Driven to Distraction (Revised)

by Edward M. Hallowell

  So can we say that ADD is a chemical imbalance? Like most questions in psychiatry, the answer is yes and then again no. No, we have not found a good way to measure the specific imbalances in the neurotransmitter systems that may be responsible for the ADD. But yes, there is enough evidence that neurochemical systems are altered in people with ADD to state that the problem derives from the chemistry of the brain. Most likely, it is a dysregulation along the catecholamine-serotonin axis, a dance where one misstep by one partner creates a misstep by the other, which creates another misstep by the first. Before they know it, these dance partners are out of step not just with each other but with the music—and who is to say how it happened?

  Alan Zametkin and his colleagues at the National Institutes of Mental Health may not have defined how it happened, but they did demonstrate for sure that it was happening, that the biochemical dance was different in the brains of people with ADD as compared to the brains of people without ADD. Zametkin created a bridge where before there had been only a leap of faith. His work is so important that it is worth a close look.

  Zametkin’s study in 1990 examined activity in the brain in adults with and without ADD. The study did this by watching how the brain uses glucose, its energy source, during a continuous performance task. The use of glucose is a good marker of metabolic activity. Continuous performance tasks are tests that have been designed specifically to measure attention and vigilance to stimuli. In Zametkin’s study, subjects had to indicate if and when they heard particular tones, using a push-button apparatus hooked up to a computer. This test was administered to twenty-five adults who had a childhood history of hyperactivity and were diagnosed with ADD according to Wender’s Utah Criteria. All of these adults, eighteen of whom were men and seven of whom were women, were the biological parents of children with ADD. They were matched to a group of fifty controls who did not have ADD but who shared the same demographic characteristics as themselves.

  To measure glucose metabolism, Zametkin’s group used PET scans. The PET, or positron emission tomograph, can be described as an expensive camera that records the radioactivity given off by the brain after it has used radio-labeled glucose during a specific task. Through computer manipulation, a composite of numerous data points is assembled into an image that we can look at and use for comparisons. What Zametkin found using this technique was a deficit in glucose uptake, and hence energy use, in the brains of subjects with ADD as compared to controls. Overall, the ADD group metabolized glucose at rates 8 percent lower than the control group.

  The reduction in glucose uptake was widespread throughout different regions of the brain. Most informative is that the decrease in metabolic activity was largest in the prefrontal and premotor regions of the brain. The frontal region is the major regulator of behavior. It keeps impulses in check, allows us to plan and anticipate, and serves as the place where we initiate behavior. It gets input from the lower brain, which regulates arousal, screens out irrelevant stimuli, and serves as the seat of fight-or-flight reactions. It receives input from the limbic system, the seat of emotion, hunger, thirst, sexuality, and other physiological impulses. And it probably is the site of working memory, the combination of moment-to-moment experience and long-term memory. Thus the frontal lobes synthesize sensory and cognitive information, they orchestrate attention, and they function as the gateway to action.

  As Zametkin pointed out, the results of the PET scans indicating depressed frontal lobe activity are consistent with what other researchers have claimed to be the functional neuroanatomy of ADD. Both J. A. Mattes and C. T. Gualtieri have speculated that the frontal lobes were involved in ADD because of the similarity between ADD symptoms and frontal-lobe syndromes resulting from injuries or lesions to the frontal areas. This observation was codified by the work of G. J. Chelune in 1986 as the frontal-lobe hypothesis, which posited that hyperactivity and impulsivity are basically a form of disinhibition. According to this hypothesis, many of the symptoms of ADD arise because the brain loses its ability to put on the brakes sufficiently. This is due to disturbed inhibition in the cortex, or outer layer, of the brain. Without cortical inhibition, the brain fails to block inappropriate responses and fails to send out appropriate inhibitory messages. According to Chelune’s frontal-lobe hypothesis, the cortex of the frontal lobe is where the action is—or isn’t—in ADD. Inhibition breaks down; impulsivity and hyperactivity rise concurrently.

