title: Epigenetic regulation of the DRD4 gene and dimensions of attention-deficit/hyperactivity disorder in children.
abstract: Recent evidence suggests that epigenetic regulation of the DRD4 gene may characterise specific aspects of ADHD symptomology. We tested associations between ADHD symptoms and epigenetic changes to the DRD4 gene in DNA extracted from blood and saliva in N = 330 children referred for a variety of behavioural and emotional problems. ADHD was indexed using DSM diagnoses as well as mother, father, and teacher reports. Methylation levels were assayed for the island of 18 CpG sites in the DRD4 receptor gene. A nearby SNP, rs3758653, was also genotyped as it has previously been shown to influence methylation levels. There was high consistency of methylation levels across CpG sites and tissue sources, and higher methylation levels were associated with the major allele of SNP rs3758653. Higher methylation levels were associated with more severe ADHD independent of SNP status, tissue source, ethnicity, environmental adversity, and comorbid conduct problems. The association applied specifically to the cognitive/attentional, rather than hyperactivity problems that characterise ADHD. The results indicate that epigenetic regulation of the DRD4 gene in the form of increased methylation is associated with the cognitive/attentional deficits in ADHD.
authors.affiliation: School of Psychology, University of New South Wales, Sydney, NSW, 2052, Australia. mark.dadds@sydney.edu.au.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Dadds
authors.affiliation: School of Psychology, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Olivia
authors.initials: O
authors.lastname: Schollar-Root
authors.affiliation: School of Psychology, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Rhoshel
authors.initials: R
authors.lastname: Lenroot
authors.affiliation: School of Psychology, University of New South Wales, Sydney, NSW, 2052, Australia.
authors.forename: Caroline
authors.initials: C
authors.lastname: Moul
authors.affiliation: University of Sydney, Sydney, NSW, 2006, Australia.
authors.forename: David J
authors.initials: DJ
authors.lastname: Hawes
mesh_terms: D000483:Alleles; D001288:Attention / Q000502:physiology*; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology; D002648:Child; D002675:Child, Preschool; D003071:Cognition / Q000502:physiology*; D044127:Epigenesis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D050638:Receptors, Dopamine D4 / Q000235:genetics*
chemical_list: D050638:Receptors, Dopamine D4
keywords: ADHD; Attention problems; Dopamine receptor; Epigenetic; Methylation