Meta-Analysis of the Association Between the 7-Repeat Allele of the Dopamine D 4 Receptor Gene and Attention Deficit Hyperactivity Disorder

Harvard University, Cambridge, Massachusetts, United States
American Journal of Psychiatry (Impact Factor: 12.3). 08/2001; 158(7):1052-7. DOI: 10.1176/appi.ajp.158.7.1052
Source: PubMed


Family, twin, and adoption studies show attention deficit hyperactivity disorder (ADHD) to have a substantial genetic component. Although several studies have shown an association between ADHD and the 7-repeat allele of the dopamine D(4) receptor gene (DRD4), several studies have not. Thus, the status of the ADHD-DRD4 association is uncertain.
Meta-analysis was applied to case-control and family-based studies of the association between ADHD and DRD4 to assess the joint evidence for the association, the influence of individual studies, and evidence for publication bias.
For both the case-control and family-based studies, the authors found 1) support for the association between ADHD and DRD4, 2) no evidence that this association was accounted for by any one study, and 3) no evidence for publication bias.
Although the association between ADHD and DRD4 is small, these results suggest that it is real. Further studies are needed to clarify what variant of DRD4 (or some nearby gene) accounts for this association.

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    • "Although the association between ADHD and DRD4 is small, these results suggest that it is real. Faraone et al, 91 2001 For both the case-control and the family-based studies, the authors found (1) support for the association between ADHD and DRD4; (2) no evidence that this association was accounted for by any one study; and (3) no evidence for publication bias. DRD4 exon 3 polymorphisms (48-bp VNTR) "
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    • "Thispolymorphism(DRD4-III)wasassociatedwithbehaviors andtraitsthatarerelatedtoempathy.Anexampleofthisis theassociationbetweenDRD4-IIIpolymorphismandaltruistic behavior(Bachner-Melmanetal.,2005),andthepossiblerole ofthepolymorphisminADHD(Faraoneetal.,2001),a disorderthatwasshowntoberelatedtoToMdeficitsand reducedempathy(Uekermannetal.,2010).Anotherinteresting investigationfocusedonthefunctionofDRD4-IIIpolymorphism inrepresentationalToM(RTM)–theabilitytoexplicitly understandthatother'smentalstates(beliefs,desires,knowledge) areperson-specificrepresentationsoftheworld(Lackneretal., 2012).ThisstudyhassuggestedthatvariationsintheDRD4- IIImaypredictpreschoolers'performanceinRTM,showing thatindividualswithtwoshorteralleles(4repeatsorless) outperformedthosewithoneortwolongeralleles(6repeatsor more),(Lackneretal.,2010). "
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    • "Recently, it has been suggested that DRD4 behaves not as a " vulnerability " gene but as a " plasticity " gene (Belsky et al., 2009; Wells et al., 2013). The vulnerability gene hypothesis conceptualizes the long variant of DRD4 as a risk factor for psychiatric disorders such as ADHD (Faraone et al., 2001), and the likelihood of that disorder will increase in the face of adverse environment (Belsky and Hartman, 2014). In contrast, the plasticity gene idea contends that, rather than being more susceptible to adverse environmental influences, long allele carriers show increased susceptibility to environmental influences in general (Belsky and Hartman, 2014). "
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