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2019, Psychoneuroendocrinology
Stress-the International Journal on The Biology of Stress, 2010
The effects of maternal stress during pregnancy may depend, in part, on the timing in gestation of the occurrence of stress. The aim of the present study was to examine the effect of stage of gestation on maternal psychophysiological responses to stress using a standardized laboratory paradigm and on the cortisol response to awakening (CAR). A longitudinal design was employed to quantify maternal psychophysiological stress reactivity [changes in heart rate (HR), blood pressure, salivary cortisol, and psychological distress in response to the trier social stress test (TSST)] and the CAR at approximately 17 and 31 weeks gestation in a sample of 148 women. To account for the possible effects of habituation when being exposed to the same stress protocol twice, a non-pregnant comparison group (CG, N = 36) also underwent these assessments at two time points, with a comparable time interval between the assessments. In both groups, the TSST elicited significant changes in maternal HR, mean arterial pressure, and psychological distress levels but not a significant increase in cortisol levels. Among the pregnant women (pregnant group(PG)), the stressor-induced increases in HR, blood pressure, and psychological distress were significantly lower at the second (31 weeks gestation) compared to the first (17 weeks gestation) assessment of pregnancy (all p < 0.01). The maternal CAR was also significantly attenuated in later compared to earlier gestation (p = 0.003). In the CG, there were no significant differences in psychophysiological stress responses and in the CAR across the two assessments. Among pregnant women there is a progressive attenuation of psychophysiological stress responses with advancing gestation. This attenuation is unlikely to be attributable to habituation. Individual differences in the degree of attenuation of stress responses over gestation may represent a novel marker of stress susceptibility in human pregnancy.
European journal of obstetrics, gynecology, and reproductive biology, 2012
Objective: Psychosocial stressors are consistently associated with antenatal anxiety and depression, while the impact of cortisol has proved inconsistent. Most studies have focused either on psychological or physiological stress indices. We investigated both subjective and endocrinologic indices of distress in the same subjects. Study design: We performed a cross-sectional study in late pregnancy in 79 women to investigate associations between the factors involved in anxiety and depression. Outcome measures were the Beck Depression Inventory (BDI), State-Trait Anxiety Inventory (STAI), Perceived Stress Scale, a Likert-like scale for fear of delivery, a structured interview to assess health and socioeconomic status, and fasting plasma cortisol levels measured in the morning. Results: High BDI and STAI scores were associated with high levels of perceived stress and fear of delivery, but not with levels of plasma cortisol typical of the gestation phase. A multiple regression analysis revealed that subjective feelings of distress explained over 50% of the variation in BDI and STAI scores. Plasma cortisol was not a significant predictor of psychometric scores and did not show significant correlation with them in correlation analyses, and subjects with low and high cortisol levels showed similar psychometric scores. Conclusion: Antenatal depression and anxiety were significantly associated with subjective feelings of distress but not with increased cortisol. This finding may be explained by the blunted cortisol stress responses characteristic of pregnancy. The mechanisms mediating the effects of subjective distress remain obscure: likely candidates include monoamine neurotransmission, and/or stress-induced changes in glucocorticoid receptor expression or distribution.
Acta Obstetricia et Gynecologica Scandinavica, 2012
Psychoneuroendocrinology, 2018
Accumulating evidence suggests that antenatal maternal stress is associated with altered behavioral and physiological outcomes in the offspring, however, whether this association is causal and the underlying biological mechanisms remain largely unknown. While the most studied mediator of maternal stress influences on the fetus has generally been cortisol, alternative novel markers of stress or inflammation warrant further consideration. The current investigation explored the influence of variations in self-reported symptoms of distress, stress hormones and inflammatory markers on infant birth outcomes and early stress regulation. The sample consisted of 104 pregnant women (mean gestational age=34.76; SD=1.12) and their healthy newborns. Maternal self-reported symptoms of depression and anxiety were evaluated through the Edinburgh Postnatal Depression Scale and the State-Trait Anxiety Inventory and levels of serum Interleukine-6 (IL-6), C-Reactive Protein (CRP), salivary cortisol and alpha amylase (sAA) were measured in late pregnancy. Newborns' cortisol and behavioral response to the heel-stick was assessed 48-72 hours after birth. The associations between maternal stress measures and infant birth outcomes and stress reactivity, adjusted for potential confounders, were examined through hierarchical linear regressions and hierarchical linear models. Higher maternal IL-6 levels were associated with smaller head circumference at birth, while diurnal sAA levels were positively associated with birthweight. Maternal diurnal cortisol was related to newborn's stress reactivity: a flatter infant cortisol response to the heel-stick was associated with greater maternal cortisol increases after awakening during pregnancy, while greater infant behavioural reactivity was related to a flatter maternal diurnal cortisol profile. The observational nature of these data does not allow for causal inferences but the current findings illustrate that antenatal factors related to alterations in maternal stress and immune response systems are associated with supporting fetal growth and neonatal stress reactivity. This may have implications for later health and psychological outcomes.
