DAT1 methylation is associated with methylphenidate response on oppositional and hyperactive-impulsive symptoms in children and adolescents with ADHD.
To examine the association of the DNA methylation of DAT1 and DRD4 gene with methylphenidate (MPH) response in attention deficit hyperactivity disorder (ADHD).



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.



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.



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.
a Department of Psychiatry , The First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
Kaijing
K
Ding
b Department of Psychiatry , The Second Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
Jianzhong
J
Yang
c BMRC, Sheffield Hallam University , Howard Street , Sheffield , UK.
Gavin P
GP
Reynolds
d State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology , Chinese Academy of Sciences (CAS) , Kunming , Yunnan , PR China.
Bing
B
Chen
d State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology , Chinese Academy of Sciences (CAS) , Kunming , Yunnan , PR China.
Jingru
J
Shao
a Department of Psychiatry , The First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
Ruixiang
R
Liu
e National Clinical Research Centre for Mental Disorders, Peking University Sixth Hospital , Beijing , PR China.
Qiujin
Q
Qian
a Department of Psychiatry , The First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
Hua
H
Liu
a Department of Psychiatry , The First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
Runxu
R
Yang
d State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology , Chinese Academy of Sciences (CAS) , Kunming , Yunnan , PR China.
Jianfan
J
Wen
a Department of Psychiatry , The First Affiliated Hospital of Kunming Medical University , Kunming , Yunnan , PR China.
Chuanyuan
C
Kang
D019958:Attention Deficit and Disruptive Behavior Disorders / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D019175:DNA Methylation; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000008:administration & dosage / Q000494:pharmacology*; D017063:Outcome Assessment, Health Care; D050638:Receptors, Dopamine D4 / Q000235:genetics
C493599:DRD4 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D018765:Dopamine Uptake Inhibitors; C493214:SLC6A3 protein, human; D050638:Receptors, Dopamine D4; D008774:Methylphenidate
Attention deficit hyperactivity disorder; DNA methylation; dopamine receptor D4 gene (DRD4); dopamine transporter gene (DAT1/SLC6A3); methylphenidate efficacy