Posttraumatic stress disorder, alone or additively with early life adversity, is associated with obesity and cardiometabolic risk.

PubMed

Farr, O M; Ko, B-J; Joung, K E; Zaichenko, L; Usher, N; Tsoukas, M; Thakkar, B; Davis, C R; Crowell, J A; Mantzoros, C S

2015-05-01

There is some evidence that posttraumatic stress disorder (PTSD) and early life adversity may influence metabolic outcomes such as obesity, diabetes, and cardiovascular disease. However, whether and how these interact is not clear. We analyzed data from a cross-sectional and longitudinal study to determine how PTSD severity influences obesity, insulin sensitivity, and key measures and biomarkers of cardiovascular risk. We then looked at how PTSD and early life adversity may interact to impact these same outcomes. PTSD severity is associated with increasing risk of obesity, diabetes, and cardiovascular disease, with higher symptoms correlating with higher values of BMI, leptin, fibrinogen, and blood pressure, and lower values of insulin sensitivity. PTSD and early life adversity have an additive effect on these metabolic outcomes. The longitudinal study confirmed findings from the cross sectional study and showed that fat mass, leptin, CRP, sICAM-1, and sTNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. Copyright © 2015 Elsevier B.V. All rights reserved.

Association of BDNF Val66Met Polymorphism and Brain BDNF Levels with Major Depression and Suicide.

PubMed

Youssef, Mariam M; Underwood, Mark D; Huang, Yung-Yu; Hsiung, Shu-Chi; Liu, Yan; Simpson, Norman R; Bakalian, Mihran J; Rosoklija, Gorazd B; Dwork, Andrew J; Arango, Victoria; Mann, J John

2018-06-01

Brain-derived neurotrophic factor is implicated in the pathophysiology of major depressive disorder and suicide. Both are partly caused by early life adversity, which reduces brain-derived neurotrophic factor protein levels. This study examines the association of brain-derived neurotrophic factor Val66Met polymorphism and brain brain-derived neurotrophic factor levels with depression and suicide. We hypothesized that both major depressive disorder and early life adversity would be associated with the Met allele and lower brain brain-derived neurotrophic factor levels. Such an association would be consistent with low brain-derived neurotrophic factor mediating the effect of early life adversity on adulthood suicide and major depressive disorder. Brain-derived neurotrophic factor Val66Met polymorphism was genotyped in postmortem brains of 37 suicide decedents and 53 nonsuicides. Additionally, brain-derived neurotrophic factor protein levels were determined by Western blot in dorsolateral prefrontal cortex (Brodmann area 9), anterior cingulate cortex (Brodmann area 24), caudal brainstem, and rostral brainstem. The relationships between these measures and major depressive disorder, death by suicide, and reported early life adversity were examined. Subjects with the Met allele had an increased risk for depression. Depressed patients also have lower brain-derived neurotrophic factor levels in anterior cingulate cortex and caudal brainstem compared with nondepressed subjects. No effect of history of suicide death or early life adversity was observed with genotype, but lower brain-derived neurotrophic factor levels in the anterior cingulate cortex were found in subjects who had been exposed to early life adversity and/or died by suicide compared with nonsuicide decedents and no reported early life adversity. This study provides further evidence implicating low brain brain-derived neurotrophic factor and the brain-derived neurotrophic factor Met allele in major depression risk. Future studies should seek to determine how altered brain-derived neurotrophic factor expression contributes to depression and suicide.

Does the Size of the Effect of Adverse Events at High Ages on Daily-Life Physical Functioning Depend on the Economic Conditions Around Birth?

PubMed

Scholte, Robert; van den Berg, Gerard J; Lindeboom, Maarten; Deeg, Dorly J H

2017-01-01

This paper considers determinants of physical functional limitations in daily-life activities at high ages. Specifically, we quantify the extent to which the impact of adverse life events on this outcome is larger in case of exposure to adverse economic conditions early in life. Adverse life events include bereavement, severe illness in the family, and the onset of chronic diseases. We use a longitudinal data set of individuals born in the first decades of the 20th century. The business cycle around birth is used as an indicator of economic conditions early in life. We find that the extent to which functional limitations suffer from the onset of chronic diseases is larger if the individual was born in a recession. The long-run effect of economic conditions early in life on functional limitations at high ages runs primarily via this life event. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Parenting begets parenting: A neurobiological perspective on early adversity and the transmission of parenting styles across generations.

PubMed

Lomanowska, A M; Boivin, M; Hertzman, C; Fleming, A S

2017-02-07

The developing brains of young children are highly sensitive to input from their social environment. Nurturing social experience during this time promotes the acquisition of social and cognitive skills and emotional competencies. However, many young children are confronted with obstacles to healthy development, including poverty, inappropriate care, and violence, and their enhanced sensitivity to the social environment means that they are highly susceptible to these adverse childhood experiences. One source of social adversity in early life can stem from parenting that is harsh, inconsistent, non-sensitive or hostile. Parenting is considered to be the cornerstone of early socio-emotional development and an adverse parenting style is associated with adjustment problems and a higher risk of developing mood and behavioral disorders. Importantly, there is a growing literature showing that an important predictor of parenting behavior is how parents, especially mothers, were parented themselves. In this review, we examine how adversity in early-life affects mothering behavior in later-life and how these effects may be perpetuated inter-generationally. Relying on studies in humans and animal models, we consider evidence for the intergenerational transmission of mothering styles. We then describe the psychological underpinnings of mothering, including responsiveness to young, executive function and affect, as well as the physiological mediators of mothering behavior, including hormones, brain regions and neurotransmitters, and we consider how development in these relevant domains may be affected by adversity experienced in early life. Finally, we explore how genes and early experience interact to predict mothering behavior, including the involvement of epigenetic mechanisms. Understanding how adverse parenting begets adverse parenting in the next generation is critical for designing interventions aimed at preventing this intergenerational cycle of early adversity. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Impact of Early Life Adversity on Reward Processing in Young Adults: EEG-fMRI Results from a Prospective Study over 25 Years

PubMed Central

Boecker, Regina; Holz, Nathalie E.; Buchmann, Arlette F.; Blomeyer, Dorothea; Plichta, Michael M.; Wolf, Isabella; Baumeister, Sarah; Meyer-Lindenberg, Andreas; Banaschewski, Tobias

2014-01-01

Several lines of evidence have implicated the mesolimbic dopamine reward pathway in altered brain function resulting from exposure to early adversity. The present study examined the impact of early life adversity on different stages of neuronal reward processing later in life and their association with a related behavioral phenotype, i.e. attention deficit/hyperactivity disorder (ADHD). 162 healthy young adults (mean age = 24.4 years; 58% female) from an epidemiological cohort study followed since birth participated in a simultaneous EEG-fMRI study using a monetary incentive delay task. Early life adversity according to an early family adversity index (EFA) and lifetime ADHD symptoms were assessed using standardized parent interviews conducted at the offspring's age of 3 months and between 2 and 15 years, respectively. fMRI region-of-interest analysis revealed a significant effect of EFA during reward anticipation in reward-related areas (i.e. ventral striatum, putamen, thalamus), indicating decreased activation when EFA increased. EEG analysis demonstrated a similar effect for the contingent negative variation (CNV), with the CNV decreasing with the level of EFA. In contrast, during reward delivery, activation of the bilateral insula, right pallidum and bilateral putamen increased with EFA. There was a significant association of lifetime ADHD symptoms with lower activation in the left ventral striatum during reward anticipation and higher activation in the right insula during reward delivery. The present findings indicate a differential long-term impact of early life adversity on reward processing, implicating hyporesponsiveness during reward anticipation and hyperresponsiveness when receiving a reward. Moreover, a similar activation pattern related to lifetime ADHD suggests that the impact of early life stress on ADHD may possibly be mediated by a dysfunctional reward pathway. PMID:25118701

Contributions of early adversity to pro-inflammatory phenotype in infancy: the buffer provided by attachment security.

PubMed

Measelle, Jeffrey R; Ablow, Jennifer C

2018-02-01

Adversity early in life is associated with systemic inflammation by adolescence and beyond. At present, few studies have investigated the associations between different forms of adversity and inflammation during infancy, making it difficult to specify the origins of disease vulnerability. This study examined the association between multiple forms of early adversity - socioeconomic status disadvantage, familial stress, maternal depression, and security of attachment - and individual differences in a composite measure of pro-inflammatory cytokines (IL-1β, IL-6, IL-8, and tumor necrosis factor-alpha) and the inflammatory protein C-reactive protein that were collected via saliva when (n = 49) children were 17 months old. In addition to gauging the direct effects of adversity, we also tested the hypothesis that infants' attachment relationship with their mother might buffer infants against the immunologic effects of early adversity. Results show that familial stress, maternal depression, and security of attachment were directly associated with infant salivary inflammation and that attachment status moderated the effect of maternal depression. The findings suggest that exposure to certain forms of adversity very early in life may engender a pro-inflammatory phenotype with possible life-long implications for health.

Early Life Conditions, Adverse Life Events, and Chewing Ability at Middle and Later Adulthood

PubMed Central

Watt, Richard G.; Tsakos, Georgios

2014-01-01

Objectives. We sought to determine the extent to which early life conditions and adverse life events impact chewing ability in middle and later adulthood. Methods. Secondary analyses were conducted based on data from waves 2 and 3 of the Survey of Health, Ageing, and Retirement in Europe (SHARE), collected in the years 2006 to 2009 and encompassing information on current chewing ability and the life history of persons aged 50 years or older from 13 European countries. Logistic regression models were estimated with sequential inclusion of explanatory variables representing living conditions in childhood and adverse life events. Results. After controlling for current determinants of chewing ability at age 50 years or older, certain childhood and later life course socioeconomic, behavioral, and cognitive factors became evident as correlates of chewing ability at age 50 years or older. Specifically, childhood financial hardship was identified as an early life predictor of chewing ability at age 50 years or older (odds ratio = 1.58; 95% confidence interval = 1.22, 2.06). Conclusions. Findings suggest a potential enduring impact of early life conditions and adverse life events on oral health in middle and later adulthood and are relevant for public health decision-makers who design strategies for optimal oral health. PMID:24625140

Non-Verbal Reasoning Ability and Academic Achievement as Moderators of the Relation between Adverse Life Events and Emotional and Behavioural Problems in Early Adolescence: The Importance of Moderator and Outcome Specificity

ERIC Educational Resources Information Center

Flouri, Eirini; Tzavidis, Nikos

2011-01-01

This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural…

Modeling life course pathways from adverse childhood experiences to adult mental health.

PubMed

Jones, Tiffany M; Nurius, Paula; Song, Chiho; Fleming, Christopher M

2018-06-01

Although the association between adverse childhood experiences (ACEs) and adult mental health is becoming well established, less is known about the complex and multiple pathways through which ACEs exert their influence. Growing evidence suggests that adversity early in life conveys not only early impacts, but also augments risk of stress-related life course cascades that continue to undermine health. The present study aims to test pathways of stress proliferation and stress embodiment processes linking ACEs to mental health impairment in adulthood. Data are from the 2011 Behavioral Risk Factor Surveillance Survey, a representative sample of Washington State adults ages 18 and over (N = 14,001). Structural equation modeling allowed for testing of direct and indirect effects from ACEs though low income status, experiences of adversity in adulthood, and social support. The model demonstrated that adult low income, social support and adult adversity are in fact conduits through which ACEs exert their influence on mental health impairment in adulthood. Significant indirect pathways through these variables supported hypotheses that the effect of ACEs is carried through these variables. This is among the first models that demonstrates multiple stress-related life course pathways through which early life adversity compromises adult mental health. Discussion elaborates multiple service system opportunities for intervention in early and later life to interrupt direct and indirect pathways of ACE effects. Copyright © 2018 Elsevier Ltd. All rights reserved.

Kindling of Life Stress in Bipolar Disorder: Effects of Early Adversity.

PubMed

Shapero, Benjamin G; Weiss, Rachel B; Burke, Taylor A; Boland, Elaine M; Abramson, Lyn Y; Alloy, Lauren B

2017-05-01

Most theoretical frameworks regarding the role of life stress in bipolar disorders (BD) do not incorporate the possibility of a changing relationship between psychosocial context and episode initiation across the course of the disorder. The kindling hypothesis theorizes that over the longitudinal course of recurrent affective disorders, the relationship between major life stressors and episode initiation declines (Post, 1992). The present study aimed to test an extension of the kindling hypothesis in BD by examining the effect of early life adversity on the relationship between proximal life events and prospectively assessed mood episodes. Data from 145 bipolar participants (59.3% female, 75.2% Caucasian, and mean age of 20.19 years; SD = 1.75 years) were collected as part of the Temple-Wisconsin Longitudinal Investigation of Bipolar Spectrum Project (112 Bipolar II; 33 Cyclothymic disorder). Participants completed a self-report measure of early adversity at baseline and interview-assessed mood episodes and life events at regular 4-month follow-ups. Results indicate that early childhood adversity sensitized bipolar participants to the effects of recent stressors only for depressive episodes and not hypomanic episodes within BD. This was particularly the case with minor negative events. The current study extends prior research examining the kindling model in BD using a methodologically rigorous assessment of life stressors and mood episode occurrence. Clinicians should assess experiences of early adversity in individuals with BD as it may impact reactivity to developing depressive episodes in response to future stressors. Copyright © 2017. Published by Elsevier Ltd.

Early Life Adversity as a Predictor of Sense of Purpose during Adulthood

ERIC Educational Resources Information Center

Hill, Patrick L.; Turiano, Nicholas A.; Burrow, Anthony L.

2018-01-01

Feeling a sense of purpose in life appears to hold consistent benefits for positive aging and well-being. As such, it is important to consider the potential factors that promote or hinder the development of purposefulness over the lifespan. For instance, it remains unclear whether early life experiences, particularly adverse ones, may hold lasting…

Fish early life stage: Developing AOPs to support targeted reduction and replacement

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse chronic toxicity outcomes (e.g., impacts on growth and survival). Development and characterization of adverse outcome pathways (AOPs) related...

Neurobiological consequences of childhood trauma.

PubMed

Nemeroff, Charles B

2004-01-01

There is considerable evidence to suggest that adverse early-life experiences have a profound effect on the developing brain. Neurobiological changes that occur in response to untoward early-life stress can lead to lifelong psychiatric sequelae. Children who are exposed to sexual or physical abuse or the death of a parent are at higher risk for development of depressive and anxiety disorders later in life. Preclinical and clinical studies have shown that repeated early-life stress leads to alterations in central neurobiological systems, particularly in the corticotropin-releasing factor system, leading to increased responsiveness to stress. Clearly, exposure to early-life stressors leads to neurobiological changes that increase the risk of psychopathology in both children and adults. Identification of the neurobiological substrates that are affected by adverse experiences in early life should lead to the development of more effective treatments for these disorders. The preclinical and clinical studies evaluating the consequences of early-life stress are reviewed.

Early life adversity influences stress response association with smoking relapse.

PubMed

al'Absi, Mustafa; Lemieux, Andrine; Westra, Ruth; Allen, Sharon

2017-11-01

We examined the hypothesis that stress-related blunting of cortisol in smokers is particularly pronounced in those with a history of severe life adversity. The two aims of this study were first to examine hormonal, craving, and withdrawal symptoms during ad libitum smoking and after the first 24 h of abstinence in smokers who experienced high or low levels of adversity. Second, we sought to examine the relationship between adversity and hypothalamic-pituitary-adrenal (HPA) hormones to predict relapse during the first month of a smoking cessation attempt. Hormonal and self-report measures were collected from 103 smokers (49 women) during ad libitum smoking and after the first 24 h of abstinence. HPA hormones were measured during baseline rest and in response to acute stress in both conditions. All smokers were interested in smoking cessation, and we prospectively used stress response measures to predict relapse during the first 4 weeks of the smoking cessation attempt. The results showed that high adversity was associated with higher distress and smoking withdrawal symptoms. High level of early life adversity was associated with elevated HPA activity, which was found in both salivary and plasma cortisol. Enhanced adrenocorticotropic hormone (ACTH) stress response was evident in high-adversity but not in low-adversity relapsers. This study demonstrated that early life adversity is associated with stress-related HPA responses. The study also demonstrated that, among smokers who experienced a high level of life adversity, heightened ACTH and cortisol responses were linked with increased risk for smoking relapse.

Discovering and annotating fish early life-stage (FELS) adverse outcome pathways: Putting the research strategy into practice

EPA Science Inventory

In May 2012, a HESI-sponsored expert workshop yielded a proposed research strategy for systematically discovering, characterizing, and annotating fish early life-stage (FELS) adverse outcome pathways (AOPs) as well as prioritizing AOP development in light of current restrictions ...

Initial investigation of a hypothesized link between thyroid peroxidase inhibition and fish early-life stage toxicity

EPA Science Inventory

There is an interest in developing alternatives to the fish early-life stage (FELS) test (OECD test guideline 210), for predicting adverse outcomes (e.g., impacts on growth and survival) using less resource-intensive methods. Development and characterization of adverse outcome pa...

Developmental Constraints in a Wild Primate

PubMed Central

Lea, Amanda J.; Altmann, Jeanne; Alberts, Susan C.; Tung, Jenny

2015-01-01

Early-life experiences can dramatically affect adult traits. However, the evolutionary origins of such early-life effects are debated. The predictive adaptive response hypothesis argues that adverse early environments prompt adaptive phenotypic adjustments that prepare animals for similar challenges in adulthood. In contrast, the developmental constraints hypothesis argues that early adversity is generally costly. To differentiate between these hypotheses, we studied two sets of wild female baboons: those born during low-rainfall, low-quality years and those born during normal-rainfall, high-quality years. For each female, we measured fertility-related fitness components during years in adulthood that matched and mismatched her early conditions. We found support for the developmental constraints hypothesis: females born in low-quality environments showed greater decreases in fertility during drought years than females born in high-quality environments, even though drought years matched the early conditions of females born in low-quality environments. Additionally, we found that females born in low-quality years to high-status mothers did not experience reduced fertility during drought years. These results indicate that early ecological adversity did not prepare individuals to cope with ecological challenges in later life. Instead, individuals that experienced at least one high-quality early environment—either ecological or social—were more resilient to ecological stress in later life. Together, these data suggest that early adversity carries lifelong costs, which is consistent with the developmental constraints hypothesis. PMID:25996865

Gene–environment interplay in Drosophila melanogaster: Chronic food deprivation in early life affects adult exploratory and fitness traits

PubMed Central

Burns, James Geoffrey; Svetec, Nicolas; Rowe, Locke; Mery, Frederic; Dolan, Michael J.; Boyce, W. Thomas; Sokolowski, Marla B.

2012-01-01

Early life adversity has known impacts on adult health and behavior, yet little is known about the gene–environment interactions (GEIs) that underlie these consequences. We used the fruit fly Drosophila melanogaster to show that chronic early nutritional adversity interacts with rover and sitter allelic variants of foraging (for) to affect adult exploratory behavior, a phenotype that is critical for foraging, and reproductive fitness. Chronic nutritional adversity during adulthood did not affect rover or sitter adult exploratory behavior; however, early nutritional adversity in the larval period increased sitter but not rover adult exploratory behavior. Increasing for gene expression in the mushroom bodies, an important center of integration in the fly brain, changed the amount of exploratory behavior exhibited by sitter adults when they did not experience early nutritional adversity but had no effect in sitters that experienced early nutritional adversity. Manipulation of the larval nutritional environment also affected adult reproductive output of sitters but not rovers, indicating GEIs on fitness itself. The natural for variants are an excellent model to examine how GEIs underlie the biological embedding of early experience. PMID:23045644

Childhood abuse affects emotional closeness with family in mid- and later life.

PubMed

Savla, J Tina; Roberto, Karen A; Jaramillo-Sierra, Ana L; Gambrel, Laura Eubanks; Karimi, Hassan; Butner, L Michelle

2013-06-01

Knowledge about the effects of early life adversity on kin relationships in later years is sparse. The purpose of this study was to examine if childhood abuse and adversity negatively influences emotional closeness with family in mid- and later life. A second goal was to determine the role of psychosocial resources and personality traits in buffering the effects of early adversities. Gender and cohort differences were explored to see if men were differentially affected than women and whether middle-aged adults (35-49 years old) were differentially affected than older adults (50-74 years old) by the effects of childhood abuse and adversity. Using retrospective accounts of early family abuse and adversities of 1,266 middle aged adults and 1,219 older adults from a large population-based survey, the National Survey of Midlife Development in United States (MIDUS), separate multiple regression analyses were conducted for the two cohorts to examine the effects of childhood emotional and physical abuse and family adversities on perceived emotional closeness with family. Interaction effects between childhood abuse and adversity (e.g., being expelled from school, death of sibling, parental divorce, losing a home to a natural disaster) with psychosocial resources (perceived control and self acceptance), personality characteristics (extraversion and neuroticism), and gender were examined. Results of OLS regressions suggest emotional and physical abuse predicted family closeness in middle-aged adults. Conversely, only emotional abuse predicted family closeness in older adults. Moderation models revealed that high levels of self acceptance were associated with better maintenance of emotional closeness among middle-aged adults who were emotionally and physically abused as children. Older adults with lower extraversion who experienced emotional abuse or reported greater number of adversities in childhood were found to be at higher risk for lower emotional closeness with family. Early life adversities were more detrimental for women. Findings suggest that the aftermath of childhood abuse does not dissipate with time, but continues to influence family relationships in mid- and later life. Identifying the links between childhood adversities and adult relationships can help identify strategic points for intervention to reduce the long-term effects of accumulated adverse experiences over the life course. Published by Elsevier Ltd.

Early Imaging and Adverse Neurodevelopmental Outcome in Asphyxiated Newborns Treated With Hypothermia.

PubMed

Al Amrani, Fatema; Kwan, Saskia; Gilbert, Guillaume; Saint-Martin, Christine; Shevell, Michael; Wintermark, Pia

2017-08-01

Brain injury can be identified as early as day two of life in asphyxiated newborns treated with hypothermia, when using diffusion magnetic resonance imaging (MRI). However, it remains unclear whether these diffusion changes can predict future neurodevelopment. This study aimed to determine whether abnormal early diffusion changes in newborns treated with hypothermia are associated with adverse neurodevelopmental outcome at age two years. Asphyxiated newborns treated with hypothermia were enrolled prospectively. They underwent magnetic resonance imaging (MRI) at specific time points over the first month of life, including diffusion-weighted imaging and diffusion-tensor imaging. Apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values were measured in different regions of interest. Adverse neurodevelopmental outcome was defined as cerebral palsy, global developmental delay, and/or seizure disorder around age two years. ADC and FA values were compared between the newborns developing or not developing adverse outcome. Twenty-nine asphyxiated newborns treated with hypothermia were included. Among the newborns developing adverse outcome, ADC values were significantly decreased on days two to three of life and increased around day ten of life in the thalamus, posterior limb of the internal capsule, and the lentiform nucleus. FA values decreased in the same regions around day 30 of life. These newborns also had increased ADC around day ten of life and around day 30 of life, and decreased FA around day 30 of life in the anterior and posterior white matter. Diffusion changes that were evident as early as day two of life, when the asphyxiated newborns were still treated with hypothermia, were associated with later abnormal neurodevelopmental outcome. Copyright © 2017 Elsevier Inc. All rights reserved.

Cerebrospinal fluid corticotropin-releasing factor and perceived early-life stress in depressed patients and healthy control subjects.

PubMed

Carpenter, Linda L; Tyrka, Audrey R; McDougle, Christopher J; Malison, Robert T; Owens, Michael J; Nemeroff, Charles B; Price, Lawrence H

2004-04-01

Previous studies have reported elevated concentrations of cerebrospinal fluid (CSF) corticotropin-releasing factor (CRF) in patients with major depression. Elevations of CSF CRF have also been reported in adult laboratory animals exposed to the stress of brief maternal deprivation or maternal neglect in the neonatal or preweaning period. The present study was designed to determine whether major depression and a history of perceived early adversity in childhood are independently associated with elevated CSF CRF concentrations in adults. In this case-control study, 27 medication-free adults with major depression and 25 matched controls underwent standardized lumbar puncture for collection of a single CSF sample at 1200. Subjects provided data about significant adverse early-life experiences and rated their global perceived level of stress during pre-school and preteen years on a six-point Likert scale. The mean difference in CSF CRF between depressed patients and controls did not reach statistical significance. In a regression model, perceived early-life stress was a significant predictor of CSF CRF, but depression was not. Perinatal adversity and perceived adversity in the preteen adversity years (ages 6-13 years) were both independently associated with decreasing CSF CRF concentrations. The relationship observed between perceived early-life stress and adult CSF CRF concentrations in this study closely parallels recent preclinical findings. More work is needed to elucidate the critical nature and timing of early events that may be associated with enduring neuroendocrine changes in humans.

Adversity in Preschool-Aged Children: Effects on Salivary Interleukin-1β

PubMed Central

Tyrka, Audrey R.; Parade, Stephanie H.; Valentine, Thomas R.; Eslinger, Nicole M.; Seifer, Ronald

2016-01-01

Exposure to early life adversity is linked to impaired affective, cognitive, and behavioral functioning and increases risk for various psychiatric and medical conditions. Stress-induced increases in pro-inflammatory cytokines may be a biological mechanism of these effects. Few studies have examined cytokine levels in children experiencing early life adversity, and very little research has investigated cytokines or other markers of inflammation in saliva. In the present study, we examined salivary IL-1β and C-reactive protein (CRP) levels in relation to stress exposure in 40 children aged 3 to 5 years who were enrolled in a larger study of early life adversity. Childhood maltreatment status was assessed via review of child welfare records, and contextual stress exposure, traumatic life event history, and symptoms of psychopathology were assessed via caregiver interviews at a home visit. In a subsequent visit, salivary IL-1β and CRP were obtained before and after participation in four emotion-eliciting tasks. Number of past month contextual stressors, lifetime contextual stressors, and traumatic life events each demonstrated a significant main effect on IL-1β. Baseline IL-1β was positively associated with each of the significant main-effect adversities. Post-challenge IL-1β displayed positive associations with each adversity variable, but were not significant. CRP was not significantly associated with any of the adversity variables. Given evidence suggesting involvement of IL-1β in the neuropathology of psychiatric conditions, these results may have important implications for developmental outcomes. PMID:25997772

The international society for developmental psychobiology Sackler symposium: early adversity and the maturation of emotion circuits--a cross-species analysis.

PubMed

Callaghan, Bridget L; Sullivan, Regina M; Howell, Brittany; Tottenham, Nim

2014-12-01

Early-life caregiving shapes the architecture and function of the developing brain. The fact that the infant-caregiver relationship is critically important for infant functioning across all altricial species, and that the anatomical circuits supporting emotional functioning are highly preserved across different species, suggests that the results of studies examining the role of early adversity and emotional functioning should be translatable across species. Here we present findings from four different research laboratories, using three different species, which have converged on a similar finding: adversity accelerates the developmental trajectory of amygdala-prefrontal cortex (PFC) development and modifies emotional behaviors. First, a rodent model of attachment learning associated with adversity is presented showing precocial disruption of attachment learning and emergence of heightened fear learning and emotionality. Second, a model of infant-mother separation is presented in which early adversity is shown to accelerate the developmental emergence of adult-like fear retention and extinction. Third, a model of early life adversity in Rhesus monkeys is presented in which a naturally occurring variation in maternal-care (abuse) is shown to alter the functioning of emotion circuits. Finally, a human model of maternal deprivation is presented in which children born into orphanages and then adopted abroad exhibit aberrant development of emotion circuits. The convergence of these cross-species studies on early life adversity suggests that adversity targets the amygdala and PFC and has immediate impact on infant behavior with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. © 2014 Wiley Periodicals, Inc.

Stress and resource pathways connecting early socioeconomic adversity to young adults' physical health risk.

PubMed

Wickrama, Kandauda K A S; Lee, Tae Kyoung; O'Neal, Catherine Walker; Kwon, Josephine A

2015-05-01

Although research has established the impact of early stress, including stressful life contexts, and early resources, such as educational attainment, on various adolescent health outcomes, previous research has not adequately investigated "integrative models" incorporating both stress and resource mediational pathways to explain how early socioeconomic adversity impacts physical health outcomes, particularly in early life stages. Data on early childhood/adolescent stress and socioeconomic resources as well as biomarkers indicating physical health status in young adulthood were collected from 11,798 respondents (54 % female) over a 13-year period from youth participating in the National Study of Adolescent Health (Add Health). Physical health risk in young adulthood was measured using a composite index of nine regulatory biomarkers of cardiovascular and metabolic systems. Heterogeneity in stress and socioeconomic resource pathways was assessed using latent class analysis to identify clusters, or classes, of stress and socioeconomic resource trajectories. The influence of early socioeconomic adversity on young adults' physical health risk, as measured by biomarkers, was estimated, and the role of stress and socioeconomic resource trajectory classes as linking mechanisms was assessed. There was evidence for the influence of early socioeconomic adversity on young adults' physical health risk directly and indirectly through stress and socioeconomic resource trajectory classes over the early life course. These findings suggest that health models should be broadened to incorporate both stress and resource experiences simultaneously. Furthermore, these findings have prevention and intervention implications, including the importance of early socioeconomic adversity and key intervention points for "turning" the trajectories of at-risk youth.

Early-Life Persistent Vitamin D Deficiency Alters Cardiopulmonary Responses to Particulate Matter-Enhanced Atmospheric Smog in Adult Mice

EPA Science Inventory

This study demonstrates that early-life persistent vitamin D deficiency alters the cardiopulmonary response to smog in mice and may increase risk of adverse effects. Early life nutritional deficiencies can lead to increased cardiovascular susceptibility to environme...

Genetic moderation of multiple pathways linking early cumulative socioeconomic adversity and young adults' cardiometabolic disease risk.

PubMed

Wickrama, Kandauda A S; Lee, Tae Kyoung; O'Neal, Catherine Walker

2018-02-01

Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined. Second, moderation of these pathways by the serotonin transporter linked polymorphic region gene (5-HTTLPR) was examined. There was evidence for the association between early socioeconomic adversity and young adults' cardiometabolic disease risk directly and indirectly through educational attainment and accelerated transitions. These direct and mediating pathways were amplified by the 5-HTTLPR polymorphism. These findings elucidate how early adversity can have an enduring influence on young adults' cardiometabolic disease risk directly and indirectly through psychosocial resources and life stressors and their genetic moderation. This information suggests that effective intervention and prevention programs should focus on early adversity, youth educational attainment, and their transition to young adulthood.

Does adversity early in life affect general population suicide rates? A cross-national study.

PubMed

Shah, Ajit; Bhandarkar, Ritesh

2011-01-01

Adversity early in life has been suggested as a protective factor for elderly suicides. However, studies examining this relationship in general population suicide rates are scarce. The relationship between general population suicide rates and four proxy measures of adversity earlier in life was examined using data from the World Health Organization and the United Nations data banks. General population suicide rates were negatively correlated with the percentage of children under the age of 5 years who were underweight, the percentage of children under the age of 5 years who were under height, the percentage of infants with low birth weight babies, and the percentage of the general population that was undernourished. The only independent predictor general population suicide rates in both sexes, on multiple regression analysis, was the Gini coefficient (a measure of income inequality). Income inequality may lead to low birth weight, undernourishment, underweight and under height because income inequality results in poor access to healthcare and nutrition. These adversities may increase child mortality rates and reduce life expectancy. Those surviving into adulthood in countries with greater adversity early in life may be at reduced risk of suicide because of selective survival of those at reduced risk of suicide due to constitutional or genetic factors and development of greater tolerance to hardship in adulthood. ‎

MRI uncovers disrupted hippocampal microstructure that underlies memory impairments after early-life adversity.

PubMed

Molet, Jenny; Maras, Pamela M; Kinney-Lang, Eli; Harris, Neil G; Rashid, Faisal; Ivy, Autumn S; Solodkin, Ana; Obenaus, Andre; Baram, Tallie Z

2016-12-01

Memory and related cognitive functions are progressively impaired in a subgroup of individuals experiencing childhood adversity and stress. However, it is not possible to identify vulnerable individuals early, a crucial step for intervention. In this study, high-resolution magnetic resonance imaging (MRI) and intra-hippocampal diffusion tensor imaging (DTI) were employed to examine for structural signatures of cognitive adolescent vulnerabilities in a rodent model of early-life adversity. These methods were complemented by neuroanatomical and functional assessments of hippocampal network integrity during adolescence, adulthood and middle-age. The high-resolution MRI identified selective loss of dorsal hippocampal volume, and intra-hippocampal DTI uncovered disruption of dendritic structure, consistent with disrupted local connectivity, already during late adolescence in adversity-experiencing rats. Memory deteriorated over time, and stunting of hippocampal dendritic trees was apparent on neuroanatomical analyses. Thus, disrupted hippocampal neuronal structure and connectivity, associated with cognitive impairments, are detectable via non-invasive imaging modalities in rats experiencing early-life adversity. These high-resolution imaging approaches may constitute promising tools for prediction and assessment of at-risk individuals in the clinic. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Effect of Early Adversity and Childhood Internalizing Symptoms on Brain Structure in Young Men.

PubMed

Jensen, Sarah K G; Dickie, Erin W; Schwartz, Deborah H; Evans, C John; Dumontheil, Iroise; Paus, Tomáš; Barker, Edward D

2015-10-01

Early adversity is an important risk factor that relates to internalizing symptoms and altered brain structure. To assess the direct effects of early adversity and child internalizing symptoms (ie, depression, anxiety) on cortical gray matter (GM) volume, as well as the extent to which early adversity associates with variation in cortical GM volume indirectly via increased levels of internalizing symptoms. A prospective investigation of associations between adversity within the first 6 years of life, internalizing symptoms during childhood and early adolescence, and altered brain structure in late adolescence (age, 18-21 years) was conducted in a community-based birth cohort in England (Avon Longitudinal Study of Parents and Children). Participants from the cohort included 494 mother-son pairs monitored since the mothers were pregnant (estimated date of delivery between April 1, 1991, and December 31, 1992). Data collection for the present study was conducted between April 1, 1991, and November 30, 2010; the neuroimaging data were collected between September 1, 2010, and November 30, 2012, and data analyses for the present study occurred between January 25, 2013, and February 15, 2015. Risk factors were adversity within the first 6 years of the child's life (including prenatal exposure) and the child's internalizing symptoms between age 7 and 13 years. Early childhood adversity. The main outcome was GM volume of cortical regions previously associated with major depression measured through T1-weighted magnetic resonance images collected in late adolescence. Among 494 young men included in this analysis, early adversity was directly associated with lower GM volumes in the anterior cingulate cortex (β = -.18; P = .01) and higher GM volume in the precuneus (β = .18; P = .009). Childhood internalizing symptoms were associated with lower GM volume in the right superior frontal gyrus (β = -.20; P = .002). Early adversity was also associated with higher levels of internalizing symptoms (β = .37; P < .001), which, in turn, were associated with lower superior frontal gyrus volume (ie, an indirect effect) (β = -.08; 95% CI, -0.14 to -0.01; P = .02). Adversity early in life was associated with higher levels of internalizing symptoms as well as with altered brain structure. Early adversity was related to variation in brain structure both directly and via increased levels of internalizing symptoms. These findings may suggest that some of the structural variation often attributed to depression might be associated with early adversity in addition to the effect of depression.

The Public Health Burden of Early Adversity

ERIC Educational Resources Information Center

Schlueter, Lisa J.; Watamura, Sarah Enos

2017-01-01

Severe and chronic stress in early childhood has enormous physical and mental health costs across an individual's lifespan. Unfortunately, exposure to early life adversity is common, and costs accrue to individuals and society. This article highlights several promising approaches to buffer children from the negative health consequences associated…

Sex-Specific and Strain-Dependent Effects of Early Life Adversity on Behavioral and Epigenetic Outcomes

PubMed Central

Kundakovic, Marija; Lim, Sean; Gudsnuk, Kathryn; Champagne, Frances A.

2013-01-01

Early life adversity can have a significant long-term impact with implications for the emergence of psychopathology. Disruption to mother-infant interactions is a form of early life adversity that may, in particular, have profound programing effects on the developing brain. However, despite converging evidence from human and animal studies, the precise mechanistic pathways underlying adversity-associated neurobehavioral changes have yet to be elucidated. One approach to the study of mechanism is exploration of epigenetic changes associated with early life experience. In the current study, we examined the effects of postnatal maternal separation (MS) in mice and assessed the behavioral, brain gene expression, and epigenetic effects of this manipulation in offspring. Importantly, we included two different mouse strains (C57BL/6J and Balb/cJ) and both male and female offspring to determine strain- and/or sex-associated differential response to MS. We found both strain-specific and sex-dependent effects of MS in early adolescent offspring on measures of open-field exploration, sucrose preference, and social behavior. Analyses of cortical and hippocampal mRNA levels of the glucocorticoid receptor (Nr3c1) and brain-derived neurotrophic factor (Bdnf) genes revealed decreased hippocampal Bdnf expression in maternally separated C57BL/6J females and increased cortical Bdnf expression in maternally separated male and female Balb/cJ offspring. Analyses of Nr3c1and Bdnf (IV and IX) CpG methylation indicated increased hippocampal Nr3c1 methylation in maternally separated C57BL/6J males and increased hippocampal Bdnf IX methylation in male and female maternally separated Balb/c mice. Overall, though effect sizes were modest, these findings suggest a complex interaction between early life adversity, genetic background, and sex in the determination of neurobehavioral and epigenetic outcomes that may account for differential vulnerability to later-life disorder. PMID:23914177

Childhood adverse life events and parental psychopathology as risk factors for bipolar disorder.

PubMed

Bergink, V; Larsen, J T; Hillegers, M H J; Dahl, S K; Stevens, H; Mortensen, P B; Petersen, L; Munk-Olsen, T

2016-10-25

Childhood adverse events are risk factors for later bipolar disorder. We quantified the risks for a later diagnosis of bipolar disorder after exposure to adverse life events in children with and without parental psychopathology. This register-based population cohort study included all persons born in Denmark from 1980 to 1998 (980 554 persons). Adversities before age 15 years were: familial disruption; parental somatic illness; any parental psychopathology; parental labour market exclusion; parental imprisonment; placement in out-of-home care; and parental natural and unnatural death. We calculated risk estimates of each of these eight life events as single exposure and risk estimates for exposure to multiple life events. Main outcome variable was a diagnosis of bipolar disorder after the age of 15 years, analysed with Cox proportional hazard regression. Single exposure to most of the investigated adversities were associated with increased risk for bipolar disorder, exceptions were parental somatic illness and parental natural death. By far the strongest risk factor for bipolar disorder in our study was any mental disorder in the parent (hazard ratio 3.53; 95% confidence interval 2.73-4.53) and the additional effects of life events on bipolar risk were limited. An effect of early adverse life events on bipolar risk later in life was mainly observed in children without parental psychopathology. Our findings do not exclude early-life events as possible risk factors, but challenge the concept of adversities as important independent determinants of bipolar disorder in genetically vulnerable individuals.

The inter- and intra- generational transmission of family poverty and hardship (adversity): A prospective 30 year study

PubMed Central

Bor, William; Ahmadabadi, Zohre; Williams, Gail M.; Alati, Rosa; Mamun, Abdullah A.; Scott, James G.; Clavarino, Alexandra M.

