GABAAR Modulator for Postpartum Depression.

During the postpartum period, the brain's inhibitory GABAA receptors may not recover in time following their reduced numbers during pregnancy. This is likely the cause of postpartum depression prevalent in ∼12% of childbearing women. A new therapy for this condition consists of administering a synthetic neurosteroid during the postpartum period to alleviate the mood disorder. To view this Bench to Bedside, open or download the PDF.

Cryo-EM structures reveal native GABAA receptor assemblies and pharmacology.

Type A γ-aminobutyric acid receptors (GABAARs) are the principal inhibitory receptors in the brain and the target of a wide range of clinical agents, including anaesthetics, sedatives, hypnotics and antidepressants1-3. However, our understanding of GABAAR pharmacology has been hindered by the vast number of pentameric assemblies that can be derived from 19 different subunits4 and the lack of structural knowledge of clinically relevant receptors. Here, we isolate native murine GABAAR assemblies containing the widely expressed α1 subunit and elucidate their structures in complex with drugs used to treat insomnia (zolpidem (ZOL) and flurazepam) and postpartum depression (the neurosteroid allopregnanolone (APG)). Using cryo-electron microscopy (cryo-EM) analysis and single-molecule photobleaching experiments, we uncover three major structural populations in the brain: the canonical α1ß2γ2 receptor containing two α1 subunits, and two assemblies containing one α1 and either an α2 or α3 subunit, in which the single α1-containing receptors feature a more compact arrangement between the transmembrane and extracellular domains. Interestingly, APG is bound at the transmembrane α/ß subunit interface, even when not added to the sample, revealing an important role for endogenous neurosteroids in modulating native GABAARs. Together with structurally engaged lipids, neurosteroids produce global conformational changes throughout the receptor that modify the ion channel pore and the binding sites for GABA and insomnia medications. Our data reveal the major α1-containing GABAAR assemblies, bound with endogenous neurosteroid, thus defining a structural landscape from which subtype-specific drugs can be developed.

Blood extracellular vesicles carrying brain-specific mRNAs are potential biomarkers for detecting gene expression changes in the female brain.

The absence of non-invasive tests that can monitor the status of the brain is a major obstacle for psychiatric care. In order to address this need, we assessed the feasibility of using tissue-specific gene expression to determine the origin of extracellular vesicle (EV) mRNAs in peripheral blood. Using the placenta as a model, we discovered that 26 messenger RNAs that are specifically expressed in the placenta are present in EVs circulating in maternal blood. Twenty-three of these transcripts were either exclusively or highly expressed in maternal blood during pregnancy only and not in the postpartum period, verifying the feasibility of using tissue-specific gene expression to infer the tissue of origin for EV mRNAs. Using the same bioinformatic approach, which provides better specificity than isolating L1 cell-adhesion molecule containing EVs, we discovered that 181 mRNAs that are specifically expressed in the female brain are also present in EVs circulating in maternal blood. Gene set enrichment analysis revealed that these transcripts, which are involved in synaptic functions and myelination, are enriched for genes implicated in mood disorders, schizophrenia, and substance use disorders. The EV mRNA levels of 13 of these female brain-specific transcripts are associated with postpartum depression (adjusted p-vals = 3 × 10-5 to 0.08), raising the possibility that they can be used to infer the state of the brain. In order to determine the extent to which EV mRNAs reflect transcription in the brain, we compared mRNAs isolated from cells and EVs in an iPSC-derived brain microphysiological system differentiated for 3 and 9 weeks. We discovered that, although cellular and extracellular mRNA levels are not identical, they do correlate, and it is possible to extrapolate cellular RNA expression changes in the brain via EV mRNA levels. Our findings bring EV mRNAs to the forefront of peripheral biomarker development efforts in psychiatric diseases by demonstrating the feasibility of inferring transcriptional changes in the brain via blood EV mRNA levels.

Bidirectional association between autoimmune disease and perinatal depression: a nationwide study with sibling comparison.

