches the muscles.

We cannot simply generalize these results from the studies that have been conducted with animals to humans. In these studies researcher forced the development of the tumor, which was caused by the injection of tumor cells. Stress has not caused these tumors and it is not about the effect of stress on naturally occurring tumors. In addition, most of these studies are based on tumors that are caused by viruses. In humans, most tumors are caused by genetic factors and exposure to carcinogens from the environment. These types of tumors have not been investigated in animal studies.

Retrospective studies in humans seem to show that stress increases the risk of cancer. In addition, a number of studies have shown a link between major stressors, such as the loss of a loved one, and the onset of colon cancer five to ten years later. Studies have also been done on women who had themselves checked for breast cancer. The history of stress experiences of these women was also checked. Then it was examined which of these women appeared to have breast cancer and which did not. Some of these studies showed a link between stress history and breast cancer. However, this study is not entirely reliable, because these women are generally fairly good at assessing whether they will have breast cancer, based on, for example, a family history of this disease or their own exposure to risk factors.

All in all, there appears to be good evidence for a link between stress and cancer on the basis of prospective studies. For example, having depression is linked to stress and an increased excretion of glucocorticoids. A famous study of two thousand men showed that depression was associated with a doubled risk of getting cancer. However, prospective studies in other populations show a negligible relationship between stress and cancer. However, the link between stress and cancer may also have something to do with the lifestyle route. For example, women who have worked in night shifts for years appear to have a higher risk of breast cancer. However, this is not due to stress, but to the fact that they have a lower level of melatonin, a hormone that responds to light. A deficiency of this hormone increases the risk of breast cancer, among other things.

In people with AIDS, in whom the immune system is suppressed, different types of cancer are more common. People who receive an organ transplant are also more likely to have skin cancer because they are given glucocorticoids to prevent their immune system from rejecting the new organ. However, this is not proof of the link between cancer and stress, because stress never suppresses the immune system that much. Moreover, it is only a small number of people who have AIDS or get an organ transplant that gets cancer. Furthermore, it is only a few types of cancer that generally occur more often. The other types are still very rare.

All in all, there is little support for the theory that stress would increase the risk of cancer. Some researchers think there is a particular kind of personality that is more susceptible to get cancer. Poor handling of stress, suppression of emotions, leniency and accommodating would then be important characteristics of this personality. Most investigations into such a personality traits were retrospective. However, some prospective studies have also been conducted that show a small connection.

In general, however, we have insufficient evidence to assume that there is a link between stress and cancer. A few studies have also been carried out to investigate whether stress increases the risk of cancer returning if it has healed. The results vary, but in general there seems to be no connection.

What is the influence of stress on the course of cancer?

Different coping strategies predict different results during the course of cancer. People who fight for it and remain optimistic live longer than those who become depressed, deny and suppress it. These findings led to various studies in which clinicians tried to intervene, so that stress could be reduced and so that these people remained more optimistic and kept fighting. Psychiatrist David Spiegel has done a study in which he investigated the effect of group therapy. He thought it would only reduce the psychological stress in patients. But it also turned out to extend the lifespan by an average of eighteen months. Group therapy therefore also has a beneficial biological effect.

In 2001, however, an article appeared in the well-known New England Journal of Medicine, about a study that found no effect on survival time. According to Spiegel, this is due to the fact that doctors often withheld cancer. They would rather not make the shameful, hopeless situation known to patients. Later (around 1990) it was possible but not mandatory to make the situation known to the patients, because the doctors recognized the psychological importance of it. Then they could fight something. Moreover, the importance of stress reduction was clear to everyone. That is why almost everyone sought social support and it was very difficult to get people for the control group who did not receive group therapy. These test subjects often sought help, if necessary from people who were not officially registered as psychologists.

Regarding the psychoneuroimmune route, some studies have shown that psychosocial interventions can reduce glucocorticoid levels. However, an over-active stress response does not predict the extent of a shorter cancer survival. The immune system appears to work better in cancer patients with more psychosocial support. Patients with breast cancer who had a lot of psychosocial support were found to have more natural destruction cells than patients with less psychosocial support. But the amount of activity of these natural destruction cells did not seem to lead to a longer lifespan.

It is quite possible that the lifestyle route plays an important role in the relationship between stress and the course of cancer, but this is very difficult to prove. This is because about a quarter of the patients do not take their medication properly. When someone is affiliated with a therapy group, he or she is encouraged by the stories of fellow sufferers to take the medication properly.

All in all, there seems to be no connection between a history of stress and an increased risk of cancer or a relapse. There does seem to be a connection between different personalities and a greater risk of cancer, but it has not been scientifically proven whether this has to do with the physiology of stress or whether it is due to a certain lifestyle.

What does Siegel say about the cure for cancer?

Being too positive about cancer can also have a negative effect. If you think you have the power to prevent or cure cancer by thinking positively, you can see it as your own fault if you die of cancer anyway. Influential health experts, such as Siegel, stimulate patients to have this overly positive attitude. For example, in his bestseller "Love, medicine and miracles," Siegel said that one can heal by daring to love. This makes it appear that cancer is caused by such psychosocial factors and that it can be cured if the patient loves enough. If a patient does not heal, this would be due to a personal shortage of these positive traits. This is however not how cancer works.

Furthermore, several examples of miracles are given in the book by Siegel. An example of this is that people cured cancer because they learned to love and dare. Elsewhere in the book, Siegel says that childhood cancer is indirectly the fault of the parents because they have not given the child enough love, while children are in extra need for this. He also says that patients should not view their illness as God's will, but rather as their deviation from God's will. Siegel has had a fairly large influence with these ideas. For example, some breast cancer patients claimed that stress had caused their disease.

The author indicates that one must be very careful and sure of his statement, before displaying something found in an investigation as the norm. Once something is viewed as the norm, it is very difficult to look at it objectively again and find exceptions to the norm.

Practice questions

1. What are the functions of B- and T-cells?

2. The immune system is suppressed during prolonged stress. The initial explanation for this was that the body tries to save energy and fuel. However, this is could not be the only explanation, since ...

Answers to the practice questions

1. T-cells reproduce after binding to a macorphage. Killer cells are then activated, that destroy the invading cell. T-helper cells stimulate B-cells, that make antibodies and memory cells; that recognize the type of invading cell the next time. 

2. Cells of the immune system are broken down and removed during stress, which in fact do costs energy.

What influence does stress have on pain perception? - Chapter 9

What is the origin of pain perception?

Pain arises in receptors that are spread throughout our bodies. Some types of pain are located deep in the body, such as muscle pain and pain due to damage to the organs. Other types of pain are more on the surface, such as pain when we have cut ourselves or burned our skin.

Some pain receptors only provide information about pain, others provide information about both pain and everyday observations. These two are distinguished by intensity. It gives a pleasant feeling when our heat receptors are stimulated by warm water, but when they come into contact with boiling water, it hurts.

All receptors send nerve projections to the spinal cord. For example, a 'spinal reflex' can be activated, in which neurons from the spinal cord quickly give instructions to the muscles, for example to pull your hand away from a burning flame. Information about the painful stimuli is also sent to the brain.

What is the influence of senses on pain perception?

How strong a pain signal is depends on which other sensory information has gone to the brain at the same time. That is why it is so pleasant to be massaged when you have sore muscles.

Patrick Wall and Ronald Melzack discovered that the nerve projections (the ends that bring information about pain to the spinal cord) are not all the same, but that they are differentiated. For example, there are nerve projections that transmit information about acute, sharp, sudden pain and nerve projections that account for slow, constant pain.

There are two types of neurons that are involved in information about pain, called X and Y. The first (X) is the neuron that transmits pain information to the brain. The second (Y) is also called an interneuron. When Y is stimulated, Y ensures that X is not activated.

Imagine feeling a sharp, painful stimulus. The information is passed on to the nerve projection that passes on information about acute, sudden pain. This stimulates both neuron X and Y. As a result, X sends a signal to the spinal cord, then Y acts up, causing X to be switched off again.

When you feel a slow pain, the information is passed on to the nerve projection that is responsible for the slow pain. The X neuron is also stimulated in this case, and it lets the brain know that the person is in pain. But this time, the nerve projection prevents the action of Y, resulting in X firing again, and you will feel a nagging, slow pain, such a pain that you feel days after you get burned.

Physiologist David Yeomans added the following: the fast nerve projections encourage you to move at lightning speed (away from danger), and the slow nerve projections make you immobile, so that you can heal.

The two types of nerve projections can respond to each other, and we often use them. Prolonged, nagging pain (such as sore muscles or an insect bite) can be temporarily stopped by stimulating the Y interneuron, causing X to be temporarily switched off. This is the theory behind the fact that people often scratch around the insect bite, so that the pain is gone for a moment. It is also used in the medical world; for example, in people with chronic pain syndromes a small electrode is placed in the 'fast pain route', with a stimulator attached to the hip of the person. This effectively reduces the pain.

What does allodynia mean?

Allodynia is a condition in which pain is felt even long after the painful stimulus has stopped or; long after the injury has healed. This condition can cause one to feel pain in response to a stimulus that should not be painful at all.

Allodynia can have various causes. The cause can be at the level of the pain receptors themselves, whereby receptors that are located outside the hurting area can be easily irritable. Allodynia can also occur when neurons in the 'pain pathway' are injured. The third cause is often seen in both types of diabetes: Increased blood glucose levels can increase the risk of atherosclerotic plaque. As a result, insufficient energy goes to the vessels, which causes damage to the nerves that depend on this energy. It is then especially the fast nerve projections that need more energy, so therefore they are damaged more quickly. The person then loses the ability to 'turn off' the Y interneuron. What others experience as a pain that passes quickly,a diabetic then experiences as a chronic pain.

What is meant by subjective pain interpretation?

The interpretation that the brain gives to pain can be very subjective. For example, it may happen that someone who has been given a medicine that kills the tumor cells is not bothered by it, while this pain can normally be very annoying.

This phenomenon was investigated in the 1980s. The extent to which patients who had just had a bile surgery were using painkillers. One group of patients had a view of trees. The second group overlooked a white wall. The first group was found to use significantly fewer painkillers than the second. Other studies with patients with chronic pain showed that the manipulation of psychological variables, such as the degree of control over events, has a major influence on the amount of pain killers used. This indicates that the brain has no objective measure of pain.

Three important issues regarding how the brain interprets pain are:

• The emotional perception of pain can be disconnected from the objective amount of pain. In other words: how much pain you feel and how unpleasant it is, are in fact two different things.

• The emotional parts of the brain can not only change the way you respond to pain information, but these areas of the brain can also change the way the spinal cord responds to certain pain stimuli.

• Stress has a major influence on the way in which the brain interprets pain.

What does stress-related analgesia mean?

When we talk about stress-related analgesia, we are talking about the fact that stress can cause pain to be felt less or even not at all. An example of this is occured on the battlefield in World War II. Anestiologist Henry Beecher examined wounded soldiers and compared them with wounded civilians. He discovered that 80 percent of civilians asked for morphine, while only a third of soldiers did. In sports, too, it can happen that we are so focused on the activity that we can ignore an injury. The perception of pain will arrive later for these patients.

Many scientists would relate this phenomenon to the field of psychosomatics, but in reality, analgesia is a biological phenomenon.

Research has shown that stressed rats on a glowing plate lift their feet later than rats that were not stressed.

The best proof that stress-related analgesia is a real phenomenon is the neurochemistry behind it. It covers various different opiate drugs, such as heroin, morphine and opium, which all have the same chemical structure. In the 1970s, 3 groups of neuroscientists almost simultaneously discovered that these opiate drugs bind to specific opiate receptors in the brain. For example, they discovered how opiates block pain: they activate the 'pathways' that flatten the sensitivity of the X neuron. Now a question remains: Why would the brain contain receptors for a chemical compound found in poppy plants? At first it was thought that a neurotransmitter or hormone would probably be created in the body that is similar to opiates in terms of their chemical structure. A while later,  three different natural painkillers (opioids) were discovered in the human body: enkephalins, dynorphins and endorphins. The word "opiates" refers to pain killers that are not produced by the body, "opioids" are chemicals that are created by the body. Because the study started with the term 'opiates', these receptors are called 'opiate receptors'.

Opioids also explained the effect of acupuncture. Acupuncture stimulates the release of large amounts of opioids. This was investigated by blocking the activity of opioids, using a drug that blocks the opiate receptor. When this kind of receptor is blocked, acupuncture does not affect the pain.

The placebo effect is the phenomenon that a person's health can improve, or the person experiences that his or her health improves, solely because they believe that the medical procedure performed on them has worked: regardless of whether it actually has helped. Patients in the experimental group of a study receive a drug that actually works, while the control group in a study receives treatment that does not really help; such as a fake pill. The placebo phenomenon is explained by opioids that are released in the body.

Opioids are also released during the event of stress. This was reported by Roger Guillemin: In his study, he demonstrated that stress in the pituitary gland stimulates the release of a certain type of endorphin, called beta-endorphin.

What is meant by tress-related hyperalgesia and fibromyalgia?

Stress-related hyperalgesia refers to the phenomenon of the pain not being aggravated by stress, but pain being experienced as "more pleasant". This is a phenomenon that actually only occurs in the patients mind. For example, it may happen that your arm starts to hurt when you see the nurse coming in carrying a needle. The emotional parts of the brain then become hyper-reactive. These emotional parts of the brain are involved in our experience of fear. Brain-mapping studies show that these parts become active during hyperalgesia. People who score high on tests for neurotiscism and anxiety are more susceptible to hyperalgesia during stress.

So, it is quite striking that stress can flatten out our perception of pain. Yet, our brains can also do the opposite. Sapolsky claims that analgesia is more common in conditions of extreme physical pain. For example: half of your body is burned, your ankle is sprained and you are trying to save someone from a burning house. Hyperalgesia, for example, occurs in a situation in which your shoulder hurts, when you think you have a melanoma, or when you consider that your doctor is on a holiday for three days.

Fibromyalgia is a mysterious syndrome in which people have remarkably reduced pain tolerance and sensitive spots all over the body, while doctors cannot find any biological cause of it. People suffering from this syndrome have abnormally high levels of brain activity that regulate the emotional assessment of pain.

Practice question:

1. Why are people inclined to scratch their insect bites?

2. Explain the placebo-effect.

Answer to the practice question:

1. We stimulate interneuron Y; by scratching and hurting the bitten area; to draw away the attention from neuron X; the itch that the insect bite causes.

2. People can come to believe that a treatment they are taking is effective, resulting in them having reduced symptoms, or even no symptoms at all. In fact, the treatment does not really work. So in a psychological way, placebo treatment reduces the pain the person experiences.

How does the memory work under the influence of stress? - Chapter 10

How does the memory work?

The memory consists of different parts. First, we make a distinction between the long-term memory and the short-term memory.

The long-term memory contains the information that you do not need á la minute, but which you are always able to refer to when someone for example asks you about something. Think, for example, of your own name, your telephone number, but also the name of the queen or what year it is.

Information that you only need for a short period of time is stored in the short-term memory. An example of this is that you may look up a telephone number in a telephone book, remember it briefly and forget it again after you hang up the phone. You also rely on your short-term memory when you have a conversation: Through the short-term memory, you are able to remember what someone has just said. Neuropsychologists have discovered that there is a certain part of the long-term memory that stores memories that go far back into childhood, such as the name of the village where you used to live, your mother tongue, the smell of your grandmother's meals, et cetera. This kind of information is stored in the part of the brain that is distinguished from the parts in which more recent memories are stored. For people with dementia, a large part of the long-term memory is damaged, but the part with the memories of their past often remains intact. This information is stored in the part of the brain that is distinguished from parts in which more recent memories are stored. 

Another important distinction, is the difference we assume between the explicit (also called 'declarative' memory) and the implicit memory (which contains an important sub-memory; called the 'procedural memory'). The explicit memory contains memories about facts and events, such as: today is a Monday, my dentist has big eyebrows, etc. For these memories, you are aware that you know them.

The implicit procedural memory, on the other hand, consists of skills and habits. You need them when doing certain automatic activities, such as cycling. You don't have to think about how to cycle while you are cycling; you 'just do it'. Actions can be stored in the explicit memory first, after which they are able to transfer to your implicit memory store. For example, when you've only recently started playing the piano, you consciously consider how to place your hands on the keyboard. At a certain point, you find out that you are able to do it it automatically: So, this action is no longer explicit, but has become implicit and now belongs to your procedural memory. When this happens, you may have the idea that your hands have taken over the actions from your brain.

The memory can be very disturbed when you try to make an implicit memory explicit. This can happen, for example, with someone who learns to play a musical instrument rather quickly and at a certain point suddenly starts to think about what he or she is actually doing. It is also an effective trick from the branch of sports. When your tennis player is better than you, you can say: “Wow, you are good at that! Can you explain to me how you do that? How do you position your fingers?” There is a good chance that the opponent will start thinking about his actions, and thinking too much about his actions, which can cause him to fail. Or; try to explain to someone how to hold a pen. While this is normally a fully automatic task, it will be almost impossible for you to explain it to someone else.

Just as there are different types of memory, there are different areas of the brain involved in storing and recalling memories. Important parts are the cortex and the hippocampus. These two components are damaged in a patient with Alzheimer's disease. When you compare the human memory with a computer, the cortex is your hard drive, in which memories are stored. The hippocampus is the keyboard, providing the means to store and retrieve memories from the hard disk. The part of your memory that takes care of bodily movements is the cerebellum.

The distinction between the explicit and implicit memory, as well as its neuroanatomical basis, was discovered around 1950 on the basis of one of the most tragic cases in neurology: patient HM. He was a patient with a severe form of epilepsy that originated in his hippocampus. HM was resistant to treatments with drugs that were available at the time. As a final way out, a large part of his hippocampus was surgically removed. The result was that he was no longer able to convert his short-term memories into long-term memories. What was particularly striking about his case, is that HM still knew how to perform automatic activities just as well as before, and just as well as other people. For example, he could solve a puzzle within the same amount of time that someone without epilepsy would need.

