THE NEUROTRANSMITTERS
It is useful to think of the brain as a system of message networks that are connected to one another, like a telephone network. Behavior is determined when one part of the brain dials the “phone number” of another part of the brain. The “phone call” is transmitted through the nerves. A message from one nerve cell to another nerve cell in the brain is transmitted by means of chemicals. These chemicals, called neurotransmitters, trigger the electrical signals that produce our thoughts, our emotions, our memories, our sleep patterns, and our will. When everything goes as it should, the phone calls made in our brains are completed as dialed; when something goes wrong—when there’s too much or too little of one of the necessary neurotransmitters—we get a wrong number or a busy signal.
The brain has literally millions of nerve cells, each of which sends messages within itself by means of electricity. That electricity, which is generated chemically, moves from one end of the nerve to the other end. When it gets to the end, the nerve does not connect directly to another nerve. Nerves end in a space called a synapse. That’s where the neurotransmitters come in. They float across that space, touch other nerves, and cause a chemical reaction that creates more electricity and sends the message on. The body is very careful about protecting and saving everything it produces, so once a nerve has sent its signal, it will attempt to take the chemicals back and store them until they’re needed again—a kind of “recycling” project in the brain. The process is called reuptake.
The messages that the neurotransmitters send from nerve to nerve are governed by three factors: first, which specific nerves are connected by these chemicals; second, the intensity of the connection, which in turn governs the strength of the signal; and third, the pattern of connections: where a set of nerves goes and to what part of the brain it sends messages. In describing the significance of the signal’s strength, a colleague of mine uses a model he calls “I’m a Little Teapot.” As he describes it, the rate at which someone pouring tea from a teapot sends the liquid into the cup depends on how much he tips the teapot; similarly, a strong signal in the brain results in a lot of messages. If the pourer of the tea puts his finger in the spout, no tea will come out no matter how much he tips the teapot, not unlike what happens when a brain signal is blocked by chemicals. If he tips the teapot over too fast, the tea will probably slosh out over the lid. Again, too strong a signal will send too many messages in the brain, and to the wrong destination.
The critical factor here is to regulate the strength of the signal that is “poured” into the synapse. While there are literally dozens of chemicals capable of transmitting their own messages, three seem to be the most critical, because we can measure them easily, because their actions are consistent with our hypotheses about the physiology of brain disorders, and because we have medications that can alter their functions. The three basic chemicals—neurotransmitters—that affect the process are:
Serotonin. This neurotransmitter is related to anxiety, depression, and aggression.
Dopamine. This neurotransmitter affects the perception of reality.
Norepinephrine. This neurotransmitter affects attention and concentration.
There are other important neurotransmitters in the brain, such as hormones, which send messages that bring on a woman’s premenstrual syndrome, among other things; catecholamines (including adrenaline), which affect arousal patterns (the “fight or flight” reactions) and raise blood pressure; and histamine, which stops up the ears and makes the nose run. All of these neurotransmitters can be affected and often are (with hormone replacement therapy or antihistamines, for instance), but in the treatment of child and adolescent psychiatric disorders we are dealing mostly with the Big Three: serotonin, dopamine, and norepinephrine. Those words will come up many times in these pages as we examine the psychiatric disorders that affect children and adolescents.
THE DELICATE BALANCE
Every muscle in the body has an opposing muscle. For example, the biceps muscle makes the arm go up, and the triceps muscle makes it go down. The same is true for the central nervous system. Every nerve or nerve action has an opposing nerve action. When the sides are evenly balanced, everything runs smoothly; but when one side is stronger than the other, there are problems. In psychopharmacology—the treatment of psychiatric disorders with medication—we try to restore the brain’s chemical balance, so that the body and the brain may maintain some equilibrium. Someone driving a car on which the wheels on the right are spinning faster than the wheels on the left will go around in circles, never getting anywhere. The only way to get the car moving forward is to balance the motion of the wheels. That’s roughly what we try to do—adjust the brain so that all of its wheels are spinning forward at the same rate of speed.
Good psychopharmacology effects changes that are subtle. It doesn’t mean sedating a patient or making him super-alert; it involves getting the patient back on an even keel. When we treat a child with attention deficit hyperactivity disorder (see Chapter 7), our goal is to increase the child’s ability to pay attention. If he pays too much attention, he may become suspicious or obsessive and not be able to get anything done. If he pays too little attention, he can’t be productive either. In treating the child with ADHD, usually with daily doses of Ritalin or some other stimulant, we try to find the middle ground, where balance is restored and a child is paying exactly the right amount of attention. This is true of all the brain disorders that we treat with medication. Our aim is always the same: to restore a chemical balance in the brain.
Pulling off this balancing act is often easier said than done. The body has many ways to regulate itself. In correcting a balance problem we choose one place to regulate the neurotransmission, but that one place is not necessarily the only spot that will work. There’s more than one way to increase or decrease a specific neurotransmitter. Different drugs may work at different sites on the brain and achieve the same effect.
