The effects of early life stress on neurobehavioral development in children and adolescents: Mediation by the HPA axis

Early-life stress during the prenatal and postnatal periods affects the formation of neural networks that influence brain function throughout life. Previous studies have indicated that maternal separation (MS), a typical rodent model equivalent to early-life stress and, more specifically, to child abuse and/or neglect in humans, can modulate the hypothalamic–pituitary–adrenal (HPA) axis, affecting subsequent neuronal function and emotional behavior. However, the neural basis of the long-lasting effects of early-life stress on brain function has not been clarified. In the present review, we describe the alterations in the HPA-axis activity—focusing on serum corticosterone (CORT)—and in the end products of the HPA axis as well as on the CORT receptor in rodents. We then introduce the brain regions activated during various patterns of MS, including repeated MS and single exposure to MS at various stages before weaning, via an investigation of c-Fos expression, which is a biological marker of neuronal activity. Furthermore, we discuss the alterations in behavior and gene expression in the brains of adult mice exposed to MS. Finally, we ask whether MS repeats itself and whether intergenerational transmission of child abuse and neglect is possible.

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Influence of early life stress on later hypothalamic–pituitary–adrenal axis functioning and its covariation with mental health symptoms: A study of the allostatic process from childhood into adolescence

Development and Psychopathology ◽

10.1017/s0954579411000484 ◽

2011 ◽

Vol 23 (4) ◽

pp. 1039-1058 ◽

Cited By ~ 122

Author(s):

Marilyn J. Essex ◽

Elizabeth A. Shirtcliff ◽

Linnea R. Burk ◽

Paula L. Ruttle ◽

Marjorie H. Klein ◽

...

Keyword(s):

Mental Health ◽

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Specific Activity ◽

Early Life Stress ◽

Hierarchical Linear Model ◽

Mental Health Symptoms ◽

Health Symptoms ◽

Hypothalamic Pituitary Adrenal

AbstractThe hypothalamic–pituitary–adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

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Developmental stress and social phenotypes: integrating neuroendocrine, behavioural and evolutionary perspectives

Philosophical Transactions of the Royal Society B Biological Sciences ◽

10.1098/rstb.2016.0242 ◽

2017 ◽

Vol 372 (1727) ◽

pp. 20160242 ◽

Cited By ~ 18

Author(s):

Karen A. Spencer

Keyword(s):

Hpa Axis ◽

Social Behaviour ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Developmental Stress ◽

Positive Effects ◽

Neuroendocrine Axis ◽

Complex Relationships ◽

Social Behaviours

The social world is filled with different types of interactions, and social experience interacts with stress on several different levels. Activation of the neuroendocrine axis that regulates the response to stress can have consequences for innumerable behavioural responses, including social decision-making and aspects of sociality, such as gregariousness and aggression. This is especially true for stress experienced during early life, when physiological systems are developing and highly sensitive to perturbation. Stress at this time can have persistent effects on social behaviours into adulthood. One important question remaining is to what extent these effects are adaptive. This paper initially reviews the current literature investigating the complex relationships between the hypothalamic-pituitary-adrenal (HPA) axis and other neuroendocrine systems and several aspects of social behaviour in vertebrates. In addition, the review explores the evidence surrounding the potential for ‘social programming’ via differential development and activation of the HPA axis, providing an insight into the potential for positive effects on fitness following early life stress. Finally, the paper provides a framework from which novel investigations could work to fully understand the adaptive significance of early life effects on social behaviours. This article is part of the themed issue ‘Physiological determinants of social behaviour in animals'.