2018-01-01

Background Children exposed to family poverty have been found to have higher morbidity and mortality rates, poorer mental health and cognitive outcomes and reduced life chances across a wide range of life domains. There is, however, very little known about the extent to which poverty is experienced by children over their early life course, particularly in community samples. This study tracks changes in family poverty and the main factors that predict family poverty (adverse life experiences) over a 30-year period since the birth of the study child. Methods Data are from a prospective, longitudinal, birth cohort study conducted in Brisbane, Australia. Consecutive families were recruited at the mothers’ first obstetrical visit at one of two major obstetrical hospitals in Brisbane. Data are available for 2087 families with complete data at the 30-year follow-up. Poverty was measured using family income at each time point (adjusted for inflation). Findings Poverty affects about 20% of families at any time point. It is common for families to move in and out of poverty, as their circumstances are affected by such adversities as unemployment and marital breakdown. Over the period of the study about half the families in the study experienced poverty on at least one occasion. Only a very small minority of families experienced persistent poverty over the 30-year duration of the study. Logistic regressions with time lag show that family poverty predicts subsequent adversities and adverse events predict subsequent poverty. Conclusions Experiences of poverty and adversity are common and may vary greatly over the child’s early life course. In assessing the health consequences of poverty, it is important to distinguish the timing and chronicity of early life course experiences of poverty and adversity. PMID:29360828

The inter- and intra- generational transmission of family poverty and hardship (adversity): A prospective 30 year study.

PubMed

Najman, Jake M; Bor, William; Ahmadabadi, Zohre; Williams, Gail M; Alati, Rosa; Mamun, Abdullah A; Scott, James G; Clavarino, Alexandra M

2018-01-01

Children exposed to family poverty have been found to have higher morbidity and mortality rates, poorer mental health and cognitive outcomes and reduced life chances across a wide range of life domains. There is, however, very little known about the extent to which poverty is experienced by children over their early life course, particularly in community samples. This study tracks changes in family poverty and the main factors that predict family poverty (adverse life experiences) over a 30-year period since the birth of the study child. Data are from a prospective, longitudinal, birth cohort study conducted in Brisbane, Australia. Consecutive families were recruited at the mothers' first obstetrical visit at one of two major obstetrical hospitals in Brisbane. Data are available for 2087 families with complete data at the 30-year follow-up. Poverty was measured using family income at each time point (adjusted for inflation). Poverty affects about 20% of families at any time point. It is common for families to move in and out of poverty, as their circumstances are affected by such adversities as unemployment and marital breakdown. Over the period of the study about half the families in the study experienced poverty on at least one occasion. Only a very small minority of families experienced persistent poverty over the 30-year duration of the study. Logistic regressions with time lag show that family poverty predicts subsequent adversities and adverse events predict subsequent poverty. Experiences of poverty and adversity are common and may vary greatly over the child's early life course. In assessing the health consequences of poverty, it is important to distinguish the timing and chronicity of early life course experiences of poverty and adversity.

Toward Understanding How Early-Life Stress Reprograms Cognitive and Emotional Brain Networks.

PubMed

Chen, Yuncai; Baram, Tallie Z

2016-01-01

Vulnerability to emotional disorders including depression derives from interactions between genes and environment, especially during sensitive developmental periods. Adverse early-life experiences provoke the release and modify the expression of several stress mediators and neurotransmitters within specific brain regions. The interaction of these mediators with developing neurons and neuronal networks may lead to long-lasting structural and functional alterations associated with cognitive and emotional consequences. Although a vast body of work has linked quantitative and qualitative aspects of stress to adolescent and adult outcomes, a number of questions are unclear. What distinguishes 'normal' from pathologic or toxic stress? How are the effects of stress transformed into structural and functional changes in individual neurons and neuronal networks? Which ones are affected? We review these questions in the context of established and emerging studies. We introduce a novel concept regarding the origin of toxic early-life stress, stating that it may derive from specific patterns of environmental signals, especially those derived from the mother or caretaker. Fragmented and unpredictable patterns of maternal care behaviors induce a profound chronic stress. The aberrant patterns and rhythms of early-life sensory input might also directly and adversely influence the maturation of cognitive and emotional brain circuits, in analogy to visual and auditory brain systems. Thus, unpredictable, stress-provoking early-life experiences may influence adolescent cognitive and emotional outcomes by disrupting the maturation of the underlying brain networks. Comprehensive approaches and multiple levels of analysis are required to probe the protean consequences of early-life adversity on the developing brain. These involve integrated human and animal-model studies, and approaches ranging from in vivo imaging to novel neuroanatomical, molecular, epigenomic, and computational methodologies. Because early-life adversity is a powerful determinant of subsequent vulnerabilities to emotional and cognitive pathologies, understanding the underlying processes will have profound implications for the world's current and future children.

Early adversity and learning: implications for typical and atypical behavioral development.

PubMed

Hanson, Jamie L; van den Bos, Wouter; Roeber, Barbara J; Rudolph, Karen D; Davidson, Richard J; Pollak, Seth D

2017-07-01

Children who experience early adversity often develop emotion regulatory problems, but little is known about the mechanisms that mediate this relation. We tested whether general associative learning processes contribute to associations between adversity, in the form of child maltreatment, and negative behavioral outcomes. Eighty-one participants between 12 and 17 years of age were recruited for this study and completed a probabilistic learning Task. Forty-one of these participants had been exposed to physical abuse, a form of early adversity. Forty additional participants without any known history of maltreatment served as a comparison group. All participants (and their parents) also completed portions of the Youth Life Stress Interview to understand adolescent's behavior. We calculated measures of associative learning, and also constructed mathematical models of learning. We found that adolescents exposed to high levels of adversity early in their lives had lower levels of associative learning than comparison adolescents. In addition, we found that impaired associative learning partially explained the higher levels of behavioral problems among youth who suffered early adversity. Using mathematical models, we also found that two components of learning were specifically affected in children exposed to adversity: choice variability and biases in their beliefs about the likelihood of rewards in the environment. Participants who had been exposed to early adversity were less able than their peers to correctly learn which stimuli were likely to result in reward, even after repeated feedback. These individuals also used information about known rewards in their environments less often. In addition, individuals exposed to adversity made decisions early in the learning process as if rewards were less consistent and occurred more at random. These data suggest one mechanism through which early life experience shapes behavioral development. © 2017 Association for Child and Adolescent Mental Health.

Early adversity and learning: implications for typical and atypical behavioral development

PubMed Central

Hanson, Jamie L.; van den Bos, Wouter; Roeber, Barbara J.; Rudolph, Karen D.; Davidson, Richard J.; Pollak, Seth D.

2017-01-01

Background Children who experience early adversity often develop emotion regulatory problems, but little is known about the mechanisms that mediate this relation. We tested whether general associative learning processes contribute to associations between adversity, in the form of child maltreatment, and negative behavioral outcomes. Methods Eighty-one participants between 12 and 17 years of age were recruited for this study and completed a probabilistic learning Task. Forty-one of these participants had been exposed to physical abuse, a form of early adversity. Forty additional participants without any known history of maltreatment served as a comparison group. All participants (and their parents) also completed portions of the Youth Life Stress Interview to understand adolescent’s behavior. We calculated measures of associative learning, and also constructed mathematical models of learning. Results We found that adolescents exposed to high levels of adversity early in their lives had lower levels of associative learning than comparison adolescents. In addition, we found that impaired associative learning partially explained the higher levels of behavioral problems among youth who suffered early adversity. Using mathematical models, we also found that two components of learning were specifically affected in children exposed to adversity: choice variability and biases in their beliefs about the likelihood of rewards in the environment. Conclusions Participants who had been exposed to early adversity were less able than their peers to correctly learn which stimuli were likely to result in reward, even after repeated feedback. These individuals also used information about known rewards in their environments less often. In addition, individuals exposed to adversity made decisions early in the learning process as if rewards were less consistent and occurred more at random. These data suggest one mechanism through which early life experience shapes behavioral development. PMID:28158896

Childhood adversity predicts reduced physiological flexibility during the processing of negative affect among adolescents with major depression histories.

PubMed

Daches, Shimrit; Kovacs, Maria; George, Charles J; Yaroslavsky, Ilya; Kiss, Eniko; Vetró, Ágnes; Dochnal, Roberta; Benák, István; Baji, Ildikó; Halas, Kitti; Makai, Attila; Kapornai, Krisztina; Rottenberg, Jonathan

2017-11-01

Adversity during early development has been shown to have enduring negative physiological consequences. In turn, atypical physiological functioning has been associated with maladaptive processing of negative affect, including its regulation. The present study therefore explored whether exposure to adverse life events in childhood predicted maladaptive (less flexible) parasympathetic nervous system functioning during the processing of negative affect among adolescents with depression histories. An initially clinic-referred, pediatric sample (N=189) was assessed at two time points. At Time 1, when subjects were 10.17years old (SD=1.42), on average, and were depressed, parents reported on adverse life events the offspring experienced up to that point. At Time 2, when subjects were 17.18years old (SD=1.28), and were remitted from depression, parents again reported on adverse life events in their offspring's lives for the interim period. At time 2, subjects' parasympathetic nervous system functioning (quantified as respiratory sinus arrhythmia) also was assessed at rest, during sad mood induction, and during instructed mood repair. Extent of adverse life events experienced by T1 (but not events occurring between T1 and T2) predicted less flexible RSA functioning 7years later during the processing of negative affect. Adolescents with more extensive early life adversities exhibited less vagal withdrawal following negative mood induction and tended to show less physiological recovery following mood repair. Early adversities appear to be associated with less flexible physiological regulatory control during negative affect experience, when measured later in development. Stress-related autonomic dysfunction in vulnerable youths may contribute to the unfavorable clinical prognosis associated with juvenile-onset depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Sleep and Behavior in Cross-Fostering Rats: Developmental and Sex Aspects.

PubMed

Santangeli, Olena; Lehtikuja, Henna; Palomäki, Eeva; Wigren, Henna-Kaisa; Paunio, Tiina; Porkka-Heiskanen, Tarja

2016-12-01

Adverse early-life events induce behavioral psychopathologies and sleep changes in adulthood. In order to understand the molecular level mechanisms by which the maltreatment modifies sleep, valid animal models are needed. Changing pups between mothers at early age (cross-fostering) may satisfyingly model adverse events in human childhood. Cross-fostering (CF) was used to model mild early-life stress in male and female Wistar rats. Behavior and BDNF gene expression in the basal forebrain (BF), cortex, and hypothalamus were assessed during adolescence and adulthood. Spontaneous sleep, sleep homeostasis, and BF extracellular adenosine levels were assessed in adulthood. CF rats demonstrated increased number of REM sleep onsets in light and dark periods of the day. Total REM and NREM sleep duration was also increased during the light period. While sleep homeostasis was not severely affected, basal level of adenosine in the BF of both male and female CF rats was lower than in controls. CF did not lead to considerable changes in behavior. Even when the consequences of adverse early-life events are not observed in tests for anxiety and depression, they leave a molecular mark in the brain, which can act as a vulnerability factor for psychopathologies in later life. Sleep is a sensitive indicator for even mild early-life stress. © 2016 Associated Professional Sleep Societies, LLC.

Early life adversity potentiates the effects of later life stress on cumulative physiological dysregulation.

PubMed

Dich, Nadya; Hansen, Åse Marie; Avlund, Kirsten; Lund, Rikke; Mortensen, Erik Lykke; Bruunsgaard, Helle; Rod, Naja Hulvej

2015-01-01

Previous research indicates that early life adversity may heighten stress reactivity and impair mechanisms for adaptive coping, suggesting that experience of stress in early life may also potentiate adults' physiological vulnerability to stress in later life. The study tested this hypothesis by investigating whether the experience of stressful events and circumstances (SEC) in childhood or adolescence amplified the effect of adulthood SEC on physiological dysregulation (allostatic load, AL) in later midlife. Observational data were used in the present study. Physiological functioning was measured in later midlife (participants' age ranged from 49 to 63 years). Both childhood/adolescence and adulthood SEC were reported retrospectively on the same occasion. Participants were 5309 Danish men and women from Copenhagen Aging and Midlife Biobank (CAMB). SEC included socioeconomic and family factors. The AL index was based on nine cardiovascular, metabolic, and immune biomarkers. Experience of SEC in both early life and adulthood independently predicted higher AL. In men, experience of SEC in early life also potentiated the effect of SEC in adulthood on AL. The results provide further insight into the mechanisms behind the "biological embedding" of childhood stress.

Additive Contributions of Childhood Adversity and Recent Stressors to Inflammation at Midlife: Findings from the MIDUS Study

ERIC Educational Resources Information Center

Hostinar, Camelia E.; Lachman, Margie E.; Mroczek, Daniel K.; Seeman, Teresa E.; Miller, Gregory E.

2015-01-01

We examined the joint contributions of self-reported adverse childhood experiences (ACEs) and recent life events (RLEs) to inflammation at midlife, by testing 3 competing theoretical models: stress generation, stress accumulation, and early life stress sensitization. We aimed to identify potential mediators between adversity and inflammation.…

The three-hit concept of vulnerability and resilience: towards understanding adaptation to early-life adversity outcome

PubMed Central

Daskalakis, Nikolaos P.; Bagot, Rosemary C.; Parker, Karen J.; Vinkers, Christiaan H.; de Kloet, E. R.

2013-01-01

Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual’s predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. PMID:23838101

The three-hit concept of vulnerability and resilience: toward understanding adaptation to early-life adversity outcome.

PubMed

Daskalakis, Nikolaos P; Bagot, Rosemary C; Parker, Karen J; Vinkers, Christiaan H; de Kloet, E R

2013-09-01

Stressful experiences during early-life can modulate the genetic programming of specific brain circuits underlying emotional and cognitive aspects of behavioral adaptation to stressful experiences later in life. Although this programming effect exerted by experience-related factors is an important determinant of mental health, its outcome depends on cognitive inputs and hence the valence an individual assigns to a given environmental context. From this perspective we will highlight, with studies in rodents, non-human primates and humans, the three-hit concept of vulnerability and resilience to stress-related mental disorders, which is based on gene-environment interactions during critical phases of perinatal and juvenile brain development. The three-hit (i.e., hit-1: genetic predisposition, hit-2: early-life environment, and hit-3: later-life environment) concept accommodates the cumulative stress hypothesis stating that in a given context vulnerability is enhanced when failure to cope with adversity accumulates. Alternatively, the concept also points to the individual's predictive adaptive capacity, which underlies the stress inoculation and match/mismatch hypotheses. The latter hypotheses propose that the experience of relatively mild early-life adversity prepares for the future and promotes resilience to similar challenges in later-life; when a mismatch occurs between early and later-life experience, coping is compromised and vulnerability is enhanced. The three-hit concept is fundamental for understanding how individuals can either be prepared for coping with life to come and remain resilient or are unable to do so and succumb to a stress-related mental disorder, under seemingly identical circumstances. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of whole-mount in situ hybridization as a tool for pathway-based toxicological research with early-life stage fathead minnows

EPA Science Inventory

Early-life stage fish can be more sensitive to chemical exposure than adult fish. Therefore, determining possible adverse outcome pathways (AOPs) for early-life stages is crucial. To determine chemical effects and/or mechanisms of action in exposed fish embryos and larvae, whole-...

Black-White Disparity in Young Adults' Disease Risk: An Investigation of Variation in the Vulnerability of Black Young Adults to Early and Later Adversity.

PubMed

Wickrama, Kandauda A S; Bae, Dayoung; O'Neal, Catherine Walker

2016-08-01

Socioeconomic adversity in early years and young adulthood are risk factors for poor health in young adulthood. Population differences in exposure to stressful socioeconomic conditions partly explain the higher prevalence of disease among black young adults. Another plausible mechanism is that blacks are differentially vulnerable to socioeconomic adversity (differential vulnerability hypothesis), which has not been adequately investigated in previous research. The present study investigated variation in the vulnerability of black young adults leading to cardiometabolic (CM) disease risk. We used a nationally representative sample of 8,824 adolescents who participated in the Add Health study. Early and later adversity was measured using a cumulative index of social and material adversity in adolescence and young adulthood. CM disease risk was assessed using nine biomarkers. Path analysis within a structural equation modeling framework was used. The findings indicated that both early and later socioeconomic adversity act as stressors with independent additive influences on young adults' CM disease risk, consistent with the differential exposure hypothesis. Moreover, the results showed that black youth are less vulnerable to early socioeconomic adversity than whites, but they are more vulnerable to later adversity. The findings provide support for the unique and additive influences of early and later socioeconomic adversity on CM disease risk contributing to the black-white health disparity in young adulthood. The results also suggest that vulnerability to adversity varies depending on the life stage, which highlights the need for life-stage specific interventions to mitigate the existing black-white disparity in young adults' physical health. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Cortisol Reactivity to Social Stress as a Mediator of Early Adversity on Risk and Adaptive Outcomes

ERIC Educational Resources Information Center

Conradt, Elisabeth; Abar, Beau; Lester, Barry M.; LaGasse, Linda L.; Shankaran, Seetha; Bada, Henrietta; Bauer, Charles R.; Whitaker, Toni M.; Hammond, Jane A.

2014-01-01

Children chronically exposed to stress early in life are at increased risk for maladaptive outcomes, though the physiological mechanisms driving these effects are unknown. Cortisol reactivity was tested as a mediator of the relation between prenatal substance exposure and/or early adversity on adaptive and maladaptive outcomes. Data were drawn…

Racial and socioeconomic disparities in body mass index among college students: understanding the role of early life adversity.

PubMed

Curtis, David S; Fuller-Rowell, Thomas E; Doan, Stacey N; Zgierska, Aleksandra E; Ryff, Carol D

2016-10-01

The role of early life adversity (ELA) in the development of health disparities has not received adequate attention. The current study examined differential exposure and differential vulnerability to ELA as explanations for socioeconomic and racial disparities in body mass index (BMI). Data were derived from a sample of 150 college students (M age  = 18.8, SD = 1.0; 45 % African American; 55 % European American) who reported on parents' education and income as well as on exposure to 21 early adverse experiences. Body measurements were directly assessed to determine BMI. In adjusted models, African American students had higher BMI than European Americans. Similarly, background socioeconomic status was inversely associated with BMI. Significant mediation of group disparities through the pathway of ELA was detected, attenuating disparities by approximately 40 %. Furthermore, ELA was more strongly associated with BMI for African Americans than for European Americans. Efforts to achieve health equity may need to more fully consider early adversity.

Exposure to socioeconomic adversity in early life and risk of depression at 18 years: The mediating role of locus of control.

PubMed

Culpin, Iryna; Stapinski, Lexine; Miles, Ömür Budanur; Araya, Ricardo; Joinson, Carol

2015-09-01

Previous studies have linked exposure to early socioeconomic adversity to depression, but the mechanisms of this association are not well understood. Locus of control (LoC), an individual's control-related beliefs, has been implicated as a possible mechanism, however, longitudinal evidence to support this is lacking. The study sample comprised 8803 participants from a UK cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Indicators of early socioeconomic adversity were collected from the antenatal period to 5 years and modelled as a latent factor. Depression was assessed using the Clinical Interview Schedule-Revised (CIS-R) at 18 years. LoC was assessed with the Nowicki-Strickland Internal-External (CNSIE) scale at 16 years. Using structural equation modelling, we found that 34% of the total estimated association between early socioeconomic adversity and depression at 18 years was explained by external LoC at 16 years. There was weak evidence of a direct pathway from early socioeconomic adversity to depression after accounting for the indirect effect via external locus of control. Socioeconomic adversity was associated with more external LoC, which, in turn, was associated with depression. Attrition may have led to an underestimation of the direct and indirect effect sizes in the complete case analysis. Results suggest that external LoC in adolescence is one of the factors mediating the link between early adversity and depression at 18 years. Cognitive interventions that seek to modify maladaptive control beliefs in adolescence may be effective in reducing risk of depression following early life adversity. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

BDNF Val 66 Met and 5-HTTLPR genotype moderate the impact of early psychosocial adversity on plasma brain-derived neurotrophic factor and depressive symptoms: a prospective study.

PubMed

Buchmann, Arlette F; Hellweg, Rainer; Rietschel, Marcella; Treutlein, Jens; Witt, Stephanie H; Zimmermann, Ulrich S; Schmidt, Martin H; Esser, Günter; Banaschewski, Tobias; Laucht, Manfred; Deuschle, Michael

2013-08-01

Recent studies have emphasized an important role for neurotrophins, such as brain-derived neurotrophic factor (BDNF), in regulating the plasticity of neural circuits involved in the pathophysiology of stress-related diseases. The aim of the present study was to examine the interplay of the BDNF Val⁶⁶Met and the serotonin transporter promoter (5-HTTLPR) polymorphisms in moderating the impact of early-life adversity on BDNF plasma concentration and depressive symptoms. Participants were taken from an epidemiological cohort study following the long-term outcome of early risk factors from birth into young adulthood. In 259 individuals (119 males, 140 females), genotyped for the BDNF Val⁶⁶Met and the 5-HTTLPR polymorphisms, plasma BDNF was assessed at the age of 19 years. In addition, participants completed the Beck Depression Inventory (BDI). Early adversity was determined according to a family adversity index assessed at 3 months of age. Results indicated that individuals homozygous for both the BDNF Val and the 5-HTTLPR L allele showed significantly reduced BDNF levels following exposure to high adversity. In contrast, BDNF levels appeared to be unaffected by early psychosocial adversity in carriers of the BDNF Met or the 5-HTTLPR S allele. While the former group appeared to be most susceptible to depressive symptoms, the impact of early adversity was less pronounced in the latter group. This is the first preliminary evidence indicating that early-life adverse experiences may have lasting sequelae for plasma BDNF levels in humans, highlighting that the susceptibility to this effect is moderated by BDNF Val⁶⁶Met and 5-HTTLPR genotype. Copyright © 2013. Published by Elsevier B.V.

Childhood trauma and parental style: Relationship with markers of inflammation, oxidative stress, and aggression in healthy and personality disordered subjects.

PubMed

Fanning, Jennifer R; Lee, Royce; Gozal, David; Coussons-Read, Mary; Coccaro, Emil F

2015-12-01

Recent studies suggest that early life trauma is associated with elevations in circulating markers of inflammation in human subjects. History of aggression as a behavior, or aggression as a personality trait, is also associated with elevations of these inflammatory markers. Since early life trauma is associated with the development and maintenance of aggression in later life we examined the relationship of early life adversity, plasma inflammation markers (IL-6 and CRP) and oxidative stress markers (8-OH-DG and 8-ISO), and aggression in adult subjects with (n=79) and without (n=55) personality disorder. We used a series of mediated and moderated path models to test whether the effects of early adversity on later aggression may be mediated through markers of inflammation. Childhood abuse and parental control were associated with basal IL-6 and CRP concentrations. Path modeling suggested that childhood abuse was associated with aggression indirectly through CRP while parental control influenced aggression indirectly through IL-6 and CRP. Furthermore, these effects were independent of the effect of current depression. The results suggest that disruption of inflammatory processes represent one pathway by which early adversity influences aggression. Copyright © 2015 Elsevier B.V. All rights reserved.

An experimental demonstration that early-life competitive disadvantage accelerates telomere loss

PubMed Central

Nettle, Daniel; Monaghan, Pat; Gillespie, Robert; Brilot, Ben; Bedford, Thomas; Bateson, Melissa

2015-01-01

Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings (Sturnus vulgaris) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life. PMID:25411450

An experimental demonstration that early-life competitive disadvantage accelerates telomere loss.

PubMed

Nettle, Daniel; Monaghan, Pat; Gillespie, Robert; Brilot, Ben; Bedford, Thomas; Bateson, Melissa

2015-01-07

Adverse experiences in early life can exert powerful delayed effects on adult survival and health. Telomere attrition is a potentially important mechanism in such effects. One source of early-life adversity is the stress caused by competitive disadvantage. Although previous avian experiments suggest that competitive disadvantage may accelerate telomere attrition, they do not clearly isolate the effects of competitive disadvantage from other sources of variation. Here, we present data from an experiment in European starlings (Sturnus vulgaris) that used cross-fostering to expose siblings to divergent early experience. Birds were assigned either to competitive advantage (being larger than their brood competitors) or competitive disadvantage (being smaller than their brood competitors) between days 3 and 12 post-hatching. Disadvantage did not affect weight gain, but it increased telomere attrition, leading to shorter telomere length in disadvantaged birds by day 12. There were no effects of disadvantage on oxidative damage as measured by plasma lipid peroxidation. We thus found strong evidence that early-life competitive disadvantage can accelerate telomere loss. This could lead to faster age-related deterioration and poorer health in later life.

Effect of socioeconomic status disparity on child language and neural outcome: how early is early?

PubMed

Hurt, Hallam; Betancourt, Laura M

2016-01-01

It is not news that poverty adversely affects child outcome. The literature is replete with reports of deleterious effects on developmental outcome, cognitive function, and school performance in children and youth. Causative factors include poor nutrition, exposure to toxins, inadequate parenting, lack of cognitive stimulation, unstable social support, genetics, and toxic environments. Less is known regarding how early in life adverse effects may be detected. This review proposes to elucidate "how early is early" through discussion of seminal articles related to the effect of socioeconomic status on language outcome and a discussion of the emerging literature on effects of socioeconomic status disparity on brain structure in very young children. Given the young ages at which such outcomes are detected, the critical need for early targeted interventions for our youngest is underscored. Further, the fiscal reasonableness of initiating quality interventions supports these initiatives. As early life adversity produces lasting and deleterious effects on developmental outcome and brain structure, increased focus on programs and policies directed to reducing the impact of socioeconomic disparities is essential.

Social consequences of early socioeconomic adversity and youth BMI trajectories: gender and race/ethnicity differences.

PubMed

Bae, Dayoung; Wickrama, K A S; O'Neal, Catherine Walker

2014-08-01

The present study investigated the mediating effects of adolescent BMI trajectories on socioeconomic continuity over the early life course using a nationally representative sample of 11,075 respondents. This study considered both the initial severity as well as change over time in BMI as psycho-physiological mediators. Consistent with the life course pathway model and the cumulative advantage and disadvantage principle, the results suggested that early socioeconomic adversity is associated with youth BMI trajectories over time, which in turn, impair young adult socioeconomic attainment. The results also revealed important gender and racial/ethnic differences in the hypothesized associations. These findings elucidate how early adversity exerts an enduring long-term influence on social attainment in young adulthood. Further, the findings suggest that effective obesity intervention and prevention programs should focus not only on the severity of obesity but also on growth in BMI over the early years. Copyright © 2014 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Investigating Alternatives to the Fish Early Life-Stage Test: A Strategy for Discovering and Annotating Adverse Outcome Pathways for Early Fish Development

EPA Science Inventory

The fish early life-stage (FELS) test (OECD Test Guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an on-going effort to develop efficient and cost-effec...

Non-verbal reasoning ability and academic achievement as moderators of the relation between adverse life events and emotional and behavioural problems in early adolescence: the importance of moderator and outcome specificity.

PubMed

Flouri, Eirini; Tzavidis, Nikos

2011-02-01

This study was carried out to model the functional form of the effect of contextual risk (number of adverse life events) on emotional and behavioural problems in early adolescence, and to test how intelligence and academic achievement compare as moderators of this effect. The effect of number of adverse life events on emotional and behavioural problems was non-quadratic. Intelligence rather than academic achievement moderated the association between contextual risk and children's emotional and behavioural problems. However, the interaction effect was significant only on peer problems. These findings suggest that both moderator and outcome specificity should be considered when evaluating the role of intellectual competence in the association between contextual risk and children's emotional and behavioural problems.

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications

PubMed Central

Pohl, Calvin S.; Medland, Julia E.

2015-01-01

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. PMID:26451004

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study

PubMed Central

Gemmill, Alison; Weir, David; Adler, Nancy E.; Prather, Aric A.

2016-01-01

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging. PMID:27698131

Lifespan adversity and later adulthood telomere length in the nationally representative US Health and Retirement Study.

PubMed

Puterman, Eli; Gemmill, Alison; Karasek, Deborah; Weir, David; Adler, Nancy E; Prather, Aric A; Epel, Elissa S

2016-10-18

Stress over the lifespan is thought to promote accelerated aging and early disease. Telomere length is a marker of cell aging that appears to be one mediator of this relationship. Telomere length is associated with early adversity and with chronic stressors in adulthood in many studies. Although cumulative lifespan adversity should have bigger impacts than single events, it is also possible that adversity in childhood has larger effects on later life health than adult stressors, as suggested by models of biological embedding in early life. No studies have examined the individual vs. cumulative effects of childhood and adulthood adversities on adult telomere length. Here, we examined the relationship between cumulative childhood and adulthood adversity, adding up a range of severe financial, traumatic, and social exposures, as well as comparing them to each other, in relation to salivary telomere length. We examined 4,598 men and women from the US Health and Retirement Study. Single adversities tended to have nonsignificant relations with telomere length. In adjusted models, lifetime cumulative adversity predicted 6% greater odds of shorter telomere length. This result was mainly due to childhood adversity. In adjusted models for cumulative childhood adversity, the occurrence of each additional childhood event predicted 11% increased odds of having short telomeres. This result appeared mainly because of social/traumatic exposures rather than financial exposures. This study suggests that the shadow of childhood adversity may reach far into later adulthood in part through cellular aging.

Offenders in emerging adulthood: School maladjustment, childhood adversities, and prediction of aggressive antisocial behaviors.

PubMed

Wallinius, Märta; Delfin, Carl; Billstedt, Eva; Nilsson, Thomas; Anckarsäter, Henrik; Hofvander, Björn

2016-10-01

Early psychosocial adversities and maladjustment, such as childhood maltreatment and school adjustment problems, have been linked to an increased risk of aggressive antisocial behaviors. Yet, clinical studies of subjects at the highest risk of persistence in such behaviors are rare, especially during the life-changing transition years of emerging adulthood. This study describes early predictors of aggressive antisocial behaviors in a large, nationally representative cohort of Swedish, male violent offenders in emerging adulthood (age range = 18-25 years; N = 270). First, data on psychosocial background characteristics and aggressive antisocial behaviors (including age at onset) are provided. Second, early predictors of aggressive antisocial behaviors are tested in bivariate and multivariate interactive models. The offenders demonstrated a diversity of early onset adversities and disruptive behaviors, in line with established risk factors for subsequent criminality and adverse outcomes in a variety of life domains. Severe school adjustment problems, especially bullying others and early onset truancy, were important and interrelated predictors of aggressive antisocial behaviors over the lifetime, whereas childhood adversities such as parental substance or alcohol abuse and repeated exposure to violence at home during childhood were interrelated predictors of aggressive antisocial behaviors, albeit with less statistical importance. The findings stress the importance of early identification of individuals in the risk zone of developing severe and persistent aggressive antisocial behaviors and of early preventive interventions directed toward families with high-risk profiles. The findings also provide initial guidelines on which psychosocial background risk factors that need to be considered first-hand in early interventions. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Early Adverse Environments and Genetic Influences on Age at First Sex: Evidence for Gene × Environment Interaction

ERIC Educational Resources Information Center

Carlson, Marie D.; Mendle, Jane; Harden, K. Paige

2014-01-01

Youth who experience adverse environments in early life initiate sexual activity at a younger age, on average, than those from more advantaged circumstances. Evolutionary theorists have posited that ecological stress precipitates earlier reproductive and sexual onset, but it is unclear how stressful environments interact with genetic influences on…

Assessing the interplay of childhood adversities with more recent stressful life events and conditions in predicting panic pathology among adults from the general population.

PubMed

Asselmann, E; Stender, J; Grabe, H J; König, J; Schmidt, C O; Hamm, A O; Pané-Farré, C A

2018-01-01

Although research suggests that (a) childhood adversities and more recent stressful life events/conditions are risk factors for panic pathology and that (b) early life stress increases vulnerability to later psychopathology, it remains unclear whether childhood adversities amplify the association between more recent stressful life events/conditions and panic pathology. Data were derived from a general population sample (Study of Health in Pomerania, SHIP). Lifetime panic pathology was assessed with the Munich Composite International Diagnostic Interview (M-CIDI). Childhood adversities (emotional, physical and sexual abuse; emotional and physical neglect) were assessed with the Childhood Trauma Questionnaire (CTQ). More recent separation/loss events and long-lasting stressful conditions were assessed with the Stralsund Life Event List (SEL). Individuals with lifetime panic pathology (fearful spell, panic attack or panic disorder, N = 286) were compared to controls without any psychopathology (N = 286, matched for sex and age). Conditional logistic regressions revealed that childhood adversities as well as more recent separation/loss events and long-lasting stressful conditions were associated with panic pathology (OR 1.1-2.5). Moreover, more recent separation/loss events - but not long-lasting stressful conditions - interacted statistically with each of the examined childhood adversities except for sexual abuse in predicting panic pathology (OR 1.1-1.3). That is, separation/loss events were associated more strongly with panic pathology among individuals with higher childhood adversities. Data were assessed retrospectively and might be subject to recall biases. Findings suggest that early childhood adversities amplify the risk of developing panic pathology after experiencing separation or loss events. Copyright © 2017. Published by Elsevier B.V.

Mental health consequences of stress and trauma: allostatic load markers for practice and policy with a focus on Indigenous health.

PubMed

Berger, Maximus; Juster, Robert-Paul; Sarnyai, Zoltán

2015-12-01

Mental health, well-being, and social life are intimately related as is evident from the higher incidence of psychiatric illness in individuals exposed to social stress and adversity. Several biological pathways linking social adversity to health outcomes are heavily investigated in the aims of facilitating early identification and prevention of adverse health outcomes. We provide a practice-orientated overview of the allostatic load model and how it relates to metabolic and cardiovascular comorbidity in psychiatric disorders. Allostatic load brings together a set of neuroendocrine, metabolic, immune and cardiovascular biomarkers that are elevated in individuals with adverse early life experiences and are predictive of cardiovascular and metabolic risk in psychiatric illness of critical importance for Indigenous Australians. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Early-Life Effects on Adult Physical Activity: Concepts, Relevance, and Experimental Approaches.

PubMed

Garland, Theodore; Cadney, Marcell D; Waterland, Robert A

Locomotion is a defining characteristic of animal life and plays a crucial role in most behaviors. Locomotion involves physical activity, which can have far-reaching effects on physiology and neurobiology, both acutely and chronically. In human populations and in laboratory rodents, higher levels of physical activity are generally associated with positive health outcomes, although excessive exercise can have adverse consequences. Whether and how such relationships occur in wild animals is unknown. Behavioral variation among individuals arises from genetic and environmental factors and their interactions as well as from developmental programming (persistent effects of early-life environment). Although tremendous progress has been made in identifying genetic and environmental influences on individual differences in behavior, early-life effects are not well understood. Early-life effects can in some cases persist across multiple generations following a single exposure and, in principle, may constrain or facilitate the rate of evolution at multiple levels of biological organization. Understanding the mechanisms of such transgenerational effects (e.g., exposure to stress hormones in utero, inherited epigenetic alterations) may prove crucial to explaining unexpected and/or sex-specific responses to selection as well as limits to adaptation. One area receiving increased attention is early-life effects on adult physical activity. Correlational data from epidemiological studies suggest that early-life nutritional stress can (adversely) affect adult human activity levels and associated physiological traits (e.g., body composition, metabolic health). The few existing studies of laboratory rodents demonstrate that both maternal and early-life exercise can affect adult levels of physical activity and related phenotypes. Going forward, rodents offer many opportunities for experimental studies of (multigenerational) early-life effects, including studies that use maternal exposures and cross-fostering designs.

Maternal anxiety from pregnancy to 2 years postpartum: transactional patterns of maternal early adversity and child temperament.

PubMed

Agrati, Daniella; Browne, Dillon; Jonas, Wibke; Meaney, Michael; Atkinson, Leslie; Steiner, Meir; Fleming, Alison S

2015-10-01

The aims of this study were to examine the anxiety trajectories of women from pregnancy to 2 years postpartum and to assess the influence of their early life experiences and the temperament of the child on these trajectories. We evaluated state anxiety (State-Trait Anxiety Inventory) at pregnancy and 3, 6, 12, 18, and 24 months postpartum and determined its course as a function of self-reported early adverse experiences (Childhood Trauma Questionnaire) and the temperament of the child at 18 months (Early Child Behavior Questionnaire). Based on growth curve modeling, we found that anxiety followed a general U-shape pattern from gestation to 2 years postpartum, which was modified by early life experience of women. Greater early adversity was associated with higher gestational anxiety, followed by a marked decrease once the baby was born, and subsequent increase during the later postpartum period. The temperament of the child also modulated anxiety trajectories. Thus, mothers of children high in negative affectivity and who also experienced greater early adversity had elevated and flat anxiety trajectories, while child extraversion was associated with increasing anxiety courses approaching 2 years postpartum. These results show that maternal anxiety dynamically changes through the postpartum period with a course that is affected by previous and current experiences.

Moderate Childhood Stress Buffers Against Depressive Response to Proximal Stressors: A Multi-Wave Prospective Study of Early Adolescents

PubMed Central

Shapero, Benjamin G.; Hamilton, Jessica L.; Stange, Jonathan P.; Liu, Richard T.; Y.Abramson, Lyn; Alloy, Lauren B.

2015-01-01

Although the majority of research in the field has focused on childhood stressors as a risk factor for psychopathology, a burgeoning body of literature has focused on the possible steeling effect of moderate types of stressful events. The current study investigated the effects of proximal life stressors on prospective changes in depressive symptoms, and whether a history of moderate childhood adversity would moderate this relationship in a multi-wave study of a diverse community sample of early adolescents (N = 163, 52% female, 51% Caucasian). Hierarchical linear modeling was run with four waves of data. Adolescents with greater moderately severe early life events evinced a blunted depressive symptom response to changes in proximal stressful events in the previous 9 months, compared to those with fewer early moderately severe experiences of adversity. These results held after controlling for between-subject factors such as race, gender, severe early life stress, and average stress over the four waves of data. Findings indicate that greater exposure to moderate childhood stressors may buffer against the negative effects of subsequent stressors, suggesting the importance of a nuanced developmental approach to studying the effects of early life stress. PMID:25911194

LONG-TERM EFFECTS OF ADVERSE ENVIRONMENTS DURING DEVELOPMENT: EFFECTS ON ADULTHOOD IN RATS EXPOSED TO TOXICANTS OR UNDERNUTRITION IN UTERO.

EPA Science Inventory

Studies have shown correlations between in utero and early life environments and diseases later in life, including hypertension, coronary heart disease, diabetes, obesity, schizophrenia, early onset chronic renal failure, cancer and compromised repro-duction. Current development...

Maternal Early Life Experiences and Parenting: The Mediating Role of Cortisol and Executive Function

ERIC Educational Resources Information Center

Gonzalez, Andrea; Jenkins, Jennifer M.; Steiner, Meir; Fleming, Alison S.

2012-01-01

Objective: Research suggests that early life adversity may affect subsequent parenting. Animal studies investigating mechanisms of transmission have focused on biological factors; whereas research in humans has emphasized cognitive and psychosocial factors. We hypothesized that neuropsychological and physiological factors would act as mediators…

Developmental influences on fertility decisions by women: an evolutionary perspective

PubMed Central

Tickner, M.; McAllister, L. S.; Sheppard, P.