Biological Psychology, 2014
Pregnancy anxiety is a potent predictor of adverse birth and infant outcomes. The goal of the current study was to examine one potential mechanism whereby these effects may occur by testing associations between pregnancy anxiety and maternal salivary cortisol on 4 occasions during pregnancy in a sample of 448 women. Higher mean levels of pregnancy anxiety over the course of pregnancy predicted steeper increases in cortisol trajectories compared to lower pregnancy anxiety. Significant differences between cortisol trajectories emerged between 30 and 31 weeks of gestation. Results remained significant when adjusted for state anxiety and perceived stress. Neither changes in pregnancy anxiety over gestation, nor pregnancy anxiety specific to only a particular time in pregnancy predicted cortisol. These findings provide support for one way in which pregnancy anxiety may influence maternal physiology and contribute to a growing literature on the complex biological pathways linking pregnancy anxiety to birth and infant outcomes.
Stress: The International Journal on the Biology of Stress, 2010
Hypothalamic-pituitary-adrenal (HPA) activity is altered postpartum and has been associated with several puerperal disorders. However, little is known about the association of maternal HPA activity during pregnancy with maternal HPA responsiveness to stress after parturition. Within a longitudinal study with an experimental component, we assessed in 22 women the salivary cortisol awakening response (CAR) at the 36th week of gestation and 6 weeks postpartum, as well as pituitary-adrenal and emotional responses to a psychosocial laboratory stressor at 8 weeks postpartum. CAR in late pregnancy negatively predicted maternal adrenocorticotropin (ACTH; ß ¼ 2 0.60; P ¼ 0.003), plasma cortisol (ß ¼ 2 0.69, P , 0.001), and salivary cortisol (ß ¼ 20.66; P ¼ 0.001) but not emotional stress reactivity (all P. 0.05) at 8 weeks postpartum, whereas CAR at 6 weeks postpartum failed to predict hormonal (ACTH: ß ¼ 0.02; P ¼ 0.933, plasma cortisol: ß ¼ 20.23; P ¼ 0.407, salivary cortisol: ß ¼ 2 0.15; P ¼ 0.597) or emotional (all P. 0.05) stress responses at 8 weeks postpartum. The activity of the HPA axis during pregnancy is associated with maternal HPA responsiveness to stress postpartum. Putative biological underpinnings warrant further attention. A better understanding of stress-related processes peripartum may pave the way for the prevention of associated puerperal disorders.
Hormones and Behavior, 2009
Epidemiological studies have reported associations between measures of size and weight at birth and disease risk in later life. Alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to prenatal stress has been proposed as one underlying mechanism. The present study investigated in humans the association of prenatal psychosocial stress exposure with subsequent HPA axis regulation in adult life, with a focus on measures of response to challenge and feedback sensitivity. Healthy young adults whose mothers experienced severe stress during their pregnancy in form of major negative life events (e.g. death of someone close; prenatal stress (PS) group, n = 31) and an age-matched comparison group (CG, n = 30) underwent the Trier Social Stress Test (TSST) and a 1 μg ACTH 1-24 stimulation test. In addition, a diurnal cortisol profile was assessed. ACTH concentrations following a standardized behavioural challenge paradigm (TSST) were marginally significantly higher in PS subjects than in CG subjects (p = .06). Pre-TSST adrenocortical (cortisol) levels were lower (p = .007), whereas the increase in cortisol in response to the TSST was higher (p = .03) in PS subjects compared to CG subjects. Cortisol concentrations following a pharmacological stimulation test simulating pituitary activity (ACTH 1-24 test) were significantly lower in PS than in CG subjects (p = .006). No differences emerged between the two groups in basal diurnal cortisol levels. This study provides first evidence in humans of an association between prenatal psychosocial stress exposure and subsequent alterations in the regulation of the HPA axis.
