G × E interaction in the organization of attachment: mothers’ responsiveness as a moderator of children’s genotypes

Because of its universal nature, attachment between infants and their caregivers has been a perennial research topic (Bowlby, 1969/1982; Cassidy & Shaver, 1999). Intense controversies ensued regarding its assessment, determinants, and implications, particularly the roles of biologically-founded child temperament (typically assessed behaviorally or through parental reports) versus qualities of early care. Although scholars continue to differ in how much emphasis they place on one or the other set of factors, the consensus in the field has largely coalesced around acknowledging both sets of influences (Goldsmith & Harman, 1994; Kochanska, 1998; Rothbart & Bates, 2006; Thompson, 2006; Vaughn & Bost, 1999). That consensus reflects a more general shared assumption in behavioral sciences that a comprehensive understanding of adaptive and maladaptive development requires an integration of both genetic and environmental influences (Kendler & Prescott, 2006; Rutter, 2002, 2006, 2007). Advances in molecular genetics and the subsequent rise in interdisciplinary collaborations between geneticists and behavioral scientists have robustly invigorated that approach. Analyses of how genes and environments interact – Genotype × Environment (G × E) interactions – have been particularly fruitful (Rutter, Moffitt, & Caspi, 2006). A G × E interaction occurs when environmental experience moderates the effect of a person’s genotype on physical or mental health outcomes, or when a genotype moderates an environmental effect (Moffitt, Caspi, & Rutter, 2005). In socio-emotional development, the 5-HTTLPR polymorphism, linked to the serotonergic system, has been among the most often studied. Serotonin is an inhibitory neurotransmitter in the central nervous system that has been linked with the regulation of mood and emotions. The 5-HTTLPR polymorphism has two common alleles, the short (s) and the long (l ). The short allele (s) has been linked to reduced 5-HTT transcription efficiency, lower transporter levels, and diminished serotonin uptake compared to individuals with the long (l) allele. Individuals who are either homozygous for the short allele (ss) or heterozygous (sl) have been found to be at risk for a range of emotional and behavioral maladaptive outcomes. Dysfunctions in the serotonergic system have been strongly implicated in broadly ranging psychopathology, including under-regulated, impulsive, excessively and inappropriately aggressive, risk-taking behavior, deficits of executive functions, alcohol use, as well as depressive or anxious disorders (Brown & Hariri, 2006; Lesch et al., 1996; Lucki, 1998; Posner, Rothbart, & Sheese, 2007; Sourbrie, 1986; van Goozen, Fairchild, Snoek, & Harold, 2007; Westernberg, Murphy & den Boer, 1996). Perhaps most importantly, animal and human research has produced converging evidence of interactions between the genetic risk associated with 5-HTTLPR polymorphism (having a short allele) and environmental influences. Generally, those studies have shown that the link between the genetic risk and maladaptive outcomes is moderated by qualities of the environment. Specifically, individuals with a short allele develop significant problems when they are also exposed to sub-optimal or stressful environmental conditions. Monkeys with a short allele show multiple behavioral problems, but only if they have been peer raised, and not if they have been reared in natural, supportive mother–infant relationships (Champoux et al., 2002; Suomi, 2004, 2005, 2006). Adults with a short allele are likely to develop depression, but only if they also experienced multiple stressful life events (Caspi et al., 2003). Children with a short allele are at risk for depression, but only if they have been exposed to maltreatment, abuse, or neglect (Kaufman et al., 2004, 2006); they are also at risk for fearfulness, but only if they grew up in a family with poor social support (Fox et al., 2005). Very few studies, however, have addressed G × E interactions in the development of infant attachment organization (security vs. insecurity) using molecular genetic measures of 5-HTTLPR and robust observational assessments of the environment. Most of the extant research has addressed specifically attachment disorganization; furthermore, that work has focused mostly on the genes related to the dopamine system. Genotypes associated with the dopamine system (7-repeat allele of the dopamine D4 receptor, DRD4, Lakatos et al., 2000; DRD4 and the -521 C/T promoter gene, Gervai et al., 2005; Lakatos et al., 2002) have been linked to disorganized attachment, but that link has not been consistently replicated (Bakermans-Kranenburg & van IJzendoorn, 2004). Additionally, a previous study failed to