Pathways from maternal depression to young adult offspring depression: an exploratory longitudinal mediation analysis.
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ABSTRACT:
SUBMITTER: Koukounari A
PROVIDER: S-EPMC5484332 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Effects of maternal aging on the offspring cognitive function remain controversial in population-based investigations, and information available in animal studies is very limited. We investigated the impact of a delayed first natural pregnancy on pregnancy outcomes in the mouse model. Spatial learning capacity in young adult mouse offspring was observed by step-down passive avoidance task and Morris water maze (MWM). Maternal serum ?-klotho was measured by ELISA. Morphological characteristics of fetoplacental unit and offspring brain were identified by H&E and immunohistochemistry. Klotho, VDR and other related genes expression were quantified by real-time-RT-PCR and western blot. We found delayed pregnancy reduced fertility in female mice by three-fold (Young vs. Old: 5.0% vs. 20.7%), and increased adverse pregnant outcomes by eight-fold (Young vs. Old: 3.0% vs. 27.5%). Mice born to old mothers exhibited shorter retention trial latency in passive avoidance task and longer latency to find the platform in MWM, suggesting worse performance on the tests that measure learning and memory. Serum ?-klotho level was lower in old female mice before pregnancy, whereas became comparable after pregnancy. Vitamin D receptor (VDR) expression, both in mRNA and protein, markedly decreased during the early stage of fetoplacental unit in old mice, especially in trophoblast giant cells when compared with that of young mice. Importantly, consistent with fetoplacental unit, VDR expression also declined in hippocampus from offspring born to old mice. These results suggest that young adult offspring from aged mothers exhibited worse cognitive function and the reduced VDR expression during fetoplacental development might play an important role.
| S-EPMC5883138 | biostudies-literature
Project description:Maternal immune activation (MIA) during pregnancy impacts offspring neurodevelopmental trajectories and induces lifelong consequences, including emotional and cognitive alterations. Using the polyinosinic:polycytidilic acid (PIC) MIA model we have previously demonstrated enhanced depression-like behavior in adult MIA offspring, which was associated with reduced expression of the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2) in the hippocampus. Since VEGF mediates the effects of various antidepressant agents, we here set out to explore whether VEGF administration could rescue the depression-like behavioral deficits in MIA offspring. To test our hypothesis, control and MIA offspring were intracerebroventricularly (i.c.v.) infused with either VEGF or vehicle solution and depression-related behavior was assessed in the sucrose preference test (SPT) and the tail suspension test (TST). As a surrogate of VEGF activity, the phosphorylation of the extracellular signal-regulated kinase (ERK) in hippocampus was quantified. We found that VEGF treatment reduced depression-related behavioral despair in the TST in MIA offspring but had no effect on anhedonia-like behavior in the SPT. While VEGF administration induced the phosphorylation of ERK in the hippocampus of control offspring, this effect was blunted in the MIA offspring. We conclude that VEGF administration, at the dosage tested, beneficially affects some aspects of the depression-like phenotype in the adult MIA offspring, inviting further studies using different dosage regimes to further explore the therapeutic potential of VEGF treatment in MIA-related changes in brain function and behavior.
| S-EPMC7226255 | biostudies-literature
Project description:Maternal fructose exposure (MFE) programs the development of metabolic syndrome (MetS) in young adult offspring. Epidemiological data indicate that MetS may increase the risks of overactive bladder (OAB) symptoms. However, it remains unknown whether MFE programs MetS-associated bladder dysfunction in adult offspring. Using Sprague-Dawley rats, we investigated the effects of MFE during pregnancy and lactation on developmental programming of MetS-associated bladder dysfunction. In addition, next generation sequencing technology was used to identify potential transcripts involved in the programmed bladder dysfunction in adult male offspring to MFE. We found that MFE programmed the MetS-associated OAB symptoms (i.e., an increase in micturition frequency and a shortened mean inter-contractile interval) in young adult male offspring, alongside significant alterations in bladder transcripts, including Chrm2, Chrm3, P2rx1, Trpv4, and Vipr2 gene expression. At protein level, the expressions of M2-, M3-muscarinic and P2X1 receptor proteins were upregulated in the MFE bladder. Functionally, the carbachol-induced detrusor contractility was reduced in the MFE offspring. These data suggest that alterations in the bladder transcripts and impairment of the bladder cholinergic pathways may underlie the pathophysiology of programmed bladder dysfunction in adult offspring to MFE.
