Another approach to understanding the process has been to study a strain of mice that have been genetically altered to eliminate a dopamine transporter gene. These animals display behavioral symptoms that are said to replicate those of ADHD in children and also to respond to stimulants, observations that implicate an abnormality of dopamine and serotonin. This idea is provocative because several genetic linkage studies have suggested an association between ADHD and a polymorphism of the gene that codes for the same dopamine transporter gene. Furthermore, copy number variations in genes that relate to development, a rich field for study in autism, give rise to global forms of cognitive delay that display prominent features of ADHD. Most of these are duplications or deletions that congregate on chromosomes 15 and 16.
Apart from the reports of parents and teachers and observation of the child, one is aided in the diagnosis of ADHD (and other learning disabilities) by psychometry. An observant psychologist, in performing intelligence tests, notes distractibility and difficulty in sustaining any activity. Erratic performance that is not the result of a defect in comprehension is also characteristic. The Vanderbilt Assessment Scale is a checklist that is completed with parents or teachers.
Treatment of ADHD The treatment of the hyperactive child can proceed reasonably only after medical and psychologic evaluations have clarified the context in which the hyperactivity occurs. If the child is hyperactive and inattentive mainly in school and less so in an unstructured environment, it may be that mild developmental delay or a specific cognitive deficiency or dyslexia, which prevents scholastic success, is a source of frustration and boredom. The child then turns to other activities that may happen to disturb the classroom. Or the hyperactive child may have failed to acquire self-control because of a disorganized home life, and the overactivity may be but one manifestation of anxiety or intolerance of constraint. Clearly problems such as these require a modification of the educational program.
For overactive children of normal intelligence who have failed to control their impulses, who at all times have boundless energy, require little sleep, exhibit a wriggling restlessness (the “choreiform syndrome” of Prechtl and Stemmer), and manifest incessant exploratory activity that repeatedly gets them into mischief, even to their own dismay, medical therapy is justified. Paradoxically, stimulants have a quieting effect on these children, whereas sedatives may do the opposite.
Methylphenidate is the drug most widely used and its use has been validated in several studies. Children weighing less than 30 kg are given 5 mg each morning on school days for 2 weeks, after which the dose can be raised to 5 mg morning and noon. Children weighing more than 30 kg can be given a single 20-mg sustained-release tablet each morning. If methylphenidate proves ineffective after several weeks or cannot be tolerated, dextroamphetamine 2.5 to 5 mg three times daily or a mixed amphetamine-dextroamphetamine is suitable substitute. Atomoxetine, a norepinephrine inhibitor, is also effective and is not classified as a stimulant but has caused a few cases of liver failure. If these agents control the activity and improve school performance (they can be continued for a number of years), there is then no need to alter the child’s school program. It is not clear if there should be a long-term concern about hypertension, but the blood pressure is not generally measured at frequent intervals. If stimulants are ineffective, tricyclic antidepressants, particularly desipramine, may be tried. Multiple medications should be generally avoided. Classroom behavioral conditioning techniques and psychotherapy may be needed for brief periods but are not as effective as medication. Remedial education is reserved for recalcitrant cases. Biederman and Faraone have summarized approaches to treatment.