Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders
Autor: | Bhavik Shah, Erika L. Nurmi, Fiona Whelan, Lawrence Scahill, L. E. Arnold, K. K. Badashova, Benedetto Vitiello, Mark Davies, Christopher J. McDougle, Shirley Chuang, David J. Posey, James T. McCracken, Elaine Tierney, Michael G. Aman |
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Jazyk: | angličtina |
Rok vydání: | 2013 |
Předmět: |
medicine.medical_specialty
Child Development Disorders autism spectrum disorders dopamine genetics hyperactivity methylphenidate Attention Deficit Disorder with Hyperactivity Biogenic Monoamines Central Nervous System Stimulants Child Child Development Disorders Pervasive Humans Methylphenidate Pharmacology Molecular Medicine Genetics Medicine (all) Placebo 03 medical and health sciences 0302 clinical medicine Internal medicine Monoaminergic mental disorders medicine Pharmacology & Pharmacy Pervasive business.industry Pharmacology and Pharmaceutical Sciences medicine.disease Crossover study 030227 psychiatry 3. Good health Tolerability Autism Original Article Monoamine oxidase B business MET Positive 030217 neurology & neurosurgery medicine.drug |
Zdroj: | The Pharmacogenomics Journal The pharmacogenomics journal, vol 14, iss 3 |
ISSN: | 1473-1150 1470-269X |
Popis: | Methylphenidate (MPH) reduces hyperactive-impulsive symptoms common in children with autism spectrum disorders (ASDs), however, response and tolerability varies widely. We hypothesized monoaminergic gene variants may moderate MPH effects in ASD, as in typically developing children with attention-deficit/hyperactivity disorder. Genotype data were available for 64 children with ASD and hyperactivity who were exposed to MPH during a 1-week safety/tolerability lead-in phase and 58 who went on to be randomized to placebo and three doses of MPH during a 4-week blinded, crossover study. Outcome measures included the Clinical Global Impression-Improvement (CGI-I) scale and the Aberrant Behavior Checklist (ABC-hyperactivity index). A total of 14 subjects discontinued the study because of MPH side effects. Subjects were genotyped for variants in DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA and MAOB, and COMT. Forty-nine percent of the sample met positive responder criteria. In this modest but relatively homogeneous sample, significant differences by DRD1 (P=0.006), ADRA2A (P |
Databáze: | OpenAIRE |
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