Search

ObjectiveWomen exposed to childhood maltreatment (CM) are more likely to exhibit insensitive parenting, which may have consequences for their offspring's development. Variation in the oxytocin-receptor gene (OXTR) moderates risk of CM-associated long-term sequelae associated with mother-child attachment, although functionality of previously investigated single nucleotide polymorphisms (SNPs) remained elusive. Here, we investigated the role of OXTR rs237895, a brain tissue expression quantitative trait locus (eQTL), as a moderator of the relationship between CM and maternal behavior (MB) and the association between MB and offspring attachment security.MethodOf 110 women with information on rs237895 genotype (T-allele = 64, CC = 46), 107 had information on CM (CTQ) and 99 on standardized observer-based ratings of MB at 6 months postpartum (responsivity and detachment), which were used in principal component analysis to obtain a latent factor representing MB. Offspring (n = 86) attachment was evaluated at 12 months of age. Analyses predicting MB were adjusted for socioeconomic status, age, postpartum depression, and genotype-based ethnicity. Analyses predicting child attachment were adjusted for infant sex, socioeconomic status, and postpartum depression.Resultsrs237895 significantly moderated the relationship between CM and MB (F1;66 = 7.99, p < .01), indicating that CM was associated with maternal insensitivity only in high-OXTR-expressing T-allele carriers but not in low-OXTR-expressing CC homozygotes. Moreover, maternal insensitivity predicted offspring insecure attachment (B = -0.551; p < .05).ConclusionWomen with a high OXTR expressing genotype are more susceptible to CM-related impairments in MB that, in turn, predict attachment security in their children, supporting the role of the OT system in the intergenerational transmission of risk associated with maternal CM.

Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.

A recent article in this journal reported a number of gene × environment interactions involving a serotonin transporter-gene network polygenic score and a composite index of prenatal adversity predicting several problem behavior outcomes at 48 months (e.g., anxious/depressed, pervasive developmental problems) and at 60 months (e.g., withdrawal, internalizing problems), yet did not illuminate the nature or form these genetic × environment interactions took. Here we report results of six additional analyses to evaluate whether these interactions reflected diathesis-stress or differential-susceptibility related processes. Analyses of the regions of significance and proportion of interaction index are consistent with the diathesis-stress model, seemingly because of the truncated nature of the adversity score (which did not extend to supportive/positive prenatal experiences/exposures); in contrast, the proportion (of cases) affected index favors the differential-susceptibility model. These results suggest the need for future studies to extend measurement of the prenatal environment to highly supportive experiences and exposures.

Maternal behavior (MB) is observable across mammals and represents an important feature of environmental variation during early postnatal development. Oxytocin (OT) plays a crucial role in MB. Even prior to childbirth, pregnancy induces epigenetic and other downstream changes in the maternal OT-system, likely mediated by the actions of steroid hormones. However, little is known about the nature and consequences of epigenetic modifications in the maternal OT-encoding gene (OXT) during pregnancy. Our study aims to investigate temporal dynamics of OXT promoter DNA methylation (DNAm) throughout pregnancy in predicting MB in humans. In 107 mother-child dyads, maternal OXT DNAm was serially analyzed in whole blood in early, mid and late pregnancy. MB was coded based on standardized mother-child interactions at six months postpartum. After controlling for cellular heterogeneity, race/ethnicity, age, and socioeconomic status, OXT-promoter DNAm exhibited a dynamic profile during pregnancy (b = 0.026, t=-3.37, p

Objective: To investigate whether childcare support from grandparents and domestic helpers is associated with family well‐being in Singapore, with a focus on parent and child psychological well‐being as well as the quality of interactions and relationships within the family. Background: Research on the implications of childcare support from maternal grandparents, paternal grandparents, and domestic helpers for family well‐being remains a gap in the literature. This involvement could enhance family well‐being through instrumental assistance and emotional encouragement in childcare. However, it could also create a negative emotional climate for families if the relationship of the mother with the grandparents or domestic helper is marked by conflict. Method: This study used questionnaire data from 615 mother–child dyads from the birth cohort, Growing Up in Singapore Towards healthy Outcomes. The exposure variable was children's caregiving arrangements assessed at child ages 4.5 and 6 years, and the outcome variables were maternal well‐being, maternal parenting, and family functioning measured at concurrent assessments, and child well‐being assessed at age 10 years. Results: Childcare support from maternal grandparents, but not from paternal grandparents or domestic helpers, showed concurrent associations with warmer parenting by mothers at child ages 4.5 and 6 years. Early childcare support from domestic helpers at child age 6 years predicted higher depressive symptoms in children at age 10 years. Conclusion: Our findings suggest that childcare support from maternal grandparents, who are most likely to share a close bond and value system with mothers, could be most beneficial for families in Singapore. [ABSTRACT FROM AUTHOR]

