Loss of transient receptor potential channel 5 causes obesity and postpartum depression.

Hypothalamic neural circuits regulate instinctive behaviors such as food seeking, the fight/flight response, socialization, and maternal care. Here, we identified microdeletions on chromosome Xq23 disrupting the brain-expressed transient receptor potential (TRP) channel 5 (TRPC5). This family of channels detects sensory stimuli and converts them into electrical signals interpretable by the brain. Male TRPC5 deletion carriers exhibited food seeking, obesity, anxiety, and autism, which were recapitulated in knockin male mice harboring a human loss-of-function TRPC5 mutation. Women carrying TRPC5 deletions had severe postpartum depression. As mothers, female knockin mice exhibited anhedonia and depression-like behavior with impaired care of offspring. Deletion of Trpc5 from oxytocin neurons in the hypothalamic paraventricular nucleus caused obesity in both sexes and postpartum depressive behavior in females, while Trpc5 overexpression in oxytocin neurons in knock-in mice reversed these phenotypes. We demonstrate that TRPC5 plays a pivotal role in mediating innate human behaviors fundamental to survival, including food seeking and maternal care.

The role of stress in perinatal depression and anxiety - A systematic review.

Perinatal depression (PND) and anxiety affect around 20% of women, but available pharmacotherapy is not sufficiently effective in 20-60% of them, indicating a need for better understanding of these diseases. Since stress is a significant risk factor for PND, the aim was to examine the role of biological, environmental and psychological stress in PND and anxiety through a systematic literature search. Overall 210 studies were included, among which numerous rodent studies showed that perinatal stress induced depressive-like and anxious behavior, which was associated with HPA-axis alterations and morphological brain changes. Human studies indicated that the relationship between cortisol and perinatal depression/anxiety was not as clear and with many contradictions, although social and psychological stress were clearly positively associated with PND. Finally, oxytocin, synthetic neuroactive steroid and n-3 PUFA diet have been identified as potentially beneficial in the therapy of PND and anxiety, worth to be investigated in the future.

Perinatal depression and risk of maternal cardiovascular disease: a Swedish nationwide study.

BACKGROUND AND AIMS: Increasing evidence suggests that some reproductive factors/hazards are associated with a future risk of cardiovascular disease (CVD) in women. While major (non-perinatal) depression has consistently been associated with CVD, the long-term risk of CVD after perinatal depression (PND) is largely unknown. METHODS: A nationwide population-based matched cohort study involving 55 539 women diagnosed with PND during 2001-14 in Sweden and 545 567 unaffected women individually matched on age and year of conception/delivery was conducted. All women were followed up to 2020. Perinatal depression and CVD were identified from Swedish national health registers. Using multivariable Cox models, hazard ratios (HR) of any and type-specific CVD according to PND were estimated. RESULTS: The mean age at the PND diagnosis was 30.8 [standard deviation (SD) 5.6] years. During the follow-up of up to 20 years (mean 10.4, SD 3.6), 3533 (6.4%) women with PND (expected number 2077) and 20 202 (3.7%) unaffected women developed CVD. Compared with matched unaffected women, women with PND had a 36% higher risk of developing CVD [adjusted HR = 1.36, 95% confidence interval (CI): 1.31-1.42], while compared with their sisters, women with PND had a 20% higher risk of CVD (adjusted HR = 1.20, 95% CI 1.07-1.34). The results were most pronounced in women without a history of psychiatric disorder (P for interaction < .001). The association was observed for all CVD subtypes, with the highest HR in the case of hypertensive disease (HR = 1.50, 95% CI: 1.41-1.60), ischaemic heart disease (HR = 1.37, 95% CI: 1.13-1.65), and heart failure (HR 1.36, 95% CI: 1.06-1.74). CONCLUSIONS: Women with PND are at higher risk of CVD in middle adulthood. Reproductive history, including PND, should be considered in CVD risk assessments of women.

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.

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.

