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Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression.

ABSTRACT: Postpartum depression (PPD) affects up to 20% of mothers and has negative consequences for both mother and child. Although exposure to psychosocial stress during pregnancy and abnormalities in the hypothalamic pituitary adrenal (HPA) axis have been linked to PPD, molecular changes in the brain that contribute to this disease remain unknown. This study utilized a novel chronic psychosocial stress paradigm during pregnancy (CGS) to investigate the effects of psychosocial stress on maternal behavior, neuroendocrine function, and gene expression changes in molecular regulators of the HPA axis in the early postpartum period. Postpartum female mice exposed to CGS display abnormalities in maternal behavior, including fragmented and erratic maternal care patterns, and the emergence of depression and anxiety-like phenotypes. Dysregulation in postpartum HPA axis function, evidenced by blunted circadian peak and elevation of stress-induced corticosterone levels, was accompanied by increased CRH mRNA expression and a reduction in CRH receptor 1 in the paraventricular nucleus of the hypothalamus (PVN). We further observed decreased PVN expression of nuclear steroid hormone receptors associated with CRH transcription, suggesting these molecular changes could underlie abnormalities in postpartum HPA axis and behavior observed. Overall, our study demonstrates that psychosocial stress during pregnancy induces changes in neuroendocrine function and maternal behavior in the early postpartum period and introduces our CGS paradigm as a viable model that can be used to further dissect the molecular defects that lead to PPD.

SUBMITTER: Zoubovsky SP

PROVIDER: S-EPMC7026416 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression.

Zoubovsky Sandra P SP Hoseus Sarah S Tumukuntala Shivani S Schulkin Jay O JO Williams Michael T MT Vorhees Charles V CV Muglia Louis J LJ

Translational psychiatry 20200116 1

Postpartum depression (PPD) affects up to 20% of mothers and has negative consequences for both mother and child. Although exposure to psychosocial stress during pregnancy and abnormalities in the hypothalamic pituitary adrenal (HPA) axis have been linked to PPD, molecular changes in the brain that contribute to this disease remain unknown. This study utilized a novel chronic psychosocial stress paradigm during pregnancy (CGS) to investigate the effects of psychosocial stress on maternal behavio ...[more]

PMID: 32066677

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Project description:BackgroundNeighborhood stressors (e.g., crime and deprivation) have been associated with adverse pregnancy outcomes including preterm birth and low birth weight. A potential mechanism is disruption of maternal endocrine pathways. While stress hormones (e.g., cortisol) have received much attention, other relevant hormones, including sex steroids, have been overlooked.MethodsPregnant women in the Understanding Pregnancy Signals and Infant Development (UPSIDE) study contributed biospecimens, questionnaires, and medical record data (n = 262). In each trimester, maternal serum total testosterone [TT], estrone, estradiol, and estriol were measured using LC/MS-MS and serum free testosterone was measured by equilibrium dialysis. In the third trimester, participants reported on neighborhood stress over the last year through the validated City Stress Inventory. We examined two subscales: 11-item neighborhood disorder (e.g., vacant buildings, crime) and 7-item exposure to violence (personal experiences of violence). Composite scores were calculated and examined categorically (quartile (Q) for neighborhood disorder and any/none for exposure to violence). We fitted linear mixed models examining associations between neighborhood stressors and sex steroid hormones across pregnancy as well as trimester-specific linear regression models, all adjusting for confounders. Secondarily, we stratified by fetal sex. Results are presented as percentage change (∆%) and 95% confidence interval (CI) in hormones.ResultsMost participants (73%) reported one or more exposures to neighborhood disorder; 22% reported any exposure to violence. In adjusted models, neighborhood disorder was associated with higher TT across pregnancy (Q2: %∆= 37.3, 95%CI: 13.2, 66.5; Q3: %∆= 22.2, 95%CI: 1.2, 47.5; and Q4: %∆= 25.7, 95%CI: 1.6, 55.3), with the strongest associations observed in the third trimester (Q2: %∆= 38.0, 95%CI: 10.6, 72.1; Q3: %∆= 29.2, 95%CI: 4.4, 59.9; and Q4: %∆=33.4, 95%CI: 4.9, 69.6). In stratified models, neighborhood disorder was associated with higher TT among women carrying male fetuses (%∆ range: 48.2-84.8). Exposure to violence was not associated with any hormones.ConclusionNeighborhood disorder is associated with higher maternal testosterone levels, which may have implications for maternal and child health. Additional research is needed to understand the mechanisms by which neighborhood stress impacts endocrine physiology.

Project description:ObjectiveTo capture multidimensional maternal psychosocial stress using responses from the Edinburgh Postnatal Depression Scale (EPDS) and Cohen's Perceived Stress Scale (PSS) administered during pregnancy, and to identify sociodemographic, biological, and health behavioral correlates of the stress domains.MethodsUsing data from 1,079 pregnant women, we implemented principal component analysis on EPDS and PSS responses and retained factors based on the Scree plot and Eigenvalues >1. We then used linear regression to identify perinatal correlates of each domain.ResultsWe identified three stress domains: "Feeling Overwhelmed," "Anhedonia," and "Lack of Control," which accounted for 10.6% of variance in questionnaire responses. In multivariable analyses, household income ≤$70,000 (β = 0.21 confidence interval [95% CI: 0.05-0.39]), primiparity (0.36 [0.02-0.71]), inadequate (0.21 [0.04-0.39]) or excessive gestational weight gain (0.27 [0.11-0.42]), and Healthy Eating Index (HEI) score ≤57 (0.14 [0.00-0.28]) were associated with Feeling Overwhelmed. Older age (0.02 [0.00-0.03] per 1-year), Hispanic ethnicity (0.19 [0.00-0.38]), and HEI score ≤57 (0.15 [0.02-0.28]) were associated with Anhedonia. Non-Hispanic Black race/ethnicity (0.37 [0.10-0.63]), not having graduated from college (0.16 [-0.02 to 0.35]), having a partner born outside the United States (0.17 [-0.02 to 0.37]), household size of ≥5 persons (0.21 [-0.02 to 0.37]), receiving public assistance (0.18 [-0.02 to 0.37]), and prenatal smoking (0.32 [0.05-0.59]) were associated with Lack of Control.ConclusionsThree domains of maternal psychosocial stress during pregnancy (Feeling Overwhelmed, Anhedonia, and Lack of Control) were differentially related to sociodemographic, biological, and health behavioral characteristics that may be targets for interventions to ameliorate stress in pregnant women.Clinical trial registry: The Healthy Start study is registered as an observational study at clinicaltrials.gov (NCT #002273297).

Dataset Information

Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression.

Publications

Chronic psychosocial stress during pregnancy affects maternal behavior and neuroendocrine function and modulates hypothalamic CRH and nuclear steroid receptor expression.

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