Life Events Shape Us

2018 ◽  
Author(s):  
Jack M. Gorman
Keyword(s):  
Life Events ◽  
Brain Function ◽  
Early Life ◽  
Life Experiences ◽  
Regulation Of Gene Expression ◽  
Laboratory Animals ◽  
Early Life Adversity ◽  
Psychiatric Conditions ◽  
The 1960S ◽  
The Brain

Psychiatry downplayed the importance of life events in causing mental illness from the 1960s on, favoring a view that all disorders except one are the result of abnormal genes affecting chemical processes in the brain. Studying the exception, posttraumatic stress disorder (PTSD), when it was defined in 1980 helped lead to renewed recognition that early life adversity is central to all psychiatric conditions. At the same time, neuroscientists showed that early life experiences are capable of changing life-long behavior and brain function in laboratory animals. One mechanism by which this occurs is through the epigenetic regulation of gene expression. Epigenetics is the way that the expression levels of genes are controlled without changing the underlying genetic code. Epigenetics is an attractive way of understanding how individual life experiences are translated in the brain into each person’s unique set of emotions, behaviors, abilities, and risks for psychiatric abnormalities.

scholarly journals Repeated Three-Hour Maternal Separation Induces Depression-Like Behavior and Affects the Expression of Hippocampal Plasticity-Related Proteins in C57BL/6N Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Yaoyao Bian ◽  
Lili Yang ◽  
Zhongli Wang ◽  
Qing Wang ◽  
Li Zeng ◽  
...  
Keyword(s):  
Early Life ◽  
Maternal Separation ◽  
Forced Swimming Test ◽  
Life Experiences ◽  
Tail Suspension Test ◽  
Early Life Stages ◽  
Early Life Adversity ◽  
Swimming Test ◽  
Related Proteins ◽  
The Brain

Adverse early life experiences can negatively affect behaviors later in life. Maternal separation (MS) has been extensively investigated in animal models in the adult phase of MS. The study aimed to explore the mechanism by which MS negatively affects C57BL/6N mice, especially the effects caused by MS in the early phase. Early life adversity especially can alter plasticity functions. To determine whether adverse early life experiences induce changes in plasticity in the brain hippocampus, we established an MS paradigm. In this research, the mice were treated with mild (15 min, MS15) or prolonged (180 min, MS180) maternal separation from postnatal day 2 to postnatal day 21. The mice underwent a forced swimming test, a tail suspension test, and an open field test, respectively. Afterward, the mice were sacrificed on postnatal day 31 to determine the effects of MS on early life stages. Results implied that MS induces depression-like behavior and the effects may be mediated partly by interfering with the hippocampal GSK-3β-CREB signaling pathway and by reducing the levels of some plasticity-related proteins.

scholarly journals Effects of early life adversity on immediate early gene expression: Systematic review and 3-level meta-analysis of rodent studies

PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0253406
Author(s):  
Heike Schuler ◽  
Valeria Bonapersona ◽  
Marian Joëls ◽  
R. Angela Sarabdjitsingh
Keyword(s):  
Systematic Review ◽  
Life Events ◽  
Early Life ◽  
Current Knowledge ◽  
Early Gene ◽  
Immediate Early ◽  
Early Life Adversity ◽  
Functional Changes ◽  
Potential Marker ◽  
The Brain

Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA (alteration of maternal care) on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced additional hits. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naïve, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.

scholarly journals Effects of early life adversity on immediate early gene expression: systematic review and 3-level meta-analysis of rodent studies

2021 ◽  
Author(s):  
Heike Schuler ◽  
Valeria Bonapersona ◽  
Marian Joels ◽  
Ratna Angela Sarabdjitsingh
Keyword(s):  
Systematic Review ◽  
Life Events ◽  
Early Life ◽  
Negative Life Events ◽  
Early Gene ◽  
Immediate Early ◽  
Early Life Adversity ◽  
Functional Changes ◽  
Potential Marker ◽  
The Brain

Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced multiple negative life events. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naive, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.

scholarly journals The differential calibration of the HPA axis as a function of trauma versus adversity: A systematic review and p-curve meta-analyses

2021 ◽  
Author(s):  
Niki H. Kamkar ◽  
Cassandra J Lowe ◽  
J. Bruce Morton
Keyword(s):  
Hpa Axis ◽  
Early Life ◽  
Life Experiences ◽  
Curve Analysis ◽  
Early Life Adversity ◽  
Cortisol Reactivity ◽  
Evidential Value ◽  
Dsm 5 ◽  
Meta Analyses ◽  
The Relationship

Although there is an abundance of evidence linking the function of the hypothalamic-pituitary-adrenal (HPA) axis to adverse early-life experiences, the precise nature of the association remains unclear. Some evidence suggests early-life adversity leads to cortisol hyper-reactivity, while other evidence suggests adversity leads to cortisol hypo-reactivity. Here, we distinguish between trauma and adversity, and use p-curves to interrogate the conflicting literature. In Study 1, trauma was operationalized according to DSM-5 criteria; the p-curve analysis included 68 articles and revealed that the literature reporting associations between trauma and blunted cortisol reactivity contains evidential value. Study 2 examined the relationship between adversity and cortisol reactivity. Thirty articles were included in the analysis, and p-curve demonstrated that adversity is related to heightened cortisol reactivity. These results support an inverted U-shaped function relating severity of adversity and cortisol reactivity, and underscore the importance of distinguishing between “trauma” and “adversity”.

