Maternal stress in pregnancy exerts powerful programming effects into the next generation. Yet it remains unclear whether and how adversity from other times in the woman’s life influences her prenatal stress and her offspring’s stress functioning. In a sample of 217 Black American mother-infant dyads, we examined whether different types of maternal stress were differentially related to her infant’s stress functioning within the first few months after birth. We prospectively assessed maternal distress (perceived stress, depression, and anxiety) early and late in pregnancy, infant behavioral adaption in the context of a mild stressor at 2 weeks of age, and infant diurnal cortisol at 3–6 months of age. We additionally collected retrospective reports of maternal experiences of lifetime discrimination and childhood adversity. Maternal distress experienced late, but not early, in pregnancy predicted lower infant attention in the context of a stressor. Moreover, lifetime experiences of discrimination indirectly impacted infant attention by increasing maternal distress late in pregnancy. These effects were specific to infant behavioral adaptation and were not related to infant diurnal cortisol levels. However, infant diurnal cortisol levels were associated with maternal experiences of discrimination from prior to pregnancy and adversity from the mother’s childhood even after controlling for prenatal distress. Our results underscore the cascading nature of stress across mothers’ lifespan and across generations.
The infant gut microbiome has lifelong implications on health and immunity but there is still limited understanding of the microbiome differences and similarities between children in low- and middle-income countries (LMICs) vs. high-income countries (HICs). Here, we describe and compare the microbiome profile of children aged under 48 months in two urban areas: Maputo, Mozambique and Atlanta, USA using shotgun metagenomics. The gut microbiome of American children showed distinct development, characterized by higher alpha diversity after infancy, compared to the same age group of African children, and the microbiomes clustered separately based on geographic location or age. The abundances of antibiotic resistance genes (ARGs) and virulence factors (VFs) were significantly higher in Maputo children, driven primarily by several primary and opportunistic pathogens. Most notably, about 50% of Maputo children under the age of two were positive for enterotoxigenic (ETEC) and typical enteropathogenic (EPEC) Escherichia coli diagnostic genes while none of the Atlanta age-matched children showed such a positive signal. In contrast, commensal species such as Phocaeicola vulgatus and Bacteroides caccae were more abundant in Atlanta, potentially reflecting diets rich in animal protein and susceptibility to inflammatory diseases. Overall, our results suggest that the different environments characterizing the two cities have significant, distinctive signatures on the microbiota of children and its development over time. Lack of safe water, sanitation, and hygiene (WASH) conditions and/or unsafe food sources may explain the higher enteric pathogen load among children in Maputo.
Recent evidence suggests that maternal childhood adversity may have an intergenerational impact, with children of adversity-exposed mothers exhibiting elevated symptoms of psychopathology. At the same time, many children demonstrate resilience to these intergenerational effects. Among the variety of factors that likely contribute to resilience, the composition of the gut microbiome may play a role in buffering the negative impacts of trauma and stress. The current prospective cohort study tested the novel hypothesis that offspring gut microbiome composition is a potential moderator in the relationship between maternal exposure to childhood adversity and offspring symptomatology (i.e., internalizing, externalizing, and posttraumatic stress symptoms). Maternal childhood adversity was self-reported during pregnancy via the Childhood Trauma Questionnaire and Adverse Childhood Experiences (ACEs) survey, and offspring symptomatology was assessed with the Child Behavior Checklist/1.5–5 when offspring were 2–4 years old. Offspring fecal samples were collected between these timepoints (i.e., during 6- to 24-month follow-up visits) for microbiome sequencing. Results indicated that maternal ACEs and the relative abundances of Bifidobacterium, Lactobacillus, and Prevotella were associated with offspring symptomatology. However, there was little evidence that microbial abundance moderated the association between maternal adversity and offspring symptoms. Overall, these findings further our understanding of how the gut microbiome associates with psychopathology, and informs future studies aimed at targeting modifiable factors that may buffer the intergenerational effects of childhood adversity.
