Early life stress and development: potential mechanisms for adverse outcomes

Abstract Background Chronic and/or extreme stress in early life, often referred to as early adversity, childhood trauma, or early life stress, has been associated with a wide range of adverse effects on development. However, while early life stress has been linked to negative effects on a number of neural systems, the specific mechanisms through which early life stress influences development and individual differences in children’s outcomes are still not well understood. Main text The current paper reviews the existing literature on the neurobiological effects of early life stress and their ties to children’s psychological and behavioral development. Conclusions Early life stress has persistent and pervasive effects on prefrontal–hypothalamic–amygdala and dopaminergic circuits that are at least partially mediated by alterations in hypothalamic–pituitary–adrenal axis function. However, to date, this research has primarily utilized methods of assessment that focus solely on children’s event exposures. Incorporating assessment of factors that influence children’s interpretation of stressors, along with stressful events, has the potential to provide further insight into the mechanisms contributing to individual differences in neurodevelopmental effects of early life stress. This can aid in further elucidating specific mechanisms through which these neurobiological changes influence development and contribute to risk for psychopathology and health disorders.

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Abstract 17: Early Life Stress Sensitizes The Angiotensin II-elicited Hypertensive Response

Hypertension ◽

10.1161/hyp.76.suppl_1.17 ◽

2020 ◽

Vol 76 (Suppl_1) ◽

Author(s):

Baojian Xue ◽

Terry Beltz ◽

Fang Guo ◽

David M Pollock ◽

Jennifer S Pollock ◽

...

Keyword(s):

Mrna Expression ◽

Proinflammatory Cytokines ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Male Rats ◽

Sprague Dawley ◽

Cns Inflammation ◽

Wide Range ◽

The Brain

Separation of neonatal rodent pups from their mothers has been used as a model to study the effects of early life stress (ELS) on behavioral and physiological responses in adults. Using an Induction-Delay-Expression experimental paradigm, our previous studies demonstrate that a wide range of stressors administered during an induction period produces hypertensive response sensitization (HTRS) in response to a subsequent pro-hypertensive stimulus. HTRS is accompanied by activation of the brain renin-angiotensin system (RAS) and CNS inflammation. The present study investigated whether ELS induces HTRS and changes in brain-related underlying mechanisms. Rat neonates from Sprague-Dawley breeders were subjected to ELS by separating them each morning from their mothers for 3 h on postnatal days 2 to 14. Pups from non-handled litters formed control groups. At 10 weeks of age, male rats were used to evaluate blood pressure and autonomic function using telemetric probes and pharmacological methods. In addition, in separate control and ELS groups, the lamina terminalis (LT) structures and the hypothalamic paraventricular nucleus (PVN) were analyzed for mRNA expression of RAS components and proinflammatory cytokines. Adult ELS rats as compared to non-separated controls exhibited 1) HTRS during expression testing using 2 week ANG II infusions (120 ng/kg/min s.c.; ELS animals, Δ45.5±4.5 mmHg vs. controls, Δ22.4±3.1 mmHg); 2) a greater reduction in mean arterial pressure following ganglionic blockade (hexamethonium, 30 mg/kg, ip), 3) increased sympathetic drive to the heart (atenolol, 8 mg/kg, ip), 4) decreased vagal tone (atropine, 8 mg/kg, ip), and 5) increased mRNA expression of several components of the brain RAS and proinflammatory cytokines in the LT and PVN. These results suggest that maternal ELS may predispose individuals to hypertension that is mediated by upregulation of the brain RAS and proinflammatory cytokines and increased sympathetic drive to the cardiovascular system.

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Early Life Stress and Substance Use Disorders: Underlying Neurobiology and Pathways to Adverse Outcomes

Adversity and Resilience Science ◽

10.1007/s42844-020-00005-7 ◽

2020 ◽

Vol 1 (1) ◽

pp. 29-47 ◽

Cited By ~ 3

Author(s):

Dylan Kirsch ◽

Charles M. Nemeroff ◽

Elizabeth T. C. Lippard

Keyword(s):

Substance Use ◽

Substance Use Disorders ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Adverse Outcomes

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The adaptive and maladaptive continuum of stress responses – a hippocampal perspective

Reviews in the Neurosciences ◽

10.1515/revneuro-2014-0083 ◽

2015 ◽

Vol 26 (4) ◽

Cited By ~ 17

Author(s):

Deepika Suri ◽

Vidita A. Vaidya

Keyword(s):

Stress Responses ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Negative Consequences ◽

Functional Responses ◽

Physiological Level ◽

Early Stress ◽

Wide Range ◽

Potential Factors

AbstractExposure to stressors elicits a spectrum of responses that span from potentially adaptive to maladaptive consequences at the structural, cellular and physiological level. These responses are particularly pronounced in the hippocampus where they also appear to influence hippocampal-dependent cognitive function and emotionality. The factors that influence the nature of stress-evoked consequences include the chronicity, severity, predictability and controllability of the stressors. In addition to adult-onset stress, early life stress also elicits a wide range of structural and functional responses, which often exhibit life-long persistence. However, the outcome of early stress exposure is often contingent on the environment experienced in adulthood, and could either aid in stress coping or could serve to enhance susceptibility to the negative consequences of adult stress. This review comprehensively examines the consequences of adult and early life stressors on the hippocampus, with a focus on their effects on neurogenesis, neuronal survival, structural and synaptic plasticity and hippocampal-dependent behaviors. Further, we discuss potential factors that may tip stress-evoked consequences from being potentially adaptive to largely maladaptive.