Although major depression, characterized by a pro-inflammatory profile, genetically overlap with autoimmune disease (AD) and the perinatal period involve immune system adaptations and AD symptom alterations, the bidirectional link between perinatal depression (PND) and AD is largely unexplored. Hence, the objective of this study was to investigate the bidirectional association between PND and AD. Using nationwide Swedish population and health registers, we conducted a nested case-control study and a matched cohort study. From 1,347,901 pregnancies during 2001-2013, we included 55,299 incident PND, their unaffected full sisters, and 10 unaffected matched women per PND case. We identified 41 subtypes of AD diagnoses recorded in the registers and compared PND with unaffected population-matched women and full sisters, using multivariable regressions. Women with an AD had a 30% higher risk of subsequent PND (95% CI 1.2-1.5) and women exposed to PND had a 30% higher risk of a subsequent AD (95% CI 1.3-1.4). Comparable associations were found when comparing exposed women with their unaffected sisters (nested case-control OR: 1.3, 95% CI 1.2-1.5, matched cohort HR: 1.3, 95% CI 1.1-1.6), and when studying antepartum and postpartum depression. The bidirectional association was more pronounced among women without psychiatric comorbidities (nested case-control OR: 1.5, 95% CI 1.4-1.6, matched cohort HR: 1.4, 95% CI 1.4-1.5) and strongest for multiple sclerosis (nested case-control OR: 2.0, 95% CI 1.6-2.3, matched cohort HR: 1.8, 95% CI 1.0-3.1). These findings demonstrate a bidirectional association between AD and PND independent of psychiatric comorbidities, suggesting possibly shared biological mechanisms. If future translational science confirms the underlying mechanisms, healthcare providers need to be aware of the increased risk of PND among women with ADs and vice versa.

Experience and Reporting of Postnatal Depression Across Cultures: A Comparison Using Anchoring Vignettes of Mothers in the United Kingdom and India.

Postnatal mental health is often assessed using self-assessment questionnaires in epidemiologic research. Differences in response style, influenced by language, culture, and experience, may mean that the same response may not have the same meaning in different settings. These differences need to be identified and accounted for in cross-cultural comparisons. Here we describe the development and application of anchoring vignettes to investigate the cross-cultural functioning of the Edinburgh Postnatal Depression Scale (EPDS) in urban community samples in India (n = 549) and the United Kingdom (n = 828), alongside a UK calibration sample (n = 226). Participants completed the EPDS and anchoring vignettes when their children were 12-24 months old. In an unadjusted item-response theory model, UK mothers reported higher depressive symptoms than Indian mothers (d = 0.48, 95% confidence interval: 0.358, 0.599). Following adjustment for differences in response style, these positions were reversed (d = -0.25, 95% confidence interval: -0.391, -0.103). Response styles vary between India and the United Kingdom, indicating a need to take these differences into account when making cross-cultural comparisons. Anchoring vignettes offer a valid and feasible method for global data harmonization.

Molecular basis underlying default mode network functional abnormalities in postpartum depression with and without anxiety.

Although Postpartum depression (PPD) and PPD with anxiety (PPD-A) have been well characterized as functional disruptions within or between multiple brain systems, however, how to quantitatively delineate brain functional system irregularity and the molecular basis of functional abnormalities in PPD and PPD-A remains unclear. Here, brain sample entropy (SampEn), resting-state functional connectivity (RSFC), transcriptomic and neurotransmitter density data were used to investigate brain functional system irregularity, functional connectivity abnormalities and associated molecular basis for PPD and PPD-A. PPD-A exhibited higher SampEn in medial prefrontal cortex (MPFC) and posterior cingulate cortex (PPC) than healthy postnatal women (HPW) and PPD while PPD showed lower SampEn in PPC compared to HPW and PPD-A. The functional connectivity analysis with MPFC and PPC as seed areas revealed decreased functional couplings between PCC and paracentral lobule and between MPFC and angular gyrus in PPD compared to both PPD-A and HPW. Moreover, abnormal SampEn and functional connectivity were associated with estrogenic level and clinical symptoms load. Importantly, spatial association analyses between functional changes and transcriptome and neurotransmitter density maps revealed that these functional changes were primarily associated with synaptic signaling, neuron projection, neurotransmitter level regulation, amino acid metabolism, cyclic adenosine monophosphate (cAMP) signaling pathways, and neurotransmitters of 5-hydroxytryptamine (5-HT), norepinephrine, glutamate, dopamine and so on. These results reveal abnormal brain entropy and functional connectivities primarily in default mode network (DMN) and link these changes to transcriptome and neurotransmitters to establish the molecular basis for PPD and PPD-A for the first time. Our findings highlight the important role of DMN in neuropathology of PPD and PPD-A.