2016-01-01

Developmental environments are crucial for shaping our life course. Elements of the early social and biological environments have been consistently associated with reproduction in humans. To date, a strong focus has been on the relationship between early stress, earlier menarche and first child birth in women. These associations, found predominately in high-income countries, have been usefully interpreted within life-history theory frameworks. Fertility, on the other hand—a missing link between an individual's early environment, reproductive strategy and fitness—has received little attention. Here, we synthesize this literature by examining the associations between early adversity, age at menarche and fertility and fecundity in women. We examine the evidence that potential mechanisms such as birth weight, childhood body composition, risky health behaviours and developmental influences on attractiveness link the early environment and fecundity and fertility. The evidence that menarche is associated with fertility and fecundity is good. Currently, owing to the small number of correlational studies and mixed methodologies, the evidence that early adversity predicts fecundity and fertility is not conclusive. This area of research is in its infancy; studies examining early adversity and adult fertility decisions that can also examine likely biological, social and psychological pathways present opportunities for future fertility research. PMID:27022073

Early-life stress origins of gastrointestinal disease: animal models, intestinal pathophysiology, and translational implications.

PubMed

Pohl, Calvin S; Medland, Julia E; Moeser, Adam J

2015-12-15

Early-life stress and adversity are major risk factors in the onset and severity of gastrointestinal (GI) disease in humans later in life. The mechanisms by which early-life stress leads to increased GI disease susceptibility in adult life remain poorly understood. Animal models of early-life stress have provided a foundation from which to gain a more fundamental understanding of this important GI disease paradigm. This review focuses on animal models of early-life stress-induced GI disease, with a specific emphasis on translational aspects of each model to specific human GI disease states. Early postnatal development of major GI systems and the consequences of stress on their development are discussed in detail. Relevant translational differences between species and models are highlighted. Copyright © 2015 the American Physiological Society.

The influence of living conditions in early life on life satisfaction in old age.

PubMed

Deindl, Christian

2013-03-01

This article examines the influence of living conditions in early life on life satisfaction in old age in eleven Western European countries. It combines the influence of individual conditions, for example housing and family background, with country characteristics in the decade of birth. Using pooled data from the second and third wave of the Survey of Health, Ageing and Retirement in Europe, multilevel models show that early life living conditions have an influence on life satisfaction in old age. Furthermore, interaction effects between current and past living conditions show that adverse living conditions strengthen the effect of early life on life satisfaction in later life and therefore are an indication of cumulative inequality over the life course. Copyright © 2012 Elsevier Ltd. All rights reserved.

IS THERE A VIABILITY-VULNERABILITY TRADEOFF? SEX DIFFERENCES IN FETAL PROGRAMMING

PubMed Central

SANDMAN, CURT A; GLYNN, LAURA M; DAVIS, ELYSIA POGGI

2013-01-01

OBJECTIVE In this paper we evaluate the evidence for sex differences in fetal programming within the context of the proposed viability-vulnerability tradeoff. METHODS We briefly review the literature on the factors contributing to primary and secondary sex ratios. Sex differences in fetal programming are assessed by summarizing previously published sex difference findings from our group (6 studies) and also new analyses of previously published findings in which sex differences were not reported (6 studies). RESULTS The review and reanalysis of studies from our group are consistent with the overwhelming evidence of increasing risk for viability among males exposed to environmental adversity early in life. New evidence reported here support the argument that females, despite their adaptive agility, also are influenced by exposure to early adversity. Two primary conclusions are (i) female fetal exposure to psychobiological stress selectively influences fear/anxiety, and (ii) the effects of female fetal exposure to stress persist into preadolescence. These persisting effects are reflected in increased levels of anxiety, impaired executive function and neurological markers associated with these behaviors. CONCLUSIONS A tacit assumption is that females, with their adaptive flexibility early in gestation, escape the consequences of early life exposure to adversity. We argue that the consequences of male exposure to early adversity threatens their viability, effectively culling the weak and the frail and creating a surviving cohort of the fittest. Females adjust to early adversity with a variety of strategies, but their escape from the risk of early mortality and morbidity has a price of increased vulnerability expressed later in development. PMID:24119938

Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men.

PubMed

Chatzittofis, Andreas; Savard, Josephine; Arver, Stefan; Öberg, Katarina Görts; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

2017-06-01

Background and aims There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case-control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire - Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery-Åsberg Depression Rating Scale - Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men.

Interpersonal violence, early life adversity, and suicidal behavior in hypersexual men

PubMed Central

Chatzittofis, Andreas; Savard, Josephine; Arver, Stefan; Öberg, Katarina Görts; Hallberg, Jonas; Nordström, Peter; Jokinen, Jussi

2017-01-01

Background and aims There are significant gaps in knowledge regarding the role of childhood adversity, interpersonal violence, and suicidal behavior in hypersexual disorder (HD). The aim of this study was to investigate interpersonal violence in hypersexual men compared with healthy volunteers and the experience of violence in relation to suicidal behavior. Methods This case–control study includes 67 male patients with HD and 40 healthy male volunteers. The Childhood Trauma Questionnaire – Short Form (CTQ-SF) and the Karolinska Interpersonal Violence Scale (KIVS) were used for assessing early life adversity and interpersonal violence in childhood and in adult life. Suicidal behavior (attempts and ideation) was assessed with the Mini-International Neuropsychiatric Interview (version 6.0) and the Montgomery–Åsberg Depression Rating Scale – Self-rating. Results Hypersexual men reported more exposure to violence in childhood and more violent behavior as adults compared with healthy volunteers. Suicide attempters (n = 8, 12%) reported higher KIVS total score, more used violence as a child, more exposure to violence as an adult as well as higher score on CTQ-SF subscale measuring sexual abuse (SA) compared with hypersexual men without suicide attempt. Discussion Hypersexuality was associated with interpersonal violence with higher total scores in patients with a history of suicide attempt. The KIVS subscale exposure to interpersonal violence as a child was validated using the CTQ-SF but can be complemented with questions focusing on SA for full assessment of early life adversity. Conclusion Childhood adversity is an important factor in HD and interpersonal violence might be related to suicidal behavior in hypersexual men. PMID:28467102

Parents' education and the risk of major depression in early adulthood.

PubMed

Park, Alison L; Fuhrer, Rebecca; Quesnel-Vallée, Amélie

2013-11-01

Early-life low socioeconomic position (SEP) increases the risk of adult major depression; however, associations vary according to the measure of SEP and adults' life stage. Although maternal education often predicts offspring health better than other SEP indicators, including paternal education, it is unclear how maternal and paternal education differentially influence early-adult depression, and how early-life and adult risk factors may mediate the association. Longitudinal data come from the Canadian National Population Health Survey from 1994/1995 to 2006/2007, restricted to a sample (N = 1,267) that was aged 12-24 years in 1994/1995. Past-year major depressive episode (MDE) was assessed in 2004/2005 and 2006/2007 using the Composite International Diagnostic Interview Short Form for Major Depression. Logistic regression models were used to estimate odds ratios (OR) and 95 % confidence intervals (CI) for the association between both maternal and paternal education and MDE, adjusting for respondent's demographics, early-life adversities, adult SEP, psychosocial factors, and physical health. Offsprings of mothers with less than secondary school education had higher odds of MDE (adjusted OR 2.04, 95 % CI 1.25-3.32) relative to those whose mothers had more education. Paternal education was not associated with MDE. Although adult income, student status, psychosocial stress, and several early-life adversities remained associated with MDE in the fully adjusted model, the estimate for maternal education was not reduced. Maternal education was associated with MDE in early adulthood, independent of paternal education and other early-life and early-adult risk factors.

Reproductive Toxicity of T Cells in Early Life: Abnormal Immune Development and Postnatal Diseases.

PubMed

Liu, Han-Xiao; Jiang, Aifang; Chen, Ting; Qu, Wen; Yan, Hui-Yi; Ping, Jie

2017-01-01

Immunity is a balanced status with adequate biological defenses to recognize and fight "non-self", as well as adequate tolerance to recognize "self". To maintain this immune homeostasis, a well-organized T cell immune network is required, which in part depends on the well-controlled development of alternative effector T cells, with different cytokine repertoires. Recent researches have pointed that developing fetal T cells network is a remarkably sensitive toxicological target for adverse factors in early life. Epidemiological and experimental studies showed an inseparable relationship between T cell developmental toxicity and immune diseases in adults. Considering that the inflammatory and immune disorders have become a growing health problem worldwide, increasing attention is now being paid to the T cell developmental toxicity. We propose that adverse factors may have programming effects on the crucial functions of immune system during early life which is critical for fetal T cell development and the establishment of the distinct T cell repertoires balance. The permanently disturbed intrathymic or peripheral T cell development may in turn lead to the immune disorders in later life. In this manuscript, we reviewed how adverse factors affected T cell development in early-life with the consequence of the immune dysfunction and immune diseases, and further elucidate the mechanisms. These mechanisms will be helpful in prevention and treatment of the increased prevalence of immune diseases by interfering those pathways. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Building an Evidence-Based Mental Health Program for Children with History of Early Adversity

ERIC Educational Resources Information Center

Kroupina, Maria; Vermeulen, Marlous; Moberg, Stephanie

2015-01-01

Adoption is a major intervention in a child's life, however internationally adopted (IA) children remain at risk for long-term neurodevelopmental and mental health issues due to the fact that most of them have a history of early adversity prior to their adoption. In the last 20 years, extensive research with this population has increased the…

Life adversities and suicidal behavior in young individuals: a systematic review.

PubMed

Serafini, Gianluca; Muzio, Caterina; Piccinini, Giulia; Flouri, Eirini; Ferrigno, Gabriella; Pompili, Maurizio; Girardi, Paolo; Amore, Mario

2015-12-01

Suicidal behavior in young people is a significant public health problem. However, it is not yet clear whether adversities (adverse life events) may be related to suicidality in adolescence and early adulthood. This paper aimed to investigate systematically the association between the type/number of adverse life events and experiences and suicidal behavior in young people. We developed a detailed strategy to search relevant articles in Pubmed, Scopus, PsycInfo, and Science Direct (January 1980-January 2015) about adverse life events and suicidal behavior. Adverse life events and experiences included maltreatment and violence, loss events, intra-familial problems, school and interpersonal problems. Studies were restricted to suicidal behavior in young people aged 10-25 years. The search yielded 245 articles, of which 28 met our inclusion criteria. Most studies reported a strong association between adversities and suicidality (both suicidal ideation and attempts). Based on the main results, the number of adversities or negative life events experienced seemed to have a positive dose-response relationship with youth suicidal behavior. However, the type of event experienced also appeared to matter: one of the most consistent findings was the association between suicidal behavior and experience of sexual abuse. More prospective studies are needed to elucidate the relative importance of risk accumulation and risk specificity for youth suicide.

Childhood and later life stressors and increased inflammatory gene expression at older ages.

PubMed

Levine, M E; Cole, S W; Weir, D R; Crimmins, E M

2015-04-01

Adverse experiences in early life have the ability to "get under the skin" and affect future health. This study examined the relative influence of adversities during childhood and adulthood in accounting for individual differences in pro-inflammatory gene expression in late life. Using a pilot-sample from the Health and Retirement Study (N = 114) aged from 51 to 95, OLS regression models were run to determine the association between a composite score from three proinflammatory gene expression levels (PTGS2, ILIB, and IL8) and 1) childhood trauma, 2) childhood SES, 3) childhood health, 4) adult traumas, and 5) low SES in adulthood. Our results showed that only childhood trauma was found to be associated with increased inflammatory transcription in late life. Furthermore, examination of interaction effects showed that childhood trauma exacerbated the influence of low SES in adulthood on elevated levels of inflammatory gene expression-signifying that having low SES in adulthood was most damaging for persons who had experienced traumatic events during their childhood. Overall our study suggests that traumas experienced during childhood may alter the stress response, leading to more sensitive reactivity throughout the lifespan. As a result, individuals who experienced greater adversity in early life may be at higher risk of late life health outcomes, particularly if adulthood adversity related to SES persists. Copyright © 2015. Published by Elsevier Ltd.

Perinatal programming of emotional brain circuits: an integrative view from systems to molecules

PubMed Central

Bock, Jörg; Rether, Kathy; Gröger, Nicole; Xie, Lan; Braun, Katharina

2014-01-01

Environmental influences such as perinatal stress have been shown to program the developing organism to adapt brain and behavioral functions to cope with daily life challenges. Evidence is now accumulating that the specific and individual effects of early life adversity on the functional development of brain and behavior emerge as a function of the type, intensity, timing and the duration of the adverse environment, and that early life stress (ELS) is a major risk factor for developing behavioral dysfunctions and mental disorders. Results from clinical as well as experimental studies in animal models support the hypothesis that ELS can induce functional “scars” in prefrontal and limbic brain areas, regions that are essential for emotional control, learning and memory functions. On the other hand, the concept of “stress inoculation” is emerging from more recent research, which revealed positive functional adaptations in response to ELS resulting in resilience against stress and other adversities later in life. Moreover, recent studies indicate that early life experiences and the resulting behavioral consequences can be transmitted to the next generation, leading to a transgenerational cycle of adverse or positive adaptations of brain function and behavior. In this review we propose a unifying view of stress vulnerability and resilience by connecting genetic predisposition and programming sensitivity to the context of experience-expectancy and transgenerational epigenetic traits. The adaptive maturation of stress responsive neural and endocrine systems requires environmental challenges to optimize their functions. Repeated environmental challenges can be viewed within the framework of the match/mismatch hypothesis, the outcome, psychopathology or resilience, depends on the respective predisposition and on the context later in life. PMID:24550772

Early parental loss and depression history: associations with recent life stress in major depressive disorder.

PubMed

Slavich, George M; Monroe, Scott M; Gotlib, Ian H

2011-09-01

Although exposure to early adversity and prior experiences with depression have both been associated with lower levels of precipitating life stress in depression, it is unclear whether these stress sensitization effects are similar for all types of stress or whether they are specific to stressors that may be particularly depressogenic, such as those involving interpersonal loss. To investigate this issue, we administered structured, interview-based measures of early adversity, depression history, and recent life stress to one hundred adults who were diagnosed with major depressive disorder. As predicted, individuals who experienced early parental loss or prolonged separation (i.e., lasting one year or longer) and persons with more lifetime episodes of depression became depressed following lower levels of life stress occurring in the etiologically-central time period of three months prior to onset of depression. Importantly, however, additional analyses revealed that these effects were unique to stressors involving interpersonal loss. These data highlight potential stressor-specific effects in stress sensitization and demonstrate for the first time that individuals exposed to early parental loss or separation, and persons with greater histories of MDD, may be selectively sensitized to stressors involving interpersonal loss. Copyright © 2011 Elsevier Ltd. All rights reserved.

Adiposity moderates links from early adversity and depressive symptoms to inflammatory reactivity to acute stress during late adolescence.

PubMed

Chiang, Jessica J; Bower, Julienne E; Irwin, Michael R; Taylor, Shelley E; Fuligni, Andrew J

2017-11-01

Both early adversity and depression are associated with heightened inflammation. However, few studies have focused on inflammatory reactivity to psychosocial stress and examined adiposity as a potential moderator. Yet, repeated heightened inflammatory reactivity over time is thought to contribute to low-grade chronic inflammation and adipose tissue is a key source of pro-inflammatory cytokines. The purpose of the present study was to examine whether early adversity and depressive symptoms were related to stress-induced inflammation and whether these associations varied by total body and abdominal adiposity as measured by body mass index (BMI) and waist circumference (WC) in a sample of late adolescents. Participants reported on their early family environment and current depressive symptoms, had their height, weight, and WC assessed for adiposity markers, and provided blood samples for IL-6 assessment before and after a standardized laboratory stress task. No main effect of early adversity on IL-6 reactivity to acute stress was observed. However, significant interactions between early adversity and BMI and WC emerged. Greater exposure to early adversity was associated with greater IL-6 responses only among adolescents with higher BMI or WC. The same pattern of findings was observed for depressive symptoms. Additionally, moderated mediation analyses indicated that among adolescents with greater adiposity, early adversity indirectly influenced IL-6 reactivity via current depressive symptoms. These findings contribute to our understanding of vulnerability factors that may amplify the associations between early adversity and depressive symptoms and inflammation during relatively early stages of life. Copyright © 2017 Elsevier Inc. All rights reserved.

Life adversity in depressed and non-depressed older adults: A cross-sectional comparison of the brief LTE-Q questionnaire and life events and difficulties interview as part of the CASPER study.

PubMed

Donoghue, Hjördis M; Traviss-Turner, Gemma D; House, Allan O; Lewis, Helen; Gilbody, Simon

2016-03-15

There is a paucity of research on the nature of life adversity in depressed and non-depressed older adults. Early life events work used in-depth interviews; however, larger epidemiological trials investigate life adversity using brief questionnaires. This study investigates the type of life adversity experienced in later life and its association with depression and compares adversity captured using a brief (LTE-Q) and in-depth (LEDS) measure. 960 participants over 65 years were recruited in UK primary care to complete the PHQ-9 and LTE-Q. A sub-sample (n=19) completed the LEDS and a question exploring the subjective experience of the LTE-Q and LEDS. Important life adversity was reported on the LTE-Q in 48% of the sample. In the LTE-Q sample the prevalence of depression (PHQ-9≥10) was 12%. Exposure to recent adversity was associated with doubling of the odds of depression. The LTE-Q only captured a proportion of adversity measured by the LEDS (42% vs 84%). Both measures showed health, bereavement and relationship events were most common. The cross-sectional design limits the extent to which inferences can be drawn around the direction of causality between adversity and depression. Recall in older adults is questionable. UK older adults face adversity in areas of health, bereavement and relationships which are associated with depression. This has clinical relevance for psychological interventions for older adults to consider social context and social support. It helps identify the strengths and weaknesses of a brief adversity measure in large scale research. Further research is needed to explore the mechanisms of onset and direction of causality. Copyright © 2016 Elsevier B.V. All rights reserved.

Early life adversity and adult biological risk profiles.

PubMed

Friedman, Esther M; Karlamangla, Arun S; Gruenewald, Tara L; Koretz, Brandon; Seeman, Teresa E

2015-01-01

To determine whether there is a relationship between early life adversity (ELA) and biological parameters known to predict health risks and to examine the extent to which circumstances in midlife mediate this relationship. We analyzed data on 1180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States. ELA assessments were based on childhood socioeconomic disadvantage (i.e., on welfare, perceived low income, and less educated parents) and other stressors (e.g., parental death, parental divorce, and parental physical abuse). The outcome variable was cumulative allostatic load (AL), a marker of biological risk. We also incorporate information on adult circumstances, including than following: education, social relationships, and health behaviors. Childhood socioeconomic adversity and physical abuse were associated with increased AL (B = 0.094, standard error = 0.041, and B = 0.263, standard error = 0.091 respectively), with nonsignificant associations for parental divorce and death with AL. Adult education mediated the relationship between socioeconomic ELA and cumulative AL to the point of nonsignificance, with this factor alone explaining nearly 40% of the relationship. The association between childhood physical abuse and AL remained even after adjusting for adult educational attainments, social relationships, and health behaviors. These associations were most pronounced for secondary stress systems, including inflammation, cardiovascular function, and lipid metabolism. The physiological consequences of early life socioeconomic adversity are attenuated by achieving high levels of schooling later on. The adverse consequences of childhood physical abuse, on the other hand, persist in multivariable-adjusted analysis.

Developmental influences on fertility decisions by women: an evolutionary perspective.

PubMed

Coall, D A; Tickner, M; McAllister, L S; Sheppard, P

2016-04-19

Developmental environments are crucial for shaping our life course. Elements of the early social and biological environments have been consistently associated with reproduction in humans. To date, a strong focus has been on the relationship between early stress, earlier menarche and first child birth in women. These associations, found predominately in high-income countries, have been usefully interpreted within life-history theory frameworks. Fertility, on the other hand--a missing link between an individual's early environment, reproductive strategy and fitness--has received little attention. Here, we synthesize this literature by examining the associations between early adversity, age at menarche and fertility and fecundity in women. We examine the evidence that potential mechanisms such as birth weight, childhood body composition, risky health behaviours and developmental influences on attractiveness link the early environment and fecundity and fertility. The evidence that menarche is associated with fertility and fecundity is good. Currently, owing to the small number of correlational studies and mixed methodologies, the evidence that early adversity predicts fecundity and fertility is not conclusive. This area of research is in its infancy; studies examining early adversity and adult fertility decisions that can also examine likely biological, social and psychological pathways present opportunities for future fertility research. © 2016 The Author(s).

Early-life nutritional effects on the female reproductive system.

PubMed

Chan, K A; Tsoulis, M W; Sloboda, D M

2015-02-01

There is now considerable epidemiological and experimental evidence indicating that early-life environmental conditions, including nutrition, affect subsequent development in later life. These conditions induce highly integrated responses in endocrine-related homeostasis, resulting in persistent changes in the developmental trajectory producing an altered adult phenotype. Early-life events trigger processes that prepare the individual for particular circumstances that are anticipated in the postnatal environment. However, where the intrauterine and postnatal environments differ markedly, such modifications to the developmental trajectory may prove maladaptive in later life. Reproductive maturation and function are similarly influenced by early-life events. This should not be surprising, because the primordial follicle pool is established early in life and is thus vulnerable to early-life events. Results of clinical and experimental studies have indicated that early-life adversity is associated with a decline in ovarian follicular reserve, changes in ovulation rates, and altered age at onset of puberty. However, the underlying mechanisms regulating the relationship between the early-life developmental environment and postnatal reproductive development and function are unclear. This review examines the evidence linking early-life nutrition and effects on the female reproductive system, bringing together clinical observations in humans and experimental data from targeted animal models. © 2015 Society for Endocrinology.

Impacts of prenatal nutrition on animal production and performance: a focus on growth and metabolic and endocrine function in sheep.

PubMed

Khanal, Prabhat; Nielsen, Mette Olaf

2017-01-01

The concept of foetal programming (FP) originated from human epidemiological studies, where foetal life nutrition was linked to health and disease status later in life. Since the proposal of this phenomenon, it has been evaluated in various animal models to gain further insights into the mechanisms underlying the foetal origins of health and disease in humans. In FP research, the sheep has been quite extensively used as a model for humans. In this paper we will review findings mainly from our Copenhagen sheep model, on the implications of late gestation malnutrition for growth, development, and metabolic and endocrine functions later in life, and discuss how these implications may depend on the diet fed to the animal in early postnatal life. Our results have indicated that negative implications of foetal malnutrition, both as a result of overnutrition and, particularly, late gestation undernutrition, can impair a wide range of endocrine functions regulating growth and presumably also reproductive traits. These implications are not readily observable early in postnatal life, but are increasingly manifested as the animal approaches adulthood. No intervention or cure is known that can reverse this programming in postnatal life. Our findings suggest that close to normal growth and slaughter results can be obtained at least until puberty in animals which have undergone adverse programming in foetal life, but manifestation of programming effects becomes increasingly evident in adult animals. Due to the risk of transfer of the adverse programming effects to future generations, it is therefore recommended that animals that are suspected to have undergone adverse FP are not used for reproduction. Unfortunately, no reliable biomarkers have as yet been identified that allow accurate identification of adversely programmed offspring at birth, except for very low or high birth weights, and, in pigs, characteristic changes in head shape (dolphin head). Future efforts should be therefore dedicated to identify reliable biomarkers and evaluate their effectiveness for alleviation/reversal of the adverse programming in postnatal life. Our sheep studies have shown that the adverse impacts of an extreme, high-fat diet in early postnatal life, but not prenatal undernutrition, can be largely reversed by dietary correction later in life. Thus, birth (at term) appears to be a critical set point for permanent programming in animals born precocial, such as sheep. Appropriate attention to the nutrition of the late pregnant dam should therefore be a priority in animal production systems.

Early life stress, MAOA, and gene-environment interactions predict behavioral disinhibition in children.

PubMed

Enoch, M-A; Steer, C D; Newman, T K; Gibson, N; Goldman, D

2010-02-01

Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism (MAOA-LPR) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth-3 years) stressors to influence behavior in prepubertal children. The Avon Longitudinal Study of Parents and Children, UK, is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years. In both sexes, exposure to family adversity and stressful life events in the first 3 years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3.5 years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1.5 and 2.5 years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity. In a general population sample of prepubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR- stressful life event interactions specifically predicted hyperactivity.

Adverse Childhood Experiences and Child Health in Early Adolescence

PubMed Central

Flaherty, Emalee G.; Thompson, Richard; Dubowitz, Howard; Harvey, Elizabeth M; English, Diana J.; Everson, Mark D.; Proctor, Laura J.; Runyan, Desmond K.

2013-01-01

Objective 1) Examine the relationship between previous adverse childhood experiences and somatic complaints and health problems in early adolescence, and 2) examine the role of the timing of adverse exposures. Design Prospective analysis of the Longitudinal Studies of Child Abuse and Neglect interview data when children were 4, 6, 8, 12 and 14 years old. Setting Children reported or at risk for maltreatment in the South, East, Midwest, Northwest, and Southwest United States LONGSCAN sites Participants 933 children. Main Exposures Eight categories of adversity (psychological maltreatment, physical abuse, sexual abuse, neglect, caregiver’s substance use/alcohol abuse, caregiver’s depressive symptoms, caregiver treated violently, and criminal behavior by household member) experienced during the first 6 years of life, the second six years of life, the most recent 2 years, and overall adversity Outcome Measures Child health problems including poor health, illness requiring a doctor, somatic complaints and any health problem at age 14. Results More than 90% of the youth had experienced an adverse childhood event by age 14. There was a graded relationship between adverse childhood exposures and any health problem, while 2 and ≥3 adverse exposures were associated with somatic complaints. Recent adversity uniquely predicted poor health, somatic complaints and any health problem. Conclusions Childhood adversities, particularly recent adversities, already impair the health of young adolescents. Increased efforts to prevent and mitigate these experiences may improve the health of adolescents and adults. PMID:23645114

Associations between early life adversity and executive function in children adopted internationally from orphanages

PubMed Central

Hostinar, Camelia E.; Stellern, Sarah A.; Schaefer, Catherine; Carlson, Stephanie M.; Gunnar, Megan R.

2012-01-01

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery. PMID:23047689

Associations between early life adversity and executive function in children adopted internationally from orphanages.

PubMed

Hostinar, Camelia E; Stellern, Sarah A; Schaefer, Catherine; Carlson, Stephanie M; Gunnar, Megan R

2012-10-16

Executive function (EF) abilities are increasingly recognized as an important protective factor for children experiencing adversity, promoting better stress and emotion regulation as well as social and academic adjustment. We provide evidence that early life adversity is associated with significant reductions in EF performance on a developmentally sensitive battery of laboratory EF tasks that measured cognitive flexibility, working memory, and inhibitory control. Animal models also suggest that early adversity has a negative impact on the development of prefrontal cortex-based cognitive functions. In this study, we report EF performance 1 y after adoption in 2.5- to 4-y-old children who had experienced institutional care in orphanages overseas compared with a group of age-matched nonadopted children. To our knowledge, this is the youngest age and the soonest after adoption that reduced EF performance has been shown using laboratory measures in this population. EF reductions in performance were significant above and beyond differences in intelligence quotient. Within the adopted sample, current EF was associated with measures of early deprivation after controlling for intelligence quotient, with less time spent in the birth family before placement in an institution and lower quality of physical/social care in institutions predicting poorer performance on the EF battery.

Life course pathways of adverse childhood experiences toward adult psychological well-being: A stress process analysis.

PubMed

Nurius, Paula S; Green, Sara; Logan-Greene, Patricia; Borja, Sharon

2015-07-01

Growing evidence suggests that toxic stressors early in life not only convey developmental impacts but also augment risk of proliferating chains of additional stressors that can overwhelm individual coping and undermine recovery and health. Examining trauma within a life course stress process perspective, we posit that early childhood adversity carries a unique capacity to impair adult psychological well-being both independent of and cumulative with other contributors, including social disadvantage and stressful adult experiences. This study uses data from a representative population-based health survey (N=13,593) to provide one of the first multivariate assessments of unique, cumulative, and moderated effects of adverse childhood experiences (ACEs) toward explaining 3 related yet distinct measures of adult mental health: perceived well-being, psychological distress, and impaired daily activities. Results demonstrate support for each set of hypothesized associations, including exacerbation and amelioration of ACEs effects by adult stress and resilience resources, respectively. Implications for services and future research are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

Life Course Pathways of Adverse Childhood Experiences Toward Adult Psychological Well-Being: A Stress Process Analysis

PubMed Central

Nurius, Paula S.; Green, Sara; Logan-Greene, Patricia; Borja, Sharon

2015-01-01

Growing evidence suggests that toxic stressors early in life not only convey developmental impacts but also augment risk of proliferating chains of additional stressors that can overwhelm individual coping and undermine recovery and health. Examining trauma within a life course stress process perspective, we posit that early childhood adversity carries a unique capacity to impair adult psychological well-being both independent of and cumulative with other contributors, including social disadvantage and stressful adult experiences. This study uses data from a representative population-based health survey (N = 13,593) to provide one of the first multivariate assessments of unique, cumulative, and moderated effects of adverse childhood experiences (ACEs) toward explaining 3 related yet distinct measures of adult mental health: perceived well-being, psychological distress, and impaired daily activities. Results demonstrate support for each set of hypothesized associations, including exacerbation and amelioration of ACEs effects by adult stress and resilience resources, respectively. Implications for services and future research are discussed. PMID:25846195

Psychological resilience and the gene regulatory impact of posttraumatic stress in Nepali child soldiers.

PubMed

Kohrt, Brandon A; Worthman, Carol M; Adhikari, Ramesh P; Luitel, Nagendra P; Arevalo, Jesusa M G; Ma, Jeffrey; McCreath, Heather; Seeman, Teresa E; Crimmins, Eileen M; Cole, Steven W

2016-07-19

Adverse social conditions in early life have been linked to increased expression of proinflammatory genes and reduced expression of antiviral genes in circulating immune cells-the conserved transcriptional response to adversity (CTRA). However, it remains unclear whether such effects are specific to the Western, educated, industrialized, rich, and democratic (WEIRD) cultural environments in which previous research has been conducted. To assess the roles of early adversity and individual psychological resilience in immune system gene regulation within a non-WEIRD population, we evaluated CTRA gene-expression profiles in 254 former child soldiers and matched noncombatant civilians 5 y after the People's War in Nepal. CTRA gene expression was up-regulated in former child soldiers. These effects were linked to the degree of experienced trauma and associated distress-that is, posttraumatic stress disorder (PTSD) severity-more than to child soldier status per se. Self-perceived psychological resilience was associated with marked buffering of CTRA activation such that PTSD-affected former child soldiers with high levels of personal resilience showed molecular profiles comparable to those of PTSD-free civilians. These results suggest that CTRA responses to early life adversity are not restricted to WEIRD cultural contexts and they underscore the key role of resilience in determining the molecular impact of adverse environments.

The effect of early life stress on the cognitive phenotype of children with an extra X chromosome (47,XXY/47,XXX).

PubMed

van Rijn, Sophie; Barneveld, Petra; Descheemaeker, Mie-Jef; Giltay, Jacques; Swaab, Hanna

2018-02-01

Studies on gene-environment interactions suggest that some individuals may be more susceptible to life adversities than others due to their genetic profile. This study assesses whether or not children with an extra X chromosome are more vulnerable to the negative impact of early life stress on cognitive functioning than typically-developing children. A total of 50 children with an extra X chromosome and 103 non-clinical controls aged 9 to 18 years participated in the study. Cognitive functioning in domains of language, social cognition and executive functioning were assessed. Early life stress was measured with the Questionnaire of Life Events. High levels of early life stress were found to be associated with compromised executive functioning in the areas of mental flexibility and inhibitory control, irrespective of group membership. In contrast, the children with an extra X chromosome were found to be disproportionally vulnerable to deficits in social cognition on top of executive dysfunction, as compared to typically-developing children. Within the extra X group the number of negative life events is significantly correlated with more problems in inhibition, mental flexibility and social cognition. It is concluded that children with an extra X chromosome are vulnerable to adverse life events, with social cognition being particularly impacted in addition to the negative effects on executive functioning. The findings that developmental outcome is codependent on early environmental factors in genetically vulnerable children also underscores opportunities for training and support to positively influence the course of development.

DNA methylation at stress-related genes is associated with exposure to early life institutionalization

PubMed Central

Non, Amy L.; Hollister, Brittany M.; Humphreys, Kathryn L.; Childebayeva, Ainash; Esteves, Kyle; Zeanah, Charles H.; Fox, Nathan A.; Nelson, Charles A.; Drury, Stacy S.

2017-01-01

Objectives Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the percent time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. Materials and Methods We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. Results An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. Discussion These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. PMID:27218411

Epigenetic Risk Factors in PTSD and Depression

PubMed Central

Raabe, Florian Joachim; Spengler, Dietmar

2013-01-01

Epidemiological and clinical studies have shown that children exposed to adverse experiences are at increased risk for the development of depression, anxiety disorders, and posttraumatic stress disorder (PTSD). A history of child abuse and maltreatment increases the likelihood of being subsequently exposed to traumatic events or of developing PTSD as an adult. The brain is highly plastic during early life and encodes acquired information into lasting memories that normally subserve adaptation. Translational studies in rodents showed that enduring sensitization of neuronal and neuroendocrine circuits in response to early life adversity are likely risk factors of life time vulnerability to stress. Hereby, the hypothalamic-pituitary-adrenal (HPA) axis integrates cognitive, behavioral, and emotional responses to early-life stress and can be epigenetically programed during sensitive windows of development. Epigenetic mechanisms, comprising reciprocal regulation of chromatin structure and DNA methylation, are important to establish and maintain sustained, yet potentially reversible, changes in gene transcription. The relevance of these findings for the development of PTSD requires further studies in humans where experience-dependent epigenetic programing can additionally depend on genetic variation in the underlying substrates which may protect from or advance disease development. Overall, identification of early-life stress-associated epigenetic risk markers informing on previous stress history can help to advance early diagnosis, personalized prevention, and timely therapeutic interventions, thus reducing long-term social and health costs. PMID:23966957

Youth and young adult suicide: a study of life trajectory.

PubMed

Séguin, Monique; Renaud, Johanne; Lesage, Alain; Robert, Marie; Turecki, Gustavo

2011-07-01

Explore the unique developmental challenges and early adversity faced by youth and young adult who died of suicide. Sixty-seven suicide victims (SG) were compared with 56 living control with no suicidal ideations in the last year, matched for age, gender, and geographical region. Mixed methods were used: consensus DSM-IV diagnoses were formulated based on Structured Clinical Interview for DSM-IV (SCID)-I and -II interviews complemented by medical charts. Life calendar method was conducted with closest third party informant. Life-history calendar served to measure life events and adversity throughout the life course and were analyzed by attributing burden of adversity score per five-year segment, which was then cluster-analyzed to define suicide victim profiles. During the last year, mood disorders, abuse and dependence disorders, and anxiety disorder were between 8 and 63 times more likely to be present in the suicide group. Between 0 and 4 years old, 50% of children in the SG were exposed to abuse, physical and/or sexual violence; 60% between 5 and 9 years old; and by the time they were 10-14 years old, 77% were exposed to these forms of violence. In the control group, the respective figures were 14%, 18% and 34%. In the suicide group, the trajectories leading to suicide are different as we observe two different subgroups, one with early-onset and one with later-onset of adversity. To a large extent, people in the suicide group were exposed to major adversity and they were more likely to present cumulative comorbid disorders. Copyright © 2011 Elsevier Ltd. All rights reserved.

Alternatives to the Fish Early Life-Stage Test: A Research Strategy for Discovering and Annotating Adverse Outcome Pathways During Fish Development

EPA Science Inventory

The OECD 210 fish early life]stage (FELS) test is the primary guideline test used to estimate chronic fish toxicity, as well as support ecological risk assessments and chemical management programs around the world. As a step toward developing alternatives to the FELS test, a HES...

Early life adversity and telomere length: a meta-analysis.

PubMed

Ridout, K K; Levandowski, M; Ridout, S J; Gantz, L; Goonan, K; Palermo, D; Price, L H; Tyrka, A R

2018-04-01

Early adversity, in the form of abuse, neglect, socioeconomic status and other adverse experiences, is associated with poor physical and mental health outcomes. To understand the biologic mechanisms underlying these associations, studies have evaluated the relationship between early adversity and telomere length, a marker of cellular senescence. Such results have varied in regard to the size and significance of this relationship. Using meta-analytic techniques, we aimed to clarify the relationship between early adversity and telomere length while exploring factors affecting the association, including adversity type, timing and study design. A comprehensive search in July 2016 of PubMed/MEDLINE, PsycINFO and Web of Science identified 2462 studies. Multiple reviewers appraised studies for inclusion or exclusion using a priori criteria; 3.9% met inclusion criteria. Data were extracted into a structured form; the Newcastle-Ottawa Scale assessed study quality, validity and bias. Forty-one studies (N=30 773) met inclusion criteria. Early adversity and telomere length were significantly associated (Cohen's d effect size=-0.35; 95% CI, -0.46 to -0.24; P<0.0001). Sensitivity analyses revealed no outlier effects. Adversity type and timing significantly impacted the association with telomere length (P<0.0001 and P=0.0025, respectively). Subgroup and meta-regression analyses revealed that medication use, medical or psychiatric conditions, case-control vs longitudinal study design, methodological factors, age and smoking significantly affected the relationship. Comprehensive evaluations of adversity demonstrated more extensive telomere length changes. These results suggest that early adversity may have long-lasting physiological consequences contributing to disease risk and biological aging.

Biological Perspectives on the Effects of Early Psychosocial Experience

ERIC Educational Resources Information Center

Marshall, Peter J.; Kenney, Justin W.

2009-01-01

There is much current interest in how adverse experiences early in life might affect certain elements of physiological, behavioral, and psychological functioning across the lifespan. Recent conceptual frameworks for studying the effects of early experience have involved constructs such as experience-expectant, experience-dependent, and…

Understanding behavioral effects of early life stress using the reactive scope and allostatic load models

PubMed Central

HOWELL, BRITTANY R.; SANCHEZ, MAR M.

