Prenatal Anxiety Predicts Individual Differences in Cortisol in Pre-Adolescent Children

doi:10.1016/j.biopsych.2005.03.032

Biological Psychiatry

Volume 58, Issue 3, 1 August 2005, Pages 211-217

https://doi.org/10.1016/j.biopsych.2005.03.032 Get rights and content

Background

Animal studies suggest that prenatal stress is associated with long-term disturbance in hypothalamic-pituitary-adrenal (HPA) axis function, but evidence in humans is lacking. This study examined the long-term association between prenatal anxiety and measures of diurnal cortisol at age 10 years.

Methods

Measures of cortisol were collected at awakening, 30 min after awakening, and at 4 pm and 9 pm on 3 consecutive days in a sample of 10-year-olds (n = 74) from the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of mothers and children on whom measures of anxiety and depression were collected in pregnancy and the postpartum period. Analyses examined the links between symptoms of prenatal anxiety and multiple indicators of cortisol, an index of HPA axis functioning.

Results

Prenatal anxiety was significantly associated with individual differences in awakening and afternoon cortisol after accounting for obstetric and sociodemographic risk (partial correlations were .32 and .25, p < .05). The effect for awakening cortisol remained significant after controlling for multiple postnatal assessments of maternal anxiety and depression.

Conclusions

This study provides the first human evidence that prenatal anxiety might have lasting effects on HPA axis functioning in the child and that prenatal anxiety might constitute a mechanism for an increased vulnerability to psychopathology in children and adolescents.

Section snippets

Subjects

The ALSPAC is a prospective study of women, their partners, and an index child. The 14,541 enrolled pregnancies (from April 1, 1991 to December 31, 1992) represented 85%–90% of the eligible population resident in three health authorities around Bristol, United Kingdom (Golding et al 2001). Of these, 14,138 surviving children (13,995 mothers) are being followed. The average age of the women at pregnancy was 28 years and ranged from 14 to 46 years; less than 5% were younger than 20 years, and

Results

Preliminary analyses indicated that there was the usual and substantial diurnal variation in cortisol levels for each of the 3 days assessed, with close correspondence among diurnal curves for the 3 days (Figure 1). There was not a significant increase in cortisol from awakening to 30 min after awakening in the group as a whole [means (SD): 10.4 (3.2) and 10.2 (4.1), respectively; paired t test, t(69) =.38]. Stability of individual differences in cortisol values across the 3 days was moderate.

Discussion

We found that anxiety in late pregnancy was associated with individual differences in measures of cortisol in pre-adolescents. The link between prenatal anxiety and offspring HPA axis function was strongest at 32 weeks’ gestation and especially robust for awakening cortisol. These results provide the strongest evidence to date that prenatal stress is associated with longer-term impact on the HPA axis of the human offspring, a finding repeatedly demonstrated in animal investigations.

There was

References (52)

E.P.M. Brouwers et al.
Maternal anxiety during pregnancy and subsequent infant development
Infant Behav Dev
(2001)
J.R. Challis et al.
Current topicThe placental corticotrophin-releasing hormone-adrenocorticotrophin axis
Placenta
(1995)
C.L. Coe et al.
Prenatal stress diminishes neurogenesis in the dentate gyrus of juvenile rhesus monkeys
Biol Psychiatry
(2003)
J.A. DiPietro et al.
Fetal response to induced maternal stress
Early Hum Dev
(2003)
M.A. Ellenbogen et al.
High levels of cortisol among adolescent offspring of parents with bipolar disorderA pilot study
Psychoneuroendocrinology
(2004)
M.J. Essex et al.
Maternal stress beginning in infancy may sensitize children to later stress exposureEffects on cortisol and behavior
Biol Psychiatry
(2002)
A. Feder et al.
Twenty-four-hour cortisol secretion patterns in prepubertal children with anxiety of depressive disorders
Biol Psychiatry
(2004)
V. Glover et al.
Antenatal maternal anxiety is linked with atypical handedness in the child
Early Hum Dev
(2004)
R.S. Goland et al.
Placental corticotropin-releasing hormone and the hypercortisolism of pregnancy
Am J Obstet Gynecol
(1994)
S. Goldberg et al.
Cortisol concentrations in 12- to 18-month-old infantsStability over time, location, and stressor
Biol Psychiatry
(2003)

S.L. Halligan et al.

