Developmental mediation of genetic variation in response to the Fast Track prevention program

Abstract

We conducted a developmental analysis of genetic moderation of the effect of the Fast Track intervention on adult externalizing psychopathology. The Fast Track intervention enrolled 891 children at high risk to develop externalizing behavior problems when they were in kindergarten. Half of the enrolled children were randomly assigned to receive 10 years of treatment with a range of services and resources provided to the children and their families and the other half to usual care (controls). We previously showed that the effect of the Fast Track intervention on participants’ risk of externalizing psychopathology at age 25 years was moderated by a variant in the Glucocorticoid Receptor Gene (NR3C1). Children who carried copies of the A-allele of the single-nucleotide polymorphism rs10482672 had the highest risk of externalizing psychopathology if they were in the control arm of the trial and the lowest risk of externalizing psychopathology if they were in the treatment arm. In this study, we test a developmental hypothesis about the origins of this for-better-and-for-worse gene-by-intervention interaction (GxI): That the observed GxI effect on adult psychopathology is mediated by the proximal impact of intervention on childhood externalizing problems and adolescent substance use and delinquency. We analyzed longitudinal data tracking the 270 European-American children in the Fast Track RCT with available genetic information (129 intervention children and 141 control-group peers, 69% male) from kindergarten through age 25 years. Results show that the same pattern of “for-better-and-for-worse” susceptibility to intervention observed at the age-25 follow-up was evident already during childhood. At the elementary school follow-ups and at the middle/high-school follow-ups, rs10482672 predicted better adjustment among children receiving the Fast Track intervention, and worse adjustment among children in the control condition. In turn, these proximal GxI effects early in development mediated the ultimate GxI effect on externalizing psychopathology at age 25 years. We discuss the contribution of these findings to the growing literature on genetic susceptibility to environmental intervention.

The PAX Good Behavior Game: One Model for Evolving a More Nurturing Society

“…As PAX GBG is a universal prevention intervention, the overall effects are likely to be small in terms of clinical effect sizes such as Cohen’s d (Greenberg & Abenavoli 2017 ) and provide greater benefits to risk groups, such as documented in the Hopkins’ studies. This is also consistent with genetic studies on “differential susceptibility” (Albert et al 2015 ; Belsky & van IJzendoorn 2017 ; Boyce 2016 ).…”

Genetic differential susceptibility on trial: Meta-analytic support from randomized controlled experiments

“…Third, macrotrials, or field trials, are broad educational, parent training, or social programs that aim at changing general life circumstances for target groups including proximal and more distal components of their environment (Albert et al, 2015 [ Kohen et al, 2011;Van den Hoofdakker et al, 2012). This is the type of trial that might be implemented on a large scale and is closest to the daily realities of parents, practitioners, or policymakers.…”

“…Third, macrotrials , or field trials, are broad educational, parent training, or social programs that aim at changing general life circumstances for target groups including proximal and more distal components of their environment (Albert et al, 2015 [this issue]; Bakermans-Kranenburg et al, 2008; Beach, Brody, Lei, & Philibert, 2010; Bockting, Mocking, Lok, Koeter, & Schene, 2013; Brett et al, 2015 [this issue]; Brody, Chen, & Beach, 2013; Brody, Chen, Beach, Kogan, et al 2014; Brody et al, 2006; Brody, Yu, & Beach, 2015 [this issue]; Cicchetti, Rogosch, and Toth, 2011; Cleveland et al, 2015 [this issue]; Kohen et al, 2011; Van den Hoofdakker et al, 2012). This is the type of trial that might be implemented on a large scale and is closest to the daily realities of parents, practitioners, or policymakers.…”

Neuroplasticity of selective attention: Research foundations and preliminary evidence for a gene by intervention interaction

“…Previous gene × intervention studies mainly focused on precursors and markers of developmental psychopathology (52)(53)(54)(55)(56)(57). In this context, particular attention was paid to the investigation of interactions between specific candidate genes and interventions on problem behaviors, in particular on externalizing behavior problems from toddlerhood through adolescence (52, 53, 55, 58) and the use of substances such as tobacco and alcohol in adolescence (54,56,(59)(60)(61).…”