Archives for March 2007

A key aspect of a healthy adaptational response to stress is the time course. Responses must be initiated rapidly, maintained for a proper amount of time, and then turned off to ensure an optimal result. An over-response to stress or the failure to shut off a stress response can have negative biological consequences for an individual. Healthy human responses to stress involve three components:

The brain handles (mediates) the immediate response. This response signals the adrenal medulla to release epinephrine and norepinephrine. The hypothalamus (a central area in the brain) and the pituitary gland initiate (trigger) the slower maintenance response by signaling the adrenal cortex to release cortisol and other hormones. Many neural (nerve) circuits are involved in the behavioral response. This response increases arousal, focuses attention, inhibits feeding and reproductive behavior, reduces pain perception, and redirects behavior.

The combined results of these three components of the stress response maintain the internal balance (homeostasis), increase energy production and utilization, and alter electrolyte (chemical elements) and fluid balance in the body. They also gear up the organism for a quick reaction through the sympathetic nervous system (SNS). The SNS operates by increasing the heart rate, increasing blood pressure, redirecting blood flow to the heart, muscles, and brain and away from the gastrointestinal tract, and releasing fuel to help fight or flee the danger.

A key to the understanding of the negative aspects of stress is the concept of milieu intérieur (the internal environment of the body), which was first advanced by the great French physiologist, Claude Bernard. In this concept, he described the principles of dynamic equilibrium. In dynamic equilibrium, constancy, a steady state (situation) in the internal bodily environment, is essential to survival. Therefore, external changes in the environment or external forces that change the internal balance must be reacted to and compensated for if the organism is to survive. Examples of such external forces include temperature, oxygen concentration in the air, the expenditure of energy, and the presence of predators. In addition, diseases were also stressors that threatened the constancy of the milieu interieur.

The great neurologist Walter Cannon coined the term homeostasis to further define the dynamic equilibrium that Bernard had described. He also was the first to recognize that stressors could be emotional as well as physical. Through his experiments, he demonstrated the "fight or flight" response that man and other animals share when threatened. Further, Cannon traced these reactions to the release of powerful neurotransmitters from a part of the adrenal gland, the medulla. The adrenal medulla secretes two neurotransmitters, epinephrine (also called adrenaline) and norepinephrine (noradrenaline), in the response to stress. The release of these neurotransmitters leads to the physiologic effects seen in the fight or flight response, e.g., a rapid heart rate, increased alertness, etc.

Hans Selye, another early scientist who studied stress, extended Cannon's observations. He included, as part of the body's stress response system, the pituitary gland, a small gland at the base of the brain. He described the control by this gland of the secretion of hormones (e.g., cortisol) that are important in the physiological response to stress by the other part of the adrenal gland known as the cortex. Additionally, Selye actually introduced the term stress from physics and engineering and defined it as "mutual actions of forces that take place across any section of the body, physical or psychological."

There is now evidence that points to abnormal stress responses as being involved in causing various diseases or conditions. These include anxiety disorders, depression, high blood pressure, and cardiovascular disease, certain gastrointestinal diseases, some cancers, and even the process of aging itself. Stress also seems to increase the frequency and severity of migraine headaches, episodes of asthma, and fluctuations of blood sugar in diabetics.

There also is scientific evidence showing that people experiencing psychological stress are more prone to develop colds and other infections than their less-stressed peers. Overwhelming psychological stress (such as the events of 9-11) can cause both temporary (transient) and long-lasting (chronic) symptoms of a serious psychiatric illness called posttraumatic stress disorder (PTSD).

Stress is simply a fact of nature -- forces from the outside world affecting the individual. The individual responds to stress in ways that affect the individual as well as their environment. Hence, all living creatures are in a constant interchange with their surroundings (the ecosystem), both physically and behaviorally. This interplay of forces, or energy, is of course present in the relationships between all matter in the universe, whether it is living (animate) or not living (inanimate). However, there are critical

differences in how different living creatures relate to their environment. These differences have far-reaching consequences for survival. Because of the overabundance of stress in our modern lives, we usually think of stress as a negative experience, but from a biological point of view, stress can be a neutral, negative, or positive experience.

Stress has driven evolutionary change (the development and natural selection of species over time). Thus, the species that adapted best to the causes of stress (stressors) have survived and evolved into the plant and animal kingdoms we now observe. Man, because of the evolution of the human brain, especially the part called the neo-cortex, is the most adaptive creature on the planet. This adaptability is largely due to the changes and stressors that we have faced and mastered. Therefore, we, unlike other animals, can live in any climate or ecosystem, at various altitudes, and avoid the danger of predators.

Moreover, most recently, we have learned to live in the air, under the sea, and even in space, where no living creatures that we know of have ever survived.

The modern idea of depression appears similar to the much older concept of melancholia. The name melancholia derives from black bile.

Clinical depression was originally considered to be a chemical imbalance in transmitters in the brain, a theory based on observations made in the 1950s of the effects of reserpine and isoniazid in altering monoamine neurotransmitter levels and affecting depressive symptoms. Since these suggestions, many other causes for clinical depression have been proposed.

Clinical depression affects about 16% of the population on at least one occasion in their lives. In some countries, such as Australia, one in four women and one in eight men will suffer from depression. The mean age of onset, from a number of studies, is in the late 20s. About twice as many females as males report or receive treatment for clinical depression, though this imbalance is shrinking over the course of recent history; this difference seems to completely disappear after the age of 50–55. Clinical depression is currently the leading cause of disability in North America as well as other countries, and is expected to become the second leading cause of disability worldwide (after heart disease) by the year 2020, according to the World Health Organization.

