주의력결핍 과잉행동장애에서 도파민 운반체 유전자의 10-Repeat Allele Homozygosity와 [123I]IPT SPECT로 측정한 도파민 운반체 밀도가 Methylphenidate 치료 반응에 미치는 영향

Effect of Homozygosity for 10-Repeat Allele at Dopamine Transporter Gene and Dopamine Transporter Density Assessed with [123I]IPT SPECT on Response to Methylphenidate Treatment in Attention Deficit Hyperactivity Disorder

Objectives：The symptoms of attention-deficit/hyperactivity disorder (ADHD) can be treated with methylphenidate, a potent blocker of the dopamine transporter (DAT). The homozygosity of the 10-repeat allele at dopamine transporter gene (DAT1) seems to be associated with a poor response to methylphenidate (MPH) in children with ADHD. In present study, we investigated association between DAT density using I-123N-(3-iodopropen-2-yl)-2β-carbomethoxy-3beta-(4-chlorophenyl)tropane ([123I]IPT SPECT) and the homozygosity for 10-repeat allele at DAT1, and response to MPH in children with ADHD. Methods：Eleven drug-naive children with ADHD were included in the study and treated with MPH for about 8 weeks. After the genotyping and SPECT were performed, we compared DAT density between ADHD children with and without the homozygosity for the 10-repeat allele at DAT1 and investigated correlation between the homozygosity for the 10-repeat allele and response to MPH. Results：ADHD children with 10/10 genotype (n=7) had a significantly higher DAT density in basal ganglia than the children without 10/10 genotype (n=4)(Right：z=-2.65, p=0.008；Left：z=-2.65, p=0.008). We found that while only 28.6% (2/7) of the subject with 10/10 genotype showed good response (≥50% improvement) to MPH treatment, 100% (4/4) of the subjects without 10/10 genotype showed good response to MPH treatment (χ2 test：F=5.238, df=1, p=0.022). Conclusion：Our findings support an association between homozygosity for the 10-repeat allele at DAT1 and the DAT density assessed in vivo and correlation between the homozygosity for the 10-repeat allele and poor response to MPH.