2015-01-01

The mechanisms through which early life stress leads to psychopathology are thought to involve allostatic load, the “wear and tear” an organism is subjected to as a consequence of sustained elevated levels of glucocorticoids caused by repeated/prolonged stress activations. The allostatic load model described this phenomenon, but has been criticized as inadequate to explain alterations associated with early adverse experience in some systems, including behavior, which cannot be entirely explained from an energy balance perspective. The reactive scope model has been more recently proposed and focuses less on energy balance and more on dynamic ranges of physiological and behavioral mediators. In this review we examine the mechanisms underlying the behavioral consequences of early life stress in the context of both these models. We focus on adverse experiences that involve mother–infant relationship disruption, and dissect those mechanisms involving maternal care as a regulator of development of neural circuits that control emotional and social behaviors in the offspring. We also discuss the evolutionary purpose of the plasticity in behavioral development, which has a clear adaptive value in a changing environment. PMID:22018078

Early Life Stress, MAOA, and Gene-Environment Interactions Predict Behavioral Disinhibition in Children

PubMed Central

Enoch, Mary-Anne; Steer, Colin D.; Newman, Timothy K.; Gibson, Nerea; Goldman, David

2009-01-01

Several, but not all, studies have shown that the monoamine oxidase A functional promoter polymorphism (MAOA-LPR) interacts with childhood adversity to predict adolescent and adult antisocial behavior. However, it is not known whether MAOA-LPR interacts with early life (pre-birth – 3 years) stressors to influence behavior in pre-pubertal children. The Avon Longitudinal Study of Parents and Children, U.K., is a community-representative cohort study of children followed from pre-birth onwards. The impact of family adversity from pre-birth to age 3 years and stressful life events from 6 months to 7 years on behavioral disinhibition was determined in 7500 girls and boys. Behavioral disinhibition measures were: mother-reported hyperactivity and conduct disturbances (Strengths and Difficulties Questionnaire) at ages 4 and 7 years. In both sexes, exposure to family adversity and stressful life events in the first three years of life predicted behavioral disinhibition at age 4, persisting until age 7. In girls, MAOA-LPR interacted with stressful life events experienced from 6 months to 3 ½ years to influence hyperactivity at ages 4 and 7. In boys, the interaction of MAOA-LPR with stressful life events between 1 ½ and 2 ½ years predicted hyperactivity at age 7 years. The low activity MAOA-LPR variant was associated with increased hyperactivity in girls and boys exposed to high stress. In contrast, there was no MAOA-LPR interaction with family adversity. In a general population sample of pre-pubertal children, exposure to common stressors from pre-birth to 3 years predicted behavioral disinhibition, and MAOA-LPR - stressful life event interactions specifically predicted hyperactivity. PMID:19804559

Early cranial ultrasound changes as predictors of outcome during first year of life in term infants with perinatal asphyxia.

PubMed

Boo, N Y; Chandran, V; Zulfiqar, M A; Zamratol, S M; Nyein, M K; Haliza, M S; Lye, M S

2000-08-01

To identify the types of early cranial ultrasound changes that were significant predictors of adverse outcome during the first year of life in asphyxiated term infants. This was a prospective cohort study. Shortly after birth, cranial ultrasonography was carried out via the anterior fontanelles of 70 normal control infants and 104 asphyxiated infants with a history of fetal distress and Apgar scores of less than 6 at 1 and 5 min of life, or requiring endotracheal intubation and manual intermittent positive pressure ventilation for at least 5 min after birth. Neurodevelopmental assessment was carried out on the survivors at 1 year of age. Abnormal cranial ultrasound changes were detected in a significantly higher proportion (79.8%, or n = 83) of asphyxiated infants than controls (39.5%, or n = 30) (P < 0.0001). However, logistic regression analysis showed that only three factors were significantly associated with adverse outcome at 1 year of life among the asphyxiated infants. These were: (i) decreasing birthweight (for every additional gram of increase in birthweight, adjusted odds ratio (OR) = 0.999, 95% confidence interval (CI) 0.998, 1.000; P = 0.047); (ii) a history of receiving ventilatory support during the neonatal period (adjusted OR = 8.3; 95%CI 2.4, 28.9; P = 0.0009); and (iii) hypoxic-ischaemic encephalopathy stage 2 or 3 (adjusted OR = 5.8; 95%CI 1.8, 18.6; P = 0.003). None of the early cranial ultrasound changes was a significant predictor. Early cranial ultrasound findings, although common in asphyxiated infants, were not significant predictors of adverse outcome during the first year of life in asphyxiated term infants.

Recent life events and psychosis: The role of childhood adversities.

PubMed

Mansueto, Giovanni; Faravelli, Carlo

2017-10-01

Life events are commonly reported to be related to psychosis. However, less attention has been given to the role that recent events play on psychosis, in relation to exposure to childhood adversity. The current study aimed to evaluate the relationship between recent events and psychosis, taking into account the role of early adversities. 78 psychotic patients and 156 controls were enrolled. Childhood adversity was evaluated using a validated semi-structured interview and the Childhood Experience of Care and Abuse Questionnaire. Recent events were recorded using a semi-structured interview with a normative and contextual approach. The diagnosis of psychosis was made according to Jablenski's criteria. Chi-square, t-test, odds ratio, and binary logistic regression statistical analyses were performed. Psychotic patients reported an excess of recent events. The occurrence of more than one recent event increased the risk of psychosis; there was a cumulative effect between recent and childhood events on psychosis. Recent events were significantly related to psychosis, even in the absence of childhood adversity or when adjusted for it. Our findings suggested that the effect of recent events on psychosis may be amplified by previous exposure to early adversity. Recent events alone, could be also linked to psychosis independently of childhood adversity. Copyright © 2017 Elsevier B.V. All rights reserved.

The Drosophila foraging gene human orthologue PRKG1 predicts individual differences in the effects of early adversity on maternal sensitivity.

PubMed

Sokolowski, H Moriah; Vasquez, Oscar E; Unternaehrer, Eva; Sokolowski, Dustin J; Biergans, Stephanie D; Atkinson, Leslie; Gonzalez, Andrea; Silveira, Patricia P; Levitan, Robert; O'Donnell, Kieran J; Steiner, Meir; Kennedy, James; Meaney, Michael J; Fleming, Alison S; Sokolowski, Marla B

2017-04-01

There is variation in the extent to which childhood adverse experience affects adult individual differences in maternal behavior. Genetic variation in the animal foraging gene, which encodes a cGMP-dependent protein kinase, contributes to variation in the responses of adult fruit flies, Drosophila melanogaster , to early life adversity and is also known to play a role in maternal behavior in social insects. Here we investigate genetic variation in the human foraging gene ( PRKG1 ) as a predictor of individual differences in the effects of early adversity on maternal behavior in two cohorts. We show that the PRKG1 genetic polymorphism rs2043556 associates with maternal sensitivity towards their infants. We also show that rs2043556 moderates the association between self-reported childhood adversity of the mother and her later maternal sensitivity. Mothers with the TT allele of rs2043556 appeared buffered from the effects of early adversity, whereas mothers with the presence of a C allele were not. Our study used the Toronto Longitudinal Cohort (N=288 mother-16 month old infant pairs) and the Maternal Adversity and Vulnerability and Neurodevelopment Cohort (N=281 mother-18 month old infant pairs). Our findings expand the literature on the contributions of both genetics and gene-environment interactions to maternal sensitivity, a salient feature of the early environment relevant for child neurodevelopment.

Long term effects of early adversity on cognitive function.

PubMed

Richards, M; Wadsworth, M E J

2004-10-01

To investigate long term effects of early adverse circumstances on cognitive function. Associations between early material home circumstances, parental divorce, maternal management and understanding, and cognitive function in childhood, adolescence, and adulthood were analysed using multiple linear regression, controlling for sex, parental SES, and birth order in 1339 males and females from the MRC National Survey of Health and Development. Early adverse circumstances were strongly associated with lower cognitive ability in childhood and adolescence, and were detectable on measures of verbal ability, memory, and speed and concentration in midlife. However, these long term effects were mostly explained by the effects of adversity on childhood or adolescent cognitive ability or by differences in educational attainment and adult social class. An exception was the effect of poor material home conditions on visual search speed at 53 years, which was maintained after controlling for adolescent ability, as well as further control for educational attainment, adult social class, physical growth, cigarette smoking, and affective state. There was no evidence of more rapid decline in memory and psychomotor function across middle age in those exposed to early adversity. The effect of early adversity on cognitive function tracks across the life course at least as far as middle age, although there was little evidence from this study of effect amplification over this interval. Nevertheless, in view of the persistence of child poverty in the industrialised world, these findings give cause for concern.

DNA methylation at stress-related genes is associated with exposure to early life institutionalization.

PubMed

Non, Amy L; Hollister, Brittany M; Humphreys, Kathryn L; Childebayeva, Ainash; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A; Drury, Stacy S

2016-09-01

Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the proportion of time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed. A group of children from the same geographic area, with no history of institutionalized caregiving, were also recruited. DNA methylation status was determined in DNA extracted from buccal epithelial cells of children at age 12. An inverse association was identified such that more time spent in institutional care was associated with lower DNA methylation at specific CpG sites within both genes. These results suggest a lasting impact of early severe social deprivation on methylation patterns in these genes, and contribute to a growing literature linking early adversity and epigenetic variation in children. Am J Phys Anthropol 161:84-93, 2016.. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Maternal Separation Does Not Produce a Significant Behavioral Change in Mice

PubMed Central

Tan, Shawn; Ho, Hin San; Song, Anna Yoonsu; Low, Joey

2017-01-01

Early life adversities together with genetic predispositions have been associated with elevated risks of neuropsychiatric disorders during later life. In order to investigate the underlying mechanisms, many chronic, early-life stress paradigms in multiple animal models have been developed. Previously, studies reported that maternal separation (MS) in the early postnatal stages triggers depression-and/or anxiety-like behaviors in rats. However, similar studies using mice have reported inconsistent behavioral outcomes. In this study, we sought to assess behavioral outcomes from two different early-life stress paradigms; a conventional 3-hour MS and a maternal separation with early weaning (MSEW) paradigm using C57BL/6J male mice with independent cohorts. Our data demonstrated that both MS and MSEW paradigms did not produce reported behavioral anomalies. Therefore, MS paradigms in mice require further validation and modification. PMID:29302206

Investments for Future: Early Childhood Development and Education

ERIC Educational Resources Information Center

Kartal, Hulya

2007-01-01

Investments relevant to the first years of life are directly connected to the future of societies. It can be argued that investments for early childhood development and education are one of the best ways of decreasing social inequality caused by adverse environments which hinder development in early ages and tackling poverty by reducing the rate…

Increased behavioral output but intact goal-directed and habitual responding for food reward following early-life social deprivation in rats.

PubMed

Lomanowska, Anna M; Kraemer, Gary W

2014-09-01

Early-life social adversity, such as child neglect and institutionalized rearing, is associated with later-life difficulties of inhibitory control that may reflect altered attribution of salience to external stimuli. Studies in rats demonstrate that early-life social deprivation results in enhanced responsiveness to reward stimuli and conditioned reward cues. This study examined whether these effects are related to fundamental changes in appetitive conditioning processes involving instrumental goal-directed and habitual responding for food reward. Rats were reared either by the mother (maternal rearing; MR) or in complete isolation from the mother and litter (artificial rearing; AR) and tested as adults in two appetitive conditioning tasks. AR and MR rats did not differ in the amount of goal-directed effort they exerted to obtain food reward on progressive ratio schedules of reinforcement. AR and MR rats also did not differ in the shift from goal-directed to habitual responding on a random interval schedule and they were equally sensitive to changes in reward value. The major difference between AR and MR rats was that AR rats exhibited more non-instrumental responses (empty food magazine entries, ineffective lever presses). Thus, early-life social deprivation of rats through AR affects the expression of unreinforced extraneous behaviors when motivational requirements are high, but does not affect conditioned goal-directed and habitual responding to reward. The findings have implications for understanding what aspects of responsiveness to external stimuli may be selectively affected in disorders of inhibition associated with early-life social adversity. Copyright © 2014 Elsevier B.V. All rights reserved.

Early life social stress induced changes in depression and anxiety associated neural pathways which are correlated with impaired maternal care.

PubMed

Murgatroyd, Christopher A; Peña, Catherine J; Podda, Giovanni; Nestler, Eric J; Nephew, Benjamin C

2015-08-01

Exposures to various types of early life stress can be robust predictors of the development of psychiatric disorders, including depression and anxiety. The objective of the current study was to investigate the roles of the translationally relevant targets of central vasopressin, oxytocin, ghrelin, orexin, glucocorticoid, and the brain-derived neurotrophic factor (BDNF) pathway in an early chronic social stress (ECSS) based rodent model of postpartum depression and anxiety. The present study reports novel changes in gene expression and extracellular signal related kinase (ERK) protein levels in the brains of ECSS exposed rat dams that display previously reported depressed maternal care and increased maternal anxiety. Decreases in oxytocin, orexin, and ERK proteins, increases in ghrelin receptor, glucocorticoid and mineralocorticoid receptor mRNA levels, and bidirectional changes in vasopressin underscore related work on the adverse long-term effects of early life stress on neural activity and plasticity, maternal behavior, responses to stress, and depression and anxiety-related behavior. The differences in gene and protein expression and robust correlations between expression and maternal care and anxiety support increased focus on these targets in animal and clinical studies of the adverse effects of early life stress, especially those focusing on depression and anxiety in mothers and the transgenerational effects of these disorders on offspring. Copyright © 2015 Elsevier B.V. All rights reserved.

Development of a Method to Obtain More Accurate General and Oral Health Related Information Retrospectively

PubMed Central

A, Golkari; A, Sabokseir; D, Blane; A, Sheiham; RG, Watt

2017-01-01

Statement of Problem: Early childhood is a crucial period of life as it affects one’s future health. However, precise data on adverse events during this period is usually hard to access or collect, especially in developing countries. Objectives: This paper first reviews the existing methods for retrospective data collection in health and social sciences, and then introduces a new method/tool for obtaining more accurate general and oral health related information from early childhood retrospectively. Materials and Methods: The Early Childhood Events Life-Grid (ECEL) was developed to collect information on the type and time of health-related adverse events during the early years of life, by questioning the parents. The validity of ECEL and the accuracy of information obtained by this method were assessed in a pilot study and in a main study of 30 parents of 8 to 11 year old children from Shiraz (Iran). Responses obtained from parents using the final ECEL were compared with the recorded health insurance documents. Results: There was an almost perfect agreement between the health insurance and ECEL data sets (Kappa value=0.95 and p < 0.001). Interviewees remembered the important events more accurately (100% exact timing match in case of hospitalization). Conclusions: The Early Childhood Events Life-Grid method proved to be highly accurate when compared with recorded medical documents. PMID:28959773

The effect of childhood trauma on spatial cognition in adults: a possible role of sex.

PubMed

Syal, Supriya; Ipser, Jonathan; Phillips, Nicole; Thomas, Kevin G F; van der Honk, Jack; Stein, Dan J

2014-06-01

Although animal evidence indicates that early life trauma results in pervasive hippocampal deficits underlying spatial and cognitive impairment, visuo-spatial data from adult humans with early childhood adversity are lacking. We administered 4 tests of visuo-spatial ability from the Cambridge Neuorpsychological Test Automated Battery (CANTAB) to adults with a history of childhood trauma (measured by the Childhood Trauma Questionnaire) and a matched sample of healthy controls (trauma/control = 27/28). We observed a significant effect of trauma history on spatial/pattern learning. These effects could not be accounted for by adverse adult experiences, and were sex-specific, with prior adversity improving performance in men but worsening performance in women, relative to controls. Limitations include the small sample size and reliance of our study design on a retrospective, self report measure. Our results suggest that early adversity can lead to specific and pervasive deficits in adult cognitive function.

Attentional avoidance of fearful facial expressions following early life stress is associated with impaired social functioning.

PubMed

Humphreys, Kathryn L; Kircanski, Katharina; Colich, Natalie L; Gotlib, Ian H

2016-10-01

Early life stress is associated with poorer social functioning. Attentional biases in response to threat-related cues, linked to both early experience and psychopathology, may explain this association. To date, however, no study has examined attentional biases to fearful facial expressions as a function of early life stress or examined these biases as a potential mediator of the relation between early life stress and social problems. In a sample of 154 children (ages 9-13 years) we examined the associations among interpersonal early life stressors (i.e., birth through age 6 years), attentional biases to emotional facial expressions using a dot-probe task, and social functioning on the Child Behavior Checklist. High levels of early life stress were associated with both greater levels of social problems and an attentional bias away from fearful facial expressions, even after accounting for stressors occurring in later childhood. No biases were found for happy or sad facial expressions as a function of early life stress. Finally, attentional biases to fearful faces mediated the association between early life stress and social problems. Attentional avoidance of fearful facial expressions, evidenced by a bias away from these stimuli, may be a developmental response to early adversity and link the experience of early life stress to poorer social functioning. © 2016 Association for Child and Adolescent Mental Health.

Hazards to Early Development: The Biological Embedding of Early Life Adversity.

PubMed

Nelson, Charles A

2017-10-11

The number of children under 18 years of age has increased worldwide over the past decade. This growth spurt is due, in part, to remarkable progress in child survival. Alas, surviving early hazards, like prematurity or infectious disease, does not guarantee that children's development will not be compromised by other hazards as they grow older. Throughout the world, children continue to be confronted with a large number of biological and psychosocial challenges that greatly limit their developmental potential. The focus of this article is how such adverse experiences impact the developing brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1

PubMed Central

Kumsta, R; Marzi, S J; Viana, J; Dempster, E L; Crawford, B; Rutter, M; Mill, J; Sonuga-Barke, E J S

2016-01-01

Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6–43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10−5). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes. PMID:27271856

Severe psychosocial deprivation in early childhood is associated with increased DNA methylation across a region spanning the transcription start site of CYP2E1.

PubMed

Kumsta, R; Marzi, S J; Viana, J; Dempster, E L; Crawford, B; Rutter, M; Mill, J; Sonuga-Barke, E J S

2016-06-07

Exposure to adverse rearing environments including institutional deprivation and severe childhood abuse is associated with an increased risk for mental and physical health problems across the lifespan. Although the mechanisms mediating these effects are not known, recent work in rodent models suggests that epigenetic processes may be involved. We studied the impact of severe early-life adversity on epigenetic variation in a sample of adolescents adopted from the severely depriving orphanages of the Romanian communist era in the 1980s. We quantified buccal cell DNA methylation at ~400 000 sites across the genome in Romanian adoptees exposed to either extended (6-43 months; n=16) or limited duration (<6 months; n=17) of severe early-life deprivation, in addition to a matched sample of UK adoptees (n=16) not exposed to severe deprivation. Although no probe-wise differences remained significant after controlling for the number of probes tested, we identified an exposure-associated differentially methylated region (DMR) spanning nine sequential CpG sites in the promoter-regulatory region of the cytochrome P450 2E1 gene (CYP2E1) on chromosome 10 (corrected P=2.98 × 10(-5)). Elevated DNA methylation across this region was also associated with deprivation-related clinical markers of impaired social cognition. Our data suggest that environmental insults of sufficient biological impact during early development are associated with long-lasting epigenetic changes, potentially reflecting a biological mechanism linking the effects of early-life adversity to cognitive and neurobiological phenotypes.

Effects of early life adversity on cortisol/salivary alpha-amylase symmetry in free-ranging juvenile rhesus macaques.

PubMed

Petrullo, Lauren A; Mandalaywala, Tara M; Parker, Karen J; Maestripieri, Dario; Higham, James P

2016-11-01

Early life adversity (ELA) affects physiological and behavioral development. One key component is the relationship between the developing Hypothalamic-Pituitary-Adrenal (HPA) axis and the Sympathetic Nervous System (SNS). Recent studies suggest a relationship between early life adversity and asymmetry in cortisol (a measure of HPA activation) and salivary alpha-amylase (sAA: a correlate of SNS activation) responses to stress among human children, but to our knowledge there have been no comparable studies in nonhumans. Here, we investigate the responses of these two analytes in "low stress" and "high stress" situations in free-ranging juvenile rhesus macaques (Macaca mulatta) on Cayo Santiago, Puerto Rico. Behavioral data on maternal maltreatment were collected during the first 3months of life to determine individual rates of ELA, and saliva samples were collected from subjects noninvasively during juvenility. Irrespective of ELA, salivary alpha-amylase levels were lower in low stress situations and higher in high stress situations. For cortisol however, high ELA subjects exhibited higher low stress concentrations and blunted acute responses during high stress situations compared to moderate and low ELA subjects. Cortisol and sAA values were positively correlated among low ELA subjects, suggesting symmetry, but were uncorrelated or negatively correlated among moderate and high ELA subjects, suggesting asymmetry in these individuals. These findings indicate dysregulation of the stress response among juveniles maltreated during infancy: specifically, attenuated cortisol reactivity coupled with typical sAA reactivity characterize the stress response profiles of juveniles exposed to higher rates of ELA during the first 3months of life. Copyright © 2016 Elsevier Inc. All rights reserved.

Stress-Induced Elevation of Oxytocin in Maltreated Children: Evolution, Neurodevelopment, and Social Behavior

ERIC Educational Resources Information Center

Seltzer, Leslie J.; Ziegler, Toni; Connolly, Michael J.; Prososki, Ashley R.; Pollak, Seth D.

2014-01-01

Child maltreatment often has a negative impact on the development of social behavior and health. The biobehavioral mechanisms through which these adverse outcomes emerge, however, are not clear. To better understand the ways in which early life adversity affects subsequent social behavior, changes in the neuropeptide oxytocin (OT) in children…

Epigenetics and child abuse: Modern-day Darwinism--The miraculous ability of the human genome to adapt, and then adapt again.

PubMed

Gershon, Naomi B; High, Pamela C

2015-12-01

It has long been recognized that early adversity can have life-long consequences, and the extent to which this is true is gaining increasing attention. A growing body of literature implicates Adverse Childhood Experiences, including physical, sexual, and emotional abuse, in a broad range of negative health consequences including adult psychopathology, cardiovascular, and immune disease. Increasing evidence from animal, clinical, and epidemiological studies highlight the critical role of epigenetic programing, such as DNA methylation and histone modification, in altering gene expression, brain structure and function, and ultimately life-course trajectories. This review outlines our developing insight into the interplay between our human biology and our changing environment, and explores the growing evidence base for how interventions may prevent and ameliorate damage inflicted by toxic stress in early life. © 2015 Wiley Periodicals, Inc.

Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament.

PubMed

Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A; Münsterkötter, Anna L; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter; Lonsdorf, Tina B

2016-04-01

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. © The Author (2015). Published by Oxford University Press.

Mismatch or allostatic load? Timing of life adversity differentially shapes gray matter volume and anxious temperament

PubMed Central

Kuhn, Manuel; Scharfenort, Robert; Schümann, Dirk; Schiele, Miriam A.; Münsterkötter, Anna L.; Deckert, Jürgen; Domschke, Katharina; Haaker, Jan; Kalisch, Raffael; Pauli, Paul; Reif, Andreas; Romanos, Marcel; Zwanzger, Peter

2016-01-01

Traditionally, adversity was defined as the accumulation of environmental events (allostatic load). Recently however, a mismatch between the early and the later (adult) environment (mismatch) has been hypothesized to be critical for disease development, a hypothesis that has not yet been tested explicitly in humans. We explored the impact of timing of life adversity (childhood and past year) on anxiety and depression levels (N = 833) and brain morphology (N = 129). Both remote (childhood) and proximal (recent) adversities were differentially mirrored in morphometric changes in areas critically involved in emotional processing (i.e. amygdala/hippocampus, dorsal anterior cingulate cortex, respectively). The effect of adversity on affect acted in an additive way with no evidence for interactions (mismatch). Structural equation modeling demonstrated a direct effect of adversity on morphometric estimates and anxiety/depression without evidence of brain morphology functioning as a mediator. Our results highlight that adversity manifests as pronounced changes in brain morphometric and affective temperament even though these seem to represent distinct mechanistic pathways. A major goal of future studies should be to define critical time periods for the impact of adversity and strategies for intervening to prevent or reverse the effects of adverse childhood life experiences. PMID:26568620

Childhood adversities and post-traumatic stress disorder: evidence for stress sensitisation in the World Mental Health Surveys.

PubMed

McLaughlin, Katie A; Koenen, Karestan C; Bromet, Evelyn J; Karam, Elie G; Liu, Howard; Petukhova, Maria; Ruscio, Ayelet Meron; Sampson, Nancy A; Stein, Dan J; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Borges, Guilherme; Demyttenaere, Koen; Dinolova, Rumyana V; Ferry, Finola; Florescu, Silvia; de Girolamo, Giovanni; Gureje, Oye; Kawakami, Norito; Lee, Sing; Navarro-Mateu, Fernando; Piazza, Marina; Pennell, Beth-Ellen; Posada-Villa, José; Ten Have, Margreet; Viana, Maria Carmen; Kessler, Ronald C

2017-11-01

Background Although childhood adversities are known to predict increased risk of post-traumatic stress disorder (PTSD) after traumatic experiences, it is unclear whether this association varies by childhood adversity or traumatic experience types or by age. Aims To examine variation in associations of childhood adversities with PTSD according to childhood adversity types, traumatic experience types and life-course stage. Method Epidemiological data were analysed from the World Mental Health Surveys ( n = 27 017). Results Four childhood adversities (physical and sexual abuse, neglect, parent psychopathology) were associated with similarly increased odds of PTSD following traumatic experiences (odds ratio (OR) = 1.8), whereas the other eight childhood adversities assessed did not predict PTSD. Childhood adversity-PTSD associations did not vary across traumatic experience types, but were stronger in childhood-adolescence and early-middle adulthood than later adulthood. Conclusions Childhood adversities are differentially associated with PTSD, with the strongest associations in childhood-adolescence and early-middle adulthood. Consistency of associations across traumatic experience types suggests that childhood adversities are associated with generalised vulnerability to PTSD following traumatic experiences. © The Royal College of Psychiatrists 2017.

A Life History Assessment of Early Childhood Sexual Abuse in Women

ERIC Educational Resources Information Center

Vigil, Jacob M.; Geary, David C.; Byrd-Craven, Jennifer

2005-01-01

Life history theory provided a framework for examining the relations among child sexual abuse (CSA), childhood adversity, and patterns of reproductive development and behavior. A community survey that assessed CSA, life history variables (e.g., age of menarche), and social and family background was administered to 623 women (mean age=26.9 years).…

Risk factors for alcoholism in the Oklahoma Family Health Patterns project: impact of early life adversity and family history on affect regulation and personality.

PubMed

Sorocco, Kristen H; Carnes, Nathan C; Cohoon, Andrew J; Vincent, Andrea S; Lovallo, William R

2015-05-01

This study examined the impact of early lifetime adversity (ELA) on affect regulation and personality in persons with family history (FH+) and without (FH-) a family history of alcoholism. We examined the impact of early life adversity in healthy young adults, 18-30 years of age enrolled in a long-term study on risk for alcohol and other substance abuse. ELA was assessed by a composite score of low socioeconomic status and personal experience of physical or sexual abuse and/or separation from parents before age 16, resulting in a score of 0, 1-2, or >3 adverse events. Unstable affect regulation and personality variables were obtained via self-report measures. Higher ELA scores were seen in FH+ (χ(2)=109.2, p<0.0001) and in women (χ(2)=17.82, p=0.0019). Although higher ELA predicted less emotional stability and more behavioral undercontrol, further analysis including both FH and ELA showed that FH+ persons are prone to poor affect regulation, negative moods, and have risky drinking and drug abuse tendencies independent of ELA level. ELA predicts reduced stress reactivity and poorer cognitive control over impulsive behaviors as shown elsewhere. The present work shows that FH+ have poor mood regulation and antisocial characteristics. The greater prevalence of ELA in FH+ persons indicates that life experience and FH+ work in tandem to result in risky patterns of alcohol and drug experimentation to elevate risk for alcoholism. Further studies of genetic and environmental contributions to alcoholism are called for. Published by Elsevier Ireland Ltd.

Early Motherhood and Subsequent Life Outcomes

ERIC Educational Resources Information Center

Boden, Joseph M.; Fergusson, David M.; Horwood, L. John

2008-01-01

Background: Early motherhood has been linked with a number of adverse outcomes, including mental health difficulties and barriers to completing educational qualifications and workforce participation. The present study examined the extent to which these linkages could be explained by the influence of social, family, and background factors that were…

Adverse Effects of Iodine-derived Intravenous Radiopaque Contrast Media.

PubMed

Matthews, Eric P

2015-01-01

Although the advent of nonionic low-osmolar contrast agents has reduced the probability of a reaction to radiopaque contrast media derived from tri-iodinated benzoic acid, reactions still occur. Radiologic technologists must understand and know how to manage adverse effects of contrast media. Prompt attention to patients who exhibit the early signs of an adverse reaction can help to ensure the reaction does not progress to become severe or life-threatening.

Early Life Stress, Air Pollution, Inflammation, and Disease: An Integrative Review and Immunologic Model of Social-Environmental Adversity and Lifespan Health.

PubMed

Olvera Alvarez, Hector A; Kubzansky, Laura D; Campen, Matthew J; Slavich, George M

2018-06-03

Socially disadvantaged individuals are at greater risk for simultaneously being exposed to adverse social and environmental conditions. Although the mechanisms underlying joint effects remain unclear, one hypothesis is that toxic social and environmental exposures have synergistic effects on inflammatory processes that underlie the development of chronic diseases, including cardiovascular disease, diabetes, depression, and certain types of cancer. In the present review, we examine how exposure to two risk factors that commonly occur with social disadvantage-early life stress and air pollution-affect health. Specifically, we identify neuroimmunologic pathways that could link early life stress, inflammation, air pollution, and poor health, and use this information to propose an integrated, multi-level model that describes how these factors may interact and cause health disparity across individuals based on social disadvantage. This model highlights the importance of interdisciplinary research considering multiple exposures across domains and the potential for synergistic, cross-domain effects on health, and may help identify factors that could potentially be targeted to reduce disease risk and improve lifespan health. Copyright © 2018. Published by Elsevier Ltd.

Public health implications and risks for children and families resettled after exposure to armed conflict and displacement.

PubMed

Calam, Rachel

2017-05-01

Early adverse experiences can precede long-term negative effects on physical health. Children experiencing armed conflict, flight and displacement, and refugee life may be at enhanced risk. Recent psychobiological models integrating knowledge about perinatal and childhood stress with susceptibility to chronic illnesses in later life make clear the pressing need for protective provision for war-affected children, who experience multiple traumas and continuing stressors. There is increasing recognition of the mechanisms linking physical and mental health with adult diseases seen as developmental disorders with origins early in life. Biological embedding models propose links between early adversity and increased vulnerability to later disease and premature death. Threat is central for children and families whose lives are changed by war and displacement, and may activate biological and behavioural systems that could increase the risk of long-term ill-health. Applying these models to understanding the experiences of refugees and the translation of these into the care provided and ways of monitoring and protecting long-term population health could potentially promote interventions to reduce longer term and secondary harms.

Like Father, like Child: Early Life Family Adversity and Children's Bullying Behaviors in Elementary School.

PubMed

de Vries, Else E; Verlinden, Marina; Rijlaarsdam, Jolien; Jaddoe, Vincent W V; Verhulst, Frank C; Arseneault, Louise; Tiemeier, Henning

2017-12-19

Family adversity has been associated with children's bullying behaviors. The evidence is, however, dominated by mothers' perceptions of the family environment and a focus on mothers' behaviors. This prospective population-based study examined whether children's bullying behaviors were associated with mother- and father-reported family adversity, assessed before and after child birth. Peer-nominations were used to assess bullying behaviors of 1298 children in elementary school (mean age 7.5 years). The following paternal risk factors were prospectively associated with children's bullying behaviors: (1) father-reported prenatal family distress, (2) fathers' hostility at preschool age, and (3) fathers' harsh disciplinary practices at preschool age, but effect sizes were relatively small. The effect of maternal risk factors was less consistent, only mother-reported family distress in childhood was associated with children's bullying behaviors. The associations were independent of background family risk factors (i.e., life stress, contextual factors, and other background factors such as parental education and risk taking record) and early childhood externalizing problems. Moreover, our results indicated that father-reported family adversity predicted children's bullying behaviors over and above the background family risk factors, early childhood externalizing problems and mother-reported family adversity. We also demonstrated that the association of fathers' prenatal hostility and family distress with subsequent bullying behavior of their child at school was partly mediated by fathers' harsh disciplinary practices at preschool age. Our findings highlight the importance of fathers' behaviors in the development of children's bullying behaviors.

An ESA Robotic Package to Search for Life on Mars

NASA Technical Reports Server (NTRS)

Westall, F.; Brack, A.; Clancy, P.; Hofmann, B.; Horneck, G.; Kurat, G.; Maxwell, J.; Ori, G. G.; Pillinger, C.; Raulin, F.

1999-01-01

Similarities in the early histories of Mars and Earth suggest that life may have arisen on Mars as it did on Earth. The early life forms on Mars were probably simple organisms, similar to terrestrial prokaryotes. In fact, given the early deterioration of the Martian climate, it is unlikely that life on Mars could ever have reached more sophisticated evolution. Based on the present knowledge of Mars, the possibility of extant life at the surface is small. However, given the adaptability of terrestrial prokaryotes under adverse conditions, it is not excluded. Any extant life is hypothesized to reside in the permafrost in a dormant state until "reanimated" by impact-caused hydrothermal activity. Using this rationale, a group of European scientists worked together to conceive a hypothetical strategy to search for life on Mars. A possible configuration for a lander/rover is outlined.

Predator odor exposure of rat pups has opposite effects on play by juvenile males and females

PubMed Central

Stockman, Sara L.; McCarthy, Margaret M.

2017-01-01

Juvenile social play behavior is one of the earliest sexually differentiated behaviors to emerge. In rats, as with most other species that play, males engage in more rough-and-tumble play compared to females. Exposure to early life adversity is a major driver of adult health and can manifest differently in males and females. However, the effects of adverse early life exposure on play behavior in the juvenile period are poorly understood. To address this, male and female neonatal rats were exposed to predator odor (PO), for 5 min/day on PN1-PN3. At the time of exposure to PO, both male and female pups suppressed ultrasonic vocalization and displayed more freezing behavior. Circulating corticosterone increased in males immediately following PO exposure but not in females. The enduring effects of PO exposure were opposite in males compared to females in that PO exposed males decreased social play, while PO exposed females increased play behavior compared to same sex controls. PO exposure did not significantly affect cell genesis in the neonatal dentate gyrus of either sex. PO exposure did not affect anxiety-like behavior assessed in the juvenile period or in adulthood, nor did it affect social interactions in adulthood. This work provides new insight into how sex may interact with adverse early life events to contribute to development of the social consequences of such exposures. PMID:27569603

Early childhood adversities and risk of eating disorders in women: A Danish register-based cohort study.

PubMed

Larsen, Janne Tidselbak; Munk-Olsen, Trine; Bulik, Cynthia M; Thornton, Laura M; Koch, Susanne Vinkel; Mortensen, Preben Bo; Petersen, Liselotte

2017-12-01

Previous studies evaluating the association between early childhood adversities and eating disorders have yielded conflicting results. The aim of this study is to examine the association between a range of adversities and risk of anorexia nervosa (AN), bulimia nervosa (BN), and eating disorder not otherwise specified (EDNOS) in 495,244 women. In this nationwide, register-based cohort study, nine types of early childhood adversity (family disruption, residential instability, placement in out-of-home care, familial death, parental somatic illness, parental psychiatric illness, parental disability, severe parental criminality, and parental substance use disorder) were defined and exposure during the first 6 years of life was determined. Hazard ratios for eating disorders were calculated using Cox regression. Few adversities were significantly associated with AN, and for each, the presence of the adversity was associated with lower risk for AN. BN, and EDNOS were positively associated with several types of adversities. AN rates were unchanged or reduced by up to 54% by adversities, whereas rates of BN and EDNOS were unchanged or increased by adversities by up to 49 and 89%, respectively. Our findings indicate that childhood adversities appear to be associated with an increased risk of BN and in particular EDNOS, whereas they seem to be either unassociated or associated with a decreased risk of AN. © 2017 Wiley Periodicals, Inc.

Early blood glucose profile and neurodevelopmental outcome at two years in neonatal hypoxic-ischaemic encephalopathy

PubMed Central

2011-01-01

Background To examine the blood glucose profile and the relationship between blood glucose levels and neurodevelopmental outcome in term infants with hypoxic-ischaemic encephalopathy. Methods Blood glucose values within 72 hours of birth were collected from 52 term infants with hypoxic-ischaemic encephalopathy. Hypoglycaemia [< 46.8 mg/dL (2.6 mmol/L)] and hyperglycaemia [> 150 mg/dL (8.3 mmol/L)] were correlated to neurodevelopmental outcome at 24 months of age. Results Four fifths of the 468 blood samples were in the normoglycaemic range (392/468:83.8%). Of the remaining 76 samples, 51.3% were in the hypoglycaemic range and (48.7%) were hyperglycaemic. A quarter of the hypoglycaemic samples (28.2%:11/39) and a third of the hyperglycaemic samples (32.4%:12/37) were recorded within the first 30 minutes of life. Mean (SD) blood glucose values did not differ between infants with normal and abnormal outcomes [4.89(2.28) mmol/L and 5.02(2.35) mmol/L, p value = 0.15] respectively. In term infants with hypoxic-ischaemic encephalopathy, early hypoglycaemia (between 0-6 hours of life) was associated with adverse outcome at 24 months of age [OR = 5.8, CI = 1.04-32)]. On multivariate analysis to adjust for grade of HIE this association was not statistically significant. Late hypoglycaemia (6-72 hours of life) was not associated with abnormal outcome [OR = 0.22, CI (0.04-1.14)]. The occurrence of hyperglycaemia was not associated with adverse outcome. Conclusion During the first 72 hours of life, blood glucose profile in infants with hypoxic-ischaemic encephalopathy varies widely despite a management protocol. Early hypoglycaemia (0-6 hours of life) was associated with severe HIE, and thereby; adverse outcome. PMID:21294901

Early-Life Social Origins of Later-Life Body Weight: The Role of Socioeconomic Status and Health Behaviors over the Life Course

PubMed Central

Logan, Ellis Scott; Richman, Aliza

2014-01-01

Using the 1957-2004 data from the Wisconsin Longitudinal Study, we apply structural equation modeling to examine gender-specific effects of family socioeconomic status (SES) at age 18 on body weight at age 65. We further explore SES and health behaviors over the life course as mechanisms linking family background and later-life body weight. We find that early-life socioeconomic disadvantage is related to higher body weight at age 65 and a steeper weight increase between midlife and late life. These adverse effects are stronger among women than men. Significant mediators of the effect of parents' SES include adolescent body mass (especially among women) as well as exercise and SES in midlife. Yet, consistent with the critical period mechanism, the effect of early-life SES on late-life body weight persists net of all mediating variables. This study expands current understanding of life-course mechanisms that contribute to obesity and increase biological vulnerability to social disadvantage. PMID:24767590

Developmental Origins of Chronic Kidney Disease: Should We Focus on Early Life?

PubMed Central

Tain, You-Lin; Hsu, Chien-Ning

2017-01-01

Chronic kidney disease (CKD) is becoming a global burden, despite recent advances in management. CKD can begin in early life by so-called “developmental programming” or “developmental origins of health and disease” (DOHaD). Early-life insults cause structural and functional changes in the developing kidney, which is called renal programming. Epidemiological and experimental evidence supports the proposition that early-life adverse events lead to renal programming and make subjects vulnerable to developing CKD and its comorbidities in later life. In addition to low nephron endowment, several mechanisms have been proposed for renal programming. The DOHaD concept opens a new window to offset the programming process in early life to prevent the development of adult kidney disease, namely reprogramming. Here, we review the key themes on the developmental origins of CKD. We have particularly focused on the following areas: evidence from human studies support fetal programming of kidney disease; insight from animal models of renal programming; hypothetical mechanisms of renal programming; alterations of renal transcriptome in response to early-life insults; and the application of reprogramming interventions to prevent the programming of kidney disease. PMID:28208659

Early Adversity and Developmental Outcomes: Interaction Between Genetics, Epigenetics, and Social Experiences Across the Life Span.