These are some symptoms that people have when they're depressed:

• depressed mood or sadness most of the time (for what may seem like no reason)
• lack of energy and feeling tired all the time
• inability to enjoy things that used to bring pleasure
• withdrawal from friends and family
• irritability, anger, or anxiety
• inability to concentrate
• significant weight loss or gain
• significant change in sleep patterns (inability to fall asleep, stay asleep, or get up in the morning)
• feelings of guilt or worthlessness
• aches and pains (even though nothing is physically wrong)
• pessimism and indifference (not caring about anything in the present or future)
• thoughts of death or suicide

When someone has five or more of these symptoms most of the time for 2 weeks or longer, that person is probably depressed. Sometimes people go through bouts where these symptoms are really intense; other times these same feelings could be present at a lower level all the time for years. Some people have just one episode of depression, or they may go on to have more than one after being better for a while. When a person has had more than one bout with major depression, a doctor will diagnose the person as having major depressive disorder.

For some people, depression can be intense and occur in bouts that last for weeks at a time. For others, depression can be less severe but can linger at a low level for years.

Doctors who treat depression distinguish between these two forms, diagnosing the more severe, short-lasting form as major depression, and the longer-lasting but less severe form as dysthymia.

A third form of depression that may be diagnosed is called adjustment disorder with depressed mood. It refers to a depressive reaction to a specific life event (such as a death, divorce, or other loss) when the adjustment to the loss takes longer than the normally expected time frame or is more severe than expected and interferes with the person's daily activities.

Bipolar disorder (also sometimes called manic depressive illness) is another depressive condition that involves periods of major depression mixed with periods of mania. Mania is the term for abnormally high mood and extreme bursts of unusual activity or energy.

Depression involves the brain's delicate chemistry - specifically, it involves chemicals called neurotransmitters. These chemicals assist in transmitting messages between nerve cells in the brain.

Certain neurotransmitters regulate mood. When they are not available in sufficient quantities, the result can be depression.

The brain's response to stressful events, such as any of those described above, may alter the balance of neurotransmitters and result in depression.

Sometimes, a person may experience depression without any particular sad or stressful event that they can point to. People who have a genetic predisposition to depression may be more prone to the imbalance of neurotransmitter activity that is part of depression.

Medications that are used to treat depression work by helping to restore the proper balance of neurotransmitters.

..A depressive disorder is a syndrome (group of symptoms) that reflects a sad mood exceeding normal sadness or grief.
..Depressive disorders are characterized not only by negative thoughts, moods, and behaviors, but also by specific changes in bodily functions (e.g., eating, sleeping, and sexual activity).
..One in 10 people will have a depressive disorder in their lifetime, and in 1 of 10 cases, the depression is a fatal disease as a result of suicide. Some types of depression, especially bipolar depression, run in families.
..Depression is diagnosed only clinically in that there is no laboratory test or x-ray for depression. Therefore, it is crucial to see a health practitioner as soon as you notice symptoms of depression in yourself, your friends, or family.
..The first step in getting appropriate treatment is a complete physical and psychological evaluation to determine whether the person, in fact, has a depressive disorder.
..Depression is not a weakness, but a serious illness with biological, psychological, and social aspects to its cause, symptoms, and treatment. A person cannot will it away.
..Untreated, it will worsen. Under-treated, it will return.
..There are many safe and effective medications, particularly the SSRIs, that can be of great help in depression.
..For full recovery from a mood disorder, regardless of whether there is a precipitating factor or it seems to come out of the blue, treatments with medications and/or electroconvulsive therapy (ECT) and psychotherapy are necessary.
..In the future, through depression research and education, we will continue to improve our treatments, decrease society's burden, and hopefully develop preventive measures.

The future is very bright for the treatment of depression. We are close to having genetic markers for bipolar disorder. Soon after, we hope to also have them for major depression. That way, we can know of a child's vulnerability to depression from birth and try to create preventive strategies. For example, we can teach parents early warning signs so that they can get treatment for their children, if necessary, to ward off future problems.

The new world of pharmacogenetics holds the promise of actually keeping the genes responsible for depression turned off so as to avoid the illnesses completely. Also, by studying genes, we are learning more about the matching of patients with treatment. This kind of information will be able to tell us which patients do well on which types of drugs and psychotherapy regimens.

We are learning more about the interactions of the neurochemicals in the brain. Moreover, new categories of neurochemicals, such as neuropeptides and substance P, are being studied. As a result, we will soon be able to develop new drugs that should be more effective with fewer side effects. Finally, we are learning startling things about how maternal stress early in pregnancy can profoundly affect the developing fetus. For example, we now know that maternal stress can greatly increase the risk for the fetus to develop depression as an adult. While sadness will always be part of the human condition, hopefully we will be able to lessen or eradicate the more severe mood disorders from the world to the benefit of all of us.

A complete physical and psychological diagnostic evaluation by professionals will help the depressed person decide the type of treatment that might be best for him or her. However, if the situation is urgent because a suicide seems possible, taking the patient to the emergency room is the appropriate course of action. If the patient makes a suicide gesture or attempt, a 911 call is warranted. The patient might not realize how much help he or she needs. In fact, he or she might feel undeserving of help because of the negativity and helplessness that is a part of depressive illness.

Listed below are the types of people and places that will make a referral or provide diagnostic and treatment services. Check the Yellow Pages under "mental health," "health," "social services," "suicide prevention," "hospitals," or "physicians" for phone numbers and addresses.

..Family doctors.
..Mental health specialists, such as psychiatrists, psychologists, social workers, or mental health counselors.
..Health maintenance organizations.
..Community mental health centers.
..Hospital psychiatry departments and outpatient clinics.
..University or medical school-affiliated programs.
..State hospital outpatient clinics.
..Family service/social agencies.
..Private clinics and facilities.
..Employee assistance programs.
..Local medical and/or psychiatric societies.