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2341

Journal of Clinical and Translational Science ◽

10.1017/cts.2017.132 ◽

2017 ◽

Vol 1 (S1) ◽

pp. 36-36

Author(s):

Courtney Vaughan ◽

Bethany Stangl ◽

Rajita Sinha ◽

Vijay Ramchandani

Keyword(s):

Life Events ◽

Chronic Stress ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stressful Events ◽

Computer Assisted ◽

Chronic Stressors ◽

Stress Interview ◽

The Impact

OBJECTIVES/SPECIFIC AIMS: The objective of this analysis was to characterize the impact of stress, both early life and chronic, on intravenous alcohol self-administration (IV-ASA) in healthy non-dependent drinkers using the Computer-Assisted Infusion System (CAIS). Personality measures also have shown to impact drinking behavior, particularly impulsivity. Few studies have assessed the impact of stress and impulsivity on drinking behaviors in a non-dependent population. METHODS/STUDY POPULATION: Healthy non-dependent drinkers (n=28) completed a CAIS session, where they push a button adlib to self-administer standardized IV alcohol infusions. Participants completed the Cumulative Chronic Stress interview and the Early Life Stress Questionnaire (ELSQ) for stress measures. The Cumulative Chronic Stress interview was broken up into 4 sections: major life events, life traumas, recent life events, and chronic stressors. The number of endorsed events was added up to create 4 separate scores. Subjective response and craving measures were collected serially using the Drug Effects Questionnaire (DEQ) and Alcohol Urge Questionnaire (AUQ). The Impaired Control Scale (ICS) assessed failed control over recent drinking in the past 6 months. Impulsivity was assessed using the NEO personality inventory, which included the N-impulsive sub-facet, as well as the UPPS-P Impulsive Behavior Scale. RESULTS/ANTICIPATED RESULTS: Results showed early life stress events (ELSQ) are related to more chronic stressors in the cumulative chronic stress interview (p=0.005). Participants with higher chronic stress scores showed lower subjective effects, as measured by the DEQ, following the priming exposure (p=0.036) but had more craving for alcohol as measured by the AUQ (p=0.009). A regression analysis showed the number of chronic stressful events predicted ICS failed attempts to control drinking (p=0.034), after covarying for sex. Participants with more chronic stressful events showed more impulsivity on the N-impulsivity measure (p=0.034) and the UPPS-P positive urgency measure (p=0.005). DISCUSSION/SIGNIFICANCE OF IMPACT: Non-dependent drinkers with more early life stress tend to have a higher number of chronic stressful events. More chronically stressful events were associated with feeling less effects of alcohol and higher craving for alcohol. Participants with more chronically stressful events also appear to have more failed attempts at controlling their drinking. Future analysis will assess for mediation and moderation of these factors. Chronically stressful events and impulsive behaviors could serve as important areas for intervention for better treatment outcomes for alcohol use disorders.

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Individual Differences in Vulnerability to Early Life Stress: A Role for Serotonergic Modulation of the Ventral Hippocampus

Biological Psychiatry ◽

10.1016/j.biopsych.2021.02.181 ◽

2021 ◽

Vol 89 (9) ◽

pp. S66-S67

Author(s):

Christoph Anacker

Keyword(s):

Individual Differences ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Ventral Hippocampus ◽

Serotonergic Modulation

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Corticolimbic Circuit Structure Moderates an Association Between Early Life Stress and Later Trait Anxiety

10.1101/581926 ◽

2019 ◽

Author(s):

M. Justin Kim ◽

Madeline J. Farber ◽

Annchen R. Knodt ◽

Ahmad R. Hariri

Keyword(s):

Trait Anxiety ◽

Life Stress ◽

Early Life ◽

Emotional Reactivity ◽

Early Life Stress ◽

Childhood Adversity ◽

Structural Features ◽

Individual Variability ◽

Future Research ◽

Wide Range

AbstractChildhood adversity is associated with a wide range of negative behavioral and neurodevelopmental consequences. However, individuals vary substantially in their sensitivity to such adversity. Here, we examined how individual variability in structural features of the corticolimbic circuit, which plays a key role in emotional reactivity, moderates the association between childhood adversity and later trait anxiety in 798 young adult university students. Consistent with prior research, higher self-reported childhood adversity was significantly associated with higher self-reported trait anxiety. However, this association was attenuated in participants with higher microstructural integrity of the uncinate fasciculus and greater thickness of the orbitofrontal cortex. These structural properties of the corticolimbic circuit may capture a neural profile of relative resiliency to early life stress, especially against the negative effects of childhood adversity on later trait anxiety. More generally, our findings highlight the potential utility in the simultaneous consideration of qualitatively different brain structural measures in explaining complex behavioral associations in future research.

