DAT1 methylation is associated with methylphenidate response on oppositional and hyperactive-impulsive symptoms in children and adolescents with ADHD. (19th May 2017)

• Record Type: Journal Article
• Authors: Ding, Kaijing; Yang, Jianzhong; Reynolds, Gavin P.; Chen, Bing; Shao, Jingru; Liu, Ruixiang; Qian, Qiujin; Liu, Hua; Yang, Runxu; Wen, Jianfan; Kang, Chuanyuan
• Is Part Of: World journal of biological psychiatry. Volume 18:Number 4(2017)
• Page Start: 291
• Page End: 299
• Publication Date: 2017-05-19
• Subjects: Attention deficit hyperactivity disorder -- DNA methylation -- dopamine transporter gene (DAT1/SLC6A3) -- dopamine receptor D4 gene (DRD4) -- methylphenidate efficacy; Biological psychiatry -- Periodicals; Biological Psychiatry -- Periodicals; 616.89
• DOI: 10.1080/15622975.2016.1224928
• Languages: English
• ISSNs: 1562-2975

Abstract

Abstract: Objectives: To examine the association of the DNA methylation of DAT1 and DRD4 gene with methylphenidate (MPH) response in attention deficit hyperactivity disorder (ADHD). Methods: One hundred and eleven DSM-IV defined ADHD Chinese Han children were recruited. Inattention, hyperactivity–impulsivity and oppositional symptoms were evaluated by the Swanson, Nolan and Pelham–IV–parent rating scale (SNAP-IV-P) at baseline and 6 weeks after MPH treatment. DNA methylation of CpG sites in the promoter sequences of DAT1 and DRD4 was examined for association with treatment response. Results: Greater improvement on the SNAP-IV-P total score and percentage change from baseline score were both significantly correlated with DAT1 methylation (rho =−0.222, P = .019 and rho = −0.203, P = .032, respectively). A secondary analysis demonstrated that the effect of DAT1 methylation on symptom response was primarily related to the percentage change in oppositional symptoms (rho = −0.242; P = .012), with a smaller significant effect on hyperactivity–impulsivity (rho = −0.192; P = .045). No significant correlation was found between the treatment effect on inattention and DAT1 methylation (rho = −0.101; P = .292). No significant correlation was observed between mean DRD4 methylation and measures of treatment outcome or baseline symptoms. Conclusions: Our findings provide initial evidence for the involvement of the epigenetic alterations of DAT1 in modulating the response to MPH treatment in ADHD, primarily on oppositional and hyperactive-impulsive symptoms.