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Event Related Potentials (ERPs) and other EEG Based Methods for Extracting Biomarkers of Brain Dysfunction: Examples from Pediatric Attention Deficit/Hyperactivity Disorder (ADHD)
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Event Related Potentials (ERPs) and other EEG Based Methods for Extracting Biomarkers of Brain Dysfunction: Examples from Pediatric Attention Deficit/Hyperactivity Disorder (ADHD)

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Positive effects of methylphenidate on hyperactivity are moderated by monoaminergic gene variants in children with

J T McCracken1, K K Badashova1, D J Posey2

  • 1Department of Psychiatry and Biobehavioral Sciences, University of California at Los Angeles, Semel Institute for Neuroscience, Los Angeles, CA, USA.

The Pharmacogenomics Journal
|July 17, 2013
PubMed

Insights

Genetic variations in monoaminergic genes influence how children with autism spectrum disorder (ASD) respond to methylphenidate (MPH). Specific gene variants are linked to both the effectiveness and side effects of MPH treatment in ASD.

Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Methylphenidate (MPH) is used to treat hyperactivity in autism spectrum disorder (ASD).
  • Individual responses to MPH vary significantly in children with ASD.
  • Monoaminergic gene variants may influence MPH efficacy and tolerability.

Purpose of the Study:

  • To investigate whether specific monoaminergic gene variants moderate the effects of MPH in children with ASD.
  • To identify genetic predictors of MPH response and tolerability in this population.

Main Methods:

  • Genotyping for variants in multiple monoaminergic genes (DRD1-DRD5, ADRA2A, SLC6A3, SLC6A4, MAOA, MAOB, COMT).
  • Assessed MPH efficacy using Clinical Global Impression-Improvement (CGI-I) and Aberrant Behavior Checklist (ABC-hyperactivity index).
  • Analyzed genotype-phenotype correlations for response and tolerability in 64 children with ASD.

Main Results:

  • Forty-nine percent of participants responded to MPH.
  • Significant associations found between MPH response and variants in DRD1, ADRA2A, COMT, DRD3, DRD4, SLC6A3, and SLC6A4.
  • Variants in DRD2 and DRD3 were linked to MPH tolerability issues.

Conclusions:

  • Multiple monoaminergic gene variants may explain individual differences in MPH efficacy and tolerability in children with ASD.
  • This study provides initial pharmacogenetic insights into MPH treatment for ASD.
  • Further research is warranted to validate these findings.

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