PT552. Association of the GRIN2B rs2284411 polymorphism with methylphenidate response in attention-deficit/hyperactivity disorder

Abstract

Abstract Objective: Animal studies suggest the involvement of N-methyl-D-aspartate (NMDA) receptors as a novel mechanism of methylphenidate (MPH). We investigated the association between the NMDA subunit 2B gene (GRIN2B) and the treatment response to MPH in attention-deficit/hyperactivity disorder (ADHD). Methods: A total of 75 ADHD patients aged 6–17 years completed the pre- and post-treatment assessments after 6 months of MPH administration. Treatment response was defined by changes in scores on the parent version 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 rs2284411 polymorphism with treatment response was analyzed using a series of logistic regression analyses. Results: There was a significant genotype effect in treatment response as assessed by ADHD-RS inattention (p = 0.009), hyperactivity-impulsivity (p = 0.028), and total (p = 0.023) scores, and in the CGI-I scores (p = 0.009) after adjusting for age, sex, IQ, baseline Clinical Global Impression – Severity score, baseline ADHD-RS total score, and final MPH dose. When using a stricter standard, the C/C genotype was associated with greater improvement in ADHD-RS inattention and CGI-I (p = 0.026), ADHD-RS hyperactivity-impulsivity and CGI-I (p = 0.017), and ADHD-RS total and CGI-I (p = 0.048) scores. Improvement in response time variability scores of the CPT differed between GRIN2B genotypes (p < 0.001). Conclusions: The results suggest that the GRINB rs2284411 genotype may be an important predictor of MPH response in ADHD. Further placebo-controlled randomized studies with larger samples are required.