|Добавлено: Вт Ноя 03, 2009 11:20 pm Заголовок сообщения: Methylphenidate Response in Attention-Deficit/Hyperactivity|
|J Am Acad Child Adolesc Psychiatry. 2009 Oct 23. |
A Candidate Gene Analysis of Methylphenidate Response in Attention-Deficit/Hyperactivity Disorder.
McGough JJ, McCracken JT, Loo SK, Manganiello M, Leung MC, Tietjens JR, Trinh T, Baweja S, Suddath R, Smalley SL, Hellemann G, Sugar CA.
Drs. McGough, McCracken, and Suddath are with the Semel Institute for Neuroscience & Human Behavior and David Geffen School of Medicine at the University of California, Los Angeles. Drs. Loo and Smalley are with the Center for Neurobehavioral Genetics at the UCLA Semel Institute. Dr. Manganiello is with the Lahey Clinic. Mr. Leung is with the University of California, Davis, School of Medicine. Mr. Tietjens is with the Mount Sinai School of Medicine. Dr. Trinh is with the Pepperdine University Graduate School of Education and Psychology. Ms. Baweja is with the University of California, Los Angeles. Dr. Hellemann is with the Semel Institute Statistics Core. Dr. Sugar is with the Semel Institute Statistics Core and UCLA School of Public Health. At the time of this research, Drs. Manganiello and Trinh, Mr. Leung, and Mr. Tietjens were also with the University of California, Los Angeles.
OBJECTIVE:: This study examines the potential role of candidate genes in moderating treatment effects of methylphenidate (MPH) in attention-deficit/hyperactivity disorder (ADHD). METHOD:: Eighty-two subjects with ADHD aged 6 to 17 years participated in a prospective, double-blind, placebo-controlled, multiple-dose, crossover titration trial of immediate release MPH three times daily. The subjects were assessed on a variety of parent and clinician ratings and a laboratory math test. Data reduction based on principal components analysis identified statistically derived efficacy and side effect outcomes. RESULTS:: Attention-deficit/hyperactivity disorder symptom response was predicted by polymorphisms at the serotonin transporter (SLC6A4) intron 2 VNTR (p =.01), with a suggested trend for catechol-O-methyltransferase (COMT) (p =.04). Gene x dose interactions were noted on math test outcomes for the dopamine D4 receptor (DRD4) promoter (p =.008), DRD4 exon 3 VNTR (p =.006), and SLC6A4 promoter insertion/deletion polymorphism (5HTTLPR) (p =.02). Irritability was predicted by COMT (p =.02). Vegetative symptoms were predicted by 5HTTLPR (p =.003). No significant effects were noted for the dopamine transporter (SLC6A3) or synaptosomal-associated protein 25 (SNAP25). CONCLUSIONS:: This article confirms and expands previous studies suggesting that genes moderate ADHD treatment response. The ADHD outcomes are not unitary but reflect both behavioral and learning domains that are likely influenced by different genes. Future research should emphasize candidate gene and genome-wide association studies in larger samples, symptom reduction as well as side effects outcomes, and responses over full therapeutic dose ranges to assess differences in both gene and gene x dose interactive effects.
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