Does Prenatal Maternal Distress Contribute to Sex Differences in Child Psychopathology? (original) (raw)
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Gender Differences in the Effects of Prenatal Stress on Brain Development and Behaviour
Neurochemical Research, 2007
An increased incidence of anxiety, depression and attention deficits in children has been linked to psychological stress during pregnancy. Subjection of a pregnant rat to stress at a time when the foetal limbic and hypothalamic pituitary adrenal (HPA) axes develop results in anxiogenic and depressive behaviour and learning and attention deficits in the offspring, which depend on its gender, intensity and timing of the maternal stress and behaviour being tested. Maternal stress increases corticosterone levels in the foetal brain, decreases foetal testosterone and brain aromatase activity in males, and alters brain catecholamine activity to that in females. Learning deficits, reductions in hippocampal neurogenesis, LTP and dendritic spine density in the prefrontal cortex are more readily seen in prenatally-stressed males, while anxiety, depression and increased response of the HPA axis to stress are more prevalent in females. Genders may differ in the sensitivity of developing brain areas to stress hormones.
Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner
Physiology & behavior, 2017
Prenatal stress influences fetal developmental trajectories, which may implicate glucocorticoid mechanisms. There is also emerging evidence that effects of prenatal stress on offspring development are sex-dependent. However, little is known about the prospective relationship between maternal prenatal cortisol levels and infant behaviour, and whether it may be different in male and female infants. We sought to address this question using data from a prospective longitudinal cohort, stratified by risk. The Wirral Child Health and Development Study (WCHADS) cohort (n=1233) included a stratified random sub-sample (n=216) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32weeks of pregnancy (on waking, 30-min post-waking and during the evening) and a measure of infant negative emotionality from the Neonatal Behavioural Assessment Scale (NBAS) at five weeks-of-age. General population estimates of associations among measures were obtained using inverse p...
Sex differences in the relation between prenatal maternal emotional complaints and child outcome
Early Human Development, 2009
Background: Sex differences are found in animal studies concerning the relationship between prenatal maternal stress and outcome of the offspring. Most human studies in this field have not addressed sex differences, although differences between boys and girls may elucidate the biochemical as well as psychological processes involved. Associations between prenatal maternal emotional complaints and behavioural problems of toddlers and preschoolers as assessed by both mothers and fathers are studied separately for boys and girls. Methods: Healthy Dutch Caucasian singleton, pregnant women (N = 444) answered questionnaires about anxiety and depression in every trimester of pregnancy. When their children (227 boys, 217 girls) were between 14 and 54 months old, both parents reported on their current feelings of depression and anxiety and on the behavioural problems of their children. Results: Prenatal maternal emotional complaints were found to be associated with child behavioural problems both in boys and in girls, but in different ways. Prenatal maternal emotional complaints during the first trimester were associated with total and internalizing behavioural problems for boys. Emotional complaints during the third trimester were associated with total, internalizing, as well as externalizing behavioural problems for girls. Conclusions: Differentiation according to sex and information on timing of emotional complaints during pregnancy is needed in studies concerning the relation between prenatal maternal emotional complaints and child outcome.
Sex-dependent Differences of Emotional Status in a Rat Model of Prenatal Stress
Proceedings of the Bulgarian Academy of Sciences
Untoward events during pregnancy negatively affect offspring mental development. We investigated sex-dependent differences of emotional problems in offspring with a history of prenatal stress (PNS). Female rats demonstrated decreased anxiety-like behaviour in comparison to male controls, shown in the light-dark test. Male and female offspring of prenatally stressed mothers were characterized by higher anxiety levels, compared to unstressed controls. PNS induced depression-like behaviour in both sexes without differences among them, indicated with decreased intake of sweet solution in the sucrose consumption tests and increased immobility time spent in the forced swim test. Control females showed higher plasma corticosteroid (CORT) concentrantions after acute stress and decreased recovery (120 min after the stressor) than control males. Both male and female PNS-offspring were with elevated levels of CORT in the plasma, which remained high 120 min after application of the stressogenic...
Evidence for sex differences in fetal programming of physiological stress reactivity in infancy
Development and Psychopathology, 2014
Associations between low birth weight and prenatal anxiety and later psychopathology may arise from programming effects likely to be adaptive under some, but not other, environmental exposures and modified by sex differences. If physiological reactivity, which also confers vulnerability or resilience in an environment-dependent manner, is associated with birth weight and prenatal anxiety, it will be a candidate to mediate the links with psychopathology. From a general population sample of 1,233 first-time mothers recruited at 20 weeks gestation, a sample of 316 stratified by adversity was assessed at 32 weeks and when their infants were aged 29 weeks (N= 271). Prenatal anxiety was assessed by self-report, birth weight from medical records, and vagal reactivity from respiratory sinus arrhythmia during four nonstressful and one stressful (still-face) procedure. Lower birth weight for gestational age predicted higher vagal reactivity only in girls (interaction term,p= .016), and prenat...