Furthermore, there is virtually no such thing as a “norepinephrine disease” or a “serotonin disorder” or a “dopamine disease.” Most disorders are the result of more than one neurotransmitter malfunction. It’s as if we have a man and a woman in an office building in different elevators, and we want them to get to the same floor at the same time so that they can meet and work together. The man is on an elevator—the serotonin elevator—that is stopped on the fourth floor; the woman is on the eighth floor in the dopamine elevator. In order to get them to the same level, we can do one of three things: raise the serotonin elevator up to the eighth floor; bring the dopamine elevator down to the fourth floor; or adjust both elevators so that the man and woman have their meeting on the sixth floor. Any of these is a satisfactory solution; any is possible. Our job is to find the best strategy to restore balance.
It’s important to realize that we are talking about very small amounts of chemicals here. We measure the neurotransmitter serotonin in nano-grams, which is about one 10-billionth of a pound. Dopamine is measured in picograms, roughly 10 trillionths of a pound. Brain chemicals are powerful stuff, and a minute discrepancy can have a substantial impact on a child’s behavior.
Every brain is different, of course. A drug may work beautifully for one child and do nothing for another even if both children have exactly the same disorder. Sometimes drugs have only a temporary effect. The medicines increase the level of a neurotransmitter, but over time the brain compensates for the change and says, “Wait. There’s too much of that chemical coming through,” and instinctively makes the adjustment by cutting it back. The short-term result of treatment is an increase of that neurotransmitter, but over the long term there may be an actual decrease. For all of these reasons and more it takes time and sometimes several careful trials to determine which medication, at which dosage, a child needs. The challenge is to find the right balance for each child.
OUTSIDE AGITATORS
Medicine isn’t the only thing that can bring about a chemical change in the brain. Environmental exp
eriences may also have an effect on the neurotransmitters. There is strong evidence that stress alters brain chemistry, especially in a brain that is vulnerable. Not everyone reacts the same way to a stressful or painful situation. The death of a loved one makes everyone sad, sometimes very sad for an extended period of time, but only in a few people does such an event lead to the persistent, debilitating symptoms of clinical depression (see Chapter 14). Severe illness, divorce, a change of location, physical or mental abuse—all of these will take their toll on a child’s brain. If the chemical makeup of his brain makes him vulnerable to a psychiatric disorder, outside stimuli may well bring it on.
The brain is not a constant. It adapts and changes according to the environment. One of my colleagues compares the process to a home thermostat that is always set at 68 degrees. In the winter the temperature starts to drop, so the heat goes on, brings the house back to 68 degrees, and shuts off. In the heat of summer, when the temperature rises, the air conditioner kicks on and cools the house to 68 degrees again. The brain has a kind of thermostat too. In times of stress we may get anxious or sad, but our thermostats keep us from straying too far away from our ideal set point. We’re anxious when we have to give a speech or a little depressed when we go to a funeral, but we bounce back.
Those unpleasant feelings don’t last forever, any more than the elation associated with good news lasts forever. A man who gets a promotion and a raise is ecstatic. He and his wife go out to dinner to celebrate, and they drink champagne. For a few days he’s on top of the world, but a week later things are pretty much back to normal. He doesn’t stay on top of the world for the rest of his life. His thermostat does its job.
However, some children have thermostats that aren’t set quite right, so their ability to keep their emotions and their behavior within normal boundaries is seriously impaired. Perhaps they can’t sit still or pay attention in class. Maybe they’re overanxious or depressed. They could be compulsive or have involuntary tics. In psychopharmacology we’re in the business of resetting children’s thermostats so that their heating and air conditioning systems keep the temperature just right.
PSYCHOPHARMACOLOGY 101
Our lives are basically divided into three spheres: love, run, and work. In the case of children those spheres are translated into the relationship with their parents, social interactions with their friends, and learning in school. A mild imbalance in a child’s brain—a little too much norepinephrine, for instance—usually will not cause any real distress or dysfunction. He’ll still love his parents, he’ll have friends, and he’ll function perfectly well in school. No treatment will be necessary. However, if the chemical imbalance is severe and a child’s activities in any of these areas are significantly altered for an extended period of time, we take a closer look. We may decide to alter the chemical makeup of the child’s brain with medication.
Each of the three essential chemicals in the brain is affected by different categories of drugs:
Serotonin is affected by groups of drugs called SSRIs (selective serotonin reuptake inhibitors). The best known of the SSRIs are Prozac, Zoloft and Paxil.
Dopamine is affected by drugs called neuroleptics, among them Hal-dol, Thorazine, and Mellaril.
Norepinephrine and dopamine are affected by a group of drugs called psychostimulants or, more often, just stimulants. Ritalin and Dexedrine are the two most frequently prescribed stimulants.
Norepinephrine and serotonin are affected by the TCAs (tricyclic antidepressants). The best known of the TCAs are Tofranil, Elavil, and Norpramin.
Norepinephrine is affected by the antihypertensive agents. Developed originally for patients with high blood pressure, the antihypertensives, especially Catapres and Tenex, are now used in the treatment of children’s brain disorders.
