scholarly journals Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

2021 ◽  
Vol 15 ◽  
Author(s):  
Jamie L. Hanson ◽  
Brendon M. Nacewicz
Keyword(s):  
Animal Models ◽  
Early Life ◽  
Allostatic Load ◽  
Child Poverty ◽  
Past Research ◽  
Early Life Adversity ◽  
Stress Buffering ◽  
Behavioral Studies ◽  
New Findings ◽  
The Impact

Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load,” will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.

scholarly journals Amygdala Allostasis and Early Life Adversity: Considering Excitotoxicity and Inescapability in the Sequelae of Stress

2020 ◽  
Author(s):  
Jamie Lars Hanson ◽  
Brendon Nacewicz
Keyword(s):  
Animal Models ◽  
Early Life ◽  
Allostatic Load ◽  
Child Poverty ◽  
Past Research ◽  
Early Life Adversity ◽  
Stress Buffering ◽  
Behavioral Studies ◽  
New Findings ◽  
The Impact

Early life adversity (ELA), such as child maltreatment or child poverty, engenders problems with emotional and behavioral regulation. In the quest to understand the neurobiological sequelae and mechanisms of risk, the amygdala has been of major focus. While the basic functions of this region make it a strong candidate for understanding the multiple mental health issues common after ELA, extant literature is marked by profound inconsistencies, with reports of larger, smaller, and no differences in regional volumes of this area. We believe integrative models of stress neurodevelopment, grounded in “allostatic load”, will help resolve inconsistencies in the impact of ELA on the amygdala. In this review, we attempt to connect past research studies to new findings with animal models of cellular and neurotransmitter mediators of stress buffering to extreme fear generalization onto testable research and clinical concepts. Drawing on the greater impact of inescapability over unpredictability in animal models, we propose a mechanism by which ELA aggravates an exhaustive cycle of amygdala expansion and subsequent toxic-metabolic damage. We connect this neurobiological sequela to psychosocial mal/adaptation after ELA, bridging to behavioral studies of attachment, emotion processing, and social functioning. Lastly, we conclude this review by proposing a multitude of future directions in preclinical work and studies of humans that suffered ELA.

scholarly journals Early life adversity, dispositional mindfulness, and longitudinal stress experience during the COVID-19 pandemic

2020 ◽  
Author(s):  
Annika Benz ◽  
Maria Meier ◽  
Ulrike U. Bentele ◽  
Stephanie J. Dimitroff ◽  
Bernadette Denk ◽  
...  
Keyword(s):  
Perceived Stress ◽  
Life Stress ◽  
Early Life ◽  
Early Life Stress ◽  
Dispositional Mindfulness ◽  
Early Life Adversity ◽  
Stress Buffering ◽  
Psychopathological Symptoms ◽  
Increased Risk ◽  
The Impact

Experiencing severe or prolonged stressors in early life is associated with increased risk for mental and physical disorders in adulthood. Further, individuals who experienced early life stress (ELS) may use dysfunctional coping strategies like stress-related eating, in contrast to more beneficial stress buffering mechanisms e.g. based on mindfulness. Whether these mechanisms contribute to increased levels of perceived stress and symptoms of mental disorders in individuals with ELS in times of crisis is yet unclear. As part of a larger project, we assessed changes in perceived stress and psychopathological symptoms in a sample of N=102 participants (81% female; meanage=23.49, SDage= 7.11, range 18–62) from October/December 2019 (prior to the Covid-19 pandemic) to April/June 2020 (after the German government introduced Covid-19 related restrictions). Additionally, we assessed ELS and dispositional mindfulness.Perceived stress and depression significantly increased while anxiety levels decreased. No significant change was observed for somatization. ELS and dispositional mindfulness were not associated with change scores, but with perceived stress and psychopathological symptoms at both assessments. The increase in perceived stress during the pandemic in a majority of participants demonstrates the impact of the pandemic in the general population.