PubMed

Champagne, Frances A

2010-09-01

Longitudinal studies in humans demonstrate the association between prenatal and postnatal experiences of adversity and long-term changes in neurodevelopment. These studies raise the question of how experiences become incorporated at a biological level to induce persistent changes in functioning. Laboratory studies using animal models and recent analyses in human cohorts implicate epigenetic mechanisms as a possible route through which these environmental effects are achieved. In particular, there is evidence that changes in DNA methylation are associated with early life experiences with consequences for gene expression and behavior. Despite the potential stability of DNA methylation, it is apparent that this epigenetic mark can be dynamically modified through pharmacological targeting and behavioral experiences. Developmental plasticity may also be achieved through modification of the juvenile environment. Although these juvenile experiences may lead to common endpoints, there is evidence suggesting that the effects of early and later life experiences may be achieved by different molecular pathways. This review discusses evidence for the role of epigenetic mechanisms in shaping developmental trajectories in response to early life experience as well as the potential plasticity that can occur beyond the perinatal period. These studies have implications for approaches to intervention and suggest the importance of considering individual differences in genetic and epigenetic vulnerability in developing treatment strategies. © The Author(s) 2010.

Do Cherished Children Age Successfully? Longitudinal Findings from the VA Normative Aging Study

PubMed Central

Lee, Lewina O.; Aldwin, Carolyn M.; Kubzansky, Laura D.; Chen, Edith; Mroczek, Daniel K.; Wang, Joyce M.; Spiro, Avron

2015-01-01

Although early adversity has been linked to worse mental and physical health in adulthood, few studies have investigated the pathways through which positive and negative dimensions of early experiences can jointly influence psychological well-being in later life. This study examined: (1) profiles of early experiences across multiple domains; (2) the relations of these profiles to hedonic and eudaimonic well-being in later life; and (3) whether midlife social support mediated these relations. We first conducted latent class analysis of early experiences using data from 1,076 men in the VA Normative Aging Study who completed the Childhood Experiences Scale (age: M=69, SD=7). Analyses yielded three profiles of early experiences, labeled as cherished (strong support and some losses), harshly disciplined (harsh parental discipline, low positive reinforcement, and non-normative stressors), and ordinary (few stressors and low parental attention). Next, we applied structural equation modeling to data on a subset of this sample assessed seven years later on hedonic and eudaimonic well-being (n=496; age: M=76, SD=7). In general, the cherished group reported stronger qualitative social support in midlife than the harshly disciplined and ordinary groups, which in turn was related to greater hedonic (life satisfaction, positive affect) and eudaimonic (competence, positive relations with others) well-being in later life. The cherished group also reported higher autonomy than the ordinary group, but this association was independent of midlife social support. Our findings suggest that experiencing adversity in the context of a nurturing early environment can promote successful aging through the maintenance of supportive relationships in midlife. PMID:26436456

Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

PubMed Central

Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

2014-01-01

Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be addressed. PMID:24860550

Respiratory effects of air pollution on children.

PubMed

Goldizen, Fiona C; Sly, Peter D; Knibbs, Luke D

2016-01-01

A substantial proportion of the global burden of disease is directly or indirectly attributable to exposure to air pollution. Exposures occurring during the periods of organogenesis and rapid lung growth during fetal development and early post-natal life are especially damaging. In this State of the Art review, we discuss air toxicants impacting on children's respiratory health, routes of exposure with an emphasis on unique pathways relevant to young children, methods of exposure assessment and their limitations and the adverse health consequences of exposures. Finally, we point out gaps in knowledge and research needs in this area. A greater understanding of the adverse health consequences of exposure to air pollution in early life is required to encourage policy makers to reduce such exposures and improve human health. © 2015 Wiley Periodicals, Inc.

Infant titi monkey behavior in the open field test and the effect of early adversity

PubMed Central

Larke, Rebecca H.; Toubiana, Alice; Lindsay, Katrina A.; Mendoza, Sally P.; Bales, Karen L.

2017-01-01

The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. PMID:28605039

The long reach of early adversity: Parenting, stress, and neural pathways to antisocial behavior in adulthood.

PubMed

Gard, Arianna M; Waller, Rebecca; Shaw, Daniel S; Forbes, Erika E; Hariri, Ahmad R; Hyde, Luke W

2017-10-01

Early life adversities including harsh parenting, maternal depression, neighborhood deprivation, and low family economic resources are more prevalent in low-income urban environments and are potent predictors of psychopathology, including, for boys, antisocial behavior (AB). However, little research has examined how these stressful experiences alter later neural function. Moreover, identifying genetic markers of greater susceptibility to adversity is critical to understanding biopsychosocial pathways from early adversity to later psychopathology. Within a sample of 310 low-income boys followed from age 1.5 to 20, multimethod assessments of adversities were examined at age 2 and age 12. At age 20, amygdala reactivity to emotional facial expressions was assessed using fMRI, and symptoms of Antisocial Personality Disorder were assessed via structured clinical interview. Genetic variability in cortisol signaling ( CRHR1 ) was examined as a moderator of pathways to amygdala reactivity. Observed parenting and neighborhood deprivation at age 2 each uniquely predicted amygdala reactivity to emotional faces at age 20 over and above other adversities measured at multiple developmental periods. Harsher parenting and greater neighborhood deprivation in toddlerhood predicted clinically-significant symptoms of AB via less amygdala reactivity to fearful facial expressions and this pathway was moderated by genetic variation in CRHR1 . These results elucidate a pathway linking early adversity to less amygdala reactivity to social signals of interpersonal distress 18 years later, which in turn increased risk for serious AB. Moreover, these findings suggest a genetic marker of youth more susceptible to adversity.

External-environmental and internal-health early life predictors of adolescent development.

PubMed

Hartman, Sarah; Li, Zhi; Nettle, Daniel; Belsky, Jay

2017-12-01

A wealth of evidence documents associations between various aspects of the rearing environment and later development. Two evolutionary-inspired models advance explanations for why and how such early experiences shape later functioning: (a) the external-prediction model, which highlights the role of the early environment (e.g., parenting) in regulating children's development, and (b) the internal-prediction model, which emphasizes internal state (i.e., health) as the critical regulator. Thus, by using data from the NICHD Study of Early Child Care and Youth Development, the current project draws from both models by investigating whether the effect of the early environment on later adolescent functioning is subject to an indirect effect by internal-health variables. Results showed a significant indirect effect of internal health on the relation between the early environment and adolescent behavior. Specifically, early environmental adversity during the first 5 years of life predicted lower quality health during childhood, which then led to problematic adolescent functioning and earlier age of menarche for girls. In addition, for girls, early adversity predicted lower quality health that forecasted earlier age of menarche leading to increased adolescent risk taking. The discussion highlights the importance of integrating both internal and external models to further understand the developmental processes that effect adolescent behavior.

Impact of Childhood Adversity and Vasopressin receptor 1a Variation on Social Interaction in Adulthood: A Cross-Sectional Study.

PubMed

Liu, Jia Jia; Lou, Fenglan; Lavebratt, Catharina; Forsell, Yvonne

2015-01-01

Arginine vasopressin (AVP) plays a role in social behavior, through receptor AVPR1A. The promoter polymorphism AVPR1A RS3 has been associated with human social behaviors, and with acute response to stress. Here, the relationships between AVPR1A RS3, early-life stressors, and social interaction in adulthood were explored. Adult individuals from a Swedish population-based cohort (n = 1871) were assessed for self-reported availability of social integration and social attachment and for experience of childhood adversities. Their DNA samples were genotyped for the microsatellite AVPR1A RS3. Among males, particularly those homozygous for the long alleles of AVPR1A RS3 were vulnerable to childhood adversity for their social attachment in adulthood. A similar vulnerability to childhood adversity among long allele carriers was found on adulthood social integration, but here both males and females were influenced. Data were self-reported and childhood adversity data were retrospective. Early-life stress influenced the relationship between AVPR1A genetic variants and social interaction. For social attachment, AVPR1A was of importance in males only. The findings add to previous reports on higher acute vulnerability to stress in persons with long AVPR1A RS3 alleles and increased AVP levels.

High early life mortality in free-ranging dogs is largely influenced by humans

PubMed Central

Paul, Manabi; Sen Majumder, Sreejani; Sau, Shubhra; Nandi, Anjan K.; Bhadra, Anindita

2016-01-01

Free-ranging dogs are a ubiquitous part of human habitations in many developing countries, leading a life of scavengers dependent on human wastes for survival. The effective management of free-ranging dogs calls for understanding of their population dynamics. Life expectancy at birth and early life mortality are important factors that shape life-histories of mammals. We carried out a five year-long census based study in seven locations of West Bengal, India, to understand the pattern of population growth and factors affecting early life mortality in free-ranging dogs. We observed high rates of mortality, with only ~19% of the 364 pups from 95 observed litters surviving till the reproductive age; 63% of total mortality being human influenced. While living near people increases resource availability for dogs, it also has deep adverse impacts on their population growth, making the dog-human relationship on streets highly complex. PMID:26804633

Adverse early life experience and social stress during adulthood interact to increase serotonin transporter mRNA expression

PubMed Central

Gardner, Katherine L.; Hale, Matthew W.; Lightman, Stafford L.; Plotsky, Paul M.; Lowry, Christopher A.

2009-01-01

Anxiety disorders, depression and animal models of vulnerability to a depression-like syndrome have been associated with dysregulation of serotonergic systems in the brain. To evaluate the effects of early life experience, adverse experiences during adulthood, and potential interactions between these factors on serotonin transporter (slc6a4) mRNA expression, we investigated in rats the effects of maternal separation (180 min/day from days 2–14 of life; MS180), neonatal handing (15 min/day from days 2–14 of life; MS15), or normal animal facility rearing control conditions (AFR) with or without subsequent exposure to adult social defeat on slc6a4 mRNA expression in the dorsal raphe nucleus (DR) and caudal linear nucleus. At the level of specific subdivisions of the DR, there were no differences in slc6a4 mRNA expression between MS15 and AFR rats. Among rats exposed to a novel cage control condition, increased slc6a4 mRNA expression was observed in the dorsal part of the DR in MS180 rats, relative to AFR control rats. In contrast, MS180 rats exposed to social defeat as adults had increased slc6a4 mRNA expression throughout the DR compared to both MS15 and AFR controls. Social defeat increased slc6a4 mRNA expression, but only in MS180 rats and only in the “lateral wings” of the DR. Overall these data demonstrate that early life experience and stressful experience during adulthood interact to determine slc6a4 mRNA expression. These data support the hypothesis that early life experience and major stressful life events contribute to dysregulation of serotonergic systems in stress-related neuropsychiatric disorders. PMID:19781533

Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively.

PubMed

Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J

2018-05-01

Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

Early-Life Nutritional Programming of Health and Disease in The Gambia.

PubMed

Moore, Sophie E

2017-01-01

Exposures during early life are increasingly being recognised as factors that play an important role in the aetiology of chronic non-communicable diseases (NCDs). The "Developmental Origins of Health and Disease" (DOHaD) hypothesis asserts that adverse early-life exposures - most notably unbalanced nutrition - leads to an increased risk for a range of NCDs and that disease risk is highest when there is a "mismatch" between the early- and later-life environments. Thus, the DOHaD hypothesis would predict highest risk in settings undergoing a rapid nutrition transition. We investigated the link between early-life nutritional exposures and long-term health in rural Gambia, West Africa. Using demographic data dating back to the 1940s, the follow-up of randomised controlled trials of nutritional supplementation in pregnancy, and the "experiment of nature" that seasonality in this region provides, we investigated the DOHaD hypothesis in a population with high rates of maternal and infant under-nutrition, a high burden from infectious disease, and an emerging risk of NCDs. Key Messages: Our work in rural Gambia suggests that in populations with high rates of under-nutrition in early life, the immune system may be sensitive to nutritional deficiencies early in life, resulting in a greater susceptibility to infection-related morbidity and mortality. © 2017 S. Karger AG, Basel.

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

PubMed Central

Dayer, Alexandre

2014-01-01

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. PMID:24733969

Maternal Childhood Adversity, Prepregnancy Obesity, and Gestational Weight Gain.

PubMed

Ranchod, Yamini K; Headen, Irene E; Petito, Lucia C; Deardorff, Julianna K; Rehkopf, David H; Abrams, Barbara F

2016-04-01

Growing evidence suggests that exposure to childhood adversity may influence obesity across the life course. High maternal weight complicates pregnancy and increases the risk of child obesity. This study examined the association between maternal childhood adversity and pregnancy-related weight in a large U.S. Data on 6,199 pregnancies from 2,873 women followed from 1979 to 2012 by the National Longitudinal Survey of Youth 1979 were analyzed in 2014. Associations between three adversity exposures before age 18 years (history of physical abuse, alcohol problems, or mental illness in the household) and two maternal weight outcomes (prepregnancy obesity and excessive gestational weight gain) were modeled separately using survey-adjusted log-binomial models. After adjusting for race/ethnicity and early-life socioeconomic factors, childhood physical abuse was associated with a 60% increase in the risk of prepregnancy obesity (adjusted risk ratio=1.6, 95% CI=1.1, 2.2). Household alcohol abuse was associated with a 30% increase in prepregnancy obesity (adjusted risk ratio=1.3, 95% CI=1.0, 1.7), as was household mental illness (adjusted risk ratio=1.3, 95% CI=0.8, 1.9), but the mental illness exposure was not significant. Physical abuse and household alcohol abuse were associated with a significant 20% increase in the risk of excessive gestational weight gain; mental illness was not. Adversity in early life may affect maternal weight before and during pregnancy. Screening and treating women of reproductive age for childhood adversity and its negative effects could significantly reduce obesity-related health outcomes for women and their children. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

Future Directions in the Study of Early-Life Stress and Physical and Emotional Health: Implications of the Neuroimmune Network Hypothesis.

PubMed

Hostinar, Camelia E; Nusslock, Robin; Miller, Gregory E

2018-01-01

Early-life stress is associated with increased vulnerability to physical and emotional health problems across the lifespan. The recently developed neuroimmune network hypothesis proposes that one of the underlying mechanisms for these associations is that early-life stress amplifies bidirectional crosstalk between the brain and the immune system, contributing to several mental and physical health conditions that have inflammatory underpinnings, such as depression and coronary heart disease. Neuroimmune crosstalk is thought to perpetuate inflammation and neural alterations linked to early-life stress exposure, and also foster behaviors that can further compromise health, such as smoking, drug abuse and consumption of high-fat diets. The goal of the present review is to briefly summarize the neuroimmune network hypothesis and use it as a starting point for generating new questions about the role of early-life stress in establishing a dysregulated relationship between neural and immune signaling, with consequences for lifespan physical and emotional health. Specifically, we aim to discuss implications and future directions for theory and empirical research on early-life stress, as well as for interventions that may improve the health and well-being of children and adolescents living in adverse conditions.

Personal Resources and Homelessness in Early Life: Predictors of Depression in Consumers of Homeless Multiservice Centers

ERIC Educational Resources Information Center

DeForge, Bruce R.; Belcher, John R.; O'Rourke, Michael; Lindsey, Michael A.

2008-01-01

This study explored the relationship between personal resources and previous adverse life events such as homelessness and depression. Participants were recruited from two church sponsored multisite social service centers in Anne Arundel County, Maryland. The interview included demographics and several standardized scales to assess history of…

Chaotic home environment is associated with reduced infant processing speed under high task demands.

PubMed

Tomalski, Przemysław; Marczuk, Karolina; Pisula, Ewa; Malinowska, Anna; Kawa, Rafał; Niedźwiecka, Alicja

2017-08-01

Early adversity has profound long-term consequences for child development across domains. The effects of early adversity on structural and functional brain development were shown for infants under 12 months of life. However, the causal mechanisms of these effects remain relatively unexplored. Using a visual habituation task we investigated whether chaotic home environment may affect processing speed in 5.5 month-old infants (n=71). We found detrimental effects of chaos on processing speed for complex but not for simple visual stimuli. No effects of socio-economic status on infant processing speed were found although the sample was predominantly middle class. Our results indicate that chaotic early environment may adversely affect processing speed in early infancy, but only when greater cognitive resources need to be deployed. The study highlights an attractive avenue for research on the mechanisms linking home environment with the development of attention control. Copyright © 2017 Elsevier Inc. All rights reserved.

Stressful Life Events, ADHD Symptoms, and Brain Structure in Early Adolescence.

PubMed

Humphreys, Kathryn L; Watts, Emily L; Dennis, Emily L; King, Lucy S; Thompson, Paul M; Gotlib, Ian H

2018-05-21

Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

Before the first breath: prenatal exposures to air pollution and lung development.

PubMed

Veras, Mariana Matera; de Oliveira Alves, Nilmara; Fajersztajn, Lais; Saldiva, Paulo

2017-03-01

Various environmental contaminants are known to impair the growth trajectories of major organs, indirectly (gestational exposure) or directly (postnatal exposure). Evidence associates pre-gestational and gestational exposure to air pollutants with adverse birth outcomes (e.g., low birth weight, prematurity) and with a wide range of diseases in childhood and later in life. In this review, we explore the way that pre-gestational and gestational exposure to air pollution affects lung development. We present results in topics underlining epidemiological and toxicological evidence. We also provide a summary of the biological mechanisms by which air pollution exposure possibly leads to adverse respiratory outcomes. We conclude that gestational and early life exposure to air pollutants are linked to alterations in lung development and function and to other negative respiratory conditions in childhood (wheezing, asthma) that may last into adulthood. Plausible mechanisms encompass changes in maternal physiology (e.g., hypoxia, oxidative stress and inflammation) and DNA alterations in the fetus. Evidence for pre-gestational and gestational effects on the lung is scarce compared with that on early life exposure and further studies are needed. However, the suggested mechanisms are credible and the evidence of pre-gestational and gestational air pollution exposure is robust for adverse birth outcomes. Air pollutants might change lung developmental trajectories of the unborn child predisposing it to diseases later in life highlighting the urgent need for controls on urban air pollution levels worldwide.

Predator odor exposure of rat pups has opposite effects on play by juvenile males and females.

PubMed

Stockman, Sara L; McCarthy, Margaret M

2017-01-01

Juvenile social play behavior is one of the earliest sexually differentiated behaviors to emerge. In rats, as with most other species that play, males engage in more rough-and-tumble play compared to females. Exposure to early life adversity is a major driver of adult health and can manifest differently in males and females. However, the effects of adverse early life exposure on play behavior in the juvenile period are poorly understood. To address this, male and female neonatal rats were exposed to predator odor (PO), for 5min/day on PN1-PN3. At the time of exposure to PO, both male and female pups suppressed ultrasonic vocalization and displayed more freezing behavior. Circulating corticosterone increased in males immediately following PO exposure but not in females. The enduring effects of PO exposure were opposite in males compared to females in that PO exposed males decreased social play, while PO exposed females increased play behavior compared to same sex controls. PO exposure did not significantly affect cell genesis in the neonatal dentate gyrus of either sex. PO exposure did not affect anxiety-like behavior assessed in the juvenile period or in adulthood, nor did it affect social interactions in adulthood. This work provides new insight into how sex may interact with adverse early life events to contribute to development of the social consequences of such exposures. Copyright © 2016 Elsevier Inc. All rights reserved.

Are early-life antecedents of suicide mortality associated with psychiatric disorders and suicidal ideation in midlife?

PubMed

Geoffroy, M-C; Gunnell, D; Clark, C; Power, C

2018-02-01

To establish whether previously identified early-life antecedents of suicide mortality (i.e. low birthweight, younger maternal age, higher birth order, externalizing problems and adversities) are associated with proximal psychiatric disorders and suicidal ideation, which are themselves associated with an increased risk of suicide. Participants were from the 1958 British birth-cohort (N = 8905) with information on prenatal/childhood experiences and the Clinical Interview Schedule-Revised at age 45 years. Outcomes were as follows: any internalizing disorder (anxiety disorder/depressive episode), depressive episode, alcohol use disorder and suicidal ideation. After adjustment, higher birth order (P trend = 0.043), younger maternal age (P trend = 0.017) and increased number of childhood adversities (P trend = 0.026) were associated with an increased risk of internalizing disorders. For example, the OR (95% CI) in fourth- or later-born children was 1.48 (1.06-2.07) and for young maternal age (<19 years) was 1.31 (0.89-1.91). Effect sizes were similar in magnitude for depressive episode and suicidal ideation, although associations did not reach conventional significance levels. No associations were found for low birthweight and externalizing problems (in males) and investigated outcomes. Associations for younger maternal age, higher birth order and adversities with adult internalizing disorders suggest that psychiatric disorders may be on the pathway linking some early-life factors and suicide. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Long-Term Impact of Early Life Poverty on Orbitofrontal Cortex Volume in Adulthood: Results from a Prospective Study Over 25 Years

PubMed Central

Holz, Nathalie E; Boecker, Regina; Hohm, Erika; Zohsel, Katrin; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Plichta, Michael M; Esser, Günter; Schmidt, Martin; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2015-01-01

Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0=non-exposed (N=134), 1=exposed (N=33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother–infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities. PMID:25315195

The long-term impact of early life poverty on orbitofrontal cortex volume in adulthood: results from a prospective study over 25 years.

PubMed

Holz, Nathalie E; Boecker, Regina; Hohm, Erika; Zohsel, Katrin; Buchmann, Arlette F; Blomeyer, Dorothea; Jennen-Steinmetz, Christine; Baumeister, Sarah; Hohmann, Sarah; Wolf, Isabella; Plichta, Michael M; Esser, Günter; Schmidt, Martin; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

2015-03-01

Converging evidence has highlighted the association between poverty and conduct disorder (CD) without specifying neurobiological pathways. Neuroimaging research has emphasized structural and functional alterations in the orbitofrontal cortex (OFC) as one key mechanism underlying this disorder. The present study aimed to clarify the long-term influence of early poverty on OFC volume and its association with CD symptoms in healthy participants of an epidemiological cohort study followed since birth. At age 25 years, voxel-based morphometry was applied to study brain volume differences. Poverty (0=non-exposed (N=134), 1=exposed (N=33)) and smoking during pregnancy were determined using a standardized parent interview, and information on maternal responsiveness was derived from videotaped mother-infant interactions at the age of 3 months. CD symptoms were assessed by diagnostic interview from 8 to 19 years of age. Information on life stress was acquired at each assessment and childhood maltreatment was measured using retrospective self-report at the age of 23 years. Analyses were adjusted for sex, parental psychopathology and delinquency, obstetric adversity, parental education, and current poverty. Individuals exposed to early life poverty exhibited a lower OFC volume. Moreover, we replicated previous findings of increased CD symptoms as a consequence of childhood poverty. This effect proved statistically mediated by OFC volume and exposure to life stress and smoking during pregnancy, but not by childhood maltreatment and maternal responsiveness. These findings underline the importance of studying the impact of early life adversity on brain alterations and highlight the need for programs to decrease income-related disparities.

Ventral striatal activity links adversity and reward processing in children.

PubMed

Kamkar, Niki H; Lewis, Daniel J; van den Bos, Wouter; Morton, J Bruce

2017-08-01

Adversity impacts many aspects of psychological and physical development including reward-based learning and decision-making. Mechanisms relating adversity and reward processing in children, however, remain unclear. Here, we show that adversity is associated with potentiated learning from positive outcomes and impulsive decision-making, but unrelated to learning from negative outcomes. We then show via functional magnetic resonance imaging that the link between adversity and reward processing is partially mediated by differences in ventral striatal response to rewards. The findings suggest that early-life adversity is associated with alterations in the brain's sensitivity to rewards accounting, in part, for the link between adversity and altered reward processing in children. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Update on Postnatal Steroids.

PubMed

Halliday, Henry L

2017-01-01

Antenatal steroid treatment to enhance fetal lung maturity and surfactant treatment to prevent or treat respiratory distress syndrome have been major advances in perinatal medicine in the past 40 years contributing to improved outcomes for preterm infants. Use of postnatal steroids to prevent or treat chronic lung disease in preterm infants has been less successful and associated with adverse neurodevelopmental outcomes. Although early (in the first week of life) postnatal steroid treatment facilitates earlier extubation and reduces the risk of chronic lung disease, it is associated with adverse effects, such as hyperglycemia, hypertension, gastrointestinal bleeding and perforation, hypertrophic cardiomyopathy, growth failure, and cerebral palsy, and cannot be recommended. Early treatment with hydrocortisone may also improve survival without chronic lung disease, but concerns remain about possible adverse effects such as gastrointestinal perforation and sepsis, particularly in very preterm infants. Early inhaled budesonide also reduces the incidence of chronic lung disease but there are concerns that this may occur at the expense of increased risk of death. More studies of early low-dose steroids with adequate long-term follow-up are needed before they can be recommended for the prevention of chronic lung disease. Late (after the first week of life) postnatal steroids may have a better benefit-to-harm ratio than early steroids. A Cochrane Review shows that late steroid treatment reduces chronic lung disease, the combination of death and chronic lung disease at both 28 days and 36 weeks' corrected age, and the need for later rescue dexamethasone. Adverse effects include hyperglycemia, hypertension, hypertrophic cardiomyopathy, and severe retinopathy of prematurity but without an increase in blindness. Long-term neurodevelopmental effects are not significantly increased by late postnatal steroid treatment. Current recommendations are that postnatal steroid treatment should be reserved for preterm infants who are ventilator-dependent after the first 7-14 days of life and any course should be low dose and of short duration to facilitate endotracheal extubation. Budesonide/surfactant mixtures show some promise as a means of reducing chronic lung disease in preterm infants with severe respiratory distress syndrome, but further larger studies with long-term follow-up are needed before this treatment can be recommended as a routine intervention. © 2017 S. Karger AG, Basel.

Infant titi monkey behavior in the open field test and the effect of early adversity.

PubMed

Larke, Rebecca H; Toubiana, Alice; Lindsay, Katrina A; Mendoza, Sally P; Bales, Karen L

2017-09-01

The open field test is commonly used to measure anxiety-related behavior and exploration in rodents. Here, we used it as a standardized novel environment in which to evaluate the behavioral response of infant titi monkeys (Callicebus cupreus), to determine the effect of presence of individual family members, and to assess how adverse early experience alters infant behavior. Infants were tested in the open field for 5 days at ages 4 and 6 months in four successive 5 min trials on each day. A transport cage, which was situated on one side of the open field, was either empty (non-social control) or contained the father, mother, or sibling. Infant locomotor, vocalization, and exploratory behavior were quantified. Results indicated that age, sex, social condition, and early experience all had significant effects on infant behavior. Specifically, infants were generally more exploratory at 6 months and male infants were more exploratory than females. Infants distinguished between social and non-social conditions but made few behavioral distinctions between the attachment figure and other individuals. Infants which had adverse early life experience demonstrated greater emotional and physical independence, suggesting that early adversity led to resiliency in the novel environment. © 2017 Wiley Periodicals, Inc.

Relationship of childhood adversity and neighborhood violence to a proinflammatory phenotype in emerging adult African American men: An epigenetic link.

PubMed

Janusek, Linda Witek; Tell, Dina; Gaylord-Harden, Noni; Mathews, Herbert L

2017-02-01

African American men (AAM) who are exposed to trauma and adversity during their early life are at greater risk for poor health over their lifespan. Exposure to adversity during critical developmental windows may embed an epigenetic signature that alters expression of genes that regulate stress response systems, including those genes that regulate the inflammatory response to stress. Such an epigenetic signature may increase risk for diseases exacerbated by inflammation, and may contribute to health disparity. The purpose of this study was to evaluate the extent to which exposure to early life adversity influences the psychological, cortisol, and proinflammatory response to acute stress (Trier Social Stress Test - TSST) in emerging adult AAM, ages 18-25years (N=34). Hierarchical linear modeling was used to examine the cortisol and IL-6 pattern of response to the TSST with respect to childhood adversity factors and DNA methylation of the IL-6 promoter. Findings revealed that in response to the TSST, greater levels of childhood trauma and indirect exposure to neighborhood violence were associated with a greater TSST-induced IL-6 response, and a blunted cortisol response. Reduced methylation of the IL6 promoter was related to increased exposure to childhood trauma and greater TSST-induced IL-6 levels. These results support the concept that exposure to childhood adversity amplifies the adult proinflammatory response to stress, which is related to epigenetic signature. Copyright © 2016 Elsevier Inc. All rights reserved.

Quality of life at the retirement transition: Life course pathways in an early 'baby boom' birth cohort.

PubMed

Wildman, Josephine M; Moffatt, Suzanne; Pearce, Mark

2018-06-01

Promoting quality of life (QoL) in later life is an important policy goal. However, studies using prospective data to explore the mechanisms by which earlier events influence QoL in older age are lacking. This study is the first to use prospective data to investigate pathways by which a range of measures of life-course socioeconomic status contribute to later-life QoL. The study uses data from the Newcastle Thousand Families Study cohort (N = 1142), an early 'baby-boom' birth cohort born in 1947 in Newcastle upon Tyne, an industrial city in north-east England. Using prospective survey data collected between birth and later adulthood (N = 393), a path analysis investigated the effects and relative contributions of a range of life-course socioeconomic factors to QoL at age 62-64 measured using the CASP-19 scale. Strong positive effects on later-life QoL were found for advantaged occupational status in mid-life and better self-reported health, employment and mortgage-freedom in later adulthood. Significant positive indirect effects on QoL were found from social class at birth and achieved education level, mediated through later-life socioeconomic advantage. Experiencing no adverse events by age five had a large total positive effect on QoL at age 62-64, comprising a direct effect and indirect effects, mediated through education, mid-life social class and later-life self-reported health. Results support a pathway model with the effects of factors in earlier life acting via later-life factors, and an accumulation model with earlier-life factors having large total, cumulative effects on later-life QoL. The presence of a direct effect of adverse childhood events by age five on QoL suggests a 'critical period' and indicates that policies across the life-course are needed to promote later-life QoL, with policies directed towards older adults perhaps too late to 'undo the damage' of earlier adverse events. Copyright © 2018 Elsevier Ltd. All rights reserved.

Brain Regions Related to Impulsivity Mediate the Effects of Early Adversity on Antisocial Behavior.

PubMed

Mackey, Scott; Chaarani, Bader; Kan, Kees-Jan; Spechler, Philip A; Orr, Catherine; Banaschewski, Tobias; Barker, Gareth; Bokde, Arun L W; Bromberg, Uli; Büchel, Christian; Cattrell, Anna; Conrod, Patricia J; Desrivières, Sylvane; Flor, Herta; Frouin, Vincent; Gallinat, Jürgen; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Paillère Martinot, Marie-Laure; Artiges, Eric; Nees, Frauke; Papadopoulos-Orfanos, Dimitri; Poustka, Luise; Smolka, Michael N; Jurk, Sarah; Walter, Henrik; Whelan, Robert; Schumann, Gunter; Althoff, Robert R; Garavan, Hugh

2017-08-15

Individual differences in impulsivity and early adversity are known to be strong predictors of adolescent antisocial behavior. However, the neurobiological bases of impulsivity and their relation to antisocial behavior and adversity are poorly understood. Impulsivity was estimated with a temporal discounting task. Voxel-based morphometry was used to determine the brain structural correlates of temporal discounting in a large cohort (n = 1830) of 14- to 15-year-old children. Mediation analysis was then used to determine whether the volumes of brain regions associated with temporal discounting mediate the relation between adverse life events (e.g., family conflict, serious accidents) and antisocial behaviors (e.g., precocious sexual activity, bullying, illicit substance use). Greater temporal discounting (more impulsivity) was associated with 1) lower volume in frontomedial cortex and bilateral insula and 2) greater volume in a subcortical region encompassing the ventral striatum, hypothalamus and anterior thalamus. The volume ratio between these cortical and subcortical regions was found to partially mediate the relation between adverse life events and antisocial behavior. Temporal discounting is related to regions of the brain involved in reward processing and interoception. The results support a developmental imbalance model of impulsivity and are consistent with the idea that negative environmental factors can alter the developing brain in ways that promote antisocial behavior. Copyright © 2016 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Sex differences in the consequences of early-life exposure to epidemiological stress--a life-history approach.

PubMed

Störmer, Charlotte

2011-01-01

Exposure to infectious disease in early life has been suggested to have a negative effect on later-life survival,possibly through the induction of inflammatory responses. Although a life-course perspective emphasizes the importance of both survival and reproduction for individual fitness, to date, no studies have investigated whether early-life exposure to infectious disease has an impact on reproduction as it has been suggested for later survival. To address this question, I have used family reconstitution data from a historical (18th and 19th century) human population in the Krummhörn (Germany) comparing survival and reproduction between an exposed and a non-exposed group. The exposed group comprised those exposed to a high-infectious disease load during prenatal and early postnatal development. The results show a marked sex difference in the impact of early-life exposure to infectious disease. Exposed females show no effect on their life expectancy but significantly reduced fertility (number of children). For exposed males, however, the effect on survival is opponent over time: mortality is increased during childhood but decreased in late adulthood. Above that, exposed males reproduce earlier and have a smaller proportion of surviving children. This study does not support former studies indicating a negative association between early-life disease load and later survival. I argue that due to differences in male and female life strategies, males in general are more vulnerable especially early in life. Hence, adverse environmental conditions may have a stronger effect on male survivability and reproductive performance.

Early childhood adversity, toxic stress, and the role of the pediatrician: translating developmental science into lifelong health.

PubMed

Garner, Andrew S; Shonkoff, Jack P

2012-01-01

Advances in a wide range of biological, behavioral, and social sciences are expanding our understanding of how early environmental influences (the ecology) and genetic predispositions (the biologic program) affect learning capacities, adaptive behaviors, lifelong physical and mental health, and adult productivity. A supporting technical report from the American Academy of Pediatrics (AAP) presents an integrated ecobiodevelopmental framework to assist in translating these dramatic advances in developmental science into improved health across the life span. Pediatricians are now armed with new information about the adverse effects of toxic stress on brain development, as well as a deeper understanding of the early life origins of many adult diseases. As trusted authorities in child health and development, pediatric providers must now complement the early identification of developmental concerns with a greater focus on those interventions and community investments that reduce external threats to healthy brain growth. To this end, AAP endorses a developing leadership role for the entire pediatric community-one that mobilizes the scientific expertise of both basic and clinical researchers, the family-centered care of the pediatric medical home, and the public influence of AAP and its state chapters-to catalyze fundamental change in early childhood policy and services. AAP is committed to leveraging science to inform the development of innovative strategies to reduce the precipitants of toxic stress in young children and to mitigate their negative effects on the course of development and health across the life span.

Towards Large-scale Twitter Mining for Drug-related Adverse Events.

PubMed

Bian, Jiang; Topaloglu, Umit; Yu, Fan

2012-10-29

Drug-related adverse events pose substantial risks to patients who consume post-market or Drug-related adverse events pose substantial risks to patients who consume post-market or investigational drugs. Early detection of adverse events benefits not only the drug regulators, but also the manufacturers for pharmacovigilance. Existing methods rely on patients' "spontaneous" self-reports that attest problems. The increasing popularity of social media platforms like the Twitter presents us a new information source for finding potential adverse events. Given the high frequency of user updates, mining Twitter messages can lead us to real-time pharmacovigilance. In this paper, we describe an approach to find drug users and potential adverse events by analyzing the content of twitter messages utilizing Natural Language Processing (NLP) and to build Support Vector Machine (SVM) classifiers. Due to the size nature of the dataset (i.e., 2 billion Tweets), the experiments were conducted on a High Performance Computing (HPC) platform using MapReduce, which exhibits the trend of big data analytics. The results suggest that daily-life social networking data could help early detection of important patient safety issues.

Dissecting the molecular mechanisms of gene x environment interactions: implications for diagnosis and treatment of stress-related psychiatric disorders

PubMed Central

Binder, Elisabeth B.

2017-01-01

ABSTRACT Epidemiological studies indicate a combined contribution of genetic and environmental factors, mainly exposure to adverse life events, in the risk for psychiatric disease. Understanding how adverse life events interact with genetic predisposition on the molecular level to shape risk and resilience to psychiatric disorders may yield important insight into disease mechanism. Using the example of the molecular mechanisms of interaction of functional genetic variants within the stress-regulating gene FKBP5 and early adversity, it is delineated how this interaction could contribute to transdiagnostic disease risk via a combined genetic and epigenetic disinhibition of FKBP5 transcription. This knowledge may now allow to develop biomarkers for a transdiagnostic subset of psychiatric patients and to personalize treatment. PMID:29372006

Childhood adversity is linked to differential brain volumes in adolescents with alcohol use disorder: a voxel-based morphometry study.

PubMed

Brooks, Samantha J; Dalvie, Shareefa; Cuzen, Natalie L; Cardenas, Valerie; Fein, George; Stein, Dan J

2014-06-01

Previous neuroimaging studies link both alcohol use disorder (AUD) and early adversity to neurobiological differences in the adult brain. However, the association between AUD and childhood adversity and effects on the developing adolescent brain are less clear, due in part to the confound of psychiatric comorbidity. Here we examine early life adversity and its association with brain volume in a unique sample of 116 South African adolescents (aged 12-16) with AUD but without psychiatric comorbidity. Participants were 58 adolescents with DSM-IV alcohol dependence and with no other psychiatric comorbidities, and 58 age-, gender- and protocol-matched light/non-drinking controls (HC). Assessments included the Childhood Trauma Questionnaire (CTQ). MR images were acquired on a 3T Siemens Magnetom Allegra scanner. Volumes of global and regional structures were estimated using SPM8 Voxel Based Morphometry (VBM), with analysis of covariance (ANCOVA) and regression analyses. In whole brain ANCOVA analyses, a main effect of group when examining the AUD effect after covarying out CTQ was observed on brain volume in bilateral superior temporal gyrus. Subsequent regression analyses to examine how childhood trauma scores are linked to brain volumes in the total cohort revealed a negative correlation in the left hippocampus and right precentral gyrus. Furthermore, bilateral (but most significantly left) hippocampal volume was negatively associated with sub-scores on the CTQ in the total cohort. These findings support our view that some alterations found in brain volumes in studies of adolescent AUD may reflect the impact of confounding factors such as psychiatric comorbidity rather than the effects of alcohol per se. In particular, early life adversity may influence the developing adolescent brain in specific brain regions, such as the hippocampus.

Neurodevelopmental consequences of pediatric cancer and its treatment: applying an early adversity framework to understanding cognitive, behavioral, and emotional outcomes.

PubMed

Marusak, Hilary A; Iadipaolo, Allesandra S; Harper, Felicity W; Elrahal, Farrah; Taub, Jeffrey W; Goldberg, Elimelech; Rabinak, Christine A

2018-06-01

Today, children are surviving pediatric cancer at unprecedented rates, making it one of modern medicine's true success stories. However, we are increasingly becoming aware of several deleterious effects of cancer and the subsequent "cure" that extend beyond physical sequelae. Indeed, survivors of childhood cancer commonly report cognitive, emotional, and psychological difficulties, including attentional difficulties, anxiety, and posttraumatic stress symptoms (PTSS). Cognitive late- and long-term effects have been largely attributed to neurotoxic effects of cancer treatments (e.g., chemotherapy, cranial irradiation, surgery) on brain development. The role of childhood adversity in pediatric cancer - namely, the presence of a life-threatening disease and endurance of invasive medical procedures - has been largely ignored in the existing neuroscientific literature, despite compelling research by our group and others showing that exposure to more commonly studied adverse childhood experiences (i.e., domestic and community violence, physical, sexual, and emotional abuse) strongly imprints on neural development. While these adverse childhood experiences are different in many ways from the experience of childhood cancer (e.g., context, nature, source), they do share a common element of exposure to threat (i.e., threat to life or physical integrity). Therefore, we argue that the double hit of early threat and cancer treatments likely alters neural development, and ultimately, cognitive, behavioral, and emotional outcomes. In this paper, we (1) review the existing neuroimaging research on child, adolescent, and adult survivors of childhood cancer, (2) summarize gaps in our current understanding, (3) propose a novel neurobiological framework that characterizes childhood cancer as a type of childhood adversity, particularly a form of early threat, focusing on development of the hippocampus and the salience and emotion network (SEN), and (4) outline future directions for research.