  In addition to giving support to Chelune’s hypothesis, Zametkin’s findings also support the 1984 work of H. C. Lou and his colleagues, who found decreased blood flow in the frontal regions of the brain in people with ADD. Lou’s study also indicated a deficit in blood flow in the right hemisphere of the brain as compared to the left. This is intriguing, as some researchers think that ADD is related to right-hemisphere dysfunction. The right hemisphere generally controls our so-called executive or decision-making capacities, our visual-spatial abilities, and our ability to process many sources of stimuli simultaneously. Some specific deficits associated with right-hemisphere dysfunction include topographagnosia (getting lost a lot!) and social-emotional learning disabilities. Martha Denckla, a specialist in the neuropsychiatry of learning disabilities, points out that right-hemisphere problems could prevent one from grasping configurations of many details, “getting the big picture,” so to speak. Certainly, the picture that is painted of right-hemisphere disabilities sounds just like the complaints we hear from patients about always losing their keys, always getting lost, never paying attention to the big picture, and never quite understanding other people.

  Is there accordance between what may be the functional neuroanatomy of ADD and the role of specific neurotransmitter systems? Yes, indeed. The prefrontal areas of the brain are rich in catecholamines, and some research has shown that aged monkeys whose prefrontal cortices are deficient in dopamine and norepinephrine perform poorly in delayed-response tests. Delayed-response tests, like continuous-performance tests, measure attention and vigilance; they also measure the functioning of working memory. In addition, dopamine forms a pathway between the motor center and the frontal regions of the brain, and another pathway from the limbic center to the frontal regions of the brain. Dopamine neurons from these lower areas pass through the central frontal lobe to reach the prefrontal cortex. This doesn’t prove anything, but it does suggest a role for dopamine in connecting motor activity, emotion, attention, and impulse control, since dopamine neurons run through the regions of the brain that regulate these functions.

  Recently, it has been speculated that dopamine may even regulate the overall output of the cortex. A problem with the use of the catecholamines by the frontal areas would account for the lack of impulse control, the attention problems, and learning problems. And although it is more than probable that other neurotransmitters and other brain structures influence the expression of ADD, the catecholamine-frontal area relationship is too clearly illustrative of ADD characteristics to dismiss.

  Interestingly enough, the role of working memory may be significant in the ADD syndrome. As investigated and defined by Patricia Goldman-Rakic, working memory could be the cause of many of the clinical manifestations of the syndrome, since working memory controls our ability to review our past experience, evaluate our current experience, and plan for the future. Rakic vividly describes what would happen if working memory were to fail: the world would be viewed by the brain as a series of disconnected events, like a series of unrelated slides, rather than as a continuous sequence, like a movie. We have heard the world as poignantly described by our patients with ADD, sometimes in the same words. Life seems discontinuous. There is no sense of history. Each new experience is met cold.

  As is known by clinicians who work with the ADD population, and by parents of ADD children, and by adults who have ADD, one of the most frustrating aspects of ADD is the inability to profit from one’s experience, the inability to focus on consequences, the inability to navigate through tasks or social situations or the world at large
by using what has been learned previously. If working memory is expressed in the frontal areas of the brain, and if the frontal areas of people with ADD are underactive, could we conclude that people with ADD have impaired working memory? Probably not conclusively. Yet future research might prove this, as our methods of investigation and measurement become more sophisticated.

  What none of this explains is why ADD seems to run in families and seems to be passed down through the generations. Most of the studies that have examined the familial risk of ADD have been epidemiological, either looking at the incidence of ADD in parents, offspring, and siblings, or looking at its preponderance among fraternal and identical twins. The work of Joseph Biederman and colleagues has shown that up to about 30 percent of parents of ADD children have ADD themselves. Other researchers have found a similar rate of ADD among parents. Research also indicates that relatives of ADD children have a greater risk for ADD than the relatives of controls. No research to date has been able to investigate the statistical likelihood that ADD adults will have ADD children, though existing research, and scientific intuition, leads us to believe that if you have ADD, there is certainly an increased probability that one of your children will have ADD. What we cannot do as yet is put a number on that increased probability.