Exposure to postnatal depression predicts elevated cortisol in adolescent offspring

Biol Psychiatry

(2004)

A.C. Huizink et al.

Psychological measures of prenatal stress as predictors of infant temperament

J Am Acad Child Adolesc Psychiatry

(2002)

C.O. Ladd et al.

Long-term behavioral and neuroendocrine adaptations to adverse early experience

Prog Brain Res

(2000)

S. Maccari et al.

Prenatal stress and long-term consequencesImplications of glucocorticoid hormones

Neurosci Biobehav Rev

(2003)

I.L. Ward et al.

Prenatal stress feminizes juvenile play patterns in male rats

Physiol Behav

(1991)

E.A. Young et al.

Cortisol pulsatility and its role in stress regulation and health

Front Neuroendocrinol

(2004)

R. Ader et al.

Prenatal maternal anxiety and offspring emotionality in the rat

Psychol Rep

(1963)

D.J. Barker

The fetal origins of adult disease

Proc R Soc Lond B Biol Sci

(1995)

Y. Ben-Shlomo et al.

A life course approach to chronic disease epidemiologyConceptual models, empirical challenges and interdisciplinary perspectives

Int J Epidemiol

(2002)

J. Birtchnell et al.

The total score of the Crown-Crisp Experiential IndexA useful and valid measure of psychoneurotic pathology

Br J Med Psychol

(1988)

D. Cicchetti et al.

Stress and developmentBiological and psychological consequences

Dev Psychopathol

(2001)

A. Clow et al.

The awakening cortisol responseMethodological issues and significance

Stress

(2004)

C.L. Coe et al.

Prenatal stress diminishes the cytokine response of leukocytes to endotoxin stimulation in juvenile rhesus monkeys

J Clin Endocrinol Metab

(2002)

J.L. Cox et al.

Detection of postnatal depressionDevelopment of the 10 item Edinburgh Postnatal Depression Scale

Br J Psychiatry

(1987)

R. Gitau et al.

Fetal HPA stress responses to invasive procedures are independent of maternal responses

J Clin Endocrinol Metab

(2001)

J. Golding et al.

ALSPAC—The Avon Longitudinal Study of Parents and Children. I. Study methodology

Paediatr Perinat Epidemiol

(2001)

Cited by (394)

