Epigenetic age (EA) acceleration (i.e., higher EA relative to chronological age) has been associated with adverse health outcomes and mortality in adults; and early pubertal development in ...adolescence. However, potential associations between gestational EA deviation (i.e., accelerated or decelerated EA relative to chronological age) at birth and childhood mental health outcomes remain poorly understood. This study aimed to investigate the association between gestational EA deviation and developmental and mental health outcomes in early childhood - a critical period of neurodevelopment.
Data were analysed from the Drakenstein Child Health Study (DCHS), a longitudinal birth cohort study in South Africa. Using DNAm data from umbilical cord blood samples, gestational EA deviation at birth was calculated as the residuals after regressing predicted EA estimates on chronological gestational age. Child developmental and mental health outcomes were assessed with the Bayley Scales of Infant and Toddler Development Third Edition and Child Behavior Checklist. Initially, bivariate linear regression was employed to explore unadjusted associations between gestational EA residuals at birth, and child developmental and mental health outcomes. Thereafter, multivariable linear regression models were used to determine adjusted associations. All models were controlled for socioeconomic status (SES), maternal substance use (alcohol consumption and tobacco smoking), maternal HIV status, maternal anaemia, child anthropometric measures (child sex, birthweight, gestational age), and the first 10 genomic principal components to adjust for population stratification.
A study sample of 275 children from the DCHS was included in this analysis. In the adjusted multivariable models, no significant associations were found between gestational EA deviation at birth and developmental or mental health outcomes in the index children, between ages 24 and 60 months. However, trend-level associations between gestational EA deviation at birth and externalising symptoms were observed at 24 months, for both the unadjusted model (β = −0.185, p = 0.0718) and the adjusted model (β = -0.169, p= 0.104).
These preliminary findings suggest a need for further, more well-powered studies to investigate the potential clinical and translational utility of gestational EA deviation at birth.
The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case-control molecular genetic data across 11 multiethnic studies to quantify PTSD ...heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h
) for European-American females of 29% that is similar to h
for schizophrenia and is substantially higher than h
in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD-for both European- and African-American individuals-and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.
Background
Maternal antenatal depression may be particularly prevalent in low‐ and middle‐income countries, but there is a paucity of data on its effect on birth outcomes in such settings. We ...investigated risk factors for antenatal depression and the associations between depression and infant birth outcomes in the Drakenstein Child Health Study (DCHS), a birth cohort study in the Western Cape, South Africa.
Methods
The prevalence of depression in pregnant women enrolled in the DCHS from primary care antenatal clinics was measured using the Beck Depression Inventory (BDI‐II). Predictors of antenatal depression were investigated using logistic regression, and the associations between depression and infant birth outcomes were examined in linear regression models.
Results
Among 726 pregnant women (median age: 26 years), 156 (21%) had BDI‐II scores suggesting depression. Independent predictors of depression included single marital status, low socioeconomic status (SES), recent stressful life events, unplanned pregnancy, childhood trauma, and past‐year intimate partner violence. No association was observed between antenatal depression and preterm birth. Strong associations were observed between antenatal depression and decreased infant weight‐for‐age (WAZ) and head circumference‐for‐age (HCAZ) z‐scores at birth. In multivariable analysis, the association between depression and decreased HCAZ remained significant, when adjusted for clinic, SES, and recent stressful life events.
Conclusions
Antenatal depression and associated risk factors are highly prevalent in this setting and are associated with adverse fetal growth. Maternal mental health may be an important predictor of infant growth in utero.
•Perinatal depressive symptom trajectories are understudied in sub-Saharan Africa.•A majority of women had mild levels of depressive symptoms.•The group with persistent severe symptoms had the most ...risk factors.•Depressive symptom trajectories differed by community context.
Perinatal depression affects 21–50% of women in South Africa and poses significant health risks to mothers and children. Trajectories of depressive symptoms change over time and have not been well characterized during the perinatal period in low and middle-income countries.
