The etiology of attention deficit hyperactivity disorder (ADHD) is unknown. It probably results from the interplay of genetic and environmental factors.

The positive response of the core symptoms of ADHD to medications suggests a biochemical basis for the disease. The effectiveness of a variety of different compounds in reducing symptoms suggests an etiology in more than one neurotransmitter system. Changes in the dopaminergic and noradrenergic systems are necessary for clinical efficacy of medications in this disorder.

Genetic factors have been implicated as a cause of ADHD. Goodman and Stevenson54,55 examined 570 twin pairs and, based on questionnaire data, found that concordance with ADHD was 51% in monozygotic twins and 33% in dizygotic twins. In a study of twins using DSM criteria, structured interviews, and parent and teacher ratings, similar conclusions were reached.56 Adoption studies in conjunction with twin studies suggest that the heritability of ADHD is between 0.60 and 0.80. Increasing evidence implicates polymorphisms of the dopamine receptor genes DRD2 and DRD4 and the dopamine transporter gene DAT1 in the genesis of ADHD.57

A variety of neuroimaging studies have investigated the pathophysiology of ADHD. Many of these have been structural CT (computed tomography) or MRI (magnetic resonance imaging) studies. These studies have implicated abnormalities in the right frontal cortex and smaller subcortical structures.58 Functional brain imaging studies, including PET (positron emission tomography) and regional cerebral blood flow studies, generally also implicate the frontosubcortical system.

A number of theories have been related to environmental causes:

• Theories that food additives47 and excessive sugar48 have a role in the genesis of ADHD have not been supported by most scientific studies.
• Prenatal exposure to alcohol is highly correlated with ADHD symptoms.51
• Early studies suggested that high lead levels could lead to marked distractibility,49 but later studies found that the effects of lead were greatest in the lowest socioeconomic groups and were correlated with prenatal exposure to alcohol.50

Several studies examining the effect of other prenatal or perinatal events on the risk of developing ADHD found minimal evidence that these factors are contributing.52

A variety of family and social environmental factors, including marital distress and family dysfunction, have been implicated as risk factors for developing or modifying the course of childhood psychiatric disorders. However, no clear-cut evidence links these factors specifically to ADHD.53

Adapted from: Hirsch GS and Koplewicz HS. Attention-deficit hyperactivity disorder. In: Devinsky O and Westbrook LE, eds. Epilepsy and Developmental Disabilities. Boston: Butterworth-Heinemann; 2001;187–204.
With permission from Elsevier (www.elsevier.com).
Reviewed and revised June 2004 by Steven C. Schachter, MD, epilepsy.com Editorial Board.