Investigating heart rate variability measures during pregnancy as predictors of postpartum depression and anxiety: an exploratory study.

Perinatal affective disorders are common, but standard screening measures reliant on subjective self-reports might not be sufficient to identify pregnant women at-risk for developing postpartum depression and anxiety. Lower heart rate variability (HRV) has been shown to be associated with affective disorders. The current exploratory study aimed to evaluate the predictive utility of late pregnancy HRV measurements of postpartum affective symptoms. A subset of participants from the BASIC study (Uppsala, Sweden) took part in a sub-study at pregnancy week 38 where HRV was measured before and after a mild stressor (n = 122). Outcome measures were 6-week postpartum depression and anxiety symptoms as quantified by the Edinburgh Postnatal Depression Scale (EPDS) and the Beck Anxiety Inventory (BAI). In total, 112 women were included in a depression outcome analysis and 106 women were included in an anxiety outcome analysis. Group comparisons indicated that lower pregnancy HRV was associated with depressive or anxious symptomatology at 6 weeks postpartum. Elastic net logistic regression analyses indicated that HRV indices alone were not predictive of postpartum depression or anxiety outcomes, but HRV indices were selected as predictors in a combined model with background and pregnancy variables. ROC curves for the combined models gave an area under the curve (AUC) of 0.93 for the depression outcome and an AUC of 0.83 for the anxiety outcome. HRV indices predictive of postpartum depression generally differed from those predictive of postpartum anxiety. HRV indices did not significantly improve prediction models comprised of psychological measures only in women with pregnancy depression or anxiety.

The Maternal Microbiome as a Map to Understanding the Impact of Prenatal Stress on Offspring Psychiatric Health.

Stress and psychiatric disorders have been independently associated with disruption of the maternal and offspring microbiome and with increased risk of the offspring developing psychiatric disorders, both in clinical studies and in preclinical studies. However, the role of the microbiome in mediating the effect of prenatal stress on offspring behavior is unclear. While preclinical studies have identified several key mechanisms, clinical studies focusing on mechanisms are limited. In this review, we discuss 3 specific mechanisms by which the microbiome could mediate the effects of prenatal stress: 1) altered production of short-chain fatty acids; 2) disruptions in TH17 (T helper 17) cell differentiation, leading to maternal and fetal immune activation; and 3) perturbation of intestinal and microbial tryptophan metabolism and serotonergic signaling. Finally, we review the existing clinical literature focusing on these mechanisms and highlight the need for additional mechanistic clinical research to better understand the role of the microbiome in the context of prenatal stress.

Interactions of perinatal depression versus anxiety and infants' early temperament trajectories.

This study examines the interplay between maternal depression/anxiety and infant temperament's developmental trajectory in 1687 Swedish-speaking mother-infant dyads from Uppsala County (2009-2019), Sweden. The sample includes a high proportion of university-educated individuals and a low share of foreign-born participants. Maternal depressive and anxiety symptoms were assessed using the Edinburgh Postnatal Depression Scale during gestational weeks 17 and 32 and postpartum at week 6. Multinomial regression explored associations between maternal variables and infant temperament trajectories at 6 weeks, 12 months, and 18 months. Prenatal anxiety is associated with the high-rising infant difficult temperament trajectory, while prenatal depression/anhedonia is associated with the stable-medium trajectory, attenuated postpartum. Associations between infant temperament and maternal mood depended on timing (pre/postpartum) and symptom type (depression/anhedonia vs. anxiety).

Benefits of maternally-administered infant massage for mothers of hospitalized preterm infants: a scoping review.