Wheel Running During Pregnancy Alleviates Anxiety-and Depression-Like Behaviors During the Postpartum Period in Mice: The Roles of NLRP3 Neuroinflammasome Activation, Prolactin, and the Prolactin Receptor in the Hippocampus.

Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1 h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.

The association between postpartum depressive symptoms and contraception.

BACKGROUND: Postpartum depression affects 10% to 20% of birthing people and is associated with changes in healthcare use. Little is known about the association between postpartum depressive symptoms and choice to use contraception; however, both untreated or undertreated depression and short interpregnancy intervals pose substantial perinatal health risks. OBJECTIVE: This study aimed to evaluate whether postpartum depressive symptoms are associated with changes in decisions to use any method of contraception. STUDY DESIGN: This retrospective cohort study included birthing people who delivered between 2017 and 2022 and were referred to a collaborative care program for mental healthcare. Through this program, birthing people with mental health conditions have access to specialized perinatal mental healthcare and prospective symptom monitoring via a patient registry. Postpartum depressive symptoms are assessed via the Patient Health Questionnaire-9, and scores were stratified by severity according to clinical cutoffs. Contraceptive method choice was determined by documentation in the electronic health record and dichotomized as "none" if the participant declined all forms of contraception both at delivery and at the postpartum visit. Bivariable and multivariable analyses were performed. RESULTS: Of the 1871 participants that met the inclusion criteria, 160 (8.5%) had postpartum Patient Health Questionnaire-9 scores of >14, representing moderately severe or worse depressive symptoms, and 43 (2.3%) had severe (Patient Health Questionnaire-9 of >19) depressive symptoms. Birthing people with higher Patient Health Questionnaire-9 scores were more likely to have medical comorbidities; to have a higher body mass index; to self-identify as Black, Native Hawaiian or Pacific Islander, or Hispanic or Latina; and to have a preterm delivery and less likely to be married or nulliparous than those with Patient Health Questionnaire-9 scores of ≤14. There was no difference in any other sociodemographic or clinical characteristics. The choice to use any contraceptive method decreased with increasing depressive symptoms in bivariable and multivariable analyses, reaching statistical significance in birthing people with severe depressive symptoms (adjusted odds ratio, 2.92; 95% confidence interval, 1.46-5.84). CONCLUSION: Severe perinatal depressive symptoms are associated with a declination of any form of postpartum contraception. This finding becomes increasingly relevant as abortion access continues to be threatened across the United States, compounding the potential effect of opting not to use contraception.

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.

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 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.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

The relationship between postpartum negative life events and postpartum depression: a moderated mediation model of neuroticism and psychological flexibility.

BACKGROUND: Postpartum depression (PPD) is a major public health problem worldwide. Previous studies have shown that postpartum negative life events and neuroticism are both important risk factors for PPD. However, few studies have considered the role of protective factors in the influence of postpartum negative life events and neuroticism on PPD. Based on the diathesis-stress model and Acceptance and Commitment Therapy (ACT), a moderated mediating model was established to examine the mediating role of neuroticism between postpartum negative life events and PPD, as well as the moderating role of psychological flexibility in this mediating effect. METHODS: A sample of 776 parturients from three different Grade A hospitals in China were assessed using the Edinburgh Postpartum Depression Scale, the Postpartum Negative Life Events Scale, the Neuroticism Subscale of the Big Five Personality Scale, and the Acceptance and Action Questionnaire- II. RESULTS: PPD, postpartum negative life events, neuroticism, and experiential avoidance were significantly positively correlated with one another. Neuroticism partially mediated the relationship between postpartum negative life events and PPD. In this mediation model, the direct path and the second half of the mediation path were moderated by psychological flexibility. Specifically, the links between postpartum negative life events and PPD, as well as between neuroticism and PPD, were stronger when psychological flexibility was low, but weaker when psychological flexibility was high. CONCLUSIONS: The results show that psychological flexibility plays an important role in buffering the negative effects of postpartum negative life events and neuroticism on PPD. These findings provide implications for the prevention and intervention of PPD using an ACT approach.

