Abstract
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
| Original language | English (US) |
|---|---|
| Pages (from-to) | 295-302 |
| Number of pages | 8 |
| Journal | Pharmacogenomics Journal |
| Volume | 14 |
| Issue number | 3 |
| DOIs | |
| State | Published - 2014 |
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Keywords
- autism spectrum disorders
- dopamine
- genetics
- hyperactivity
- methylphenidate
ASJC Scopus subject areas
- Pharmacology
- Molecular Medicine
- Genetics
- Medicine(all)
Cite this
Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders. / McCracken, J. T.; Badashova, K. K.; Posey, D. J.; Aman, M. G.; Scahill, L.; Tierney, Elaine; Arnold, L. E.; Vitiello, B.; Whelan, F.; Chuang, S. Z.; Davies, M.; Shah, B.; McDougle, C. J.; Nurmi, E. L.
In: Pharmacogenomics Journal, Vol. 14, No. 3, 2014, p. 295-302.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with autism spectrum disorders
AU - McCracken, J. T.
AU - Badashova, K. K.
AU - Posey, D. J.
AU - Aman, M. G.
AU - Scahill, L.
AU - Tierney, Elaine
AU - Arnold, L. E.
AU - Vitiello, B.
AU - Whelan, F.
AU - Chuang, S. Z.
AU - Davies, M.
AU - Shah, B.
AU - McDougle, C. J.
AU - Nurmi, E. L.
PY - 2014
Y1 - 2014
N2 - 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
AB - 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
KW - autism spectrum disorders
KW - dopamine
KW - genetics
KW - hyperactivity
KW - methylphenidate
UR - http://www.scopus.com/inward/record.url?scp=84901287116&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901287116&partnerID=8YFLogxK
U2 - 10.1038/tpj.2013.23
DO - 10.1038/tpj.2013.23
M3 - Article
C2 - 23856854
AN - SCOPUS:84901287116
VL - 14
SP - 295
EP - 302
JO - Pharmacogenomics Journal
JF - Pharmacogenomics Journal
SN - 1470-269X
IS - 3
ER -