Genetics - Attention-deficit and Disruptive Behavior Disorders

Genetics

Research data support the familial transmission of ADHD and CD and suggest that these disorders may share common famil-ial vulnerabilities (Biederman et al., 1992). Estimates of heritability range from 60 to 80% for ADHD (Sherman et al., 1997) and from 30 to 70% for CD (Slutske et al., 1997).

Newer molecular genetic studies have identified a number of individual genes as potential candidate genes in the AD-DBDs. Evidence of altered DA activity in ADHD has focused on the search for candidate genes among DA system genes, including the DA D2, DA D4 and DA D5 receptor genes and the DA trans-porter gene (DAT1; with the strongest evidence for the 7-repeat allele of DRD4 (Swanson et al., 1998), which mediates a blunted intracellular response to DA, and the 10-repeat allele of DAT1 (Daly et al., 1999), which is linked to elevated DA reuptake. Preliminary data have also linked the 10-repeat allele of DAT1 with poor response to methylphenidate (Winsberg and Comings, 1999), which acts primarily by inhibiting the DA transporter in the striatum.

Several 5-HT system genes have been identified as candi-dates for study in CD. These include the genes encoding the en-zymes tryptophan hydroxylase (TPH)) and monoamine oxidase A (MAOA), which are involved in the synthesis and metabolism of 5-HT, respectively.