It has long been thought that every individual neuron in the cortex would have its own task. This idea originated by research in the 60s, done by David Hubel and Torstein Wiesel from Harvard University: They discovered that there was a part of the visual cortex in which every neuron responded to only one thing, namely a bright spot that is located on the retina. These neurons respond to a succession of activity on neighboring spots on the retina, and projections run to a neuron in the next layer. The neurons therefore correspond to a "straight line". A series of these neurons has projections going to the next layer, because every neuron at that cortical level corresponds to a certain moving light line. This particular discovery made people believe that there must be a fourth level, in which each neuron corresponds to a certain collection of light lines. People also thought there would be a fifth, sixth, seventh (etc.) level, in which a neuron could responds to one specific thing, namely your grandmother's face seen from a certain angle or perspective. The neuron next to it responds to the face again, yet from a completely different angle.

However, memory information is stored in greater neural networks rather than in single neurons. These neural networks are fixed rows of neurons. The first layer consists of neurons of the Hubel and Wiesel type, with each neuron recognizing one type of fact. For example, Neuron 1 recognizes Gauguin, 2 recognizes Van Gogh and 3 Monet. They are therefore specialized in one task. These three neurons send information to the second layer, which we will now briefly call neurons A to E. For example, 1 passes on information to A, B and C, 2 to B, C and D and 3 to C, D and E. Neuron A therefore only has information about Gaugin's drawings; E only knows something about Monet, but C has information about impressionism, to which all three drawings belong. This neuron therefore knows that what one perceives considers paintings that have been painted in the impressionistic style. Neurons B and D are also 'impressionism neurons', but they are less good than neuron C; because they "know" fewer examples.

Neuroscientists perceive that learning and storing information happens through the strengthening of some branches of a neural network. How is this reinforcement achieved? A neuron secretes chemical messengers. We also refer to these messengers as neurotransmitters. The neurotransmitters go into the synapse, which is a small hole between the branches of two neurons. Via the synapse, the message is passed from one neuron to another, by means of the neurotransmitter. There are many different types of neurotransmitters. For example, synapses in the hippocampus and cortex use the most irritable neurotransmitter there is, namely glutamate. In addition to the fact that they respond so easily to stimulation, glutamatergic synapses have two properties that are very important for our memory. The first one is that the synapses are non-linear in their function. What does this mean? For other neurotransmitters, when a number of neurotransmitters is secreted the next neuron is stimulated. When more neurotransmitter is excreted, the amount stimulation will also increasae. With glutamatergic synapses, nothing happens when only a little bit of the neurotransmitter is released. Even when a slightly larger amount is excreted, still nothing happens. Only when a certain threshold is exceeded, the second neuron suddenly becomes active. It is just like a professor who gives an incomprehensible lecture: people listen but forget about it very quickly again. However, when the information is repeated and repeated over and over again, a student may suddenly experience a so-called 'aha-erlebnis'. 

The second property of glutamatergic synapses is just as important. Under the right circumstances, some event takes place when a synapse has received a sufficient number of excreted neurotransmitters. The synapse may namely become more active, resulting in that it will be more easily stimulated the next time.

More and more evidence is being found for the idea that the formation of new memories happens through the formation of new connections between neurons and even by the formation of new neurons.

How can short-term stress lead to improved memory?

Short term stressors can improve memory. This is the optimal type of stress, which we call 'stimulation'; during the experience of this type of stress we are more alert and focused. This effect has been shown by studies with laboratory animals as well as with humans. An important study in this area was conducted by Larry Cahill and James McCaugh at the University of California. They read a story to a control group that was not that exciting: “a boy and his mother walk through the city, past various shops. They cross the street and arrive at the hospital where the boy's father works. He shows them the X-ray room.” A story was read to the experimental group that was different from the story that was read to the control group. At the core of the story, something very emotional happened. The story went like this: “a boy and his mother walk through the city, past various stores. They cross the street ... where the boy is hit by a car! He is taken to the hospital and taken to the x-ray room ...” When the test subjects were tested weeks later, it turned out that they could repeat their story better than the control group. Yet, this only applied to the middle, emotional part of the story. This discovery corresponds to the so-called phenomenon of the 'flashbulb memory': It states that people can vividly remember an exciting or event that has great emotional value to it. The memory process for emotional events is therefore stimulated, although the accuracy of the memory will not always be of a very high level. The memory for the neutral parts of the story turned out to be not any better than the memory of the control group.

This research also showed how this effect influences our memory. When you listen to a stressful story, your stress response is activated. The sympathetic nervous system acts up, which ensures that epinephrine and norepinephrine enter your bloodstream. Sympathetic stimulation is very important; which was demonstrated by Cahil and McCaugh, who gave test subjects a drug that blocked their sympathetic activation (the beta-blocker propanolol, the drug that is normally also used to lower blood pressure). The result was that subjects from the experimental group did not remember the story any better than people from the control group did.

The sympathetic nervous system takes the hippocampus into a more alert and activated state, making memory formation easier. The process of memory formation takes place in the amygdala. The sympathetic nervous system also has a second way to stimulate cognition. A lot of energy is needed for this process, so the sympathetic nervous system helps by mobilizing glucose in the blood stream and increases the power with which the blood is pumped to the brain. For this reason, the body has a very good adaptive memory. When a stressor occurs, the best thing to remember from your memory is how you got here in this situation. It is also important that you consider what you did wrong during the stressor, so that you can do better the next time.

In addition, a mild increase in glucocorticoid levels also benefits memory formation. This process takes place in the hippocampus, where the increased glucocorticoid content helps the long-term memory. Finally, there are some mechanisms through which moderate, short-term stress makes the sensory receptors more sensitive. The sense of smell, sense of touch and cochlear cells in the ears need less stimulation to be able to send the information to the brain.

How can persistent stress cause poorer memory?

Educationalists call it the 'reverse-U relationship': the fact that memory improves in times of short-term stress, but however deteriorates when this stressor persists. This deterioration has been demonstrated in numerous studies with laboratory rats and with a range of stressors. The same effect was determined in studies where the rats were injected in order to raise their glucocorticoid level.

Studies have shown that other brain functions, such as the implicit memory, are not affected by stress. Older memories are also more susceptible to become inconsistent due to stress than newer memories.

People with Cushing syndrome develop tumors that cause far too many glucocorticoids to be secreted. As a result, the patient has a high risk of having increased blood pressure, diabetes, immune suppression, reproductive problems, and so on. However, they also develop memory problems, this is also called "Cushingooid dementia". The explicit memory will particularly be affected for these people. This is also often the case when people are treated with glucocorticoids for a long time.

Stress also disrupts executive functions. By executive functions, we mean the things that we do with stored facts; so how we store them as strategically as possible and how they dominate our assessments and decisions. This happens in the part of the brain that is called the prefrontal cortex.

What are the damaging effects of stress on the hippocampus?

How does long-term stress disrupt the part of the memory that is dependent on the hippocampus? Research on laboratory animals has shown various effects.

• First of all, stress ensures that neurons in the hippocampus no longer work. Even when no glucocorticoids are produced (for example, in a rat of which the adrenal glands were removed), stress still disrupts long-term potentiation in the hippocampus. Extreme activation of the sympathetic nervous system is responsible for this. Yet most research on this topic is focused on glucocorticoids. When the stress becomes more than moderate, the hormone no longer stimulates long-term potentiation, on the contrary, it disrupts the process. Why does a rising glucocorticoid level to a certain value increase communication between neurons and when it has risen too far, it does the opposite? Ron de Kloet from Utrecht University discovered the answer. The hippocampus has large quantities of two different types of glucocorticoid receptors. However, the hormone is about ten times better at binding to one type of receptor (the high affinity receptor) than to the other (the low affinity receptor). When the glucocorticoid content rises a little, a large part of the hormone effect is mediated by the high affinity receptor. When the stressor becomes larger, the low affinity receptor is also activated. Activation of the former receptor improves memory functions, while activation of the second receptor reduces memory functions.

• The amygdala also plays an important role in this process. The amygdala is strongly activated during major stressors and sends a large, influential projection to the hippocampus. This activation ensures that stress disrupts the function of the hippocampus. When the amygdala is damaged in a rat, or is disconnected from the hippocampus, stress no longer damages the part of the memory in which the hippocampus is involved.

• Secondly, neural networks are disconnected. Axons and dendrites are very important when it comes to neural communication and neural networks. Bruce McEwen has shown that after a few weeks of stress, these compounds start to atrophy in rats and then (partly) break down.

• Thirdly, the formation of new neurons is prevented. Formation of new neurons is also called neurogenesis. Normally, new neurons are also formed in adults. However, it was thought for years that this was not the case. Two characteristics of neurogenesis are very important. The first characteristic is that the hippocampus is one of the places in the brain where these new neurons originate. The second characteristic is that the extent to which neurogenesis takes place can be regulated. Learning, an enriched environment, exercise or exposure to estrogen can all increase the level of neurogenesis. Stress and glucocorticoids, on the other hand, can prevent neurogenesis. It is not yet known whether and how quickly neurogenesis recovers after the stressor has ended. There is also not much certainty about the function of neurogenesis. On the one hand there are studies that claim that, under the right conditions, many new neurons arise and that these form connections to other neurons. These new connections are needed for different forms of learning. On the other hand, these results are very much doubted by other researchers.

• Fourthly, hippocampal neurons are threatened. In the beginning of the stressor the energy supply to the brain increases, but when the stressor lasts for 30 minutes, this glucose supply returns to normal levels. If the stressor persists even longer, the glucose supply is reduced to 25%; especially in the hippocampus. This effect is due to glucocorticoids. It is not serious for healthy neurons, but neurons that are in a neurological crisis are more likely to die. When rats are stimulated to have an epileptic heart attack, the higher the glucocorticoid level will be during this heart attack, so the more hippocampal neurons die. The same applies to rats with cardiac arrest, in which oxygen and glucose supply to the brain is cut off. There is even evidence that hippocampal neurons can be killed as a result of prolonged stress or glucocorticoids. Research has shown that guinea pigs exposed to higher glucocorticoid levels than the body can ever produce can damage the brain. And in 1980 it was shown that "glucocorticoid neurotoxicity" occurred not only in the laboratory, where very large amounts were administered, but also in the normal life of rats. Stress and glucocorticoids accelerate the degeneration of the aging hippocampus. When you remove the rat's adrenal glands, so that fewer glucocorticoids are produced, this process is delayed. The glucocorticoid content also determines the amount of memory loss.

There are a number of problems that can arise due to the influence of stress on the hippocampus:

1. Cushing's syndrome. People with this syndrome produce very high glucocorticoid levels due to tumors. The consequences of this are damage to the parts of the memory in which the hippocampus is involved. With 'brain-imaging' techniques, it can be seen that these people have a decrease in the volume of their hippocampus. The greater the glucocorticoid secretion, the greater the loss of volume in the hippocampus and the greater the memory problems.

2. Posttraumatic stress disorder (PTSD). This anxiety disorder can be caused by a variety of traumatic stressors. People with PTSD who have been exposed to repeated trauma (for example soldiers or people who have been abused several times) have smaller hippocampi. The following also applies to this disorder: the more trauma's a person has experienced, the more severe the volume reduction will be.

3. Severe depression. This mental illness is intertwined with long-term stress. The longer the stressor takes place, the greater the volume reduction of the hippocampus. Furthermore, depressed persons mainly have a reduced hippocampus when the type of depression they have is intertwined with an increased glucocorticoid content.

4. Repeated jetlags. For people who have a career as a pilot or steward, the following generally applies: the shorter the average amount of time they have to recover from their jet lag during their careers, the smaller the hippocampus and the greater the resulting memory problems.

5. Become older. People with an increase in glucocorticoid levels have, on average, a greater chance of volume reduction of the hippocampus and memory reduction.

6. Interactions between glucocorticoids and neurological damage: A number of studies show that the higher the glucocorticoid content, the greater the neurological damage.

All these studies provide evidence that glucocorticoids damage the human hippocampus. There are, however, a number of counter-evidence for these investigations. For example, there are studies that show that people with PTSD have a lower glucocorticoid content. If this is the case, it cannot possibly be the casse that the abnormal secretion of hormones damages the hippocampus. The hormones nevertheless form a plausible explanation. PTSD patients are more sensitive to glucocorticoids.

Moreover, it is not clear whether the decrease in volume in the hippocampus is due to the trauma itself, or to the post-traumatic period that follows. There is also a theory that claims that you are more prone to develop PTSD after being exposed to trauma when you already have a smaller hippocampus.

Finally, we have just discussed studies that are only correlative: It is therefore difficult to demonstrate a causal relationship between an increased glucocorticoid level and atrophy of the hippocampus. It may just as well be that an increased glucocorticoid content is caused by atrophy, rather than the other way around. There are, however, good reasons to think that there is indeed a causal link between PTSD and an increased glucocorticoid level. An example of this is the fact that when the glucocorticoid level returns to a normal state in people with Cushing's syndrome, the hippocampus slowly returns to its original size as well.

Practice questions:

1. What is Cushingoid dementia?

2. Is there a causal relationship between having a small hippocampus and developing PTSD after a trauma?

Answers to the practice questions:

1. It occurs in people with Cushing's syndrome who excrete an increased level of glucocorticoids. This results in damage to the hippocampus, and possibly in Cushingoid dementia.

2. There is a correlation between a smaller hippocampus and having PTSD; however, research is not sure yet about a potential causal relationship.

How is sleep influenced by stress? - Chapter 11

What are the basic principles of sleep?

People spend a third of their lives sleeping. Sleep is a state in which many processes in our body run at a lower pace. However, this does not apply to the brain. The brain is even more active during sleep than when you are awake. The brain causes the eyelids to contract, memories are stored and problems are solved.

There are different types of sleep:

• Superficial sleep, from which you wake up quickly (this sleep is also known as phases 1 and 2). You are in this phase when you have only just fallen asleep.

• Deep sleep (also known as phases 3 and 4 or 'slow wave sleep'). This type of sleep follows superficial sleep.

• REM (Rapid Eye Movement) sleep, the phase of sleep in which we dream. During this phase, our eyes go back and forth very quickly, hence the name given to this phase. The legs of a dog also move during this sleep. We are in this phase of sleep after we have slept superficially and deeply.

This cycle repeats approximately every ninety minutes. The brain also works in different ways during the different phases. This can be investigated by letting people sleep in a brain scanner while you measure the activity of the different areas of the brain.

When you sleep deeply, the brain regions associated with excitement are calm. This also applies to the regions involved in muscle movements. The brain areas that are responsible for storing and retrieving memories do not have a major decrease in their metabolism during sleep. But the paths along which information goes to and from these regions are shut down, so the regions become isolated. The parts of the brain that respond to sensory information are somewhat shut down, but the parts that give meaning, integrate and associate this information undergo a greater change. The result is a 'sleeping brain'.

Energy is restored during deep sleep. This has been learned because research has shown that the degree of sleep deprivation is not a great predictor of the total time you will sleep, but it is for the total time that you are in deep sleep. During this sleep, the energy that you have lost is 'replenished'.

During REM sleep, a completely different image is seen in the brain. In general, there is an increase in activity. Some areas are metabolically even more active than when you are awake. Examples of this are parts that control muscle movements, memory and processing of sensory information and areas of the brain stem that are involved in breathing and heartbeat. There is also an increase in activity in the limbic system, which is involved in emotion. With regard to visual perception, there is not much increase in activity in the cortex that first responds to visual information, but in the area that integrates visual information. This causes someone to dream.

Why is a dream often so unrealistic, illogical, hyper-emotional and without order? This is because during REM sleep there is little metabolism in the frontal cortex, the part of our brain that is involved in cognitive and emotional functions such as decision making, planning, social behavior and impulse control. When the frontal cortex is damaged, one person starts to say strange things and undertake activities that another person would only think about, but would not do. So, there is less inhibition.

Sleeping is necessary. One can live longer without food than without sleep. There must be times when the brain runs at half power to replenish the energy supply. Although the brain only takes up about 3% of your body, it needs a quarter of the body's total energy.

Some scientists speculate that sleep is needed to cool the brain from all activities. Another function of sleep is dreaming. If you do not sleep one night and the night after, you will have more REM sleep than normal, which would almost give you the idea that you have built up a sort of 'dream deficit'.

Sleep can also play an important role in solving a problem, in forming new memories and in storing information from the previous day, even information that you hardly knew at the end of the day. Proof of this is that when you teach an animal a task and then disrupt its sleep, the new information is not stored. Other supporting evidence is that if you are exposed to a lot of new information one day, you will be in REM sleep longer during the night. The number of times you have gone through the different types of sleep during a night also predicts the extent to which new information will be remembered the next day. This would also be the reason why small children sleep so much. They experience a lot of new things, so they'll have to sleep a lot as well.

McNaughton found evidence of a completely different nature. He discovered that the same neurons in the hippocampus that had been involved in learning new information during the day, were also active at night. Activation patterns were also the same at night and during the day.

What causes sleep deprivation?

Various things change in the body during the phase of deep sleep. First of all, the sympathetic nervous system makes way for the parasymphatic nervous system. The glucocorticoid content also decreases. There has been years of evidence that there is a 'corticotropin inhibiting factor' (CIF) that blocks the secretion of ACTH, thereby reducing the secretion of glucocorticoids. Nobody knows exactly what this CIF is about, but it is thought that it is a substance in the brain that causes you to fall into a deep sleep. That is why it is also called 'delta sleep-inducing factor'. During REM sleep, more glucocorticoids are shed out by the brain and the sympathetic nervous system comes back in force.

The stress response is switched off during sleep. About an hour before you wake up, the CRH, ACTH and glucocorticoid levels go up. These hormones play a role in ending sleep.

Someone who abstains from sleep has higher levels of the above-mentioned hormones. The sympathetic nervous system is overly activated and the production of growth hormones is inhibited. The increased level of glucocorticoids during sleep deprivation play a role in breaking down stored amounts of energy. That is also the reason why when we study late into the night, we often find out in the morning that we don't remember much about it. This has also been researched. For people who got enough rest, the frontal cortex lit up while doing a task. In subjects who experiences sleep deprivation, the frontal cortex was also activated, but also large parts of the rest of the cortex.