OBJECTIVES: Infant massage (IM) is a well-studied, safe intervention known to benefit infants born preterm. Less is known about the benefits of maternally-administrated infant massage for mothers of preterm infants who often experience increased rates of anxiety and depression in their infants' first year of life. This scoping review summarizes the extent, nature, and type of evidence linking IM and parent-centered outcomes. METHODS: The Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for scoping reviews (PRISMA-ScR) protocol was followed using three databases: PubMed, Embase, and CINAHL. Thirteen manuscripts evaluating 11 separate study cohorts met pre-specified inclusion criteria. RESULTS: Six primary topics related to the influence of infant massage on parent outcomes emerged: 1) anxiety, 2) perceived stress, 3) depressive symptoms, 4) maternal-infant interaction, 5) maternal satisfaction, and 6) maternal competence. Emerging evidence supports that infant massage, when administered by mothers, benefits mothers of preterm infants by reducing anxiety, stress, and depressive symptoms and improving maternal-infant interactions in the short-term, but there is limited evidence to support its effectiveness on these outcomes in longer periods of follow-up. Based on effect size calculations in small study cohorts, maternally-administered IM may have a moderate to large effect size on maternal perceived stress and depressive symptoms. CONCLUSIONS: Maternally-administered IM may benefit mothers of preterm infants by reducing anxiety, stress, depressive symptoms, and by improving maternal-infant interactions in the short-term. Additional research with larger cohorts and robust design is needed to understand the potential relationship between IM and parental outcomes.

The microbiota-gut-brain axis and perceived stress in the perinatal period.

Perinatal perceived stress can contribute to worse health outcomes for the parent-child dyad. Given the emerging relationship between the microbiota-gut-brain axis and stress, this study sought to elucidate connections between bowel symptoms and the gut microbiome in relation to perceived stress at three time points in the perinatal period: two during pregnancy and one postpartum. Ninety-five pregnant individuals participated in a prospective cohort study from April 2017 to November 2019. Researchers assessed Perceived Stress Scale-10 (PSS); bowel symptoms (according to the IBS Questionnaire); psychiatrist assessment of new onset or exacerbated depression and anxiety; and fecal samples analyzed for alpha diversity (measures of gut microbiome diversity utilizing Shannon, Observed OTUs, and Faith's PD) at each timepoint. Covariates included weeks of gestation and weeks postpartum. PSS scores were divided into "Perceived Self-Efficacy" and "Perceived Helplessness." Increased gut microbial diversity was associated with decreased bowel symptoms, decreased overall perceived stress, increased ability to cope with adversity, and decreased distress in the postpartum period. This study found a significant association between a less diverse microbial community, lower self-efficacy early in pregnancy, and greater bowel symptoms and perceived helplessness later in the perinatal period, relationships that may ultimately point to novel diagnostic methods and interventions for perceived stress based on the microbiota-gut-brain axis.

Interactions between perceived stress and microbial-host immune components: two demographically and geographically distinct pregnancy cohorts.

Higher stress during pregnancy associates with negative outcomes and elevated inflammation. The gut microbiota, reflecting environment and social interactions, alongside host immune responses have the potential to better understand perceived stress and identify when stress is excessive in pregnancy. Two U.S. cohorts of 84 pregnant individuals, composed of urban women of color and suburban white women, completed the Perceived Stress Scale-10 (PSS-10) and provided fecal and blood samples at two time points. Confirmatory Factor Analysis assessed the robustness of a two-factor PSS-10 model (Emotional Distress/ED and Self-Efficacy/SE). Gut microbiota composition was measured by 16 S rRNA amplicon sequencing and the immune system activity was assessed with a panel of 21 T-cell related cytokines and chemokines. ED levels were higher in the suburban compared to the urban cohort, but levels of SE were similar. ED and SE levels were associated with distinct taxonomical signatures and the gut microbiota data improved the prediction of SE levels compared with models based on socio-demographic characteristics alone. Integration of self-reported symptoms, microbial and immune information revealed a possible mediation effect of Bacteroides uniformis between the immune system (through CXCL11) and SE. The study identified links between distinct taxonomical and immunological signatures with perceived stress. The data are congruent with a model where gut microbiome and immune factors, both impacting and reflecting factors such as close social relationships and dietary fiber, may modulate neural plasticity resulting in increased SE during pregnancy. The predictive value of these peripheral markers merit further study.

Cross-continental collaboration for understanding postpartum major depression with psychotic features.

Purpose: Assess postpartum depression and psychotic symptoms from three continents. Methods: Compare numbers of women with depression and psychotic symptoms, mania with or without psychotic features, or transient non-affective psychosis and medication choice. Results: The prevalence of postpartum depression and psychosis and treatment choice differed at each site. Conclusions: Best treatment for postpartum depression with psychotic features has not been established yet. Cross-continental collaboration with similar assessments holds promise to develop best practices for these high risk mother-infant dyads.

Differentiated mental health patterns in pregnancy during COVID-19 first two waves in Sweden: a mixed methods study using digital phenotyping.