A longitudinal multi-centric cohort study assessing infant neurodevelopment delay among women with persistent postpartum depression in Nepal.

BACKGROUND: Infant neurodevelopment in the first years after birth is determined by multiple factors, including parental care and maternal mental wellbeing. In this study, we aim to assess the impact of persistent maternal depressive symptoms during the first 3 months postpartum on infant neurodevelopment at 6 months. METHODS: Using a longitudinal cohort design, 1253 mother-infant pairs were followed up at 7, 45, and 90 days to assess postpartum depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS); infants were followed up at 6 months to assess neuro-developmental status using the WHO's Infant and Young Child Development (IYCD) tool. A generalized linear regression model was used to assess the association between persistent postpartum depressive symptoms and infant neurodevelopmental delay at 6 months. A generalized linear mixed model (GLMM) with a hospital as a random intercept was used to assess the persistent postpartum depressive symptoms with an IYCD score. Linear regression was used to compare the IYCD scores between exposure groups. RESULTS: In the study population, 7.5% of mothers had persistent depressive symptoms, and 7.5% of infants had neurodevelopmental delay. Infants born to mothers with persistent depressive symptoms had a higher proportion of neurodevelopmental delay than infants born to women without persistent symptoms (48.6% vs 5.1%; p < 0.001). In the adjusted regression model, infants whose mothers had persistent depressive symptoms at 7, 45, and 90 days had a 5.21-fold increased risk of neurodevelopmental delay (aRR, 5.21; 95% CI, 3.17, 8.55). Mean scores in the motor domain (12.7 vs 15.2; p < 0.001) and language domain (6.4 vs 8.5; p < 0.001) were significant when a mother had persistent depression vs. no depression. Mean scores in the general behavioral domain (5.9 vs 10.4, p < 0.001) and the socio-emotional domain (15.4 vs 17.7; p < 0.001) were significantly different when a mother had persistent depression vs no persistent depression. CONCLUSIONS: Our results suggest that 6-month-old infants are at higher risk for neurodevelopment delays if their mother reports persistent symptoms of depression from 7 to 90 days postpartum. The neurodevelopmental delay can be observed in all functional domains. Preventive intervention to reduce maternal postpartum depression may reduce the impact on infant developmental delay.

Association of Diabetes Mellitus in Pregnancy and Perinatal Depression.

OBJECTIVE: Diabetes is frequently linked with depression, and both conditions are common complications during pregnancy. However, research findings exploring the relationship between diabetes mellitus in pregnancy (DMP) and perinatal depression (PND) have been inconsistent. Thus, this study seeks to examine the association between DMP and PND in a prospective population-based cohort. METHODS: Women aged 18 to 48 years ( n = 4459) were identified from the Biology, Affect, Stress, Imaging and Cognition study. The diagnosis of DMP was based on International Classification of Diseases code O24 from medical records and was classified as pregestational, gestational, or unspecified diabetes. PND was assessed using psychometric instruments, clinical interviews, and/or register data and categorized into antepartum or postpartum depression. Multivariable logistic regressions were used to study the associations of DMP with antepartum and postpartum depression. The association between DMP and continuous depression scores, antepartum and postpartum, was investigated with multivariable linear regressions. RESULTS: Of 4459 pregnancies, 949 women had antepartum depression (21.2%) and 1123 had postpartum depression (25%). DMP had a prevalence of 1.2%. Women with DMP had twofold higher odds for postpartum depression compared with women without DMP. Although no association was observed between DMP and antepartum depression, DMP was associated with higher antepartum depression scores. CONCLUSIONS: Our study shows an association between DMP and PND, which might be considered a risk factor when screening for high-risk groups.