Co-exposure to tobacco and marijuana has become common in areas where recreational marijuana use is legal. To assist in the determination of the combined health risks of this co-exposure, an analytical method capable of simultaneously measuring tobacco and marijuana metabolites is needed to reduce laboratory costs and the required sample volume. So far, no such analytical method exists. Thus, we developed and validated a method to simultaneously quantify urinary levels of trans-3′-hydroxycotinine (3OH-COT), cotinine (COT), and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol (COOH-THC) to assess co-exposure to tobacco and marijuana. Urine (200 µL) was spiked with labelled internal standards and enzymatically hydrolyzed to liberate the conjugated analytes before extraction using solid-supported liquid-liquid extraction (SLE) with ethyl acetate serving as an eluent. The target analytes were separated on a C18 (4.6 × 100 mm, 5 μm) analytical column with a gradient mobile phase elution and analyzed using tandem mass spectrometry with multiple reaction monitoring of target ion transitions. Positive electrospray ionization (ESI) was used for 3OH-COT and COT, while negative ESI was used for COOH-THC. The total run time was 13 min. The extraction recoveries were 18.4–23.9 % (3OH-COT), 65.1–96.8 % (COT), and 80.6–95.4 % (COOH-THC). The method limits of quantification were 5.0 ng/mL (3OH-COT) and 2.5 ng/mL (COT and COOH-THC). The method showed good accuracy (82.5–98.5 %) and precision (1.22–6.21 % within-day precision and 1.42–6.26 % between-day precision). The target analytes were stable for at least 144 h inside the autosampler (10 °C). The analyses of reference materials and 146 urine samples demonstrated good method performance. The use of a 96-well plate for preparation makes the method useful for the analysis of large numbers of samples.
Objective: Previous longitudinal studies have demonstrated prospective relationships between maternal sleep quality and subsequent psychological distress in the postpartum period. Despite evidence for prospective relationships between mood and subsequent sleep quality in adult populations, this direction has not been examined in postpartum women. We aimed to test prospective relationships between sleep quality and subsequent psychological distress, as well as the plausible reverse possibility, in a sample of Black American postpartum mothers (n = 146). Participants: Mothers were recruited prenatally from two hospitals in a Southeastern city of the United States. Eligible and interested mothers enrolled in a follow-up study on infant development. Data from the current study were obtained during the follow-up study. Method: Mothers reported on their psychological distress (i.e., anxiety, depression, stress) and sleep quality at 3- and 6-months postpartum. We performed hierarchical linear regressions to explore whether 1) maternal sleep quality at 3-months postpartum would predict maternal psychological distress at 6-months postpartum, after adjustment for mothers’ earlier psychological distress, and 2) whether psychological distress at 3-months postpartum would predict maternal sleep quality at 6-months postpartum, after adjustment for mothers’ earlier sleep quality. Results: Maternal sleep quality at 3-months postpartum was not a significant predictor of psychological distress at 6-months postpartum. However, maternal psychological distress at 3-months postpartum was a significant predictor of sleep quality at 6-months postpartum. Conclusions: Mothers’ psychological distress earlier in the postpartum was a significant predictor of their later sleep quality. Replication is needed in large, prospective studies, with results stratified by race/ethnicity.
Prenatal cannabis use and maternal stress have been proposed as risk factors for autism spectrum disorder (ASD). Black mothers and mothers of lower socioeconomic status (SES) may be especially likely to experience high levels of stress. This study examined the impact of prenatal cannabis use and maternal stress (i.e., prenatal distress, racial discrimination, and lower SES) on child ASD-related behaviors in a sample of 172 Black mother-child pairs. We found that prenatal stress was significantly associated with ASD-related behaviors. Prenatal cannabis use did not predict ASD-related behaviors and did not interact with maternal stress to predict ASD-related behaviors. These findings replicate previous work on prenatal stress-ASD associations and add to the limited literature on prenatal cannabis-ASD associations in Black samples.
BACKGROUND: Anxiety disorders tend to precede onset of comorbid depression. Several researchers have suggested a causal role for anxiety in promoting depressive episodes, but few studies have identified specific mechanisms. The current study proposes an interpersonal model of comorbidity, where anxiety disorders disrupt interpersonal functioning, which in turn elevates risk for depression. METHODS: At age 15 (T1), 815 adolescents oversampled for maternal depression completed diagnostic interviews, social chronic stress interviews, and self-report measures. At age 20 (T2), participants repeated all measures and reported on self-perceived interpersonal problems. At approximately age 23 (T3), a subset of participants (n= 475) completed a self-report depressive symptoms measure. RESULTS: Consistent with other samples, anxiety disorders largely preceded depressive disorders. Low sociability and interpersonal oversensitivity mediated the association between T1 social anxiety disorder and later depression (including T2 depressive diagnosis and T3 depressive symptoms), controlling for baseline. Interpersonal oversensitivity and social chronic stress similarly mediated the association between generalized anxiety disorder before age 15 and later depression. CONCLUSIONS: Interpersonal dysfunction may be one mechanism through which anxiety disorders promote later depression, contributing to high comorbidity rates.