European Child & Adolescent Psychiatry, 2014
Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often proposed mechanism, namely that involving the HPA axis and cortisol, as well as other less well-studied but possibly relevant and complementary mechanisms. We present evidence for a role of the following mechanisms: compromised placental functioning, including the 11b-HSD2 enzyme, increased catecholamines, compromised maternal immune system and intestinal microbiota, and altered health behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the postnatal environment and the fetus are also discussed. We conclude that maternal prenatal psychosocial stress is a complex phenomenon that affects maternal emotions, behavior and physiology in many ways, and may influence the physiology and functioning of the fetus through a network of different pathways. The review concludes with recommendations for future research that helps our understanding of the mechanisms by which maternal prenatal stress exerts its effect on the fetus.
Psychopharmacology, 2016
Anxiety during pregnancy has been linked to adverse maternal health outcomes, including postpartum depression (PPD). However, there has been limited study of biological mechanisms underlying behavioral predictors of PPD during pregnancy. Considering the shared etiology of chronic stress amongst antenatal behavioral predictors, the primary goal of this pilot study was to examine associations among stress-related physiological factors (including GABA-ergic neurosteroids) and stress-related behavioral indices of anxiety during pregnancy. Fourteen nulliparous women in their second trimester of a singleton pregnancy underwent speech and mental arithmetic stress, following a 2-week subjective and objective recording of sleep-wake behavior. Lower cortisol, progesterone, and a combined measure of ALLO + pregnanolone throughout the entire stressor protocol (area under the curve, AUC) were associated with greater negative emotional responses to stress, and lower cortisol AUC was associated wi...
Stress: The International Journal on the Biology of Stress, 2010
Early life factors can shape the development of hypothalamic pituitary adrenal (HPA) axis. Maternal prenatal stress might constitute such an early environmental factor. As little is known about the relation between maternal prenatal stress and cortisol reactivity in human offspring, we performed a longitudinal study including four assessments of infant cortisol reactivity to stressful events in a non-clinical population. General and pregnancy-related feelings of stress and anxiety, as well as circadian cortisol levels, were measured in 173 mothers in the last trimester of pregnancy. Infant cortisol reactivity was measured at 5 weeks to a bathing session, at 8 weeks to a vaccination, at 5 months to a stressful mother -infant interaction (still face procedure), and at 12 months to a maternal separation (strange situation procedure). Maternal prenatal fear of bearing a handicapped child was a consistent predictor of infant cortisol reactivity. Although the effects were mild, higher fear was significantly related to higher salivary cortisol reactivity to the bathing session and to decreased cortisol reactivity to vaccination and maternal separation. Thus, pregnancy-specific anxieties predict infant cortisol reactivity in the first year of life, but the direction of the effect depends on infant age and/or the nature of the stressor. While this specific anxiety was a better predictor than stress experience or maternal cortisol concentrations, the underlying mechanisms of these associations remain unclear. Future studies should try to incorporate multiple measures of HPA-axis reactivity during development when studying the long-term consequences of maternal prenatal stress.
High anxiety levels during pregnancy commonly lead to clinical complications that affect the mother/child's prenatal and perinatal health. Such complications are thought to result from combining deficiencies of the endocrine milieu and decreased immune tolerance that support pregnancy. It is yet unclear whether pregnant women subjected to moderate anxiety develop a similar state of endocrine deficits and compromised immune tolerance. Here, we evaluated this issue by monitoring endocrine and immune parameters during pregnancy in a sample of women suffering of moderate anxiety. The health of mothers and children, as well as the outcome of the pregnancies were also revised and recorded. Moderately anxious pregnant women present increments of state anxiety, serum cortisol and progesterone, but not of estradiol, as pregnancy progressed. No variations of leukocyte anti-and pro-inflammatory cytokine mRNA expression were found along pregnancy. However, these pregnant women did show an increased frequency of gestational and perinatal complications, conditions that had no major consequences for their health and that of their children at birth. Hence, moderate anxiety renders the mother to be susceptible to develop diseased states during or by the end of pregnancy, while keeping the endocrine milieu and immune tolerance reasonably in place.
