Maternal prenatal stress and placental gene expression of NR3C1 and HSD11B2: The effects of maternal ethnicity.

BACKGROUND: Prenatal stress is associated with altered fetal and infant development. Previous studies have suggested that these effects may be mediated in part via altered functioning of placental enzymes and receptors involved in the HPA-axis, including the glucocorticoid receptor (NR3C1) and HSD11B2, the enzyme which metabolises cortisol. However, previous studies have not examined the potential ethnicity effects on these associations. This study aimed to characterise the association between maternal prenatal stress and placental genes expression and subsequently, any potential effect of maternal ethnicity. METHOD: Pregnant women(n=83) were recruited prior to elective caesarean section and assessed for trait anxiety, depression and life events. Placentas were collected and placental gene expression of NR3C1 and HSD11B2 were analysed. We examined associations between maternal prenatal stress and placental gene expression, and the tested for a possible moderating effect of maternal ethnicity(59.0% Caucasian;41.0% non-Caucasian:12.0% South Asian;6.0% African/African-American;14.4% Other;8.4% Mixed). RESULTS: Analyses demonstrated a trend in the association between both maternal trait anxiety and depression symptoms with placental gene expression of NR3C1(adj.β=0.220,p=0.067;adj.β=0.212,p=0.064 respectively). We found a significant interaction with maternal ethnicity(β=0.249;p=0.033). In Caucasian women only prenatal trait anxiety and depressive symptoms were associated with an increase in placental NR3C1 expression(adj.β=0.389,p=0.010;adj.β=0.294;p=0.047 respectively). Prenatal life events were associated with a down regulation of HSD11B2(adj.β=0.381;p=0.008), but only in Caucasians. CONCLUSION: These results support previous findings of an association between maternal prenatal stress and the expression of placental genes associated with the HPA-axis, but only in Caucasians. These ethnic specific findings are novel and require replication in different populations

The effects of isatin (indole-2, 3-dione) on pituitary adenylate cyclase-activating polypeptide-induced hyperthermia in rats

BACKGROUND: Previous studies have demonstrated that centrally administered natriuretic peptides and pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) have hyperthermic properties. Isatin (indole-2, 3-dione) is an endogenous indole that has previously been found to inhibit hyperthermic effects of natriuretic peptides. In this study the aim was to investigate the effects of isatin on thermoregulatory actions of PACAP-38, in rats. RESULTS: One μg intracerebroventricular (icv.) injection of PACAP-38 had hyperthermic effect in male, Wistar rats, with an onset of the effect at 2 h and a decline by the 6(th) h after administration. Intraperitoneal (ip.) injection of different doses of isatin (25-50 mg/kg) significantly decreased the hyperthermic effect of 1 μg PACAP-38 (icv.), whereas 12.5 mg/kg isatin (ip.) had no inhibiting effect. Isatin alone did not modify the body temperature of the animals. CONCLUSION: The mechanisms that participate in the mediation of the PACAP-38-induced hyperthermia may be modified by isatin. The capability of isatin to antagonize the hyperthermia induced by all members of the natriuretic peptide family and by PACAP-38 makes it unlikely to be acting directly on receptors for natriuretic peptides or on those for PACAP in these hyperthermic processes