The impact of early life gut colonization on metabolic and obesogenic outcomes: what have animal models shown us?

2015 ◽  
Vol 7 (1) ◽  
pp. 15-24 ◽  
Author(s):  
J. G. Wallace ◽  
W. Gohir ◽  
D. M. Sloboda
Keyword(s):  
Animal Models ◽  
Gut Microbiota ◽  
Early Life ◽  
Maternal Obesity ◽  
Communicable Disease ◽  
Critical Periods ◽  
Early Life Adversity ◽  
Gut Colonization ◽  
Increased Risk ◽  
The Impact

The rise in the occurrence of obesity to epidemic proportions has made it a global concern. Great difficulty has been experienced in efforts to control this growing problem with lifestyle interventions. Thus, attention has been directed to understanding the events of one of the most critical periods of development, perinatal life. Early life adversity driven by maternal obesity has been associated with an increased risk of metabolic disease and obesity in the offspring later in life. Although a mechanistic link explaining the relationship between maternal and offspring obesity is still under investigation, the gut microbiota has come forth as a new factor that may play a role modulating metabolic function of both the mother and the offspring. Emerging evidence suggests that the gut microbiota plays a much larger role in mediating the risk of developing non-communicable disease, including obesity and metabolic dysfunction in adulthood. With the observation that the early life colonization of the neonatal and postnatal gut is mediated by the perinatal environment, the number of studies investigating early life gut microbial establishment continues to grow. This paper will review early life gut colonization in experimental animal models, concentrating on the role of the early life environment in offspring gut colonization and the ability of the gut microbiota to dictate risk of disease later in life.

scholarly journals Maternal separation in rodents: a journey from gut to brain and nutritional perspectives

2019 ◽  
Vol 79 (1) ◽  
pp. 113-132 ◽  
Author(s):  
Marion Rincel ◽  
Muriel Darnaudéry
Keyword(s):  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Human Subjects ◽  
Early Life Stress ◽  
Long Term Effects ◽  
Early Life Adversity ◽  
Critical Window ◽  
Beneficial Impact ◽  
The Impact

The developmental period constitutes a critical window of sensitivity to stress. Indeed, early-life adversity increases the risk to develop psychiatric diseases, but also gastrointestinal disorders such as the irritable bowel syndrome at adulthood. In the past decade, there has been huge interest in the gut–brain axis, especially as regards stress-related emotional behaviours. Animal models of early-life adversity, in particular, maternal separation (MS) in rodents, demonstrate lasting deleterious effects on both the gut and the brain. Here, we review the effects of MS on both systems with a focus on stress-related behaviours. In addition, we discuss more recent findings showing the impact of gut-directed interventions, including nutrition with pre- and probiotics, illustrating the role played by gut microbiota in mediating the long-term effects of MS. Overall, preclinical studies suggest that nutritional approaches with pro- and prebiotics may constitute safe and efficient strategies to attenuate the effects of early-life stress on the gut–brain axis. Further research is required to understand the complex mechanisms underlying gut–brain interaction dysfunctions after early-life stress as well as to determine the beneficial impact of gut-directed strategies in a context of early-life adversity in human subjects.

Basic mechanisms of, and treatment targets for, stress-related disorders

2020 ◽  
pp. 829-839
Author(s):  
Bruce S. McEwen
Keyword(s):  
Early Life ◽  
Allostatic Load ◽  
Life Experiences ◽  
The Body ◽  
The Social ◽  
Wear And Tear ◽  
Short Run ◽  
Social And Physical Environment ◽  
The Impact ◽  
The Brain

The response to the social and physical environment involves two-way communication between the brain and the body and epigenetic adaptation (‘allostasis’) via mediators of the cardiovascular, immune, metabolic, neuroendocrine, and neural mechanisms. Chronic stress causes wear and tear on the brain and body (‘allostatic load and overload’), reflecting also the impact of health-damaging behaviours and lasting effects of early life experiences interacting with genetic predispositions. Hormonal and other mediators of allostasis promote adaptation in the short run but cause allostatic load/overload when they are overused or dysregulated. The brain is key because it determines what is threatening and the physiological and behavioural responses, while showing structural remodelling that affects its function. Besides pharmaceuticals, there are ‘top–down’ interventions, like physical activity, that engage ‘the wisdom of the body’ to change itself, as well as the impact of policies of government and business that encourage individuals to manage their own lives and promote increased ‘healthspan’.

