Interaction of Dopamine Transporter Genotype with Prenatal Smoke Exposure on ADHD Symptoms

Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Germany.
The Journal of pediatrics (Impact Factor: 3.79). 03/2008; 152(2):263-9. DOI: 10.1016/j.jpeds.2007.07.004
Source: PubMed


To demonstrate that children homozygous for the 10-repeat allele of the common dopamine transporter (DAT1) polymorphism who were exposed to maternal prenatal smoke exhibited significantly higher hyperactivity-impulsivity than children without these environmental or genetic risks.
We performed a prospective longitudinal study from birth into early adulthood monitoring the long-term outcome of early risk factors. Maternal prenatal smoking was determined during a standardized interview with the mother when the child was 3 months old. At age 15 years, 305 adolescents participated in genotyping for the DAT1 40 base pair variable number of tandem repeats polymorphism and assessment of inattention, hyperactivity-impulsivity, and oppositional defiant/conduct disorder symptoms with the Kiddie-Sads-Present and Lifetime Version.
There was no bivariate association between DAT1 genotype, prenatal smoke exposure and symptoms of attention deficit hyperactivity disorder. However, a significant interaction between DAT1 genotype and prenatal smoke exposure emerged (P = .012), indicating that males with prenatal smoke exposure who were homozygous for the DAT1 10r allele had higher hyperactivity-impulsivity than males from all other groups. In females, no significant main effects of DAT1 genotype or prenatal smoke exposure or interaction effects on any symptoms were evident (all P > .25).
This study provides further evidence for the multifactorial nature of attention deficit hyperactivity disorder and the importance of studying both genetic and environmental factors and their interaction.

Download full-text


Available from: Günter Esser, Jan 27, 2014
  • Source
    • "Moreover, several male-specific associations between SLC6A3/ DAT1 40 bp-VNTR and behavioral phenotypes were already reported (e.g. prenatal smoke exposure and ADHD (Becker et al. 2008), number of sexual partners (Guo et al. 2007a), violent delinquency (Guo et al. 2007b) and sleep–wake cycles (Valomon et al. 2014 "
    [Show abstract] [Hide abstract]
    ABSTRACT: Several recent lines of evidence are proving an important role for dopamine in the aging process and in the determination of life span. Components of the dopaminergic system may represent good candidates for longevity studies. Herein, we tested the possible association of the functional SLC6A3/DAT1 40-bp VNTR with life-expectancy in a healthy population of Central Italy (N = 993) by applying a genetic-demographic approach that takes into account the demographic information and different survival rates between sexes for modeling the survival of specific allele carriers in the population. Male carriers of S*/S* genotype showed a lower survival chance across most of the lifespan respect to the survival of DAT1*L-carriers (P = 0.021). The same analyses gave non-significant results in females. Several studies already reported significant sex differences in dopamine metabolism and its related biological pathways. Thus, we can hypothesize that the SLC6A3/DAT1 40 bp-VNTR may affect life expectancy in a sex-specific way. Moreover, it is conceivable that DAT1 S*/S* carriers, who are prone to assume "risk" type behaviors, may be dropped out of the "healthy" population by a sort of "demographic selection".
    Full-text · Article · Jan 2015 · Biogerontology
  • Source
    • "Future work should examine this idea empirically and evaluate whether males are differentially susceptible to positive environmental conditions (e.g., proper nutrition) during pregnancy in such a way as to decrease DBD risk. This type of work has important implications for the development of prevention strategies, suggesting that pregnant women, particularly those expecting boys, may especially benefit from refraining from use of alcohol and nicotine during pregnancy (Becker et al., 2008; Bennett et al., 2007). Notably, results were significant using measures that did not contain shared source variance (i.e., when utilizing teacher report of symptoms and parent report of prenatal stressor exposure), although, interestingly , results did not hold using parent-report of symptoms. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Disruptive Behavior Disorders (DBD) exhibit a sex-biased prevalence rate favoring boys, and prenatal testosterone exposure appears to be part of the complex etiology of these disorders. The current study examines whether high prenatal testosterone exposure may heighten risk for DBD symptoms in males by increasing susceptibility to negative environmental conditions such as maternal nicotine and alcohol use during pregnancy. Participants were 109 three- to six-year-olds (64% male; 72% with DBD) and their 109 primary caregivers and 55 daycare providers/teachers who completed a multi-informant diagnostic procedure. A proxy of prenatal testosterone exposure, finger-length ratios, interacted with maternal report of prenatal nicotine use to predict teacher-rated hyperactivity-impulsivity during preschool, for boys, but not girls, although the three-way interaction was not significant. Prenatal testosterone interacted with prenatal alcohol exposure to predict teacher-rated hyperactivity-impulsivity and ODD symptoms differentially based on child sex (significant three-way interaction). Boys with higher levels of prenatal testosterone who were also exposed to higher levels of nicotine and alcohol during pregnancy exhibited increased hyperactivity-impulsivity during early childhood, but girls did not exhibit this same pattern. Thus, high prenatal testosterone exposure seems to increase risk for DBD symptoms particularly in males by increasing susceptibility to prenatal environmental stressors.
    Full-text · Article · Jul 2014 · Neurotoxicology and Teratology
  • Source
    • "In the most recent meta-analysis,19 significant evidence of association was found with the 480-bp allele of the most commonly studied polymorphism (a VNTR in the 3′ untranslated region (UTR) region of the gene) as well as with other polymorphisms in the same gene. The substantial heterogeneity reported could be the result of multiple polymorphisms in this gene increasing risk to ADHD or gene–environment interaction between the 3′ UTR VNTR and prenatal factors, such as maternal alcohol consumption22 or maternal smoking during pregnancy,23 although these associations have not been widely replicated. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) affects around 1-3% of children. There is a high level of comorbidity with developmental and learning problems as well as with a variety of psychiatric disorders. ADHD is highly heritable, although there is no single causal risk factor and non-inherited factors also contribute to its aetiology. The genetic and environmental risk factors that have been implicated appear to be associated with a range of neurodevelopmental and neuropsychiatric outcomes, not just ADHD. The evidence to date suggests that both rare and multiple common genetic variants likely contribute to ADHD and modify its phenotype. ADHD or a similar phenotype also appears to be more common in extreme low birth weight and premature children and those exposed to exceptional early adversity. In this review, the authors consider recent developments in the understanding of risk factors that influence ADHD.
    Full-text · Article · Sep 2011 · Archives of Disease in Childhood
Show more