In school, children have to function in a classroom for a significant amount of time every day, across the better part of their childhood and later adolescent years. As in every social setting, children evaluate classmates and form opinion on who they do and do not like. As a consequence of this evaluation, some children will become highly preferred and liked among many of their peers. These highly preferred children have been found to develop high-quality friendships (Parker and Asher
1993), have positive relationships with teachers (Hughes et al.
2006), and generally show favorable developmental outcomes such as prosocial behavior (Bierman and Erath
2006). However, the dark side of the peer evaluation process is that some children become disliked and poorly preferred by their classmates, which is a robust predictor of maladjustment. For instance, these children are at risk of peer victimization and friendlessness (Van Lier and Koot
2010) and poor support or rejection by teachers (Leflot et al.
2011). As such, it may come as no surprise that children who are poorly preferred by their peers are at risk of developing behavioral problems (Ladd
2006; Van Lier and Koot
2010).
Thus, there is a vast body of research linking children’s social standing among peers, also known as “peer social preference” (Coie et al.
1982), to childhood adjustment and maladjustment. However, individual differences in the predictive links are striking. Recent findings have suggested that the genetic make-up of children may be of relevance in understanding why children are more or less affected by their social environment (for a meta-analysis, see Bakermans-Kranenburg and van IJzendoorn
2011). That is, several studies have indicated that the dopamine receptor D4 gene (DRD4) may render children susceptible to environmental influences “for better and for worse” (Bakermans-Kranenburg and van IJzendoorn
2011, p. 39). According to this viewpoint, carriers of the 7-repeat allele (DRD4-7r) may be disproportionally susceptible for developing negative behavioral outcomes in an adverse environment, but are also more likely to respond with positive behavioral outcomes when in a favorable environment (Belsky and Hartman
2014). In the present study, we aimed to investigate the possible moderating role of DRD4 in the prospective association between low and high levels of peer social preference and the development of conduct problems and prosocial behavior, among children attending elementary school who were followed annually from age 9 to 12 years.
DRD4 7-Repeat Allele and Environmental Influences
According to the differential susceptibility hypothesis (Belsky
1997; Belsky and Hartman
2014), some genetic variants may render individuals more malleable to negative as well as positive environments with respect to subsequent development, while other individuals—depending on their genetic make-up—are altogether less influenced by their environment. In a nutshell, this viewpoint proposes that, in order to increase reproductive fitness it makes evolutionary sense that some children are more susceptible to their environment than others (Belsky
1997; Belsky and Hartman
2014). That is, parents may (subconsciously or consciously) aim to modify children’s behavior so that it matches the environmental requirements. If the future environment is predicted correctly, a beneficial behavior-environment match occurs that may support the offspring’s health and reproductive fitness. However, given that future environmental circumstances are uncertain, for some children a mismatch occurs, potentially resulting in adverse outcomes. Thus, if within a family some children are born with a genetic disposition that renders them highly susceptible to their environment and others have a genetic disposition that renders them less susceptible, the probability that for all offspring such a detrimental mismatch takes place decreases (example adapted from Belsky
1997).
A potential candidate gene that may further our understanding of individual differences in sensitivity to the environment is the dopamine receptor D4 gene, DRD4 (Bakermans-Kranenburg and van IJzendoorn
2011; Belsky and Hartman
2014). DRD4 regulates dopamine receptor activity in the brain, particularly in brain regions of the mesocorticolimbic dopamine pathway (Oak et al.
2000). The neurotransmitter dopamine plays a major role in reward, punishment, attention and motivation mechanisms related to social interaction and learning. Furthermore, dopamine may signal the salience of social events and is a key factor in the imprinting of motivational importance to environmental factors (Trainor
2011).
The coding DNA sequence of DRD4 is highly polymorphic, resulting in receptor variants that may be functionally different. In this regard, the 48-bp tandem repeat (48-bp VNTR) in the third exon, consisting of 2–11 repeats, has received much research attention in behavior genetics. It has been shown that DRD4 has higher potency for dopamine-mediated coupling to adenylyl cyclase in the presence of the short 2-repeat and 4-repeat alleles, than when receptors are encoded by the 7-repeat allele, known as DRD4-7r (Oak et al.
