Genetics of attention deficit/hyperactivity disorder (ADHD)

Genetics of attention deficit/hyperactivity disorder (ADHD) ADHD is the most common psychiatric disorder with onset in childhood. The condition is characterized by inattention and/or hyperactivity and impulsivity which is associated with cognitive, social and academic impairments. It has been estimated that in up to 60% of patients, these impairments persist into adulthood. Males are affected more than females (4:1). ADHD is a familial disorder with a population-based prevalence of about 10% and a prevalence rate in siblings of approximately 25%. Detailed studies of the disorder suggest that there is a five- to sixfold increase in firstdegree relatives of affected persons. However, as with other psychiatric disorders, the finding of familial aggregation alone does not necessarily lead to the conclusion that the disorder is of genetic origin as such studies do not separate genetic from environmental factors. Twin studies have been useful in discriminating the genetic from environmental factors. The concordance rate for monozygotic versus dizygotic twins has been estimated at 51% and 33% respectively, and it has been estimated that approximately half the variance in the trait factors of hyperactivity and inattentiveness are accounted for by the genetic basis of the disorder. There is evidence that, in ADHD, there is an incompletely penetrant autosomal-dominant gene; the penetrance of the gene being calculated as 46% in boys and 31% in girls. Molecular genetic studies have been particularly fruitful in evaluating the neurochemical basis of the disorder. Genes involved in the dopaminergic system were considered to be important as the most effective symptomatic treatment of the condition has been methylphenidate and dextroamphetamine, drugs which potentiate the release, and inhibit the reuptake, of dopamine.Of the genes for the dopamine receptors which have been studied, the candidate gene for the dopamine D4 receptor has been shown to be positively associated with ADHD. However, not all investigators have verified this finding. One of the major limitations in studies of the genetics of behavioural disorders in children arises from the overlap with other conditions. For example, nearly 50% of the patients with ADHD also have co-morbid conduct disorders. In addition, a subtype of the disorder may exist in those children in which the disorder persists into adulthood. An additional problem arises from the overlap between ADHD and bipolar disorder; this has been estimated to be as high as 16%. In CONCLUSION, although positive genetic studies have been reported and subsequently replicated, the results must be treated with caution as they are based on small sample sizes with restricted statistical power andcomplicated by co-morbid illnesses. Nevertheless, preliminary evidence suggests that ADHD, like many major psychiatric disorders, does have a genetic basis.