The Dopamine Receptor D4 Gene (DRD4) Moderates Family Environmental Effects on ADHD

Abstract

Attention-Deficit/Hyperactivity Disorder (ADHD) is a prime candidate for exploration of gene-by-environment interaction (i.e., G × E), particularly in relation to dopamine system genes, due to strong evidence that dopamine systems are dysregulated in the disorder. Using a G × E design, we examined whether the DRD4 promoter 120-bp tandem repeat polymorphism, previously associated with ADHD, moderated the effects of inconsistent parenting and marital conflict on ADHD or Oppositional-Defiant Disorder (ODD). Participants were 548 children with ADHD and non-ADHD comparison children and their parents. Homozygosity for the DRD4 promoter 120-bp tandem repeat insertion allele increased vulnerability for ADHD and ODD only in the presence of inconsistent parenting and appeared to increase susceptibility to the influence of increased child self-blame for marital conflict on ADHD inattention. DRD4 genotypes may interact with these proximal family environmental risk factors by increasing the individual’s responsivity to environmental contingencies.

Association of Positive and Negative Parenting Behavior with Childhood ADHD: Interactions with Offspring Monoamine Oxidase A (MAO-A) Genotype

“…The G×E observed for negative parenting was robust for inattention symptoms, supporting previous work that negative parenting adversely affects ADHD dimensions and EB (Martel et al 2010;Pfiffner et al 2005). However, negative parenting is influenced by environmental and genetic factors (Martel et al 2010), including in response to the child's negative behavior (Lytton 1990).…”

“…The G×E observed for negative parenting was robust for inattention symptoms, supporting previous work that negative parenting adversely affects ADHD dimensions and EB (Martel et al 2010;Pfiffner et al 2005). However, negative parenting is influenced by environmental and genetic factors (Martel et al 2010), including in response to the child's negative behavior (Lytton 1990). Lee et al (2010) reported that the association of maternal DAT1 genotype and negative parenting was moderated by the child's EB, suggesting that parenting (although conceptualized in this study as an environmental influence) is, itself, also potentially influenced by G×E.…”

“…Lee et al (2010) reported that the association of maternal DAT1 genotype and negative parenting was moderated by the child's EB, suggesting that parenting (although conceptualized in this study as an environmental influence) is, itself, also potentially influenced by G×E. MAO-A genotype may increase sensitivity to parenting through its influence on behavioral and emotional regulation, dimensions which underlie ADHD (Martel et al 2010) and are linked to DA and serotonin pathways in the amygdala, prefrontal cortex, and basal ganglia (Davidson et al 2006). In particular, the amygdala is sensitive to both environmental punishment and reward (Holland and Gallagher 1999).…”

Should We Subtype ADHD According to the Context in Which Symptoms Occur? Criterion Validity of Recognising Context-Based ADHD Presentations

“…In the home, for example, negative parenting practices such as harsh or inconsistent discipline have been identified as important risk factors for, as well as outcomes of, disruptive behaviour disorders such as ADHD, conduct disorder and oppositional defiant disorder [15][16][17]. Analogous transactions may occur in the school environment where, for example, relationships with teachers can be affected by but can also shape disruptive behaviour problems [18][19][20].…”

Gene–Environment Interactions in the Etiology of Human Violence

“…COMT has a key role in inactivating dopamine in the prefrontal cortex. Usually, the A1 allele of a 3 0 Taq1 polymorphism in DRD2, the 7-repeat (7r) allele of a 48-bp VNTR polymorphism in exon 3 of DRD4 (for another polymorphism, Martel et al 2011), and the 10-repeat (10r) allele of a 40-bp VNTR polymorphism in DAT are considered as ''risk alleles,'' which may be linked to a less efficient dopaminergic system (Pavlov et al 2012). For COMT, homozygosity for the val allele of the Val158Met polymorphism is frequently regarded as risk genotype.…”