Gene-by-environment (GxE) interactions are crucial for understanding the differential susceptibility of vulnerable versus resilient individuals to non-optimal caregiving environments. The last decade has produced some GxE studies in the psychiatric and developmental field (e.g., Fox, Hane, & Pine, 2007; Kaufman et al., 2004
), and their number is increasing. At this point one replicated and robust finding has been established, namely the moderating role of the monoamine oxidase A (MAOA) genotype for the impact of childhood maltreatment on the development of antisocial behavior (Kim-Cohen et al., 2006
), confirming the results of Caspi et al.’s (2002)
groundbreaking study on the interplay between genetic and environmental factors in the cycle of violence. In the current study we examine the moderating role of DRD4 genotype on the impact of experiences of parental problems on subsequent resolution of loss or trauma.
Unresolved state of mind with respect to loss or trauma is evidenced by brief lapses in monitoring of speech during discussion of loss or trauma in the Adult Attachment Interview (AAI, Main, Hesse, & Goldwyn, 2008
; Main, Kaplan, & Cassidy, 1985
), the gold standard to assess adults’ representations of attachment. Meta-analytically, unresolved state of mind is overrepresented in adult clinical populations in general (Bakermans-Kranenburg & Van IJzendoorn 2009
), and more specifically in borderline personality disordered individuals, subjects with experiences of abuse, and suicidal individuals. Severity of unresolved loss or trauma is strongly related to post-traumatic stress symptoms (Harari et al., 2009
; Nye et al., 2008
; Stovall-McClough, & Cloitre, 2006
). In turn, unresolved state of mind – when present in parents - is a robust predictor of infant disorganized attachment (Madigan et al., 2006
), a severe type of insecure attachment predicting later child psychopathology, underscoring the clinical significance of the unresolved classification (Hesse & Main, 2006
; Lyons-Ruth & Jacobvitz, 2008
; Van IJzendoorn, Schuengel, & Bakermans-Kranenburg, 1999
Interestingly, the association between parental unresolved loss or trauma and infant disorganization may be moderated by the child’s genetic variation at critical monoaminergic loci. One such locus may be the DRD4 exon 3 variable nucleotide repeat (VNTR). At 11p15 locus, humans possess between 2 and 10 copies of a 48 base pair motif in the third cytoplasmic loop of the protein, affecting signal transmission. The 4 repeat motif is the most common allele in individuals of Northern European ancestry while the 7 repeat allele is less frequent. In a study involving mothers selected on the basis of at least one important loss (through death) experience, maternal unresolved loss was associated with infant disorganized attachment, but only for children who carried the less common dopamine D4 receptor 7-repeat (DRD4-7R) allele (Van IJzendoorn & Bakermans-Kranenburg, 2006
). The DRD4 receptor gene polymorphism may affect attentional, motivational, and reward mechanisms (Robbins & Everitt, 1999
), and the 7R allele has been linked to lower dopamine reception efficiency (Schoots & Van Tol, 2003
). DRD4-7R has been associated with pathological impulsive behavior and substance abuse in adults and with Attention Deficit Hyperactivity Disorder (ADHD) in children (Ebstein, 2006
; Roussos, Giakoumaki, & Bitsios, 2009
; Swanson et al., 2007
), and in one study with disorganized attachment in infants (Lakatos et al., 2000
), though this finding could not be replicated in other studies (Bakermans-Kranenburg & Van IJzendoorn, 2007
; Spangler, Johann, Ronai, & Zimmerman, 2009).
In a second study on the moderating effect of DRD4 genotype, we found that children with the DRD4-7R allele were more vulnerable to their mothers’ insensitive parenting in that they displayed more externalizing behaviors compared to both children with the DRD4-7R allele and sensitive mothers, and children without the DRD4-7R, irrespective of maternal responsiveness (Bakermans-Kranenburg & Van IJzendoorn, 2006
). However, children with the DRD4-7R allele in comparison with all other groups showed the lowest levels of externalizing problem behavior when they had sensitive mothers. In a similar vein, Sheese, Voelker, Rothbarth, and Posner (2007)
, focusing on sensation seeking, found that children with a DRD4-7R allele were more influenced by parenting quality. For these children, lower quality parenting was associated with higher levels of sensation seeking and higher quality parenting with less sensation seeking; whereas children without the DRD4-7R allele were not affected by parenting quality.
