The EGDS provides a unique opportunity to blend the knowledge learned from rigorous tests of the social mediation and reactive pathway hypotheses with knowledge learned from efficacious preventive intervention trials to inform the development of highly-specified, genetically-informed preventive intervention trials. We believe that the field is at an optimal juncture to pursue such translational work and merge knowledge across the two fields in order to move beyond the separate examination of focused interventions that test enhanced parent–child interactions with little consideration of specific genetic influences and genetic studies that describe environmentally mediated and moderated effects but do not directly apply this knowledge to benefit children and families. Developmental models that specify the mediating and moderating processes whereby neurobiological influences, genetic factors, and family environmental processes jointly produce maladaptive behaviors are becoming well–developed and lead quite naturally to consideration of how preventive interventions could be implemented to alter multi-determined maladaptive trajectories (e.g., van Goozen, Snoek, Fairchild, & Harold, 2007
EGDS provides an opportunity to draw on the work described throughout this manuscript to test theory-based hypotheses about the mechanisms of G×E. We can integrate this knowledge with the extant knowledge about family-environmental mediators of child adjustment (e.g., Eddy & Chamberlain, 2001; Martinez & Forgatch, 2001
) to generate hypotheses about how to adapt evidence-based psychosocial interventions to disrupt well-specified mechanisms of expression of adverse genetic influence. Specific hypotheses regarding the outcomes of a genetically-informed preventive intervention trial would be twofold.
First, if successful, genetically-informed interventions would alter parental responses to heritable evocative behavior in their children, leading to a mean level shift in behavior among children in the intervention condition. Evidence for mean level shifts in child and parenting behavior has been noted in randomized preventive intervention trials (Chamberlain & Reid, 1998
; DeGarmo & Forgatch, 2005
). However, pure psychosocial studies are not able to differentiate whether the mediators of change are genetically influenced. Refining our intervention models to consider the pathways whereby genetic characteristics of the child may influence parenting behavior should enable us to develop more precise and effective interventions.
Second, in a genetically-informed preventive intervention trial, we would hypothesize that the rank-order correlations between birth parents and child characteristics that were the foci of the intervention would be diminished or eliminated, whereas those that were not the foci of the intervention would remain equivalent between the intervention and control conditions, reflecting the specificity of the genetically-influenced processes targeted for intervention (see earlier discussion on the specificity of environmental mediation of genetic influences as shown in ). Thus, the social mediation pathway would be disrupted and adverse heritable traits in the child would not be associated with adverse social responses in families in the intervention condition, with families in the control condition continuing to evidence such pathways. Unique to G×E studies, this hypothesis can test the specificity of the social environment on hypothesized child behaviors.
To highlight the translational process across genetic research and preventive intervention research, we provide below an illustration of how Multidimensional Treatment Foster Care (MTFC), an intervention model with replicated efficacy, might be further enhanced by consideration of the type of genetically-informed research reviewed in this manuscript. We use MTFC solely as an illustrative example; similar extensions of this translational approach can be generated with any number of efficacious interventions targeting a wide array of maladaptive outcomes across development.
MTFC was originally developed to provide a community-based alternative to incarceration for boys with serious and chronic delinquency. It consists of a family-based intervention model in which youth from the child welfare and juvenile justice systems are placed with highly trained and supervised foster homes with state-certified foster parents. Youth and their caregivers are provided a set of seven coordinated services, including; a) daily telephone contact with the foster parents to monitor case progress and foster parents adherence to the MTFC model, b) weekly group supervision and support meetings for foster parents, c) foster parent's use of an individualized daily behavior management program for the youth, d) individual therapy for youth, e) family therapy (for the family of origin) focusing on parent management strategies, f) close monitoring of school attendance, performance, and homework completion, g) case management to coordinate the interventions in the foster family, peer, and school settings. Program staff on call at all times for foster and biological parents, and psychiatric consultation is provided as needed (Chamberlain, 2003
). Although the MTFC model has demonstrated efficacy in preventing delinquency outcomes and placement disruptions across genders, developmental age ranges, and contexts (Chamberlain, Leve, & DeGarmo, 2007
; Chamberlain & Reid, 1998
; Fisher, Burraston, & Pears, 2005
; Leve, Chamberlain, & Reid, 2005
; Price et al., 2007
), there remain some youth who receive MTFC services but who fail
to make improvements and/or maintain stable placement settings upon completion of treatment.