Mechanisms Underlying the Association Between Early-Life Adversity and Physical Health: Charting a Course for the Future.

PubMed

Bush, Nicole R; Lane, Richard D; McLaughlin, Katie A

Early-life adversities (ELA) are associated with subsequent pervasive alterations across a wide range of neurobiological systems and psychosocial factors that contribute to accelerated onset of health problems and diseases. In this article, we provide an integrated perspective on recent developments in research on ELA, based on the articles published in this Special Issue of Psychosomatic Medicine. We focus on the following: 1) the distinction between specific versus general aspects of ELA with regard to the nature of exposure (e.g., physical and sexual abuse, emotional abuse or neglect, relative socioeconomic deprivation), biological and behavioral correlates of ELA, and differences across diseases; 2) the importance of timing in the critical phases of exposure to ELA; and 3) adaptive versus dysfunctional responses to ELA and their consequences for biological and behavioral risk factors for adverse health outcomes. This article concludes with outlining important new targets for research in this area, including the neurobiology of affect as a mechanism linking ELA to adverse health outcomes, and the need for large-scale longitudinal investigations of multisystem processes relevant to ELA in diverse samples, starting prenatally, continuing to late adolescence, and with long-term follow-up assessments that enable evaluation of incident disease outcomes.

Early life adversity reduces stress reactivity and enhances impulsive behavior: Implications for health behaviors

PubMed Central

Lovallo, William R.

2012-01-01

Altered reactivity to stress, either in the direction of exaggerated reactivity or diminished reactivity, may signal a dysregulation of systems intended to maintain homeostasis and a state of good health. Evidence has accumulated that diminished reactivity to psychosocial stress may signal poor health outcomes. One source of diminished cortisol and autonomic reactivity is the experience of adverse rearing during childhood and adolescence. The Oklahoma Family Health Patterns Project has examined a cohort of 426 healthy young adults with and without a family history of alcoholism. Regardless of family history, persons who had experienced high degrees of adversity prior to age 16 had a constellation of changes including reduced cortisol and heart rate reactivity, diminished cognitive capacity, and unstable regulation of affect, leading to behavioral impulsivity and antisocial tendencies. We present a model whereby this constellation of physiological, cognitive, and affective tendencies is consistent with altered central dopaminergic activity leading to changes in brain function that may foster impulsive and risky behaviors. These in turn may promote greater use of alcohol other drugs along with adopting poor health behaviors. This model provides a pathway from early life adversity to low stress reactivity that forms a basis for risky behaviors and poor health outcomes. PMID:23085387

Severe adverse life events and depressive symptoms among women with, or at risk for, HIV infection in four cities in the United States of America.

PubMed

Moore, J; Schuman, P; Schoenbaum, E; Boland, B; Solomon, L; Smith, D

1999-12-03

To examine frequency and predictors of severe adverse life events and depressive symptoms among HIV-infected women and a comparison group of uninfected women. Analysis of baseline data collected from HIV-infected and uninfected women in a prospective cohort study of HIV infection and women, the HIV Epidemiologic Research Study. The sample of 871 HIV-infected and 439 demographically and behaviorally similar uninfected women were recruited from four metropolitan areas in the USA. Women provided interview information that included sociodemographic characteristics, sexual and drug-using behaviors, and social and psychological functioning. The outcome measures were number of severe adverse life events (e.g., insufficient money for necessities, physical attack or rape, death of a person close to them) and levels of depressive symptoms. HIV-infected and uninfected women reported numerous adverse life events and high levels of depressive symptoms. The two groups, however, did not differ on either outcome measure. Low socio-economic status, injecting drug and crack cocaine use, and high risk sexual activity were related to reports of more adverse events and depressive symptoms for both groups. HIV-infected and uninfected women in socially and economically disadvantaged environments experience many adverse events and high levels of depressive symptoms. HIV infection, at least during the early phase, may be less important than socio-environmental factors in predicting negative psychosocial outcomes for women.

Mechanisms Underlying Latent Disease Risk Associated with Early-Life Arsenic Exposure: Current Research Trends and Scientific Gaps

PubMed Central

Bailey, Kathryn A.; Smith, Allan H.; Tokar, Erik J.; Graziano, Joseph H.; Kim, Kyoung-Woong; Navasumrit, Panida; Ruchirawat, Mathuros; Thiantanawat, Apinya; Suk, William A.; Fry, Rebecca C.

2015-01-01

Background Millions of individuals worldwide, particularly those living in rural and developing areas, are exposed to harmful levels of inorganic arsenic (iAs) in their drinking water. Inorganic As exposure during key developmental periods is associated with a variety of adverse health effects, including those that are evident in adulthood. There is considerable interest in identifying the molecular mechanisms that relate early-life iAs exposure to the development of these latent diseases, particularly in relationship to cancer. Objectives This work summarizes research on the molecular mechanisms that underlie the increased risk of cancer development in adulthood that is associated with early-life iAs exposure. Discussion Epigenetic reprogramming that imparts functional changes in gene expression, the development of cancer stem cells, and immunomodulation are plausible underlying mechanisms by which early-life iAs exposure elicits latent carcinogenic effects. Conclusions Evidence is mounting that relates early-life iAs exposure and cancer development later in life. Future research should include animal studies that address mechanistic hypotheses and studies of human populations that integrate early-life exposure, molecular alterations, and latent disease outcomes. Citation Bailey KA, Smith AH, Tokar EJ, Graziano JH, Kim KW, Navasumrit P, Ruchirawat M, Thiantanawat A, Suk WA, Fry RC. 2016. Mechanisms underlying latent disease risk associated with early-life arsenic exposure: current research trends and scientific gaps. Environ Health Perspect 124:170–175; http://dx.doi.org/10.1289/ehp.1409360 PMID:26115410

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

Interpersonal Trauma and Depressive Symptoms in Early Adolescents: Exploring the Moderating Roles of Parent and School Connectedness

ERIC Educational Resources Information Center

Schwerdtfeger Gallus, Kami L.; Shreffler, Karina M.; Merten, Michael J.; Cox, Ronald B., Jr.

2015-01-01

Interpersonal traumas experienced early in life adversely impact psychological well-being in children and adolescents, yet the specific role that social support can have in reducing negative outcomes following trauma exposure is unclear. Using a general population sample of seventh-grade students in an urban public school district in the South…

Sexually Dimorphic Responses to Early Adversity: Implications for Affective Problems and Autism Spectrum Disorder

PubMed Central

Davis, Elysia Poggi; Pfaff, Donald

2014-01-01

During gestation, development proceeds at a pace that is unmatched by any other stage of the lifecycle. For these reason the human fetus is particularly susceptible not only to organizing influences, but also to pathogenic disorganizing influences. Growing evidence suggests that exposure to prenatal adversity leads to neurological changes that underlie lifetime risks for mental illness. Beginning early in gestation, males and females show differential developmental trajectories and responses to stress. It is likely that sex-dependent organization of neural circuits during the fetal period influences differential vulnerability to mental health problems. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two developmental disorders: affective problems (greater female prevalence) and autism spectrum disorder (greater male prevalence). Recent prospective studies illustrating the neurodevelopmental consequences of fetal exposure to stress and stress hormones for males and females are considered here. Plausible biological mechanisms including the role of the sexually differentiated placenta are discussed. We consider in this review evidence that sexually dimorphic responses to early life stress are linked to two sets of developmental disorders: affective problems (greater female prevalence) and autism spectrum disorders (greater male prevalence). PMID:25038479

TERATOLOGY v2.0 – building a path forward

EPA Science Inventory

Unraveling the complex relationships between environmental factors and early life susceptibility in assessing the risk for adverse pregnancy outcomes requires advanced knowledge of biological systems. Large datasets and deep data-mining tools are emerging resources for predictive...

Infant Medical Trauma in the Neonatal Intensive Care Unit (IMTN): A Proposed Concept for Science and Practice.

PubMed

DʼAgata, Amy L; Young, Erin E; Cong, Xiaomei; Grasso, Damion J; McGrath, Jacqueline M

2016-08-01

Trauma is an innately subjective experience ensuing from a deeply distressing event. Research has demonstrated that while the environment of the neonatal intensive care unit (NICU) is capable of providing extraordinary lifesaving measures following birth, the experience may be disruptive to several key aspects of early development, placing infants at risk for adverse behavioral, cognitive, and emotional outcomes. This article provides rationale for the concept of Infant Medical Trauma in the NICU (IMTN) as a means of describing this unique stress experience. A triad of cumulative early life NICU experiences (stress, parental separation, and pain) is proposed to influence an infant's swinging neurodevelopmental pendulum amid the potential outcomes of risk and resilience. Creating language that describes the infant experience brings meaning and calls caregivers and parents to action to consider strategies that may improve long-term health. Actively seeking opportunities to decrease the allostatic load of at-risk infants may support an infant's pendulum to swing toward a path of resilience, thereby moderating his or her early life adverse experience.

The Impact of Adverse Child and Adult Experiences on Recovery from Serious Mental Illness

PubMed Central

Stumbo, Scott P.; Yarborough, Bobbi Jo H.; Paulson, Robert I.; Green, Carla A.

2015-01-01

Objective To compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. Methods As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a two-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Results Child and adult exposures to adverse experiences were high, at 91% and 82% respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning, social functioning, and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Conclusions and Implications for Practice Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. PMID:26053533

Neurobehavioral determinants of nutritional security in fetal growth-restricted individuals.

PubMed

Portella, André Krumel; Silveira, Patrícia Pelufo

2014-12-01

Fetal growth restriction results from a failure to achieve a higher growth potential and has been associated with many maternal conditions, such as chronic diseases (infections, hypertension, and some cases of diabetes and obesity), exposures (tobacco smoke, drugs), and malnutrition. This early adversity induces a series of adaptive physiological responses aimed at improving survival, but imposing increased risk for developing chronic nontransmittable diseases (obesity, type II diabetes, cardiovascular disease) in the long term. Recently, mounting evidence has shown that fetal growth impairment is related to altered feeding behavior and preferences through the life course. When living in countries undergoing nutritional transition, in which individuals experience the coexistence of underweight and overweight problems (the "double burden of malnutrition"), fetal growth-restricted children can be simultaneously growth restricted and overweight-a double burden of malnutrition at the individual level. Considering food preferences as an important aspect of nutrition security, we will summarize the putative neurobiological mechanisms at the core of the relationship between fetal growth and nutrition security over the life course and the evidence linking early life adversity to later food preferences. © 2014 New York Academy of Sciences.

Visualizing Changes in Cdkn1c Expression Links Early-Life Adversity to Imprint Mis-regulation in Adults.

PubMed

Van de Pette, Mathew; Abbas, Allifia; Feytout, Amelie; McNamara, Gráinne; Bruno, Ludovica; To, Wilson K; Dimond, Andrew; Sardini, Alessandro; Webster, Zoe; McGinty, James; Paul, Eleanor J; Ungless, Mark A; French, Paul M W; Withers, Dominic J; Uren, Anthony; Ferguson-Smith, Anne C; Merkenschlager, Matthias; John, Rosalind M; Fisher, Amanda G

2017-01-31

Imprinted genes are regulated according to parental origin and can influence embryonic growth and metabolism and confer disease susceptibility. Here, we designed sensitive allele-specific reporters to non-invasively monitor imprinted Cdkn1c expression in mice and showed that expression was modulated by environmental factors encountered in utero. Acute exposure to chromatin-modifying drugs resulted in de-repression of paternally inherited (silent) Cdkn1c alleles in embryos that was temporary and resolved after birth. In contrast, deprivation of maternal dietary protein in utero provoked permanent de-repression of imprinted Cdkn1c expression that was sustained into adulthood and occurred through a folate-dependent mechanism of DNA methylation loss. Given the function of imprinted genes in regulating behavior and metabolic processes in adults, these results establish imprinting deregulation as a credible mechanism linking early-life adversity to later-life outcomes. Furthermore, Cdkn1c-luciferase mice offer non-invasive tools to identify factors that disrupt epigenetic processes and strategies to limit their long-term impact. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Longitudinal associations of experiences of adversity and socioeconomic disadvantage during childhood with labour force participation and exit in later adulthood.

PubMed

Fahy, A E; Stansfeld, S A; Smuk, M; Lain, D; van der Horst, M; Vickerstaff, S; Clark, C

2017-06-01

The Extending Working Lives (EWL) agenda seeks to sustain employment up to and beyond traditional retirement ages. This study examined the potential role of childhood factors in shaping labour force participation and exit among older adults, with a view to informing proactive interventions early in the life-course to enhance individuals' future capacity for extending their working lives. Childhood adversity and socioeconomic disadvantage have previously been linked to ill-health across the life-span and sickness benefit in early adulthood. This study builds upon previous research by examining associations between childhood adversity and self-reported labour force participation among older adults (aged 55). Data was from the National Child Development Study - a prospective cohort of all English, Scottish, & Welsh births in one week in 1958. There was evidence for associations between childhood adversity and increased risk of permanent sickness at 55 years - which were largely sustained after adjustment for educational disengagement and adulthood factors (mental/physical health, qualifications, socioeconomic disadvantage). Specifically, children who were abused or neglected were more likely to be permanently sick at 55 years. In addition, among males, those in care, those experiencing illness in the home, and those experiencing two or more childhood adversities were more likely to be permanently sick at 55 years. Childhood factors were also associated with part-time employment and retirement at 55 years. Severe childhood adversities may represent important distal predictors of labour force exit at 55 years, particularly via permanent sickness. Notably, some adversities show associations among males only, which may inform interventions designed to extend working lives. Copyright © 2017 Elsevier Ltd. All rights reserved.

Long-term health and socioeconomic consequences of early-life exposure to the 1959-1961 Chinese Famine.

PubMed

Fan, Wen; Qian, Yue

2015-01-01

This research investigates long-term consequences of early-life malnutrition by examining effects of the 1959-1961 Chinese Famine. Taking into account temporal and geographic variations in famine severity, we construct a difference-in-differences estimator to identify effects of early-life exposure to famine on perceived health and socioeconomic outcomes in midlife. Using a sample of 1716 adults born in 1955-1966 in rural China from a nationally representative survey-the 2005 Chinese General Social Survey-we find that the famine had adverse effects on mid-life health for males born into families where at least one parent was a Communist Party member and females regardless of parental party membership. Being born during the famine had no effects on years of education or income for either gender. Quantile regressions suggest intense mortality selection among males who had no party-affiliated parents. Our study highlights the importance of timing and contexts of life experiences in shaping health. Copyright © 2014 Elsevier Inc. All rights reserved.

Early-life exposure to air pollutants and adverse pregnancy outcomes: protocol for a prospective cohort study in Beijing

PubMed Central

Song, Jing; Wei, Ling; Ma, Ying; Tian, Ning; Huang, Shi Yun; Dai, Yin Mei; Zhao, Li Hong; Kong, Yuan Yuan

2017-01-01

Introduction The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Methods and analysis Here, 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. Ethics and dissemination This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. Trial registration number This study has been registered in WHO International Clinical Trial Register—Chinese Clinical Trial Registry under registration number ChiCTR-ROC-16010181 (http :// www.chictr.org.cn / showproj.aspx ?proj=17328). PMID:28871018

The effects of pre-natal-, early-life- and indirectly-initiated exposures to maximum adversities on the course of schizophrenia.

PubMed

Levine, Stephen Z; Levav, Itzhak; Yoffe, Rinat; Pugachova, Inna

2014-09-01

The effects of pre-natal-, early-life- and indirectly-initiated exposures to protracted maximum adversity on the course of schizophrenia are unknown. To compare the aforementioned Holocaust directly exposed subgroups with an indirectly exposed subgroup on the course of schizophrenia. The study population were: Israeli Jews in-uterus or born in Nazi-occupied or dominated European nations by the end of the persecution of the Jews, who were alive in 1950, and who had a last discharge diagnosis of schizophrenia in the Israel National Psychiatric Case Registry by 2013 (N=4933). The population was disaggregated into subgroups who (1) migrated after WWII and who had (1a) pre-natal (n=584, 11.8%) and (1b) early-life (n=3709, 75.2%) initiated exposures to the maximum adversities of the Holocaust, and (2) indirectly exposed individuals to the Holocaust who migrated before the Nazi-era persecution begun (n=640, 13%). Recurrent event survival analyses were computed to examine the psychiatric re-hospitalization risk of the study subgroups, unadjusted and adjusted for age of onset of the disorder and sex. The pre-natal initiated exposure subgroup had a significantly (p<0.05) greater risk of psychiatric re-hospitalizations for schizophrenia than the other subgroups (unadjusted: HR=3.39, 95% CI 2.95, 3.90; adjusted: HR=2.28, 2.00, 2.60). This result replicated in sensitivity analyses for: Poland-born individuals, the years 1922 and 1935; and followed at least 10 years and to the year 2000. Pre-natal initiated exposure to the maximal adversity of the holocaust constitutes a consistent risk factor for a worse course of schizophrenia, a possible byproduct of neurodevelopment disruptions induced by maternal stress and/or famine and/or infections. Copyright © 2014 Elsevier B.V. All rights reserved.

Life stress and mental disorders in the South African Stress and Health study

PubMed Central

Seedat, Soraya; Stein, Dan J; Jackson, Pamela B; Heeringa, Steven G; Williams, David R; Myer, Landon

2011-01-01

Background Although stressful life events (SLEs) are associated with psychopathology, the contribution from distal and proximal events and the specificity of their association with common mental disorders require further exploration. We examined the association of recent life events and past adversities to mood, anxiety, substance use and impulse control disorders in South Africa. Methods Data were analysed from the South African Stress and Health study, a population-based study of mental disorders in a nationally representative sample of 4 351 adults. Psychiatric disorders were assessed with the Composite International Diagnostic Interview (CIDI). This included questions covering early and later SLEs (negative life events, relationship stress, partner violence, social strain and adverse events during childhood) and various socio-demographic variables. Logistic regression models were constructed for 3 957 respondents (2 371 female, 1 586 male) with no missing covariate data, to assess life stress and socio-demographic predictors of 12-month and lifetime disorder. Results Recent negative life events and relationship problems were significant predictors of any 12-month disorder and any lifetime disorder. Physical partner violence predicted any lifetime disorder. There was evidence of specificity for the prediction of mood versus anxiety disorders, with childhood adversity specifically associated with mood disorders but not anxiety disorders. Single marital status was the strongest socio-demographic predictor of any 12-month and any lifetime disorder. Conclusions Stressful life events, distal and proximal, contribute significantly and independently to the prediction of major psychiatric disorders among South Africans, underscoring the importance of screening adversities in adults with common mental disorders, and of providing appropriate adjunctive interventions. PMID:19588801

Growing up with adversity: From juvenile justice involvement to criminal persistence and psychosocial problems in young adulthood.

PubMed

Basto-Pereira, Miguel; Miranda, Ana; Ribeiro, Sofia; Maia, Ângela

2016-12-01

Several studies have been carried out to investigate the effect of child maltreatment on juvenile justice involvement and future criminal life. However, little is known about the impact of other forms of adversity, beyond abuse and neglect, on juvenile delinquency and criminal persistence. The effect of early adversity on psychosocial problems is underexplored, particularly in juvenile delinquents. This study, using the Childhood Adverse Experiences (ACE) questionnaire, a tool accessing the exposure to different types of abuse, neglect and serious household dysfunction, explored the role of each adverse experience on juvenile justice involvement, persistence in crime and psychosocial problems during young adulthood. A Portuguese sample of 75 young adults with official records of juvenile delinquency in 2010/2011, and 240 young adults from a community sample completed ACE questionnaire and measures of psychosocial adjustment. Seven out of ten adverse experiences were significantly more prevalent in young adults with juvenile justice involvement than in the community sample, after matching the main demographic variables. The strongest predictor of juvenile justice involvement and criminal persistence during early adulthood was sexual abuse. Dimensions of child/adolescent emotional maltreatment and a mental illness in the household predicted a set of psychosocial problems in young adulthood. This study indicates that early adversity is significantly related to juvenile justice involvement, criminal persistence and psychosocial problems. This study also suggests that each experience has a different role in this process. There is an urgent need to screen, prevent and stop serious adversity. Future scientific directions and recommendations for policies are provided. Copyright © 2016 Elsevier Ltd. All rights reserved.

Being born under adverse economic conditions leads to a higher cardiovascular mortality rate later in life: evidence based on individuals born at different stages of the business cycle.

PubMed

van den Berg, Gerard J; Doblhammer-Reiter, Gabriele; Christensen, Kaare

2011-05-01

We connect the recent medical and economic literatures on the long-run effects of early-life conditions by analyzing the effects of economic conditions on the individual cardiovascular (CV) mortality rate later in life, using individual data records from the Danish Twin Registry covering births since the 1870s and including the cause of death. To capture exogenous variation of conditions early in life, we use the state of the business cycle around birth. We find significant negative effects of economic conditions around birth on the individual CV mortality rate at higher ages. There is no effect on the cancer-specific mortality rate. From variation within and between monozygotic and dizygotic twin pairs born under different conditions, we conclude that the fate of an individual is more strongly determined by genetic and household-environmental factors if early-life conditions are poor. Individual-specific qualities come more to fruition if the starting position in life is better.

Illuminating the clinical significance of alexithymia subtypes: A cluster analysis of alexithymic traits and psychiatric symptoms.

PubMed

Kajanoja, J; Scheinin, N M; Karlsson, L; Karlsson, H; Karukivi, M

2017-06-01

Alexithymia is a personality construct involving difficulties identifying and verbalizing feelings, and an externally oriented thinking style. There is preliminary evidence for alexithymia subtypes that may carry different risk profiles for psychiatric illness. The aim of this study was to gain support for the existence of alexithymia subtypes and further characterize their clinical relevance. To identify possible subtypes, a cluster analysis was conducted for individuals with high alexithymic traits (N=113). Current depressive and anxiety symptoms, self-reported psychiatric medical history, and self-reported early life adversity were compared between subtypes. The cluster analysis was replicated with the low (N=2471) and moderate (N=290) alexithymia groups. We identified two alexithymia subtypes. Compared to type A, type B alexithymia was associated with higher levels of difficulties in identifying feelings, and was more strongly associated with current depressive (Cohen's d=0.77, p<0.001) and anxiety symptoms (Cohen's d=0.82, p<0.001), and self-reported early life adversity (Cohen's d 0.42, p=0.048). Compared to type A, type B alexithymia was also associated with a higher prevalence of self-reported diagnosis of major depressive- (30.2% vs. 8.3%) and anxiety disorder (18.9% vs. 3.3%). The results of this study support the hypothesis of alexithymia subtypes, and add support to the growing evidence showing that alexithymia is likely a heterogeneous and dimensional phenomenon. The subtype (type B) with most pronounced difficulties in identifying feelings may be associated with a higher risk for psychiatric illness compared to type A alexithymia, and may exhibit a more severe history of early life adversity. Copyright © 2017 Elsevier Inc. All rights reserved.

Brain regional differences in social encounter-induced Fos expression in male and female rats after post-weaning social isolation.

PubMed

Ahern, Megan; Goodell, Dayton J; Adams, Jessica; Bland, Sondra T

2016-01-01

Early life adversity has been related to a number of psychological disorders including mood and other disorders that can manifest as inappropriate or aggressive responses to social challenges. The present study used post-weaning social isolation (PSI) in rats, a model of early life adversity, to examine its effects on Fos protein expression produced by exposure to a novel social encounter. We have previously reported that the social encounter-induced increase in Fos expression in the medial prefrontal cortex observed in group-housed controls (GRP) was attenuated in rats that had experienced PSI. Here we assessed Fos expression in other brain regions thought to be involved in emotion regulation and social behavior. Male and female rats were housed in same-sex groups or in isolation (ISO) for 4 weeks beginning on postnatal day (P) 21 and were exposed to a single 15 min social encounter with a novel same-sex conspecific on P49. Fos positive cells were assessed using immunohistochemistry in 16 regions within the forebrain. Exposure to a novel conspecific increased Fos expression in the forebrain of GRP rats in a region- and sex-specific fashion. This increase was blunted or absent in ISO rats within many regions including cortical regions, thalamus, habenula, dentate gyrus, lateral septum, and basolateral amygdala. In several regions, the increase in Fos was greater in male than in female group housed rats. Negative relationships were observed between social interactions and Fos in some regions. Forebrain hypofunction produced by early-life adversity may be involved in socially inappropriate behavior. Copyright © 2015 Elsevier B.V. All rights reserved.

Exposure to the Lebanon War of 2006 and effects on alcohol use disorders: the moderating role of childhood maltreatment.

PubMed

Keyes, Katherine M; Shmulewitz, Dvora; Greenstein, Eliana; McLaughlin, Kate; Wall, Melanie; Aharonovich, Efrat; Weizman, Abraham; Frisch, Amos; Spivak, Baruch; Grant, Bridget F; Hasin, Deborah

2014-01-01

Civilian populations now comprise the majority of casualties in modern warfare, but effects of war exposure on alcohol disorders in the general population are largely unexplored. Accumulating literature indicates that adverse experiences early in life sensitize individuals to increased alcohol problems after adult stressful experiences. However, child and adult stressful experiences can be correlated, limiting interpretation. We examine risk for alcohol disorders among Israelis after the 2006 Lebanon War, a fateful event outside the control of civilian individuals and uncorrelated with childhood experiences. Further, we test whether those with a history of maltreatment are at greater risk for an alcohol use disorder after war exposure compared to those without such a history. Adult household residents selected from the Israeli population register were assessed with a psychiatric structured interview; the analyzed sample included 1306 respondents. War measures included self-reported days in an exposed region. Among those with a history of maltreatment, those in a war-exposed region for 30+ days had 5.3 times the odds of subsequent alcohol disorders compared to those exposed 0 days (95%C.I. 1.01-27.76), controlled for relevant confounders; the odds ratio for those without this history was 0.5 (95%C.I. 0.25-1.01); test for interaction: X(2)=5.28, df=1, P=0.02. Experiencing a fateful stressor outside the control of study participants, civilian exposure to the 2006 Lebanon War, is associated with a heightened the risk of alcohol disorders among those with early adverse childhood experiences. Results suggest that early life experiences may sensitize individuals to adverse health responses later in life. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Exposure to the Lebanon War of 2006 and effects on alcohol use disorders: The moderating role of childhood maltreatment☆

PubMed Central

Keyes, Katherine M.; Shmulewitz, Dvora; Greenstein, Eliana; McLaughlin, Kate; Wall, Melanie; Aharonovich, Efrat; Weizman, Abraham; Frisch, Amos; Spivak, Baruch; Grant, Bridget F.; Hasin, Deborah

2013-01-01

Background Civilian populations now comprise the majority of casualties in modern warfare, but effects of war exposure on alcohol disorders in the general population are largely unexplored. Accumulating literature indicates that adverse experiences early in life sensitize individuals to increased alcohol problems after adult stressful experiences. However, child and adult stressful experiences can be correlated, limiting interpretation. We examine risk for alcohol disorders among Israelis after the 2006 Lebanon War, a fateful event outside the control of civilian individuals and uncorrelated with childhood experiences. Further, we test whether those with a history of maltreatment are at greater risk for an alcohol use disorder after war exposure compared to those without such a history. Methods Adult household residents selected from the Israeli population register were assessed with a psychiatric structured interview; the analyzed sample included 1306 respondents. War measures included self-reported days in an exposed region. Results Among those with a history of maltreatment, those in a war-exposed region for 30+ days had 5.3 times the odds of subsequent alcohol disorders compared to those exposed 0 days (95%C.I. 1.01–27.76), controlled for relevant confounders; the odds ratio for those without this history was 0.5 (95%C.I. 0.25–1.01); test for interaction: X2 = 5.28, df = 1, P = 0.02. Conclusions Experiencing a fateful stressor outside the control of study participants, civilian exposure to the 2006 Lebanon War, is associated with a heightened the risk of alcohol disorders among those with early adverse childhood experiences. Results suggest that early life experiences may sensitize individuals to adverse health responses later in life. PMID:24262650

The impact of adverse child and adult experiences on recovery from serious mental illness.

PubMed

Stumbo, Scott P; Yarborough, Bobbi Jo H; Paulson, Robert I; Green, Carla A

2015-12-01

The purpose of this study was to compare effects of adverse childhood experiences and adverse adult experiences on recovery from serious mental illnesses. As part of a mixed-methods study of recovery from serious mental illnesses, we interviewed and administered questionnaires to 177 members of a not-for-profit health plan over a 2-year period. Participants had a diagnosis of bipolar disorder, affective psychosis, schizophrenia, or schizoaffective disorder. Data for analyses came from standardized self-reported measures; outcomes included recovery, functioning, quality of life, and psychiatric symptoms. Adverse events in childhood and adulthood were evaluated as predictors. Child and adult exposures to adverse experiences were high, at 91% and 82%, respectively. Cumulative lifetime exposure to adverse experiences (childhood plus adult experiences) was 94%. In linear regression analyses, adverse adult experiences were more important predictors of outcomes than adverse childhood experiences. Adult experiences were associated with lower recovery scores, quality of life, mental and physical functioning and social functioning and greater psychiatric symptoms. Emotional neglect in adulthood was associated with lower recovery scores. Early and repeated exposure to adverse events was common in this sample of people with serious mental illnesses. Adverse adult experiences were stronger predictors of worse functioning and lower recovery levels than were childhood experiences. Focusing clinical attention on adult experiences of adverse or traumatic events may result in greater benefit than focusing on childhood experiences alone. (c) 2015 APA, all rights reserved).

Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

PubMed

Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

2016-01-01

Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

PubMed

Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

2017-02-07

In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Prenatal and Early Life Exposure to Traffic Pollution and Cardiometabolic Health in Childhood

PubMed Central

Fleisch, Abby F.; Luttmann-Gibson, Heike; Perng, Wei; Rifas-Shiman, Sheryl L.; Coull, Brent A.; Kloog, Itai; Koutrakis, Petros; Schwartz, Joel D.; Zanobetti, Antonella; Mantzoros, Christos S.; Gillman, Matthew W.; Gold, Diane R.; Oken, Emily

2016-01-01

Background Prenatal exposure to traffic pollution has been associated with faster infant weight gain, but implications for cardiometabolic health in later childhood are unknown. Methods Among 1,418 children in Project Viva, a Boston-area pre-birth cohort, we assessed anthropometric and biochemical parameters of cardiometabolic health in early (median age 3.3 years) and mid- (median age 7.7 years) childhood. We used spatiotemporal models to estimate prenatal and early life residential PM2.5 and black carbon exposure as well as traffic density and roadway proximity. We performed linear regression analyses adjusted for sociodemographics Results Children whose mothers lived close to a major roadway at the time of delivery had higher markers of adverse cardiometabolic risk in early and mid-childhood. For example, total fat mass was 2.1kg (95%CI: 0.8, 3.5) higher in mid-childhood for children of mothers who lived < 50 m vs. ≥ 200m from a major roadway. Black carbon exposure and traffic density were generally not associated with cardiometabolic parameters, and PM2.5 exposure during the year prior was paradoxically associated with improved cardiometabolic profile Conclusions Infants whose mothers lived close to a major roadway at the time of delivery may be at later risk for adverse cardiometabolic health. PMID:26843357

BEHAVIOR OF PERSISTENT BIOACCUMULATIVE TOXICANTS IN FISH EARLY LIFE STAGES

EPA Science Inventory

Whether through environmental criteria or site-specific risk assessments, many EPA programs rely on linking environmental exposures to levels of adverse effect (or no effect) in fish and wildlife. While empirical relationships of exposure to effect can be used for such assessmen...

Arsenic Metabolism and Distribution in Developing Organisms

EPA Science Inventory

A growing body of evidence suggests that exposure to inorganic arsenic during early life has long term adverse effects. The extent of exposure to inorganic arsenic and its methylated metabolites in utero is determined not only by the rates of formation and transfer of arsenicals...

Early life persistent vitamin D deficiency exacerbates arrhythmias and autonomic imbalance following acrolein exposure in mice.

EPA Science Inventory

Epidemiological and animal data have conclusively linked adverse cardiovascular outcomes to air pollution exposure. As such, cardiovascular function is maintained by adequate levels of certain essential micronutrients like vitamin D. Unfortunately, vitamin D deficiency (VDD) has ...

[Epigenetics and obesity].

PubMed

Casanello, Paola; Krause, Bernardo J; Castro-Rodríguez, José A; Uauy, Ricardo

Current evidence supports the notion that exposure to various environmental conditions in early life may induce permanent changes in the epigenome that persist throughout the life-course. This article focuses on early changes associated with obesity in adult life. A review is presented on the factors that induce changes in whole genome (DNA) methylation in early life that are associated with adult onset obesity and related disorders. In contrast, reversal of epigenetic changes associated with weight loss in obese subjects has not been demonstrated. This contrasts with well-established associations found between obesity related DNA methylation patterns at birth and adult onset obesity and diabetes. Epigenetic markers may serve to screen indivuals at risk for obesity and assess the effects of interventions in early life that may delay or prevent obesity in early life. This might contribute to lower the obesity-related burden of death and disability at the population level. The available evidence indicates that epigenetic marks are in fact modifiable, based on modifications in the intrauterine environment and changes in food intake, physical activity and dietary patterns patterns during pregnancy and early years of adult life. This offers the opportunity to intervene before conception, during pregnancy, infancy, childhood, and also in later life. There must be documentation on the best preventive actions in terms of diet and physical activity that will modify or revert the adverse epigenetic markers, thus preventing obesity and diabetes in suceptible individuals and populations. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Influences of maternal nutritional status on vascular function in the offspring.

PubMed

Poston, Lucilla

2007-08-01

Fetal growth restriction leading to low birthweight is associated with increased risk of ischaemic heart disease and hypertension in later life. Increasingly, it is recognised that cardiovascular risk may also be initiated in early life when the fetus and neonate are exposed to maternal nutritional excess. This review summarises the studies in man and animals that have investigated the potential role of vascular disorders in the aetiology of atherosclerosis and hypertension arising from early life nutritional deprivation or excess. Malfunction of the arterial endothelial cell layer in the offspring has been frequently described in association with both maternal under and overnutritional states and may play a permissive role in the origin of these disorders. Also prevalent is evidence for increased stiffness of the large arteries which may contribute to systolic hypertension. Further investigation is required into the intriguing suggestion that early life nutritional imbalance may adversely influence vascular angiogenesis leading to rarefaction and increased peripheral vascular resistance.

Zidovudine for the prevention of vertical HIV transmission: a decision analytic approach.

PubMed

Rouse, D J; Owen, J; Goldenberg, R L; Vermund, S H

1995-08-01

The purpose of this study was to quantify the benefits of maternal-neonatal zidovudine (ZDV) administration for the prevention of vertical human immunodeficiency virus (HIV) transmission against the potential risks of drug-induced complications in uninfected children. A decision analysis model was created with use of a Markov cohort simulation, for evaluating both survival and quality of life for two hypothetical cohorts of HIV-exposed neonates: one with in utero and neonatal exposure to preventive ZDV therapy and the other not exposed. The model included the probability of congenital HIV infection with and without ZDV treatment (estimates derived from AIDS Clinical Trials Group study 076), the yearly probability of death with and without congenital HIV infection, a range of probabilities of adverse effects from ZDV use, and a range of ages in life when any adverse effect would manifest. In a series of scenarios, the impact of different estimates for the quality-of-life decrement from any adverse ZDV effect in HIV-uninfected children was assessed, and threshold values for this estimate were established, i.e., critical values below which withholding ZDV would be the preferred choice. Across a wide range of estimates for multiple contingencies, ZDV use was associated with a greater number of quality-adjusted life years than was non-use. Only in implausible, pessimistic scenarios (i.e., a high incidence of profound adverse effects beginning early in life) would withholding ZDV be the rational choice for an asymptomatic HIV-infected pregnant woman.(ABSTRACT TRUNCATED AT 250 WORDS)

Does Father Absence Place Daughters at Special Risk for Early Sexual Activity and Teenage Pregnancy?

PubMed Central

Ellis, Bruce J.; Bates, John E.; Dodge, Kenneth A.; Fergusson, David M.; Horwood, L. John; Pettit, Gregory S.; Woodward, Lianne

2009-01-01

The impact of father absence on early sexual activity and teenage pregnancy was investigated in longitudinal studies in the United States (N = 242) and New Zealand (N = 520), in which community samples of girls were followed prospectively from early in life (5 years) to approximately age 18. Greater exposure to father absence was strongly associated with elevated risk for early sexual activity and adolescent pregnancy. This elevated risk was either not explained (in the U.S. study) or only partly explained (in the New Zealand study) by familial, ecological, and personal disadvantages associated with father absence. After controlling for covariates, there was stronger and more consistent evidence of effects of father absence on early sexual activity and teenage pregnancy than on other behavioral or mental health problems or academic achievement Effects of father absence are discussed in terms of life-course adversity, evolutionary psychology, social learning, and behavior genetic models. PMID:12795391

Early-Life Exposure to Non-Nutritive Sweeteners and the Developmental Origins of Childhood Obesity: Global Evidence from Human and Rodent Studies.

PubMed

Archibald, Alyssa J; Dolinsky, Vernon W; Azad, Meghan B

2018-02-10

Non-nutritive sweeteners (NNS) are increasingly consumed by children and pregnant women around the world, yet their long-term health impact is unclear. Here, we review an emerging body of evidence suggesting that early-life exposure to NNS may adversely affect body composition and cardio-metabolic health. Some observational studies suggest that children consuming NNS are at increased risk for obesity-related outcomes; however, others find no association or provide evidence of confounding. Fewer studies have examined prenatal NNS exposure, with mixed results from different analytical approaches. There is a paucity of RCTs evaluating NNS in children, yielding inconsistent results that can be difficult to interpret due to study design limitations (e.g., choice of comparator, multifaceted interventions). The majority of this research has been conducted in high-income countries. Some rodent studies demonstrate adverse metabolic effects from NNS, but most have used extreme doses that are not relevant to humans, and few have distinguished prenatal from postnatal exposure. Most studies focus on synthetic NNS in beverages, with few examining plant-derived NNS or NNS in foods. Overall, there is limited and inconsistent evidence regarding the impact of early-life NNS exposure on the developmental programming of obesity and cardio-metabolic health. Further research and mechanistic studies are needed to elucidate these effects and inform dietary recommendations for expectant mothers and children worldwide.

Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages

PubMed Central

Lauterstein, Dana E.; Tijerina, Pamella B.; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S.; Gordon, Terry; Klein, Catherine B.; Zelikoff, Judith T.