2000; Schoots and Van Tol
2003). Decreased postsynaptic inhibition due to the 7-repeat allele results in lower dopaminergic tone and a suboptimal response to dopamine. This is associated with heightened reward-related reactivity in the ventral striatum and reward-related behaviors like impulsivity (Forbes et al.
2009). In addition, the mesocorticolimbic dopamine pathway is associated with the functioning of the anterior cingulate cortex, which is related to processing punishment and reward stimuli. Changes in dopamine levels due to the DRD4 polymorphism could thus enhance social-environmental signals related to reward and punishment (Posner and Rothbart
2009). Indeed, subjects with the 7-repeat allele show increased reactivity to social-environmental stimuli compared to subjects without this allele, as evidenced by findings from brain imaging, observational and experimental studies in humans and animals (Grady et al.
2013; Sheese et al.
2007). When confronted with emotional stimuli, carriers of the DRD4-7r allele were found to show more brain activity than non-carriers in brain regions associated with attention to and appraisal of negative emotional stimuli, as well as in brain regions involved in preparation for action (Gehricke et al.
2015). To the best of our knowledge, as of yet no studies have used functional brain imaging to investigate whether brain regions that are involved in reactivity and attention with regard to negative stimuli also apply to positive stimuli. However, observational research has indicated that individuals with the 7-repeat allele show heightened sensitivity to positive parenting environments when compared to individuals without this allele (Bakermans-Kranenburg and van IJzendoorn
2011). Together, these findings may suggest that individuals with a 7-repeat allele of the DRD4 gene are more susceptible to their environment than individuals without this allele, irrespective of whether this environment is positive or negative. Furthermore, some authors suggested that the dopaminergic system is key to the development of social behavior (Insel
2003). This statement is supported by the fact that on a behavioral level DRD4-7r has been related to aggression in children (Schmidt et al.
2002), to conduct problems and oppositional behavior in individuals with Attention Deficit Hyperactivity Disorder (ADHD; Holmes et al.
2002; Kirley et al.
2004), and to diminished levels of prosocial behavior (Anacker et al.
2013; DiLalla et al.
2009; Jiang et al.
2013).
A recent meta-analysis showed that children with less efficiently functioning dopamine-related genetic variants (of which DRD4 was the most studied gene) do worse in negative parental rearing environments than children without such alleles (Bakermans-Kranenburg and van IJzendoorn
2011). At the same time, the authors concluded that children with susceptibility alleles are also likely to profit most from positive rearing environments (Bakermans-Kranenburg and van IJzendoorn
2011). Despite that the results presented in that meta-analysis generally supported the differential susceptibility hypothesis, the study of differential susceptibility of DRD4 to the social environment is far from complete.
First, although gene–environment interaction (G × E) studies of DRD4 in the parenting context are fairly common, only a few studies focused on the peer environment (i.e., DiLalla et al.,
2009; Kretschmer et al.
2013). As said, children in elementary school function in the presence of their peers for a large proportion of their day. Consequently, the peer environment becomes increasingly important for the development of school-aged children (Sroufe et al.
2009). None of the studies that investigated the peer environment × DRD4 interaction effects focused on the elementary school period. DiLalla et al. (
2009) found that preschoolers carrying the DRD4-7r allele showed more aggression during peer-play in an environment where there was little peer aggression, while in a highly aggressive environment all children showed aggressive behavior regardless of genotype. No evidence of G × E was found for the association between peers’ prosocial behavior and children’s own prosocial behavior in that study. Kretschmer et al. (
2013) focused on victimization and social well-being during adolescence as predictors of delinquency. These authors found that, in contrast to previous findings and their own hypotheses, the adolescents who did
not have the DRD4-7r allele, as opposed to those who did have this allele, were more susceptible to the effects of victimization and social well-being. Thus, information on the elementary school peer environment is lacking and the scarce studies with regard to moderation by DRD4 genotype in the relation between peer experiences and (mal)adjustment have produced inconclusive findings.