Diagnosis of peripartum depression disorder: A state-of-the-art approach from the COST Action Riseup-PPD.

BACKGROUND: Peripartum depression (PPD) is a major depression disorder (MDD) episode with onset during pregnancy or within four weeks after childbirth, as defined in DSM-5. However, research suggests that PPD may be a distinct diagnosis. The goal of this study was to summarize the similarities and differences between PPD and MDD by synthesizing the current research on PPD diagnosis concerning different clinical features and give directions for improving diagnosis of PPD in clinical practice. METHODS: To lay the groundwork for this narrative review, several databases were searched using general search phrases on PPD and its components of clinical diagnosis. RESULTS: When compared to MDD, peripartum depression exhibits several distinct characteristics. PPD manifests with a variety of symptoms, i.e., more anxiety, psychomotor symptoms, obsessive thoughts, impaired concentration, fatigue and loss of energy, but less sad mood and suicidal ideation, compared to MDD. Although PPD and MDD prevalence rates are comparable, there are greater cross-cultural variances for PPD. Additionally, PPD has some distinct risk factors and mechanisms such as distinct ovarian tissue expression, premenstrual syndrome, unintended pregnancy, and obstetric complications. CONCLUSION: There is a need for more in-depth research comparing MDD with depression during pregnancy and the entire postpartum year. The diagnostic criteria should be modified, particularly with (i) addition of specific symptoms (i.e., anxiety), (ii) onset specifier extending to the first year following childbirth, (iii) and change the peripartum onset specifier to either "pregnancy onset" or "postpartum onset". Diagnostic criteria for PPD are further discussed.

Blood metabolomic and postpartum depression: a mendelian randomization study.

BACKGROUND: Postpartum depression is a complex mental health condition that often occurs after childbirth and is characterized by persistent sadness, anxiety, and fatigue. Recent research suggests a metabolic component to the disorder. This study aims to investigate the causal relationship between blood metabolites and postpartum depression using mendelian randomization (MR). METHODS: This study used a bi-directional MR framework to investigate the causal relationship between 1,400 metabolic biomarkers and postpartum depression. We used two specific genome-wide association studies datasets: one with single nucleotide polymorphisms data from mothers diagnosed with postpartum depression and another with blood metabolite data, both of which focused on people of European ancestry. Genetic variants were chosen as instrumental variables from both datasets using strict criteria to improve the robustness of the MR analysis. The combination of these datasets enabled a thorough examination of genetic influences on metabolic profiles associated with postpartum depression. Statistical analyses were conducted using techniques such as inverse variance weighting, weighted median, and model-based estimation, which enabled rigorous causal inference from the observed associations. postpartum depression was defined using endpoint definitions approved by the FinnGen study's clinical expert groups, which included leading experts in their respective medical fields. RESULTS: The MR analysis identified seven metabolites that could be linked to postpartum depression. Out of these, one metabolite was found to be protective, while six were associated with an increased risk of developing the condition. The results were consistent across multiple MR methods, indicating a significant correlation. CONCLUSIONS: This study emphasizes the potential of metabolomics for understanding postpartum depression. The discovery of specific metabolites associated with the condition sheds new insights on its pathophysiology and opens up possibilities for future research into targeted treatment strategies.

Association between postpartum depression and postpartum hemorrhage: A systematic review and meta-analysis.