2016-01-01

Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13–16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4–6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology. PMID:27077873

Frontal Cortex Transcriptome Analysis of Mice Exposed to Electronic Cigarettes During Early Life Stages.

PubMed

Lauterstein, Dana E; Tijerina, Pamella B; Corbett, Kevin; Akgol Oksuz, Betul; Shen, Steven S; Gordon, Terry; Klein, Catherine B; Zelikoff, Judith T

2016-04-12

Electronic cigarettes (e-cigarettes), battery-powered devices containing nicotine, glycerin, propylene glycol, flavorings, and other substances, are increasing in popularity. They pose a potential threat to the developing brain, as nicotine is a known neurotoxicant. We hypothesized that exposure to e-cigarettes during early life stages induce changes in central nervous system (CNS) transcriptome associated with adverse neurobiological outcomes and long-term disease states. To test the hypothesis, pregnant C57BL/6 mice were exposed daily (via whole body inhalation) throughout gestation (3 h/day; 5 days/week) to aerosols produced from e-cigarettes either with nicotine (13-16 mg/mL) or without nicotine; following birth, pups and dams were exposed together to e-cigarette aerosols throughout lactation beginning at postnatal day (PND) 4-6 and using the same exposure conditions employed during gestational exposure. Following exposure, frontal cortex recovered from ~one-month-old male and female offspring were excised and analyzed for gene expression by RNA Sequencing (RNA-Seq). Comparisons between the treatment groups revealed that e-cigarette constituents other than nicotine might be partly responsible for the observed biological effects. Transcriptome alterations in both offspring sexes and treatment groups were all significantly associated with downstream adverse neurobiological outcomes. Results from this study demonstrate that e-cigarette exposure during early life alters CNS development potentially leading to chronic neuropathology.

Environmental adversity and children's early trajectories of problem behavior: The role of harsh parental discipline.

PubMed

Flouri, Eirini; Midouhas, Emily

2017-03-01

This study was performed to examine the role of harsh parental discipline in mediating and moderating the effects of environmental adversity (family socioeconomic disadvantage and adverse life events) on emotional and behavioral problems across early-to-middle childhood. The sample included 16,916 children (48% female; 24% non-White) from the U.K.'s Millennium Cohort Study. We analyzed trajectories of conduct, hyperactivity, and emotional problems, measured at ages 3, 5, and 7 years, using growth curve models. Harsh parental discipline was measured at these ages with parent-reported items on the frequency of using the physical and verbal discipline tactics of smacking, shouting at, and "telling off" the child. As expected, family socioeconomic disadvantage and adverse life events were significantly associated with emotional and behavioral problems. Harsh parental discipline was related to children's trajectories of problems, and it moderated, but did not explain, the effect of environmental risk on these trajectories. High-risk children experiencing harsh parental discipline had the highest levels of conduct problems and hyperactivity across the study period. In addition, harsh parental discipline predicted an increase in emotional symptoms over time in high-risk children, unseen in their counterparts experiencing low levels of harsh parental discipline. However, children in low-risk families were also negatively affected by harsh parental discipline concurrently and over time. In conclusion, harsh parental discipline predicted emotional and behavioral problems in high- and low-risk children and moderated the effects of family poverty and adversity on these problems. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Socio-economic status, family disruption and residential stability in childhood: relation to onset, recurrence and remission of major depression.

PubMed

Gilman, S E; Kawachi, I; Fitzmaurice, G M; Buka, L

2003-11-01

Childhood adversity significantly increases the risk of depression, but it is unclear whether this risk is most pronounced for depression occurring early in life. In the present study, we examine whether three aspects of childhood adversity--low socio-economic status (SES), family disruption, and residential instability--are related to increased risk of depression during specific stages of the life course. We also examine whether these aspects of childhood adversity are related to the severity of depression. A sample of 1089 of the 4140 births enrolled in the Providence, Rhode Island cohort of the National Collaborative Perinatal Project was interviewed between the ages of 18 and 39. Measures of parental SES, childhood family disruption and residential instability were obtained upon mother's enrolment and at age 7. Age at onset of major depressive episode, lifetime number of depressive episodes, and age at last episode were ascertained via structured diagnostic interviews. Survival analysis was used to identify risk factors for depression onset and remission and Poisson regression was used to model the recurrence rate of depressive episodes. Low parental SES, family disruption and a high level of residential instability, defined as three or more family moves, were related to elevated lifetime risks of depression; the effects of family disruption and residential instability were most pronounced on depression onset by age 14. Childhood adversity was also related to increased risk of recurrence and reduced likelihood of remission. Childhood social disadvantage significantly influences risk of depression onset both in childhood and in adulthood. Early childhood adversity is also related to poor prognosis.

Long-term effects of peer victimization on social outcomes through the fourth decade of life in individuals born at normal or extremely low birthweight.

PubMed

Day, Kimberly L; Van Lieshout, Ryan J; Vaillancourt, Tracy; Saigal, Saroj; Boyle, Michael H; Schmidt, Louis A

2017-09-01

Exposure to early adversity is known to have deleterious effects on brain-behaviour relations across the lifespan and across a range of domains. Here, we tested a cumulative risk hypothesis of adult social functioning and health outcomes in the fourth decade of life, using the oldest known longitudinally followed cohort of survivors of extremely low birthweight (ELBW; <1,000 g). We investigated the additional impact of peer victimization in youth on social outcomes at age 29-36 years in ELBW survivors and matched normal birthweight (NBW; >2,500 g) participants. In the combined sample, peer victimization was associated with lower likelihood of having children and household income, poorer family functioning and self-esteem, more loneliness and chronic health conditions, less social support, and increased likelihood for contact with police. Moderation analyses indicated that among ELBW survivors, compared to their NBW counterparts, victimization was more strongly associated with being convicted of a crime and with having chronic health conditions. These findings highlight the negative long-term impact of peer victimization on all children and that some outcomes may be differentially affected by prenatal and early post-natal environments. Statement of contribution What is already known on this subject Exposure to early adversity has deleterious effects on brain-behaviour relations across the lifespan. Extremely premature children have higher rates of exposure to adversities, including peer victimization. Peer victimization is associated with adverse outcomes in adulthood in those born at term. What does this study add? Victimization negatively impacts the social outcomes of those born extremely premature and at term into adulthood. Associations appear to be affected by individual differences in prenatal and early post-natal environments. Intervention is crucial when peer victimization occurs in children at risk, as well as those typically developing. © 2016 The British Psychological Society.

Early Life in a Barren Environment Adversely Affects Spatial Cognition in Laying Hens (Gallus gallus domesticus)

PubMed Central

Tahamtani, Fernanda M.; Nordgreen, Janicke; Nordquist, Rebecca E.; Janczak, Andrew M.

2015-01-01

Spatial cognition in vertebrates is adversely affected by a lack of environmental complexity during early life. However, to our knowledge, no previous studies have tested the effect of early exposure to varying degrees of environmental complexity on specific components of spatial cognition in chickens. There are two main rearing systems for laying hens in the EU: aviaries and cages. These two systems differ from one another in environmental complexity. The aim of the present study was to test the hypothesis that rearing in a barren cage environment relative to a complex aviary environment causes long-lasting deficits in the ability to perform spatial tasks. For this purpose, 24 white Dekalb laying hens, half of which had been reared in an aviary system and the other half in a conventional cage system, were tested in a holeboard task. Birds from both treatment groups learnt the task; however, the cage-reared hens required more time to locate rewards and had poorer levels of working memory. The latter finding supports the hypothesis that rearing in a barren environment causes long-term impairment of short-term memory in chickens. PMID:26664932

Fetal programming as a predictor of adult health or disease: the need to reevaluate fetal heart function.

PubMed

Miranda, Joana O; Ramalho, Carla; Henriques-Coelho, Tiago; Areias, José Carlos

2017-11-01

Epidemiologic and experimental evidence suggests that adverse stimuli during critical periods in utero permanently alters organ structure and function and may have persistent consequences for the long-term health of the offspring. Fetal hypoxia, maternal malnutrition, or ventricular overloading are among the major adverse conditions that can compromise cardiovascular development in early life. With the heart as a central organ in fetal adaptive mechanisms, a deeper understanding of the fetal cardiovascular physiology and of the echocardiographic tools to assess both normal and stressed pregnancies would give precious information on fetal well-being and hopefully may help in early identification of special risk groups for cardiovascular diseases later in life. Assessment of cardiac function in the fetus represents an additional challenge when comparing to children and adults, requiring advanced training and a critical approach to properly acquire and interpret functional parameters. This review summarizes the basic fetal cardiovascular physiology and the main differences from the mature postnatal circulation, provides an overview of the particularities of echocardiographic evaluation in the fetus, and finally proposes an integrated view of in utero programming of cardiovascular diseases later in life, highlighting priorities for future clinical research.

Prevalence of negative life events and chronic adversities in European pre- and primary-school children: results from the IDEFICS study

PubMed Central

2012-01-01

Background Children are not always recognized as being susceptible to stress, although childhood stressors may originate from multiple events in their everyday surroundings with negative effects on children’s health. Methods As there is a lack of large-scale, European prevalence data on childhood adversities, this study presents the prevalence of (1) negative life events and (2) familial and social adversities in 4637 European pre- and primary-school children (4–11 years old), using a parentally-reported questionnaire embedded in the IDEFICS project (‘Identification and prevention of Dietary- and lifestyle-induced health EFfects In Children and infantS’). Results The following findings were observed: (1) Certain adversities occur only rarely, while others are very regular (i.e. parental divorce); (2) A large percentage of children is shielded from stressors, while a small group of children is exposed to multiple, accumulating adversities; (3) The prevalence of childhood adversity is influenced by geographical location (e.g. north versus south), age group and sex; (4) Childhood adversities are associated and co-occur, resulting in potential cumulative childhood stress. Conclusions This study demonstrated the importance of not only studying traumatic events but also of focusing on the early familial and social environment in childhood stress research and indicated the importance of recording or monitoring childhood adversities. PMID:23173879

EPA’s Children’s Environmental Health Roadmap: applying the 21st century vision to prenatal development (Teratology)

EPA Science Inventory

Understanding the complex relationships between environmental exposures and early life susceptibility in assessing the risk for adverse pregnancy outcomes requires advanced knowledge of biological systems. This broad research is one of several drivers for the Children’s Environme...

Epigenetics and depression: return of the repressed.

PubMed

Dalton, Victoria S; Kolshus, Erik; McLoughlin, Declan M

2014-02-01

Epigenetics has recently emerged as a potential mechanism by which adverse environmental stimuli can result in persistent changes in gene expression. Epigenetic mechanisms function alongside the DNA sequence to modulate gene expression and ultimately influence protein production. The current review provides an introduction and overview of epigenetics with a particular focus on preclinical and clinical studies relevant to major depressive disorder (MDD). PubMed and Web of Science databases were interrogated from January 1995 up to December 2012 using combinations of search terms, including "epigenetic", "microRNA" and "DNA methylation" cross referenced with "depression", "early life stress" and "antidepressant". There is an association between adverse environmental stimuli, such as early life stress, and epigenetic modification of gene expression. Epigenetic changes have been reported in humans with MDD and may serve as biomarkers to improve diagnosis. Antidepressant treatments appear to reverse or initiate compensatory epigenetic alterations that may be relevant to their mechanism of action. As a narrative review, the current report was interpretive and qualitative in nature. Epigenetic modification of gene expression provides a mechanism for understanding the link between long-term effects of adverse life events and the changes in gene expression that are associated with depression. Although still a developing field, in the future, epigenetic modifications of gene expression may provide novel biomarkers to predict future susceptibility and/or onset of MDD, improve diagnosis, and aid in the development of epigenetics-based therapies for depression. © 2013 Published by Elsevier B.V.

Childhood adverse life events, disordered eating, and body mass index in US Military service members.

PubMed

Bakalar, Jennifer L; Barmine, Marissa; Druskin, Lindsay; Olsen, Cara H; Quinlan, Jeffrey; Sbrocco, Tracy; Tanofsky-Kraff, Marian

2018-03-02

US service members appear to be at high-risk for disordered eating. Further, the military is experiencing unprecedented prevalence of overweight and obesity. US service members also report a high prevalence of childhood adverse life event (ALE) exposure. Despite consistent links between early adversity with eating disorders and obesity, there is a dearth of research examining the association between ALE exposure and disordered eating and weight in military personnel. An online survey study was conducted in active duty personnel to examine childhood ALE history using the Life Stressor Checklist - Revised, disordered eating using the Eating Disorder Examination - Questionnaire total score, and self-reported body mass index (BMI, kg/m 2 ). Among 179 respondents, multiple indices of childhood ALE were positively associated with disordered eating. Traumatic childhood ALE and subjective impact of childhood ALE were associated with higher BMI and these associations were mediated by disordered eating. Findings support evaluating childhood ALE exposure among service members with disordered eating and weight concerns. Moreover, findings support the need for prospective research to elucidate these relationships. © 2018 Wiley Periodicals, Inc.

Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.

PubMed

Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2018-01-01

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger AG, Basel.

Inequality in oral health related to early and later life social conditions: a study of elderly in Norway and Sweden.

PubMed

Gülcan, Ferda; Ekbäck, Gunnar; Ordell, Sven; Lie, Stein Atle; Åstrøm, Anne Nordrehaug

2015-02-10

A life course perspective recognizes influences of socially patterned exposures on oral health across the life span. This study assessed the influence of early and later life social conditions on tooth loss and oral impacts on daily performances (OIDP) of people aged 65 and 70 years. Whether social inequalities in oral health changed after the usual age of retirement was also examined. In accordance with "the latent effect life course model", it was hypothesized that adverse early-life social conditions increase the risk of subsequent tooth loss and impaired OIDP, independent of later-life social conditions. Data were obtained from two cohorts studies conducted in Sweden and Norway. The 2007 and 2012 waves of the surveys were used for the present study. Early-life social conditions were measured in terms of gender, education and country of birth, and later-life social conditions were assessed by working status, marital status and size of social network. Logistic regression and Generalized Estimating Equations (GEE) were used to analyse the data. Inverse probability weighting (IPW) was used to adjust estimates for missing responses and loss to follow-up. Early-life social conditions contributed to tooth loss and OIDP in each survey year and both countries independent of later-life social conditions. Lower education correlated positively with tooth loss, but did not influence OIDP. Foreign country of birth correlated positively with oral impacts in Sweden only. Later-life social conditions were the strongest predictors of tooth loss and OIDP across survey years and countries. GEE revealed significant interactions between social network and survey year, and between marital status and survey year on tooth loss. The results confirmed the latent effect life course model in that early and later life social conditions had independent effects on tooth loss and OIDP among the elderly in Norway and Sweden. Between age 65 and 70, inequalities in tooth loss related to marital status declined, and inequalities related to social network increased.

Family Member Deaths in Childhood Predict Systemic Inflammation in Late Life.

PubMed

Norton, Maria C; Hatch, Daniel J; Munger, Ronald G; Smith, Ken R

2017-01-01

Biological and epidemiological evidence has linked early-life psychosocial stress with late-life health, with inflammation as a potential mechanism. We report here the association between familial death in childhood and adulthood and increased levels of high-sensitivity C-reactive protein (CRP), a marker of systemic inflammation. The Cache County Memory Study is a prospective study of persons initially aged 65 and older in 1995. In 2002, there were 1,955 persons in the study with data on CRP (42.3 percent male, mean [SD] age = 81.2 [5.8] years), linked with objective data on family member deaths. Using logistic regression, high (> 10 mg/L) versus low (≤ 10 mg/L) CRP was regressed on cumulative parental, sibling, spouse, and offspring deaths during childhood and during early adulthood, adjusted for family size in each period (percentage family depletion; PFD). Findings revealed PFD during childhood to be significantly associated with CRP (OR = 1.02, 95% CI [1.01, 1.04]). Individuals with two or more family deaths were 79 percent more likely to have elevated CRP than those with zero family deaths (OR = 1.79, 95% CI [1.07, 2.99]). Early adulthood PFD was not related to CRP. This study demonstrates a link between significant psychosocial stress in early life and immune-inflammatory functioning in late life, and suggests a mechanism explaining the link between early-life adversity and late-life health.

A Population-based Study Evaluating the Association between Surgery in Early Life and Child Development at Primary School Entry.

PubMed

O'Leary, James D; Janus, Magdalena; Duku, Eric; Wijeysundera, Duminda N; To, Teresa; Li, Ping; Maynes, Jason T; Crawford, Mark W

2016-08-01

It is unclear whether exposure to surgery in early life has long-term adverse effects on child development. The authors aimed to investigate whether surgery in early childhood is associated with adverse effects on child development measured at primary school entry. The authors conducted a population-based cohort study in Ontario, Canada, by linking provincial health administrative databases to children's developmental outcomes measured by the Early Development Instrument (EDI). From a cohort of 188,557 children, 28,366 children who underwent surgery before EDI completion (age 5 to 6 yr) were matched to 55,910 unexposed children. The primary outcome was early developmental vulnerability, defined as any domain of the EDI in the lowest tenth percentile of the population. Subgroup analyses were performed based on age at first surgery (less than 2 and greater than or equal to 2 yr) and frequency of surgery. Early developmental vulnerability was increased in the exposed group (7,259/28,366; 25.6%) compared with the unexposed group (13,957/55,910; 25.0%), adjusted odds ratio, 1.05; 95% CI, 1.01 to 1.08. Children aged greater than or equal to 2 yr at the time of first surgery had increased odds of early developmental vulnerability compared with unexposed children (odds ratio, 1.05; 95% CI, 1.01 to 1.10), but children aged less than 2 yr at the time of first exposure were not at increased risk (odds ratio, 1.04; 95% CI, 0.98 to 1.10). There was no increase in odds of early developmental vulnerability with increasing frequency of exposure. Children who undergo surgery before primary school age are at increased risk of early developmental vulnerability, but the magnitude of the difference between exposed and unexposed children is small.

Neonatal tactile stimulation reverses the effect of neonatal isolation on open-field and anxiety-like behavior, and pain sensitivity in male and female adult Sprague-Dawley rats.

PubMed

Imanaka, A; Morinobu, S; Toki, S; Yamamoto, S; Matsuki, A; Kozuru, T; Yamawaki, S

2008-01-10

It is well known that early life events induce long-lasting psychophysiological and psychobiological influences in later life. In rodent studies, environmental enrichment after weaning prevents the adulthood behavioral and emotional disturbances in response to early adversities. We compared the behavioral effect of neonatal isolation (NI) with the effect of NI accompanied by tactile stimulation (NTS) to determine whether NTS could reverse or prevent the effects of NI on the adulthood behavioral and emotional responses to environmental stimuli. In addition, we also examined the sex difference of the NTS effect. Measurements of body weights, an open-field locomotor test, an elevated plus maze test, a hot-plate test, and a contextual fear-conditioning test were performed on postnatal day 60. As compared with rats subjected to NI, rats subjected to NTS showed significantly higher activity and exploration in the open-field locomotor test, lower anxiety-like behavior in the elevated plus maze test, and significantly prolonged latencies in the hot-plate test, and this effect was equal among males and females. In the contextual fear-conditioning test, whereas NTS significantly reduced the enhanced freezing time due to NI in females, no significant difference in the freezing time between NI and NTS was found in males. These findings indicate that adequate tactile stimulation in early life plays an important role in the prevention of disturbances in the behavioral and emotional responses to environmental stimuli in adulthood induced by early adverse experiences.

The effects of early life adversity on the immune system.

PubMed

Elwenspoek, Martha M C; Kuehn, Annette; Muller, Claude P; Turner, Jonathan D

2017-08-01

Early life adversity (ELA) is associated with a higher risk for diseases in adulthood. Although the pathophysiological effects of ELA are varied, there may be a unifying role for the immune system in all of the long-term pathologies such as chronic inflammatory disorders (autoimmune diseases, allergy, and asthma). Recently, significant efforts have been made to elucidate the long-term effects ELA has on immune function, as well as the mechanisms underlying these immune changes. In this review, we focus on data from human studies investigating immune parameters in relation to post-natal adverse experiences. We describe the current understanding of the 'ELA immune phenotype', characterized by inflammation, impairment of the cellular immune system, and immunosenescence. However, at present, data addressing specific immune functions are limited and there is a need for high-quality, well powered, longitudinal studies to unravel cause from effect. Besides the immune system, also the stress system and health behaviors are altered in ELA. We discuss probable underlying mechanisms based on epigenetic programming that could explain the ELA immune phenotype and whether this is a direct effect of immune programming or an indirect consequence of changes in behavior or stress reactivity. Understanding the underlying mechanisms will help define effective strategies to prevent or counteract negative ELA-associated outcomes. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Impact of Early-Life Vitamin D Deficiency on Adverse Cardiopulmonary Responses to Atmospheric Smog in Mice

EPA Science Inventory

Although it has been well established that air pollution contributes to cardiovascular morbidity and mortality, the role of nutrition in altering susceptibility has not been adequately addressed. Low levels of micronutrients like vitamin D in childhood can result in chronic probl...

Metal-induced Dysregulation of the NF-kB Pathway in a Detroit Michigan's Children Cohort

EPA Science Inventory

Heavy metal exposure can have adverse effects on childhood development, and early life exposures have been shown to modify key biological pathways. We set out to evaluate the genome-wide effects of metals exposure in the Mechanistic Indicators of Childhood Asthma (MICA) study, wh...

Repeated intranasal oxytocin administration in early life dysregulates the HPA axis and alters social behavior

USDA-ARS?s Scientific Manuscript database

Aggression and social stress are major welfare concerns when regrouping captive animals, with detrimental effects on health. In contrast, positive social interactions can reduce the adverse effects of social stress in humans and other animal species. This reduction may be mediated by oxytocin (OT), ...

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine.

PubMed

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-05-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

Early-life exposure to air pollutants and adverse pregnancy outcomes: protocol for a prospective cohort study in Beijing.

PubMed

Song, Jing; Chen, Yi; Wei, Ling; Ma, Ying; Tian, Ning; Huang, Shi Yun; Dai, Yin Mei; Zhao, Li Hong; Kong, Yuan Yuan

2017-09-03

The association between early exposure to ambient air pollution and adverse pregnancy outcomes in China is unclear. This study will assess the risk of early-life exposure to air pollutants in Beijing and explore the viability of 8-hydroxydeoxyguanosine (8-OHdG) as a biological indicator to assess oxidative stress induced by early-life exposure to air pollution. Here , 2500 women with singleton pregnancies and their infants will be recruited from the Beijing Obstetrics and Gynecology Hospital. We will collect nine types of biological samples, including maternal serum, urine, placental tissue, umbilical cord tissue and umbilical cord blood during all three trimesters. The air pollution data (particulate matter (PM)2.5, PM10 and similar factors) will be recorded at official fixed-site monitoring stations closest to where the pregnant women live. We plan to assess the effect of air pollutants on adverse pregnancy outcomes and infant respiratory and circulatory disease using Cox regression and competitive risk analysis and explore possible critical windows of exposure during pregnancy using daily pollutant concentrations averaged over various periods of pregnancy combined with individual activity and physiological parameters. Maternal and umbilical cord blood samples (1000 samples) will be randomly selected for 8-OHdG assays to assess the correlation between exposures to air pollutants and oxidative stress. We will determine whether air pollutant exposure or 8-OHdG levels are associated with adverse pregnancy outcomes. SPSS and SAS statistical software will be used for data analysis. Cox regression and competing risk analysis will be used to compute the HR and population attributable risk. This research protocol has already been approved by the Medical Ethics Committee of Beijing Obstetrics and Gynecology Hospital. Written informed consent will be obtained from all study participants prior to enrolment. The results will be published in peer-reviewed journals or disseminated through conference presentations. This study has been registered in WHO International Clinical Trial Register-Chinese Clinical Trial Registry under registrationnumber ChiCTR-ROC-16010181 (http :// www.chictr.org.cn / showproj.aspx ?proj=17328). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Promoting Healthy Child Development via a Two-Generation Translational Neuroscience Framework: The Filming Interactions to Nurture Development Video Coaching Program.

PubMed

Fisher, Philip A; Frenkel, Tahl I; Noll, Laura K; Berry, Melanie; Yockelson, Melissa

2016-12-01

In this article, we focus on applying methods of translational neuroscience to two-generation, family-based interventions. In recent years, a small but growing body of evidence has documented the reversibility of some of the neurobiological effects of early adversity in the context of environmental early interventions. Some of these interventions are now being implemented at scale, which may help reduce disparities in the face of early life stress. Further progress may occur by extending these efforts to two-generation models that target caregivers' capabilities to improve children's outcomes. In this article, we describe the content and processes of the Filming Interactions to Nurture Development (FIND) video coaching intervention. We also discuss the two-generation, translational neuroscience framework on which FIND is based, and how similar approaches can be developed and scaled to mitigate the effects of adversity.

Promoting Healthy Child Development via a Two-Generation Translational Neuroscience Framework: The Filming Interactions to Nurture Development Video Coaching Program

PubMed Central

Fisher, Philip A.; Frenkel, Tahl I.; Noll, Laura K.; Berry, Melanie; Yockelson, Melissa

2017-01-01

In this article, we focus on applying methods of translational neuroscience to two-generation, family-based interventions. In recent years, a small but growing body of evidence has documented the reversibility of some of the neurobiological effects of early adversity in the context of environmental early interventions. Some of these interventions are now being implemented at scale, which may help reduce disparities in the face of early life stress. Further progress may occur by extending these efforts to two-generation models that target caregivers’ capabilities to improve children’s outcomes. In this article, we describe the content and processes of the Filming Interactions to Nurture Development (FIND) video coaching intervention. We also discuss the two-generation, translational neuroscience framework on which FIND is based, and how similar approaches can be developed and scaled to mitigate the effects of adversity. PMID:28936231

Early-Life Stressors, Personality Development, and Fast Life Strategies: An Evolutionary Perspective on Malevolent Personality Features.

PubMed

Csathó, Árpád; Birkás, Béla

2018-01-01

Life history theory posits that behavioral adaptation to various environmental (ecological and/or social) conditions encountered during childhood is regulated by a wide variety of different traits resulting in various behavioral strategies. Unpredictable and harsh conditions tend to produce fast life history strategies, characterized by early maturation, a higher number of sexual partners to whom one is less attached, and less parenting of offspring. Unpredictability and harshness not only affects dispositional social and emotional functioning, but may also promote the development of personality traits linked to higher rates of instability in social relationships or more self-interested behavior. Similarly, detrimental childhood experiences, such as poor parental care or high parent-child conflict, affect personality development and may create a more distrustful, malicious interpersonal style. The aim of this brief review is to survey and summarize findings on the impact of negative early-life experiences on the development of personality and fast life history strategies. By demonstrating that there are parallels in adaptations to adversity in these two domains, we hope to lend weight to current and future attempts to provide a comprehensive insight of personality traits and functions at the ultimate and proximate levels.

Allostatic load mediates the impact of stress and trauma on physical and mental health in Indigenous Australians.

PubMed

Sarnyai, Zoltán; Berger, Maximus; Jawan, Isabella

2016-02-01

A considerable gap exists in health and social emotional well-being between Indigenous people and non-Indigenous Australians. Recent research in stress neurobiology highlights biological pathways that link early adversity and traumas as well as life stresses to ill health. We argue that the neurobiological stress response and its maladaptive changes, termed allostatic load, provide a useful framework to understand how adversity leads to physical and mental illness in Indigenous people. In this paper we review the biology of allostatic load and make links between stress-induced systemic hormonal, metabolic and immunological changes and physical and mental illnesses. Exposure to chronic stress throughout life results in an increased allostatic load that may contribute to a number of metabolic, cardiovascular and mental disorders that shorten life expectancy in Indigenous Australians. © The Royal Australian and New Zealand College of Psychiatrists 2015.

Epigenetic mechanisms in developmental programming of adult disease

PubMed Central

Chen, Man; Zhang, Lubo

2011-01-01

Adverse insults during intrauterine life can result in permanent changes in the physiology and metabolism of the offspring, which in turn leads to an increased risk of disease in adulthood. This is an adaptational response by the fetus to changes in the environmental signals that it receives during early life to ensure its survival and prepare itself for postnatal life. Increasing evidence suggests that the epigenetic regulation of gene expression patterns has a crucial role in the developmental programming of adult disease. This review summarizes recent studies of epigenetic mechanisms and focuses particularly on studies that explore identifiable epigenetic biomarkers in the promoters of specific disease-associated genes. Such biomarkers would enable early recognition of children who might be at risk of developing adult disease with fetal origins. PMID:21945859

Life Course Pathways to Racial Disparities in Cognitive Impairment among Older Americans*

PubMed Central

Zhang, Zhenmei; Hayward, Mark D.; Yu, Yan-Liang

2016-01-01

Blacks are especially hard hit by cognitive impairment at older ages compared to whites. Here, we take advantage of the Health and Retirement Study (1998–2010) to assess how this racial divide in cognitive impairment is associated with the racial stratification of life course exposures and resources over a 12-year period among 8,946 non-Hispanic whites and blacks aged 65 and older in 1998. We find that blacks suffer from a higher risk of moderate/severe cognitive impairment at baseline and during the follow-up. Blacks are also more likely to report childhood adversity and to have grown up in the segregated South, and these early-life adversities put blacks at a significantly higher risk of cognitive impairment. Adulthood socioeconomic status is strongly associated with the risk of cognitive impairment, net of childhood conditions. However, racial disparities in cognitive impairment, though substantially reduced, are not eliminated when controlling for these life course factors. PMID:27247126

Commentary: Childhood exposure to environmental adversity and the well-being of people with intellectual disabilities.

PubMed

Emerson, E

2013-07-01

People with intellectual disabilities have poorer health than their non-disabled peers. They are also more likely to be exposed to a wide range of environmental adversities in childhood. Research undertaken in the general population has demonstrated that exposure to environmental adversity in childhood can have an adverse impact on health and well-being across the life course. Recently, research in this area has added new breadth and depth to our understanding of: (1) the extent to which cumulative exposure to environmental adversities across the life course, but especially in early childhood, can reduce health and well-being; (2) the social, psychological and biological mediating pathways through which environmental adversities may impair health; (3) the processes associated with resilience and vulnerability in the face of exposure to adversity; and (4) the social significance of these effects in accounting for the magnitude of the inequalities in health that are apparent both between and within populations. This new knowledge is making a significant contribution to the development of social policies that seek to combine health gain with the reduction in health inequalities. This paper attempts to apply this knowledge to research aimed at understanding and improving the health and well-being of people with intellectual disabilities. © 2012 The Author. Journal of Intellectual Disability Research © 2012 John Wiley & Sons Ltd, MENCAP & IASSID.

Life Course Pathways of Adversities Linking Adolescent Socioeconomic Circumstances and Functional Somatic Symptoms in Mid-Adulthood: A Path Analysis Study

PubMed Central

Jonsson, Frida; San Sebastian, Miguel; Strömsten, Lotta M. J.; Hammarström, Anne; Gustafsson, Per E.

2016-01-01

While research examining the health impact of early socioeconomic conditions suggests that effects may exist independently of or jointly with adult socioeconomic position, studies exploring other potential pathways are few. Following a chain of risk life course model, this prospective study seeks to examine whether pathways of occupational class as well as material and social adversities across the life course link socioeconomic disadvantage in adolescent to functional somatic symptoms in mid-adulthood. Applying path analysis, a multiple mediator model was assessed using prospective data collected during 26 years through the Northern Swedish Cohort. The sample contained 987 individuals residing in the municipality of Luleå, Sweden, who participated in questionnaire surveys at age 16, 21, 30 and 42. Socioeconomic conditions (high/low) in adolescence (age 16) were operationalized using the occupation of the parents, while occupational class in adulthood (manual/non-manual) was measured using the participant’s own occupation at age 21 and 30. The adversity measurements were constructed as separate age specific parcels at age 21 and 30. Social adversity included items pertaining to stressful life events that could potentially harm salient relationships, while material adversity was operationalized using items concerning unfavorable financial and material circumstances. Functional somatic symptoms at age 42 was a summary measure of self-reported physical symptoms, palpitation and sleeping difficulties that had occurred during the last 12 months. An association between socioeconomic conditions at age 16 and functional somatic symptoms at age 42 (r = 0.068) which was partially explained by people’s own occupational class at age 21 and then material as well as social adversity at age 30 was revealed. Rather than proposing a direct and independent health effect of the socioeconomic conditions of the family, the present study suggests that growing up in an unfavorable socioeconomic environment might be a source for a chain of adverse material and social living situations, which in turn affects adult health. PMID:27214206

Evidence for Interplay between Genes and Parenting on Infant Temperament in the First Year of Life: Monoamine Oxidase a Polymorphism Moderates Effects of Maternal Sensitivity on Infant Anger Proneness

ERIC Educational Resources Information Center

Pickles, Andrew; Hill, Jonathan; Breen, Gerome; Quinn, John; Abbott, Kate; Jones, Helen; Sharp, Helen

2013-01-01

Background: The low expression polymorphism of the MAOA gene in interaction with adverse environments (G × E) is associated with antisocial behaviour disorders. These have their origins in early life, but it is not known whether MAOA G × E occurs in infants. We therefore examined whether MAOA G × E predicts infant anger proneness, a temperamental…

Childhood adversity, social support networks and well-being among youth aging out of care: An exploratory study of mediation.

PubMed

Melkman, Eran P

2017-10-01

The goals of the present study are to examine the relationship between childhood adversity and adult well-being among vulnerable young adults formerly placed in substitute care, and to investigate how characteristics of their social support networks mediate this association. A sample of 345 Israeli young adults (ages 18-25), who had aged out of foster or residential care, responded to standardized self-report questionnaires tapping their social support network characteristics (e.g., network size or adequacy) vis-à-vis several types of social support (emotional, practical, information and guidance), experiences of childhood adversity, and measures of well-being (psychological distress, loneliness, and life satisfaction). Structural equation modelling (SEM) provided support for the mediating role of social support in the relationship between early adversity and adult well-being. Although network size, frequency of contact with its members, satisfaction with support, and network adequacy, were all negatively related to early adversity, only network adequacy showed a major and consistent contribution to the various measures of well-being. While patterns were similar across the types of support, the effects of practical and guidance support were most substantial. The findings suggest that the detrimental long-term consequences of early adversity on adult well-being are related not only to impaired structural aspects of support (e.g., network size), but also to a decreased ability to recognize available support and mobilize it. Practical and guidance support, more than emotional support, seem to be of critical importance. Copyright © 2017 Elsevier Ltd. All rights reserved.

Early-Life Stress Affects Stress-Related Prefrontal Dopamine Activity in Healthy Adults, but Not in Individuals with Psychotic Disorder

PubMed Central

Kasanova, Zuzana; Hernaus, Dennis; Vaessen, Thomas; van Amelsvoort, Thérèse; Winz, Oliver; Heinzel, Alexander; Pruessner, Jens; Mottaghy, Felix M.

2016-01-01

Early life stress may have a lasting impact on the developmental programming of the dopamine (DA) system implicated in psychosis. Early adversity could promote resilience by calibrating the prefrontal stress-regulatory dopaminergic neurotransmission to improve the individual’s fit with the predicted stressful environment. Aberrant reactivity to such match between proximal and distal environments may, however, enhance psychosis disease risk. We explored the combined effects of childhood adversity and adult stress by exposing 12 unmedicated individuals with a diagnosis of non-affective psychotic disorder (NAPD) and 12 healthy controls (HC) to psychosocial stress during an [18F]fallypride positron emission tomography. Childhood trauma divided into early (ages 0–11 years) and late (12–18 years) was assessed retrospectively using a questionnaire. A significant group x childhood trauma interaction on the spatial extent of stress-related [18F]fallypride displacement was observed in the mPFC for early (b = -8.45, t(1,23) = -3.35, p = .004) and late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). In healthy individuals, the spatial extent of mPFC DA activity under acute psychosocial stress was positively associated with the severity of early (b = 7.23, t(11) = 3.06, p = .016) as well as late childhood trauma (b = -7.86, t(1,23) = -2.48, p = .023). Additionally, a trend-level main effect of early childhood trauma on subjective stress response emerged within this group (b = -.7, t(11) = -2, p = .07), where higher early trauma correlated with lower subjective stress response to the task. In the NAPD group, childhood trauma was not associated with the spatial extent of the tracer displacement in mPFC (b = -1.22, t(11) = -0.67), nor was there a main effect of trauma on the subjective perception of stress within this group (b = .004, t(11) = .01, p = .99). These findings reveal a potential mechanism of neuroadaptation of prefrontal DA transmission to early life stress and suggest its role in resilience and vulnerability to psychosis. PMID:27007554

Early adversity and neural correlates of executive function: implications for academic adjustment.

PubMed

McDermott, Jennifer M; Westerlund, Alissa; Zeanah, Charles H; Nelson, Charles A; Fox, Nathan A

2012-02-15

Early adversity can negatively impact the development of cognitive functions, although little is known about whether such effects can be remediated later in life. The current study examined one facet of executive functioning - inhibitory control - among children who experienced institutional care and explored the impact of a foster care intervention within the context of the Bucharest Early Intervention Project (BEIP). Specifically, a go/nogo task was administered when children were eight years old and behavioral and event-related potential (ERP) measures were collected. Results revealed that children assigned to care as usual (i.e. institutional care) were less accurate and exhibited slower neural responses compared to children assigned to the foster care intervention and children who had never been institutionalized. However, children in both the care as usual and foster care groups exhibited diminished attention processing of nogo cues as assessed via P300 amplitude. Foster care children also showed differential reactivity between correct and error responses via the error-related negativity (ERN) as compared to children in the care as usual group. Combined, the results highlight perturbations in neural sources of behavioral and attention problems among children experiencing early adversity. Potential implications for academic adjustment in at risk children are discussed. Copyright © 2011 Elsevier Ltd. All rights reserved.

The cardio-protective diet

PubMed Central

Sivasankaran, S.

2010-01-01

Globalization has made calorie rich, cheap, convenient marketed foods the main menu for the common man. Indians are particularly susceptible to the adverse outcomes of this dietary change because of ethnic, epigenetic reasons and sarcopenic adiposity (less muscle more fat for the same body weight). Children have smaller body frame making them more susceptible to adverse effects of hyperglycaemia leading to stress on beta cells and their damage. This has resulted in escalation of lifestyle diseases by three-fold, that too at our younger age group at lower body mass indices. Preventive measures are necessary in early life to protect the beta cells, to achieve a metabolically healthy society. This will help in sustaining optimal beta cell function throughout a person’s life. Modification in dietary habits by educating the society, proper food labelling and legal regulation, restricting calorie, sugar, saturated fat, trans-fat and salt intake has proved its benefits in the developed world. Changes in the quality of food is as important as restricting calorie intake. This includes facilitation of increased consumption of dietary fiber, complex carbohydrates, nuts, fruits and vegetables. Restrictions are needed to reduce trans-fats, saturated fats and cooking habits such as deep frying which oxidizes cholesterol and lipids. Foods with long shelf-life shorten the life line because of their salt, sugar or trans-fat content. Individual meals need to be targeted in the general dietary guidelines, to minimize the post-prandial metabolic insult. In general, we need healthy start to early life particularly the first twenty years of life so that the habits cultured during childhood are sustained for the rest of productive years. PMID:21150013

Changes in sleep quality and levels of psychological distress during the adaptation to university: The role of childhood adversity.

