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.