Psychoneuroendocrinology, 2019
Background: Elevated maternal glucocorticoids during pregnancy may impact on fetal development in a sexdependent way, leading to increased amygdala activation and increased risk for internalising disorders in females. Based on evidence implicating reduced amygdala activation in callous-unemotional (CU) traits, we predicted that elevated maternal cortisol in pregnancy would be associated with lower CU traits and elevated anxious-depressed symptoms, only in girls. Methods: Participants were 225 members of a stratified subsample within an epidemiological longitudinal cohort (WCHADS). Salivary cortisol was measured over two days at 32 weeks gestation (on waking, 30-min postwaking and during the evening) and the log of the area under the curve (LogAUC) was calculated as an index of diurnal cortisol. Mothers reported on child CU traits and anxious-depressed symptoms at 2.5, 3.5 and 5.0 years of age. Results: As predicted there was a sex of child by cortisol interaction (p < .001) whereby elevated maternal cortisol was associated with lower child CU traits, explaining 25% of the variance, in girls, but not in boys. This effect remained when controlling for relevant confounders and anxious-depressed symptoms. By contrast, elevated maternal cortisol did not predict higher anxious-depressed symptoms in girls. Conclusions: The study adds to growing evidence for sex-dependent effects of elevated maternal cortisol during pregnancy on early child psychopathology, consistent with mediation by elevated amygdala activation. The conditions under which, in girls, this is associated with heightened responsiveness to others' distress characteristic of low CU traits, or with increased affective symptoms, require further study.
2018
The foetal brain is highly susceptible to stress in late pregnancy, with lifelong effects of stress on physiology and behaviour. The present study aimed to determine the physiological and behavioural effects of prenatal stress during the prepubertal period of female and male rats. We subjected pregnant Sprague-Dawley rats to a restraint stress protocol from gestational day 14 to 21, a critical period for foetal brain susceptibility to stress effects. Male and female offspring were subsequently assessed at postnatal day 24 for anxiety-and depressive-like behaviours, as well as spontaneous social interaction. We also assessed maternal behaviours and 2 stress markers: basal vs acute-evoked stress levels of serum corticosterone and body weight gain. Prenatal stress did not affect the maternal behaviour, whereas both female and male offspring had higher body weight gain. On the other hand, lower levels of corticosterone after acute stress stimulation, as well as anxiety-and depressive-like behaviours, were only evident in stressed males compared to control males. These results suggest that prenatal stress induced sex-specific effects on hypothalamic-pituitary- adrenal (HPA) axis activity and on behaviour during prepuberty. The HPA axis of prenatally stressed male rats was less active compared to control males, and they were also more anxious and experienced depressive-like behaviours. These results are useful with respect to studying the neurobiological basis of childhood depression at a preclinical level.
Psychoneuroendocrinology, 2010
Stress during pregnancy can impair biological and behavioral responses in the adult offspring and some of these effects are associated with structural changes in specific brain regions. Furthermore, these outcomes can vary according to strain, gender, and type and duration of the maternal stress. Indeed, early stress can induce sexually dimorphic long-term effects on diverse endocrine axes, including subsequent responses to stress. However, whether hypothalamic structural modifications are associated with these endocrine disruptions has not been reported. Thus, we examined the gender differences in the long-term effects of prenatal and adult immobilization stress on the hypothalamic-pituitary-adrenocortical (HPA) axis and the associated changes in hypothalamic structural proteins. Pregnant Wistar rats were subjected to immobilization stress three times daily (45 min each) during the last week of gestation. One half of the offspring were subjected to the same regimen of stress on 10 consecutive days starting at postnatal day (PND) 90. At sacrifice (PND 180), serum corticosterone levels were significantly higher in females compared to males and increased significantly in females subjected to both stresses with no change in males. Prenatal stress increased pituitary ACTH content in males, with no effect in females. Hypothalamic CRH mRNA levels were significantly increased by prenatal stress in females, but decreased in male rats. In females neither stress affected hypothalamic cell death, as determined by cytoplasmic histone-associated DNA fragment levels or proliferation, determined by proliferating cell nuclear antigen levels (PCNA); however, in males there was a significant decrease in cell death in response to prenatal stress and a decrease in PCNA levels with
Frontiers in Neuroendocrinology, 2014
Comorbidity of major depressive disorder (MDD) and cardiovascular disease (CVD) represents the fourth leading cause of morbidity and mortality worldwide, and women have a two times greater risk than men. Thus understanding the pathophysiology has widespread implications for attenuation and prevention of disease burden. We suggest that sex-dependent MDD-CVD comorbidity may result from alterations in fetal programming consequent to the prenatal maternal environments that produce excess glucocorticoids, which then drive sex-dependent developmental alterations of the fetal hypothalamic-pituitary-adrenal (HPA) axis circuitry impacting mood, stress regulation, autonomic nervous system (ANS), and the vasculature in adulthood. Evidence is consistent with the hypothesis that disruptions of pathways associated with gamma aminobutyric acid (GABA) in neuronal and vascular development and growth factors have critical roles in key developmental periods and adult responses to injury in heart and brain. Understanding the potential fetal origins of these sex differences will contribute to development of novel sexdependent therapeutics.