Within-individual relationships between mother-to-infant bonding and postpartum depressive symptoms: a longitudinal study.

BACKGROUND: Although the importance of the dynamic intra-individual relationship between mother-to-infant bonding and postpartum depressive symptoms has been widely recognized, the complex interplay between them is not well understood. Furthermore, the potential role of prenatal depressive symptoms and infant temperament in this relationship remains unclear. This study aims to examine the bidirectional influence of mother-to-infant bonding on postpartum depressive symptoms within individuals and to elucidate whether prenatal depressive symptoms and infant temperament would influence deviations from stable individual states. METHODS: Longitudinal data were collected from 433 women in early pregnancy. Of these, 360 participants completed the main questionnaires measuring impaired mother-to-infant bonding and postpartum depressive symptoms at least once during the postpartum period. Data were collected at early and late pregnancy and several postpartum time points: shortly after birth and at one, four, ten, and 18 months postpartum. We also assessed prenatal depressive symptoms and infant temperament. A random-intercept cross-lagged panel model was used. RESULTS: Within-individual variability in mother-to-infant bonding, especially anger and rejection, significantly predicted subsequent postpartum depressive symptoms. However, the inverse relationship was not significant. Additionally, prenatal depressive symptoms and difficult infant temperament were associated with greater within-individual variability in impaired mother-to-infant bonding and postpartum depressive symptoms. CONCLUSIONS: The present study demonstrated that the within-individual relationship between mother-to-infant bonding and postpartum depressive symptoms is likely non-bidirectional. The significance of the findings is underscored by the potential for interventions aimed at improving mother-to-infant bonding to alleviate postpartum depressive symptoms, suggesting avenues for future research and practice.

Gut microbiota dysbiosis contributes to depression-like behaviors via hippocampal NLRP3-mediated neuroinflammation in a postpartum depression mouse model.

Postpartum depression (PPD) is a severe mental disorder that affects approximately 10---20% of women after childbirth. The precise mechanism underlying PPD pathogenesis remains elusive, thus limiting the development of therapeutics. Gut microbiota dysbiosis is considered to contribute to major depressive disorder. However, the associations between gut microbiota and PPD remain unanswered. Here, we established a mouse PPD model by sudden ovarian steroid withdrawal after hormone-simulated pseudopregnancy-human (HSP-H) in ovariectomy (OVX) mouse. Ovarian hormone withdrawal induced depression-like and anxiety-like behaviors and an altered gut microbiota composition. Fecal microbiota transplantation (FMT) from PPD mice to antibiotic cocktail-treated mice induced depression-like and anxiety-like behaviors and neuropathological changes in the hippocampus of the recipient mice. FMT from healthy mice to PPD mice attenuated the depression-like and anxiety-like behaviors as well as the inflammation mediated by the NOD-like receptor protein (NLRP)-3/caspase-1 signaling pathway both in the gut and the hippocampus, increased fecal short-chain fatty acids (SCFAs) levels and alleviated gut dysbiosis with increased SCFA-producing bacteria and reduced Akkermansia in the PPD mice. Also, downregulation of NLRP3 in the hippocampus mitigated depression-like behaviors in PPD mice and overexpression of NLRP3 in the hippocampal dentate gyrus induced depression-like behaviors in naïve female mice. Intriguingly, FMT from healthy mice failed to alleviate depression-like behaviors in PPD mice with NLRP3 overexpression in the hippocampus. Our results highlighted the NLRP3 inflammasome as a key component within the microbiota-gut-brain axis, suggesting that targeting the gut microbiota may be a therapeutic strategy for PPD.

Brexanolone Treatment in a Real-World Patient Population: A Case Series and Pilot Feasibility Study of Precision Neuroimaging.

