W Roger Mills-Koonce, Karen Grewen, Nisha Gottredson O’Shea Brenda Pearson, Chelsea Grace Strange, Samantha E Meltzer-Brody, Jerry Dolph Guintivano, Alison M Stuebe

Background: Perinatal depression affects >400,000 mother-child dyads in the United States every year and is associated with numerous adverse maternal and child developmental outcomes. Previous research implicates the dysregulation of oxytocin and the hypothalamic-pituitary-adrenal (HPA) axis functioning in mothers and children as potential mechanisms mediating or moderating the transmission of risk associated with maternal depression.

Objective: The Mood, Mother and Child study will examine the psychobiological sources of risk and resilience within mother-child dyads affected by maternal depression. This manuscript describes (1) the study rationale and aims, (2) the research design and procedures and how they were altered in response to the COVID-19 pandemic, and (3) the data analysis plan to test the study hypotheses.

Methods: This is a prospective longitudinal study with an embedded randomized controlled trial that examines (1) correlations among postpartum depression and anxiety symptoms, maternal and child oxytocin and HPA axis functioning, and child developmental outcomes and (2) the causal relationship between exogenous oxytocin and HPA reactivity. This study is funded by the National Institute of Child Health and Human Development with institutional review board approval.

Results: Recruitment and data collection have commenced, and the expected results will be available in 2024. Analyses are presented for testing the proposed hypotheses.

Conclusions: The unique combination of a prospective longitudinal research design with an embedded randomized controlled trial will allow the Mood, Mother and Child study to apply a developmental lens to the study of maternal depression and anxiety symptoms from birth to middle childhood and the psychobiological mechanisms promoting risk and resiliency for both mother and child outcomes. This will be the first study that simultaneously evaluates (1) the role of oxytocin using multiple methodologies, (2) the causal relationships between exogenous oxytocin and HPA axis functioning among mothers with differing levels of depression and anxiety symptoms, and (3) the multiple mediating and moderating roles of parenting behaviors and maternal and child psychobiological characteristics. The goals of these aims are to provide insights into the psychobiological effects of oxytocin in women and inform future clinical trials to treat perinatal mood disorders.

Trial registration: ClinicalTrials.gov NCT03593473; https://classic.clinicaltrials.gov/ct2/show/NCT03593473.

D. Mehta, K. Grewen, B. Pearson, S. Wani, L. Wallace, A. K. Henders, et al.

Maternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29-53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4-2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

PMID: 33664235

Whitley J, Wouk K, Bauer AE, Grewen K, Gottfredson NC, Meltzer-Brody S, Propper C, Mills-Koonce R, Pearson B, Stuebe A.

This study aimed to quantify the relationship between postpartum depression and anxiety, oxytocin, and breastfeeding. We conducted a longitudinal prospective study of mother-infant dyads from the third trimester of pregnancy to 12 months postpartum. A sample of 222 women were recruited to complete the Beck Depression Inventory II and Spielberger State-Trait Anxiety Inventory-state subscale, participate in observed infant feeding sessions at 2 and 6 months postpartum, and provide venous blood samples during feeding. Maternal venous oxytocin levels in EDTA-treated plasma and saliva were determined by enzyme immunoassay with extraction and a composite measure of area under the curve (AUC) was used to define oxytocin across a breastfeeding session. Linear regression was used to estimate associations between postpartum depression and anxiety as predictors and oxytocin AUC during breastfeeding as the outcome at both 2 and 6 months postpartum. Mixed models accounting for correlations between repeated oxytocin measures were used to quantify the association between current depression and/or anxiety symptoms and oxytocin profiles during breastfeeding. We found no significant differences in oxytocin AUC across a feed between depressed or anxious women and asymptomatic women at either 2 or 6 months postpartum. Repeated measures analyses demonstrated no differences in oxytocin trajectories during breastfeeding by symptom group but possible differences by antidepressant use. Our study suggests that external factors may influence the relationship between oxytocin, maternal mood symptoms, and infant feeding.

PMID: 31911347

Epublished ahead of print in Breastfeeding Medicine, August 2019

Stuebe AM, Meltzer-Brody S, Propper C, Pearson B, Beiler P, Elam M, Walker C, Mills-Koonce R, Grewen K

Purpose: We sought to determine the role of depression and anxiety in breastfeeding cessation.

Materials and Methods:Participants underwent a baseline visit with a structured clinical interview in the third trimester of pregnancy. Monthly phone interviews assessed current mood symptoms and infant feeding status. We assessed the association between baseline mood and infant feeding outcomes using Cox proportional hazards regression, adjusting for infant feeding intention and sociodemographic confounders.

Results: We enrolled 222 mother-infant dyads in late pregnancy, of whom 206 completed assessments through 12 months postpartum. We enriched our study with symptomatic women by enrolling 87 women with current depression or anxiety (Current), 64 women with a history of depression or anxiety (Past), and 71 women with no psychiatric history (Never). In multivariable-adjusted analyses, baseline diagnosis was not associated with breastfeeding outcome, but baseline symptoms of depression (Beck Depression Inventory ≥11) or anxiety (Spielberger State Anxiety ≥40) were associated with earlier introduction of formula (depression: adj hazard ratio [HR] 1.52, 95% confidence interval [CI] 1.01-2.30; anxiety: 1.70, 95% CI 1.01-2.87); and any cessation of breastfeeding (depression: adj HR 2.02, 95% CI 1.23-3.31; anxiety: 1.83, 95% CI 1.00-3.33), as were depression symptoms among women who were being treated with antidepressants, compared with untreated asymptomatic women (formula: adj HR 2.27, 95% CI 1.29-4.02; cessation: 2.32, 95% CI 1.17-4.61). History of childhood trauma (adj HR 1.34, 95% CI 1.12-1.61), disordered eating symptoms (adj HR 1.22, 95% CI 1.02-1.46), and poor sleep quality in pregnancy (adj HR 1.32, 95% CI 1.09-1.60) were independently associated with earlier introduction of formula.

Conclusions: Baseline mood symptoms were independently associated with earlier formula introduction and cessation of breastfeeding. History of childhood trauma, disordered eating symptoms and poor sleep quality were associated with earlier formula introduction. Targeted support may enable women with these symptoms to achieve their feeding goals.

PMID:31424266