From the previous chapters we already know that long-term stress and glucocorticoids can damage the hippocampus and the associated explicit memory. Kei Cho from the University of Bristol investigated aircraft guards who worked for two different airlines. At company 1, you were given a rest period of 15 days after you had been on a transcontinental flight, during which you would get a major jet lag. At the company of airline 2, you were given only five days off after the continental flight arrived. Guards at company 2 therefore did not get a larger jet lag, but did get a shorter time to recover.

Cho only examined people who had done this job for at least five years. He discovered that guards from the second company had a more damaged explicit memory on average, higher glucocorticoid levels and also a smaller temporal lobe (the part of the brain in which the hippocampus is located).

How can stress act like a sleep disruptor?

The hormone CRH stimulates ATCH during stress, eliminating glucocorticoids. However, this is not the only function of CRH; it also generates a fear response and makes you feel awake and alert. When you inject a sleeping rat with CRH, its sympathetic nervous system is activated. Due to the physical consequences that occur after activation of the sympathetic nervous system, it will be difficult for the rat to fall asleep again. It is therefore not surprising that about 75 percent of all cases of insomnia are caused by a the presence of a major stressor in the person's life. Many studies also indicate that "poor sleepers" tend to have higher levels of glucocorticoid in their blood.

Stress does not only influence the amount of sleep you get, but also the quality of sleep. When sleep decreases as a result of a CRH injection, the deep sleep phase is shortened, which is exactly the phase of sleep that you need to restore your energy. Now, sleep is dominated by more superficial sleep phases, from which you wake up quickly.

The phase of deep sleep fulfills the function of energy storage. In this phase, a characteristic pattern can be recognized which we call the 'delta power range'. This can be seen by means of an EEG. When people are stressed or injected with glucocorticoids; the latter artificially causing a stress response, this phase takes up only little time.

A vicious circle is created as stress and sleep deprivation reinforce each other. Sleep deprivation activates the stress response and an activated stress response causes us to sleep shorter and more superficially, which in turn causes more stress. 

A research study has been done that asked whether the participant's expectation of going to bed late would make him or her stressed enough to sleep poorly. The researchers said to a group of volunteers that "they could sleep as long as they wanted". Most woke up around nine o'clock. Around eight o'clock their levels of stress hormones started to rise. How should we interpret this? These people had enough sleep, were fully recovered and had energy again and at around eight o'clock their brains 'knew' that they had to secrete hormones, waking the person up. But the second group of test subjects was told to get up at six o'clock. And what happened? Their hormone levels also increased, at already five o'clock in the morning. The latter phenomenon was caused by the effect of stress. If you are told that you are awakened at an earlier time than you want, but you are not allowed to know what time, then the stress hormone level will be increased throughout the entire night.

Fragmented sleep is also very bad for the human body. Even though a person sleeps longer than usual, regular interruptions in sleep make him feel like he or she is still tired when he gets up. However, the most harmful thing is fragmented sleep in combination with unpredictability.

Practice questions:

1. What are the different phases of sleep?

2. During which of those phases of sleep does dreaming occur?

3. How come that a bad recovery from a jet lag impairs your memory?

Answers to the practice questions:

1. The first two phases are superficial sleep, then come phase 3 and 4; which are phases of deep sleep. Lastly, the phase of REM sleep occurs.

2. During the phase of REM sleep.

3. Not being able to recover from a jet lag causes increased glucocorticoid levels, which in the long term can impair and damage the hippocampus. The hippocampus is essential for explicit memory; so this will become impaired.

How do stress, aging and mortality influence each other? - Chapter 12

Awareness of the fact that life is finite and that one will die at a certain point begins in puberty. The older people get, the more they are concerned about this. With age comes the defects, such as dementia, pain and muscles that no longer respond the way we want. The shortcomings come as soon as we have grown up, but we also learn to appreciate life and ourselves more and more.

Many people in the non-Western world are not afraid of death. They also don't mind aging. Often age and power go together with them. For example, think of tribal chiefs, these are often the oldest members of a tribe.

Gerontologists, who investigate the aging processes, have increasingly found evidence that almost everyone is getting older with a certain degree of success. Moreover, the quality of social relationships often improves, although the quantity decreases. There are also certain cognitive skills that improve with age. People tend to know more and have more factual knowledge. Moreover, older people often see themselves as healthier than most others and they are often happier and experience fewer negative emotions. The negative emotions they do experience, don't last that long either.

Studies that make images of the brain and brain activity (brain-imaging studies) show that negative images have less impact and positive ones more, compared to young people.

How do older organisms deal with stress?

It has been found that older organisms cannot cope very well with stress. Old age can be seen in various ways as a poor ability to cope with stress. As a result, older organisms are often emotionally fragile and vulnerable.

Many aspects of the body and mind of the elderly are effective, as long as they are not put under pressure. When exposed to physical, cognitive or psychological stressors, such as illness or time constraints, different functions no longer work as well.

Aging also affects the stress response. This may be because the stress response is not activated sufficiently when necessary. Individual cells have different defenses that they can use against a certain challenge. This could be seen as a cellular stress response. These different cellular stress responses respond less and less effectively to challenges during old age.

The stress response of entire organs also works in approximately the same way.

If, for example, healthy test subjects, without a heart disease, are allowed to participate in a study and challenge their heart function by having these people do certain exercises, it appears that the hearts of older people respond less adequately than the hearts of younger people. This is because the heart and vessels of older people do not respond as well to epinephrine and norepinephrine as younger people. Yet older people in particular excrete more epinephrine and norepinephrine.

The brains of old and young rats contain approximately the same amount of energy. But when the system is put under pressure, by blocking the supply of oxygen and nutrients, energy levels decrease faster in the brains of older rats. Another example is the body temperature. This does not change with age, but older people have a less good stress response to changes in heat. They can adjust less quickly when they have been very cold or very hot.

Cognition also changes in older people. When old and young people have to take an IQ test without a time limit, the results are about the same. However, if a time limit is set for the test and the cognitive system is stressed as a result, the scores decrease for both the elderly and the young. However, the scores for older people decrease more than for younger people.

The problem with aging can therefore be due to a too small stress response. However, sometimes there is also too much of a stress response. It is possible that the stress response is permanently activated, or that it takes too long to switch it off again at the end of the stressor.

Older individuals are less able to reduce the levels of epinephrine, norepinephrine and glucocorticoids to their basic level. Even when there is no stressor, the levels of these hormones are increased in the elderly. This has an unfavorable effect.

What is the influence of stress on old salmon?

Research has shown that a very large amount of stress can increase the risk of some age-related diseases. Moreover, it has been found that in various animal species an excessive amount of glucocorticoids is the cause of death as they age.

Salmon die soon after they have laid eggs. Nobody knows for sure why this is. What biologists know is that the excretion of glucocorticoids is completely disrupted in these salmon that subsequently die. So this seems to be a cause. If you catch a salmon shortly after it has laid eggs, it will have large glands in the kidneys (adrenal glands), ulcers in the digestive tract and kidney disorders, its immune system no longer works properly and it will suffer from parasites and infections. Moreover, this salmon will have very many glucocorticoids in the blood stream. This is because the brain is no longer able to measure the amount of glucocorticoids in the blood and continues to send signals to the adrenal glands to excrete more glucocorticoids. These then mobilize the various diseases to develop that this salmon suffers from. When the adrenal glands are removed from a salmon that has just laid eggs, this salmon will live a year longer. The glucocorticoids are therefore the cause of these diseases.

However, this system does not only occur with different types of salmon, but also with certain marsupial mice from Australia. These two animal species are not related to each other, which means that they have evolved in the same way independently of each other.

What causes chronic stress?

It seems that stress influences aging in animals. Rubner, a German physiologist, has researched the relationship between how different animal species live and how they die. Among other things, he measured the heart rate of these animals. He concluded that a body can only go on for a certain amount of time, that there is a certain number of beats, breaths and the like that a body can perform. After that the body is, as it were, "used up" and dies. For example, a rat that has about 400 heart beats per minute lives for about two years and an elephant, which has about 35 heart beats per minute, reaches an average age of sixty years. For example, Rubner stated that some species live longer than others. This would also explain the individual differences within animal species.When someone is often stressed and therefore has a faster heartbeat and the like, the body will sooner be 'used up' and this person will die younger.

Rubner's ideas have not survived, but they have ensured that many others suggest that the environment influences the wear and tear of the body. This fits within the concept of stress.

Excessive stress increases the risk on various diseases, and the symptoms become more common as we age. During aging, some aspects of the regulation of the excretion of glucocorticoids are disrupted.

This may be due to negative feedback inhibition, or end-product inhibition. When a certain amount of something becomes larger, the chance that more is being cut out becomes smaller. This is because there is a sensor that transmits this. You can compare this phenomenon with the water reservoir of the toilet, which does not overflow when the toilet is filled again.

Most hormonal systems work according to this feedback mechanism.

The brain causes glucocorticoids to be excreted by letting CRH and ACTH excrete through the pituitary gland. The brain measures the amount of glucocorticoids in the blood stream to know if they need to excrete more, or less CRH. The amount of glucocorticoids must be at a certain basic value. If this is not the case, increased or decreased amounts of CRH are excreted to achieve this balance. However, this basic value can shift. For example, the basic level during stress is different from normal.

When someone is injected with artificial glucocorticoids (dexamethasone), the body usually responds to this and the pituitary gland secretes less CRH and ACTH, so that the level of glucocorticoids falls again. Such a person is 'dexamethasone-responsive'. However, if the feedback regulation does not work properly, this person will continue to excrete the hormones. Such a person is 'dexamethasone resistant'. This also happens with old people and with certain animal species. The glucocorticoid feedback regulation no longer works so well. This also explains why old organisms excrete an enormous amount of glucocorticoids, even when they do not experience stress or during the recovery period after a stressor. This is due to the degeneration of a certain part of the brain during aging.

There are only a limited number of places in the body that have receptors that measure the amount of glucocorticoids. The most important place is the hippocampus.

It has been found that neurons of the hippocampus can be damaged during aging. One of the consequences of this is that far too many glucocorticoids are excreted. The neurons in the obsolete hippocampus are damaged by exposure to glucocorticoids. Because of this damage, even more glucocorticoids are shed out, causing even more damage to the hippocampus, and so on. So when someone is often exposed to intense stress, or has been given glucocorticoids as a medicine for a disease, this can speed up the process. The hippocampus will be damaged more quickly and the glucocorticoid content will then be higher.

However, it is not the case that the dysfunctions described above are an integral part of aging. There are also organisms where this is not the case.

Practice question:

1. What kind of neurological evidence was found that supports the idea that older people experience fewer negative emotions?

Answer to the practice question:

1. Brain-imaging studies have shown that older people's brains respond less to negative images, and more to positive images.

What is meant by psychological stress? - Chapter 13

In the field of biology, various sub-areas come together, including physiology and psychology. Each sub-area makes its own specific contributions. For example, it was discovered that the brain has different feedback systems. These systems indicate whether, for example, the ideal level of glucocorticoids has already been reached or not. Sometimes the brain mainly measures the quantity of glucocorticoids in the body. The other times, it mainly measures the speed at which this level changes. The various sub-areas have also discovered together that the body is not only able to perceive something more stressful, but that it can also perfectly estimate how far and how quickly certain levels will deviate from their ideal level.

It was later discovered that psychological factors can regulate the stress response. Two stressors that are completely identical and disrupt allostase in the body to the same extent can nevertheless be perceived and assessed differently by the body. Even psychological factors alone, without physical factors, are able to cause a stress response. Selye and Mason have done a lot of research on these issues.

What are the building blocks of the psychological factors?

The physiologist Jay Weiss has done an experiment in rats to see what effect psychological factors have on stress. A rat regularly received mild electrical shocks. Over time, the rat developed a permanently increased stress response. Among other things, he got an increased heart rate and an increased excretion of glucocorticoid. This rat would have a good chance of getting a stomach ulcer in the long run. Another rat received exactly the same shocks of the same intensity and with the same regularity, but if he received a shock, this rat could gnaw at a log. This log was an outlet for his frustrations. As a result, this rat had a much lower risk of developing a stomach ulcer.

It is found to be important to be able to express frustration when undergoing stress. This can be done in several ways, such as through sports or another hobby. People are even able to alleviate the stress response only by imagining this outlet of frustration. Thinking in detail about the route you always run gives almost the same reduction in the stress response as running itself. An outlet for frustration is effective if it can distract you from the stressor. It must also be something that you enjoy doing, so that you realize that there is still a lot in life to be happy about. Sports in particular are a good outlet, because they allow you to lose all the energy that you had released for the stressor through the stress response.

You can also project your frustration and aggression onto others. This is primarily a specialty of monkeys. When a male has lost a fight with another male, the loser often beats a small monkey (often a child of the winner) to release his frustration. This monkey himself has little chance of a stomach ulcer, but does give others one. Also, studies with monkeys showed that the result of this is reduced stress, as the monkeys are surrounded by friends, so when social support is given. However, when monkeys are in an environment with strangers, the stress response worsens.

Just as with monkeys, social support works positively for people as well. Research has been done to people who were exposed to a stressor, such as giving a speech, with and without a supportive, present friend. These studies showed that people who had a friend with them showed a smaller cardiovascular stress response. Moreover, people with a permanent partner and / or good friends have longer life expectancy.

In people who are socially isolated, the sympathetic nervous system is extremely active. These people therefore also suffer from heart diseases more often. Social support can also exist at community level. When you are in a minority group, the more likely you are to develop illnesses due to stress, the fewer others there are in your minority group.

Another factor that has an effect on stress is predictability . Predictability ensures that you know when a stressor is coming and when it is not coming. This has a stress-reducing effect. If you are warned, you know exactly what to expect. If there is no warning, then there is nothing wrong and you don't have to worry about a possible stressor. An example is the fact that you are way less worried when you lie on the dentist's chair and the dentist says: "the drilling is almost over", then he says: "it is difficult to determine how far I have to go on . "

When someone is often exposed to a certain stressor, a habituation reaction occurs at a given moment. This reduces the stress response.

If there are no stressors but the predictability of other, standard processes is disrupted, this can also lead to a stress response. For example, a mouse is always fed at exactly the same times. If you suddenly deviate from these times and feed the mouse at random, this mouse will get stressed. This happens even despite the fact that the mouse receives exactly the same amount of food and its body is in an allostatic balance.

There are also situations where a stress response is more common in someone whose reality is less stressful in the outside world. For example, imagine two birds; one lives in Antarctica, where the temperature is on average 5 degrees, and now it is 5 degrees as well. The other lives in the tropics, where the average temperature is 80 degrees, and it is now 60 degrees. The second bird will have a stress response. Another example takes place during the Nazi bombing of England. The city of London was bombed every night. The outer areas were 'only' bombed approximately once a week. People in the outlying areas were therefore exposed to fewer stressors, but these stressors were less predictable. These people got stomach ulcers more often than those who lived in the center of the city. A less serious but also less predictable stressor therefore leads to more stress.

Sapolsky suggests that there is nevertheless a difference between people and animals. He thinks that people can influence the magnitude of the stress response during the stressor. He bases this on the fact that people use different coping strategies, depending on how long the stressor will last.

What is the role of control in a stress response?

Another important factor with regard to the stress response is control. Studies with rats have shown that rats that have control over their stressor exhibit a stress response to a lesser extent. They gave the rats the opportunity to stop the stressor by pressing a lever. These rats had a lower stress response than if they did not have this control. When this opportunity was subsequently removed by removing the lever from the cage, the stress response increased considerably.

It also works if the rat just thinks it's in control. To this end, they took a rat who was trained to press the lever during the stressor exposes. They then disengaged the lever from the mechanism, so that it no longer worked, but that the rat could still press the lever (so it thought that it still worked). They then exposed the rat to less severe stressors (for example, fewer electrical shocks). The rat then thought that the reduced stressors were the result of his leverage control of the stressor. These rats also exhibited a smaller stress response.

This research shows that it also works just to think that you have control. The same results came from similar human experiments. These studies also showed that the stress response was the same for people who controlled the stressor by pressing a button, as for people who could control the stressor, but did not do this. The conviction that you have control over the stressor is therefore more important than actually making use of this opportunity (for example by pressing a button).

However, exercising control must be voluntary. For example, if a rat was able to reduce the number of electric shocks by running in a wheel, the stress response would decrease if the rat voluntarily did so. However, if the rat was forced to run in the wheel, it had a very large stress response.

Occupational stress is caused by a lack of control rather than by too much control and responsibility. Especially when a lot is asked of you in your profession, yet you have little control, you have a greater risk of getting cardiovascular diseases. The lack of control in particular plays a major role in this. Control is also very important in the case with rewards. Studies of both pigeons and rats have shown that they would rather receive food as a reward for doing a simple task than if they were given this food without having to do anything. A strong link has been demonstrated between control and predictive information. If you have a schedule about the course of events and you suddenly come into a new situation, where that schedule does not fit completely, you experience more excitement and vigilance. You will immediately start looking for a new scheme for control and predictability in this new situation.

Another important component in reducing the stress response is the feeling that the situation is improving. If a mouse receives fifty shocks per hour on one day and twenty on the other, this mouse will exhibit a smaller stress response. However, a mouse that receives ten shocks one day and suddenly another twenty, will show a greater stress response. Also a greater stress response than the mouse that went from fifty to twenty shocks, despite having the same number of shocks. For one mouse it is an improvement of the situation, while for the other mouse it is a deterioration.

The psychological factors of control, predictability, social support, expressions of frustration and a stressor view improvement or deterioration of the situation have an important influence on the stress response.

There is also an overlap between these factors. This can be positive (two factors together ensure an even smaller stress response) or negative. For example, predictability can outweigh the observation that the situation is getting better. A monkey that stood at the bottom of the hierarchy and suddenly gets much higher due to manipulation of the researchers, without expecting it, can experience a lot of stress. So he has a better position, but the unpredictability of it causes stress. However, you cannot reduce a stress response by manipulating the above factors to a maximum level. The right amount of unpredictability etc. provides stimulation. Complete predictability at work, for example, can cause employees to get bored, while a certain degree of unpredictability can lead to more challenges and enjoyment at work.

What is the influence of predictability on a stress response?

