Attention-Deficit Disorder
This disorder is most commonly found among school-age boys, who are at least four times more likely to express the symptoms than are young girls. These children have difficulty applying themselves to tasks that require a sustained mental effort, they can be easily distracted, they may have difficulty remaining seated without fidgeting and they may impulsively blurt out answers in the classroom or fail to wait their turn. Although normal children occasionally display these symptoms, attention-deficit disorder is diagnosed when the behavior's persistence and severity impedes the child's social development and education.Early speculation about the causes of attention-deficit disorder focused on potential sources of stress within the child's family, including marital discord, poor parenting, psychiatric illness, alcoholism or drug abuse. It has become progressively clear, however, that stress within the family cannot explain the incidence of the disorder. There is now little doubt that the disorder has a genetic basis.
Evidence in support of this notion comes from patterns of inheritance in the families of children with the disorder and from studies of identical twins. For example, consider instances in which full siblings and half-siblings (who have only half of the genetic identity of full siblings) are both raised in the same family environment. If the behavioral symptoms of attention-deficit disorder were "learned" in the family, then the incidence of the disorder should be the same for full siblings as it is for half-siblings. In fact, half-siblings of children with attention-deficit disorder have a significantly lower frequency of the disorder than full siblings (Lopez 1965). In another study, investigators found that if one identical twin had attention-deficit disorder, there was a 100 percent probability that the other also had the disorder. In contrast, the incidence of concordance among nonidentical twins was only 17 percent. This result has been supported by two other independent studies of identical twins (Willerman 1973). Finally, one of us (Comings) and his coworkers found that the A1 allele of the dopamine D2 receptor gene was present in 49 percent of the children with attention-deficit disorder compared to only 27 percent of the controls (Comings et al. 1991).
Some other recent work has linked attention-deficit disorder with another impulsive disorder: Tourette syndrome. More than 100 years ago the French neurologist Giles de la Tourette described a condition that was characterized by compulsive swearing, multiple muscle tics and loud noises. He found that the disorder usually appeared in children between 7 to 10 years old, with boys more likely to be affected than girls. Tourette suggested that the condition might be inherited.
In the early 1980s one of us (Comings) and his colleagues studied 246 families in which at least one member of the family had Tourette disorder. The study indicated that virtually all cases of Tourette syndrome are genetic (Comings et al. 1991). Subsequent studies also found that there was a high incidence of impulsive, compulsive, addictive, mood and anxiety disorders on both sides of the affected individual's family (Comings and Comings 1987). The A1 allele was implicated in a recent report showing that nearly 45 percent of the people diagnosed with Tourette disorder carried the aberrant gene (Comings et al. 1991). Moreover, the A1 allele had the highest incidence among people who had the severest manifestations of the disorder.
As mentioned earlier, Tourette syndrome appears to be tightly coupled to attention-deficit disorder. In studies of the two disorders, it was found that 50 to 80 percent of the people with Tourette syndrome also had attention-deficit disorder. Furthermore, an increased number of relatives of individuals with Tourette disorder also had attention-deficit/hyperactivity disorder (Knell and Comings 1993). It now appears that Tourette syndrome is a complex illness that may include attention-deficit disorder, conduct disorder, obsessive, compulsive and addictive disorders and other related disorders. The close coupling between these disorders has led one of us (Comings) to propose that Tourette syndrome is a severe form of attention-deficit disorder (Comings and Comings 1989; Comings 1995).
The high frequency of the A1 allele among people with Tourette syndrome and attention-deficit disorder raises the question of whether other genes affecting dopaminergic function might also be involved in these disorders. Two others that have been considered are the gene for the enzyme dopamine B-hydroxylase, which converts dopamine to norepinephrine, and the gene for the dopamine transporter, which takes dopamine back into the presynaptic terminal after it is released into the synapse. In both cases, variant forms of these genes are associated with Tourette syndrome (Comings et al. 1996c). The anomalous dopamine B-hydroxylase gene (the "DBH Taq B1" allele) was further associated with learning disabilities, conduct disorder and substance abuse, whereas the variant of the dopamine transporter (the "10 repeat" allele) was also associated with alcohol abuse, depression and obsessive-compulsive disorder. This observation was supported by other work showing that the 10 repeat allele for the dopamine transporter gene was associated with attention-deficit/hyperactivity disorder (Cook et al. 1995). Moreover, elevated levels of the dopamine transporter molecule have been found in the brains of patients with Tourette syndrome (Malison et al. 1995).
If these dopamine-related molecules are indeed associated with various behavioral disorders, it might be expected that having more than one variant would increase the severity or the likelihood of having a disorder. Indeed, this is the case: The severity of attention-deficit disorder, conduct disorder, substance abuse and mood disorders progressively increased from individuals carrying none of the genes to those who carried all three genes (Comings et al. 1996c).
Given the widespread prevalence of attention-deficit disorder among children, and its frequent association with alcoholism, drug dependence and other behavioral disorders, it may be that childhood attention-deficit disorder is a predisposing cause to various disorders among adults. For example, there is a significant correlation between attention-deficit hyperactivity disorder and adult drug abuse (Gittleman, Mannuzza, Shenker and Bonagura 1985).