PURPOSE/BACKGROUND: Brexanolone is approved for postpartum depression (PPD) by the United States Food and Drug Administration. Brexanolone has outperformed placebo in clinical trials, but less is known about the efficacy in real-world patients with complex social and medical histories. Furthermore, the impact of brexanolone on large-scale brain systems such as changes in functional connectivity (FC) is unknown. METHODS/PROCEDURES: We tracked changes in depressive symptoms across a diverse group of patients who received brexanolone at a large medical center. Edinburgh Postnatal Depression Scale (EPDS) scores were collected through chart review for 17 patients immediately prior to infusion through approximately 1 year postinfusion. In 2 participants, we performed precision functional neuroimaging (pfMRI), including before and after treatment in 1 patient. pfMRI collects many hours of data in individuals for precision medicine applications and was performed to assess the feasibility of investigating changes in FC with brexanolone. FINDINGS/RESULTS: The mean EPDS score immediately postinfusion was significantly lower than the mean preinfusion score (mean change [95% CI]: 10.76 [7.11-14.40], t (15) = 6.29, P < 0.0001). The mean EPDS score stayed significantly lower at 1 week (mean difference [95% CI]: 9.50 [5.23-13.76], t (11) = 4.90, P = 0.0005) and 3 months (mean difference [95% CI]: 9.99 [4.71-15.27], t (6) = 4.63, P = 0.0036) postinfusion. Widespread changes in FC followed infusion, which correlated with EPDS scores. IMPLICATIONS/CONCLUSIONS: Brexanolone is a successful treatment for PPD in the clinical setting. In conjunction with routine clinical care, brexanolone was linked to a reduction in symptoms lasting at least 3 months. pfMRI is feasible in postpartum patients receiving brexanolone and has the potential to elucidate individual-specific mechanisms of action.

Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression.

Postpartum depression (PPD) is a leading cause of morbidity and mortality among women. Clinically, the administration and withdrawal of supraphysiologic estradiol and progesterone (E2 + P) can cause affective symptom reoccurrence in women with a history of PPD, but not matched controls. To investigate the cellular basis underlying this differential affective response, lymphoblastoid cell lines (LCLs) were derived from women with and without past PPD and compared transcriptomically in hormone conditions mimicking pregnancy and parturition: supraphysiologic E2 + P-addback; supraphysiologic E2 + P-withdrawal; and no added E2 + P (Baseline). RNA-sequencing identified unique differentially expressed genes (DEGs) in all hormone conditions, but the majority tended to be downregulated in PPD and observed in E2 + P-addback. Two of these DEGs were evolutionarily conserved cellular stress regulators: IMPACT, an integrative response protein maintaining translational homeostasis, and WWTR1, a transcriptional coactivator in the 'Hippo' pathway mediating cell proliferation and survival. Correspondingly, significant gene network modules were linked to cell cycle progression, estrogen response, and immune dysregulation, suggesting innate differences in intracellular signaling in PPD. In certain hormone conditions, PPD LCLs displayed increased GATA3 expression (an upstream regulator of IMPACT and WWTR1) and differentially phosphorylated eiF2α (the ultimate downstream target of IMPACT). Taken together, these transcriptomic data primarily implicate innately dysregulated cellular responses as potentially influencing mood and/or escalating PPD risk. Furthermore, the intrinsic downregulation of IMPACT's translation and WWTR1's transcription networks may suggest a novel link between PPD and a compromised ability to maintain homeostasis in the context of cellular stress occurring during pregnancy and parturition.

Is peripartum anhedonia a missing target?

The perinatal period is an extremely delicate phase that can involve a high risk for onset of depressive disorders. The Edinburgh Postnatal Depression Scale (EPDS) is a widely validated instrument for assessing perinatal depressive symptoms, including the dimension of anhedonia. There are studies suggesting that the neural mechanism underlying the occurrence of anhedonia in patients with major depressive disorder (MDD) and bipolar depression (BD) might be distinct. Anhedonia seems to represent a more stable and frequent symptom in women with postpartum bipolar relative to unipolar depressive disorder and is associated with significantly higher depressive symptom severity. Perinatal medicine is an important component of women's health. Treatment of anhedonia can be challenging, and the most effective treatment can be a combination of psychotherapy and medication, but the screening of anhedonia in peripartum women can prevent the development of other psychiatric disorders and maladaptive behaviors.

Prevalence and risk factors for postpartum depression 2 months after a vaginal delivery: a prospective multicenter study.