| S-EPMC5050417 | biostudies-literature
Project description:ImportanceFew studies from low-and-middle income countries have investigated long-term associations between maternal postnatal depression and offspring internalizing (ie, depressive and anxiety) symptoms, and none have investigated interactions in this association.ObjectiveTo investigate the association between maternal postnatal depression and offspring internalizing symptoms from adolescence to adulthood and the interaction with exposure to socioeconomic adversity and with the child's sex.Design, setting, and participantsThis secondary analysis used data from Birth to Twenty Plus (BT20+), a prospective birth cohort study of children born in Soweto, South Africa, and followed up until age 28 years. Data were collected from 1990 to 2018, and data were analyzed for this study from February 16 through December 15, 2020.ExposuresMaternal postnatal depression self-reported by mothers 6 months after childbirth.Main outcomes and measuresThe main outcome was offspring internalizing symptoms, assessed at offspring ages 14 years, 22 years, and 28 years and modeled longitudinally. Participants with the highest probability of experiencing high internalizing symptoms (ie, those in the top 20% of the distribution) from age 14 to 28 years were categorized as belonging to the high internalizing symptoms trajectory (vs the low trajectory). Socioeconomic adversity was measured with an index (continuous variable) including low maternal education, household crowding, low assets, and low maternal age. This variable was further stratified into more than 1 SD above the mean index, more than 1 SD below the mean index, and from 1 SD below to 1 SD above the mean index to conduct subgroup analyses. Associations were investigated using multivariable regression models.ResultsAmong 1087 participants born in Soweto, South Africa (543 [50.0%] male participants; 544 [50.0%] female participants), 118 individuals (10.8%) showed a high trajectory of internalizing symptoms from age 14 to 28 years vs 969 individuals (89.1%) with a low trajectory. Children exposed to maternal postnatal depression had statistically significantly increased odds of following the high trajectory (adjusted odds ratio [aOR] per 1-SD increase in maternal postnatal depression, 1.20; 95% CI, 1.02-1.41). This increase in odds differed by exposure to socioeconomic adversity and by child sex: for male participants, the increase in odds was greater in a context of higher vs lower socioeconomic adversity (eg, for >1 SD above the mean: aOR, 3.28; 95% CI, 1.06-10.14 vs for >1 SD below the mean: aOR, 0.98; 95% CI, 0.64-1.50; P for interaction = .12), while for female participants, the increase in odds was greater in a context of lower vs higher socioeconomic adversity (eg, for >1 SD below the mean: aOR, 1.82; 95 % CI, 1.12-2.98 vs for >1 SD above the mean: aOR, 0.59; 95 % CI, 0.30-1.17; P for interaction = .002) (P for 3-way interaction = .003).Conclusions and relevanceThis study found that postnatal depression was associated with higher odds of persistently increased internalizing symptoms among offspring from adolescence to adulthood in a middle-income country, with variation by socioeconomic adversity and sex. These findings suggest that better understanding of these associations is needed to implement targeted interventions and maximize the impact of public health initiatives aimed at breaking the intergenerational transmission of mental health problems.
| S-EPMC8377574 | biostudies-literature
Project description:Exploratory mediation analysis refers to a class of methods used to identify a set of potential mediators of a process of interest. Despite its exploratory nature, conventional approaches are rooted in confirmatory traditions, and as such have limitations in exploratory contexts. We propose a two-stage approach called exploratory mediation analysis via regularization (XMed) to better address these concerns. We demonstrate that this approach is able to correctly identify mediators more often than conventional approaches and that its estimates are unbiased. Finally, this approach is illustrated through an empirical example examining the relationship between college acceptance and enrollment.
