A current update on ADHD pharmacogenomics.
Pharmacological treatment for attention deficit hyperactivity disorder, although highly effective, presents a marked variability in clinical response, optimal dosage needed and tolerability. Clinical and neurobiological investigations have juxtaposed findings on both response to medication and etiologic factors, generating the hypothesis that genetic factors may underlie differences in treatment outcome. Over the last decade, research has focused on the catecholaminergic system to investigate a potential role of genotype on pharmacological effect. Despite an increasing number of associations reported (for methylphenidate, nine in 2005, 24 in 2008 and 52 reported in the current article), the identification of clinically relevant genetic predictors of treatment response remains a challenge. At present, additional studies are required to allow for a shift from a trial-and-error approach to a more rational pharmacologic regimen that takes into account the likelihood of treatment effectiveness at the individual level.
ADHD Program, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350-2201, Porto Alegre, RS, 90035-003, Brazil.
Christian
C
Kieling
Júlia P
JP
Genro
Mara H
MH
Hutz
Luis Augusto
LA
Rohde
D000293:Adolescent; D018759:Adrenergic Uptake Inhibitors / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069445:Atomoxetine Hydrochloride; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D002394:Catechol O-Methyltransferase / Q000235:genetics / Q000378:metabolism; D000697:Central Nervous System Stimulants / Q000493:pharmacokinetics / Q000627:therapeutic use; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008774:Methylphenidate / Q000493:pharmacokinetics / Q000627:therapeutic use; D010597:Pharmacogenetics; D011437:Propylamines / Q000493:pharmacokinetics / Q000627:therapeutic use; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000378:metabolism; D050638:Receptors, Dopamine D4 / Q000235:genetics / Q000378:metabolism
C547768:ADRA2A protein, human; D018759:Adrenergic Uptake Inhibitors; D000697:Central Nervous System Stimulants; C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D011437:Propylamines; D018341:Receptors, Adrenergic, alpha-2; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride; D002394:Catechol O-Methyltransferase