Catechol-O-methyltransferase Val158-Met polymorphism and a response of hyperactive-impulsive symptoms to methylphenidate: A replication study from South Korea.
We investigated the association between the catechol-O-methyltransferase (COMT) Val(158)-Met (rs4680) genotype and both subjective and objective treatment responses to methylphenidate in Korean children with attention-deficit/hyperactivity disorder (ADHD). We enrolled 120 medication-naïve children with ADHD in an open-label, 8-week trial of methylphenidate. The participants were genotyped and evaluated using the Clinical Global Impression Scale and the ADHD Rating Scale-IV (ADHD-RS), and completed the Continuous Performance Test (CPT) before and after treatment. We found a significant association between the COMT Val/Val genotype and a good response, in terms of hyperactive-impulsive scores on the ADHD-RS (odds ratio (OR) = 2.61; p = 0.044) and response-time variability on the CPT (OR = 2.66; p = 0.028). The association of the COMT Val/Val genotype with a good response, in terms of response time variability, was significant in both the sub-sample of combined-type (OR = 3.45; p = 0.026) and sub-sample of inattentive-type (OR = 5.52; p = 0.029); but the association with a good response in terms of hyperactive-impulsive scores was not significant in sub-sample analyses. Although the reported nominally significant associations did not stay significant after correcting for multiple testing, our results support previous findings about the possible involvement of the COMT (Val(158)-Met) polymorphism in the treatment response to methylphenidate in children with ADHD.
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Subin
S
Park
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jae-Won
JW
Kim
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Bung-Nyun
BN
Kim
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Min-Sup
MS
Shin
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea.
Hee-Jeong
HJ
Yoo
Division of Child and Adolescent Psychiatry, Department of Psychiatry, Seoul National University College of Medicine, Seoul, Republic of Korea soochurl@snu.ac.kr.
Soo-Churl
SC
Cho
D000293:Adolescent; D000294:Adolescent Behavior / Q000187:drug effects*; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000523:psychology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D002648:Child; D002652:Child Behavior / Q000187:drug effects*; D005260:Female; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D016017:Odds Ratio; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D056910:Republic of Korea; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
Attention deficit hyperactivity disorder; catechol-O-methyltransferase; drug response; effectiveness; genotype; methylphenidate