Gene-environment interaction in hyperkinetic conduct disorder (HD + CD) as indicated by season of birth variations in dopamine receptor (DRD4) gene polymorphism

Neurosci Lett. 2004 Aug 19;366(3):282-6. doi: 10.1016/j.neulet.2004.05.049.


Recently, an interaction between season of birth and the expression of candidate genes has been suggested. Season of birth variations in tryptophan hydroxylase (TPH), the serotonin transporter (5-HTTLPR) and the dopamine D4 receptor (DRD4) gene polymorphisms are different for affective disorders and schizophrenia. The DRD4 gene has been postulated as a candidate gene for attention-deficit-hyperactivity disorder (ADHD), equivalent to hyperkinetic disorder (HD). The seven-repeat long variant of this gene (DRD4*7) in comparison to the short repeat variants of the DRD4 gene polymorphism, has been found to be associated with ADHD. A seasonal pattern of birth has also been proposed for different subtypes of ADHD. Therefore, in a subgroup of children with HD and conduct disorder (CD) and in healthy controls, we investigated a possible association between the DRD4*7 allele and HD + CD in association with the season of birth. Supporting this hypothesis, we found an interaction between the seasons of birth and the expression of the DRD4 candidate gene in children with HD + CD as well as in controls, which differ significantly from each other. Depending on the season of birth, children carrying the DRD4*7R allele showed different relative risks for developing HD + CD.

Publication types

  • Comparative Study

MeSH terms

  • Adolescent
  • Attention Deficit Disorder with Hyperactivity / complications
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Birth Rate
  • Chi-Square Distribution
  • Child
  • Conduct Disorder / complications
  • Conduct Disorder / genetics*
  • Environment*
  • Genetic Predisposition to Disease
  • Humans
  • Incidence
  • Polymorphism, Genetic*
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D4
  • Seasons*
  • Tandem Repeat Sequences / genetics


  • DRD4 protein, human
  • Receptors, Dopamine D2
  • Receptors, Dopamine D4