INTRODUCTION: Postpartum depression (PPD) is a growing mental health concern worldwide and has detrimental effects on the social and cognitive health of both mothers and infants. This review was performed to assess the risk of PPD in women with postpartum hemorrhage (PPH) and to identify potential moderators. MATERIAL AND METHODS: The review protocol was registered in the PROSPERO database on June 17, 2023 (registration number: CRD42023432955). Two researchers independently performed a literature search of the PubMed, Embase, and Web of Science databases for articles published before May 25, 2023, with no filters and no language or location restrictions. Study quality was evaluated using the Newcastle-Ottawa Scale. The primary outcome was the odds ratio (OR) and 95% confidence interval (CI) of PPD in women with vs. without PPH. We performed sensitivity analyses and meta-regression analyses to resolve heterogeneity. Meta-regression analyses included the effects of age, maternal smoking, marital status, preterm labor, maternal education level, preeclampsia, anemia during pregnancy, and cesarean section. RESULTS: In total, seven studies involving 540 558 participants met the eligibility criteria and were included in the meta-analysis. Women with PPH were at increased risk of PPD compared with women without PPH (OR 1.10; 95% CI 1.03-1.16), and heterogeneity was low (I2 = 23%; τ2 = 0.0007; p = 0.25). Moreover, the results of the sensitivity analyses showed that the I2 value decreased from 23% to 0% after excluding one particular study, which may have been a source of heterogeneity. In the meta-regression analyses, the OR of PPD was greatly affected by maternal smoking (OR -0.26; 95% CI -0.30 to -0.22; p < 0.001). However, we did not observe any effects for maternal age, marital status, preterm labor, maternal education level, preeclampsia, anemia during pregnancy, or cesarean section. CONCLUSIONS: Women with PPH must be closely monitored because they have a higher risk of PPD than women without PPH. Early recognition and management of these patients will improve treatment outcomes, maternal health, and newborn development.

Association between postpartum depression and breastfeeding self-efficacy in mothers: a systematic review and meta-analysis.

BACKGROUND: Depression is one of the most common mental disorders in the postpartum period. Depression can decrease self-efficacy in breastfeeding by reducing the mother's self-confidence. Considering the conflicting results regarding the relationship between postpartum depression and breastfeeding self-efficacy, this systematic review was conducted to investigate the relationship between breastfeeding self-efficacy and postpartum depression. METHOD: In this systematic review, published articles in PubMed, Scopus, Web of Sciences, Cochrane Library, and Google Scholar databases were searched using English keywords "Self-efficacy, breastfeeding, breastfeeding Self-efficacy, depression, postpartum depression" without publication date limit. Data analysis was done with employing STATA14 software. Heterogeneity was assessed using I2 index which was 0%. Therefore, the fixed effects method was used to combine the data and perform meta-analysis. RESULT: The results of the meta-analysis showed that based on the fixed effect method, depression was associated with decreased breastfeeding self-efficacy on the first day (SMD = 0.62, 95%CI: -0.830, -0.41, p = 0.0001) and on the third day (SMD = 0.84, 95% CI: -0.55,1.14, p = 0.0001). The Begg and Manzumdar test revealed no publication bias, with p = 0.317. CONCLUSION: Postpartum depression may be associated with a decrease in the mother's breastfeeding self-efficacy and placing mother in a condition to pay low attention to her maternal role. Therefore, healthcare providers should provide adequate support according to the needs of mothers and develop diagnostic and treatment protocols to improve the level of maternal health.

Perinatal posttraumatic stress disorder as a predictor of mother-child bonding quality 8 months after childbirth: a longitudinal study.