Contrasting results were found in a combined sample of American high-risk and Hungarian low-risk families (Gervai et al., 2007
), with stronger associations between parenting and infant disorganization for infants without the DRD4 7-R allele than for infants with the DRD4 7-repeat allele. Interestingly, Propper and colleagues found that in European American families correlations between parenting and externalizing behavior were larger for children carrying the DRD4 7-R allele than for those without DRD4 7-R, whereas the reverse was the case for African American children (Propper, Willoughby, Halpern, Carbone, & Cox, 2007).
Recently, Schmidt, Fox, Perez-Edgar, and Hamer (2009)
presented an “endophenotypical model” of the influence of the DRD4 gene on infant temperament (depending on frontal EEG asymmetry). Among children with right frontal EEG asymmetry at 9 months, those with DRD4 7-R had significantly more difficulties focusing and sustaining attention at 48 months than those without the DRD4 7-R allele. However, children who exhibited left frontal EEG asymmetry at 9 months and who possessed the DRD4 7-R allele were significantly more soothable at 48 months than other children.
Such outcomes suggest that conceptualizing the DRD4-7R allele exclusively in risk-factor terms is misguided, as this variant – at least for Caucasian children – seems to heighten susceptibility to a wide variety of environments, with supportive contexts possibly promoting positive outcomes, and risky contexts fostering negative outcomes (Belsky, Bakermans-Kranenburg, & Van IJzendoorn, 2007
). Indeed, in an intervention experiment aimed at enhancing maternal responsiveness and positive discipline strategies, which can be considered the first experimental GxE test in human development, it was demonstrated that children with the DRD4-7R allele profited most from positive changes in the family environment (Bakermans-Kranenburg et al., 2008a
). A meta-analytic combination of GxE studies on children under 10 years of age showed that dopamine-related genes may be involved in heightening the susceptibility to the environment, for better and for worse (Bakermans-Kranenburg & Van IJzendoorn, in press).
Not only children but also adults may be differentially susceptible to environmental influences, for better and for worse. The DRD4 and COMT val/met polymorphisms (both implicated in the dopaminergic system) appear to moderate the association between parents’ daily hassles and their responsive parenting. More daily hassles have been associated with less responsive parenting only among parents with a DRD4-7R allele as well as a COMT val allele (Van IJzendoorn, Bakermans-Kranenburg, & Mesman, 2008
). At the same time, in the case of fewer daily hassles this group showed higher
levels of responsive parenting, supporting the idea that DRD4-7R variant may heighten susceptibility to a wide variety of environments (Ding et al., 2002
). Chotai and colleagues found differential effects of season of birth on psychiatric disorders for carriers of the DRD4-7R allele. Birth in February was associated with more depression, but birth in May with less depression, perhaps due to differential susceptibility to seasonal influences during embryonic or perinatal development (Chotai, Serretti, Lattuada, Lorenzi, & Lilli, 2003
). Most GxE studies focus however on experiences that took place after the prenatal or perinatal period, and show an emphasis on the negative effects of adverse events; e.g., Dragan and Oniszczenko (2009)
documented that among flood survivors in Poland (aged 14-62 years) carriers of the DRD4-7R allele had more intense PTSD symptoms. Reiner and Spangler (2010)
noted however that carriers of the DRD4-7R allele with unloving caregiver recollections more often had a secure representation of attachment than their counterparts without the DRD4-7R allele.
In the current study we test whether adopted adults who are carriers of the DRD4-7R allele are more vulnerable to negative childhood parenting experiences such as marital fights, parental depression or alcohol problems. A previous study on a partly overlapping sample (n
= 67 overlapping cases) showed a main effect of the serotonin transporter promoter (5-HTTLPR) polymorphism on unresolved loss or trauma as assessed with the AAI (Caspers et al., 2009
). Carriers of the short allele of the 5-HTTLPR showed an increased risk for unresolved state of mind. In the current study we examine the additional effect of an adverse childhood context for adoptees with and without the DRD4-7R allele, and we tested for a potential interaction effect of DRD4 and 5-HTTLPR, as for instance documented by Schmidt, Fox, and Hamer (2007) for children and by Armbruster and colleagues (2009)
for adults. We hypothesized that the presence of DRD4-7R allele would moderate the association between experienced parental problems and unresolved state of mind. Based on a susceptibility model, we predicted higher scores for unresolved loss or trauma in participants with the DRD4-7R allele who experienced parental problems in their childhood and lower scores in participants with the DRD4-7R allele who did not experience parental problems. Following the steps for testing differential susceptibility as delineated by Belsky et al. (2007)
, we tested the specificity of the model by replacing the susceptibility factor (5-HTTLPR instead of DRD4) and outcome (depression instead of unresolved loss or trauma).