The research presented throughout this manuscript provides clues as to the mechanisms through which individual treatment failures may arise, and has direct implications for improving the efficacy of interventions by disrupting specified gene-environment interplay. Drawing from the model in , some youths' inherited maladaptive tendencies may evoke non-optimal caregiving environments, thereby leading to delinquent behaviors. Consistent with the social mediational pathway, successful MTFC intervention cases may represent those families in which the intervention helped caregivers effectively disregard the genetic predispositions that the child presented with, thereby preventing the escalation of risk. Conversely, less successful cases may be those in which the caregiver's monitoring, discipline, and support/warmth behaviors were influenced by the adverse genetic influences in the child, thereby escalating problem behavior, or cases in which the child's sensitivity and reactivity to such caregiver behavior was not ameliorated as a result of the intervention. A preventive intervention trial that utilized a prospective adoption sample such as EGDS would allow such associations between specific genetically-influenced child characteristics and specific parenting responses to be disentangled and subsequently targeted for intervention at the dyadic or family level. For example, a genetically-enhanced intervention might augment the standard MTFC intervention with components designed to help caregivers identify the associations between the child's inherited maladaptive characteristics and their own caregiving responses, and then use the role modeling, family therapy, and individual therapy approaches that form the core of the basic MTFC model to focus on breaking the associations between children's inherited risk behaviors and non-optimal caregiving responses.
Building on this MTFC example, hypothetical results that support the effectiveness of a modified intervention to reduce or eliminate adverse genetic influences on individual differences in children while at the same time increasing their exposure to a warm and sensitive caregiving environment are shown in . As is shown on the left half of the figure, support for the first hypothesis would be indicated by a mean level shift of children's psychopathology, such that children in the intervention condition whose caregiving families had been given the genetically-informed version of the intervention would manifest lower levels of psychopathology compared to children in the control condition. However, the expression of genetic influences would remain identical across the two conditions. The right half of the figure illustrates support for the second hypothesis, that the evocative correlations between a child's genetic predisposition and the response of the social environment would be disrupted in the intervention condition. Such a pattern of findings would provide support for the social mediation hypothesis.
Hypothetical results supporting the effectiveness of an intervention to reduce adverse genetic influences on individual differences in psychopathology.
Drawing on evidence for the mechanisms of G×E interaction described throughout this manuscript, the illustrations in can be further specified by including groups of families that vary across social contexts (e.g., depressed and nondepressed parents, economically stressed and non–economically stressed families, and maritally stressed and non–maritally stressed families). The evidence reviewed above would suggest that the hypothesized social mediation pathway would likely be influenced by levels of social contextual stress and that interventions might be more likely to show group differences when the specific nature of the associations between the social context and parenting is considered and carefully targeted.
Finally, an additional advance that G×E studies can offer to the development of preventive interventions is to help specify the optimal recipient and developmental period for a preventive intervention. For example, when specific developmental periods and/or specific behavioral characteristics support the social mediation pathway, members of the social environment that act as responders to the individual's genetically influenced characteristics may be the optimal entry into breaking the maladaptive cycle. Alternatively, when specific developmental periods and/or specific behavioral characteristics support the reactive pathway, preventive interventions that target the individual and train him/her to be less reactive to the social environment may be the more optimal intervention path.
The work summarized in this manuscript provides detailed clues as to where to search for mechanisms of G×E interaction and how an understanding of such mechanisms can help further specify preventive interventions for families at risk. Although G×E interaction studies and A×E studies have their divergences, we have demonstrated here how both are essential to furthering the understanding of the basic developmental processes that affect the likelihood that an individual with a given set of characteristics and given genes will be more or less likely to develop healthy outcomes as a function of his/her environment. Future research could be optimized by integrating what we are learning from A×E research with what we are learning from G×E research. Specifically, we need to know how polymorphisms that are associated with psychopathology in adolescents and adults are presented at the behavioral level in toddlers and preschoolers, prior to the onset of problem behavior. The blending of knowledge from these two areas of Gene × Environment interaction research will provide the strongest clues for where, when, and how to intervene to prevent the onset of psychopathology in children, adolescents, and adults.