Attention-deficit/hyperactivity disorder: advancing on pharmacogenomics.
Attention-deficit/hyperactivity disorder (ADHD) is a highly prevalent psychiatric disorder. An impressive volume of literature documents both a strong participation of genetics in its etiology and a high rate of response to medication. However, few studies on the pharmacogenomics of ADHD have been conducted to date. This systematic review aims to present a critical discussion of findings from recent investigations. The majority of studies have focused on individual polymorphisms of the dopaminergic genes, with special emphasis on variants of the dopamine transporter gene (DAT1). Almost all studies have assessed the effects of genes in the response to methylphenidate (MPH). Some preliminary results suggest an association between homozygosity for the 10-repeat allele at DAT1 and poor response to MPH. However, other studies have reported contrasting findings. Very few investigations addressed the role of non-dopaminergic genes or gene-gene interactions in ADHD pharmacogenomics. Recent findings suggesting an association between response to MPH and an MspI polymorphism in the promoter region of the alpha2A-adrenoceptor gene (ADRA2A) are discussed. Pharmacogenomic studies of ADHD are in their infancy, and comparability between studies is difficult due to the use of different methodological approaches. As such, multi-site collaborative efforts to obtain larger samples with standardized methodology should be encouraged.
Polanczyk
Guilherme
G
Federal University of Rio Grande do Sul, ADHD Out-Patient Clinic, Child and Adolescent Psychiatric Division, Hospital de Clínicas de Porto Alegre, Brazil.
Zeni
Cristian
C
Genro
Julia P
JP
Roman
Tatiana
T
Hutz
Mara H
MH
Rohde
Luis Augusto
LA
D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D018765:Dopamine Uptake Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008774:Methylphenidate / Q000627:therapeutic use*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic
D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; C493214:SLC6A3 protein, human; D008774:Methylphenidate