Postpartum depression (PPD) is a significant mental health concern, especially for women in vulnerable populations. Oxytocin (OT), a hormone essential for a variety of maternal tasks, including labor, lactation, and infant bonding, has also been hypothesized to have a role in postpartum depression. Women are routinely given synthetic oxytocin to induce or augment labor and to prevent postpartum hemorrhage. The aim of this study was to review the quality and reliability of literature that examines potential relationships between OT and PPD to determine if there is sufficient data to reliably assess the strength of these relationships. We conducted a literature search in December of 2018 using five databases (PubMed, Web of Science, Embase, PsycInfo, and CINAHL). Eligible studies were identified, selected, and appraised using the Newcastle-Ottawa quality assessment scale and Cochrane Collaboration's tool for assessing risk of bias, as appropriate. Sixteen studies were included in the analysis and broken into two categories: correlations of endogenous OT with PPD and administration of synthetic OT with PPD. Depressive symptoms were largely measured using the Edinburgh Postnatal Depression Scale. OT levels were predominately measured in plasma, though there were differences in laboratory methodology and control of confounders (primarily breast feeding). Of the twelve studies focused on endogenous oxytocin, eight studies suggested an inverse relationship between plasma OT levels and depressive symptoms. We are not able to draw any conclusions regarding the relationship between intravenous synthetic oxytocin and postpartum depression based on current evidence due to the heterogeneity and small number of studies (n = 4). Considering limitations of the current literature and the current clinical prevalence of synthetic OT administration, we strongly recommend that rigorous studies examining the effects of synthetic OT exposure on PPD should be performed as well as continued work in defining the relationship between endogenous OT and PPD.
Selective serotonin/norepinephrine reuptake inhibitors (collectively, SRIs) are the most commonly prescribed antidepressant agents for the treatment of depression in pregnancy. SRIs affect maternal and placental serotonin signaling, which might impact fetal brain development. Alterations in serotonin signaling might also impact the developing gut–brain axis (GBA) via alterations in the fetal enteric nervous system (ENS). Emerging evidence suggests that gestational SRI exposure may be associated with offspring gastrointestinal problems. However, prospective human studies of the effects of fetal SRI exposure on the ENS and function are absent in the literature. In this paper we present data demonstrating significant associations between prenatal SRI exposure and children's gastrointestinal (GI) problems in two well-characterized, prospective cohorts of preschool and later childhood individuals. The results support the hypothesis that prenatal SRI exposure can increase the risk for childhood GI difficulties. Further research is warranted on the potential SRI-induced changes to the child gut including the role of the microbiome and the GBA in the development of GI problems.
Previous studies suggest epigenetic alterations may contribute to the association between maternal prenatal depression and adverse offspring outcomes. Developmental researchers have recently begun to examine these associations in relation to epigenetic age acceleration/deceleration, a biomarker of developmental risk that reflects the deviation between epigenetic age and chronological age. In the perinatal period, preliminary studies indicate that maternal prenatal depression may lead to epigenetic age deceleration in newborns, which may predict adverse developmental outcomes. The present study examined the relationship between maternal prenatal exposures (i.e., depression, stress, and SSRI use) and offspring epigenetic age deceleration in 303 mother-offspring dyads. Women were recruited in the first trimester of pregnancy and followed longitudinally until delivery. Maternal depression, perceived stress, and SSRI use were assessed at each prenatal visit. Newborn epigenetic age was determined via cord blood samples. Results indicated maternal prenatal stress was not associated with newborn epigenetic age deceleration (ΔR2=0.002; p=0.37). Maternal prenatal depression was associated with decelerated epigenetic age (ΔR2=0.01, p=0.04), but this relationship did not hold when accounting for maternal use of SSRIs (ΔR2=0.002, p=0.43). Conversely, maternal SSRI use significantly predicted newborn epigenetic age deceleration over and above the influence of maternal depression (ΔR2=0.03, p=0.001). These findings suggest maternal prenatal SSRI use may significantly contribute to the previously documented association between maternal prenatal depression and epigenetic age deceleration. Further studies are needed to examine how these epigenetic differences at birth may contribute to adverse outcomes in later development.