  Twin studies repeatedly find higher rates of ADD in identical twins as compared to fraternal twins. What does this really mean? Fraternal twins are genetically related in the same way as siblings are—the only difference being that fraternal twins share the same environment for the first nine months of development. Identical twins, on the other hand, share not only the same prenatal and postnatal environment, but also the same genetic material. A higher incidence of ADD in people who share the same genetic blueprint, versus those who share everything but, means that the genetic makeup of the individual must be influencing the expression of the disorder. One large study (127 sets of identical twins and 111 sets of fraternal twins) recently found that in 51 percent of the identical sets both twins had ADD, while only 33 percent of those in the fraternal group shared the ADD diagnosis.

  We might wonder why we don’t see 100 percent concordance in identical twins. Nobody seems to know the answer. Identical-twin studies of most genetically based disorders, including schizophrenia, show about a 50 percent concordance rate. The ADD twin studies reflect this same pattern and are considered to be valid evidence that there is a genetic predisposition to the disorder.

  The strongest evidence for the genetic underpinnings of ADD may be yet to come. As we saw when looking at the progression of research into the neurobiology of ADD, solid scientific inquiry usually begins with speculation, advances through testable hypotheses and replicable findings, and culminates in empirical evidence. The work of Biederman and others confirms that something genetic is happening in this disorder. But what is it? One of the first clues might be contained in a controversial 1991 study published in the Journal of the American Medical Association by a nationwide team of investigators headed by David Comings and Brenda Comings. This study considered the role played by a particular dopamine receptor in neuropsychiatric disorders. The receptor, called the D2 receptor, is made by a particular gene. The gene has been implicated in early-onset hereditary alcoholism. Scientists have postulated that it may be associated with a number of other psychiatric disorders.

  The team used a sample of more than three hundred people. They discovered that the gene was found more frequently in patients with Tourette’s syndrome, ADD, autism, and alcoholism than in those without. The investigators do not claim in their report that the gene is the primary cause of the preceding disorders. But they do claim it is a modifying gene—a gene that makes some neuropsychiatric disorders worse if these disorders already are present, due to some unknown, primary gene. The Comings team concludes that their study supports a genetic basis for ADD. Although some researchers do not agree with the findings for various technical reasons, the study may signal the next wave of sophistication determining the genetic basis of ADD by linking it with other kinds of disorders. For example, if one base gene governs a certain brain formation, it may be that other modifying genes can produce a variety of syndromes by playing variations, so to speak, on the formation governed by the basic gene.

  At the least, current evidence supports the contention that ADD is a syndrome of genetic origin where one’s biological system has experienced some kind of change—be it chemical, neuroanatomical, or maturational—and has been rendered out of balance. It is the lack of balance, the dysregulation of the body’s neurobiological system, that impairs one’s ability to pay selective attention to one’s surroundings. The world becomes a land without street signs, the individual a car in bad need of a tune-up. The vastness of the attentional system partially accounts for the variation of ADD “types.” Where one individual needs an oil change, the next needs spark plugs replaced. Where one individual is withdrawn and overwhelmed by stimuli, the next is hyperactive and can’t get enough stimuli. Where one is frequently anxious, the other is depressed. To compensate, each develops his or her own coping strategies that developmentally add to, or subtract from, the brain’s various subsystems. So Mr. A becomes a stand-up comedian, and manic. Ms. B becomes an architectural wizard with obsessive-compulsive traits. Their offspring become a sculptor and a stunt pilot. None of them can balance their checkbook. And all of them wish they had more time in the day.