Predictability does not always have an effect. If you are warned about something that is very unlikely (for example, being hit by a meteor) you will not think much about this and will probably ignore the warning. Even if you are warned about something that is very likely, it will have little effect. If someone warns you that you will almost always be stuck in traffic when you drive to work, you will not think about this much longer. This is so obvious that a warning adds nothing.

A warning that comes shortly before the stressor (for example five seconds) or very long (for example five years) before the stressor is given has hardly any effect on the stress response. In the first case you have almost no time to worry, and in the second case the stressor lasts so long that it makes little sense to worry. A warning for a very stressful event, on the other hand, will ensure a greater stress response. For example, if you are warned that you will have a serious accident the next day, causing your legs to become paralyzed, this causes a greater stress response. You anticipate a major stressor in advance, which has a cumulative effect. Also giving a vague warning can lead to a greater stress response. You try to prepare yourself for the stressor, but you do not know exactly for what type of stressor. For example, you are told that something bad will happen the next day, but you don't know what exactly. The result is that you will be on your guard all day long for what can happen. This too has a cumulative effect on creating a stress response.

What effect does control have on the stress response?

Control can have both a beneficial and unfavorable effect on the stress response. It has an unfavorable effect if you think you have control over a stressor, but in reality this control is not there at all. You can then think that it is your fault that the stressor occurred since you also could have prevented it. This ensures a greater stress response. An example of this is the mouse, which receives electric shocks, and can press a lever that is not coupled to the shock mechanism and therefore has no effect. It is possible that the mouse feels that it is in control of the stressor, which reduces the stressor. He thinks: it's annoying, but wouldn't it be much more annoying if I didn't have that leverage? However, it is also possible that he finds out that he has no control over the stressor, which makes him wonder what is wrong with him. For example, people will say that the other person could do nothing about it and not have to feel guilty if they provide social support. People also often blame the victim to get rid of their our feelings of guilt. An example of this is victims of rape who start thinking that they dressed inappropriately at the time and were therefore raped.

People who have a strong internal locus of control (and therefore tend to attribute events to themselves) have a greater stress response than people who have an external locus of control (and therefore attribute most events to the environment) as they are confronted with an uncontrollable event.

Despite the nuanced statements that have just been made regarding control and predictability, it is generally the case that the less controllability and predictability a person experiences, the greater the risk of a stress-related illness. Other factors that are important include whether or not having an outlet for frustration, social support, and whether or not the stressor is worsening.

Practice questions

1. A researcher gives a group of rats food on predictable moments, and another group of rats the same amounts of food, only then on unpredictable moments. Will the second group of rats have a stress response and why?

Answers to the practice questions

1. Yes, they will have a stress response, since even a positive trigger can become a stressor in the case of unpredictability.

In what sense can stress lead to depression, and vice versa? - Chapter 14

Depression is a common psychological disorder that can have serious consequences for mental health. For example, it can be life-threatening and the families of people suffering from depression may fall apart. Five to twenty percent of the population suffers from at least one major depression during his or her life, including a period of hospitalization, medication use or a significant period of the inability to function properly. The number of people experiencing depression has only grown in recent years.

Everyone can feel sad from time to time, but in the case of a real depression the symptoms last for at least two weeks and are more severe. This can lead people to think about or even commit suicide, and losing their social contacts because they lie in bed all day, lose their job, and so on.

What are the symptoms of depression?

A symptom of depression is a lack of pleasure and motivation in life. People suffering from depression can no longer see and appreciate the fun and good things in life. This characteristic is also called 'anhedonia'. Hedonism is contradictory to this; it is the pursuit of pleasure. By anhedonia we refer to the inability to experience pleasure. Anhedonia is sometimes also called dysphoria. People with dysphoria do not feel pleasure at all but will think of pleasant things which they don't have.

For people without depression, mood varies slightly throughout the day. People who are depressed mainly experience negative emotions and very few positive ones. The classic picture of depression means that people with this disease feel to have nothing to enjoy. Nowadays this picture is somewhat nuanced.

In the case of major depression, a person is overwhelmed by despair. This also includes emotions such as guilt and sadness. These emotions are also common in minor, everyday 'depressions', but people with major depression can become very desperate. There can be complex layers to these emotions. There is not only the direct feeling of guilt with regard to a certain event, but also guilt because they have the disorder and, for example, because their family suffers from it. In some patients, feelings of sadness and guilt can also take on the form of delusions. These delusions are not similar to those that a schizophrenic person experiences. In the case of depression, the depressed person thinks about things being much worse than they really are. An example of this is the story about an older woman who gets a heart attack. She is recovering, however she is convinced that her situation is getting worse. One day she is able to walk one round through the hospital. She runs two laps the next day. She explains to her family that she is worse than yesterday. Her family does not understand her, because she walked two laps instead of one today! The woman explains that the corridor through which she walked has been renovated; making the hall smaller. The laps that the woman has walked today are really no more than the laps she did yesterday. However, this woman's assumption is delusional. People who suffer from depression often suffer from these kinds of delusions.

The emotions behind the mental analysis and evaluation of things are disrupted in people with depression, so that their everyday world is interpreted in such a way that it leads to depressive conclusions. Thoughts arise that it everything is terrible and everything gets worse. The depressed person may also believe that the situation is his or her own fault.

Cognitive therapists therefore see depression mainly as a mental disorder rather than a disorder of emotions, because people suffering from depression perceive the world in a very negative way. Beck and other colleagues have found evidence for this. In their research they showed their test subjects two pictures; in quick succession of each other or simultaneously. On one picture there was a group of people who were having a nice dinner together. On the other picture was the same group of people gathered around a coffin. Depressed people remember the funeral picture significantly more often than non-depressed people. This shows that these people mainly pay attention to the gloomy things in everyday life.

Another symptom of major depression is psychomotor retardation. This refers to the fact that people who suffer from depression speak and move more slowly. Everything costs them a lot of effort and concentration; more than they cost the average person. It is often too much to get out of bed in the morning. People with psychomotor retardation almost never commit suicide because this too costs them too much energy. Only when their energy level increases a bit, will they be emotionally able to commit suicide. 

For depressed persons, the feeling of being in control of the ups and downs in daily life is getting smaller.

Depression is a real disease. Many things in the body of people with depression work in a peculiar way. These are called vegetative symptoms.

When an average person does not feel well for a while, they often eat and / or sleep more in the belief that this will make them feel somewhat better. This is actually the opposite of the vegetative symptoms that occur in most people with major depression. They tend to sleep and eat less. They generally fall asleep easily, but wake up much earlier and cannot sleep anymore, which leads to exhaustion after a while. Moreover, the sleeping pattern is also disturbed.

People who are very depressed often have an elevated glucocorticoid level. From the psychological point of view, it becomes clear that depressed people are struggling with some sort of aggressive kind of mental struggles. When we consider this, it is actually not surprising that these people have an increased stress hormone level. Glucocorticoids can damage aspects of the memory that are dependent on the hippocampus. The increased glucocorticoid content thus explains another characteristic of depression, namely the problems with the part of the memory that is dependent on the hippocampus. Moreover, recent research has shown that the hippocampus in depressed persons is smaller than average. 

There are different types of depression. For example, there is unipolar depression, where a person's mood fluctuates between very depressed and about normal. There is also bipolar depression, also known as manic depression, where a person fluctuates between very depressed and wild, disorganized hyperactivity. The latter is also referred to as a mania. The term "mania" is quite ambiguous, because it is commonly used to indicate a madness in which people constantly talk, laugh and make gestures. However, the mania from a manic depression is very different in nature. People in this manic state can go on for days on end with an average of three hours of sleep per night, but feel extremely energetic. They talk for hours non-stop, are easily distracted and have difficulty concentrating because their thoughts are constantly changing. People in this state can have emotional eruptions that are dangerous to themselves and / or the environment.For example, they take poison to prove that they are immortal, burn their houses or give away their savings to a stranger. This disease is therefore very destructive. 

The very different types and variability of depression suggest that there is not one underlying disease, but that there are several diseases, all of which have different biological characteristics. Some types of depression have a clear rhythm, such as with manic depression. As a result, something seems to be underlying biological.

Another example of depression is the 'seasonal affective disorders' (SAD), where patients are only depressed in a certain season (usually in the winter). This appears to be related to light exposure. Recent research has shown that there are receptors in the retina that send a direct signal to the limbic system. This limbic system regulates the emotions in the brain. A lack of light in the winter could cause people to become depressed.

What is the biology behind depression?

There is reasonable evidence that something is wrong with the chemical status of people with depression. To understand this, you must first know how brain cells communicate with each other. When a neuron is activated, it transmits an electrical signal from the dendrites to the cell body through the axon to the end of the axon, which is called the axon terminal. When this electrical signal reaches the axon terminal, it excretes chemical messengers, neurotransmitters, that flow through the synapse. These neurotransmitters then attach themselves to certain receptors of the adjacent dendrites, causing the second neuron to be electrically charged. When the neurotransmitters have done their job, they are in some cases taken up again by the axon terminal of the first neuron. In other cases they are seen as waste materials and they are get rid of. If the neurotransmitters are not cleaned up properly, they remain in the synapse, giving the second neuron a stronger signal than normal.

There are different types of neurotransmitters (probably a few hundred), and they all transmit different signals at different places in the body. There is evidence to suggest that the neurotransmitters norepinephrine, serotonin and dopamine come in an abnormal levels in depressed people. The best evidence for this is that medication treating depression increase the amount of these neurotransmitters. 

Tricyclides, a certain type of antidepressant, stop the reuptake of these neurotransmitters in the axon terminals. As a result, the neurotransmitters stay in the synapse for a longer period of time, and there is a chance that they will activate the second neuron a second and perhaps a third time.

MAO inhibitors, another type of antidepressant, block the re-uptake of these neurons by stopping the action of the enzyme, monoamine oxidase, or MAO. This also ensures that the neurotransmitters stay in the synapse longer and may activate the second neuron a few more times.

From the above it seems logical to conclude that if the antidepressants cause the presence of more neurotransmitters such as norepinephrine, serotonin and dopamine and the depression disappears, people suffering from depression should therefore have been deficient in these neurotransmitters. However, in reality it is not that simple. To begin with, these antidepressants work on norepinephrine, serotonin, and dopamine. It is therefore unclear which of these three neurotransmitters is influencing the disease. It is also unclear whether depression actually results from a lack of these neurotransmitters in the synapses. This has to do with timing. When tricyclides are administered to a healthy subject, the amount of neurotransmitters in the synapses changes within a few hours, while for depressed subjects this will take a few weeks. An explanation for this is that the first neuron secretes too many neurotransmitters. This makes the second neuron less sensitive to the neurotransmitters. When antidepressants cause the first neuron to secrete even more neurotransmitters, they cross the sensitive boundary and the second neuron starts working again. According to this explanation, depressed people do not have too few neurotransmitters, rather too many. Initially, the second neuron would become even more insensitive and the symptoms of the depression would worsen. After that, the sensitivity of the second neuron will become almost normal again, so that the symptoms of depression disappear. It has been found that receptors for the neurotransmitters are located on the dendrites, but also at the axon terminal of the first neuron. When the first neuron transmits neurotransmitters through the axon, most of it will attach to the receptors in the dendrites. However, some will return and attach themselves to the receptors at the axon terminal of the first neuron. Based on the number of neurotransmitters that have returned, the first neuron can make decisions about whether it has secreted enough neurotransmitters or not. However, if the first neuron makes a wrong estimation based on the number of returned neurotransmitters, the first neuron may overestimate the amount of neurotransmitters that is secreted. As a result, more and more neurotransmitters are subsequently secreted, causing the symptoms of depression.

Swallowing antidepressants will make the receptors of the neurotransmitters norepinephrine, serotonin and dopamine more sensitive during the first few weeks. An important aspect in this theory is that the autoreceptors on the first neuron become more sensitive than the receptors on the second neuron. As a result, the first neuron transmits enough neurotransmitters to activate the second neuron. This reduces the symptoms of depression. So there is still uncertainty about how exactly the biology of depression works and which theory is the right one.

There are many different relationships between neurotransmitters and their function, causing depressive symptoms. For example, serotonin appears to have something to do with inhibited ideas in depression, as a result of which these people continue to have negative thoughts without being in control of them. That is why SSRIs (antidepressants that block the secretion of serotonin) are especially prescribed in people with obsessive compulsive disorder. These are people who, for example, are constantly worried that they have left the gas stove on, constantly check that everything is locked and that they often want to wash their hands. They are kind of trapped in a brain that keeps running in circles of thoughts and feelings. 

Norepinephrine provides a number of projections of the locus coeruleus, an area in the brain. It seems to play a role in activating other parts of the brain. A shortage of norepinephrine explains why other brain regions are not activated and how psychomotor retardation can occur.

Dopamine mainly has to do with pleasure and pleasure experience. A dopamine deficiency appears to be related to the lack of zest for life experienced by people suffering from depression. In rats, an area in the brain has been discovered, which is called the "pleasure path". When this area was stimulated with electrons when the rats pressed a lever, the rats did nothing else than press that lever. This was more important for these rats than food, sex or drugs; as if the rats were addicted. People also have such a pleasure route. This pleasure route seems to use dopamine a lot. This is also apparent from the euphoric effect of drugs that resemble dopamine (for example, cocaine). It is therefore likely that depression has to do with too little dopamine and therefore dysfunction of the pleasure path.

It is still unclear whether there are other neurotransmitters that have anything to do with depression. For example, researchers have discovered 'substance P'. This substance P plays a role in the perception of pain. Recent studies have shown that the suppression of substance P acts in some individuals as antidepressants.

What is the neurologicla basis of depression?

The hypothalamus regulates vital life processes, such as the heartbeat and breathing. The hypothalamus is also constantly busy with secreting hormones and controlling the autonomic nervous system. Above the hypothalamus lies the limbic system, which regulates emotions. Mammals and humans have large limbic systems; this system is however very small for lizards. Lizards are known for not having such a complex emotional life. Above the limbic system lies the cortex, which deals with abstract cognitions, philosophy and practical memories (for example, the memory where your car keys are located). Every animal has such a cortex, but it is primarily the specialty of primates.

Viewed from a very simple perspective, depression arises because the cortex has a negative idea (for example, the death of a partner) and convinces the other parts of the brain that it is just as realistic as a real physical stressor. People with chronic depression almost always have these negative thoughts. If the cortex is cut off and split from the other parts of the brain, the depression would be remedied because the cortex can no longer send signals to the other parts of the brain. In some cases this appears to work. However, during surgery, the entire cortex is not cut away from the other parts of the brain, but only the 'anterior cingulate cortex' (ACC). This part of the brain is very concerned with emotions and especially negative emotions. When you stimulate the ACC electronically, these people feel anxious. The neurons in the ACC mainly respond to pain and in particular the feelings of pain. When one hypnotizes someone and says that he will not feel that his hand is in ice cold water, the parts of the spinal cord that cause the pain perception will be active, but not the ACC, so the person will have no feelings of pain. You can stimulate ACC by showing test subjects pictures of people and asking them to pay attention to the emotions they display. However, if you show test subjects pictures and ask them to focus on questions such as "have these pictures been taken indoors or outdoors?", The ACC is not stimulated. The ACC is also triggered, among other things, when widows are shown a photo of their deceased husband, while their ACC is not going to be stimulated by showing a photo of a stranger. The resting state of the ACC is elevated in people with depression.

The amygdala also appears to be hyperactive in people with depression. When someone who is depressed is shown a photo of a frightened face, the amygdala is not activated as strongly as in someone who is not suffering from depression. However, when someone who is depressed is shown a picture of a sad face, the amygdala is very strongly activated.

Davidson has shown that the different sides of the prefrontal cortex are also very responsive to the mood. Activation of the left part of the prefrontal cortex is associated with a positive mood, activation of the right part of the prefrontal cortex is associated with a negative mood. In depressed people, the left part of the prefrontal cortex is generally less active and the right part is more active.

Depression also appears to contain a genetic component. For example, it appears to be more common in some families. The more individuals are genetically related, the more genes they share and the greater the chance that they exhibit the same characteristics of depression. Research in fraternal twins has shown that if one of the two has a history of depression, the other has a twenty-five percent chance of developing depression, since fifty percent of their genes are the same. With identical twins, the chance is fifty percent, because their genes are completely alike. When a child of a depressed mother is adopted at a young age by a mother who is not depressed, the child has a greater chance of having a depression. This seems to be the strongest evidence for the fact that depression has a genetic component. However, it is not yet known which genes suffer from depression.

There may be a link between the immune system and depression, but this is rather about the idea that illness can make you depressed. However, it is more likely that a chronic illness, which is related to over-activation of the immune system, leads more to depression than other illnesses that are just as bad and persist for just as long, but that have nothing to do with the immune system. 

Cytokines, the messengers between immune cells, act on norepinephrine, serotonin and dopamine. Therefore, cytokines can attribute to an onset of depression. The treatment of some types of cancer consists of the administration of cytokines, which increases the risk of depression. Abnormal levels of other hormones often go hand in hand with depression. For example, people who excrete too little thyroid hormones can develop major depression. These people can also offer resistance to the effects of antidepressants.

It has also been found that more women than men suffer from unipolar depression. But also in the case of bipolar depression, women tend to have more depressive periods than men. According to cognitive theory, this is due to the way men and women think and deal with their symptoms. Women often think about annoying events for a long time and want to discuss it with others, while men do not want to think about the annoying event and prefer to get active, to be able to do something completely different. Another theory provides a more psychosocial explanation. According to this theory, depression is like a disorder that is the result of a lack of power and control. Because women in most societies have less power and control over their living conditions than men, they have a greater risk of becoming depressed. Another theory states that depression actually occurs just as often in men as in women, but that men are less likely to act like it and give in to it. This gives men a greater chance of becoming addicted to drugs or alcohol, for example. 

These theories above are weak, considering that bipolar depression occurs just as often in men as in women. It is only a unipolar depression that occurs more often in women than in men. What these theories mostly forget about is that women are at greater risk of developing depression around certain reproduction times, such as menstruation, menopause, and the first few weeks after giving birth. Several researchers think that this is due to large fluctuations in the hormones estrogen and progesterone. This has been investigated by administering amounts of estrogen and progesterone to women in an artificial way and then measuring their depression. This happens, for example, when taking birth control. In addition, these hormones can regulate certain neurochemical events in the brain, including the metabolism of neurotransmitters such as norepinephrine and serotonin. More research is needed to determine whether the hormonal fluctuations explain depression among women as a whole.