To utilize modern tools to assess depressive and anxiety symptoms, wellbeing and life conditions in pregnant women during the first two waves of the COVID-19 pandemic in Sweden. Pregnant women (n = 1577) were recruited through the mobile application Mom2B. Symptoms of depression, anxiety and wellbeing were assessed during January 2020-February 2021. Movement data was collected using the phone's sensor. Data on Google search volumes for "Corona" and Covid-related deaths were obtained. Qualitative analysis of free text responses regarding maternity care was performed. Two peaks were seen for depressive symptoms, corresponding to the two waves. Higher prevalence of anxiety was only noted during the first wave. A moderating effect of the two waves in the association of depression, anxiety, and well-being with Covid deaths was noted; positive associations during the first wave and attenuated or became negative during the second wave. Throughout, women reported on cancelled healthcare appointments and worry about partners not being allowed in hospital. The association of mental health outcomes with relevant covariates may vary during the different phases in a pandemic, possibly due to adaptation strategies on a personal and societal/healthcare level. Digital phenotyping can help healthcare providers and governmental bodies to in real time monitor high-risk groups during crises, and to adjust the support offered.

A Brexanolone Treatment Program at an Academic Medical Center: Patient Selection, 90-Day Posttreatment Outcomes, and Lessons Learned.

BACKGROUND: Brexanolone is the first U.S. Food and Drug Administration-approved drug for the treatment of postpartum depression. Brexanolone is a positive allosteric modulator of the GABAA receptor and is given over 60 hours by infusion in a medical setting. This drug has been shown to be effective at significantly reducing Hamilton Rating Scale for Depression scores at 60 hours and 30 days after infusion; however, data beyond 30 days have not yet been available. There have been limited clinical programs able to offer brexanolone owing to the complexity of setting up this treatment in a medical setting. PURPOSE: This study sought to obtain follow-up data from 16 patients who received a brexanolone infusion at UNC Hospitals in Chapel Hill, NC, between October 2019 and December 2020 and were beyond the 30-day postinfusion time point. We describe the methods used to successfully implement this treatment program in an academic medical center and discuss associated challenges and lessons learned with patient selection and process improvements. METHODS: Hamilton Rating Scale for Depression scores were collected before and after infusion from 16 patients who received a brexanolone infusion at UNC. Patients were subsequently contacted for a follow-up interview to obtain Hamilton Rating Scale for Depression scores and complete a semistructured interview at least 30 days past treatment end (between 3 and 16 months after infusion). RESULTS: All 16 patients had a significant reduction in Hamilton Rating Scale for Depression scores at 60 hours, scores dropping on average from 23.9 (standard deviation = 2.6) to 7.6 (standard deviation = 2.9). Eleven of 16 patients consented to provide follow-up data. Follow-up Hamilton Rating Scale for Depression scores remained lower than postinfusion at an average of 6.7 points (standard deviation = 5.1). CONCLUSION: With a strategic cross-disciplinary approach, a Clinical Brexanolone Treatment Program was established at UNC Hospitals in 2019. Sixteen patients have been treated in the program, and 11 participated in a follow-up interview. All 11 patients gave very positive feedback about their treatment. Our program has found brexanolone to be a useful clinical tool in treating women with significant symptoms of postpartum depression.

A Qualitative Study of Religion and Spirituality in a Perinatal Psychiatry Inpatient Unit in the Southeast USA.

Religion and spirituality are important aspects of culture that can interact with mental health. They can also be central components of women's experiences during pregnancy and the postpartum period. This study aims to explore the role of religion and spirituality among women experiencing severe psychopathology during the perinatal period using qualitative interviews of women hospitalized during pregnancy or postpartum on an inpatient unit in the Southeast USA. The average age of participants was 34.2 and all identified as white, aside from one who identified as other. Though religious affiliation was varied, most participants were Christian. Each patient interviewed had a diagnosis of depressive disorder, among other comorbid diagnoses. Three main themes emerged in the subsequent analyses (1) spirituality providing a sense of healing and connectedness above and beyond religion, (2) patients seeking support from religious leaders, and (3) patients experiencing familial pressure to enact religion in a certain way, especially as it relates to child rearing. Clinical implications for each of the themes are explored.