BACKGROUND: Negative childbirth experiences can be related to the onset of perinatal post-traumatic stress symptomatology (P-PTSS), which significantly impacts the mother and the infant. As a response in the face of the discomfort caused by P-PTSS, maladaptive emotion regulation strategies such as brooding can emerge, contributing to the consolidation of post-partum depressive symptoms. Ultimately, both types of symptomatology, P-PTSS and post-partum depression, can act as risk factors for developing mother-child bonding difficulties. Still, this full set of temporal paths has to date remained untested. The present longitudinal study aimed to analyze the risk factors associated with the appearance of P-PTSS after post-partum and to test a path model considering the role of P-PTSS as an indirect predictor of bonding difficulties at eight months of postpartum. METHODS: An initial sample of pregnant women in the third trimester of gestation (N = 594) participated in a longitudinal study comprising two follow-ups at two and eight months of postpartum. The mothers completed online evaluations that included socio-demographic data and measures of psychological variables. A two-step linear regression model was performed to assess the predictive role of the variables proposed as risk factors for P-PTSS, and a path model was formulated to test the pathways of influence of P-PTSS on bonding difficulties. RESULTS: A history of psychopathology of the mother, the presence of depression during pregnancy, the presence of medical complications in the mother, and the occurrence of traumatic birth experiences all acted as significant predictors of P-PTSS, explaining 29.5% of its variance. Furthermore, the path model tested further confirmed an indirect effect of P-PTSS, triggered by a negative childbirth experience, on subsequent bonding difficulties eight months after labor through its association with higher levels of brooding and, ultimately, postpartum depression levels. A further path showed that bonding difficulties at two months postpartum can persist at eight months postpartum due to the onset of brooding and postpartum depression symptoms. CONCLUSION: We identified a set of robust predictors of P-PTSS: the mother's previous history of depression, perinatal depression during pregnancy, the presence of medical complications in the mother and the occurrence of traumatic birth experiences, which has important implications for prevention. This is particularly relevant, as P-PTSS, when triggered by a negative childbirth experience, further indirectly predicted the development of mother-child bonding difficulties through the mediation of higher use of brooding and symptoms of postpartum depression. These findings can serve as a basis for developing new longitudinal studies to further advance the understanding of perinatal mechanisms of mental health.

The comparison of the effect of non-pharmacological pain relief and pharmacological analgesia with remifentanil on fear of childbirth and postpartum depression: a randomized controlled clinical trial.

INTRODUCTION: Childbirth may be associated with psychological, social, and emotional effects and provide the background for women's health or illness throughout their life. This research aimed at comparing the impact of non-pharmacological pain relief and pharmacological analgesia with remifentanil on childbirth fear and postpartum depression. MATERIALS AND METHOD: This randomized clinical trial with two parallel arms was conducted on 66 women with term pregnancy referred to Taleghani Hospital in Tabriz for vaginal delivery during September 2022 to September 2023. First, all of the eligible participants were selected through Convenience Sampling. Then, they were randomly assigned into two groups of pharmacological analgesia with remifentanil and non-pharmacological analgesia with a ratio of 1:1 using stratified block randomization based on the number of births. Before the intervention, fear of childbirth (FOC) was measured using Delivery Fear Scale (DFS) between 4 and 6 cm cervical dilatation. Pain and fear during labor in dilatation of 8 cm were measured in both groups using VAS and DFS. After delivery, FOC was assessed using Delivery Fear Scale (W DEQ Version B) and postpartum depression using the Edinburgh's postpartum depression scale (EPDS). Significance level was considered 0.05. Mean difference (MD) was compared with Independent T-test and ANCOVA pre and post intervention. RESULTS: The mean score of FOC in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group after the intervention by controlling the effect of the baseline score (MD: -6.33, 95%, Confidence Interval (CI): -12.79 to -0.12, p = 0.04). In the postpartum period, the mean score of FOC in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group after controlling the effect of the baseline score (MD: -21.89; 95% CI: -35.12 to -8.66; p = 0.002). The mean score of postpartum depression in the non-pharmacological analgesia group was significantly lower than that in the pharmacological analgesia group (MD: -1.93, 95% CI: -3.48 to -0.37, p = 0.01). TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT): IRCT20170506033834N10. Date of registration: 05/07/2022 Date of first registration: 05/07/2022. URL: https://www.irct.ir/trial/61030; Date of recruitment start date05/07/2022. CONCLUSION: The study results indicated a reduction in FOC and postpartum depression among parturient women receiving non-pharmacological strategies with active participation in childbirth compared to women receiving pharmacological analgesia. Owing to the possible side effects of pharmacological methods for mother and fetus, non-pharmacological strategies with active participation of the mother in childbirth are recommended to reduce the FOC and postpartum depression.