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Treatment Response Studied in Attention-Deficit Disorder

Glutaminergic, noradrenergic genes may be linked to response to methylphenidate

MONDAY, Jan. 12 (HealthDay News) -- Variability in response to methylphenidate treatment for attention-deficit/hyperactivity disorder (ADHD) is likely not due to common genes of large effects, according to research published Dec. 5 in a special issue of the American Journal of Medical Genetics Part B.

Eric Mick, of Massachusetts General Hospital and Harvard Medical School in Boston, and colleagues analyzed data from a genome-wide association study of a group of children whose dermal response to a methylphenidate transdermal system was assessed. The subjects were 187 children with ADHD, mean age 9.2 years, who provided DNA samples via buccal swab. The investigators tested 319,722 single-nucleotide polymorphisms for association with change in ADHD Rating Scale-IV score linked to treatment.

No markers were found to be significantly associated, the researchers report. However, the investigators found evidence pointing to novel genes in methylphenidate response. Of most interest was the metabotropic glutamate receptor 7 gene, which is expressed in brain structures previously linked to ADHD. Evidence also suggested that two SNPs in the norepinephrine transporter gene (NET, SLC6A2) were associated.

"Moderately positive associations provide suggestive evidence that both glutaminergic and noradrenergic genes may be associated with methylphenidate response, but these conclusions should be viewed as preliminary until replicated. Clearly, more pharmacogenetic studies of interesting candidates and genome-wide pharmacogenomic studies of larger samples need to be conducted," the authors write.

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