The Relax in Pregnancy Project

Background. Many women feel anxious or stressed during pregnancy. Stress, anxiety, and depression faced by women, increase the risk of both behavioural and biological problems for the baby. These can include a lower birth weight, Attention Deficit Hyperactivity Disorder (ADHD), and potential for depression later in life (O’Connor et al., 2002). This has been suggested to be due to the stress marker cortisol and its interference in brain development. Since medication such as antidepressants can cross the placenta and directly harm the child, these methods should be avoided, and non pharmacological methods should be used (O’Connor et al., 2005). Studies have shown that music is an effective therapy for reducing stress in patients before surgical treatments. Additionally, a study conducted by Ventura and associates (2012) found that stressed pregnant women exposed to music experienced the greatest reduction in cortisol levels alone as compared to the relaxation and the control groups.Aim. The aim of this study was to determine whether listening to lullabies for about 20 minutes a day could reduce prenatal depression and anxiety levels, long term. Based on results from past studies, it was hypothesized that music would have the greatest effect in reducing prenatal anxiety and depression.Method. Women first took online surveys that assessed their mood. Women were then assigned to one of two relaxation groups. One group listened to lullabies for about 20 minutes a day, while the other group relaxed, doing deep breathing exercises for the same amount of time. Surveys were taken once a month. The amount of time spent doing exercises was recorded, and their mood periodically assessed.Results. In this study, the prenatal depression and anxiety levels as represented by the Edinburgh Postnatal Depression Scale and Spielberger State & Trait scores respectively, significantly reduced after 12 weeks of music listening. No significant reduction was found in the control groups.Possible Applications or Implications. Although much needs to be explored, these findings encourage the exploration of music as an intervention in pregnant women, in order to prevent particular neuropsychological outcomes that may occur in the developing infant due to prenatal stress and anxiety.Keywords: pregnancy, stress, neurodevelopment, music ReferencesO’Connor, T.G., Ben-Shlomo, Y., Jeron, J., Golding, J., Adams, D., & Glover, V. (2005). Prenatal Anxiety Predicts Individual Differences in Cortisol in Pre-Adolescent Children. Biol Psychiatry: 58:211- 217.O’Connor, T.G., Heron J., Golding, J., Beveridge, M., & Glover, V. (2002). Maternal Antenatal Anxiety and Children’s Behavioural/Emotional Problems at 4 Years: Report from the Avon Longitudinal Study of Parents and Children. The British Journal of Psychiatry. 180:502-508.Ventura, T., Gomes, M.C., & Carreira, T. (2012). Cortisol and Anxiety Response to a Relaxing Intervention on Pregnant Women Awaiting Amniocentesis. Psychoneuroendocrinology. 37: 148 – 156.  

Symptoms associated with the DSM IV diagnosis of depression in pregnancy and post partum

Pregnancy and the postpartum may affect symptoms of depression. However it has not yet been tested how the symptoms used for the DSM IV diagnosis of depression discriminate depressed from non depressed women perinatally. A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all associated DSM IV symptoms of depression with depressed and non depressed women in pregnancy and the postpartum period. Loss of appetite was not associated with depression either ante or postnatally. The antenatal symptom pattern was different from the postnatal. The sensitivity of the symptoms ranged from 0.7% to 51.6%, and specificity from 61.3% to 99.1%. The best discriminating symptoms were motor retardation/agitation and concentration antenatally, and motor retardation/agitation, concentration and fatigue postnatally. Depression in pregnancy and postpartum depression show significantly different symptom profiles. Appetite is not suitable for the diagnosis of depression in the perinatal perio

A role for the placenta in programming maternal mood and childhood behavioral disorders

Substantial data demonstrate that the early-life environment, including in utero, plays a key role in later life disease. In particular, maternal stress during pregnancy has been linked to adverse behavioural and emotional outcomes in children. Data from human cohort studies and experimental animal models suggest that modulation of the developing epigenome in the foetus by maternal stress may contribute to the foetal programming of disease. Here, we summarise insights gained from recent studies that may advance our understanding of the role of the placenta in mediating the association between maternal mood disorders and offspring outcomes. First, the placenta provides a record of exposures during pregnancy, as indicated by changes in the placental trancriptome and epigenome. Second, prenatal maternal mood may alter placental function to adversely impact foetal and child development. Finally, we discuss the less well established but interesting possibility that altered placental function, more specifically changes in placental hormones, may adversely affect maternal mood and later maternal behaviour, which can also have consequence for offspring well-being