Second, many previous studies have studied environmental variables that not all children will be exposed to on a daily basis and for the better part of the week, such as bully-victimization, intrusive parenting, or peer aggression (e.g., DiLalla et al.
2009; Kretschmer et al.
2013; Propper et al.
2007). It is currently not known whether moderating effects of DRD4 also extend to peer experiences that children will encounter on each typical school day. In the present study we therefore focused on children’s social preference among peers as the environmental factor of interest. Peer social preference in the classroom refers to the extent to which children are liked relative to disliked by their classmates. It is the result of a natural evaluation process that occurs in every social setting, for every individual within that setting (Coie et al.
1982; Rubin et al.
2006). Establishing a positive social standing in the larger peer-group is a key developmental task for children in elementary school, which facilitates a healthy behavioral development (Sroufe et al.
2009). Indeed, the impact of low social preference within the peer group on behavioral misconduct in children has been well documented (for overviews, see Parker et al.
2006; Rubin et al.
2006). However, and in accordance with the “for better and for worse” hypothesis, the influence of peer relations is multidirectional: being mostly disliked among peers may elevate the risk for the development of conduct problems and may hinder prosocial development; in contrast, being mostly liked may buffer against the development of conduct problems and may promote prosocial behavioral development (Ladd
2006; Twenge et al.
2007; Wentzel
2014; Wentzel and McNamara
1999; Witvliet et al.
2009). Therefore, by focusing on social preference as the environmental peer-factor of interest we aim to expand previous results found in the field of gene × peer environment interactions.
Third, and related to the previous argument, none of the previous studies focused on both negative and positive environments with regard to both negative and positive outcomes. The study by Kretschmer et al. (
2013) focused on negative and positive peer environmental factors with respect to predicting negative behavioral outcomes. The study by DiLalla et al. (
2009) focused on a positive peer environment with respect to predicting positive behavioral outcomes and a negative environment with respect to predicting negative behavioral outcomes. Other studies also focused on either the positive environment or the negative environment and/or either positive outcomes or negative outcomes (e.g., see examples in the overview of Bakermans-Kranenburg and van IJzendoorn
2011). However, less negative behavioral outcomes or even the absence of negative behavioral outcomes does not necessarily mean that behavioral outcomes are positive. This also applies vice versa: less positive behavioral outcomes or the absence of positive outcomes does not necessarily mean that behavioral outcomes are negative. The same holds for the environment: the absence of a negative environment or a less negative environment does not necessarily mean that the environment is positive, and vice versa. Ideally, the study of differential susceptibility includes both negative and positive environments as well as both negative and positive behavioral outcomes to test for all possibilities: (a) a negative environment predicting more positive behavioral outcomes and less negative behavioral outcomes and (b) a positive environment predicting less positive behavioral outcomes and more negative behavioral outcomes. To this end, we focused on peer social preference as our environmental factor of interest and conduct problems and prosocial behavior as our behavioral outcomes of interest. Peer social preference encompasses both a risk (i.e., negative social preference scores: children who are more disliked relative to liked) and a protective end (i.e., positive social preference scores: children who are more liked relative to disliked). Thus, this allows for a comprehensive test of the differential susceptibility hypothesis. That is, moderation by DRD4 genotype in both the “for better” and the “for worse” direction can be tested by including both positive and negative peer environmental factors with respect to predicting both positive and negative outcomes.
Lastly, many previous studies suffered from design limitations because most were cross-sectional or longitudinal prediction studies that were built upon the assumption that children’s environment predicts subsequent behavior and not vice versa. However, previous studies have shown that associations between social preference and behavior may be bidirectional: children’s social standing among peers may influence their behavior and their behavior may influence their social preference among peers (e.g., Van Lier and Koot
2010). Thus, when developmental models do not account for the possibility of these bidirectional effects, the direction of influence between environmental and behavioral factors may be obscured. Furthermore, by using the participants as their own controls, our longitudinal study in which the behavioral and environmental factors are assessed in parallel over 4 years enables investigating whether behavior has changed from a prior baseline level after experiencing low or high social preference.