BACKGROUND: Very little is known about the prevalence and risk factors of postpartum depression among women with vaginal births without major pregnancy complications. OBJECTIVE: This study aimed to assess the prevalence of postpartum depression and identify its characteristics 2 months after singleton vaginal delivery at or near term. STUDY DESIGN: This was an ancillary cohort study of the TRanexamic Acid for Preventing Postpartum Hemorrhage After Vaginal Delivery randomized controlled trial, which was conducted in 15 French hospitals in 2015-2016 and enrolled women with singleton vaginal deliveries after 35 weeks of gestation. After randomization, the characteristics of labor, delivery, and the immediate postpartum experience, including the experience of childbirth, were prospectively collected. Medical records provided women's other characteristics, particularly any psychiatric history. Of note, 2 months after childbirth, provisional postpartum depression diagnosis was defined as a score of ≥13 on the Edinburgh Postnatal Depression Scale, a validated self-administered questionnaire. The corrected prevalence of postpartum depression was calculated with the inverse probability weighting method to take nonrespondents into account. Associations between potential risk factors and postpartum depression were analyzed by multivariate logistic regression. Moreover, an Edinburgh Postnatal Depression Scale cutoff value of ≥11 was selected to perform a sensitivity analysis. RESULTS: The questionnaire was returned by 2811 of 3891 women (72.2% response rate). The prevalence rates of the provisional diagnosis were 9.9% (95% confidence interval, 8.6%-11.3%) defined by an Edinburgh Postnatal Depression Scale score of ≥13 and 15.5% (95% confidence interval, 14.0%-17.1%) with a cutoff value of ≥11. The characteristics associated with higher risks of postpartum depression in multivariate analysis were mostly related to prepregnancy characteristics, specifically age of <25 years (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-2.9) and advanced age (adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.6), migration from North Africa (adjusted odds ratio, 2.9; 95% confidence interval, 1.9-4.4), previous abortion (adjusted odds ratio, 1.4; 95% confidence interval, 1.0-2.0), and psychiatric history (adjusted odds ratio, 2.9; 95% confidence interval, 1.8-4.8). Some characteristics of labor and delivery, such as induced labor (adjusted odds ratio, 1.5; 95% confidence interval, 1.1-2.0) and operative vaginal delivery (adjusted odds ratio, 1.4; 95% confidence interval, 1.0-2.0), seemed to be associated with postpartum depression. In addition, bad memories of childbirth in the immediate postpartum were strongly associated with postpartum depression symptoms at 2 months after giving birth (adjusted odds ratio, 2.4; 95% confidence interval, 1.3-4.2). CONCLUSION: Approximately 10% of women with vaginal deliveries have postpartum depression symptoms, assessed by a score of ≥13 on the depression scale that was used at 2 months. Prepregnancy vulnerability factors; obstetrical characteristics, such as induced labor and operative vaginal delivery; and bad memories of childbirth 2 days after delivery were the main factors associated with this provisional diagnosis. A screening approach that targets risk factors may help to identify women at risk of postpartum depression who could benefit from early intervention.