The DSM IV diagnoses of melancholic and atypical depression in pregnancy

Atypical and melancholic subtypes of depression based on the Diagnostic and Statistical Manual (DSM) IV are important concepts, especially for biological psychiatry. The aim of this study was to determine whether the symptoms used for the diagnoses of atypical and melancholic depression can distinguish these subtypes during pregnancy. A modified version of the Structured Clinical Interview for DSM IV (SCID interview) was used that allowed assessment of all DSM IV symptoms of melancholic and atypical depression with depressed and non-depressed women in pregnancy. A Swiss cohort of 449 women was interviewed. Four diagnostic groups were compared: women with melancholic, atypical or non specified depression, and those without depression. Seventeen per cent of the cohort met SCID criteria for a depressive episode of depression at least once in pregnancy, with melancholic depression 2.4%, atypical depression 4.4% and non specified depression 10.2%. Many of the symptoms used to distinguish atypical and melancholic depression did not discriminate between these groups during pregnancy. However some, such as mood reactivity, distinct quality of mood and sleep pattern, did discriminate. Differential diagnosis between melancholic and atypical depression in pregnancy needs to be based on pregnancy specific definitions. The possible therapeutic consequences and the neurobiological basis for these findings warrant further researc

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children's responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4-15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child's rs4680 genotype, with stronger effects obtained for the val/val (G: G) genotype relative to val/met (A:G) (all p <0.01) and met/met (A: A) groups (all p <0.05). Similar findings were observed in the PREDO cohort where maternal prenatal anxiety interacted with child rs4680 to predict symptoms of ADHD at 3.5 years of age. The findings, from two cohorts, show a robust gene-environment interaction, which may contribute to inter-individual differences in the effects of maternal prenatal anxiety on developmental outcomes from childhood to mid-adolescence.Peer reviewe

Neurodevelopmental consequences in offspring of mothers with preeclampsia during pregnancy: underlying biological mechanism via imprinting genes

Purpose Preeclampsia is known to be a leading cause of mortality and morbidity among mothers and their infants. Approximately 3–8% of all pregnancies in the US are complicated by preeclampsia and another 5–7% by hypertensive symptoms. However, less is known about its long-term influence on infant neurobehavioral development. The current review attempts to demonstrate new evidence for imprinting gene dysregulation caused by hypertension, which may explain the link between maternal preeclampsia and neurocognitive dysregulation in offspring. Method Pub Med and Web of Science databases were searched using the terms “preeclampsia,” “gestational hypertension,” “imprinting genes,” “imprinting dysregulation,” and “epigenetic modification,” in order to review the evidence demonstrating associations between preeclampsia and suboptimal child neurodevelopment, and suggest dysregulation of placental genomic imprinting as a potential underlying mechanism. Results The high mortality and morbidity among mothers and fetuses due to preeclampsia is well known, but there is little research on the long-term biological consequences of preeclampsia and resulting hypoxia on the fetal/child neurodevelopment. In the past decade, accumulating evidence from studies that transcend disciplinary boundaries have begun to show that imprinted genes expressed in the placenta might hold clues for a link between preeclampsia and impaired cognitive neurodevelopment. A sudden onset of maternal hypertension detected by the placenta may result in misguided biological programming of the fetus via changes in the epigenome, resulting in suboptimal infant development. Conclusion Furthering our understanding of the molecular and cellular mechanisms through which neurodevelopmental trajectories of the fetus/infant are affected by preeclampsia and hypertension will represent an important first step toward preventing adverse neurodevelopment in infants

A role for the placenta in programming maternal mood and childhood behavioural disorders

Substantial data demonstrate that the early‐life environment, including in utero, plays a key role in later life disease. In particular, maternal stress during pregnancy has been linked to adverse behavioural and emotional outcomes in children. Data from human cohort studies and experimental animal models suggest that modulation of the developing epigenome in the foetus by maternal stress may contribute to the foetal programming of disease. Here, we summarise insights gained from recent studies that may advance our understanding of the role of the placenta in mediating the association between maternal mood disorders and offspring outcomes. First, the placenta provides a record of exposures during pregnancy, as indicated by changes in the placental trancriptome and epigenome. Second, prenatal maternal mood may alter placental function to adversely impact foetal and child development. Finally, we discuss the less well established but interesting possibility that altered placental function, more specifically changes in placental hormones, may adversely affect maternal mood and later maternal behaviour, which can also have consequence for offspring well‐being