Parent-child DRD4 genotype as a potential biomarker for oppositional, anxiety, and repetitive behaviors in children with autism spectrum disorder

Prog Neuropsychopharmacol Biol Psychiatry. 2010 Oct 1;34(7):1208-14. doi: 10.1016/j.pnpbp.2010.06.019. Epub 2010 Jun 26.

Abstract

The primary objective of the present study was to examine whether a combination of parent-child DRD4 genotypes results in more informative biomarkers of oppositional, separation anxiety, and repetitive behaviors in children with autism spectrum disorder (ASD). Based on prior research indicating the 7-repeat allele as a potential risk variant, participants were sorted into one of four combinations of parent-child genotypes. Owing to the possibility of parent-of-origin effects, analyses were conducted separately for mother-child (MC) and father-child (FC) dyads. Mothers completed a validated DSM-IV-referenced rating scale. Partial eta-squared (ηp(2)) was used to determine the magnitude of group differences: 0.01-0.06=small, 0.06-0.14=moderate, and >0.14=large. Analyses indicated that children in MC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe mother-rated oppositional-defiant (ηp(2)=0.11) and separation anxiety (ηp(2)=0.19) symptoms. Conversely, youths in FC dyads with matched genotypes had the least (7-/7-) and most (7+/7+) severe obsessive-compulsive behaviors (ηp(2)=0.19) and tics (ηp(2)=0.18). Youths whose parents were both noncarriers had less severe tics than peers with at least one parental carrier, and the effect size was large (ηp(2)=0.16). There was little evidence that noncarrier children were rated more severely by mothers who were carriers versus noncarriers. Transmission Disequilibrium Test analyses provided preliminary evidence for undertransmission of the 2-repeat allele in youths with more severe tics (p=0.02). Parent genotype may be helpful in constructing prognostic biomarkers for behavioral disturbances in ASD; however, findings are tentative pending replication with larger, independent samples.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Analysis of Variance
  • Anxiety Disorders / etiology
  • Anxiety Disorders / genetics*
  • Attention Deficit and Disruptive Behavior Disorders / etiology
  • Attention Deficit and Disruptive Behavior Disorders / genetics*
  • Biomarkers
  • Child
  • Child Development Disorders, Pervasive / complications
  • Child Development Disorders, Pervasive / genetics*
  • Child, Preschool
  • Family Health*
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Linkage Disequilibrium / genetics
  • Male
  • Obsessive-Compulsive Disorder / etiology
  • Obsessive-Compulsive Disorder / genetics
  • Parent-Child Relations
  • Parents*
  • Psychiatric Status Rating Scales
  • Receptors, Dopamine D4 / genetics*
  • Repetitive Sequences, Nucleic Acid / genetics
  • Tic Disorders / etiology
  • Tic Disorders / genetics

Substances

  • Biomarkers
  • DRD4 protein, human
  • Receptors, Dopamine D4