Pharmacogenetics of methylphenidate in childhood attention-deficit/hyperactivity disorder: long-term effects

Attention-deficit/hyperactivity disorder (ADHD) is a common neurodevelopmental disorder in which a significant proportion of patients do not respond to treatment. The objective of this study was to examine the role of genetic risk variants in the response to treatment with methylphenidate (MPH). The effectiveness of MPH was evaluated based on variations in the CGI-S and CGAS scales over a 12-month treatment period using linear mixed effects models. A total of 208 ADHD patients and 34 polymorphisms were included in the analysis. For both scales, the response was associated with time, extended-release MPH/both formulations, and previous MPH treatment. For the CGI-S scale, response was associated with SLC6A3 rs2550948, DRD4 promoter duplication, SNAP25 rs3746544, and ADGRL3 rs1868790. Interactions between the response over time and SLC6A3 and DRD2 were found in the CGI-S and CGAS scales, respectively. The proportion of the variance explained by the models was 18% for the CGI-S and 22% for the CGAS. In this long-term study, the effects of SLC6A3, DRD4, SNAP25, and ADGRL3 on response to treatment reflect those observed in previous studies. In addition, 2 previously unreported interactions with response to treatment over a 12-month period were found (SLC6A3 and DRD2).