Histamine-dependent interactions between mast cells, glia, and neurons are altered following early-life adversity in mice and humans

Early-life adversity places an individual at risk for developing functional gastrointestinal disorders later in life through unknown mechanisms. Here, we show that interactions between mast cells and glia are disrupted by early-life stress in mice and that histamine is a potential mediator of mast cell-glial interactions.

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

Proceedings of The Nutrition Society ◽

10.1017/s0029665119000958 ◽

2019 ◽

Vol 79 (1) ◽

pp. 113-132 ◽

Cited By ~ 3

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.

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

10.1101/2021.09.17.460793 ◽

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

10.31234/osf.io/5kt6z ◽

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.

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The 5-HTTLPR genotype, early life adversity and cortisol responsivity to psychosocial stress in women

BJPsych Open ◽

10.1192/bjo.2018.23 ◽

2018 ◽

Vol 4 (4) ◽

pp. 180-185 ◽

Cited By ~ 2

Author(s):

Jurate Aleknaviciute ◽

Joke H. M. Tulen ◽

Yolanda B. de Rijke ◽

Mark van der Kroeg ◽

Cornelis G. Kooiman ◽

...

Keyword(s):

Childhood Maltreatment ◽

Life Stress ◽

Early Life ◽

Psychosocial Stress ◽

Social Stress ◽

Stress Test ◽

Early Life Stress ◽

Trier Social Stress Test ◽

Early Life Adversity ◽

Personality Psychopathology

BackgroundThe serotonin transporter gene-linked polymorphic region (5-HTTLPR) has previously been associated with hypothalamus–pituitary–adrenal axis function. Moreover, it has been suggested that this association is moderated by an interaction with stressful life experiences.AimsTo investigate the moderation of cortisol response to psychosocial stress by 5-HTTLPR genotype, either directly or through an interaction with early life stress.MethodA total of 151 women, 85 of which had personality psychopathology, performed the Trier Social Stress Test while cortisol responsivity was assessed.ResultsThe results demonstrate a main effect of genotype on cortisol responsivity. Women carrying two copies of the long version of 5-HTTLPR exhibited stronger cortisol responses to psychosocial stress than women with at least one copy of the short allele (P = 0.03). However, the proportion of the variance of stress-induced cortisol responsivity explained by 5-HTTLPR genotype was not further strengthened by including early life adversity as a moderating factor (P = 0.52).ConclusionsOur results highlight the need to clarify gender-specific biological factors influencing the serotonergic system. Furthermore, our results suggest that childhood maltreatment, specifically during the first 15 years of life, is unlikely to exert a moderating influence of large effect on the relationship between the 5-HTTLPR genotype and cortisol responsivity to psychosocial stress.Declaration of interestNone.

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Methylation of the glucocorticoid receptor promoter in children: Links with parents as teachers, early life stress, and behavior problems

Development and Psychopathology ◽

10.1017/s0954579420001984 ◽

2020 ◽

pp. 1-13

Author(s):

Elena Silvia Gardini ◽

Simone Schaub ◽

Alex Neuhauser ◽

Erich Ramseier ◽

Arna Villiger ◽

...

Keyword(s):

At Risk ◽

Behavior Problems ◽

Glucocorticoid Receptor ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Parents As Teachers ◽

Cpg Site ◽

Glucocorticoid Receptor Gene ◽

And Behavior

Abstract The present study examined the effect of early life stress (ELS) on the glucocorticoid receptor gene (NR3C1) methylation, the associations between NR3C1 methylation and behavior problems, and the effect of the program Parents as Teachers (PAT) on NR3C1 methylation. Participants included 132 children, 72 assigned to the PAT intervention group and 60 to the PAT control group. Children were aged 3 years, and were living in psychosocially at-risk families. We assessed NR3C1 methylation of the NGFI-A binding regions of exon 1F via sodium bisulfite sequencing from saliva DNA. Results indicated that (a) children living in families receiving PAT had decreased methylation at one single cytosine–guanine dinucleotides (CpG) site; (b) current maternal depressive symptoms and parental disagreement were predictive of increased methylation of mean NGFI-A and three single CpG sites; and (c) increased methylation of mean NGFI-A and one single CpG site was significantly associated with increased internalizing and externalizing symptoms. In addition, mean NGFI-A was a mediator of the association between parental disagreement and a child's affective problems. These results suggest that PAT may contribute to preventing NR3C1 methylation in preschool children living in psychosocially at-risk situations, and confirm previous findings on the associations between ELS, NR3C1 methylation, and behavior problems.

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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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Sex differences in the effects of early life stress exposure on mast cells in the developing rat brain

Hormones and Behavior ◽

10.1016/j.yhbeh.2019.04.012 ◽

2019 ◽

Vol 113 ◽

pp. 76-84 ◽

Cited By ~ 4

Author(s):

Aarohi Joshi ◽

Chloe E. Page ◽

Mark Damante ◽

Courtney N. Dye ◽

Achikam Haim ◽

...