  With such diversity in the disorder, can we encompass and describe ADD in a way that is in line with research and clinical experience, and also allows us to illustrate and sort out the many symptoms and test results that we find in ADD? There are several schools of thought on the best way to understand the actual deficit in attention that plagues individuals with ADD. Each has its merit and each can serve as a metaphor for the syndrome. For instance, Paul Wender, in the early seventies, proposed that ADD was due to a decreased activation of the brain’s reward center and its connections. He believes the ADD person’s insensitivity to consequences arises from an inability to be “conditioned” with praise and punishment because of lowered activity in the neural systems that modulate reward-and-punishment responses. Wender’s argument is compelling, since it explains so many of the behavioral problems we see in ADD, and it is consistent with neuroanatomical and neurochemical studies.

  Russell Barkley similarly describes the primary problem in ADD as a deficit in the motivation system, which makes it impossible to stay on task for any length of time unless there is constant feedback, constant reward. Barkley’s work is often misunderstood and taken to mean that the child or adult is unmotivated and, therefore, lazy. But there is a difference between labeling someone as unmotivated and labeling someone as lacking the biological predisposition to stay on task without frequent reminders: one is a value judgement, the other a description of a neurological disorder. “There is no ADD while playing Nintendo,” Dr. Barkley is fond of saying, not meaning, of course, that the child will be motivated only in desirable situations, but that the rapid, ever-compelling, visually complex nature of the video game, and its constant rewards, sufficiently engage the child to rivet attention.

  Low activity in the frontal areas of the brain could explain the breakdown in goal-directed behavior and self-regulation as described by Barkley. If there is a problem in maturation or a problem in regulation of the frontal lobes and the systems that feed into them, the internal cues that keep us on task and focused on an outcome would not be loud enough or strong enough or good enough. There is another group of researchers that views the deficits in attention as a problem with arousal in the brain system. This group similarly believes that the messages ADD folks are getting are not loud enough or good enough, but they believe it’s due to the receipt of external cues, or to the lack of receipt of external cues, rather than due to a lack of internal ones.

  Larry Silver, a renowned figure for many years in the field of ADD, describes the syndrome as a faulty filter system in the lower parts of the brain known as the reticular act
ivating system. In Silver’s model this injured filter system, which is regulated by the catecholamines, doesn’t screen out irrelevant information and sensory stimuli as efficiently as it should, thereby letting everything that registers at the desk of the reticular activating system arrive in the rooms of the frontal regions of the brain. The individual is bombarded, taking care of ten thousand guests in a hotel built for one thousand, on overload all the time, receiving messages about every minute aspect of his or her experience. It is no wonder, then, that the individual would be distractible or, as Silver would argue, inclined to withdraw from it all and shut the damned hotel down.

  Another way to understand ADD is to think in terms of underarousal of the brain system. According to this view, the person with ADD does not receive enough input from the lower area of the brain to the frontal areas. Thus the distractible, hyperactive, and risk-taking behavior of ADD attempts to heighten the level of arousal in the frontal cortex. The optimal-arousal theory, as this is sometimes called, underlies some very effective and innovative learning strategies. Sydney Zentall believes that heightening the power of relevant stimuli allows the child to learn much more effectively. Because children with ADD notice and usually attend to novel stimuli, a key to educating these kids is to “dress up” educational lessons and tools with colors, animation, and diversity, while limiting all extraneous stimuli and opportunities for distraction. We have seen this strategy work in adults with ADD, as well. For example, color-coded notes, files, keys, etc., often help the adult get organized. Dr. Zentall, describing the management of her own ADD, talks of carrying small toys around in her pocketbook with which to amuse herself during boring meetings or times of low stimulation. One of the most engaging and lively of all researchers in the field of ADD, Zentall has concocted many practical ways to enhance novelty and stimulation in everyday life, such as taking notes on her own thoughts while listening to other people talk, doing at least two things at once while listening to a lecture, or adding as much color and other visual pizzazz to one’s surroundings as possible.