| S-EPMC5720177 | biostudies-literature
Project description:Animal studies and a handful of prospective human studies have demonstrated that young offspring exposed to maternal prenatal stress show abnormalities in immune parameters and hypothalamic-pituitary-adrenal (HPA) axis function. No study has examined the effect of maternal prenatal depression on offspring inflammation and HPA axis activity in adulthood, nor the putative role of child maltreatment in inducing these abnormalities. High-sensitivity C-reactive protein (hs-CRP) and awakening cortisol were measured at age 25 in 103 young-adult offspring of the South London Child Development Study (SLCDS), a prospective longitudinal birth cohort of mother-offspring dyads recruited in pregnancy in 1986. Maternal prenatal depression was assessed in pregnancy at 20 and 36 weeks; offspring child maltreatment (birth 17 years) was assessed at offspring ages 11, 16 and 25; and offspring adulthood depression (18-25 years) was assessed at age 25. Exposure to maternal prenatal depression predicted significantly elevated offspring hs-CRP at age 25 (odds ratio=11.8, 95% confidence interval (CI) (1.1, 127.0), P=0.041), independently of child maltreatment and adulthood depression, known risk factors for adulthood inflammation. In contrast, maternal prenatal depression did not predict changes in offspring adulthood cortisol; however, offspring exposure to child maltreatment did, and was associated with elevated awakening cortisol levels (B=161.9, 95% CI (45.4, 278.4), P=0.007). Fetal exposure to maternal depression during pregnancy has effects on immune function that persist for up to a quarter of a century after birth. Findings are consistent with the developmental origins of health and disease (DOHaD) hypothesis for the biological embedding of gestational psychosocial adversity into vulnerability for future physical and mental illness.
| S-EPMC5314108 | biostudies-literature
Project description:Maternal depression is associated with adverse child outcomes including antisocial behaviour (ASB). Prospective longitudinal studies have focused on the timing and cumulative exposure to maternal depression to further delineate the association and mechanisms of effect. The objective of this systematic review was to synthesise and evaluate the findings of longitudinal studies of maternal depression and offspring antisocial behaviour. Three databases were searched (Psychinfo, Web of Science, and Medline). Twenty of 5936 studies met inclusion criteria. Study quality was assessed using the Critical Appraisal Skills Programme criteria [Critical Appraisal Skills Programme (2017) CASP (cohort observation checklist). https://casp-uk.net/wpcontent/uploads/2018/01/CASP-Cohort-Study-Checklist.pdf ]. Results of individual studies were highly varied, using diverse analytical approaches and not all studies explored the independent effects of different episodes. Only three studies examined hypothesised mechanisms. Prenatal, postnatal, and later episodes of depression were all predictive of antisocial outcomes. One particular time period of depression exposure did not emerge as more predictive of offspring ASB than another. However, measures of maternal depression after the perinatal period were limited and typically included a one-off assessment of mothers' depressive symptoms that was concurrent to the assessment of offspring ASB. When cumulative exposure to maternal depression and specific timing effects were measured within the same study it was cumulative exposure that conferred the greatest risk for offspring ASB-particularly when this exposure began during the perinatal period. Findings are discussed in terms of limitations in the literature and highlight the need for future research to examine the biological and environmental mechanisms that underpin associations between maternal depression and offspring antisocial behaviour during different stages of development.
| S-EPMC7864821 | biostudies-literature
Project description:Infant feeding practices have been hypothesized to influence offspring's body mass index (BMI) later in life, and women with overweight or obesity tend to wean their infants earlier than women with healthy BMI. We, therefore, aimed to investigate how much early age of weaning mediated the maternal-offspring adiposity relationship. The study included 4920 mother-child pairs from the Avon Longitudinal Study of Parents and Children birth cohort. G-computation was applied to estimate the natural direct (NDE) and indirect (NIE) effects, via the age of weaning (<3 months, 3 months, >3 months), of maternal pre-pregnancy overweight or obesity on offspring's BMI and fat mass index. The NDE of maternal overweight or obesity on offspring BMI at 17 years old was 2.63 kg/m2 (95% CI: 2.27 to 2.99). The NIE via the age of weaning was 0.02 kg/m2 (95% CI: 0.00 to 0.04), corresponding to 0.8% of the total effect. Similar results were observed for the offspring's fat mass index. The NDE and NIE were similar to the main analyses when we looked at the relationship stratified by breastfeeding status. Our study found a minimal influence of age of weaning on the pathway between maternal and offspring adiposity, indicating the age of weaning may not be a key mediator.