The effect of digital health interventions on postpartum depression or anxiety: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: This study aimed to examine the effect of digital health interventions compared with treatment as usual on preventing and treating postpartum depression and postpartum anxiety. DATA SOURCES: Searches were conducted in Ovid MEDLINE, Embase, Scopus, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. STUDY ELIGIBILITY REQUIREMENTS: The systematic review included full-text randomized controlled trials comparing digital health interventions with treatment as usual for preventing or treating postpartum depression and postpartum anxiety. STUDY APPRAISAL AND SYNTHESIS METHODS: Two authors independently screened all abstracts for eligibility and independently reviewed all potentially eligible full-text articles for inclusion. A third author screened abstracts and full-text articles as needed to determine eligibility in cases of discrepancy. The primary outcome was the score on the first ascertainment of postpartum depression or postpartum anxiety symptoms after the intervention. Secondary outcomes included screening positive for postpartum depression or postpartum anxiety --as defined in the primary study --and loss to follow-up, defined as the proportion of participants who completed the final study assessment compared with the number of initially randomized participants. For continuous outcomes, the Hedges method was used to obtain standardized mean differences when the studies used different psychometric scales, and weighted mean differences were calculated when studies used the same psychometric scales. For categorical outcomes, pooled relative risks were estimated. RESULTS: Of 921 studies originally identified, 31 randomized controlled trials-corresponding to 5532 participants randomized to digital health intervention and 5492 participants randomized to treatment as usual-were included. Compared with treatment as usual, digital health interventions significantly reduced mean scores ascertaining postpartum depression symptoms (29 studies: standardized mean difference, -0.64 [95% confidence interval, -0.88 to -0.40]; I2=94.4%) and postpartum anxiety symptoms (17 studies: standardized mean difference, -0.49 [95% confidence interval, -0.72 to -0.25]; I2=84.6%). In the few studies that assessed screen-positive rates for postpartum depression (n=4) or postpartum anxiety (n=1), there were no significant differences between those randomized to digital health intervention and treatment as usual. Overall, those randomized to digital health intervention had 38% increased risk of not completing the final study assessment compared with those randomized to treatment as usual (pooled relative risk, 1.38 [95% confidence interval, 1.18-1.62]), but those randomized to app-based digital health intervention had similar loss-to-follow-up rates as those randomized to treatment as usual (relative risk, 1.04 [95% confidence interval, 0.91-1.19]). CONCLUSION: Digital health interventions modestly, but significantly, reduced scores assessing postpartum depression and postpartum anxiety symptoms. More research is needed to identify digital health interventions that effectively prevent or treat postpartum depression and postpartum anxiety but encourage ongoing engagement throughout the study period.

Maternal depression and child development at 3 years of age: a longitudinal study in a Brazilian child development promotion program.

BACKGROUND: We tested the hypothesis that children of non-depressed mothers perform better in a developmental test at 3 years than children of depressed mothers. METHOD: Longitudinal analysis from a trial to assess the impact of a child development promotion program in 30 Brazilian municipalities. Mothers and children were appraised at first-year post-partum, 1 and 3 years after enrollment. Child development was assessed through the Ages and Stages Questionnaire (ASQ3) and maternal depression through the Edinburgh Postnatal Depression Scale (EPDS). Crude and adjusted beta coefficients were obtained by linear regression before and after multiple imputation. RESULTS: In total, 2098 mother/child dyads were included and 8.2% of the mothers had persistent depressive symptoms. There was a decrease in ASQ3 as the number of follow-ups with EPDS ≥ 10 increased (p for trend <0.001). In adjusted analysis, the direction of the association persisted but lost statistical significance. After multiple imputation, children from mothers with EPDS ≥ 10 in three follow-ups presented a decrease of about 14 points in ASQ3 (adjusted beta coefficient = -13.79; -22.59 to -5.00) (p for trend = 0.001). CONCLUSIONS: Identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil. IMPACT: In our population study, almost one in every ten women presented persistent depression symptoms across the first 3 years postpartum. In adjusted analysis there was a detrimental impact of persistent maternal depression on child development at 3 years of age. The persistent exposure to maternal depression across early childhood negatively influences children's development. Considering its prevalence, identification of women at increased risk of depression should be among the primary health care sector priorities in maternal and child health in Brazil.

Child sleep problems, maternal sleep and self-efficacy: Sleep's complicated role in maternal depression.

Depression, poor sleep duration and low self-efficacy are common in mothers of children with sleep problems. However, research rarely extends beyond the postpartum period. This study investigated the multifaceted relationship between child sleep and maternal depression in early motherhood. A confidential survey assessed child sleep problems, maternal sleep duration, parental self-efficacy and depressive symptoms in 477 Australian mothers of children aged 3 months to 5 years. We found no relationship between child age and maternal depression, supporting our decision to look beyond postpartum depression. Robust bootstrapped mediation modelling tested the hypothesis that both maternal sleep duration and parental self-efficacy would mediate child sleep problems as predictors of maternal depression. After controlling for child age, results showed a significant parallel mediation effect, demonstrating that maternal sleep duration and parental self-efficacy both mediate the relationship between child sleep problems on maternal depression. While the total effect of child sleep problems on maternal depression was statistically significant, after partialling out the effects of other variables, child sleep problems no longer predicted maternal depression. Akaike information criterion analyses supported the full model, with both mediators explaining meaningful variance in maternal depression. This study expands our knowledge beyond the postpartum period, and divulges the disparate effects of sleep deprivation and parental self-efficacy on the relationship between child sleep and depression in early motherhood. Maternal sleep duration and self-efficacy are modifiable risk factors of maternal depression, indicating possible efficacious treatments. Parental self-efficacy stands out as a direction for clinical practice and further psychobiological study.

