Explore the vast range of titles available.

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 racially/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 SD above the mean on polygenic sensitivity, or 25% of the sample. Similar to personalized medicine, it is time to understand individual and sociocultural differences in treatment response and individualize psychosocial interventions to reduce the burden of child psychopathology and maximize well-being for children growing up in a wide range of physical environments and cultures.

We examined caregiver report of externalizing behavior from 12 to 54 months of age in 102 children randomized to care as usual in institutions or to newly created high-quality foster care. At baseline no differences by group or genotype in externalizing were found. However, changes in externalizing from baseline to 42 months of age were moderated by the serotonin transporter linked polymorphic region genotype and intervention group, where the slope for short–short (S/S) individuals differed as a function of intervention group. The slope for individuals carrying the long allele did not significantly differ between groups. At 54 months of age, S/S children in the foster care group had the lowest levels of externalizing behavior, while children with the S/S genotype in the care as usual group demonstrated the highest rates of externalizing behavior. No intervention group differences were found in externalizing behavior among children who carried the long allele. These findings, within a randomized controlled trial of foster care compared to continued care as usual, indicate that the serotonin transporter linked polymorphic region genotype moderates the relation between early caregiving environments to predict externalizing behavior in children exposed to early institutional care in a manner most consistent with differential susceptibility.

The effect of the Video-Feedback Intervention to Promote Positive Parenting and Sensitive Discipline (VIPP-SD) on daily cortisol production was tested in a randomized controlled trial with 130 families with 1- to 3-year-old children screened for their relatively high levels of externalizing behavior. Six 1.5-hr intervention sessions focusing on maternal sensitivity and discipline were conducted with individual families at their homes. Children in the intervention group showed lower cortisol levels, with a moderating role of the dopamine receptor D4 (DRD4) VNTR exon III polymorphism. The VIPP-SD program proved to be effective in decreasing daily cortisol production in children with the DRD4 7-repeat allele, but not in children without the DRD4 7-repeat allele. Our findings indicate that children are differentially susceptible to intervention effects dependent on the presence of the 7-repeat DRD4 allele.

Fragile X syndrome (FXS) is the most common single gene ( FMR1 ) disorder affecting cognitive and behavioral function in humans. This syndrome is characterized by a cluster of abnormalities including lower IQ, attention deficits, impairments in adaptive behavior and increased incidence of autism. Here, we show that young males with FXS have profound deficits in prepulse inhibition (PPI), a basic marker of sensorimotor gating that has been extensively studied in rodents. Importantly, the magnitude of the PPI impairments in the fragile X children predicted the severity of their IQ, attention, adaptive behavior and autistic phenotypes. Additionally, these measures were highly correlated with each other, suggesting that a shared mechanism underlies this complex phenotypic cluster. Studies in Fmr1 -knockout mice also revealed sensorimotor gating and learning abnormalities. However, PPI and learning were enhanced rather than reduced in the mutants. Therefore, these data show that mutations of the FMR1 gene impact equivalent processes in both humans and mice. However, since these phenotypic changes are opposite in direction, they also suggest that murine compensatory mechanisms following loss of FMR1 function differ from those in humans.

The present study examines the interaction between a polygenic score and an elementary school-based universal preventive intervention trial. The polygenic score reflects the contribution of multiple genes and has been shown in prior research to be predictive of smoking cessation and tobacco use (Uhl et al., 2014). Using data from a longitudinal preventive intervention study, we examined age of first tobacco use from sixth grade to age 18. Genetic data were collected during emerging adulthood and were genotyped using the Affymetrix 6.0 microarray. The polygenic score was computed using these data. Discrete-time survival analysis was employed to test for intervention main and interaction effects with the polygenic score. We found a main effect of the intervention, with the intervention participants reporting their first cigarette smoked at an age significantly later than controls. We also found an Intervention × Polygenic Score interaction, with participants at the higher end of the polygenic score benefitting the most from the intervention in terms of delayed age of first use. These results are consistent with Belsky and colleagues' (e.g., Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2007; Belsky & Pleuss, 2009, 2013; Ellis, Boyce, Belsky, Bakermans-Kranenburg, & van IJzendoorn, 2011) differential susceptibility hypothesis and the concept of “for better or worse,” wherein the expression of genetic variants are optimally realized in the context of an enriched environment, such as provided by a preventive intervention.

The DDD study recruited more than 13,500 families with probands with severe, probably monogenic disorders in the United Kingdom and Ireland and obtained a genetic diagnosis in approximately 41% of probands.