The association between pregnancy-related anxiety and behavioral development in 18-month-old children: The mediating effects of parenting styles and breastfeeding methods
2023, Journal of Affective Disorders
Pregnancy-related anxiety (PRA) is a distinct type of anxiety from general anxiety, affects many pregnant women, and is correlated with poor behavioral development in children. However, the mediation paths were unclear.
A total of 2032 mother-infant pairs from the Ma'anshan Birth Cohort were included in the current study. Maternal PRA was assessed in the second and third trimesters. Children's behavioral development was evaluated at the age of 18 months. In addition, information on parenting styles and breastfeeding methods was obtained at postpartum. Multivariate regression and structural equation modeling were used to examine the associations between maternal PRA and children's behavioral development.
Significant intercorrelations were found between maternal PRA, the potential mediators (parenting styles and breastfeeding methods), and 18-month-old children's ASQ scores. Parenting styles played an intermediary role in the relationship between maternal PRA and children's behavioral development (β = 0.030, 95 % confidence interval: 0.017–0.051), and the mediating effect accounted for 29.1 % of the total effect. However, breastfeeding methods did not mediate the link between PRA and children's behavior.
Depression and postpartum anxiety were not controlled for in our analysis, which left us unable to estimate the independent impact of PRA on children's behavior.
Parenting rather than breastfeeding is the mediating factor of behavioral problems in children caused by PRA.
Early predictors of sensory processing sensitivity in members of the Birth to Twenty Plus cohort
2023, Journal of Research in Personality
Sensory processing sensitivity (SPS) is a personality trait describing individuals who are more receptive to their environmental context. SPS has implications across the lifespan, but few longitudinal predictors of the trait are currently known. We examined potential predictors of adult SPS levels among 858 members of the Birth to Twenty Plus cohort. Available data included birth weight, gestational age, socioeconomic status, prenatal maternal stress (PMS), child behaviour scores, and genotypes for three loci (5-HTTLPR, DRD4, and MAOA). Highly Sensitive Person scale scores at ages 28–29 were regressed on these variables. Early gestational age (p < .01) and PMS (p = .05) were significantly associated with higher SPS. Our results tentatively support the hypothesis that prenatal adversity is associated with heightened sensitivity.
Challenges in the use of animal models and perspectives for a translational view of stress and psychopathologies
2022, Neuroscience and Biobehavioral Reviews
The neurobiology and development of treatments for stress-related neuropsychiatric disorders rely heavily on animal models. However, the complexity of these disorders makes it difficult to model them entirely, so only specific features of human psychopathology are emulated and these models should be used with great caution. Importantly, the effects of stress depend on multiple factors, like duration, context of exposure, and individual variability. Here we present a review on pre-clinical studies of stress-related disorders, especially those developed to model posttraumatic stress disorder, major depression, and anxiety. Animal models provide relevant evidence of the underpinnings of these disorders, as long as face, construct, and predictive validities are fulfilled. The translational challenges faced by scholars include reductionism and anthropomorphic/anthropocentric interpretation of the results instead of a more naturalistic and evolutionary understanding of animal behavior that must be overcome to offer a meaningful model. Other limitations are low statistical power of analysis, poor evaluation of individual variability, sex differences, and possible conflicting effects of stressors depending on specific windows in the lifespan.
CATCH (Cortisol Apta WATCH): ‘Bio-mimic alarm’ to track Anxiety, Stress, Immunity in human sweat
2021, Electrochimica Acta
This work demonstrates an electrochemical label-free cortisol aptasensor (Cortisol Apta-Watch (CATCH) for detection of cortisol from passively perspired eccrine sweat. The platform is designed to track cortisol levels in sweat to understand the implications of stress in different physiological processes of the body. The sensor platform is characterized with zeta potential, FTIR, and electrochemical measurements to understand the aptamer binding chemistry and cortisol binding sensitivity. Following this, the platform's sensitivity to cortisol analyte concentration in human sweat is evaluated using impedimetric and chronoamperometric methods. The results highlight the platform's sensitivity to cortisol with a detection limit of ~1 ng/mL in human sweat and a dynamic range of 1–256 ng/mL. The performance metrics highlight the ability of the sensor to sensitively detect cortisol in human sweat with high significance (p<0.05). These studies are demonstrated across triplicate measurements and have low RSD values (^˷<2%). The performance was also evaluated on five healthy subjects, indicating the ability to detect sweat cortisol in real time and on-body. Additionally, the developed sensing platform demonstrated excellent correlation with state-of-art reference method with a Pearson's correlation of r = 0.97 in nine human subject samples. The sensor also demonstrated that the circadian behavior of cortisol can be tracked with elevated levels in the morning and low levels in the evening in a cohort of healthy subjects. The developed aptamer-based cortisol sensing technology can aid in real-time, continuous monitoring facilitating personalized health monitoring.
Fetal programming pathway from maternal mental health to infant cortisol functioning: The role of placental 11β-HSD2 mRNA expression
2021, Psychoneuroendocrinology
Placental 11β-HSD2 has been a focus of research for understanding potential fetal programming associated with maternal emotional disorders. This study examined the pathway from antenatal mental health via placental 11β-HSD2 mRNA to cortisol regulation in the infant offspring. This study reports on data obtained from 236 participants in the Mercy Pregnancy and Emotional Wellbeing Study (MPEWS). At term, placental tissue was collected within 30 min of birth from 52 participants meeting current criteria for a depressive disorder, and 184 control participants. Depressive disorders were diagnosed using the SCID-IV. In addition, antidepressant use, depressive and anxiety symptoms were measured in early and late pregnancy. Placental 11β-HSD2 mRNA expression was measured using qRT-PCR. Infant salivary cortisol samples were taken at 12 months of age. Women on antidepressant medication and with higher trait anxiety had higher placental 11β-HSD2 expression compared to women not taking medication. Furthermore, the offspring of women taking an antidepressant and who also had a current depressive disorder and high trait anxiety had high cortisol reactivity at 12 months of age and this was mediated through 11β-HSD2 mRNA expression. In contrast, offspring of women not taking antidepressant medication with depressive disorder and high anxiety there was low cortisol reactivity observed. Our findings suggest that the relationship between maternal antenatal depression and anxiety and infant cortisol reactivity is mediated through placental 11β-HSD2 mRNA expression. Furthermore, the direction differed for women taking antidepressants, where infant cortisol reactivity was high whereas when compared to those with unmedicated depression and anxiety, where infant cortisol reactivity was low.
Developmental stress has sex-specific effects on contextual and cued fear conditioning in adulthood
2021, Physiology and Behavior
Stress-induced deviations in central nervous system development has long-term effects on adult mental health. Previous research in humans demonstrates that prenatal or adolescent stress increases the risk for psychiatric disorders. Animal models investigating the effects of stress during prenatal or adolescent development produces behavioral outcomes analogous to those observed in humans. However, whether adolescent stress exposure potentiates the effects of prenatal stress is currently unknown. Thus, the current study tested whether adolescent stress increases the impact of prenatal stress on contextual and cued fear memory in adulthood. Male and female Sprague Dawley rats were exposed to a chronic variable stress schedule during the last week of gestation, during adolescence, or during both developmental periods before undergoing fear conditioning training in adulthood. Our hypothesis predicted that the combined effects of prenatal and adolescent stress on contextual and cued fear memory would be greater than the effects of stress during either time period alone. In contrast to our hypothesis, however, we found independent effects of prenatal and adolescent stress on contextual and cued fear memory in both sexes, with no additional combined impact of stress exposure during both developmental phases. In males, developmental stress increased freezing behavior during contextual and cued testing regardless of whether stress exposure was prenatal, adolescent, or combined prenatal and adolescent stress exposure. In contrast, the effects of developmental stress in females were both test- and ovarian hormone status-dependent. During cued testing, nonstressed female freezing behavior depended on estrous cycle phase, whereas freezing behavior in stressed females did not, suggesting that developmental stress interferes with hormone-dependent cued fear memory. No effects of developmental stress or estrous cycle phase were observed for contextual fear memory in females. The results of the current study suggest that the effects of prenatal and adolescent stress on contextual and cued fear memory are not cumulative, but the effects of developmental stress on associative memory differ between males and females.