Metabolite trajectories across the perinatal period and mental health: A preliminary study of tryptophan-related metabolites, bile acids and microbial composition.

Depression and anxiety during pregnancy and postpartum are common, but affected women differ in timing, trajectories, and extent of symptoms. The objective of this pilot, feasibility study is to analyze trajectories of serotonin and tryptophan-related metabolites, bile acid metabolites, and microbial composition, in relation to psychiatric history and current symptoms across the perinatal period. Serum and fecal samples were collected from 30 women at three times points in the perinatal period and assayed with LC-MS/MS and 16S sequencing respectively. We defined mean trajectories for each metabolite, clustered individuals by metabolite trajectories, tested associations between metabolites, and examined metabolite levels in relation to microbial composition. Findings of note include: (1) changes in kynurenine and the ratio of kynurenic acid to kynurenine from second trimester to third trimester were strongly associated with baseline primary and secondary bile acids. (2) Secondary bile acid UDCA and its conjugated forms were associated with lower bacterial diversity and levels of Lachnospiraceae, a taxa known to produce Short Chain Fatty Acids. (3) History of anxiety was associated with UDCA levels, but history of major depression was not associated with any of the bile acids. (4) There was a trend towards lower dietary fiber for those with history of anxiety or depression. Overall, our results reveal substantial temporal variation in tryptophan-related metabolites and in bile acid metabolites over the perinatal period, with marked inter-individual variability. Trajectories of TRP -related metabolites, primary and secondary bile acids, and the absence or presence of microbes that produce Short Chain Fatty Acids (SCFAs) considered in concert have the potential to differentiate individuals based on perinatal adaptations that may impact mental and overall health.

Perinatal Mental Health Care In The United States: An Overview Of Policies And Programs.

In the United States, mental health conditions are the most common complications of pregnancy and childbirth, and suicide and overdose combined are the leading cause of death for new mothers. Although awareness of and action on perinatal mental health is increasing, significant gaps remain. Screening and treatment are widely recommended but unevenly implemented, and policies and funding do not adequately support the mental health of childbearing people. As a result, treatable perinatal mental health conditions can have long-term, multigenerational negative consequences. This article provides an overview of the perinatal mental health landscape in the United States by identifying serious gaps in screening, education, and treatment; describing recent federal and state policy efforts; highlighting successful models of care; and offering recommendations for robust and integrated perinatal mental health care.

Infant gut microbiome composition is associated with non-social fear behavior in a pilot study.

Experimental manipulation of gut microbes in animal models alters fear behavior and relevant neurocircuitry. In humans, the first year of life is a key period for brain development, the emergence of fearfulness, and the establishment of the gut microbiome. Variation in the infant gut microbiome has previously been linked to cognitive development, but its relationship with fear behavior and neurocircuitry is unknown. In this pilot study of 34 infants, we find that 1-year gut microbiome composition (Weighted Unifrac; lower abundance of Bacteroides, increased abundance of Veillonella, Dialister, and Clostridiales) is significantly associated with increased fear behavior during a non-social fear paradigm. Infants with increased richness and reduced evenness of the 1-month microbiome also display increased non-social fear. This study indicates associations of the human infant gut microbiome with fear behavior and possible relationships with fear-related brain structures on the basis of a small cohort. As such, it represents an important step in understanding the role of the gut microbiome in the development of human fear behaviors, but requires further validation with a larger number of participants.

Heart rate variability in late pregnancy: exploration of distinctive patterns in relation to maternal mental health.

Exploration of photoplethysmography (PPG), a technique that can be translated to the clinic, has the potential to assess the autonomic nervous system (ANS) through heart rate variable (HRV) in pregnant individuals. This novel study explores the complexity of mental health of individuals in a clinical sample responding to a task in late pregnancy; finding those with several types of past or current anxiety disorders, greater trait anxiety, or greater exposure to childhood traumatic events had significantly different HRV findings from the others in the cohort. Lower high frequency (HF), a measure of parasympathetic activity, was found for women who met the criteria for the history of obsessive-compulsive disorder (OCD) (p = 0.004) compared with women who did not meet the criteria for OCD, and for women exposed to greater than five childhood traumatic events (p = 0.006) compared with those exposed to four or less childhood traumatic events. Conversely higher low frequency (LF), a measure thought to be impacted by sympathetic system effects, and the LF/HF ratio was found for those meeting criteria for a panic disorder (p = 0.006), meeting criteria for social phobia (p = 0.002), had elevated trait anxiety (p = 0.006), or exposure to greater than five childhood traumatic events (p = 0.004). This study indicates further research is needed to understand the role of PPG and in assessing ANS functioning in late pregnancy. Study of the impact of lower parasympathetic functioning and higher sympathetic functioning separately and in conjunction at baseline and in relation to tasks during late pregnancy has the potential to identify individuals that require more support and direct intervention.