Inflammatory and Epigenetic Pathways for Perinatal Depression

2015 ◽  
Vol 18 (3) ◽  
pp. 331-343 ◽  
Author(s):  
Lindsey Garfield ◽  
Herbert L. Mathews ◽  
Linda Witek Janusek
Keyword(s):  
Early Life ◽  
Infant Health ◽  
Perinatal Depression ◽  
Life Experiences ◽  
Perinatal Period ◽  
Early Life Adversity ◽  
Targeted Interventions ◽  
Increased Risk ◽  
History Of ◽  
The Impact

Depression during the perinatal period is common and can have adverse consequences for women and their children. Yet, the biobehavioral mechanisms underlying perinatal depression are not known. Adverse early life experiences increase the risk for adult depression. One potential mechanism by which this increased risk occurs is epigenetic embedding of inflammatory pathways. The purpose of this article is to propose a conceptual model that explicates the linkage between early life adversity and the risk for maternal depression. The model posits that early life adversity embeds a proinflammatory epigenetic signature (altered DNA methylation) that predisposes vulnerable women to depression during pregnancy and the postpartum period. As proposed, women with a history of early life adversity are more likely to exhibit higher levels of proinflammatory cytokines and lower levels of oxytocin in response to the demands of pregnancy and new motherhood, both of which are associated with the risk for perinatal depression. The model is designed to guide investigations into the biobehavioral basis for perinatal depression, with emphasis upon the impact of early life adversity. Testing this model will provide a better understanding of maternal depressive risk and improve identification of vulnerable women who would benefit from targeted interventions that can reduce the impact of perinatal depression on maternal–infant health.

scholarly journals Early-Life Adversity and Dysregulation of Adult Diurnal Cortisol Rhythm

2018 ◽  
Vol 74 (1) ◽  
pp. 160-169 ◽  
Author(s):  
Arun S Karlamangla ◽  
Sharon Stein Merkin ◽  
David M Almeida ◽  
Esther M Friedman ◽  
Jacqueline A Mogle ◽  
...  
Keyword(s):  
Early Life ◽  
Parental Education ◽  
Dynamic Range ◽  
Family Welfare ◽  
Cortisol Secretion ◽  
Early Life Adversity ◽  
Diurnal Cortisol ◽  
Welfare Dependence ◽  
The Impact ◽  
Diurnal Dynamic

Abstract Objectives Exposure to life stresses can lead to diminution in the capacity of stress response systems to mount a robust response to new challenges, with blunting of dynamic range—the spread between maximal attainable and minimal resting levels. We investigate the association between early-life adversity and the dynamic range of adult diurnal cortisol secretion. Method In 35- to 86-year-old adults, cortisol assayed from 16 saliva samples over 4 consecutive days was used to compute diurnal dynamic range and area under the curve (AUC). Economic adversity in childhood was indexed by recalled parental education, family welfare dependence, and perceived financial status; and childhood social adversity by parental separation, death, and abuse. Results Adjusted for age, gender, and race/ethnicity, both childhood adversities were strongly associated with smaller adult cortisol diurnal dynamic range, but not with AUC. The association with cortisol dynamic range was explained by adult social and economic variables. Discussion Early-life adversity appears to leave a long-term imprint on cortisol secretion dynamics, reducing diurnal dynamic range without increasing total secretion. This points to the importance of examining the adaptation capacity of physiological systems when studying the impact of early-life and chronic stresses on adult health.

scholarly journals Early life adversity alters normal sex-dependent developmental dynamics of DNA methylation