View all citing articles on Scopus

View full text

Original articlePrenatal Anxiety Predicts Individual Differences in Cortisol in Pre-Adolescent Children

Background

Methods

Results

Conclusions

Section snippets

Subjects

Results

Discussion

Infant Behav Dev

Placenta

Biol Psychiatry

Early Hum Dev

Psychoneuroendocrinology

Biol Psychiatry

Biol Psychiatry

Early Hum Dev

Am J Obstet Gynecol

Biol Psychiatry

Biol Psychiatry

J Am Acad Child Adolesc Psychiatry

Prog Brain Res

Neurosci Biobehav Rev

Physiol Behav

Front Neuroendocrinol

Prenatal maternal anxiety and offspring emotionality in the rat

Psychol Rep

The fetal origins of adult disease

Proc R Soc Lond B Biol Sci

A life course approach to chronic disease epidemiologyConceptual models, empirical challenges and interdisciplinary perspectives

Int J Epidemiol

The total score of the Crown-Crisp Experiential IndexA useful and valid measure of psychoneurotic pathology

Br J Med Psychol

Stress and developmentBiological and psychological consequences

Dev Psychopathol

The awakening cortisol responseMethodological issues and significance

Stress

Prenatal stress diminishes the cytokine response of leukocytes to endotoxin stimulation in juvenile rhesus monkeys

J Clin Endocrinol Metab

Detection of postnatal depressionDevelopment of the 10 item Edinburgh Postnatal Depression Scale

Br J Psychiatry

Fetal HPA stress responses to invasive procedures are independent of maternal responses

J Clin Endocrinol Metab

ALSPAC—The Avon Longitudinal Study of Parents and Children. I. Study methodology

Paediatr Perinat Epidemiol

Original article
Prenatal Anxiety Predicts Individual Differences in Cortisol in Pre-Adolescent Children