find a main effect of the 5-HTTLPR polymorphism, or a significant interaction between 5HTTLPR and DRD4 genotypes in predicting infant disorganized attachment (Lakatos et al., 2003). Three studies have reported a G × E interaction in the context of disorganized attachment. Van IJzendoorn and Bakermans-Kranenburg (2006) found that children with the 7-repeat DRD4 allele and whose mothers had an unresolved past trauma or loss (considered an environmental risk factor) were at almost 19-fold increased risk for disorganized attachment. By contrast, Gervai et al. (2007) found that maternal disrupted communication moderated risk of disorganized attachment for children without the 7-repeat DRD4 allele but did not moderate risk for children with the 7-repeat DRD4 allele. Finally, Spangler and Zimmermann (2007) examined 5-HTTLPR polymorphism along with variation in environmental influences in the development of disorganized attachment: Children homozygous for the short allele were significantly more likely to be classified as disorganized if their mothers also demonstrated low maternal responsiveness compared to children in the other groups. To our knowledge, however, no studies have examined the role of the 5-HTTLPR polymorphism along with variation in environmental influences in the development of attachment security versus insecurity, although Bakermans-Kranenburg and van IJzendoorn (in press) specifically called for such investigation. To do so was the goal of this study. We examined a G × E interaction in the development of attachment organization, assessed using the established classic Strange Situation paradigm conducted at the end of the first year of life, in a community sample of typically developing children. Children’s genotypes (5-HTTLPR polymorphism, ss/sl versus ll ) were assessed using molecular genetic measures, and the environmental influence – maternal responsiveness – was observed in naturalistic mother–child interactions in infancy. Responsiveness has long been conceptualized as the core aspect of early care in the attachment literature. Mothers who respond more sensitively to their children are more likely to have securely attached infants, although the size of the effect tends to be modest (Ainsworth, Bell, & Stayton, 1971; for meta analyses, see Goldsmith & Alansky, 1987; de Wolff & van IJzendoorn, 1997; for a review, see Thompson, 1998). Consistent with the extant research on G × E interactions, we expected that infants with a short allele (ss/sl) would be at an increased risk for insecure attachment, but only if they also experienced relatively unresponsive maternal care, and not if they received responsive care. In other words, we expected that mothers’ responsiveness to their infants, observed in infancy (at 7 months), would moderate the effect of the infants’ 5-HTTLPR genotypes on the organization of future attachment (at 15 months). Following recent work by Belsky, and Bakermans-Kranenburg and van IJzendoorn (Belsky, 2005, 1997; Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Bakermans-Kranenburg & van IJzendoorn, in press), we further explored whether the G × E interaction would be consistent with the differential susceptibility model, or with the genetic vulnerability model (diathesis-stress). The former model assumes a form of G × E interactions such that children with certain biological predispositions (high negative reactivity, high genetic risk, including a short 5-HTT allele) are more susceptible than other children to variations in the environment, and respond more strongly than other children to both negative and positive environmental conditions. For those children, variations in experience may lead to worse or better outcomes compared to children without such predispositions. The latter model poses that for children with high genetic risk, negative environmental influences lead to particularly negative developmental outcomes, and positive environmental influences can buffer those children from the elevated risk. In this study, both models would predict that, compared to infants homozygous for the long allele, infants with a short allele and unresponsive mothers would be at a greater risk of developing insecure attachment. However, the differential susceptibility model would further predict that the variation in mothers’ responsiveness would have a greater impact – for better or worse – on infants with a short allele than on those who were homozygous for the long allele (and thus, that ss/sl infants with responsive mothers would be more likely to develop a secure attachment than ll infants). In contrast, the genetic vulnerability model would predict that whereas high maternal responsiveness might offset the genetic risk for ss/sl infants, it is unlikely to lead to better outcomes than it has for children homozygous for the long allele (ll ).