One-Day Peer-Delivered Cognitive Behavioral Therapy-Based Workshops for Postpartum Depression: A Randomized Controlled Trial.

INTRODUCTION: Myriad treatment barriers prevent birthing parents with postpartum depression (PPD) from receiving timely treatment. We aimed to determine whether a peer-delivered online 1-day cognitive behavioral therapy (CBT)-based workshop added to treatment as usual (TAU) improves PPD and its comorbidities and is more cost-effective than TAU alone. METHODS: This parallel-group, randomized controlled trial took place in Ontario, Canada (June 7, 2021, to February 18, 2022). Participants were ≥18 years old, had an infant ≤12 months old, and an Edinburgh Postnatal Depression Scale (EPDS) score ≥10. Participants were allocated to receive the workshop plus TAU (n = 202) or TAU and waitlisted to complete the workshop 12 weeks later (n = 203). The primary outcome was change in PPD (EPDS score) from enrollment to 12 weeks later. The secondary outcome was cost-effectiveness and tertiary outcomes included anxiety, social support, partner relationship quality, the mother-infant relationship, parenting stress, and infant temperament. RESULTS: Participants had a mean age of 32.3 years (SD = 4.30) and 65% were White. The workshop led to a significant reduction in EPDS scores (15.95-11.37; d = 0.92, p < 0. 01) and was associated with higher odds of exhibiting a clinically significant decrease in EPDS scores (OR = 2.03; 95% CI: 1.26-3.29). The workshop plus TAU was more cost-effective than TAU alone. It also led to improvements in postpartum anxiety, infant-focused anxiety, parenting stress, and infant temperament. CONCLUSIONS: Peer-delivered 1-day CBT-based workshops can improve PPD and are a potentially scalable low-intensity treatment that could help increase treatment access.

The Mental Health Effects and Experiences of Breastfeeding Decision-Making Among Postpartum Women Living with HIV.

Prior to January 2023, women living with HIV (WLWH) in the United States (US) were discouraged from breastfeeding due to the potential risk of mother-to-child HIV transmission through breastfeeding. Lack of breastfeeding decision-making and experience among WLWH may negatively affect maternal mental health. We implemented a quality improvement initiative to screen WLWH for postpartum depression (PPD), evaluate their attitudes toward breastfeeding, and assess their experience with breastfeeding decision-making. We collected quantitative data from WLWH using a voluntary, self-administered 6-item breastfeeding decision-making and experience survey (administered 1 month postpartum) and a 10-item Edinburgh Postnatal Depression Scale (EPDS, negative = 0-9; administered 1 and 4 months postpartum) tool. We conducted descriptive statistics and cross tabulation analysis. We analyzed 106 WLWH (93.4% non-Hispanic Black/African American; mean age 33.1 years; 82.1% HIV RNA < 200 copies/mL). One in five (19.1%) WLWH had a positive baseline EPDS screen, with the mean EPDS scores decreasing from 5.3 ± 5.4 (baseline) to 4.6 ± 4.8 (follow-up). Among 55 WLWH who provided baseline and follow-up EPDS scores, only 3/13 with a positive baseline EPDS screen had resolved depressive symptoms at follow-up. Over one-third (37.7%) of WLWH indicated feeling "sadness" when asked whether lack of breastfeeding negatively affected their feelings or emotions. Over half of WLWH (51.9%) were aware of the US breastfeeding recommendations, but the majority (60.4%) had never discussed breastfeeding options with a medical provider. Improved provider-patient discussions on infant feeding options among WLWH is needed to increase awareness of breastfeeding choices and promote informed, autonomous breastfeeding decision-making among WLWH.