Data from women enrolled in a population-based birth cohort study in Paarl, South Africa with at least 3 depression measures from pregnancy through 18 months postpartum (N = 831) were analyzed. Depressive symptoms were measured continuously using the Edinburgh Postnatal Depression Scale (EPDS). Group-based trajectory models were used to estimate trajectories of depressive symptoms during the perinatal period and multinomial multivariable models to identify predictors of trajectory group membership.
Five distinct trajectory patterns of depressive symptoms were identified: moderate levels of depressive symptoms during pregnancy but minimal postpartum (3.5%), minimal levels during pregnancy and increasing postpartum (3.7%), unstable levels peaking at 12 months postpartum (6.6%), mild levels with slight decrease postpartum (82.9%), and severe levels during pregnancy and postpartum (3.1%). Membership in the chronic severe symptom group was associated with stressful life events, sexual intimate partner violence and tobacco use.
Modeling limitations prevented determining how changes in psychosocial predictors over time may influence depressive symptom trajectories.
Mild to severe depressive symptoms during pregnancy/postpartum were common among this South African cohort. Interventions to treat women with severe chronic depressive symptoms with co-occurring psychosocial issues are urgently needed.
Epigenetic differences may help to distinguish between PTSD cases and trauma-exposed controls. Here, we describe the results of the largest DNA methylation meta-analysis of PTSD to date. Ten cohorts, ...military and civilian, contribute blood-derived DNA methylation data from 1,896 PTSD cases and trauma-exposed controls. Four CpG sites within the aryl-hydrocarbon receptor repressor (AHRR) associate with PTSD after adjustment for multiple comparisons, with lower DNA methylation in PTSD cases relative to controls. Although AHRR methylation is known to associate with smoking, the AHRR association with PTSD is most pronounced in non-smokers, suggesting the result was independent of smoking status. Evaluation of metabolomics data reveals that AHRR methylation associated with kynurenine levels, which are lower among subjects with PTSD. This study supports epigenetic differences in those with PTSD and suggests a role for decreased kynurenine as a contributor to immune dysregulation in PTSD.
Psychological stressors are prevalent during pregnancy, particularly in low- and middle-income countries (LMICs). A number of studies have demonstrated that prenatal exposure to maternal ...psychological distress may alter the expression of placental and/or umbilical cord blood (UCB) genes. However, findings have thus far been inconsistent, and the molecular mechanisms underlying these transgenerational effects are currently not well understood. This study aimed to investigate these transgenerational mechanisms using child gene expression profiles, with data from the Drakenstein Child Health Study (DCHS) – an ongoing, longitudinal birth cohort study in South Africa.
The Self-Reporting Questionnaire 20 (SRQ-20) was used as a measure of prenatal maternal psychological distress, and a cut-off score >/= 8 was used to dichotomise participants as “high-risk” versus “low-risk”. RNA sequencing of umbilical cord blood samples was performed, on newborns exposed to prenatal maternal psychological distress (N=38) and compared to unexposed newborns (N=195). The linear modelling frameworks of the Limma-Voom R-package were applied to identify differentially expressed genes (DEGs) between exposed versus unexposed neonates. Covariates in these analyses included sex of the newborn, gestational age, maternal (self-reported) ethnicity, maternal HIV status, maternal hypertension, maternal prenatal alcohol consumption, maternal prenatal smoking, batch number and RNA integrity number. Thereafter, a gene set enrichment analysis (GSEA) was undertaken to identify significantly enriched pathways.
Data from 234 mother-child dyads were included in this analysis. At genome-wide FDR < 0.05, no genes were found to be significantly differentially expressed between newborns exposed to prenatal maternal psychological distress, versus unexposed newborns, after controlling for relevant covariates. However, GSEA (at a nominal p-value < 0.01) demonstrated significant upregulation of genes differentially expressed between exposed versus unexposed newborns, in a number of MSigDB gene set pathways - namely, a) G2M checkpoint, (b) E2F targets, (c) mitotic spindle, (d) MTORC1 signalling, (e) heme metabolism and (f) oestrogen response late.