Exposure to stressors results in a spectrum of autonomic, endocrine, and behavioral responses. A key pathway in this response to stress is the hypothalamic–pituitary–adrenal (HPA) axis, which results in a transient increase in circulating cortisol, which exerts its effects through the two related ligand-activated transcription factors: the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR). Genetic polymorphisms in these receptors have been shown to influence HPA axis reactivity, and chronic dysregulation of the HPA axis has been associated with the development of several psychiatric disorders. The objective of the study was to test the association between four functional polymorphisms in NR3C1 (encoding GR: ER22/23EK-rs6189, N363S-rs6195, Bcl I-rs41423247, A3669G-rs6198) and two in NR3C2 (encoding MR: 215G/C-rs2070951, I180 V-rs5522) with childhood ADHD. Family-based association tests (FBAT) were conducted with the categorical diagnosis of ADHD, behavioral and cognitive phenotypes related to ADHD, as well as with treatment response assessed in a 2-week, double-blind, placebo-controlled trial with methylphenidate. A specific haplotype (G:A:G:G; ER22/23EK- N363S- Bcl I- A3669G) of NR3C1 showed a significant association with behaviors related to ADHD (particularly thought and attention problems, aggressive behavior), comorbidity with oppositional defiant disorder, and executive function domains. An association was also observed with treatment response (assessed by the Conners’-Teachers and Restricted Academic Situation Scale). In contrast, MR gene polymorphisms were not associated with any of the variables tested. To the best of our knowledge, this is the first report showing an association between functional polymorphisms in NR3C1 and ADHD, providing genetic evidence for involvement of the HPA axis in the disorder and treatment response.

Background A central tenet in developmental psychopathology is that childhood rearing experiences have a major impact on children’s development. Recently, candidate genes have been identified that may cause children to be differentially susceptible to these experiences (i.e., susceptibility genes). However, our understanding of the differential impact of parenting is limited at best. Specifically, more experimental research is needed. The ORCHIDS study will investigate gene-(gene-)environment interactions to obtain more insight into a) moderating effects of polymorphisms on the link between parenting and child behavior, and b) behavioral mechanisms that underlie these gene-(gene-)environment interactions in an experimental design. Methods/Design The ORCHIDS study is a randomized controlled trial, in which the environment will be manipulated with an intervention (i.e., Incredible Years parent training). In a screening, families with children aged 4–8 who show mild to (sub)clinical behavior problems will be targeted through community records via two Dutch regional healthcare organizations. Assessments in both the intervention and control condition will be conducted at baseline (i.e., pretest), after 6 months (i.e., posttest), and after 10 months (i.e., follow-up). Discussion This study protocol describes the design of a randomized controlled trial that investigates gene-(gene-)environment interactions in the development of child behavior. Two hypotheses will be tested. First, we expect that children in the intervention condition who carry one or more susceptibility genes will show significantly lower levels of problem behavior and higher levels of prosocial behavior after their parent(s) received the Incredible Years training, compared to children without these genes, or children in the control group. Second, we expect that children carrying one or more susceptibility genes will show a heightened sensitivity to changes in parenting behaviors, and will manifest higher emotional synchronization in dyadic interchanges with their parents. This may lead to either more prosocial behavior or antisocial behavior depending on their parents’ behavior. Trial registration Dutch Trial Register (NTR3594)

Previous research on adults has shown that a functional polymorphism in the promoter region of the monoamine oxidase A ( MAOA ) gene moderates the impact of childhood maltreatment on risk for developing antisocial behavior. Thus far, attempts to replicate this finding have been mixed. The current study (i) presents new data investigating this finding in a sample of 975 seven-year-old boys, and (ii) evaluates the extant data by conducting a meta-analysis of published findings. We replicated the original finding by showing that the MAOA polymorphism moderates the development of psychopathology after exposure to physical abuse, we extended the finding to childhood closer in time to the maltreatment experience, and we ruled-out the possibility of a spurious finding by accounting for passive and evocative gene–environment correlation. Moreover, meta-analysis demonstrated that across studies, the association between maltreatment and mental health problems is significantly stronger in the group of males with the genotype conferring low vs high MAOA activity. These findings provide the strongest evidence to date suggesting that the MAOA gene influences vulnerability to environmental stress, and that this biological process can be initiated early in life.

Prader–Willi syndrome (PWS) is a highly variable genetic disorder affecting multiple body systems whose most consistent major manifestations include hypotonia with poor suck and poor weight gain in infancy; mild mental retardation, hypogonadism, growth hormone insufficiency causing short stature for the family, early childhood-onset hyperphagia and obesity, characteristic appearance, and behavioral and sometimes psychiatric disturbance. Many more minor characteristics can be helpful in diagnosis and important in management. PWS is an example of a genetic condition involving genomic imprinting. It can occur by three main mechanisms, which lead to absence of expression of paternally inherited genes in the 15q11.2–q13 region: paternal microdeletion, maternal uniparental disomy, and imprinting defect.