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.

• Authors: Min-Hyeon Park, Jae-Won Kim, Young-Hui Yang, Soon-Beom Hong, Subin Park, Hyejin Kang, Boong-Nyun Kim, Min-Sup Shin, Hee Jeong Yoo, Soo-Churl Cho
• Journal: Neuroscience letters (Neurosci Lett) Vol. 514 Issue 2 Pg. 159-63 (Apr 18 2012) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 22405810 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Central Nervous System Stimulants
• Norepinephrine Plasma Membrane Transport Proteins
• Methylphenidate

Topics

• Attention Deficit Disorder with Hyperactivity (diagnostic imaging, drug therapy, genetics)
• Brain (diagnostic imaging, drug effects)
• Central Nervous System Stimulants (pharmacology, therapeutic use)
• Child
• Female
• Genotype
• Humans
• Male
• Methylphenidate (pharmacology, therapeutic use)
• Norepinephrine Plasma Membrane Transport Proteins (genetics)
• Polymorphism, Single Nucleotide
• Radionuclide Imaging
• Treatment Outcome