Serotonin and dopamine are affected by the atypical antipsychotics. The most commonly prescribed drugs in this category are Risperdal and Clozaril.
All three of the neurotransmitters—serotonin, dopamine, and nor-epinephrine—are affected by a category of drugs called the MAOIs (monamine oxidase inhibitors), which slow the metabolism of the brain’s neurotransmitters. Nardil and Parnate are the most commonly prescribed MAOIs.
(When I talk about various medicines in these pages, I usually refer to them by brand name, because in my experience that is the name with which people are most familiar. Appendix 3, Psychopharmacology at a Glance, lists the generic as well as the brand names of all the major psychiatric drugs.)
All the medicines prescribed for the treatment of brain disorders do one of four things: (1) they block the metabolism of the neurotransmitter, so that more of the neurotransmitter is available; (2) they block the place where the neurotransmitter connects, making it more difficult for the message to be sent; (3) they block the reuptake of the neurotransmitter, making the neurotransmitter more available; and (4) they block the release of the neurotransmitter. We can put this even more simply and reduce the functions to two. Either the drugs increase the availability of these chemicals and send more of a message, or they decrease the availability of the chemicals and send less of a message. We prescribe a medicine depending on whether we want to facilitate or to block the neurotransmitter message. Ritalin is a facilitator. Thorazine and Haldol are blockers. Prozac and Paxil block the reuptake, or recycling, of the neurotransmitter.
In a perfect world we would be able to zero in on a specific chemical in a particular synapse and make the change that’s needed, but the drugs available to us aren’t advanced enough at this point to treat a specific disorder. The brain is complex, and very few medications are “clean”; that is, when a patient takes a drug, it is rare that the level of only one brain chemical is affected in only one part of the brain. If a drug we prescribe affects serotonin, it will affect the serotonin everywhere in the brain, not just in the areas of the brain that are responsible for a child’s compulsions or his depression. A drug that affects dopamine levels won’t work its magic just on the area of the brain that is responsible for schizophrenia; it affects all the parts of the brain that use dopamine.
Brain disorders aren’t “clean” either. We often encounter comorbidity, a situation in which children have two or even more brain disorders at the same time. For example, attention deficit hyperactivity disorder may be co-morbid with conduct disorder; separation anxiety disorder is often co-morbid with major depressive disorder; and obsessive compulsive disorder is sometimes linked with Tourette syndrome. To complicate matters even further, brain disorders often involve more than one neurotransmitter, and there is interaction among the neurotransmitters; when we change the level of one, it may have an impact on the others. These neurotransmitters don’t react in a vacuum. Increasing the brain’s level of serotonin may, as a side effect, decrease the level of dopamine.
Unfortunately, much of what we know about brain chemistry can’t be diagnosed with blood tests, X rays, or other tools. If there’s something wrong with a child’s liver, we can give him a local anesthetic, use a long needle, do a biopsy, and find out exactly what the problem is. There’s no such thing as a routine brain biopsy; that procedure would be far too drastic for these purposes. Still, there has been some progress in the field, largely in the neuroimaging techniques, which give us new insights by allowing us to examine certain physiological and chemical processes that take place in the brain basically by producing three-dimensional images of the brain.
Neuroimaging techniques have helped us reach an important conclusion: there are brain abnormalities in adults who have brain disorders. Although studies of children and adolescents are in the very early stages, there is already reason to think that they have brain differences too. These techniques can also be very useful in helping us understand how the brain works and especially how various medicines affect the brain’s function. For all of their value, however, neuroimaging techniques are not used for diagnosis. For diagnosis the best tool always has been and probably always will be behavioral observation. No matter how many tests
a child undergoes, we base our diagnosis on a child’s history and his behavioral symptoms. These tools allow us to diagnose a brain disorder as precisely and as reliably as physicians diagnose diabetes and hypertension.
The fact is, there is a lot of information about the brain that we don’t yet have. We know that children with psychiatric disorders have a chemical imbalance in the brain that is caused by a genetic abnormality, but we don’t know what the specific abnormality is. And we don’t know precisely why these medicines work. We just know that they do work. That’s nothing new to medicine, of course. Digitalis has been around for hundreds of years. We’ve been using it for heart attacks for decades, but until relatively recently we had no idea why it works. We just knew that it did.
CHAPTER 6
The Great Medication Debate
According to his mother, 10-year-old Adam had always been a “difficult child.” When Adam and his parents came to my office for the first time, I learned that the little boy had been seeing a psychologist three times a week for five years. That’s roughly 750 sessions. Adam was still having serious trouble with his behavior. He wasn’t doing well in school, and he didn’t have any friends to speak of. I asked the parents what had taken them so long to bring their child to a psychiatrist.
“Well, Adam’s psychologist has been telling us for several years that he probably needs medication for his attention deficit hyperactivity disorder, but we were afraid to do it,” the mother replied. “We thought that it would change his personality,” added the father. “And besides, we don’t like the idea of medicating a child.”
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