Association of the GRIN2B rs2284411 polymorphism with methylphenidate response in attention-deficit/hyperactivity disorder.
We investigated the possible association between two NMDA subunit gene polymorphisms (GRIN2B rs2284411 and GRIN2A rs2229193) and treatment response to methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD).



A total of 75 ADHD patients aged 6-17 years underwent 6 months of MPH administration. Treatment response was defined by changes in scores of the ADHD-IV Rating Scale (ADHD-RS), clinician-rated Clinical Global Impression-Improvement (CGI-I), and Continuous Performance Test (CPT). The association of the GRIN2B and GRIN2A polymorphisms with treatment response was analyzed using logistic regression analyses.



The GRIN2B rs2284411 C/C genotype showed significantly better treatment response as assessed by ADHD-RS inattention ( p=0.009) and CGI-I scores ( p=0.009), and there was a nominally significant association in regard to ADHD-RS hyperactivity-impulsivity ( p=0.028) and total ( p=0.023) scores, after adjusting for age, sex, IQ, baseline Clinical Global Impression-Severity (CGI-S) score, baseline ADHD-RS total score, and final MPH dose. The GRIN2B C/C genotype also showed greater improvement at the CPT response time variability ( p<0.001). The GRIN2A G/G genotype was associated with a greater improvement in commission errors of the CPT compared to the G/A genotype ( p=0.001).



The results suggest that the GRIN2B rs2284411 genotype may be an important predictor of MPH response in ADHD.
1 Department of Research Planning, Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea.
Johanna I
JI
Kim
1 Department of Research Planning, Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea.
Jae-Won
JW
Kim
2 Animal Genomics and Bioinformatics Division, National Institute of Animal Science, Wanju, Republic of Korea.
Jong-Eun
JE
Park
3 Department of Psychiatry, Seoul National Hospital, Seoul, Republic of Korea.
Subin
S
Park
1 Department of Research Planning, Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea.
Soon-Beom
SB
Hong
4 Department of Psychiatry, College of Medicine, Chung Ang University, Seoul, Republic of Korea.
Doug Hyun
DH
Han
5 Uimyung Research Institute for Neuroscience, Sahmyook University, Seoul, Republic of Korea.
Jae Hoon
JH
Cheong
1 Department of Research Planning, Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea.
Jae-Won
JW
Choi
1 Department of Research Planning, Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea.
Sumin
S
Lee
1 Department of Research Planning, Mental Health Research Institute, National Center for Mental Health, Seoul, Republic of Korea.
Bung-Nyun
BN
Kim
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy* / Q000235:genetics*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000627:therapeutic use*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic / Q000235:genetics*; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics*; D016896:Treatment Outcome
D000697:Central Nervous System Stimulants; D008774:Methylphenidate; D016194:Receptors, N-Methyl-D-Aspartate; C121001:NR2B NMDA receptor
Attention-deficit/hyperactivity disorder; glutamate receptors; methylphenidate; pharmacogenetics