Early Life Adversity and Clinical Intimate Partner Violence in Adulthood: The Mediating Role of Interpersonal Conflict in Adolescence

2021 ◽  
pp. 088626052110572
Author(s):  
Jordan L. Thomas ◽  
Danielle Keenan-Miller ◽  
Jennifer A. Sumner ◽  
Constance Hammen
Keyword(s):  
Intimate Partner Violence ◽  
Conflict Resolution ◽  
Life Events ◽  
Partner Violence ◽  
Early Life ◽  
Interpersonal Conflict ◽  
Intimate Partner ◽  
Relationship Violence ◽  
Early Life Adversity ◽  
Prevention And Intervention

Intimate partner violence (IPV) is associated with adverse outcomes for both victims and perpetrators, though there is significant heterogeneity in manifestations of relationship violence. A growing amount of research has focused on elucidating predictors of clinical IPV—defined as severe violence involving institutional or medical intervention due to actual or potential injury—so as to better understand potential prevention and intervention targets. Early life adversity (ELA) is associated with IPV in adulthood, yet this literature focuses on discrete, retrospectively reported adversities (e.g., physical abuse and neglect) and has yet to consider clinical IPV as an outcome. Little is known about if and how broadly adverse early environments may confer risk for this specific form of relationship violence. We investigated associations between exposure to ELA prior to age five and clinical IPV victimization and perpetration by age 20 in a longitudinal, community-based sample of men and women in Australia ( N = 588). Early life adversity was prospectively indexed by maternal reports of financial hardship, child chronic illness, maternal stressful life events, maternal depressive symptoms, parental discord, and parental separation. Youth interpersonal conflict life events at age 15—an interviewer-rated assessment of episodic stressors involving conflict across relationships in mid-adolescence—was tested as a potential mediator for both victims and perpetrators. Among women, ELA predicted IPV victimization and perpetration, and interpersonal conflict life events partially mediated the link between ELA and victimization, but not perpetration. Neither ELA nor interpersonal conflict life events predicted victimization or perpetration among men. Women exposed to ELA are at-risk for conflictual interpersonal relationships later in life, including violent intimate relationships, and deficits in conflict resolution skills may be one mechanism through which ELA leads to IPV victimization among this subgroup. Violence prevention and intervention efforts should target interpersonal skills, including conflict resolution, among women and girls exposed to adverse early environments.

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’.

scholarly journals Effects of Early-Life Stress on the Brain and Behaviors: Implications of Early Maternal Separation in Rodents

2020 ◽  
Vol 21 (19) ◽  
pp. 7212
Author(s):  
Mayumi Nishi
Keyword(s):  
Child Abuse ◽  
Hpa Axis ◽  
Brain Function ◽  
Life Stress ◽  
Early Life ◽  
Maternal Separation ◽  
Early Life Stress ◽  
Emotional Behavior ◽  
Neural Basis ◽  
The Brain

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.

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 Paediatrician’s guide to epigenetics

2019 ◽  
Vol 104 (3) ◽  
pp. 297-301 ◽  
Author(s):  
Lauren Byrne ◽  
Amanda Jane Drake
Keyword(s):  
Life Events ◽  
Early Life ◽  
Normal Development ◽  
Disease Risk ◽  
Regulation Of Gene Expression ◽  
High Quality ◽  
High Quality Research ◽  
Growth Development ◽  
Underlying Mechanisms ◽  
Early Life Events

Epigenetic regulation of gene expression is critical for normal development. Dysregulation of the epigenome can lead to the development and progression of a number of diseases relevant to paediatricians, including disorders of genomic imprinting and malignancies. It has long been recognised that early life events have implications for future disease risk, and epigenetic modifications may play a role in this, although further high-quality research is needed to better understand the underlying mechanisms. Research in the field of epigenetics will contribute to a greater understanding of growth, development and disease; however, paediatricians need to be able to interpret such research critically, in order to use the potential advances brought about through epigenetic studies while appreciating their limitations.

scholarly journals Effects of early life adversity on meningeal mast cells and proinflammatory gene expression in male and female Mus musculus

2021 ◽  
Author(s):  
Natalia Duque-Wilckens ◽  
Erika Sarno ◽  
Robby E. Teis ◽  
Frauke Stoelting ◽  
Sonia Khalid ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mast Cell ◽  
Immune System ◽  
Mast Cells ◽  
Early Life ◽  
Inflammatory Markers ◽  
Disease Susceptibility ◽  
Early Life Adversity ◽  
Male And Female ◽  
The Brain

ABSTRACTExposure to early life adversity (ELA) in the form of physical and/or psychological abuse or neglect increases the risk of developing psychiatric and inflammatory disorders later in life. It has been hypothesized that exposure to ELA results in persistent, low grade inflammation that leads to increased disease susceptibility by amplifying the crosstalk between stress-processing brain networks and the immune system, but the mechanisms remain largely unexplored. The meninges, a layer of three overlapping membranes that surround the central nervous system (CNS)- duramater, arachnoid, and piamater – possess unique features that allow them to play a key role in coordinating immune trafficking between the brain and the peripheral immune system. These include a network of lymphatic vessels that carry cerebrospinal fluid from the brain to the deep cervical lymph nodes, fenestrated blood vessels that allow the passage of molecules from blood to the CNS, and a rich population of resident mast cells, master regulators of the immune system. Using a mouse model of ELA consisting of neonatal maternal separation plus early weaning (NMSEW), we sought to explore the effects of ELA on duramater mast cell histology and expression of inflammatory markers in male and female C57Bl/6 mice. We found that mast cell number, activation level, and relative expression of pseudopodia differ across duramater regions, and that NMSEW exerts region-specific effects on mast cells in males and females. Using gene expression analyses, we next found that NMSEW increases the expression of inflammatory markers in the duramater of females but not males, and that this is prevented by pharmacological inhibition of mast cells with ketotifen. Together, our results show that ELA drives sex-specific, long-lasting effects on the duramater mast cell population and immune-related gene expression, suggesting that the long-lasting effects of ELA on disease susceptibility could be partly mediated by meningeal function.

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