Mental health status of pregnant and breastfeeding women during the COVID-19 pandemic-A multinational cross-sectional study.

INTRODUCTION: Evidence on perinatal mental health during the coronavirus disease 2019 (COVID-19) pandemic and its potential determinants is limited. Therefore, this multinational study aimed to assess the mental health status of pregnant and breastfeeding women during the pandemic, and to explore potential associations between depressive symptoms, anxiety, and stress and women's sociodemographic, health, and reproductive characteristics. MATERIAL AND METHODS: A cross-sectional, web-based study was performed in Ireland, Norway, Switzerland, the Netherlands, and the UK between 16 June and 14 July 2020. Pregnant and breastfeeding women up to 3 months postpartum who were older than 18 years of age were eligible. The online, anonymous survey was promoted through social media and hospital websites. The Edinburgh Depression Scale (EDS), the Generalized Anxiety Disorder seven-item scale (GAD-7), and the Perceived Stress Scale (PSS) were used to assess mental health status. Regression model analysis was used to identify factors associated with poor mental health status. RESULTS: In total, 9041 women participated (including 3907 pregnant and 5134 breastfeeding women). The prevalence of major depressive symptoms (EDS ≥ 13) was 15% in the pregnancy cohort and and 13% the breastfeeding cohort. Moderate to severe generalized anxiety symptoms (GAD ≥ 10) were found among 11% and 10% of the pregnant and breastfeeding women. The mean (±SD) PSS scores for pregnant and breastfeeding women were 14.1 ± 6.6 and 13.7 ± 6.6, respectively. Risk factors associated with poor mental health included having a chronic mental illness, a chronic somatic illness in the postpartum period, smoking, having an unplanned pregnancy, professional status, and living in the UK or Ireland. CONCLUSIONS: This multinational study found high levels of depressive symptoms and generalized anxiety among pregnant and breastfeeding women during the COVID-19 outbreak. The study findings underline the importance of monitoring perinatal mental health during pandemics and other societal crises to safeguard maternal and infant mental health.

Changes in cerebral CB1 receptor availability after acute and chronic alcohol abuse and monitored abstinence.

Involvement of the type 1 cannabinoid receptor (CB1R) in the effects of alcohol on the brain is supported by animal experiments, but how in vivo CB1R levels are altered in alcoholic patients is still unclear. To assess the short-time effects of a binge drinking episode on CB1R availability, 20 healthy social drinkers underwent [(18)F]MK-9470-positron emission tomography (PET) at baseline and after intravenous ethanol administration (ALC ACU). Moreover, 26 alcoholic patients underwent sequential CB1R PET after chronic heavy drinking (ALC CHR) and after 1 month of abstinence (ALC ABST). Seventeen healthy subjects served as controls. Compared with baseline, ALC ACU resulted in a global increase of CB1R availability (+15.8%). In contrast, a global decreased CB1R availability was found in ALC CHR patients (-16.1%) compared with controls, which remained unaltered after abstinence (-17.0%). Voxel-based analysis showed that ALC CHR patients had reduced CB1R availability, especially in the cerebellum and parieto-occipital cortex. After abstinence, reduced CB1R availability extended also to other areas such as the ventral striatum and mesotemporal lobe. In conclusion, whereas the acute alcohol effect is an increase in CB1R availability, chronic heavy drinking leads to reduced CB1R availability that is not reversible after 1 month of abstinence. Longer follow-up is required to differentiate whether this is a compensatory effect of repeated endocannabinoid overstimulation or an enduring trait-like feature. An enhanced CB1R signaling may offer a new therapeutic direction for treatment of the negative affective state produced by alcohol withdrawal and abstinence, which is critical for the maintenance of alcohol addiction.

Chronic Fatigue Syndrome and DNA Hypomethylation of the Glucocorticoid Receptor Gene Promoter 1F Region: Associations With HPA Axis Hypofunction and Childhood Trauma.