What is the connection between stress and the biology of depression?

There is a connection between stress and depression. To begin with, people who are prone to depression tend to experience things and events as a stressors more quickly, even when compared to people with other psychiatric disorders or health problems. Many of these stressors appear to be co-caused by a lack of social support. This can create a vicious circle. More often, however, people who have undergone many stressors in their lives are more prone to developing depression. Most people who experience major depression for the first time have experienced significant stress recently. When people have experienced about four major depressions, there is a good chance that you will fall into a kind of rhythmic pattern and become depressed regularly, regardless of whether there are many stressors in your environment. For that fourth depression, the chance of a subsequent depression is just as great as for any other individual.

In rats it has been noticed that the pleasure pathways need to be stimulated more intensively to yield a positive reaction from a stressed rat. Glucocorticoids can also raise the threshold of the pleasure pathway. When someone is treated with artificial glucocorticoids, he (if there is a response) first enters a euphoric, sometimes manic state. This person often becomes depressed after about a week. The idea this is due to the increased glucocorticoid content is evident from the fact that among other people who suffer from the same disease to the same extent, but who do not get artificial glucocorticoids, depression is less common than among people who are treated with glucocorticoids. It is not possible to say with certainty it is about the amount of glucocorticoids in the body that will or will not cause depression. We can conclude the risk of depression is greater if the blood contains a large amount of glucocorticoids.

The genetic component of depression has already been discussed. However, genes only increase the risk of depression when they are combined with a stressful environment. Caspi has discovered that there is a gene in people that increases the chance of developing a depression. This gene comes in two variations. One of these variations increases the risk of depression. If you have the gene in that variation, this only increases the risk of depression if it is linked to a history of major stressors. So it is a gene that makes you particularly vulnerable in a stressful environment.

Most depressions are characterized by an over-active stress response. The sympathetic nervous system is more strongly activated and especially the glucocorticoid content is increased. However, there is also a less common form of depression, called 'atypical depression', in which the glucocorticoid content is very low. This depression mainly contains the psychomotor characteristics and leads to exhaustion, which makes you physically and psychologically unfit. 

It has been found that an increased glucocorticoid level, which occurs with most depressions, is caused by an excessive stress signal in the brain and not by a (temporary) adrenal abnormality. This is mainly due to problems with the feedback system. The brain is therefore not so good at inhibiting the secretion of glucocorticoids. Glucocorticoids can have different effects with both norepinephrine, serotonin and dopamine. They influence the amount of neurotransmitters that are synthesized, how quickly these are broken down, how many receptors there are for each neurotransmitter, how well these receptors work, and so on. Moreover, it has been shown that stress can cause many of the same physical changes as depression. Stress and glucocorticoids can cause the same abnormalities as the abnormalities that underlie depression. Increased glucocorticoid levels also seem to cause that the immune system of depressed persons is often mildly suppressed and that these people run a greater risk of osteoporosis and heart disease. There are different ways in which an increased glucocorticoid level can lead to problems with the hippocampus; an area in the brain that has to do with memory. People with major depression often have memory problems. In the case of a depression that persists for a long time, the hippocampus becomes smaller and smaller. This shrinkage occurs mainly in the subtypes of depression in which an extremely high glucocorticoid level is normal. 

In some studies, chronic depression is also associated with a reduced volume of the frontal cortex. In the brains of humans and similar animal species, the hippocampus and frontal cortex are sensitive to glucocorticoids. These shrinkages appear to be permanent.

In the beginning of the chapter, depression was seen more as something that is enormously stressful and in this way causes an increased glucocorticoid level. A larger amount of glucocorticoids was later seen as the cause of depression. 

In some people with depression, antidepressants, which inhibit the secretion of glucocorticoids, do indeed have a beneficial effect. Glucocorticoids, however, are very important and have many different effects, which means that too few glucocorticoids can also be harmful. That is why a drug has been developed that only blocks the receptors of glucocorticoids in the brain. This medicine is a lot safer and appears to work. The DHEA hormone, which is also somewhat capable of blocking glucocorticoids, also works somewhat against the symptoms of depression. However, more research is needed regarding glucocorticoids and depression.

What is the connection between stress and the psychology of major depression?

Freud thought that both mourning and depression involved losing a loved object (often a person). According to Freud, there were mixed feelings in every loving relationship, namely love and hate. In the case of a small, responsive depression (mourning), these mixed feelings are dealt with in a healthy manner. You lose a loved person, you mourn and recover from it. With a major depression you become obsessed with these mixed feelings. For example, after losing a loved one you are twice as sad; on the one hand because of the loss and on the other for the loss of a chance to talk things out for example. This also explains the intensity of the feelings of guilt often felt in major depression. When you don't get along well with someone and this person dies, this can also lead to relieved feelings. However, this also brings back feelings of guilt later on, because you feel guilty about being partially happy about the loss. That is why some people with major depression start taking on the traits of the other people they were most bothered about. Because of this, a part of the other lives on, the environment is convinced that this is really an annoying trait and the person punishes himself at the same time. Depression is sometimes called aggression that is directed inwards. These ideas from Freud sound logical, but they are difficult to incorporate into modern science, especially in biologically oriented psychiatry.

How do stress, learned helplessness and depression relate to each other?

In an Seligman and Maier's experiment, animals were exposed to pathological amounts of psychological stressors (low control and predictability, etc.). This created a condition that was very similar to depression in people. When you place a rat in a cage that is split in two halves, where the halves are alternately powered by electricity, preceded by a signal, the rat learns very quickly to sit in the right half. However, if you perform the same experiment with rats that have recently been exposed to repeated, uncontrollable stressors, the rats will not learn when to sit on which half. These rats have learned to behave helplessly because they had no control or predictability over the previous stressors. These rats then have motivational problems, they often do not even try to deal with a stressor, because they think it makes no sense. These rats also have cognitive problems and they see and think about the world in a crooked way. When they try to deal with a stressor, this does not work. According to Seligman, this is because they have learned not to pay attention to stressors, they cannot do anything about it. Even when control and control are available to the rat, the rat will not perceive this.

There are even more similarities between depression in humans and in rats. Rats can also get a kind of 'dysphoria', which means that the rat no longer takes care of itself and no longer wants to eat and have sex. He also no longer tries to cope with stress, which resembles psychomotor retardation, which we discussed before. Some rats injure themselves and have vegetative symptoms. Furthermore, they appear to have less norepinephrine in some parts of the brain and accelerate antidepressants and ECT in their recovery from the state of acquired helplessness. Learned helplessness occurs in various animal species.

Little else is needed in people: When a situation is uncontrollably unpleasant people will give up and feel helpless. Seligman and colleagues have demonstrated that insoluble tasks can lead to a sense of helplessness among participants in later social situations. There are large individual differences that ensure that some people easily fall into learned helplessness and others do not. A research by Hiroto showed that people with an external locus of control are more sensitive to learned helplessness than people with an internal locus of control. Someone with an internal locus of control therefore also has a lower risk of depression, because this person does not always look for the responsibility with himself. Other people can also teach us helplessness. For example, when a teacher regularly exposes you to his own special, uncontrollable stressors at a critical point in education, you can develop a skewed image about what you can and cannot do.

A particular study has showed that children with major reading problems could quickly learn to read a completely different language, for example Chinese, but not English (their mother tongue). These children apparently had learned that they were unable to learn to read English, but had enough intellectual capacities to do it. If a child is very stressed at a certain point in his life (for example due to the divorce of his parents) he has a greater risk of developing depression later on. 

According to Seligman, depression is therefore not a form of general pessimism, but rather pessimism with regard to one's own abilities. Depressed persons suffer from learned helplessness, according to him, so that they are no longer motivated to live, to use their cognitive capacities to see that everything is going well, or to observe pleasure.

Stress and depression

Stress, and in particular forms of extreme lack of control and outlets for, for example, frustration, can bring about various changes in a person. On the cognitive level, someone exposed to stress gets the idea that there is nowhere control or room for expressions and a kind of learned helplessness arises. Regarding affection, anhedonia arises. Psychomotor retardation can occur in behavior. Regarding neurochemistry, the signals from serotonin, epinephrine and dopamine are probably disrupted. Physically, there are changes in, among other things, appetite, sleep patterns and the sensitivity of the glucocorticoid system to feedback about the amount of glucocorticoids in the body.

All these changes can occur in the case of major depression. It may seem that depression is caused by stress. However, in this case, what is not yet explained, is how it is possible that a kind of rhythm for depression can develop after the third depression, so that stressors in the environment hardly have any influence on the onset of depression. There are several theories about this, but no good explanations.

However, stress does not lead to depression in everyone. Stress is therefore primarily a factor that makes people vulnerable to depression. Norepinephrine is excreted during stress. But stress also causes the gradual synthesis of more norepinephrine, although this excretion of norepinephrine is only of short duration in most people. Something similar happens with serotonin. This ensures that we recover and feel better again. However, some people do not recover quickly from stressors, making them more vulnerable to depression. A major stressor therefore causes the neurochemical changes that occur with depression. The more stress you have experienced earlier in your life, the smaller the stressor needs to be to get this effect. Glucocorticoids then ensure the synthesis of norepinephrine and serotonin, which ensures that you recover from the stressor. Your genes can, however, ensure that you do not recover so easily from a stressor. If this is the case, you run a greater risk of depression.

Practice questions:

1. How can learned helplessness influence or stimulate the onset of a depressive episode?

2. How did twin studies provide evidence for a genetic factor in depression?

3. What are the common abnormalities in the brain of someone who is depressed?

Answers to the practice questions:

1. Learned helplessness makes a person believe that whatever he or she will try, he will never attain his goal. This results in a lack of motivation, a lack of positive self-evaluations, and a lack of pleasure. This can lead to a depressive episode.

2. Research in fraternal twins has shown that if one of the two has a history of depression, the other has a twenty-five percent chance of developing depression as well. In this case, fifty percent of their genes are the same. With identical twins, this chance is fifty percent. Their genes are completely alike, so depression has at least some genetic component.

3. The ACC, right PFC and amygdala are overly active. The hippocampus is smaller, leading to diffuculties involving the person's memory.

What do personality, temperament and stress have to do with each other? - Chapter 15

How someone responds to a stressor can be very different. Individuals can vary greatly in the way they deal with psychological factors that relate to a stressor. These differences often lie in someone's personality and temperament. This also explains why some people are more at risk of developing stress-related illnesses than others.

An example: Jan is doing well. He has many properties and is number two in the hierarchy at his job. Moreover, he has a good chance of becoming number one. The outside world sees him as a success. But he is not satisfied. He sees everything as a competition. Moreover, he has no friends for social support, because he used his friends as an outlet in the past too much. He also has little contact with his family. This lack of social contact and the constant feeling of dissatisfaction is a major stressor for him, so that his stress response is always slightly activated. This constant stress has an effect on his body, which increases the risk of developing stress-related illnesses. He constantly has a high glucocorticoid content and high blood pressure.The first stages of atherosclerosis can also be seen.

Piet is at the same level as Jan compared to the outside world. He has achieved the same things, but in a different way. Piet works together more, helps others and therefore also receives social support. He could have become number one, but he would rather spend more time with his family. It is clear that Piet experiences less stress than Jan and therefore runs less risk of developing stress-related diseases.

What is the connection between success and stress?

Sapolsky has done research on baboons in the Serengeti. These are large, smart, social and long-lived monkeys that live in groups of 50 to 150. He discovered that baboons have different personalities and that they can therefore react differently to the same situation. He investigated the monkeys from the highest hierarchical classes.

Sapolsky wanted to get answers to the following questions about the Seregenti baboons:

• Can the baboon assess the difference between a threatening and a non-threatening situation?

• If the situation is threatening, does the baboon sit quietly or does he give the first blow?

• Does the baboon know after a fight that he has lost or won?

• If the baboon has lost, does he respond to someone, or not?

He wanted to know how they reacted to their worst rival in the group and what that meant for their stress response. When the worst rival of a man passed by and went to sleep a few meters ahead, there are two possible reactions. The male could get annoyed and attack his rival, or it could see that the rival at that moment had no intention of doing anything else. Males who became annoyed had twice as many glucocorticoids during a resting state than normal. They were therefore in a constant state of stress. Males who realized that the rival would do nothing and therefore did not start the attack , had far fewer glucocorticoids at resting levels. They were not in a constant state of stress. However, if a monkey is threatened by a rival, the level of glucocorticoids depends on the monkey's reaction. When a monkey is the first to give a blow, this level is lower than when a monkey passively waits. Sapolsky has also shown that monkeys who clearly knew when they had won or lost a fight had a lower level of glucocorticoids than monkeys who did not know that difference so well. Moreover, it turned out that monkeys who start beating someone else after a lost fight have fewer corticoids than monkeys who do not react that way.

The monkeys that have the best coping strategies have a lot of social control (they start a fight), good predictability (know when a situation is threatening and when not) and expressions of frustration (other, smaller monkeys hit when they have lost a fight) . This style remains fairly constant throughout life. Moreover, males with such a coping style stay significantly higher in the social ranking than others.

Males who often care for females without sexual intentions and who often play with the young have few glucocorticoids. They easily develop friendships and are more social. This style also remains fairly constant throughout life.

Suomi has shown that both genetic and environmental factors led to personality differences, which in turn lead to different styles of coping with stress. For example, he has shown that a young monkey has a good chance of sharing a personality trait with his father. Monkeys that have a high reactivity as a personality trait often owe this to the parenting style of their mother.

What is the link between personality types and stress-related diseases?

Various studies have been conducted among people towards the link between personality types and stress-related illnesses. For example, some studies have shown that pregnant women who are very immature and are afraid of having to share their husband's attention with a child, often have a miscarriage. On the other hand, women who are very independent and assertive are also more likely to experience miscarriages because they are afraid of having to give up their independent lives for a child. However, other researchers are very skeptical about these results. They think that these psychological explanations exist only because the disorders are not yet biologically explained. If the biological explanation is found, the psychological explanation will be easily disposed of, they think. Moreover, these investigations use retrospection to reach a conclusion. It could be that the personality traits of women are more the result of multiple miscarriages than the cause. To investigate this, the personalities of women should actually be examined before they become pregnant. Finally, it has not been demonstrated in these studies what biological effect these personality types have. For example, it is not clear what happens to the hormone balance of women with certain personality traits.

What does an anxiety disorder entail?

Stress can also have an influence on psychiatric disorders, such as anxiety disorders. There are different types of anxiety disorders, such as a general anxiety disorder, a traumatic stress disorder (that can be traced back to a specific trauma) and phobias, where someone has an extreme fear of one specific thing or situation. Claustrophobia is an example of a phobia: In this case, someone is very anxious in small spaces and can also get panic attacks in these types of situations. Compulsive disorders also fall under anxiety disorders. An example of a compulsive disorder is obsessive-compulsive disorder. The lives of people with a compulsive disorder are governed by fixed habits and routine actions. With an anxiety disorder, your imagination starts exaggerating a situation and you have an exaggerated fear response. Normal anxiety involves flights from a real situation. People who are very anxious (and prone to such a disorder) have a strong tendency to overestimate the risks of a serious event and the chance of it happening.

People with anxiety disorder - unlike people who are depressed - still try to activate a coping response time and time again. However, because they misunderstand the risks and chances of serious events, they activate a coping response almost simultaneously. As a result, they constantly experience stress and the associated stress response. The continuous maintenance of stress and the stress response provides an increased chance of developing stress-related diseases.

During panic attacks, the sympathetic nervous system is strongly activated. The sympathetic system is activated too much and way too high levels of epinephrine and norepinephrine circulate through the body. However, the level of glucocorticoids is not too high. Thus, epinephrine and norepinephrine are used primarily, which already work within a few seconds, and hardly use glucocorticoids, which start to work more slowly, sometimes only after a few hours. In the case of psychiatric disorders, an increased level of epinephrine and norepinephrine is mainly due to an attempt at coping and the energy that it costs. An increased glucocorticoid level is rather a sign that someone has given up hope and is no longer coping. This has been demonstrated with an experiment in rats. Because rats are nocturnal, they do not like bright light. The researchers placed rats in cages where it was dark in the corners, but in the middle was eating in the bright light. Rats first tried to discover a way to get to the food. They came a little closer and then withdrew quickly because they were afraid of the bright light. During this process, their epinephrine and norepinephrine levels were clearly increased. If this process went on for too long, the rats gave up and simply lay down in a dark corner. In this case their glucocorticoid level was too high and depression occurred.

What are the biological aspects of anxiety?

Some fears are congenital. For example, rats are always afraid of bright lights and terrestrial animals are always afraid if they float in the air for some reason. However, most fears are acquired. This can go through a process of learning in which certain things are associated with the trauma. For example, someone who has been bitten by a dog once may develop a fear of dogs. We can also develop a fear of things that, after generalization, resemble something that is associated with a trauma.

Organisms have a talent for developing some fears quicker than others. For example, people have a tendency to be afraid of spiders and monkeys are more afraid of snakes. But we can also become afraid of new things, such as terrorism after 11 September. These fears are implicitly taught and an autonomous response is created through conditioning. For example, if you have been bitten by a dog once, the brain may be conditioned to speed up your heartbeat every time you see a dog and activate your sympathetic system. This can happen completely unconsciously. The body responds before you are aware of the similarity between, for example, the dog that you see and the dog that ever bit you. This is also known as Pavlovian learning, because Pavlov gave a dog food after the ringing of the bell, eventually causing the dog to already produce saliva in the case when the bell rang.

Mild, short-term stress increases explanatory learning, but long-term and / or very severe stress disrupts explanatory learning. The form of unconscious, implicit and conditioned learning described above increases any form of stress in explanatory learning. This has been investigated with rats. When they exposed a rat to a loud noise, the rat received a brief stress response. If they had already administered the same rat with different stressors and the rat was then exposed to the same loud noise, the stress response was much greater.

