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Regional brain perfusion before and after treatment with methylphenidate may be associated with the G1287A polymorphism of the norepinephrine transporter gene in children with attention-deficit/hyperactivity disorder.

Abstract：

:The noradrenergic system modulates attention and arousal. Dysregulation of the noradrenergic system may be involved in the pathophysiology of attention-deficit/hyperactivity disorder (ADHD). This study intended to examine the differences in methylphenidate (MPH) treatment response and pre- and post-treatment cerebral perfusion associated with the G1287A and -3081(A/T) polymorphisms of the norepinephrine transporter (NET) gene in ADHD children. Thirty-seven drug-naïve ADHD children (8.9±1.8 years old, M=32, F=5) were genotyped. Next, baseline single-photon emission computed tomography (SPECT) and clinical assessments were carried out for ADHD subjects. After 8 weeks of MPH treatment, SPECT and clinical assessment were repeated. There were no differences in baseline clinical assessments or cerebral perfusion based on genotype. However, after treatment, ADHD children with the G/G genotype at the G1287A polymorphism showed more improvement in symptoms than children without the G/G genotype as evaluated by the Clinical Global Impressions-Improvement scale (p=0.022). Furthermore, ADHD children with the G/G genotype at the G1287A polymorphism showed hyperperfusion in the right inferior temporal gyrus (p<0.001, uncorrected) and middle temporal gyrus (p=0.001, uncorrected) compared to children without the G/G genotype. Although the results of this study should be interpreted cautiously, they suggest that polymorphisms of the NET gene may contribute to an intermediate phenotype. Further studies should clearly elucidate the relationship between treatment response and functional connectivity in the brain according to this genetic polymorphism.

journal_name

Neurosci Lett

journal_title

Neuroscience letters

authors

Park MH,Kim JW,Yang YH,Hong SB,Park S,Kang H,Kim BN,Shin MS,Yoo HJ,Cho SC

doi

10.1016/j.neulet.2012.02.079

subject

Has Abstract

pub_date

2012-04-18 00:00:00

pages

159-63

issue

eissn

0304-3940

issn

1872-7972

pii

S0304-3940(12)00305-9

journal_volume

514

pub_type

杂志文章

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Regional brain perfusion before and after treatment with methylphenidate may be associated with the G1287A polymorphism of the norepinephrine transporter gene in children with attention-deficit/hyperactivity disorder.