OBJECTIVES: Chronic fatigue syndrome (CFS) has been associated with hypothalamic-pituitary-adrenal axis hypofunction and enhanced glucocorticoid receptor (GR) sensitivity. In addition, childhood trauma is considered a major risk factor for the syndrome. This study examines DNA methylation of the GR gene (NR3C1) in CFS and associations with childhood sexual and physical trauma. METHODS: Quantification of DNA methylation within the 1F promoter region of NR3C1 was performed in 76 female patients (46 with no/mild and 30 with moderate/severe childhood trauma) and 19 healthy controls by using Sequenom EpiTYPER. Further, we examined the association of NR3C1-1F promoter methylation with the outcomes of the low-dose (0.5 mg) dexamethasone/corticotropin-releasing factor test in a subset of the study population. Mann-Whitney U tests and Spearman correlations were used for statistical analyses. RESULTS: Overall NR3C1-1F DNA methylation was lower in patients with CFS than in controls. After cytosine guanine dinucleotide (CpG)-specific analysis, CpG_1.5 remained significant after Bonferroni correction (adjusted p = .0014). Within the CFS group, overall methylation (ρ = 0.477, p = .016) and selective CpG units (CpG_1.5: ρ = 0.538, p = .007; CpG_12.13: ρ = 0.448, p = .025) were positively correlated with salivary cortisol after dexamethasone administration. There was no significant difference in NR3C1-1F methylation between traumatized and nontraumatized patients. CONCLUSIONS: We found evidence of NR3C1 promoter hypomethylation in female patients with CFS and the functional relevance of these differences was consistent with the hypothalamic-pituitary-adrenalaxis hypofunction hypothesis (GR hypersuppression). However, we found no evidence of an additional effect of childhood trauma on CFS via alterations in NR3C1 methylation.

The influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth.

BACKGROUND: This exploratory study investigates the influence of maternal cortisol and emotional state during pregnancy on fetal intrauterine growth (IUG). We expected higher basal cortisol levels, or more depressive and anxious complaints during pregnancy, to be associated with slower IUG and lower birth weight. METHODS: A total of 91 pregnant women were recruited from the antenatal clinic and were seen once each trimester. In addition to psychological assessments, a diurnal cortisol profile was derived from saliva samples. IUG was evaluated using ultrasound. RESULTS: In mid-pregnancy (trimester (T)2), basal cortisol levels significantly predicted the variance of weight (proportion of variance in growth variable explained (PVE) = 11.6%) and body mass index (BMI) at birth (PVE = 6.8%). In late pregnancy (T3) emotional state, particularly depressive symptoms (BMI at birth: PVE = 6.9%; ponderal index (PI) at birth: PVE = 8.2%; head circumference at T3: PVE = 10.3%; head circumference at birth PVE = 9.1%) and attachment (BMI at birth: PVE = 6.9%; PI at birth: PVE = 7.2%) had an influence on growth. Analysis of growth between T2 and T3 showed that attachment and cortisol in T3 had an influence on the variation in increase in estimated fetal weight (PVE = 12.5-8.6%). CONCLUSION: These data indicate basal cortisol levels were more important in T2 whereas emotional state was more important in T3.

The longitudinal course of depressive symptoms during the perinatal period: A systematic review.

BACKGROUND: Perinatal Depression (PND) is one of the most common complications (10-20 %) during the perinatal period and its clinical course and phenotypes are still an area of research. It is becoming increasingly clear that pregnant women and mothers with depression are not a homogeneous clinical group. METHODS: A systematic literature search in 4 databases revealed 359 studies, 33 relevant studies met the inclusion criteria. We only included studies with at least three assessment points in total. RESULTS: Two to six trajectory classes were identified. A three trajectories solution was most observed. All the included studies reported a low symptom trajectory but ranged from 6.5 % to 92 %. The high-symptom group was in most of the studies the smallest subgroup (1.1 % - 14.6 %). Most of the studies described episodic trajectories of depressive symptoms during the peripartum. The most common risk factor associated with a high-symptom trajectory of depressive symptoms in our study was a history of depression. Important socio-demographic predictors were: young age, ethnicity, low maternal education, low income, single relationship status or relationship problems, unplanned or unintended pregnancy and experiencing high stress levels. LIMITATIONS: The methodology and the observed PND trajectories of the included studies differed, which makes generalizability difficult in this review. CONCLUSIONS: PND is a frequent but heterogeneous disorder. Globally, four major groups could be distinguished: low, medium, high and episodic trajectories. There is a need for consensus regarding which assessment instruments to use, validated cutoff scores and similar time points of assessment.

Depression and post-traumatic stress disorder after perinatal loss in fathers: A systematic review.

BACKGROUND: Research indicates that perinatal loss can cause profound psychological consequences in parents. However, a comprehensive summary of existing quantitative literature describing the association between perinatal loss and the development of depression/depressive symptoms or post-traumatic stress disorder (PTSD)/post-traumatic stress (PTS) symptoms in fathers has not been published. METHODS: A systematic literature search (from inception to December 2021), using the PubMed, EMBASE, and Web of Science databases to articles assessing depressive or PTS symptoms, was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Only studies investigating the period of intrauterine death from 20 weeks of gestation, stillbirth, or neonatal death within the first month after birth were included. RESULTS: A final sample of 13 articles were eligible for inclusion. Some studies showed an increased risk of depressive and PTS symptoms in fathers after perinatal loss. However, many study results did not show significant differences, symptoms generally decreased over time, and the majority of studies showed higher levels of depressive and PTS symptoms in mothers, compared with fathers. CONCLUSIONS: Although the majority of the included studies showed elevated levels of depressive and/or PTSD symptoms after perinatal loss in fathers, no clear firm conclusion can be drawn, as the included studies were very heterogeneous. More homogeneous research measuring depressive and PTS symptoms in fathers is needed at the time of the loss, as the current literature available shows several limitations and gaps.