The hypocampus normally controls the explanatory memory. The hippocampus, for example, helps us to remember agreements that we made. When remembering a stress response, which happens when conditioning fears, the hippocampus plays no role. This type of memory is controlled by the amygdala. The amygdala receives information from the senses and also has a lot to do with the perception of pain. The information of the senses reaches the amygdala rather than the cortex. This makes it possible to respond to pain or a stimulus for which you have developed a fear, without being aware of that stimulus or pain. So it can happen that your heart starts beating faster before you have consciously observed the dog you are afraid of. In addition, the amygdala receives information from the autonomic nervous system. Based on this information, the amygdala decides whether or not to activate an anxiety response. For example, if your heart beats a little harder, the amygdala will trigger an anxiety response faster. The amygdala is also very sensitive to signals from the glucocorticoids. A busy amygdala can therefore activate the sympathetic nervous system. Conversely, an activated sympathetic nervous system increases the chance of the amygdala being triggered. So fear can regulate itself. The amygdala communicates through the hormone CRH. Studies of brain activity have shown the rapid effect caused by the amygdala. When people saw a picture of a scary face, the area of ​​the amygdala lit up in the scan. This reaction was also visible when the pictures were shown so quickly that it was not possible to consciously observe them.

People with an anxiety disorder see threats that others do not perceive. This is apparent from the following example: When people have to read a piece of text, they will slow down a bit when reading a threatening word. People with an anxiety disorder, however, delay much more. The amygdala of people with an anxiety disorder therefore exhibits hyperreactivity. As it were, alarms always ring in the amygdala. When test subjects from the control group are shown a picture that is slightly threatening, their amygdala will hardly be activated. For people with an anxiety disorder, this same picture will already cause the amygdala to activate. Also a threatening picture that is shown very quickly, even to quickly to be knowingly observed by test subjects from the control group, causes people with an anxiety disorder to activate the sympathetic nervous system. It is therefore very understandable that the sympathetic nervous system has been activated so often in people with an anxiety disorder.

Stress and glucocorticoids make the synapses in the amygdala more irritable and ensure that more neurons grow at the connections between the different cells. In this way, an anxiety response develops faster and easier and is also maintained. Researchers have tested this in rats. The amygdala of the rat was made irritable in an artificial way. Then the rat showed some type of anxiety disorder. An increased effect of the amygdala can therefore be clearly associated with anxiety disorders. There is also still free-floating anxiety. In this case there is a large, traumatic stressor that disrupts the function of the hippocampus and increases the effects produced by the amygdala. If you have not stored this event in your memory via your hippocampus, you can later display the same fear response when you get into a similar situation, without being aware of what you are afraid of. This fear arises unconsciously through the amygdala and also remains unconscious, because you have no memory of the earlier event that conditioned this fear response.

What are the characteristics of a type A person?

Two cardiologists, Friedman and Rosenman, have established the idea of a type A personality. People with a type A personality are very competitive, hostile, impatient and performance-oriented. These people run a greater risk of developing cardiovascular disease. Williams later discovered that of the aforementioned traits, hostility is the only significant predictor of cardiovascular disease. In these studies that showed this result, important variables such as age, weight, blood pressure, cholesterol, and smoking were controlled. It is therefore unlikely that the link between hostility and the heart is due to a factor other than hostility. Later studies, however, did not obtain these results. What became especially clear was that hostility is not only a very important factor for getting cardiovascular diseases, but also for other diseases.

Friedman and Rosenman later suggested that there was a sense of haste in the heart of hostility, and a sense of uncertainty in the heart of hastiness. This means that a lasting sense of uncertainty better predicts whether someone will develop cardiovascular disease than show hostility. When looking again at the original data from the type A studies, it turned out that not expressing anger was at least as important a predictor for getting cardiovascular disease as hostility. This was confirmed by Gross's investigations. He showed test subjects a film fragment that caused a stirring of intense emotions. He did the same for another group of test subjects, but told them to try not to express their feelings. These studies showed that the suppression of strong emotions greatly increased the intensity of the physiology that accompanies it.

There are several reasons why people who are very hostile have a higher risk of getting cardiovascular diseases. For example, it is more likely that these people smoke, eat badly and / or consume excessive alcohol. Moreover, these people tend to scare away others with their hostile behavior, so that they have less social support.

Hostility also has certain biological consequences. Studies with social provocation (for example, often disturbing while having to take a test) have shown that there were higher levels of epinephrine, norepinephrine and glucocorticoids in the blood of hostile people than of control subjects. In addition, they had higher blood pressures and other undesirable characteristics with regard to the heart and vessels.

Type A people perceive things around them more quickly as threatening stressors, which require a coping response. This coping is done in a hostile manner. Hereby they activate their stress response only even more. If the stress response is activated so often, it is also logical that they run a greater risk of cardiovascular disease.

Through therapy, the hostility in type A people can be reduced. This makes them less hostile, with the result that they run less risk of developing cardiovascular disease.

One question remains: how was the Type A behavior discovered? On a day around 1950 the chairs in the waiting room of the cardiologist practice of Friedman and Rosenman were upholstered again. The upholsterer glanced at the seats, exclaiming, "What the hell is wrong with your patients?" The seats in the waiting rooms of urologists, oncologists, neurologists and the like looked much less damaged. It was then discovered that people with heart problems are often a special kind of people. Five years later, Friedman's formal investigation into the personality of his patients began. From that moment on, numerous studies have started on personality, temperament and stress-related physiology.

Oppressive personality type

There are people (five percent of the population) who describe themselves as happy, successful and talented and, according to personality tests, they are actually. Strangely enough, these people have chronically activated stress responses because they have an oppressive personality. They describe themselves as planners, who also live in a very structured way. Everything goes according to the rules and as they have planned. They also express few emotions. They are like a rock in the surf. Others often envy them a little while they wonder why things go so smoothly with those people. Research shows that these people need social conformity, that they are afraid of social disapproval and that they feel uncomfortable with ambiguity. Furthermore, they express few emotions and they recognize few emotions in others. Moreover, the emotions they have are very black and white; they can only remember one emotion at events when they felt strong emotions. Others are then able to remember multiple emotions that were only slightly less present during the relevant event. Other research has shown that some of these people are mainly concerned with appearances. This means that they actually know the emotions and are so concerned with the suppression of it that they suffer from stress. Because they are almost constantly concerned about how they come across to others, their stress response is very often and sometimes even chronically activated. As a result, these people suffer from chronically activated stress responses. The other people with oppressive personalities may be more or less physically exhausted, precisely because they have so many plans and live in a structured way.

Davidson and Tomarken have demonstrated through EEG techniques that these individuals have an unusual increased activity in the frontal cortex. This part of the brain is primarily concerned with stopping expressions of impulsive emotions and cognitions. From the above studies it can be concluded that people with oppressive personalities experience a lot of stress when they try to develop a world without stressors.

Practice question:

1.What personality types particularly suffer from a chronic stress response?

Answer to the practice question:

1. Hostile personality types and oppressive personality types

How does pleasure look organic and how does stress influence this? - Chapter 16

A question that philosophers have been occupied with for years is: why can't anyone tickle themselves? Sarah-Jayne Blackmore from the University of London came up with a theory that you can't tickle yourself because it has no surprise effect. You know exactly when and where you will be tickled. She investigated this hypothesis by designing a tickler. The one time the test subject was allowed to control the movements of the machine and the other time the other person did this. In the first case, the person knew exactly where and when the machine would tickle. And what turned out? When another person was driving the machine, it felt tickly. The same applies if the machine unexpectedly tickled in a different place than you had driven. This study showed that unpredictability is an important factor in how people respond to tickling.

What is the neurochemistry of pleasure?

The brain has a 'pleasure pathway', which makes extensive use of the neurotransmitter dopamine. When this pathway encounter no dopamine, someone will be in a sad mood. Dopamine originates in an area deep in the brain, which is called the ventral tegmentum. Then it goes to a place called the nucleus accumbens, after which the dopamine goes to all sorts of other places, including the frontal cortex (which plays a role in decision making and impulse control), the cingulate cortex (which plays a role in sad feelings) and the amygdala (which plays a role in anxiety).

The relationship between dopamine and pleasure is small, but it is present. You can train a monkey to do a certain task, such as having it pressing ten times on a lever when a bell sounds, after which it receives food within the ten seconds that follow. Now it is obvious that when the dopamine pathway is activated, it activates neurons in the frontal cortex in response to the reward. This is also true, but something less predictable is also happening.

Schultz discovered that the greatest response is around the time the bell rings and the task starts. The pleasure is therefore present in anticipation of the reward and not the reward itself. Dopamine and anticipation of the reward, which gives a pleasant feeling, ensure that the task that is needed to obtain the reward is performed. Paul Phillips from the University of North Carolina has also demonstrated this link between dopamine and action by artificially stimulating the excretion of dopamine. The increased dopamine level caused the rats to start to push a lever. The rats were trained by increasing the interval between stimulus and response. This is also how deferment of bonus works; the core of goal-oriented behavior is expectation. For example, we may enjoy obtaining good grades, so that we pass our exam, so you can eventually graduate and get a good job. 

Schultz also did a similar investigation. He also gave the subject a signal, on which an action was to be taken, followed by a reward. The only difference was that he didn't always give the reward. The subject had a big chance of being rewarded, but also a small chance of not getting a reward. The result of this is that the dopamine content rises even further than in the case that the test animal always receives a reward. This is why 'intermittent reinforcement' works so well in psychology.

Although dopamine plays a major role in anticipating pleasure and taking action, it is not the only factor that matters. When rats are artificially withheld from dopamine, they can still respond to a reward, although to a lesser extent. Opioids probably also play a role. The dopamine pathway is most important when it comes to intense versions of anticipation. This was investigated among test subjects who were deeply in love. When you place them in a scanner and show pictures of familiar but neutral faces followed by a picture of their loved one, the dopamine level goes up considerably. If you do the same for people who have been in a relationship for years, this will not happen.

What is the connection between stress, reward and dopamine?

The fact that we start to laugh when other people tickle us is due to a combination of anticipation, the surprise element to it and the lack of control. The question that arises is the following: when does a lack of control and a lack of predictability stimulate the excretion of dopamine and when is it precisely the core of what makes psychological stress so stressful? The answer lies primarily in whether the uncertainty occurs in a good or frightening context. For example, it makes a big difference if your best friend tickles you out of love or if your greatest enemy does it out of hate. Other important factors are the duration of the experience and whether the experience comes within a broader context of control and predictability. The latter can mean, for example, that you are going to bungee jump (a very unpredictable activity) and that you reassure yourself that managers are truly the authority of the Bungee Jumping Safety Police.

An average increase in glucocorticoid levels that does not last very long ensures that the excretion of dopamine is maximized. When stress lasts a long time, the ability to learn, the synaptic plasticity and the immune defenses are affected. When people experience average and transient levels of stress, the aforementioned things actually improve. The same applies to the glucocorticoid content. When the body is exposed to this intensively and for a long time, this causes a decrease in dopamine levels, dysphoria and depression. But with average glucocorticoid exposure, dopamine secretion is increased. Transient activation of the amygdala also ensures that more dopamine is released into the body. When the propagation of glucocorticoids is linked to the activation of the sympathetic nervous system, the glucose and oxygen levels in the brain are also increased. The result is a focused, alert, lively, motivated and anticipatory feeling. We often call such transient stress "stimulation."

How is it possible that some people always look for situations that would end up giving them another stomach ulcer? Examples of such situations are making your last money at Monopoly, trying out a new recipe at an important dinner, and so on. Perhaps they only excrete a small amount of dopamine compared to others. Another cause could be that their dopamine receptors are less responsive to a dopamine signal, making it difficult to say 'no' to challenging situations. It is also possible that such situations cause larger increases in dopamine in these people, so that they experience more anticipation than other people. Another explanation is that their dopamine level drops just as far after an exciting activity, that they need an even greater challenge to regain this level again.

What is an addiction?

Many cultures have a wide variety of substances such as alcohol, nicotine and tobacco that you can become addicted to. Addiction means that you are almost forced to take the drugs, even though you know that it can have negative consequences for body and mind. It is quite difficult to detect the effects of the drugs on brain chemistry, because the drugs work very differently. For example, tobacco has a very different effect than cocaine. Although there are many differences, there is one similarity between the addictive substances: they all stimulate, although not to the same extent, the release of dopamine in the ventral tegmentus, also called nucleus accumbens. Cocaine in particular is very good at this. This substance stimulates dopamine release from the neurons in a very direct way. Other substances such as alcohol do this in much more indirect ways, which makes them less good at stimulating the release of dopamine.

In brain-imaging studies that were done while people were taking addictive drugs, it turned out that the more someone enjoys the drug, the more the dopamine pathway will be activated. In addition to addiction, the resources also ensure that you need more and more to experience the same amount of pleasure again. Therefore, more dopamine secretions are needed every time to have the same impact on the neuron. Nobody knows exactly how this mechanism works. 

The development of an addiction works as follows. In the beginning there is a 'wish' to take the resources, because a person knows what effects it has or is curious about its use. This feeling of 'wanting' is caused by the release of endogenous opiates. When a person often uses the means, the 'wanting' turns into 'needing'. It is no longer how nice it is to swallow the drugs, but how annoying it feels without using it. George Koob of the Scripps Research Institute has shown through research that when rats are withheld from a certain substance that they are addicted to, there is a ten-fold increase in CRH levels in the brain, especially in areas involved in anxiety such as the amygdala. It is therefore not surprising that an addicted person feels so bad when he or she is not in possession of the substance.

Few people recover from their addiction. People who did recover from it have a heightened risk of relapse. It can happen, for example, that someone who has recovered from his addiction for years comes to a place where he also came during the time he was still an addict, so that the will to take the substance becomes enormously strong. It then seems as if the addiction has never left. This is the 'context-dependent recoil' phenomenon: the urge is greater in certain places, especially places that you associate with drug use. This recoil has also been demonstrated in a rat. The rat was placed in a cage where he could press a lever to be injected with the drugs. The rat was then moved, after which the pressure on the lever was reduced. When he was subsequently placed back in the first cage, the rat "asked" for the means very often. What is special is that the possibility of a recoil often does not diminish with the passage of time.

The process whereby drug use is associated with a certain environment is a form of learning. The reason for this is that there are cortical and hippocampal regions that contain information about the environment. When you repeatedly use drugs in the same environment, these projections to the dopamine neurons are activated and amplified each time. If these projections are strong enough, dopamine anticipation of the drugs is only stimulated by the environment. In lab rats, it is enough to stimulate the areas associated with the dopamine neurons, and they will already fall back into drug use. It is sometimes said that there are no ex-addicts at all, but that people who no longer use them are in a context that does not trigger the use of the substance.

What is the connection between stress and drug abuse?

It is common knowledge that drug use can make you feel less stressed. People who use drugs more often describe themselves as less stressed and less anxious when a stressor occurs after taking psychoactive substances. Alcohol is best known for this and is also called 'anxiolytic', because anxiety is greatly reduced. This effect has been demonstrated in rats. When a rat is normally placed in a brightly lit cage, they look for the dark corners. Alcohol was found to shorten the time it takes for a hungry rat to overcome its fear of catching food in the lighted center of the cage. One reason for this is that agents, including alcohol, cause the glucocorticoid level to rise when they are first taken. But when used more often, they ensure that the activation of the sympathetic nervous system and CRH-related anxiety is reduced. In addition, drugs change the cognitive assessment of the stressor. This means that when you are in a state where you can barely remember your address, you will also notice it less good if something happens that is in reality very stressful. Psychostimulants therefore reduce the stress response and ensure that you do not notice the stressor. The downside to using drugs is that when blood levels fall, fear does arise. And the latter takes longer than the time that the addict enjoys using it. The solution for this is: drink even more, inject, inhale or sniff, which keeps the addiction alive.

Although it is not yet certain why it is, stress increases the chance of taking drugs again and relapsing. First of all, stress influences the development of an addiction. This has been investigated in rats; they were placed in a cage where they were injected with a certain drug (such as alcohol, amphetamines, cocaine) when they pressed a lever. It turned out that the rats that were placed under stress more often pressed the lever than rats that were relaxed. Moreover, rats exposed to unpredictable stress more often 'asked' for the drugs than rats dealing with predictable stress. When a rat or a monkey is placed in a position in which it is in a low rank, it often presses the lever. Stress also has a major influence on alcohol consumption in people.

It should be considered that stress only affects drug abuse when the stressor comes just before drug exposure. Consider, for example, the situation that you have just had annoying news at work and then pour a glass of wine immediately upon your return home. This is also called short-term stress.

Stress can even cause the risk of drug use to rise to an addictive level. We now mainly refer to stress during childhood or even stress from the mother who spreads to the unborn child. When you ensure that a pregnant rat is stressed, their youngsters will have a greater chance of pushing the lever a lot when they have become adults, causing them to use drugs. When a rat has a complication during labor, the young will do the same. And the same applies when the rat is stressed during its childhood. This works exactly the same for monkeys and humans.

Even when the addiction already exists, stress increases the amount of drug abuse. This is because glucocorticoid excretion is increased by stress, which reduces the dopamine content. That is why the addict then craves for means, so that the dopamine level rises again. Stress also ensures that a relapse occurs faster among former addicts. Research has been done on rats by placing them in a cage where the rat has access to a certain drug. After a while, the rat was moved to a cage in which he was not injected with drugs when asked, but with saline. The pressure on the lever died out as a result. When the rat was put back in the 'drug cage' a while later, drug use was picked up faster in rats that were placed under stress than in relaxed rats. 

It is not yet entirely clear what the cause is that stress increases the chance of a relapse in drug use. The effects of glucocorticoids on the excretion of dopamine may be relevant. Perhaps the stress-related sympathetic excitement is important, which is dominated by CRH in the amygdala. There is also evidence that stress increases the power of associative projections of the "pleasure pathway". Perhaps it has something to do with damage to the functioning of the frontal cortex, which normally plays a role in delaying gratification and making decisions.

Practice question:

1. How do psychostimulants reduce the stress response, making it more likely for a person to keep on using drugs during stressful times?

2. True or untrue? When there are a lot of complications during birth, the child will become more prone to develop a drug addiction in adulthood.