Disorganized attachment is a risk for mental health problems, with increasing work focused on understanding biological mechanisms. Examining late childhood brain morphology may be informative – this stage coincides with the onset of many mental health problems. Past late childhood research reveals promising candidates, including frontal lobe cortical thickness and hippocampal volume. However, work has been limited to Western samples and has not investigated mediation or moderation by brain morphology. Furthermore, past cortical thickness research included only 33 participants. The current study utilized data from 166 children from the GUSTO Asian cohort, who participated in strange situations at 18 months and MRI brain imaging at 10.5 years, with 124 administered the Child Behaviour Checklist at 10.5 years. Results demonstrated disorganization liked to internalizing problems, but no mediation or moderation by brain morphology. The association to internalizing (but not externalizing) problems is discussed with reference to the comparatively higher prevalence of internalizing problems in Singapore. [ABSTRACT FROM AUTHOR]

Analysis of DNA methylation helps to understand the effects of environmental exposures as well as the role of epigenetics in human health. Illumina, Inc. recently replaced the HumanMethylation450 BeadChip (450K) with the EPIC BeadChip, which nearly doubles the measured CpG sites to >850,000. Although the new chip uses the same underlying technology, it is important to establish if data between the two platforms are comparable within cohorts and for meta-analyses. DNA methylation was assessed by 450K and EPIC using whole blood from newborn (n = 109) and 14-year-old (n = 86) participants of the Center for the Health Assessment of Mothers and Children of Salinas. The overall per-sample correlations were very high (r >0.99), although many individual CpG sites, especially those with low variance of methylation, had lower correlations (median r = 0.24). There was also a small subset of CpGs with large mean methylation β-value differences between platforms, in both the newborn and 14-year datasets. However, estimates of cell type proportion prediction by 450K and EPIC were highly correlated at both ages. Finally, differentially methylated positions between boys and girls replicated very well by both platforms in newborns and older children. These findings are encouraging for application of combined data from EPIC and 450K platforms for birth cohorts and other population studies. These data in children corroborate recent comparisons of the two BeadChips in adults and in cancer cell lines. However, researchers should be cautious when characterizing individual CpG sites and consider independent methods for validation of significant hits.

Early life experience influences stress reactivity and mental health through effects on cognitive-emotional functions that are, in part, linked to gene expression in the dorsal and ventral hippocampus. The hippocampal dentate gyrus (DG) is a major site for experience-dependent plasticity associated with sustained transcriptional alterations, potentially mediated by epigenetic modifications. Here, we report comprehensive DNA methylome, hydroxymethylome and transcriptome data sets from mouse dorsal and ventral DG. We find genome-wide transcriptional and methylation differences between dorsal and ventral DG, including at key developmental transcriptional factors. Peripubertal environmental enrichment increases hippocampal volume and enhances dorsal DG-specific differences in gene expression. Enrichment also enhances dorsal-ventral differences in DNA methylation, including at binding sites of the transcription factor NeuroD1, a regulator of adult neurogenesis. These results indicate a dorsal-ventral asymmetry in transcription and methylation that parallels well-known functional and anatomical differences, and that may be enhanced by environmental enrichment.

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development.

Background: Harsh parenting in early childhood is related to offspring's adverse behavioral outcomes. Due to the scarcity of longitudinal neuroimaging data, few studies have explored the neurobiological underpinnings of this association, focusing on within-person variability. This study examined the temporal associations among harsh parenting, later behavioral problems, and the developmental trajectories of amygdala volume and amygdala resting-state functional connectivity (RSFC) profiles, using longitudinal neuroimaging data. Methods: The study was embedded in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. T1-weighted (296 children, 642 scans) and resting-state functional scans (256 children, 509 scans) were collected at ages 4.5, 6, 7.5, and 10.5 years. Amygdala volume and RSFC between the amygdala and six brain regions that have leading roles in emotional regulation were extracted. Harsh parenting at 4.5 years and child behavioral problems at 10.5 years were assessed via parent-report questionnaires. Linear regression and linear mixed models were applied. Results: Harsh parenting was associated with more severe externalizing problems in girls (β = 0.24, 95% CI 0.08–0.40) but not boys (p int = 0.07). In the overall sample, harsh parenting was associated with the developmental trajectories of amygdala-ACC, amygdala-OFC, and amygdala-DLPFC RSFC. In addition, the developmental trajectory of amygdala-ACC RSFC mediated the harsh parenting–externalizing problems association in girls (indirect effect = 0.06, 95% CI 0.01–0.14). Conclusions: Harsh parenting in early childhood was associated with amygdala neurocircuitry development and behavioral problems. The developmental trajectory of amygdala-ACC RSFC is a potential neural mechanism linking harsh parenting and externalizing problems in girls. [ABSTRACT FROM AUTHOR]