Taken together, the findings suggest that genes differentially expressed between newborns exposed to prenatal maternal psychological distress are significantly upregulated in pathways associated with cell cycle and growth, oestrogen response and heme metabolism. Thus, multiple biological processes may be disrupted by an unfavourable intrauterine environment. Future research to replicate these findings and investigate potential developmental sequelae of these molecular changes would be warranted.
Food insecurity during pregnancy is concerning given the increased nutritional needs of the mother for proper fetal development. However, research is lacking within the South African context to ...investigate the association of economic and psychosocial factors and food insecurity among pregnant women, using comprehensive, conceptually driven models.
This study applies the Network-Individual-Resource (NIR) Model to investigate individual, intimate dyadic, and family level predictors of perceived household food insecurity for pregnant women.
826 pregnant women enrolled in the Drakenstein Child Health Study (DCHS), a birth cohort in two communities in a peri-urban area of South Africa. Hierarchical logistic regressions were used to investigate the impact of household/family, intimate dyads, and individual tangible and mental resources on perceived household food insecurity during the critical period of pregnancy. Perceived household food insecurity was assessed through an adapted version of the USDA Household Food Security Scale – Short Form.
Among 826 pregnant women in South Africa, individual-level tangible resources (e.g. income, social assistance, HIV status) and mental resources (e. g. depression, childhood trauma) predicted perceived household food insecurity and these predictors differed by community. Intimate dyadic and family level resources did not predict household food insecurity.
Our findings of the economic and psychosocial predictors of perceived household food insecurity among pregnant women in South Africa, mirror findings in general populations. This study provides support for the extension of the NIR model to perceived household food insecurity, particularly regarding individual-level mental and tangible resources, as well as the impact of community-level factors. Future research should investigate the extent to which resource sharing occurs within networks.
•Examined perceived food insecurity predictors among pregnant women in South Africa.•Network-Individual-Resource model used to conceptualize perceived food insecurity.•Individual-level tangible and mental resources predict perceived food insecurity.•Community plays a role in the resources that predict perceived food insecurity.
There is increasing evidence indicating that air pollution exposure is associated with neuronal damage. Since pregnancy is a critical window of vulnerability, air pollution exposure during this ...period could have adverse effects on neurodevelopment. This study aims 1) to analyze associations of prenatal exposure to indoor air pollution (particulate matter with diameters ≤10 μm, PM10) and tobacco smoke with neurodevelopment and 2) to determine whether these associations are mediated by deviations of epigenetic gestational age from chronological gestational age (ΔGA).
Data of 734 children from the South African Drakenstein Child Health Study were analyzed. Prenatal PM10 exposure was measured using devices placed in the families' homes. Maternal smoking during pregnancy was determined by maternal urine cotinine measures. The Bayley Scales of Infant and Toddler Development III (BSID-III) was used to measure cognition, language and motor development and adaptive behavior at two years of age. Linear regression models adjusted for maternal age, gestational age, sex of child, ancestry, birth weight/length, and socioeconomic status were used to explore associations between air pollutants and BSID-III scores. A mediation analysis was conducted to analyze if these associations were mediated by ΔGA using DNA methylation measurements from cord blood.
An increase of one interquartile range in natural-log transformed PM10 (lnPM10; 1.58 μg/m3) was significantly associated with lower composite scores in cognition, language, and adaptive behavior sub-scores (composite score β-estimate 95%-confidence interval: −0.950 −1.821, −0.120). Maternal smoking was significantly associated with lower adaptive behavior scores (−3.386 −5.632, −1.139). Associations were not significantly mediated by ΔGA (e.g., for PM10 and cognition, proportion mediated p-value: 4% 0.52).
We found an association of prenatal exposure to indoor air pollution (PM10) and tobacco smoke on neurodevelopment at two years of age, particularly cognition, language, and adaptive behavior. Further research is needed to understand underlying biological mediators.
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•Well-characterized longitudinal birth cohort from South Africa (N = 734)•Measured indoor air pollution data (PM10) from pre- and postnatal visits•Exposure to indoor PM10 was associated with poorer cognitive development.•Investigation of epigenetic mechanisms of the PM10-neurodevelopment association
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