The Crisis of Perinatal Mental Health in the Age of Covid-19.

In the US, the COVID-19 pandemic adds a new source of stress for women in the perinatal period, a time when stress and anxiety are already heightened. The closures of physical mental health care spaces and lack of support could have devastating impacts on the health of postpartum women and their newborns. Yet, the pandemic creates an opportunity to innovate in the ways mental health care is delivered to pregnant and postpartum women. With the expanded capacity for video and telephone visits, researchers should continue to explore solutions for providing support networks to this vulnerable population.

Effects of psychological stress on adverse pregnancy outcomes and nonpharmacologic approaches for reduction: an expert review.

Both acute and chronic stress can cause allostatic overload, or long-term imbalance in mediators of homeostasis, that results in disruptions in the maternal-placental-fetal endocrine and immune system responses. During pregnancy, disruptions in homeostasis may increase the likelihood of preterm birth and preeclampsia. Expectant mothers traditionally have high rates of anxiety and depressive disorders, and many are susceptible to a variety of stressors during pregnancy. These common life stressors include financial concerns and relationship challenges and may be exacerbated by the biological, social, and psychological changes occurring during pregnancy. In addition, external stressors such as major weather events (eg, hurricanes, tornados, floods) and other global phenomena (eg, the coronavirus disease 2019 pandemic) may contribute to stress during pregnancy. This review investigates recent literature published about the use of nonpharmacologic modalities for stress relief in pregnancy and examines the interplay between psychiatric diagnoses and stressors, with the purpose of evaluating the feasibility of implementing nonpharmacologic interventions as sole therapies or in conjunction with psychotherapy or psychiatric medication therapy. Further, the effectiveness of each nonpharmacologic therapy in reducing symptoms of maternal stress is reviewed. Mindfulness meditation and biofeedback have shown effectiveness in improving one's mental health, such as depressive symptoms and anxiety. Exercise, including yoga, may improve both depressive symptoms and birth outcomes. Expressive writing has successfully been applied postpartum and in response to pregnancy challenges. Although some of these nonpharmacologic interventions can be convenient and low cost, there is a trend toward inconsistent implementation of these modalities. Future investigations should focus on methods to increase ease of uptake, ensure each option is available at home, and provide a standardized way to evaluate whether combinations of different interventions may provide added benefit.

Maternal Mental Health MATTERS.

Depression and anxiety during pregnancy and the postpartum period are common and have significant negative impacts on mother and child. Suicide is a leading cause of maternal mortality. Evidence-based efforts for screening, assessment, and treatment improve maternal and infant mental health, as well as overall family health, throughout the lives of women and children.

Toward a framework for best practices and research guidelines for perinatal depression research.

This review article highlights the current state of perinatal depression (PND) research including established standards of care and innovative research in progress. PND can have a significant adverse impact on mother, child, and family; however, to date, wide-scale identification, prevention, and treatment have been limited. PND is heterogenous in presentation with likely multifactorial etiologies for each woman. Challenges in PND research are discussed including a need for universal tools, standardized measures, benchmarks, and best practices. Current examples are reviewed that highlight approaches to novel treatment paradigms and interventions. This includes reviewing epidemiologic studies in PND research, examining the biological underpinnings of PND, and discussing examples from this field and other fields currently developing translational research that spans from bench to bedside. Current and future challenges and opportunities in developing best practices for the treatment of PND are outlined. We also discuss the use of the NIMH Research Domain Criteria approach for PND research and provide recommendations for future directions in PND research collaboration. In conclusion, greater precision in perinatal psychiatry can be possible in the future with the development of guidelines and best practices that build on current work and apply innovative and collaborative approaches of scientists, providers, patients, community members, and government officials.