Attachment insecurity and the biological embedding of reproductive strategies: Investigating the role of cellular aging.

Evolutionary-developmental psychologists have posited that individuals who grow up in stressful rearing circumstances follow faster life history strategies, thereby increasing their chances of reproduction. This preregistered study tested this stress-acceleration hypothesis in a low-risk longitudinal sample of 193 Dutch mother-child dyads, by investigating whether infant-mother attachment insecurity at 12 months of age predicted earlier pubertal onset and more callous-unemotional traits, aggression and risk-taking about a decade later. Also evaluated were the possible mediating roles of two biomarkers of accelerated aging (i.e., telomere length, epigenetic aging) at age 6. Structural equation modelling revealed no effects of attachment insecurity on biomarkers, pubertal timing or behavior. These null findings suggest that the explanatory value of evolutionary-developmental thinking might be restricted to high-risk samples, though unexplored variation in susceptibility to environmental influences might also explain the null findings.

Maternal Prenatal Anxiety and the Fetal Origins of Epigenetic Aging.

BACKGROUND: The fetal origins of mental health is a well-established framework that currently lacks a robust index of the biological embedding of prenatal adversity. The Pediatric-Buccal-Epigenetic (PedBE) clock is a novel epigenetic tool that associates with aspects of the prenatal environment, but additional validation in longitudinal datasets is required. Likewise, the relationship between prenatal maternal mental health and the PedBE clock has not been described. METHODS: Longitudinal cohorts from the Netherlands (Basal Influences on Baby Development [BIBO] n = 165) and Singapore (Growing Up in Singapore Towards Healthy Outcomes [GUSTO] n = 340) provided data on prenatal maternal anxiety and longitudinal assessments of buccal cell-derived genome-wide DNA methylation assessed at 6 and 10 years of age in BIBO, and at 3, 9, and 48 months of age in GUSTO. Measures of epigenetic age acceleration were calculated using the PedBE clock and benchmarked against an established multi-tissue epigenetic predictor. RESULTS: Prenatal maternal anxiety predicted child PedBE epigenetic age acceleration in both cohorts, with effects largely restricted to males and not females. These results were independent of obstetric, socioeconomic, and genetic risk factors, with a larger effect size for prenatal anxiety than depression. PedBE age acceleration predicted increased externalizing symptoms in males from mid- to late childhood in the BIBO cohort only. CONCLUSIONS: These findings point to the fetal origins of epigenetic age acceleration and reveal an increased sensitivity in males. Convergent evidence underscores the societal importance of providing timely and effective mental health support to pregnant individuals, which may have lasting consequences for both mother and child.

Financial stress during COVID-19: implications for parenting behaviour and child well-being.

BACKGROUND: Family financial stress and parenting behaviours are each associated with child behaviours. We sought to explore the association between parent financial stress and child socioemotional and behavioural difficulties during the COVID-19 pandemic and examine parenting behaviour, including overreactive and lax parenting approaches, as a potential mediator to this relationship. METHODS: Cross-sectional sample of parent and child data pairings in Ontario, Canada between April and November of 2020. Linear models were used to describe the relationships between financial worry, child Strengths and Difficulties Questionnaire (SDQ) total difficulties and parenting behaviours measured by the Parenting Scale 8-item (PS-8), which includes measures of both overreactive and lax parenting tendencies. Formal mediation testing was performed to assess the potential mediating role of parenting behaviour. RESULTS: 528 parent and child pairs were enrolled from largely European ancestry (78%), female (93%) and varied household income levels. Analysis revealed increased financial worry during the COVID-19 pandemic was significantly associated with increased child SDQ total difficulties scores (ß=0.23, SE=0.10, p=0.03). This relationship was mediated by reported parenting behaviour, independent of parent education, household income, parent age, parent sex, parent anxiety and child sex (total effect: ß=0.69, p=0.02, average causal mediation effects: ß=0.50, p=0.02, average direct effects: ß=0.19, p=0.08). CONCLUSION: Financial stress during the COVID-19 pandemic was associated with poorer child social and emotional well-being. Parenting behaviours measured by the PS-8 significantly mediated these effects. This work supports the importance of policies aimed to alleviate family financial stresses and highlights the potential impact such policies have on child well-being.

Histone deacetylase 1 and 2 drive differentiation and fusion of progenitor cells in human placental trophoblasts.

Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs by differentiation of underlying progenitor cells called cytotrophoblasts, which then fuse into the syncytiotrophoblast layer. Differentiation is associated with chromatin remodeling and specific changes in gene expression mediated, at least in part, by histone acetylation. However, the epigenetic regulation of human cytotrophoblast differentiation and fusion is poorly understood. In this study, we found that human syncytiotrophoblast development was associated with deacetylation of multiple core histone residues. Chromatin immunoprecipitation sequencing revealed chromosomal regions that exhibit dynamic alterations in histone H3 acetylation during differentiation. These include regions containing genes classically associated with cytotrophoblast differentiation (TEAD4, TP63, OVOL1, CGB), as well as near genes with novel regulatory roles in trophoblast development and function, such as LHX4 and SYDE1. Prevention of histone deacetylation using both pharmacological and genetic approaches inhibited trophoblast fusion, supporting a critical role of this process for trophoblast differentiation. Finally, we identified the histone deacetylases (HDACs) HDAC1 and HDAC2 as the critical mediators driving cytotrophoblast differentiation. Collectively, these findings provide novel insights into the epigenetic mechanisms underlying trophoblast fusion during human placental development.

The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells.

The development of biological markers of aging has primarily focused on adult samples. Epigenetic clocks are a promising tool for measuring biological age that show impressive accuracy across most tissues and age ranges. In adults, deviations from the DNA methylation (DNAm) age prediction are correlated with several age-related phenotypes, such as mortality and frailty. In children, however, fewer such associations have been made, possibly because DNAm changes are more dynamic in pediatric populations as compared to adults. To address this gap, we aimed to develop a highly accurate, noninvasive, biological measure of age specific to pediatric samples using buccal epithelial cell DNAm. We gathered 1,721 genome-wide DNAm profiles from 11 different cohorts of typically developing individuals aged 0 to 20 y old. Elastic net penalized regression was used to select 94 CpG sites from a training dataset (n = 1,032), with performance assessed in a separate test dataset (n = 689). DNAm at these 94 CpG sites was highly predictive of age in the test cohort (median absolute error = 0.35 y). The Pediatric-Buccal-Epigenetic (PedBE) clock was characterized in additional cohorts, showcasing the accuracy in longitudinal data, the performance in nonbuccal tissues and adult age ranges, and the association with obstetric outcomes. The PedBE tool for measuring biological age in children might help in understanding the environmental and contextual factors that shape the DNA methylome during child development, and how it, in turn, might relate to child health and disease.