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Early life stress, FK506 binding protein 5 gene (FKBP5) methylation, and inhibition-related prefrontal function: A prospective longitudinal study

Development and Psychopathology ◽

10.1017/s095457941700147x ◽

2017 ◽

Vol 29 (5) ◽

pp. 1895-1903 ◽

Cited By ~ 19

Author(s):

Madeline B. Harms ◽

Rasmus Birn ◽

Nadine Provencal ◽

Tobias Wiechmann ◽

Elisabeth B. Binder ◽

...

Keyword(s):

Inhibitory Control ◽

Life Stress ◽

Early Life ◽

Binding Protein ◽

Early Life Stress ◽

Stress Exposure ◽

Childhood Stress ◽

Fk506 Binding Protein ◽

Wide Range ◽

Prospective Longitudinal

AbstractIndividuals who have experienced high levels of childhood stress are at increased risk for a wide range of behavioral problems that persist into adulthood, yet the neurobiological and molecular mechanisms underlying these associations remain poorly understood. Many of the difficulties observed in stress-exposed children involve problems with learning and inhibitory control. This experiment was designed to test individuals' ability to learn to inhibit responding during a laboratory task. To do so, we measured stress exposure among a community sample of school-aged children, and then followed these children for a decade. Those from the highest and lowest quintiles of childhood stress exposure were invited to return to our laboratory as young adults. At that time, we reassessed their life stress exposure, acquired functional magnetic resonance imaging data during an inhibitory control task, and assayed these individuals' levels of methylation in the FK506 binding protein 5 (FKBP5) gene. We found that individuals who experienced high levels of stress in childhood showed less differentiation in the dorsolateral prefrontal cortex between error and correct trials during inhibition. This effect was associated only with childhood stress exposure and not by current levels of stress in adulthood. In addition, FKBP5 methylation mediated the association between early life stress and inhibition-related prefrontal activity. These findings are discussed in terms of using multiple levels of analyses to understand the ways in which adversity in early development may affect adult behavioral adaptation.

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Serotonin-related pathways and developmental plasticity: relevance for psychiatric disorders

Dialogues in Clinical Neuroscience ◽

10.31887/dcns.2014.16.1/adayer ◽

2014 ◽

Vol 16 (1) ◽

pp. 29-41 ◽

Cited By ~ 8

Keyword(s):

Psychiatric Disorders ◽

Neural Plasticity ◽

Life Stress ◽

Early Life ◽

Selective Serotonin Reuptake Inhibitors ◽

Developmental Plasticity ◽

Neural Circuit ◽

Early Life Stress ◽

Early Life Adversity ◽

Wide Range

Risk for adult psychiatric disorders is partially determined by early-life alterations occurring during neural circuit formation and maturation. In this perspective, recent data show that the serotonin system regulates key cellular processes involved in the construction of cortical circuits. Translational data for rodents indicate that early-life serotonin dysregulation leads to a wide range of behavioral alterations, ranging from stress-related phenotypes to social deficits. Studies in humans have revealed that serotonin-related genetic variants interact with early-life stress to regulate stress-induced cortisol responsiveness and activate the neural circuits involved in mood and anxiety disorders. Emerging data demonstrate that early-life adversity induces epigenetic modifications in serotonin-related genes. Finally, recent findings reveal that selective serotonin reuptake inhibitors can reinstate juvenile-like forms of neural plasticity, thus allowing the erasure of long-lasting fear memories. These approaches are providing new insights on the biological mechanisms and clinical application of antidepressants.

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Early life stress decreases the proliferation and numbers of adult hypothalamic neural stem cells

10.1101/831446 ◽

2019 ◽

Author(s):

Pascal Bielefeld ◽

Maralinde R. Abbink ◽

Anna R. Davidson ◽

Paul J. Lucassen ◽

Aniko Korosi ◽

...

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Neural Stem Cells ◽

Neural Stem Cell ◽

Life Stress ◽

Early Life ◽

Cell Function ◽

Early Life Stress ◽

Adult Brain ◽

Wide Range

AbstractEarly life stress (ELS) is a potent environmental factor that can confer enduring effects on brain structure and function. Exposure to stress during early life has been linked to a wide range of physiopathological consequences later in life. In particular, ELS has been shown to have lasting effects on neurogenesis in the adult brain, suggesting that ELS is a significant regulator of adult neural stem cell function. Here, we investigated the effect of ELS on the numbers and proliferation of neural stem cells in the hypothalamus of adult mice. We show that ELS has long term negative effects on hypothalamic neural stem cell numbers and on their proliferation. Specifically, ELS reduced the total numbers of PCNA+ cells present in hypothalamic areas surrounding the 3rd ventricle; the numbers of PCNA+/Sox2+/Nestin-GFP+ cells present in the medial eminence at the base of the 3rd ventricle; and the number of β-tanycytes around the ventral 3rd ventricle, without affecting the numbers of α-tanycytes in more dorsal areas. These results suggest that a reduction of proliferation and tanycyte numbers contributes to the effects of ELS on the hypothalamus and its consequent physiological alterations.

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