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The DRD4 gene and severity of tics and comorbid symptoms: main effects and interactions with delivery complications

Netty G P Bos-Veneman1, Ruud B Minderaa, Pieter J Hoekstra

  • 1Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. n.bos-veneman@accare.nl

Movement Disorders : Official Journal of the Movement Disorder Society
|July 15, 2010
PubMed

Insights

The dopamine receptor D4 (DRD4) 48-base pair (bp) variable number of tandem repeats (VNTR) gene and perinatal adversities influence tic disorder severity. Specific DRD4 alleles and complications interact to affect tic and comorbid symptom severity in children.

Area of Science:

  • Neurogenetics
  • Child Psychiatry
  • Developmental Neuroscience

Background:

  • Tic disorders are complex neurodevelopmental conditions.
  • The dopamine receptor D4 (DRD4) gene, specifically its 48-base pair (bp) variable number of tandem repeats (VNTR) polymorphism, is implicated in various neurodevelopmental disorders.
  • Perinatal adversities are known risk factors for neurodevelopmental outcomes.

Purpose of the Study:

  • To investigate the role of the DRD4 48-bp VNTR and perinatal adversities in tic severity and comorbid symptoms in children with tic disorders.
  • To examine interactions between DRD4 VNTR alleles (2R, 3R, 4R, 7R) and perinatal factors (prenatal smoking, pregnancy/delivery complications) on tic and comorbid symptom severity.

Main Methods:

  • Genotyping of the DRD4 48-bp VNTR in 110 children with tic disorders.
  • Assessment of prenatal smoking exposure and pregnancy/delivery complications via parent questionnaires.
  • Analysis of associations between DRD4 alleles, perinatal factors, and tic/comorbid symptom severity (obsessive-compulsive, depressive, anxious, autistic) using linear regressions.

Main Results:

  • The 2R allele was linked to more severe obsessive-compulsive symptoms; the 3R allele was associated with increased autistic features.
  • Pregnancy complications correlated with decreased obsessive-compulsive symptoms, while prenatal smoking exposure was linked to more severe depressive and autistic symptoms.
  • Interactions were observed: delivery complications affected tic severity differently based on 3R allele presence, and delivery complications' impact on internalizing symptoms was most pronounced in 2R allele carriers.

Conclusions:

  • The DRD4 48-bp VNTR plays a role in the etiology of tic and associated disorders.
  • Interactions between DRD4 VNTR alleles and delivery complications influence tic severity and co-occurring internalizing symptoms.
  • These findings highlight the complex interplay of genetic and environmental factors in tic disorders.

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