Early Postnatal Outcome and Care after in Utero Exposure to Lithium: A Single Center Analysis of a Belgian Tertiary University Hospital.

Knowledge of the impact of in utero exposure to lithium during the postnatal period is limited. Besides a possible teratogenic effect during the first trimester, exposure during the second and third trimesters might lead to neonatal effects. Uniform guidelines for postnatal management of these neonates are lacking. The aim was to retrospectively describe all neonates admitted to the University Hospitals Leuven after in utero exposure to lithium (January 2010 to April 2020), and to propose a postnatal care protocol. Descriptive statistics were performed. For continuous parameters with serial measurements, median population values were calculated. In total, 10 mother-neonate pairs were included. The median gestational age was 37 (interquartile range, IQR, 36-39) weeks. Neonatal plasma lithium concentration at birth was 0.65 (IQR 0.56-0.83) mmol/L with a median neonate/mother ratio of 1.02 (IQR 0.87-1.08). Three neonates needed respiratory support, 7/10 started full enteral (formula) feeding on day 1. The median length of neonatal stay was 8.5 (IQR 8-12) days. One neonate developed nephrogenic diabetes insipidus. This study reported in detail the postnatal characteristics and short-term neonatal outcomes. A postnatal care protocol was proposed, to enhance the quality of care for future neonates, and to guide parental counselling. Future prospective protocol evaluation is needed.

Postnatal depression: identification of risk factors in the short-stay maternity program in Belgium. A cross-sectional study.

BACKGROUND: Postnatal depression (PND) is one of the most frequent complications in women of childbearing age in the developed world. The onset of PND is influenced by several risk factors. In an attempt to avoid unnecessary long maternity stays, the Short Stay Maternity programme was launched, shifting care from the hospital environment to the outpatient setting. AIM: In order to develop an efficient programme to trace vulnerable women after childbirth and to provide support within primary care, the aim was to create an inventory of the risk factors for PND within the population of women participating in the short-stay programme. DESIGN & SETTING: This study is a cross-sectional study without follow-up. Women in Belgium were invited by email to participate in the Short Stay Maternity programme within 3 months of delivery. METHOD: The questionnaire addressed background features and feelings during the maternity period, supplemented with the validated Dutch version of the Edinburgh Postnatal Depression Scale (EPDS). The primary outcome measure of the questionnaire was the score on the EPDS. RESULTS: A total of 131 (27.46%) of the invited women participated. Sixteen participants (12.21%) presented with a positive score on the EPDS. The odds ratio (OR) for a positive score on the EPDS when experiencing negative feelings was 13.5 (95% confidence interval [CI] = 4.14 to 44.01). If only material support was provided, the OR for a positive EPDS score was OR 11.2 (95% CI = 2.72 to 55.5). CONCLUSION: In this study, two risk factors were identified for PND: negative feelings during pregnancy and the provision of only material support by the partner.

Newborn genome-wide DNA methylation in association with pregnancy anxiety reveals a potential role for GABBR1.

BACKGROUND: There is increasing evidence for the role of prenatal stress in shaping offspring DNA methylation and disease susceptibility. In the current study, we aimed to identify genes and pathways associated with pregnancy anxiety using a genome-wide DNA methylation approach. METHODS: We selected 22 versus 23 newborns from our Prenatal Early Life Stress (PELS) cohort, exposed to the lowest or highest degree of maternal pregnancy anxiety, respectively. Cord blood genome-wide DNA methylation was assayed using the HumanMethylation450 BeadChip (HM450, n = 45) and candidate gene methylation using EpiTYPER (n = 80). Cortisol levels were measured at 2, 4, and 12 months of age to test infant stress system (re)activity. RESULTS: Data showed ten differentially methylated regions (DMR) when comparing newborns exposed to low versus high pregnancy anxiety scores. We validated a top DMR in the GABA-B receptor subunit 1 gene (GABBR1) revealing the association with pregnancy anxiety particularly in male newborns (most significant CpG Pearson R = 0.517, p = 0.002; average methylation Pearson R = 0.332, p = 0.039). Cord blood GABBR1 methylation was associated with infant cortisol levels in response to a routine vaccination at 4 months old. CONCLUSIONS: In conclusion, our results show that pregnancy anxiety is associated with differential DNA methylation patterns in newborns and that our candidate gene GABBR1 is associated with infant hypothalamic-pituitary-adrenal axis response to a stressor. Our findings reveal a potential role for GABBR1 methylation in association with stress and provide grounds for further research.

