Excerpted from Driven to Distraction (Touchstone 1994) Copyright Edward M. Hallowell, M.D. and John J. Ratey, M.D. Reprinted with permission.

In 1904 one of the world's most prestigious medical journals, the British journal Lancet published a little doggerel verse that might be the first published account of ADD in the medical literature.

The Story of Fidgety Philip

"Let me see if Philip can
Be a little gentleman;
Let me see if he is able
To sit still for once at the table."
Thus Papa bade Phil behave;
And Mama looked very grave.
But Fidgety Phil,
He won't sit still;
He wriggles,
And giggles,
And then, I declare,
Swings backwards and forwards,
And tilts up his chair,
Just like any rocking horse--
"Philip! I am getting cross!"
See the naughty, restless child
Growing still more rude and wild,
Till his chair falls over quite.
Philip screams with all his might,
Catches at the cloth, but then
That makes matters worse again.
Down upon the ground they fall,
Glasses, plates, knives, forks and all.
How Mama did fret and frown,
When she saw them tumbling down!
And Papa made such a face!
Philip is in sad disgrace . . .

The story might start with . . . George Frederic Still, M.D., who in 1902 described a group of twenty children who were defiant, excessively emotional, passionate, lawless, spiteful, and had little inhibitory volition. This group consisted of three boys for every girl, and their troubling behaviors all had appeared before the age of eight. What was most striking to Still was that this group of kids had been raised in benign environments, with "good-enough" parenting. Indeed, those children who had been subject to poor child-rearing were excluded from his analysis. He speculated, in light of the adequate rearing these children received, there might be a biological basis to the unbounded behavior, a genetically inherited proneness toward moral corruption. He gained confidence in his theory when he discovered that some members of these children's families had psychiatric difficulties such as depression, alcoholism, and conduct problems.

While it was certainly possible that the pathology was psychological only, and was passed down from generation to generation as a kind of family neurosis, Still proposed that genetics and biology should be considered at least as much as free will in assessing the cause of these children's problems. This was a new way of thinking.

Although it would be decades before there was conclusive evidence bearing Still out, his new way of thinking was pivotal. In the nineteenth century--and before--"bad" or uncontrollable behavior in children was seen as a moral failing. Either the parents or the children or both should be held responsible. The usual "treatment" for these children was physical punishment. Pediatric textbooks from that era are full of descriptions of how to beat a child and exhortations on the necessity of doing so. As clinicians began to speculate that neurology, rather than the devil, was governing behavior, a kinder, more effective approach to child-rearing emerged.

The puzzling contradiction between upbringing and behavior in this population of children captured the imagination of turn-of-the-century psychologists. Still's observations supported the theory of William James, the father of American psychology. James saw the deficits in what he called inhibitory volition, moral control, and sustained attention as being causally related to each other through an underlying neurological defect. Cautiously, he speculated on the possibility of either a decreased threshold in the brain for inhibition of response to various stimuli, or a syndrome of disconnection within the cortex of the brain in which intellect was dissociated from "will," or social conduct.

The trail of Still and James was picked up in 1934, when Eugene Kahn and Louis H. Cohen published a piece called "Organic Driveness" in the New England Journal of Medicine. Kahn and Cohen asserted that there was a biological cause for the hyperactive, impulse-ridden, morally immature behavior of the people they were seeing who had been hit by the encephalitis epidemic of 1917-18. This epidemic left some victims chronically immobile (as those described by Oliver Sacks in his book Awakenings) and others chronically insomniac, with impaired attention, impaired regulation of activity, and poor impulse control. In other words, the characteristics plaguing this latter group were what we now take to be the diagnostic triad of ADD symptoms: distractibility, impulsivity, and restlessness. Kahn and Cohen were the first to provide an elegant description of the relationship between an organic disease and the symptoms of ADD.

At about the same time, Charles Bradley was developing another line of evidence linking ADD-like symptoms to biological roots. In 1937, Bradley reported success in using benzedrine, a stimulant, to treat behaviorally disordered children. This was a serendipitous discovery that was quite counterintuitive; why should a stimulant help hyperactive children become less stimulated? Like many important discoverers in medicine, Bradley couldn't explain his discovery; he could only report its veracity.

Soon this population of children would be labeled MBD--minimal brain dysfunction--and treated with Ritalin and Cylert, two other stimulants that were found to have a dramatic effect on the behavioral and social symptoms of the syndrome. By 1957 there was an attempt to match the symptoms of what was by then called the "hyperkinetic syndrome" with a specific anatomical structure in the brain. Maurice Laufer, in Psychosomatic Medicine, placed the location of dysfunction at the thalamus, a midbrain structure. Laufer saw hyperkinesis as proof that the work of the thalamus which was to filter stimuli, had gone awry. Although his hypothesis was never proved, it did promote the conception of the disorder as one defined by an overactivity of a part of the brain.

Throughout the sixties, clinical skill with the hyperkinetic population improved, and the clinician's powers of observation grew more attuned to the nuances of the children's behavior. It became more apparent to the clinician's eye that the syndrome somehow was due to genetically based malfunctioning of biological systems rather than to bad parenting or bad behavior. The definition of the syndrome has evolved through family studies and statistical analysis of epidemiological data that absolve parents and children of blame (although the pernicious and unfair tendency to blame parents and children persists to this day among the ill informed).

By the early seventies the definition of the syndrome included not just the behaviorally evident hyperactivity, but also the more subtle symptoms of distractibility and impulsivity. By then, we knew that ADD clustered in families and was not caused by bad parenting. We knew that the symptoms were often improved by the use of stimulant medication. We thought we knew, but couldn't prove, that ADD had a biological basis, and that it was genetically transmitted. However, this more accurate and encompassing view was not accompanied by any major new discoveries related to the biological causes of the syndrome.

Due to the lack of further biological evidence, some people argued that ADD was a mythical disorder, an excuse contrived to exonerate reprobate children and their parents. As is usually the case in psychiatry, the intensity of the debate was inversely proportional to the availability of factual information.

As in a good mystery, the journey from suspicion to proof, from speculation to empirical evidence, from Kahn and Cohen to Paul Wender and Alan Zametkin and Rachel Gittleman-Klein and the other current researchers, has been riddled with false leads, multiple possibilities, contradictory findings, and many gut reactions of all kinds.

One of the first attempts to unite the effects of the stimulants with what we know about the brain was made by C. Kornetsky, who in 1970 proposed the Catecholamine Hypothesis of Hyperactivity. Catecholamines are a class of compounds that includes the neurotransmitters norepinephrine and dopamine. Since the stimulants affect the norepinephrine and dopamine neurotransmitter systems by increasing the amount of these neurotransmitters, Kornetsky concluded that ADD possibly was caused by an underproduction or underutilization of these neurotransmitters. Although this hypothesis is still tenable, biochemical studies and clinical tests of neurotransmitter metabolites in urine over the past two decades have not been able to document the specific role of the catecholamines in ADD.

No single neurotransmitter system may be the sole regulator of ADD. Neurons can convert dopamine into norepinephrine. Many of the drugs that act on the catecholamines act on serotonin. Some of the drugs that act on serotonin can act on norepinephrine and dopamine. And we can't rule out the role of other neurotransmitters like GABA (gamma amino butyric acid), which have showed up in some biochemical studies. The most likely possibility is that the effect of dopamine and norepinephrine and serotonin is key and drugs that alter these neurotransmitters will have the most telling effect on the symptomatology of ADD.

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?