Genetic moderation of the effects of the Family Check-Up intervention on children's internalizing symptoms: A longitudinal study with a racially/ethnically diverse sample

Abstract

Development involves synergistic interplay among genotypes and the physical and cultural environments, and integrating genetics into experimental designs that manipulate the environment can improve understanding of developmental psychopathology and intervention efficacy. Consistent with Differential Susceptibility Theory, individuals can vary in their sensitivity to environmental conditions including intervention for reasons including their genotype. As a consequence, understanding genetic influences on intervention response is critical. Empirically, we tested an interaction between a genetic index representing sensitivity to the environment and the Family Check-Up intervention. Participants were drawn from the Early Steps Multisite randomized prevention trial that included a low income and racial/ethnically diverse sample of children and their families followed longitudinally (n=515). As hypothesized, polygenic sensitivity to the environment moderated the effects of the intervention on 10-year-old children’s symptoms of internalizing psychopathology, such that children who were genetically sensitive and were randomly assigned to the intervention had fewer symptoms of child psychopathology than genetically sensitive children assigned to the control condition. A significant difference in internalizing symptoms assessed with a clinical interview emerged between the intervention and control groups for those 0.493 standard deviations above the mean on polygenic sensitivity, or 25% of the sample. Similar to personalized medicine, it is time to understand individual and socio-cultural differences in treatment response and individualize psychosocial interventions to reduce the burden of child psychopathology and maximize wellbeing for children growing up in a wide range of physical environments and cultures.

Trajectories and Predictors of Children's Early-Starting Conduct Problems: Child, Family, Genetic, and Intervention Effects

“…Of these studies, Keers et al (2016) and Lemery-Chalfant, Clifford, Dishion, Shaw, and Wilson (2018) focused on the outcome of internalizing problems in middle childhood, and Musci, Masyn, Uhl, Maher, Kellam, and Ialongo (2016) and Musci et al (2018) examined onset of smoking tobacco and cannabis use in adolescence. In our previous study with the Early Steps Multsite sample, we used a polygenic score that indexed susceptibility to the environment (i.e., genetic variants in this score predicted identical twin differences in emotional problems in middle childhood in a discovery GWAS) (Lemery-Chalfant et al, 2018). We reported a significant Polygenic × Intervention interaction, such that genetically susceptible children in the FCU condition had fewer internalizing symptoms than those in the control condition.…”

Annual Research Review: Umbrella synthesis of meta‐analyses on child maltreatment antecedents and interventions: differential susceptibility perspective on risk and resilience

“…Genetic markers have been found in genes involved in the dopaminergic and serotonergic system. In particular, the carriers of the dopamine receptor D4 7-repeat alleles seem to be open to the environment, for better and for worse, as demonstrated in correlational as well as experimental studies and this genotype might be embedded in larger dopamine-related genetic pathways or polygenetic susceptibility scores (Belsky & van IJzendoorn, 2017;Keers et al, 2016;Lemery-Chalfant et al, 2018). Another marker of differential susceptibility is biological sensitivity to context, involving heightened stress and immune reactivity to negative stimuli in a chaotic and stressful environment, and at the same time elevated processing of positive stimuli in a structured, supportive environment (Boyce, 2019).…”

Cultural development and psychopathology

“…Lemery-Chalfant, Clifford, Dishion, Shaw, and Wilson (2018) investigated the role of genes in sensitivity to the effects of the Family Check-Up intervention on children's internalizing symptoms. Participants were a diverse sample of 515 youth and their families drawn from a multisite randomized prevention trial followed longitudinally.…”