Keyword(s):

Sex Differences ◽

Mast Cells ◽

Rat Brain ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stress Exposure ◽

Developing Rat

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Positive memory specificity reduces adolescent vulnerability to depression

10.1101/329409 ◽

2018 ◽

Cited By ~ 1

Author(s):

Adrian Dahl Askelund ◽

Susanne Schweizer ◽

Ian M. Goodyer ◽

Anne-Laura van Harmelen

Keyword(s):

At Risk ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Stress System ◽

Low Mood ◽

Memory Specificity ◽

Morning Cortisol ◽

One Year ◽

Positive Memories

Depression is the leading cause of ill health and disability worldwide1. A known risk factor of depression is exposure to early life stress2. Such early stress exposure has been proposed to sensitise the maturing psychophysiological stress system to later life stress3. Activating positive memories dampens acute stress responses with resultant lower cortisol response and improved mood in humans4 and reduced depression-like behaviour in mice5. It is unknown whether recalling positive memories similarly reduces adolescent vulnerability to depression. Here we used path modelling to examine the effects of positive autobiographical memory specificity on later morning cortisol and negative self-cognitions during low mood in adolescents at risk for depression due to early life stress (n = 427, age: 14 years)6. We found that experimentally assessed positive but not negative memory specificity was associated with lower morning cortisol and less negative self-cognitions during low mood one year later. Moderated mediation analyses demonstrated that positive memory specificity reduced later depressive symptoms through lowering negative self-cognitions in response to negative life events reported in the one-year interval. Positive memory specificity actively dampened the negative effect of stressors over time, thereby operating as a resilience factor reducing the risk of subsequent depression7. These findings suggest that developing methods to improve positive memory specificity in at-risk adolescents may counteract vulnerability to depression.

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The Effect of MAOA and Stress Sensitivity on Crime and Delinquency: A Replication Study

Journal of Contemporary Criminal Justice ◽

10.1177/1043986218770001 ◽

2018 ◽

Vol 34 (3) ◽

pp. 336-353 ◽

Cited By ~ 3

Author(s):

Christa C. Christ ◽

Joseph A. Schwartz ◽

Scott F. Stoltenberg ◽

Jonathan R. Brauer ◽

Jukka Savolainen

Keyword(s):

Life Stress ◽

Early Life ◽

Interactive Effect ◽

Early Life Stress ◽

Stress Sensitivity ◽

Long Term Effects ◽

Early Life Adversity ◽

Increased Risk ◽

Crime And Delinquency ◽

Meta Analyses

Across several meta-analyses, MAOA-uVNTR genotype has been associated with an increased risk for antisocial behavior among males who experienced early life adversity. Subsequently, early life stress and genetic susceptibility may have long-term effects on stress sensitivity later in life. In support of this assumption, a recent study found evidence, in two independent samples, for a three-way interaction effect (cG × E × E) such that proximate stress was found to moderate the interactive effect of MAOA-uVNTR and distal stress on crime and delinquency among males. In light of recent developments in cG × E research, we attempted to replicate these findings in an independent sample of university students. Our results failed to support any cG × E or cG × E × E effects reported in the original study. Implications of a failed replication and general concerns for future cG × E research are discussed.

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Mindfulness interventions for offsetting health risk following early life stress: Promising directions

10.31231/osf.io/r6z4v ◽

2021 ◽

Author(s):

Emily K Lindsay

Keyword(s):

At Risk ◽

Health Risk ◽

Health Outcomes ◽

Physical Health ◽

Life Stress ◽

Early Life ◽

Disease Risk ◽

Early Life Stress ◽

Present Moment ◽

At Risk Populations

Early life stress (ELS), common to childhood maltreatment, socioeconomic disadvantage, and racial discrimination, is thought to create a proinflammatory phenotype that increases risk for poor health in adulthood. Systemic change is needed to address the root causes of ELS, but a substantial number of adults are already at increased health risk by virtue of ELS exposure. Interventions that target stress pathways have the potential to interrupt the trajectory from ELS to inflammatory disease risk in adulthood. Mindfulness-based interventions (MBIs), which train acceptance toward present-moment experience, have shown promise for reducing stress and improving a variety of stress-sensitive health outcomes. Although MBIs have primarily been conducted in more advantaged populations, evidence suggests that they may be uniquely effective for improving mental health and health-related quality of life among those with a history of ELS. Whether these effects extend to physical health remains unknown. To shed light on this question, I review evidence that MBIs influence inflammatory markers in at-risk samples, explore the promise of MBIs for improving stress-related health outcomes in diverse at-risk populations, and describe adaptations to MBIs that may increase their acceptability and efficacy in populations exposed to ELS. This prior work sets the stage for well-controlled RCTs to evaluate whether MBIs influence stress and inflammatory pathways among those exposed to ELS and for pragmatic and implementation trials focused on disseminating MBIs to reach these at-risk populations. Overall, the evidence assembled here shows the potential of MBIs for offsetting physical health risk related to ELS.

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