Answer to the practice question:

1. Psychostimulants ensure that you will not notice the stressor as much, making the person believe that the stressor isn't there. So, the person will keep on abusing drugs in order not to feel stressed.

2. True; at least in the case of rats.

What is the connection between illness and rank and poverty? - Chapter 17

There are two ideas about how you can get ill. The one idea, introduced by biologists, states that you can only get sick from bacteria, viruses and genetic mutations. The second idea, however, states that you become sick with psychological stress and experiencing a lack of control and effectiveness.

However, it is very important not to look at the disease only, but also at the patient himself (as with psychological processes).  In this way, people not only take the outside world into account, such as bacteria. If you only take the influence of the outside world into account, you will also have to take into account society and the place of the patient in society, or the social context of the person. The society and the place that someone occupies in it will actually play a role in the process of illness and health, as well as the other factors mentioned.

Why are there social ranks?

There are social ranks for all animal species. These ranks ensure that there will be no fighting for every issue that occurs, but that the rights and duties of everyone in that group are clear. In some cases, social ranks are inherited and remain the same throughout their lives. In other cases, ranks may change over time. Sometimes the social ranks also depend on the situation. A person can also obtain a certain social rank by the help of others.

Social ranks may vary with monkeys. These social ranks bring different types of stress with them. For example, a low-ranking monkey will be more often the victim of higher-ranking monkeys who can, among other things, take away their food or indulge in their frustrations. In these monkeys with a lower social rank, the glucocorticoid content at rest is significantly higher than in dominant monkeys. When there is actually a stressor, their glucocorticoid response is lower and smaller than in dominant monkeys. They also recover more slowly from a stressor, have higher blood pressure at rest, the response of the heart and vessels is slow to a stressor and they have a suppressed level of good HDL cholesterol.In subordinate males, the testosterone level is more easily suppressed during stress than in dominant males. There are also fewer white blood cells circulating through the body and a lower level Insulin-like growth factor I, which helps to heal wounds.

In general, it applies to all animals that a chronically activated stress response is a characteristic of a low social rank. However, there are other animal species in which a minor role is not associated with an overactive stress response. In some animal species, a minor role is not that bad or even a push towards dominance. An example of this are South American monkeys, the marmosets. When a marmoset is subordinate, it does not mean that they have to deal with many physiological and psychological stressors. They help their more dominant sister or brother and wait until they get that role themselves. Also with dogs it is much easier to have a lower status. In contrast to the monkeys, dogs are the dominant ones with a higher glucorticoid content at rest.

Research has also shown that the social rank is created first and that a corresponding stress profile is only created afterwards. Another study of subordinate animals showed that especially those animals who were often harassed by dominant individuals and who, moreover, had hardly any opportunities for social support, had the greatest chance of an increased glucocorticoid content. A ranking therefore has different meanings for different animal species. But a rank can also have different meanings between different social groups within an animal species. For example, chimpanzees in one valley of the rainforest can have a very different culture than chimpanzees living in another valley. For example, they have different frequencies of social behavior. Differences between groups also influence the relationship between social rank and stress. A difference between the groups also has to do with the stability of the dominance hierarchy. In a stable hierarchy, the dominant individuals are in a fixed place and have the psychological benefits of their position, such as control and predictability. Often it is also the dominant individuals who have the most healthy stress responses.

However, when the hierarchy becomes unstable, it is the dominant individuals who are fighting the most because they have the most to lose. They no longer have the most healthy stress responses. A hierarchy becomes stable again when an important primate dies, an influential primate joins the group or when a new "coalition" is formed. So not only the social rank is an important predictor of individual differences in the stress response, but also the psychological significance of that rank plays a role.

Another important factor is the experience of both your own social rank and your own society. For example, if a large, aggressive male enters a group of monkeys, a monkey that is not attacked so often will not experience so much stress. The function of the immune system in this monkey will not change, while a monkey who is often attacked will suppress his immune system more. Not only the social rank, society and the way in which an individual experiences his social rank and society have an important effect on the stress response, but also the personality.

What about social rankings in people?

People also often have social ranks. For example, look at the business world. Studies have shown that it is a myth that executives would get a stress syndrome sooner. People in a higher rank often 'give' stomach ulcers to others, instead of having them themselves. Moreover, it has been found that it is generally not managers who get stress-related illnesses. They have a lot of control. It is the people in the middle management of a company who get the most stress-related diseases. This is because these people often have high task requirements and responsibility, but little control of their own.

However, the author is skeptical about human social ranking. In human history, in 99% of the cases, societies were not hierarchical. In addition, people can belong to different groups and have different grades at the same time. People can also have completely different opinions about their social rank. For example, someone who ends in the marathon as 330th will be rather low in rank in the eyes of others. But if this person started training just a few weeks before and did not expect that he would run out of the marathon at all, he would rate himself much higher. People take on themselves as well as others. Similarly, it appears that in men the testosterone level rises slightly if they win in some competitive interaction, unless they think that the profit is only due to pure happiness.

What is the connection between stress and socio-economic status?

Living in poverty often causes a lot of physical stress. People who are poor often have tiring, physical jobs where they have a relatively high risk of an industrial accident. Poor people also have to walk more often because they don't have a car. In addition, they do not have the money to invest in purchases that promote health, such as a good mattress. In addition to physical stressors, many psychological stressors also play a role. People who live in poverty often have less control and their lives are less predictable. For example, they do work on the assembly line or mainly execute orders from others. Moreover, they will often be the first to be fired in bad economic conditions.

Research has shown that unemployment among these people has a negative impact on their health, and that the impact occurs since the first threat of possible unemployment. Also, people who are poor often cannot handle stressors that efficiently. This is because they often have no reserve sources, are unable to plan the future so well, and can only respond to the current crisis. Moreover, their solutions to a current crisis often have negative consequences for the future. For example, they pay for the repair of the washing machine with the wages of the following month.

In addition to these types of stress and poor coping strategies, poverty also entails a shortage of outlets. For example, poor people are unable to quit their job to look for another job because the income is necessary to be able to pay rent. In addition, poor people usually have less social support from others. This is because they have to work very hard and sometimes even have several jobs to make ends meet. As a result, there is simply less time to maintain social contacts and to receive support.

Poverty also brings about more chronic stressors as well. There are varying results as to whether or not there are more catastrophic and more chronic stressors among the poor.

All in all, it can therefore be concluded that a low socio-economic status can be associated with chronic activation of the stress response. Even with children aged 6 and 8 from families with a low socio-economic status, it has been found that their glucocorticoid levels are on average higher than with children who come from a family with a higher socio-economic status. Poverty is also associated with an increased risk of stress-related diseases such as cardiovascular disease, stomach ulcers, but also with rheumatism and psychiatric illnesses among other things. Moreover, a low socio-economic status predicts a low birth weight.A low birth weight also has lifelong effects and can increase the risk of certain diseases.

Poverty can therefore lead to poor health. In some cases, poor health can also lead to poverty, but usually it is the other way around. Your socio-economic status at a certain point in your life predicts important characteristics of your health later in life. This has emerged from an investigation with nuns. Although they all lived exactly the same way in the monastery, their lifespan and illnesses could still be predicted from the socio-economic status they had before they entered the monastery. So the longer you live in poverty, the greater the risks to your health. There is a cumulative effect.

What role does (limited) access to health care play in stress?

In the United States, poor people do not have the same access to health care as the rich. Among other things, they have fewer checks, are tested later if something strange seems to be going on considering their health, and often receive less adequate health care. This happens especially if expensive techniques should be used. This has also been shown by recent studies. People with a low socio-economic status were less likely to receive therapy after a stroke than people with a higher socio-economic status. It also appeared to have an effect on your waiting time for an operation. However, equalizing access to health care for everyone does not appear to have sufficient improving effects. In England everyone has the same access to health care, yet the socio-economic status gradient has become worse. Furthermore, health appears to be gradual. The lower you are on the ladder of socio-economic status, the greater your chance of poorer health.

Marmot's Whitehall surveys in London showed that the heart rate mortality rate was four times higher among people of the lowest social rank compared to people of the highest rank. All socio-economic status grades were clearly shown to everyone in this study. Everyone here had roughly equal access to health care. Moreover, everyone received a wage and the chances were very high that they could continue to earn this wage (for example, they would not be fired). Access to health care therefore does not seem to play such a large role in the risks of various diseases, but especially in the socio-economic status. Poor people still have a greater chance of getting diseases where access to health care is irrelevant. Diabetes in young people and rheumatic arthritis are examples of this. Access to health care appears to play only a limited role in the risk of disease.

What are risk factors and protective factors?

In poor countries, the chance of excessive smoking and drinking among poor people is greater. In addition, poor people often have more problems with nutrition. In developing countries this is often due to a shortage of food, while in the rich countries people get more health problems due to too much unhealthy food. Moreover, less exercise is required in most jobs. The poor often have too little time and money to go to sports clubs alongside their jobs, which means that they don't get enough exercise. As a result, they are more often overweight. In addition, the living conditions of the poor are often less favorable. For example, they often live in cheaper, poorly insulated homes that can be very cold in the winter. They also often live together with more people, which increases the risk of infectious diseases.

All these factors increase the health risk. Moreover, the poor often have less education. This can help to make them less aware of all the risks to which they are exposed. They could therefore live a healthier life if they were better informed about various things, such as what is and what is not healthy food. It is not always due to too little money and / or time. People who are more educated are also often better able to solve problems and, moreover, they are often surrounded by people who are themselves better educated.

However, differences in risk factors and protective factors do not explain everything. This becomes clear when you look globally. Poor countries appear to be no happier than rich countries, even though they have fewer resources. Americans, for example, who have many rich citizens, are unhealthier and live shorter than the inhabitants of some poorer countries. Moreover, there is less air pollution in poorer countries.

All in all, poor people therefore have to deal with daily, chronic stressors. It has also been found that the degree of poverty (gradient) largely determines the degree of stress-related diseases, such as heart disease, diabetes, metabolic syndrome and psychiatric disorders. Furthermore, access to health care and risk factors do not appear to be the main causes of poorer health.

Being poor and feeling poor?

People used to experience stress in order to meet the basic needs of mankind. All these basic needs are met easily today: Everyone has a roof over their heads and everyone can eat. From this perspective, nobody is really poor. In today's society it is not so much about being poor , because everyone has enough to survive and meet their basic needs, but rather it is about feeling poor. Some people feel poorer than most people around them. The socio-economic status and the health gradient are therefore mainly based on this feeling. The amount of stress that someone experiences therefore has to do with how someone thinks their socio-economic status is, and how someone experiences it. For example, a study by Adler showed that European Americans rate themselves higher on the ladder of society than Chinese Americans. This is because the Chinese have a more collectivist culture.

The subjective perception of a person's socio-economic status is just as good a predictor of health as the actual socio-economic status, and in some cases it is even a better predictor. People who feel poor themselves run a greater risk of poor health.

Adler has also shown that the subjective socio-economic status is determined on the basis of education, income, position of the profession, satisfaction with living standards and financial security for the future. The last two points are decisive. Income tells a lot about the socio-economic status of a person (although not completely everything) and satisfaction with the standard of living is also very important. Poor people may be more satisfied with their standard of living than trillionaires, who want more and more money. Satisfaction and financial security partly correspond to the psychological factors fear (for the future) and predictability (of the socio-economic status in the future). Wilkinson has researched how people felt when working in a company where everyone's wages were fairly distributed and how people felt if these wages were not fairly distributed. This study showed that the greater the inequality between incomes, the worse the health and the higher the mortality rate. People feel poor more quickly if they are surrounded by rich people. In Louisiana (America), where the greatest income inequality exists, the mortality rate was sixty percent higher than in New Hampshire, where inequality is the smallest. However, these findings do not appear to be universal. In Denmark, for example, where there is a solid social system, these findings have not been found so strongly. It therefore depends strongly on who people compare. Thanks to urbanization, mobilization and the media, people can now also compare themselves to people they don't even know. A sense of poverty does not necessarily have to arise from a comparison with the immediate environment, although it does make the greatest contribution.

When one rises on the ladder of socio-economic status, this is accompanied by better health. But as more people rise, the steps get smaller and smaller. A country with a large income inequality will have several steps before an even level is achieved. However, the overall health level here is lower than in countries with less income inequality.

If you were to make all incomes a little more equal, the health of the poor will go up a lot, while the health of the richer people will only go down a little. However, Wilkinson has shown that in a society with more equal incomes, both the rich and the poor have better health than their duplicate in a society with the same average income, but an income distribution that is more unequal.

What factors trigger the development of poor health?

Kawachi has made the importance of a social capital very clear. A 'social capital' says something about the existence of social resources that you can use during difficult times. 'Social capital' mainly exists at the level of society and has a lot to do with volunteering and organizations that people join on their own initiative. These organizations ensure that people feel that they are part of a larger whole. It is difficult to measure the extent of social capital, but it has to do with trust, mutuality, little hostility, a lot of participation in organizations that contribute to common goals and that actually achieve something. Kawachi has demonstrated that there are fewer social capitals in societies with more inequality between incomes. In companies with less 'social capital' there is often poorer general health, poorer self-reported health and a higher mortality rate. Strong inequality in income can never go together with a lot of social capital. Inequality between incomes, little trust and little social cohesion therefore go together. Kawachi has also shown that the strongest path from income inequality to poorer health is through a social capital.

' Social capital' leads to less social isolation, less psychological stress and a faster distribution of health information. Too much social capital can, however, have adverse consequences, because everyone is indirectly forced to go with the masses. Individuals are lost because everyone has to think, believe and do the same. Another study by Kawachi also revealed that the more economic inequality there is in a society, the more crime and possession of weapons. Inequality in income explains more crime than poverty.

Another way from income inequality to poorer health is indicated by Evans, Lynch and Kaplan. If you want to improve the health and quality of life, you should invest in public goods for most average people in society, such as safe streets. However, it is better for the rich to spend this money on their own luxury, such as private schools. So inequality between incomes, low social cohesion and 'social capital', class differences and crime create an unhealthy cluster.

When comparing animals with people, there appears to be a big difference with regard to the risk of stress-related diseases due to poverty. In people, poverty clearly leads to an increased risk of stress-related diseases. With animals, this depends on more factors, such as the type of society in which the animal lives, its own experiences within that society, its coping skills, its personality and the availability of social support. This difference arose when people discovered agriculture and abandoned their existence as hunters and gatherers. With this development, poverty and the ranks in society that belong to the different incomes have also arisen. With animals there is simply no such thing.

Practice questions

1. Why is getting a level higher on the socio-economic ladder related to an increase in health?

2. Nowadays, psychological stress is a way more important cause of disease than it was before the 20th century, or even before agriculture was developed. What is the reason for this?

Answers to the practice questions

1. This has to do with the decreased amount of stressors in life that result from becoming richer; there will be fewer daily hassles and more social and material support. Also, the person in question feels like he has become less poor; which decreases stress.

2. The diseases that we die from nowadays are most of the time chronic diseases; instead of one single illness caused by a virus or bacteria. Chronic illnesses often aggravate by the influence of stress.

In which ways can stress be dealt with? - Chapter 18

Bar charts are often used in science to display research results. Young people often have a value of 100% when examining physical functions, such as the functioning of the kidneys, while this value is lower for older people. However, the mean is then indicated. What is also very important is the variability. The variability is much greater in elderly than in the young. If you look a little more closely at this, it is noticeable that there must be elderly people whose condition is quite good, because otherwise they would not be so close to the mean.

There are very big differences in the way people respond to stressors and the way their body and mind deal with these stressors. This is apparent from physical examinations that were done on people who had to perform dangerous, stressful tasks, such as a parachutist who had to land on a small platform in the sea. The majority of these participants had a very large stress response, while part of them had not become more nervous physically. The chapter on the relationship between stress, appetite and stomach ulcers revealed that there are certain personalities that are less able to deal with and handle stress. You could also think that there are certain personalities that can handle stress very well. However, this does not always seem to be the case, and there are other factors that can also play a role.

How to ensure that you can properly deal with stress

In the chapter on aging , it was demonstrated that the elderly excrete too many glucocorticoids and that this is caused by damage to neurons in the hippocampus. This damage is also caused by glucocorticoids. However, due to this damage, even more glucocorticoids are excreted. This way you end up in a negative spiral. Meaney investigated this again in rats. First he measured the memory of these rats. In general, these rats had more memory problems compared to young rats. But there was also a small group of these rats that had no memory problems. This small group appeared to have a normal glucocorticoid level, even after a stress response and their hippocampus was still undamaged. The difference between these rats was the situations of their childhood. The rats that were well treated in the first few weeks after their birth and that were touched a lot were later found to belong to the group that grew old without problems. Meaney and Sapolsky investigated this and this hypothesis was confirmed. This situation is difficult to generalize to the natural environment of rats, because there are no researchers who can pet the animals. Meaney has shown, however, that mothers in the natural environment do the same and that this has the same effect as when people do it. However, there are also other genetic and environmental factors that play a role in the aging process. It is not yet clear exactly what these are, and Meaney, among others, is still investigating this.

The question now arises: what increases the chances of successful aging in people? Many people who are very old see themselves as successful in aging. Perhaps because they have grown old, they have gained more confidence in their bodies. In a survey, old people often perceived themselves as healthier than other people of their age and had good-quality social networks. They were successful in aging that way. Vaillant has done an investigation into aging. He followed a hundred Harvard students for the rest of their lives. The people who were the healthiest, lived the longest, and were most satisfied in later life exhibited different characteristics, which were already clear before the age of fifty. These people did not smoke, drank little alcohol, moved a lot, had a normal body weight, were not depressed, had a good marriage and a good way of dealing with stress. These characteristics also emerged in other studies. Yet, one can never know for sure what the influential factors are in the case of successful aging. For example, it is also possible that someone starts smoking and drinking a lot, because of the reason that they are exposed to many major stressors. Other studies have shown that being respected and needed for at a later age also has a beneficial effect.

The study of successful aging is still relatively recent and no results of longitudinal studies are yet known. These studies do not only examine the factors that can predict successful aging, but also the cause of these factors.

How to deal with catastrophic diseases?