| S-EPMC10343873 | biostudies-literature
Project description:Maternal high-fat diet consumption predisposes to metabolic and liver dysfunction in F1 male and female at young adulthood. Purpose: We used RNA-seq to determine the liver transcriptome of male and female F1 of MO and control fed mothers. Methods: Female Wistar rat mothers ate control (C) or obesogenic (MO) diet from the time they were weaned through breeding at postnatal day (PND) 120, delivery and lactation. After weaning all male and female F1 ate control diet. At PND 110 liver and fat were collected to analyze metabolites, histology and liver differentially expressed genes. To identify the functional F1 liver changes due to MO, we evaluated the differentially expressed genes (DEGs) between MO and C males and females with separate pairwise comparisons due to the marked differences between males and females. Genes were filtered based on ≥ 1.4 fold change (FC) and nominal P value <0.05 (Student´s t-test). Results: MOF1 males presented greater physiologic and histological NAFLD characteristics than MOF1 females. RNA-seq revealed 1,365 genes significantly changed in male MOF1 liver and only 70 genes in MOF1 female compared with controls. GO and KEGG analysis identified differentially expressed genes related to metabolic process. Male MOF1 liver showed the following altered pathways: insulin signaling (22 genes), phospholipase D signaling (14 genes), NAFLD (13 genes), and glycolysis/ gluconeogenesis (7 genes). In contrast, few genes were altered in these pathways in MOF1 females. Conclusions: These results improve understanding of the mechanism by which a maternal high fat diet affects their F1. In summary, MO programs sex-dependent F1 changes in insulin, glucose and lipid signaling pathways, leading to liver dysfunction and insulin resistance. Male adult MOF1 livers show global down-regulation of genes that are required for normal function of major liver metabolic pathways. This new knowledge is important for producing sex-specific interventions.
2019-06-25 | GSE115535 | GEO
Project description:BackgroundMaternal depression is a major determinant of offspring mental health. Yet, little is understood about how the duration and timing of maternal depression shapes youth risk for depressive symptoms, which if understood could inform when best to intervene. This study aimed to determine how the timing and duration of maternal depression was related to offspring depression in emerging adulthood, and if these associations varied by sex.MethodsWe analysed data from the Avon Longitudinal Study of Parents and Children (a prenatal cohort in the Avon area of England, 1991-2003), n = 3,301. We applied the structured lifecourse modelling approach to maternal depression (assessed at 13 points from prenatal period to adolescence) and emerging adult depressive symptoms (age 21). Lifecourse models assessed were accumulation (sum of timepoints when maternal depression was reported), sensitive periods (each period assessed as one during which maternal depression has a stronger effect) and instability (frequent fluctuations in maternal depression).ResultsFemale adolescents (n = 2,132) had higher SMFQ scores (mean = 6.15, SD = 5.90) than males (n = 1,169, mean = 4.87, SD = 4.82). Maternal depression was most common in the infancy period (21.2% males; 21.4% females). For males, accumulation was the most appropriate lifecourse model; for each additional period of maternal depression, depressive symptoms in emerging adulthood increased by 0.11 (95% CI: 0.07, 0.15, one-sided p value ≤ .001). For females, exposure to maternal depression was associated with increasing depressive symptoms in emerging adulthood, with the largest effect in mid-childhood (increase of 0.27 units, 95% CI 0.03-0.50, p = .015 for difference between mid-childhood and other time-periods) and a smaller, equal effect at all other time-periods (increase of 0.07 units per time-period, 95% CI: 0.03-0.12, p = .002).ConclusionsThis study highlights the importance of ongoing maternal depression for the development of depression in offspring through to emerging adulthood. Because long-term exposure to maternal depression was particularly important, early interventions are warranted.
| S-EPMC10008452 | biostudies-literature