Psychoneuroendocrinology, 2007
The purpose of this study was to examine the effects of maternal depression and anxiety on the cortisol awakening response (CAR), a marker of the hypothalamic-pituitary-adrenal (HPA) axis function, during pregnancy. Sixty-six pregnant women were studied between 25 and 33 weeks of gestation and were identified as either Depressed (n ¼ 33) or healthy, Control (n ¼ 33), based on depression scores and lifetime psychiatric history. Saliva samples were collected (passive drool) upon awakening and at +30 and +60 min thereafter. The CAR was not significantly different between women who were depressed during pregnancy compared to healthy control women. However, women taking antidepressant (AD) medication showed an attenuated CAR (time  AD use interaction, p ¼ 0.06). Childhood maltreatment (as measured with the Childhood Trauma Questionnaire) was associated with a lower baseline cortisol concentration explaining 12% of the variance, controlling for wake-up time and AD use. There is a complex interplay of factors involved in the HPA axis regulation of vulnerable women during pregnancy, including depression,
Journal of Biophysical …
High anxiety levels during pregnancy commonly lead to clinical complications that affect the mother/child's prenatal and perinatal health. Such complications are thought to result from combining deficiencies of the endocrine milieu and decreased immune tolerance that support pregnancy. It is yet unclear whether pregnant women subjected to moderate anxiety develop a similar state of endocrine deficits and compromised immune tolerance. Here, we evaluated this issue by monitoring endocrine and immune parameters during pregnancy in a sample of women suffering of moderate anxiety. The health of mothers and children, as well as the outcome of the pregnancies were also revised and recorded. Moderately anxious pregnant women present increments of state anxiety, serum cortisol and progesterone, but not of estradiol, as pregnancy progressed. No variations of leukocyte anti-and pro-inflammatory cytokine mRNA expression were found along pregnancy. However, these pregnant women did show an increased frequency of gestational and perinatal complications, conditions that had no major consequences for their health and that of their children at birth. Hence, moderate anxiety renders the mother to be susceptible to develop diseased states during or by the end of pregnancy, while keeping the endocrine milieu and immune tolerance reasonably in place.
Australian and New Zealand Journal …, 2000
BMC Psychiatry
Background A complex interaction between cortisol and dehydroepiandrosterone-sulphate (DHEA-S) is crucial in the stress system balance; several studies have reported increased cortisol levels during chronic stress and a weak counter-regulation by DHEA-S. During pregnancy, scarce information about this system is available, although cortisol and DHEA-S play an important role in the initiation and acceleration of labor. We conducted the present study in order to determine both cortisol and DHEA-S levels during the last trimester of pregnancy in patients exhibiting severe anxiety. Methods Pregnant women during the 3rd trimester of pregnancy were evaluated by using the self-reported version of the Hamilton Anxiety Rating Scale (HARS). According to the scores obtained from the psychometric scale, participants were divided into two groups: 1) patients exhibiting a cutoff score > 15 were considered with severe anxiety (ANX) (n = 101), and control pregnant subjects (CTRL) (n = 44) with a ...
Journal of abnormal psychology, 2018
Given high health costs of depression during pregnancy and the first postnatal year, it is important to understand mechanisms involved in the emergence and perpetuation of symptoms during this time. In a series of 2 studies, we aim to clarify bidirectional relations between mothers' physiological stress regulation-stress-related activation of the hypothalamic-pituitary-adrenal (HPA) axis-and their course of depressive symptoms. In Study 1, 230 pregnant women recruited from a women's mental health program gave 3 saliva samples in the context of psychosocial stress at 24, 30, and 36-weeks gestation. They self-reported depressive symptoms across the three trimesters of pregnancy and first year postpartum. Multilevel models revealed women with elevated salivary cortisol during pregnancy showed a course of escalating ante- and postnatal symptoms, implicating HPA hyperactivation as a precursor to worsening mood problems. In Study 2, 54 mothers from a community sample self-reported...