2016 ◽  
Vol 28 (4pt2) ◽  
pp. 1259-1272 ◽  
Author(s):  
Renaud Massart ◽  
Zsofia Nemoda ◽  
Matthew J. Suderman ◽  
Sheila Sutti ◽  
Angela M. Ruggiero ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Early Life ◽  
Maternal Separation ◽  
Methylation Profile ◽  
Early Life Adversity ◽  
Developmental Evolution ◽  
Dna Methylation Profile ◽  
Males And Females ◽  
The Difference ◽  
The Impact

AbstractStudies in rodents, nonhuman primates, and humans suggest that epigenetic processes mediate between early life experiences and adult phenotype. However, the normal evolution of epigenetic programs during child development, the effect of sex, and the impact of early life adversity on these trajectories are not well understood. This study mapped the genome-wide DNA methylation changes in CD3+ T lymphocytes from rhesus monkeys from postnatal day 14 through 2 years of age in both males and females and determined the impact of maternal deprivation on the DNA methylation profile. We show here that DNA methylation profiles evolve from birth to adolescence and are sex dependent. DNA methylation changes accompany imposed weaning, attenuating the difference between males and females. Maternal separation at birth alters the normal evolution of DNA methylation profiles and targets genes that are also affected by a later stage maternal separation, that is, weaning. Our results suggest that early life events dynamically interfere with the normal developmental evolution of the DNA methylation profile and that these changes are highly effected by sex.

scholarly journals Early Life Adversity and Polygenic Risk for High Fasting Insulin Are Associated With Childhood Impulsivity

2021 ◽  
Vol 15 ◽  
Author(s):  
Aashita Batra ◽  
Lawrence M. Chen ◽  
Zihan Wang ◽  
Carine Parent ◽  
Irina Pokhvisneva ◽  
...  
Keyword(s):  
Early Life ◽  
Genetic Background ◽  
Enrichment Analysis ◽  
Nervous System Development ◽  
Risk Scores ◽  
Fasting Insulin ◽  
Early Life Adversity ◽  
Polygenic Risk ◽  
Co Morbidity ◽  
The Impact

While the co-morbidity between metabolic and psychiatric behaviors is well-established, the mechanisms are poorly understood, and exposure to early life adversity (ELA) is a common developmental risk factor. ELA is associated with altered insulin sensitivity and poor behavioral inhibition throughout life, which seems to contribute to the development of metabolic and psychiatric disturbances in the long term. We hypothesize that a genetic background associated with higher fasting insulin interacts with ELA to influence the development of executive functions (e.g., impulsivity in young children). We calculated the polygenic risk scores (PRSs) from the genome-wide association study (GWAS) of fasting insulin at different thresholds and identified the subset of single nucleotide polymorphisms (SNPs) that best predicted peripheral insulin levels in children from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort [N = 467; pt– initial = 0.24 (10,296 SNPs), pt– refined = 0.05 (57 SNPs)]. We then calculated the refined PRS (rPRS) for fasting insulin at this specific threshold in the children from the Maternal Adversity, Vulnerability and Neurodevelopment (MAVAN) cohort and investigated its interaction effect with adversity on an impulsivity task applied at 36 months. We found a significant effect of interaction between fasting insulin rPRS and adversity exposure predicting impulsivity measured by the Snack Delay Task at 36 months [β = −0.329, p = 0.024], such that higher PRS [β = −0.551, p = 0.009] was linked to more impulsivity in individuals exposed to more adversity. Enrichment analysis (MetaCoreTM) of the SNPs that compose the fasting insulin rPRS at this threshold was significant for certain nervous system development processes including dopamine D2 receptor signaling. Additional enrichment analysis (FUMA) of the genes mapped from the SNPs in the fasting insulin rPRS showed enrichment with the accelerated cognitive decline GWAS. Therefore, the genetic background associated with risk for adult higher fasting insulin moderates the impact of early adversity on childhood impulsivity.

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