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Authors: Harold Koplewicz

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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 experiences 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.

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