Dimensions in major depressive disorder and their relevance for treatment outcome.

BACKGROUND: Major depressive disorder (MDD) is a heterogeneous disease. More homogeneous psycho(patho)logical dimensions would facilitate MDD research as well as clinical practice. The first aim of this study was to find potential dimensions within a broad psychopathological assessment in depressed patients. Second, we aimed at examining how these dimensions predicted course in MDD. METHODS: Ten psychopathological variables were assessed in 75 MDD inpatients. Factor and regression analyses assessed putative relations between psychopathological factors and depression severity and outcome after 8 weeks of treatment. RESULTS: A 3-factor model (eigenvalue: 54.4%) was found, representing a psychomotor change, anhedonia and negative affect factor. Anhedonia and negative affect predicted depression severity (R(2)=0.37, F=20.86, p<0.0001). Anhedonia predicted non-response (OR 6.00, CI 1.46-24.59) and both negative affect (OR 5.69, CI 1.19-27.20) and anhedonia predicted non-remission (OR 9.28, CI 1.85-46.51). LIMITATIONS: The sample size of the study was relatively modest, limiting the number of variables included in the analysis. CONCLUSIONS: Results confirm that psychomotor change, anhedonia and negative affect are key MDD dimensions, two of which are related to treatment outcome.

Reduced reward learning predicts outcome in major depressive disorder.

BACKGROUND: Reduced reward learning might contribute to the onset and maintenance of major depressive disorder (MDD). In particular, the inability to utilize rewards to guide behavior is hypothesized to be associated with anhedonia, a core feature and potential trait marker of MDD. Few studies have investigated whether reduced reward learning normalizes with treatment and/or reward learning predicts clinical outcome. Our goal was to test whether MDD is characterized by reduced reward learning, especially in the presence of anhedonic symptoms, and to investigate the relationship between reward learning and MDD diagnosis after 8 weeks of treatment. METHODS: Seventy-nine inpatients and 63 healthy control subjects performed a probabilistic reward task yielding an objective measure of participants' ability to modulate behavior as a function of reward. We compared reward responsiveness between depressed patients and control subjects, as well as high- versus low-anhedonic MDD patients. We also evaluated whether reward-learning deficits predicted persistence of MDD after 8 weeks of treatment. RESULTS: Relative to control subjects, MDD patients showed reduced reward learning. Moreover, patients with high anhedonia showed diminished reward learning compared with patients with low anhedonia. Reduced reward learning at study entry increased the odds of a persisting diagnosis of MDD after 8 weeks of treatment (odds ratio 7.84). CONCLUSIONS: Our findings indicate that depressed patients, especially those with anhedonic features, are characterized by an impaired ability to modulate behavior as a function of reward. Moreover, reduced reward learning increased the odds for the diagnosis of MDD to persist after 8 weeks of treatment.

Investigating the influence of maternal cortisol and emotional state during pregnancy on the DNA methylation status of the glucocorticoid receptor gene (NR3C1) promoter region in cord blood.

BACKGROUND: The methylation status of the human glucocorticoid receptor gene NR3C1 in newborns has been reported to be sensitive to prenatal maternal mood. This study investigates both the association between maternal cortisol and emotional state during pregnancy and the methylation state of the promoter region of NR3C1 gene. METHODS: We examined 83 pregnant women. Psychological data and diurnal cortisol data were assessed to evaluate maternal stress once each trimester. DNA methylation at different loci of the NR3C1 gene, including exon 1B, 1D and 1F, was analyzed in genomic DNA from cord blood mononuclear cells. RESULTS: Univariable analyses indicated pregnancy related anxiety to be the strongest psychological parameter throughout pregnancy. Most significant findings concerned 1F. Particularly the methylation state of CpG9 was significantly associated with maternal emotional wellbeing. In a multivariable model the proportion of variance in methylation state of F9 explained (PVE) by pregnancy related anxiety was 7.8% (p = 0.023) during T1. Furthermore different CpG-units located at the nerve growth factor inducible protein A (NGFI-A) binding sites of 1F were associated with maternal anxiety [(F20.21: PC PRAQ and fear of integrity in T1: respectively PVE:8.9% and PVE:9.0%; Fear of delivery T2: PVE:8.0%, Fear of integrity T2: PVE:6.0% and STAI T2: PVE:5.9%) - (F12.13: PC PRAQ T1: PVE:6.9%, fear of integrity T2: PVE:6.0% and fear of delivery T2: PVE:8.0%)] and cortisol (F38.39: PVE:8.9%) in T2. CONCLUSION: These data indicate that prenatal maternal emotional state, particularly pregnancy related anxiety, are associated with the methylation state of the NR3C1 gene in the child.