Psychoneuroendocrinology, 2018
Maternal psychological distress during pregnancy is related to adverse child behavioral and emotional outcomes later in life, such as ADHD and anxiety/depression. The underlying mechanisms for this, however, are still largely unknown. The hypothalamic-pituitary-adrenal (HPA)-axis, with its most important effector hormone cortisol, has been proposed as a mechanism, but results have been inconsistent. The current study investigated the association between maternal psychological distress (i.e. anxiety and depressive symptoms) and maternal cortisol levels during pregnancy using a mixed models approach. During three pregnancy trimesters, mothers (N = 170) collected four salivary samples for two consecutive days. Mothers reported symptoms of anxiety and depression three times during pregnancy (at 13.3 ± 1.1, 20.2 ± 1.5, and 33.8 ± 1.5 weeks of pregnancy, respectively) using the anxiety subscale of the Symptom Checklist (SCL-90), the Spielberger State and Trait Anxiety Inventory (STAI), an...
Psychoneuroendocrinology, 2019
Intrauterine exposures such as maternal psychopathology and stress are known to influence the physical and mental health of the offspring. One of the proposed pathways underlying these associations is dysregulated hypothalamic-pituitary-adrenal (HPA) axis activity in the offspring. This study examined the relation of perinatal maternal symptoms of psychopathology and stress with offspring HPA axis activity at 6 years as measured by hair cortisol and cortisone concentrations. Methods: The study was part of the population-based Generation R Study, a prospective population-based cohort from fetal life onwards. 2546 children and their mothers formed the study population. Perinatal maternal psychopathology and stress were assessed by questionnaires in the second and third trimester. Principal components for both psychopathology and stress were created to reduce the number of explanatory variables. Child hair samples for cortisol and cortisone measurements were collected at the age of 6. Linear regression analysis, adjusted for covariates, was used to examine associations between maternal psychopathology and stress and child hair cortisol and cortisone levels. Results: The maternal psychopathology principal component was associated with higher child hair cortisone (adjusted B = 0.24, 95%CI 0.08;0.40, p-value < 0.01). Effect estimates of the individual dimensions ranged from 0.97 (95%CI 0.21;1.73, p-value = 0.01) for interpersonal sensitivity to 1.67 (95%CI 0.86;2.47, pvalue < 0.01) for paranoid ideation. In addition, children exposed to intrauterine stress, as measured by the principal component, had higher hair cortisone levels (adjusted B = 0.54, 95%CI 0.21;0.88, p-value < 0.01). Exposure to maternal psychopathology and stress was not associated with offspring hair cortisol. Stratification by child sex resulted in associations between maternal symptoms of psychopathology during pregnancy and child hair cortisone levels in boys and associations between maternal symptoms of stress during pregnancy and child hair cortisone levels in girls. Conclusion: Our results suggest that maternal psychopathology and stress during pregnancy are associated with long-term HPA axis activity of the offspring. The association of maternal psychopathology and stress during pregnancy with offspring hair cortisone levels is a novel finding. Future studies should examine whether these psychophysiological differences between exposed and non-exposed children underlie offspring morbidity associated with maternal psychopathology and stress during pregnancy. 1. Introduction Many intrauterine exposures are known to influence the physical and mental health of the offspring (Barker, 2004; Van den Bergh, 2011). Maternal psychopathology and stress during pregnancy are among the most common intrauterine exposures associated with a
Psychoneuroendocrinology, 1993
The purpose of this investigation was to examine: (1) the relations among cortisol reactivity (short term changes in cortisol concentration) and anxiety and depression symptoms in adolescents during pregnancy and early postpartum, and (2) cortisol reactivity and psychosocial variables as predictors of anxiety and depression symptoms in pregnancy and early postpartum. Cortisol reactivity, an index of hypothalamic-pituitary-adrenal activity, was hypothesized to be a vulnerability factor for poor physical and mental health outcomes in adolescents. Forty adolescents aged 14 to 19 years (M = 17.3, SD = 1.3) were enrolled in the study and were seen at &lt; 20 weeks gestation (T1), 34-36 weeks gestation (T2), and 2-3 weeks postpartum (T3). Blood was drawn for cortisol at T1 and T3. Psychological assessments of anxiety and depression symptoms, life optimism, and self-worth were administered at T1, T2, and T3. There were significant correlations among cortisol reactivity and anxiety and depression symptoms at T1 and T3, but the correlations were the reverse of the hypothesized direction. Pregnant adolescents with increased cortisol reactivity (cortisol concentrations that increased across a 40-min period) had fewer symptoms of anxiety and depression than other adolescents. Longitudinal analyses showed that anxiety and depression symptoms at T1 were a stronger predictor of postpartum anxiety and depression than was cortisol reactivity, life optimism, self-worth, or age at pregnancy.
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