In the 1960s, a study was conducted among parents of children who died of cancer. The aim of the research was to find out whether psychological stress stimulated the same hormonal changes in the body as physical stress does. The researchers mainly investigated the glucocorticoid levels in these parents. Their levels were higher, but there was much variance.

The researchers did discover a few styles of stress management that were associated with a lower glucocorticoid content. One of these styles was to move the major focus to something else or another concern that was less threatening. For example, consider a father who has been sitting at home with his sick child for weeks and has to take a break to get rid of his worries. The father who is afraid of going because his child could die in the meantime has a higher glucocorticoid content than the father who is afraid of going because his child would otherwise be lonely and not get his favorite stories read aloud. The latter father is therefore capable of overcoming the worries about death. This will be replaced by a smaller concern, namely the fact that his child would feel lonely. Another style had to do with denial. If the child's disease deteriorated, the parents could react in different ways. The parent who denied the seriousness of the situation and said that it would be all right had a lower glucocorticoid content than parents who were afraid of the seriousness of the situation and, as it were, looked anxiously at the doctor everytime the child would cough. A third style had to do with the religion of the parents. When the parents were very religious and attributed it to God's plan, they showed a smaller stress response. They thought that God had chosen them specifically because they were strong enough to bear this burden. In this way they draw strength from their faith. Parents who were not religious and did not want to know anything about God in general did not display the same effect, and therefore also had a higher glucocorticoid content.

Learned helplessness is a relevant factor in depression as well. There are different animal species that more or less give up life in certain situations that are beyond their control. However, research shows that here too there is great variability. Of the dogs, for example, who undergo a program for learned helplessness, a third appear to resist and do not suffer from learned helplessness. Dogs that are bred for research more often succumb to these types of programs than dogs that are used for research later in their lives. Dogs that have also lived outside the research setting know, as it were, that there are many controllable things in the world and that the things that cannot be controlled do not necessarily mean the end of the world. These dogs are able to see things in perspective better than other dogs.

Even people who mainly have an internal locus of control are more resistant to learned helplessness. An internal locus of control means that they see themselves more as the creators of their own future. They have a strong sense of control. In monkeys, males with a personality type that has to deal with few glucocorticoids in the body stay longer in a higher ranking than males with a personality type that has a low glucocorticoid content, almost three times as long. This means that they are also more likely to pass on their genes.

When a male gets older, he will drop further and further down in social rank. The young males, who used to look up to this male, can hardly believe that they can now humiliate this male whenever they want. That's why they humiliate him very often. An example of such humiliation is that they make sure the monkeys get almost no food anymore. Such an older male then has a very bad time at the bottom of the social ranking and will therefore live less long. They often move to a different group to seek their salvation, but this is a very stressful task and a dangerous thing to do, so often the males die. However, males who always had few glucocorticoids, but a large social network, do better. At a higher age they still have many social contacts and the humiliations affect them less. These monkeys do not move that often either. They often grown much older.

What are the principles for dealing with psychological stress?

Certain genes cause you to be able to cope better with stress. Also, to grow up with parents with a good socio-economic status increases your chance of growing very old. But you can also change the way you deal with stress, both physically and psychologically. For example, there is biofeedback training, in which someone is conditioned to, for example, reduce their heart rate to a calm, regular pace, lower their blood pressure and increase their lung capacity. By repeating certain activities you can change the connection between behavior and the activation of the stress response. In this way you can arrange the physical handling of stress. An example of this can be found with Norwegian soldiers. They learned to jump parachute and were very scared the first time. From a few hours before the jump to a few hours after the jump, their glucocorticoid and epinephrine levels were greatly increased and their testosterone level was very low. After having jumped more often, they learned that it was not that scary after all, and their glucocorticoid and epinephrine levels also became lower and less activated for a long time. Their testosterone levels were also suppressed less. They could therefore reduce the activation of their stress response for the moment of the physical stressor (the jump). In this way the psychological component of the stress response was filtered out. 

Social support, control, predictability and the ability to express frustration are the most important factors that we can use to manipulate our stress response.

What about self-medication and chronic pain syndromes?

Some people suffer from chronic pains. For example, if they have undergone surgery and have to recover from this operation for a long time, they may suffer pain for a very long time. It is difficult to determine how many medicines such people can get to reduce their pain, without becoming addicted to this medication or even getting an overdose. Researchers once tried out whether patients could determine their own dose. Every time a patient asked for medication, he received it. The medical world thought this would not work out very well. These patients would become addicted or even get an overdose. It was up to the medical staff to determine and monitor the medication. However, the study showed that people were well capable of self-medication and that the use of medication even declined. This can be explained on the basis of control and uncertainty. If the patients were not allowed to decide for themselves when to receive medication, they were always uncertain about whether and when the nurse would come and the time at which they would receive the medication. So when the patients were given control and predictability about the medication and indirectly about the pain, they could tolerate the pain better. When young people are confronted with a stressor, they are more likely to try to cope with this stressor better and to solve the problem than elderly. Older people will probably be more likely to try to get away from the stressor or adjust their attitude to the stressor.

In care homes, this passive, reclusive attitude among the elderly is encouraged. Elderly people often have little social support from their former environment and they often have little control over their daily activities, their finances and their own body. There are often few opportunities for expressing frustration and the elderly are often treated rather childishly. Moreover, they know that life will end soon for them and that things will only get worse in the future. Researchers have stimulated psychologists to give these elderly more responsibility over their daily activities. For example, these elderly had to sign up for certain activities and had to decide on the day before what they wanted to eat the day after. They also received a plant in their room that they had to take care of themselves. This particular research showed that the people who were given more responsibility became more active and had more social contacts. Moreover, questionnaires showed that they saw themselves as happier. They also became healthier and their mortality rate was lower than people who did not participate in this study. Other investigations in which control and responsibility were increased also found the same results. Some studies also found a reduction in glucocorticoid levels or improved immune function. In a study in which the elderly had to perform multiple different tasks, the implementation was even better when the staff encouraged them, but worse when they assisted the elderly in doing these tasks.

How does stress management work?

The foregoing shows that if we improve the psychological factors of control, predictability, social support and expressions of frustration, this will have a favorable effect in the research situation. Logically, this should also be the case with the more important psychological stressors of everyday life. However, it is not that easy. These principles only work in certain circumstances, for some types of people and for certain problems. 

An example of this can be found in the previously described study among parents of children with cancer. It turned out that the parents who denied the seriousness of a deteriorated situation experienced less stress at that time and had a lower level of glucocorticoids. However, if the child eventually did die, the stress response of these parents was greater than that of the parents who had already taken this event into account. The "denying" parents in this case had a higher level of glucocorticoids than the other parents. This shows that strategies are not always good, and that this depends on various factors.

In another study, students regularly visited the elderly in a care home. In condition A, the control condition, no students came to visit. In condition B, the students came to visit at an unannounced time. In condition C the elderly were told when the students came to visit and in the last condition (condition D) the parents were free to choose when they wanted the students to visit them. The visits and social interaction were good for condition B, C and D, although it had a more positive effect on condition B and C, because these older people experienced control and predictability. All the elderly who received visits became happier and also healthier. However, when the study was over and the students stopped coming to visit, the perception of their own happiness and health dropped to a level lower than the level they were on before they entered the study. This shows that when we give someone hope and then decrease this hope, it can even break this person. So, you could say that it works both ways.

Why is exercise so important?

There are a number of reasons why exercise is good in relieving and preventing stress. To begin with, it reduces the risk of metabolic and cardiovascular diseases. This also reduces the chance of stress aggravating these diseases. Research also shows that people who exercise regularly, with the exception of marathon riders, feel better. These people are often less neurotic, outgoing and optimistic. Even when you do research with neurotic, introverted people, it appears that exercise improves their moods. This is probably because beta-endorphins are excreted during exercise. In addition, sports often give you a good feeling through your own effectiveness and performance.

The stress response also prepares your body for sudden, intense activity of the muscles. This reduces the tension if you actually activate your stress response for more muscle activity. There is also evidence that regular exercise causes a smaller stress response compared to various psychological stressors. 

However, there are some limitations. It only improves your mood for a few hours after exercise and the stress response is somewhat weakened for a certain period of time. Then, you will return to your original levels. Moreover, physical exercise only works to reduce stress if the person in question really wants to exercise. As soon as someone is forced to move, health will only get worse. Research into this has been done in rats; they were forced to walk in a wheel. Their health deteriorated, while the health of the rats that voluntarily moved improved.

Studies have also shown that aerobics are better for health than other forms of exercise. This is probably due to the fact that you are not very out of breath during aerobics, so that you can still talk. Before exercise has an effect on your health, you must do this regularly. Doing aerobics twenty to thirty minutes a few times a week has proven to be the most effective.

Finally, too much exercise can also be harmful (see Chapter 11), even at least as bad as too little exercise. A daily meditation of fifteen to thirty minutes also has a beneficial effect on a person's health. Among other things, glucocorticoids are reduced and it influences the sympathetic system. Low blood pressure is often measured during meditation. However, it is not entirely clear whether these effects will remain for a long time afterwards. Most of the studies that attempted to show that these effects are lasting did not randomly group the participants into groups. The people who were in the meditation group were people who started meditating before the experiments already. It is possible that a specific type of person voluntary chooses to start meditating. The physical differences between the meditation group and the control group could possibly have been present before the study. It is therefore difficult to prove that meditation is the cause of the physical differences.

Why gain more control and predictability in your life?

Having information in advance about certain stressors and what to come can have a stress-reducing effect, but not always. For example, it makes little sense to get information in advance about general events that are unavoidable, or events that are very rare, such as a volcanic eruption. Nor does it make sense to get predictive information just a few seconds before a serious event, because then you don't have time to anticipate. Even before a serious event it makes no sense, because you are not concerned with it yet. When information tells little extra in advance, it can make matters worse. This is recognizable in the world after September 11, where there is a threat of "just do your job, but be extra careful." Too much information in advance can also be stressful.

Being in control can have various effects. For example, too much control can have a crippling effect. In Chapter 7 it is described that some studies show that cancer patients can influence the cause and the course of their disease through the presence of love in their lives. In that way, they think they have control over their illness, while in reality they have much less control. When their illness worsens, these people think that it is their own fault, because they think they have control over it, although this is not the case. From a psychological perspective, control is therefore not always a good thing and just increasing the amount of control that someone has is not an indicator of good stress management. In general, the more disastrous the stressor, the worse it is to believe that you had control over the outcome. It is inevitable that in this situation you start to think how much better it could have been if you had done your best just a little more. A sense of control works best for mild stressors. The sense of control in a serious situation (although you do not actually have this control) can be so endearing that it is called "John Henryism" in health psychology. This American folk hero has hammered a drill through a mountain, trying to be faster than the steam drill that made a tunnel through the mountain. He was indeed faster than the steam drill, but he bought it with his life. This phenomenon states that that one can meet all requirements, as long as he or she works hard enough. These types of people also have an internal locus of control. This type of personality works well with middle class people in a meritocratic society with many privileges. For these people, it will often lead to lifelong good health. However, for people who are poor, receive less education, are offered fewer good opportunities and live in a society where prejudice and racism are rampant, having such a personality can be a disaster. These people feel that they could be better if they only worked a little harder and did their best. John Henryism often goes together with high blood pressure and cardiovascular diseases. 

From the above it appears that stress management mainly helps with dealing with mild stressors. In more serious situations, the techniques learned during stress management will not be sufficient.

Why is social support so important?

Social support can ensure that stressors are experienced as less stressful than they otherwise would have been. But it is not the best solution in all circumstances. In this way everyone will also have stressful moments in which he would prefer to be alone. When a rodent or monkey is placed in a group while it is used to being alone, this will be a very big stressor. When a young monkey was separated from its mother, it would experience less stress than if it would be placed in a group with monkeys it already knew. If the monkey did not yet know the monkeys in the group, this did not have a stress-reducing effect, but rather caused an increase in glucocorticoid levels. Not all social situations therefore cause a reduction in the experience of stress. Moreover, it is not always stress-reducing to have more dominant peers around you. And often there are plenty of dominant peers, because about half of animals are dominant over others. Intimate social affiliation also does not always work well. In chapter 7 it was found that women who had a bad marriage more often had a suppressed immune system. This is striking, because being married is usually associated with better health. An intimate relationship with the wrong person is therefore not stress reducing, but rather stress increasing. Not only does receiving social support have a stress-reducing effect; giving social support can also have a very beneficial effect. You then feel that another one needs you, which can be a very positive feeling. However, there are also disadvantages to a strong social network. People get a sense of homogeneity and conformity, but often it is also accompanied by xenophobia.You then feel that you are needed, which is a very positive feeling. However, there are also disadvantages to a strong social network. People get a sense of homogeneity and conformity, but often it is also accompanied by xenophobia.

The idea that religion and spirituality protect against diseases, especially stress-related diseases, is very controversial. Literature shows that it has a beneficial effect when you practice a certain religion and are prayed for. It reduces the number of diseases and the death rate caused by diseases. Moreover, it speeds up the recovery from diseases. A distinction must be made between the term religion and the term spirituality. Religion has more to do with an old system full of traditions and is more formal and authoritarian, outward-looking, doctrinal and inhibits expression. Religious people are often older, less educated, they have a lower socio-economic status and are more often men than women. Spirituality refers to more inward, person-oriented, subjective and emotional  people, who offer more space for expression. In health literature, such a distinction is often not made between religion and spirituality. The studies that show the health benefits are all about whether there are real benefits. This is very uncertain, partly because the studies are almost all retrospective. Furthermore, many things that are related to religion are often measured and many things that have to do with health. If there are enough correlations, you will find a significant connection, although this connection is actually based on coincidence. So it will seem as if a connection has been found, but in reality this is not there. Another pitfall of the research is that people themselves had to indicate the degree of their religiosity, based on objective questions, for example: "How often do you go to church?" People are not always good at answering these. It is also very impossible to divide people into different groups, making it very difficult to do good research. If one looks purely at the medical measurements, there is no evidence that prayer can improve one's health. If a connection is found between religion and health improvement, it is difficult to say which of the two was first present and whether there is not just a hidden variable somewhere. This hidden variable could lead to better health; instead of religion itself. An example of a hidden variable could be the social support that someone from the church community receives. Richard Sloan from the University of Colombia and Carl Thoresen from Stanford University are big thinkers in this field. Sloan is a strong critic of the health benefits of religiosity, and Thores is a follower. Thoresen has found that when someone regularly attends religious services, this predicts a lower death rate and a reduced risk of cardiovascular disease and depression. However, he has also found that it does not predict the progress of cancer, mortality rates of people with cancer, medical disabilities and the speed of recovery from a disease. Thoresen believes that the effects are more about healthy people who stay healthy than about sick people who stay alive and recover faster. Sloan agrees with this, but also feels that the entire subject is receiving too much attention because the effects are very small. If one checks for social support and reduced risk factors, there are several reasons why religion could help. These reasons have to do with stress and the kind of God or Gods that someone believes in. For example, Christians and Jews have a God whose rules are mysterious. This God is responsible for everything that happens, although you sometimes do not know what his motives are. Such thoughts can help you deal with events because you don't have to look for the blame or cause on yourself. You can also believe in a God who has very clear rules. That way you get predictive information. For example, if you want it to rain, you must perform a rain dance. If it is not going to rain, you have not performed the dance well enough. There is always an explanation for such religions. When a deity responds to personal, specific pleas, this adds an extra feeling of control. When you see everything in this world in the form of a divine plan, this provides a lot of support. Everything has a good reason, although this is not always known to you. According to Packer, religion can be very good at reducing stressors, but it takes care of these stressors in the first place. Finally, a prayer from Reinhold Niebuhr that has a lot to do with this chapter: "God, give me self-control to accept things that I cannot change, courage to change the things that I can, and knowledge to discern the two".

Why is cognitive flexibility so important?

There are different ways to deal with stress. For example, someone can work in a problem-solving way or focus more on their emotions, good relationships they have and social support. People differ greatly in the style they use when dealing with stress. Furthermore, different styles work best in different situations. For example, if you have a difficult exam, it works better to learn hard than to convince you that it is okay not to pass the course, while the final style would be better to have after the exam.

Seligman has shown that it is very good to be able to switch between the different loci of control. In some situations it is better to have an internal locus of control, while in other situations it is better to use the external locus of control. If something good has happened, it is useful to attribute it to your own actions, while you can shift the responsibility for negative events to something that is beyond your own control.

Being able to switch to the best style for a certain situation is therefore implicitly related to cognitive flexibility. According to Antonovsky, the best predictor of a person's health is the styles of set rules and flexible strategies. It is very difficult to find a new strategy during stress, but this is often necessary. Different contrasts are mentioned in Sapolsky's book. For example, it is good to activate the stress response with a physical stressor, but not with a psychological stressor. Normally you want a low level of glucocorticoids, but during stress you prefer to have the highest possible level. When the stressor starts, you want a quick activation of your stress responsse. When the stressor has ended, you want to recover as quickly as possible. But perhaps the goal is not to have the greatest possible contrast between the normal level and the level during activation, but to have both at the same time. The basic level would then be slightly higher, while the level would be somewhat lower during activation.

There is an eighty / twenty percent rule. In the business world, for example, the following rule implies: 20 percent of customers account for 80 percent of complaints. And in criminology: 20 percent of criminals commit 80 percent of crimes. With regard to stress management, you could say that eighty percent of the stress reduction is achieved by the first twenty percent of the effort you put into reducing stress. People who suffer from depression, for example, often feel significantly better when they have made a first appointment with a therapist. At that a moment, they realize that they have a problem and want to do something about it. This insight is very important in stress management. If you want to change, you have to use your stress management on a daily basis, you really want to achieve something and not postpone it to later times. It is important to realize that we can use our own capacities to prevent various physical and emotional problems through small steps that we take every day, such as not worrying too much about certain things.

Practice questions:

1. Which of the following statements is/are true?

I Stress can accelarate the process of aging

II Elderly often deal less efficiently with stress

A) I is true

B) II is true

C) Both I and II are true

D) Both I and II are untrue

2. How does social support reduce the negative consequences of stress?

Answers to the practice questions:

1. C

2. The presence of social support makes sure that one experiences a stressor as less stressful.