Molecular genetic studies of ADHD: 1991 to 2004

Abstract

Attention deficit hyperactivity disorder (ADHD) is highly heritable but is likely a complex disorder involving multiple genes of moderate effect (Smalley [1997: Am J Hum Genet 60:1276-1282). Over 100 studies have examined the genetics of ADHD by linkage or association, though no article has presented a comprehensive overview of all published reports. We reviewed all ADHD studies, including 3 genome-wide linkage studies, and association studies of 94 polymorphisms in 33 candidate genes. To simplify comparisons across heterogeneous articles, demographics and comorbidity were ignored; analyses of subtype and haplotypes were excluded; and only the most positive finding for each polymorphism in a study was reported. Thirty-six percent of all findings were positive (P 0.05), 17% were trends (0.05 < P 0.15), and 47% were negative (P > 0.15). Studies utilizing dimensional measures of ADHD tended to result in higher rates of positive findings than those using categorical diagnoses (x 2 ¼ 5.6, P ¼ 0.018), and case-control studies tended to result in higher rates of positive findings than family-based studies (x 2 ¼ 18.8, P < 0.001). However, for either dichotomy, no significant difference remained when analyzing only studies using both methods within the same population and polymorphism. Evidence for association exists for four genes in ADHD: the dopamine D4 and D5 receptors, and the dopamine and serotonin transporters; others are promising but need further replication, including the dopamine D2 and serotonin 2A receptors. All candidate gene approaches continue to face the problem of relatively low power, given modest odds ratios for even the best replicated genes.

Association between symptoms of attention-deficit/hyperactivity disorder and bulimic behaviors in a clinical sample of severely obese adolescents

“…Several studies suggest a role of altered DRD4 and DRD2 in ADHD as well (although the alterations in DRD2 has not been replicated in other studies). 40 Given the inconsistency in the above-mentioned genetic studies, the hypothesis of common genetic alterations in bulimic behaviors and ADHD must be considered with caution, at least at the present time. Another potential common neurobiological mechanism involves alterations in the brain-derived neurotrophic factor (BDNF) gene.…”

Serotonin transporter polymorphism moderates the effects of caregiver intrusiveness on ADHD symptoms among institutionalized preschoolers

“…There is considerable evidence that genetic factors are important in the etiology of ADHD [13,14]. Like most complex disorders, ADHD is presumed to have a polygenic etiology.…”

Regional differences in cerebral perfusion associated with the α-2A-adrenergic receptor genotypes in attention deficit hyperactivity disorder

“…2,8 Although genes in the dopaminergic system have been most extensively studied in ADHD, recent studies have focused on genes in the noradrenergic and serotonergic systems. 9,10 This evidence suggests that noradrenergic dysregulation and, more specifically, alterations in α-2A-adrenergic receptor function are involved in the pathophysiology of ADHD. As a result, the α-2A-adrenergic receptor gene (ADRA2A) is potentially associated with this disorder.…”