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Human Genetics01:28

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Attention-Deficit/Hyperactivity Disorder

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Related Experiment Video

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Developing a Rat Model for Bipolar Disorder
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Do dopamine gene variants and prenatal smoking interactively predict youth externalizing behavior?

T Caitlin O'Brien1, Brian S Mustanski, Andrew Skol

  • 1Department of Medical Social Sciences, Northwestern University, 633 N. St. Clair, 19th Floor, Chicago, IL 60611, USA.

Neurotoxicology and Teratology
|September 26, 2013
PubMed
Summary

Prenatal tobacco exposure combined with the DAT1 gene significantly increases externalizing behaviors in boys. Sex differences in genetic and environmental risk for antisocial behavior warrant further investigation.

Keywords:
ADHDCDDAT1DRD4Developmental psychopathologyExternalizingGene×environmentODDPTEPrenatal tobacco exposureSESVNTRattention deficit hyperactive disorderconduct disorderdopamine receptor D4dopamine receptor geneoppositional defiant disorderprenatal tobacco exposuresocioeconomic statusvariable number tandem repeat

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Area of Science:

  • Neuroscience
  • Genetics
  • Developmental Psychology

Background:

  • Externalizing behaviors, including antisocial and substance use, are common and impairing.
  • These behaviors are highly comorbid and influenced by prenatal exposures and genetics.
  • Sex differences in the interplay of prenatal tobacco exposure and genetic factors are understudied.

Purpose of the Study:

  • To examine the interaction between prenatal tobacco exposure and genetic markers (DAT1, DRD4) in predicting externalizing behavior.
  • To investigate whether these gene-environment interactions differ by sex in adolescents.

Main Methods:

  • A community sample of 176 adolescents was prospectively assessed.
  • Prenatal tobacco exposure was measured via cotinine-corrected reports.
  • Externalizing behaviors were assessed using multi-method, multi-wave data.
  • Genetic markers DAT1 and DRD4 were analyzed.

Main Results:

  • A significant interaction between DAT1 and prenatal tobacco exposure predicted externalizing behavior in boys.
  • Boys with prenatal tobacco exposure showed increased risk with the 10r DAT1 allele.
  • A trend suggested DAT1 heterozygotes had higher risk in exposed girls.
  • DRD4 did not show a significant interaction.

Conclusions:

  • Sex-specific pathways link prenatal adversity and genetic susceptibility to externalizing behaviors.
  • The DAT1 gene moderates the effect of prenatal tobacco exposure on externalizing behaviors, with sex differences observed.
  • Findings can inform targeted prevention for at-risk youth.