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Assessment of the hypothalamic–pituitary–adrenal axis activity: glucocorticoid receptor and mineralocorticoid receptor function in depression with early life stress – a systematic review

Acta Neuropsychiatrica ◽

10.1111/j.1601-5215.2011.00610.x ◽

2012 ◽

Vol 24 (1) ◽

pp. 4-15 ◽

Cited By ~ 26

Author(s):

Cristiane Von Werne Baes ◽

Sandra M. de Carvalho Tofoli ◽

Camila Maria S. Martins ◽

Mario F. Juruena

Keyword(s):

Systematic Review ◽

Glucocorticoid Receptor ◽

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Mineralocorticoid Receptor ◽

Early Life Stress ◽

Hypothalamic Pituitary Adrenal ◽

Depressed Patients ◽

Suppression Test

Objective:The mechanisms involved in the dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, especially in the functioning of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) in depressed patients, are not well elucidated. The objective of this study was to conduct a systematic review of articles that assess the HPA axis activity from GR and MR in depressed patients and healthy controls with or without early life stress.Methods:We conducted a systematic review of articles in PubMed, SCOPUS and SciELO published between 2000 and 2011, using the following search terms:child abuse,depression,HPA axis,dexamethasone,prednisolone,fludrocortisoneandspironolactone. Thirty-four papers were selected for this review.Results:Most studies identified in this review used the dexamethasone/corticotropin-releasing hormone test and dexamethasone suppression test. In these studies, hypercortisolaemia was associated with depression. We identified three studies with the Prednisolone suppression test, only one study with the use of fludrocortisone and one with spironolactone. This review found nine studies that evaluated the HPA axis in individuals with early life stress.Conclusions:The majority of the studies assessed in this review show that early life stress leads to permanent changes in the HPA axis and may lead to development of depression in adults. The most consistent findings in the literature show increased activity of the HPA axis in depression associated with hypercortisolaemia and reduced inhibitory feedback. These findings suggest that this dysregulation of the HPA axis is partially attributable to an imbalance between GR and MR. Evidences have consistently showed that GR function is impaired in major depression, but few studies have assessed the activity of MR in depression and early life stress.

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Early life stress reduces voluntary exercise and its prevention of diet-induced obesity and metabolic dysfunction in mice

10.1101/2020.01.24.918805 ◽

2020 ◽

Author(s):

Olivia C. Eller-Smith ◽

E. Matthew Morris ◽

John P. Thyfault ◽

Julie A. Christianson

Keyword(s):

Hpa Axis ◽

Life Stress ◽

Early Life ◽

Wheel Running ◽

Control Diet ◽

Early Life Stress ◽

Voluntary Exercise ◽

Free Access ◽

Mrna Levels ◽

Diet Induced Obesity

AbstractThe development of obesity-related metabolic syndrome (MetS) involves a complex interaction of genetic and environmental factors. One environmental factor found to be significantly associated with MetS is early life stress (ELS). We have previously reported on our mouse model of ELS, induced by neonatal maternal separation (NMS), that displays altered regulation of the hypothalamic-pituitary-adrenal (HPA) axis and increased sensitivity in the urogenital organs, which was attenuated by voluntary wheel running. Here, we are using our NMS model to determine if ELS-induced changes in the HPA axis also influence weight gain and MetS. Naïve (non-stressed) and NMS male mice were given free access to a running wheel and a low-fat control diet at 4-weeks of age. At 16-weeks of age, half of the mice were transitioned to a high fat/sucrose (HFS) diet to investigate if NMS influences the effectiveness of voluntary exercise to prevent diet-induced obesity and MetS. Overall, we observed a greater impact of voluntary exercise on prevention of HFS diet-induced outcomes in naïve mice, compared to NMS mice. Although body weight and fat mass were still significantly higher, exercise attenuated fasting insulin levels and mRNA levels of inflammatory markers in epididymal adipose tissue in HFS diet-fed naïve mice. Only moderate changes were observed in exercised NMS mice on a HFS diet, although this could partially be explained by reduced running distance within this group. Interestingly, sedentary NMS mice on a control diet displayed impaired glucose homeostasis and moderately increased pro-inflammatory mRNA levels in epididymal adipose, suggesting that early life stress alone impairs metabolic function and negatively impacts the therapeutic effect of voluntary exercise.

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