PubMed

John-Henderson, Neha A; Williams, Sarah E; Brindle, Ryan C; Ginty, Annie T

2018-05-25

Stress-related sleep disturbances are common, and poor sleep quality can negatively affect health. Previous work indicates that early-life adversity is associated with compromised sleep quality later in life, but it is unknown whether it predicts greater declines in sleep quality during stressful life transitions. We propose and test a conceptual model whereby individuals who reported experiencing greater levels of child maltreatment would experience greater psychological distress during a stressful life transition, which in turn would contribute to greater declines in sleep quality, relative to their quality of sleep before the stressful transition. Controlling for potential confounding variables (e.g., age, gender), structural equation modelling demonstrated that psychological distress experienced during a stressful transition (i.e., beginning life at university) mediated the relationship between childhood emotional neglect and changes in sleep quality. The hypothesized model demonstrated a good overall fit to the data, χ 2 (15) = 17.69, p = .279, CFI = .99, TLI = .97, SRMR = .04, RMSEA = .04 (90% CI <0.001-0.09). Emotional neglect (β = .22) was positively associated with psychological distress which in turn was positively associated with poor sleep quality (β = .31) during a stressful transition. Future research should aim to understand the specific stressors in the university environment that are most challenging to individuals who faced early-life emotional maltreatment. These findings will help inform interventions to facilitate adaptation to a new environment and improve sleep quality for these university students. © 2018 The British Psychological Society.

Lifecourse Approach to Racial/Ethnic Disparities in Childhood Obesity123

PubMed Central

Dixon, Brittany; Peña, Michelle-Marie; Taveras, Elsie M.

2012-01-01

Eliminating racial/ethnic disparities in health and health care is a national priority, and obesity is a prime target. During the last 30 y in the United States, the prevalence of obesity among children has dramatically increased, sparing no age group. Obesity in childhood is associated with adverse cardio-metabolic outcomes such as hypertension, hyperlipidemia, and type II diabetes and with other long-term adverse outcomes, including both physical and psychosocial consequences. By the preschool years, racial/ethnic disparities in obesity prevalence are already present, suggesting that disparities in childhood obesity prevalence have their origins in the earliest stages of life. Several risk factors during pregnancy are associated with increased risk of offspring obesity, including excessive maternal gestational weight gain, gestational diabetes, smoking during pregnancy, antenatal depression, and biological stress. During infancy and early childhood, rapid infant weight gain, infant feeding practices, sleep duration, child’s diet, physical activity, and sedentary practices are associated with the development of obesity. Studies have found substantial racial/ethnic differences in many of these early life risk factors for childhood obesity. It is possible that racial/ethnic differences in early life risk factors for obesity might contribute to the high prevalence of obesity among minority preschool-age children and beyond. Understanding these differences may help inform the design of clinical and public health interventions and policies to reduce the prevalence of childhood obesity and eliminate disparities among racial/ethnic minority children. PMID:22332105

Cumulative Childhood Adversity, Educational Attainment, and Active Life Expectancy Among U.S. Adults

PubMed Central

Montez, Jennifer Karas; Hayward, Mark D.

2015-01-01

Studies of the early-life origins of adult physical functioning and mortality have found that childhood health and socioeconomic context are important predictors, often irrespective of adult experiences. However, these studies have generally assessed functioning and mortality as distinct processes and used cross-sectional prevalence estimates that neglect the interplay of disability incidence, recovery, and mortality. Here, we examine whether early-life disadvantages both shorten lives and increase the number and fraction of years lived with functional impairment. We also examine the degree to which educational attainment mediates and moderates the health consequences of early-life disadvantages. Using the 1998–2008 Health and Retirement Study, we examine these questions for non-Hispanic whites and blacks aged 50–100 years using multistate life tables. Within levels of educational attainment, adults from disadvantaged childhoods lived fewer total and active years, and spent a greater portion of life impaired compared with adults from advantaged childhoods. Higher levels of education did not ameliorate the health consequences of disadvantaged childhoods. However, because education had a larger impact on health than did childhood socioeconomic context, adults from disadvantaged childhoods who achieved high education levels often had total and active life expectancies that were similar to or better than those of adults from advantaged childhoods who achieved low education levels. PMID:24281740

Annual Research Review: Positive Adjustment to Adversity--Trajectories of Minimal-Impact Resilience and Emergent Resilience

ERIC Educational Resources Information Center

Bonanno, George A.; Diminich, Erica D.

2013-01-01

Background: Research on resilience in the aftermath of potentially traumatic life events (PTE) is still evolving. For decades, researchers have documented resilience in children exposed to corrosive early environments, such as poverty or chronic maltreatment. Relatively more recently, the study of resilience has migrated to the investigation of…

Effects of oxytocin administration in early life on the behavioral and physiological stress response of swine

USDA-ARS?s Scientific Manuscript database

The swine industry is moving toward the group-housing of sows. However, group-housing can result in increased aggression and social stress, with detrimental effects on swine health and productivity. In contrast, positive social relationships can reduce the adverse effects of social stress. This migh...

Evaluation of key events in the mode of action for a carry-over carcinogen in mice

EPA Science Inventory

Evaluation of key events in the mode of action for a carry-over carcinogen in mice Charles E. Wood, April D. Lake, Greg Olson, Michael H. George, Susan D. Hester, Anthony B. DeAngelo Introduction: Early life environmental exposures are established determinants for adverse health...

Lack of evidence for intergenerational reproductive effects due to prenatal and postnatal undernutrition in the female CD-1 mouse

EPA Science Inventory

The impacts of adverse environments during the prenatal and/or early postnatal periods may be manifested as functional deficits that occur later in life. Epidemiological studies have shown an association of sub-optimal pregnancy outcomes in one generation with similar events in t...

Associations among oxytocin receptor gene (OXTR) DNA methylation in adulthood, exposure to early life adversity, and childhood trajectories of anxiousness.

PubMed

Gouin, J P; Zhou, Q Q; Booij, L; Boivin, M; Côté, S M; Hébert, M; Ouellet-Morin, I; Szyf, M; Tremblay, R E; Turecki, G; Vitaro, F

2017-08-07

Recent models propose deoxyribonucleic acid methylation of key neuro-regulatory genes as a molecular mechanism underlying the increased risk of mental disorder associated with early life adversity (ELA). The goal of this study was to examine the association of ELA with oxytocin receptor gene (OXTR) methylation among young adults. Drawing from a 21-year longitudinal cohort, we compared adulthood OXTR methylation frequency of 46 adults (23 males and 23 females) selected for high or low ELA exposure based on childhood socioeconomic status and exposure to physical and sexual abuse during childhood and adolescence. Associations between OXTR methylation and teacher-rated childhood trajectories of anxiousness were also assessed. ELA exposure was associated with one significant CpG site in the first intron among females, but not among males. Similarly, childhood trajectories of anxiousness were related to one significant CpG site within the promoter region among females, but not among males. This study suggests that females might be more sensitive to the impact of ELA on OXTR methylation than males.

Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity.

PubMed

Daskalakis, Nikolaos P; Oitzl, Melly S; Schächinger, Hartmut; Champagne, Danielle L; de Kloet, E Ronald

2012-07-16

In the present study, we tested both the cumulative stress and the mismatch hypothesis of psychopathology. For this purpose the combined effects of early-life adversity and later-life stress exposure on behavioral markers of psychosis susceptibility were studied in male Wistar rats. Experiment I: rat pups divided on the basis of the levels of their maternal care experience in low, medium or high maternal care groups, were reared post-weaning in groups (Exp. IA) or in social isolation (Exp. IB) and tested at adulthood under basal conditions or after an acute corticosterone (CORT) administration. Maternal care levels were assessed by measuring the dam's licking and grooming (LG) the first postnatal week of life. Experiment II: rat pups exposed as neonates to daily sessions of 8h of maternal separation (MS) on postnatal days 3, 4 and 5 either altogether in their home cage (HOME SEP) or alone in a novel environment (NOVEL SEP), were reared post-weaning in groups and tested at adulthood under basal conditions. Adult testing included behaviors marking psychosis susceptibility: apomorphine-induced gnawing (APO-gnawing), acoustic startle response and its modulation by a prepulse stimulus (PPI). The behavior of the Medium LG offspring was used as baseline reference for all the three experiments. Experiment I: Low maternal LG history alone had limited effects on the behavior of Wistar offspring, although increased acoustic startle and increased PPI, at high prepulse intensity levels, were observed. When low maternal LG history was combined with post-weaning social isolation, basal APO-gnawing was decreased and PPI increased, compared to High LG and Med LG offspring. This reflects attenuated psychosis susceptibility. High LG offspring reared in isolation displayed, however, the highest APO-gnawing and the lowest PPI levels among rats reared in social isolation, which is indicative for increased psychosis susceptibility. These findings support the mismatch hypothesis. For demonstration of the cumulative stress hypothesis an injection of CORT in the adult Low LG offspring was required that increased APO-gnawing and reduced PPI. This CORT-induced PPI disruption was greatly enhanced after additional isolation rearing. The High LG group, either socially housed or reared in isolation, was resistant to the acute effects of CORT at adulthood. Experiment II: MS increased psychosis susceptibility only in NOVEL SEP rats that had experienced MS in the context of early social isolation. These individuals displayed increased adult APO-gnawing and reduced PPI, if reared post-weaning in a condition that does not match with their early life social environment (i.e. group housing). This finding supports the mismatch hypothesis. The outcome of environmental manipulations on developmental programming of psychosis susceptibility depends on the interplay of early-life adversity and later-life stressors in a manner that supports the mismatch hypothesis. However, evidence for the cumulative stress hypothesis arises if vulnerable individuals are exposed in later life additionally to excess of the stress hormone CORT. Copyright © 2012 Elsevier Inc. All rights reserved.

Early-Life Toxic Insults and Onset of Sporadic Neurodegenerative Diseases-an Overview of Experimental Studies.

PubMed

Tartaglione, Anna Maria; Venerosi, Aldina; Calamandrei, Gemma

2016-01-01

The developmental origin of health and disease hypothesis states that adverse fetal and early childhood exposures can predispose to obesity, cardiovascular, and neurodegenerative diseases (NDDs) in adult life. Early exposure to environmental chemicals interferes with developmental programming and induces subclinical alterations that may hesitate in pathophysiology and behavioral deficits at a later life stage. The mechanisms by which perinatal insults lead to altered programming and to disease later in life are still undefined. The long latency between exposure and onset of disease, the difficulty of reconstructing early exposures, and the wealth of factors which the individual is exposed to during the life course make extremely difficult to prove the developmental origin of NDDs in clinical and epidemiological studies. An overview of animal studies assessing the long-term effects of perinatal exposure to different chemicals (heavy metals and pesticides) supports the link between exposure and hallmarks of neurodegeneration at the adult stage. Furthermore, models of maternal immune activation show that brain inflammation in early life may enhance adult vulnerability to environmental toxins, thus supporting the multiple hit hypothesis for NDDs' etiology. The study of prospective animal cohorts may help to unraveling the complex pathophysiology of sporadic NDDs. In vivo models could be a powerful tool to clarify the mechanisms through which different kinds of insults predispose to cell loss in the adult age, to establish a cause-effect relationship between "omic" signatures and disease/dysfunction later in life, and to identify peripheral biomarkers of exposure, effects, and susceptibility, for translation to prospective epidemiological studies.

Early-Life Stress: From Neuroendocrine Mechanisms to Stress-Related Disorders.

PubMed

Pervanidou, Panagiota; Chrousos, George P

2018-06-08

Stress exposure is highly prevalent in the general population; however, the experience of stress during vulnerable periods of development has substantial and permanent effects on brain structure and function and physical health in adulthood. Stress, the state of threatened homeostasis, is generally associated with a time-limited activation of the stress system, i.e., the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous system, tailored to the stressful stimulus also known as the stressor. On the other hand, chronic stress may be associated with lingering hyper- or hyposecretion of mediators of the stress system. This chronic condition is called dyshomeostasis, allostasis, or cacostasis and is associated with increased mental and physical morbidity in the long term. Stressful or traumatic experiences during fetal life, early childhood, and adolescence have been related to persistent neuroendocrine and epigenetic changes. Further, brain structures involved in the stress response, such as those of the stress system, the hippocampus, and the amygdala, may be programmed early on for a life of adversity. © 2018 S. Karger AG, Basel.

Effects of Mineralocorticoid Receptor Overexpression on Anxiety and Memory after Early Life Stress in Female Mice

PubMed Central

Kanatsou, Sofia; Ter Horst, Judith P.; Harris, Anjanette P.; Seckl, Jonathan R.; Krugers, Harmen J.; Joëls, Marian

2016-01-01

Early-life stress (ELS) is a risk factor for the development of psychopathology, particularly in women. Human studies have shown that certain haplotypes of NR3C2, encoding the mineralocorticoid receptor (MR), that result in gain of function, may protect against the consequences of stress exposure, including childhood trauma. Here, we tested the hypothesis that forebrain-specific overexpression of MR in female mice would ameliorate the effects of ELS on anxiety and memory in adulthood. We found that ELS increased anxiety, did not alter spatial discrimination and reduced contextual fear memory in adult female mice. Transgenic overexpression of MR did not alter anxiety but affected spatial memory performance and enhanced contextual fear memory formation. The effects of ELS on anxiety and contextual fear were not affected by transgenic overexpression of MR. Thus, MR overexpression in the forebrain does not represent a major resilience factor to early life adversity in female mice. PMID:26858618

Ontogeny of memory: An update on 40 years of work on infantile amnesia.

PubMed

Madsen, Heather Bronwyn; Kim, Jee Hyun

2016-02-01

Given the profound influence that early life experiences can have upon psychosocial functioning later in life, it is intriguing that most adults fail to recall autobiographical events from their early childhood years. Infantile amnesia is the term used to describe this phenomenon of accelerated forgetting during infancy, and it is not unique to humans. Over the years, information garnered from animal studies has provided clues as to the neurobiological basis of infantile amnesia. The purpose of this review is to provide a neurobiological update on what we now know about infantile amnesia since the publication of Campbell and Spear's seminal review on the topic more than 40 years ago. We present evidence that infantile amnesia is unlikely to be explained by a unitary theory, with the protracted development of multiple brain regions and neurotransmitter systems important for learning and memory likely to be involved. The recent discovery that exposure to early life stress can alleviate infantile amnesia offers a potential explanation as to how early adversity can so profoundly affect mental health in adulthood, and understanding the neurobiological basis for this early transition may lead to the development of effective therapeutic interventions. Copyright © 2015 Elsevier B.V. All rights reserved.

PPTOX III: environmental stressors in the developmental origins of disease--evidence and mechanisms.

PubMed

Schug, Thaddeus T; Barouki, Robert; Gluckman, Peter D; Grandjean, Philippe; Hanson, Mark; Heindel, Jerold J

2013-02-01

Fetal and early postnatal development constitutes the most vulnerable time period of human life in regard to adverse effects of environmental hazards. Subtle effects during development can lead to functional deficits and increased disease risk later in life. The hypothesis stating that environmental exposures leads to altered programming and, thereby, to increased susceptibility to disease or dysfunction later in life has garnered much support from both experimental and epidemiological studies. Similar observations have been made on the long-term impact of nutritional unbalance during early development. In an effort to bridge the fields of nutritional and environmental developmental toxicity, the Society of Toxicology sponsored this work. This report summarizes novel findings in developmental toxicity as reported by select invited experts and meeting attendees. Recommendations for the application and improvement of current and future research efforts are also presented.

Mismatch or cumulative stress: toward an integrated hypothesis of programming effects.

PubMed

Nederhof, Esther; Schmidt, Mathias V

2012-07-16

This paper integrates the cumulative stress hypothesis with the mismatch hypothesis, taking into account individual differences in sensitivity to programming. According to the cumulative stress hypothesis, individuals are more likely to suffer from disease as adversity accumulates. According to the mismatch hypothesis, individuals are more likely to suffer from disease if a mismatch occurs between the early programming environment and the later adult environment. These seemingly contradicting hypotheses are integrated into a new model proposing that the cumulative stress hypothesis applies to individuals who were not or only to a small extent programmed by their early environment, while the mismatch hypothesis applies to individuals who experienced strong programming effects. Evidence for the main effects of adversity as well as evidence for the interaction between adversity in early and later life is presented from human observational studies and animal models. Next, convincing evidence for individual differences in sensitivity to programming is presented. We extensively discuss how our integrated model can be tested empirically in animal models and human studies, inviting researchers to test this model. Furthermore, this integrated model should tempt clinicians and other intervenors to interpret symptoms as possible adaptations from an evolutionary biology perspective. Copyright © 2011 Elsevier Inc. All rights reserved.

Fructose, pregnancy and later life impacts.

PubMed

Regnault, Timothy R H; Gentili, Sheridan; Sarr, Ousseynou; Toop, Carla R; Sloboda, Deborah M

2013-11-01

Fructose is an increasingly common constituent of the Westernized diet due to cost and production efficiencies. Although an integral component of our pre-industrial revolution diet, over the past two decades human and animal studies have highlighted that excessive fructose intake appears to be associated with adverse metabolic effects. Excessive intake of fructose is the combined result of increased total energy consumption and increased portion sizes of foods, which often incorporate the fructose-containing sugars sucrose and high-fructose corn-syrup (HFCS). The adverse metabolic effects following excessive fructose consumption have become a hot topic in mainstream media and there is now rigorous scientific debate regarding periods of exposure, dosage levels, interactive effects with other sugars and fats and mechanisms underlying the actions of fructose. There is still a degree of controversy regarding the extent to which sugars such as sucrose and HFCS have contributed to the current epidemic of obesity and diabetes. Furthermore, an increasing number of infants are being exposed to sugar-sweetened food and beverages before birth and during early postnatal life, highlighting the importance of determining the long-term effects of this perinatal exposure on the developing offspring. There are limited human observational and controlled studies identifying associations of excessive sweetened food and beverage consumption with poor pregnancy outcomes. Animal research has demonstrated an increased incidence of gestational diabetes as well as altered maternal, fetal and offspring metabolic function, although the long-term effects and the mechanism underlying these perturbations are ill defined. This review aims to understand the role of early life fructose exposure in modifying postnatal risk of disease in the offspring, focusing on fructose intake during pregnancy and in early postnatal life. © 2013 Wiley Publishing Asia Pty Ltd.

Enriched dairy fat matrix diet prevents early life lipopolysaccharide-induced spatial memory impairment at adulthood.

PubMed

Dinel, A L; Rey, C; Baudry, C; Fressange-Mazda, C; Le Ruyet, P; Nadjar, A; Pallet, P; Joffre, C; Layé, S

2016-10-01

Polyunsaturated fatty acids (PUFAs) are essential fatty acids, which are critical for brain development and later life cognitive functions. The main brain PUFAs are docosahexaenoic acid (DHA) for the n-3 family and arachidonic acid (ARA) for the n-6 family, which are provided to the post-natal brain by breast milk or infant formula. Recently, the use of dairy lipids (DL) in replacement of vegetable lipids (VL) was revealed to potently promote the accretion of DHA in the developing brain. Brain DHA, in addition to be a key component of brain development, display potent anti-inflammatory activities, which protect the brain from adverse inflammatory events. In this work, we evaluated the protective effect of partial replacement of VL by DL, supplemented or not with DHA and ARA, on post-natal inflammation and its consequence on memory. Mice were fed with diets poor in vegetal n-3 PUFA (Def VL), balanced in vegetal n-3/n-6 PUFA (Bal VL), balanced in dairy lipids (Bal DL) or enriched in DHA and ARA (Supp VL; Supp DL) from the first day of gestation until adulthood. At post-natal day 14 (PND14), pups received a single administration of the endotoxin lipopolysaccharide (LPS) and brain cytokine expression, microglia phenotype and neurogenesis were measured. In a second set of experiments, memory and neurogenesis were measured at adulthood. Overall, our data showed that lipid quality of the diet modulates early life LPS effect on microglia phenotype, brain cytokine expression and neurogenesis at PND14 and memory at adulthood. In particular, Bal DL diet protects from the adverse effect of early life LPS exposure on PND14 neurogenesis and adult spatial memory. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sub-lethal and lethal toxicities of elevated CO2 on embryonic, juvenile, and adult stages of marine medaka Oryzias melastigma.

PubMed

Lee, Changkeun; Kwon, Bong-Oh; Hong, Seongjin; Noh, Junsung; Lee, Junghyun; Ryu, Jongseong; Kang, Seong-Gil; Khim, Jong Seong

2018-06-06

The potential leakage from marine CO 2 storage sites is of increasing concern, but few studies have evaluated the probable adverse effects on marine organisms. Fish, one of the top predators in marine environments, should be an essential representative species used for water column toxicity testing in response to waterborne CO 2 exposure. In the present study, we conducted fish life cycle toxicity tests to fully elucidate CO 2 toxicity mechanism effects. We tested sub-lethal and lethal toxicities of elevated CO 2 concentrations on marine medaka (Oryzias melastigma) at different developmental stages. At each developmental stage, the test species was exposed to varying concentrations of gaseous CO 2 (control air, 5%, 10%, 20%, and 30%), with 96 h of exposure at 0-4 d (early stage), 4-8 d (middle stage), and 8-12 d (late stage). Sub-lethal and lethal effects, including early developmental delays, cardiac edema, tail abnormalities, abnormal pigmentation, and mortality were monitored daily during the 14 d exposure period. At the embryonic stage, significant sub-lethal and lethal effects were observed at pH < 6.30. Hypercapnia can cause long-term and/or delayed developmental embryonic problems, even after transfer back to clean seawater. At fish juvenile and adult stages, significant mortality was observed at pH < 5.70, indicating elevated CO 2 exposure might cause various adverse effects, even during short-term exposure periods. It should be noted the early embryonic stage was found more sensitive to CO 2 exposure than other developmental stages of the fish life cycle. Overall, the present study provided baseline information for potential adverse effects of high CO 2 concentration exposure on fish developmental processes at different life cycle stages in marine ecosystems. Copyright © 2018 Elsevier Ltd. All rights reserved.

Reframing the risks and losses of teen mothering.

PubMed

SmithBattle, Lee

2009-01-01

Teen mothers often face a stigmatizing gaze based on the belief that early childbearing jeopardizes their life chances and the health and development of their children. Growing evidence suggests that the poor maternal-child outcomes associated with early childbearing have been overstated and may be explained by teen mothers' childhood disadvantage and adversities. After reviewing what is currently known about the relationships between early childbearing and maternal-child outcomes, as well as teen mothers' perspectives on mothering, clinical practices are suggested that address teen mothers' concerns, strengths, aspirations, and the long-term inequities that contribute to poor outcomes.

Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence: A Putative Mechanistic Neurodevelopmental Pathway.

PubMed

Luby, Joan L; Barch, Deanna; Whalen, Diana; Tillman, Rebecca; Belden, Andy

2017-12-01

Adverse childhood experiences (ACEs) have been associated with poor mental and physical health outcomes. However, the mechanism of this effect, critical to enhancing public health, remains poorly understood. To investigate the neurodevelopmental trajectory of the association between early ACEs and adolescent general and emotional health outcomes. A prospective longitudinal study that began when patients were aged 3 to 6 years who underwent neuroimaging later at ages 7 to 12 years and whose mental and physical health outcomes were observed at ages 9 to 15 years. Sequential mediation models were used to investigate associations between early ACEs and brain structure, emotion development, and health outcomes longitudinally. Children were recruited from an academic medical center research unit. Early life adversity. Early ACEs in children aged 3 to 7 years; volume of a subregion of the prefrontal cortex, the inferior frontal gyrus, in children aged 6 to 12 years; and emotional awareness, depression severity, and general health outcomes in children and adolescents aged 9 to 15 years. The mean (SD) age of 119 patients was 9.65 (1.31) years at the time of scan. The mean (SD) ACE score was 5.44 (3.46). The mean (SD) depression severity scores were 2.61 (1.78) at preschool, 1.77 (1.58) at time 2, and 2.16 (1.64) at time 3. The mean (SD) global physical health scores at time 2 and time 3 were 0.30 (0.38) and 0.33 (0.42), respectively. Sequential mediation in the association between high early ACEs and emotional and physical health outcomes were found. Smaller inferior frontal gyrus volumes and poor emotional awareness sequentially mediated the association between early ACEs and poor general health (model parameter estimate = 0.002; 95% CI, 0.0002-0.056) and higher depression severity (model parameter estimate = 0.007; 95% CI, 0.001-0.021) in adolescence. An increase from 0 to 3 early ACEs was associated with 15% and 25% increases in depression severity and physical health problems, respectively. Study findings highlight 1 putative neurodevelopmental mechanism by which the association between early ACEs and later poor mental and physical health outcomes may operate. This identified risk trajectory may be useful to target preventive interventions.

Histone deacetylase 5 modulates the effects of social adversity in early life on cocaine-induced behavior.

PubMed

Valzania, Alessandro; Catale, Clarissa; Viscomi, Maria Teresa; Puglisi-Allegra, Stefano; Carola, Valeria

2017-03-15

Psychostimulants induce stable changes in neural plasticity and behavior in a transcription-dependent manner. Further, stable cellular changes require transcription that is regulated by epigenetic mechanisms that alter chromatin structure, such as histone acetylation. This mechanism is typically catalyzed by enzymes with histone acetyltransferase or histone deacetylase (HDAC) activity. Class IIa HDACs are notable for their high expression in important regions of the brain reward circuitry and their neural activity-dependent shuttling in and out of the cell nucleus. In particular, HDAC5 has an important modulatory function in cocaine-induced behaviors and social defeat stress-induced effects. Although a mutation in HDAC5 has been shown to cause hypersensitive responses to chronic cocaine use whether this response worsens during chronic early life stress has not been examined yet. In this study, we exposed mouse pups to two different early life stress paradigms (social isolation, ESI, and social threat, EST) to determine whether the heterozygous null mutation in HDAC5 (HDAC5+/-) moderated the effects of exposure to stress in early life on adult cocaine-induced conditioned place preference (CPP). Notably, HDAC5+/- mice that had been exposed to ESI were more susceptible to developing cocaine-induced CPP and more resistant to extinguishing this behavior. The same effect was not observed for HDAC5+/- mice experiencing EST, suggesting that only ESI induces behavioral changes by acting precisely through HDAC5-related biological pathways. Finally, an analysis of c-Fos expression performed to discover the neurobiological substrates that mediated this phenotype, identified the dorsolateral striatum as an important structure that mediates the interaction between HDAC5 mutation and ESI. Our data demonstrate that decreased HDAC5 function is able to exacerbate the long-term behavioral effects of adverse rearing environment in mouse. Copyright © 2016 Elsevier Inc. All rights reserved.

The Role of Maternal Adverse Childhood Experiences and Race in Intergenerational High-Risk Smoking Behaviors

PubMed Central

Pear, Veronica A.; Petito, Lucia C.

2017-01-01

Abstract Introduction: A history of adversity in childhood is associated with cigarette smoking in adulthood, but there is less evidence for prenatal and next-generation offspring smoking. We investigated the association between maternal history of childhood adversity, pregnancy smoking, and early initiation of smoking in offspring, overall and by maternal race/ethnicity. Methods: Data on maternal childhood exposure to physical abuse, household alcohol abuse, and household mental illness, prenatal smoking behaviors, and offspring age of smoking initiation were analyzed from the US National Longitudinal Survey of Youth 1979 (NLSY79, n = 2999 mothers) and the NLSY79 Children and Young Adults Survey (NLSYCYA, n = 6596 children). Adjusted risk ratios were estimated using log-linear regression models. We assessed multiplicative interaction by race/ethnicity for all associations and a three-way interaction by maternal exposure to adversity and race/ethnicity for the association between prenatal and child smoking. Results: Maternal exposure to childhood physical abuse was significantly associated with 39% and 20% increased risks of prenatal smoking and child smoking, respectively. Household alcohol abuse was associated with significantly increased risks of 20% for prenatal smoking and 17% for child smoking. The prenatal smoking–child smoking relationship was modified by maternal exposure to household alcohol abuse and race. There were increased risks for Hispanic and white/other mothers as compared to the lowest risk group: black mothers who did not experience childhood household alcohol abuse. Conclusions: Mothers in this national sample who experienced adversity in childhood are more likely to smoke during pregnancy and their offspring are more likely to initiate smoking before age 18. Findings varied by type of adversity and race/ethnicity. Implications: These findings support the importance of a life-course approach to understanding prenatal and intergenerational smoking, and suggest that maternal early-life history is a potentially important risk factor that could be targeted with screening and interventions to reduce smoking in pregnant women and their children. PMID:28403466

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine

PubMed Central

De Berardis, Domenico; Rapini, Gabriella; Olivieri, Luigi; Di Nicola, Domenico; Tomasetti, Carmine; Valchera, Alessandro; Fornaro, Michele; Di Fabio, Fabio; Perna, Giampaolo; Di Nicola, Marco; Serafini, Gianluca; Carano, Alessandro; Pompili, Maurizio; Vellante, Federica; Orsolini, Laura; Martinotti, Giovanni; Di Giannantonio, Massimo

2018-01-01

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon. PMID:29796248

Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders.

PubMed

Espejo, Emmanuel P; Hammen, Constance L; Connolly, Nicole P; Brennan, Patricia A; Najman, Jake M; Bor, William

2007-04-01

The goal of the present study was to determine whether exposure to adversity in childhood contributes to a differential threshold at which stressful life events provoke depressive reactions in adolescence. In addition, to address empirical and conceptual questions about stress effects, the moderating effect of anxiety disorder history was also explored. This examination was conducted in a sample of 816 children of depressed and nondepressed mothers, who were followed from birth to age 15. Information on adversities experienced in childhood was collected both from mothers during the first five years of their youth's life and from the youths themselves at age 15, and included information on the mother's relationship with her partner, maternal psychopathology, as well as youth-reported abuse. Results indicated that youths with both greater exposure to adversity in childhood and a history of an anxiety disorder displayed increased depressive severity following low levels of episodic stress compared to youths with only one or neither of these risk factors. The results are speculated to reflect the possibility that early anxiety disorders associated with exposure to adversity in childhood may be a marker of dysregulated stress responses, and may help to account for the comorbidity of depression and anxiety in some individuals.

Childhood Adversities and Adult Cardiometabolic Health: Does the Quantity, Timing, and Type of Adversity Matter?

PubMed Central

Friedman, Esther M.; Montez, Jennifer Karas; Sheehan, Connor McDevitt; Guenewald, Tara L.; Seeman, Teresa E.

2015-01-01

Objective Adverse events in childhood can indelibly influence adult health. While evidence for this association has mounted, a fundamental set of questions about how to operationalize adverse events has been understudied. Method We used data from the National Survey of Midlife Development in the United States to examine how quantity, timing, and types of adverse events in childhood are associated with adult cardiometabolic health. Results The best-fitting specification of quantity of events was a linear measure reflecting a dose–response relationship. Timing of event mattered less than repeated exposure to events. Regarding the type of event, academic interruptions and sexual/physical abuse were most important. Adverse childhood events elevated the risk of diabetes and obesity similarly for men and women but had a greater impact on women’s risk of heart disease. Discussion Findings demonstrate the insights that can be gleaned about the early-life origins of adult health by examining operationalization of childhood exposures. PMID:25903978

The Stress Acceleration Hypothesis of Nightmares

PubMed Central

Nielsen, Tore

2017-01-01

Adverse childhood experiences can deleteriously affect future physical and mental health, increasing risk for many illnesses, including psychiatric problems, sleep disorders, and, according to the present hypothesis, idiopathic nightmares. Much like post-traumatic nightmares, which are triggered by trauma and lead to recurrent emotional dreaming about the trauma, idiopathic nightmares are hypothesized to originate in early adverse experiences that lead in later life to the expression of early memories and emotions in dream content. Accordingly, the objectives of this paper are to (1) review existing literature on sleep, dreaming and nightmares in relation to early adverse experiences, drawing upon both empirical studies of dreaming and nightmares and books and chapters by recognized nightmare experts and (2) propose a new approach to explaining nightmares that is based upon the Stress Acceleration Hypothesis of mental illness. The latter stipulates that susceptibility to mental illness is increased by adversity occurring during a developmentally sensitive window for emotional maturation—the infantile amnesia period—that ends around age 3½. Early adversity accelerates the neural and behavioral maturation of emotional systems governing the expression, learning, and extinction of fear memories and may afford short-term adaptive value. But it also engenders long-term dysfunctional consequences including an increased risk for nightmares. Two mechanisms are proposed: (1) disruption of infantile amnesia allows normally forgotten early childhood memories to influence later emotions, cognitions and behavior, including the common expression of threats in nightmares; (2) alterations of normal emotion regulation processes of both waking and sleep lead to increased fear sensitivity and less effective fear extinction. These changes influence an affect network previously hypothesized to regulate fear extinction during REM sleep, disruption of which leads to nightmares. This network consists of a fear circuit that includes amygdala, hippocampus, and medial prefrontal cortex and whose substantial overlap with the stress acceleration findings allows the latter to be incorporated into a wider, more developmentally coherent framework. PMID:28620339

Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity.

PubMed

McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

2016-06-01

The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5-18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA. Copyright © 2016 Elsevier Inc. All rights reserved.

Dysregulation of the cortisol diurnal rhythm following prenatal alcohol exposure and early life adversity

PubMed Central

McLachlan, Kaitlyn; Rasmussen, Carmen; Oberlander, Tim F.; Loock, Christine; Pei, Jacqueline; Andrew, Gail; Reynolds, James; Weinberg, Joanne

2016-01-01

The hypothalamic-pituitary-adrenal (HPA) axis is impacted by a multitude of pre- and postnatal factors. Developmental programming of HPA axis function by prenatal alcohol exposure (PAE) has been demonstrated in animal models and in human infants, but remains understudied in older children and adolescents. Moreover, early life adversity (ELA), which occurs at higher rates in children with PAE than in non-exposed children, may also play a role in programming the HPA or stress response system. In a cohort of children and adolescents with PAE and ELA (PAE + ELA), we evaluated HPA function through assessment of diurnal cortisol activity compared to that in typically developing controls, as well as the associations among specific ELAs, adverse outcomes, protective factors, and diurnal cortisol. Morning and evening saliva samples were taken under basal conditions from 42 children and adolescents (5–18 years) with PAE + ELA and 43 typically developing controls. High rates of ELA were shown among children with PAE, and significantly higher evening cortisol levels and a flatter diurnal slope were observed in children with PAE + ELA, compared to controls. Medication use in the PAE + ELA group was associated with lower morning cortisol levels, which were comparable to controls. Complex associations were found among diurnal cortisol patterns in the PAE + ELA group and a number of ELAs and later adverse outcomes, whereas protective factors were associated with more typical diurnal rhythms. These results complement findings from research on human infants and animal models showing dysregulated HPA function following PAE, lending weight to the suggestion that PAE and ELA may interact to sensitize the developing HPA axis. The presence of protective factors may buffer altered cortisol regulation, underscoring the importance of early assessment and interventions for children with FASD, and in particular, for the many children with FASD who also have ELA. PMID:27286932

Resource factors for mental health resilience in early childhood: An analysis with multiple methodologies

PubMed Central

2013-01-01

Background Given that relatively little is known about the development of resilience in early childhood, this longitudinal study aimed to identify preschool resource factors associated with young children’s mental health resilience to family adversity. Methods A community sample of 474 young Australian children was assessed in preschool (mean age 4.59 years, 49% male), and again two years later after their transition into formal schooling. At each assessment, standard questionnaires were used to obtain ratings from both parents and teachers about the quality of children’s relationships with parents and teachers, children’s self-concept and self-control, mental health (Strengths and Difficulties Questionnaire), and family adversities (including stressful life events and socioeconomic disadvantage). Results Greater exposure to cumulative family adversities was associated with both greater teacher- and parent-reported child mental health difficulties two years later. Multiple methodologies for operationalizing resilience were used to identify resources associated with resilient mental health outcomes. Higher quality child–parent and child-teacher relationships, and greater child self-concept and self-control were associated with resilient mental health outcomes. With the exception of child-teacher relationships, these resources were also prospective antecedents of subsequent resilient mental health outcomes in children with no pre-existing mental health difficulties. Child–parent relationships and child self-concept generally had promotive effects, being equally beneficial for children facing both low- and high-adversity. Child self-control demonstrated a small protective effect on teacher-reported outcomes, with greater self-control conferring greater protection to children under conditions of high-adversity. Conclusions Findings suggest that early intervention and prevention strategies that focus on fostering child-adult relationship quality, self-concept, and self-control in young children may help build children’s mental health and their resilience to family adversities. PMID:23432929

Resource factors for mental health resilience in early childhood: An analysis with multiple methodologies.

PubMed

Miller-Lewis, Lauren R; Searle, Amelia K; Sawyer, Michael G; Baghurst, Peter A; Hedley, Darren

2013-02-22

Given that relatively little is known about the development of resilience in early childhood, this longitudinal study aimed to identify preschool resource factors associated with young children's mental health resilience to family adversity. A community sample of 474 young Australian children was assessed in preschool (mean age 4.59 years, 49% male), and again two years later after their transition into formal schooling. At each assessment, standard questionnaires were used to obtain ratings from both parents and teachers about the quality of children's relationships with parents and teachers, children's self-concept and self-control, mental health (Strengths and Difficulties Questionnaire), and family adversities (including stressful life events and socioeconomic disadvantage). Greater exposure to cumulative family adversities was associated with both greater teacher- and parent-reported child mental health difficulties two years later. Multiple methodologies for operationalizing resilience were used to identify resources associated with resilient mental health outcomes. Higher quality child-parent and child-teacher relationships, and greater child self-concept and self-control were associated with resilient mental health outcomes. With the exception of child-teacher relationships, these resources were also prospective antecedents of subsequent resilient mental health outcomes in children with no pre-existing mental health difficulties. Child-parent relationships and child self-concept generally had promotive effects, being equally beneficial for children facing both low- and high-adversity. Child self-control demonstrated a small protective effect on teacher-reported outcomes, with greater self-control conferring greater protection to children under conditions of high-adversity. Findings suggest that early intervention and prevention strategies that focus on fostering child-adult relationship quality, self-concept, and self-control in young children may help build children's mental health and their resilience to family adversities.

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2011 CFR

2011-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2013 CFR

2013-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

21 CFR 312.32 - IND safety reporting.

Code of Federal Regulations, 2012 CFR

2012-04-01

... considered drug related. Life-threatening adverse event or life-threatening suspected adverse reaction. An adverse event or suspected adverse reaction is considered “life-threatening” if, in the view of either the... results in any of the following outcomes: Death, a life-threatening adverse event, inpatient...

Acrolein-induced arrhythmias and autonomic imbalance due to early life persistent vitamin D deficiency in mice is mediated by the putative anti-aging factor klotho.

EPA Science Inventory

Although epidemiological, human and animal data have conclusively linked air pollution exposure to adverse cardiovascular outcomes, the severity of responses depends on a number of intrinsic (diet, underlying disease, etc) and extrinsic (e.g. co-stressors) factors. As such, cardi...

The effect of a low iron diet and early life methylmercury exposure in Daphnia pulex

PubMed Central

Hudson, Sherri L.; Doke, Dzigbodi A.; Gohlke, Julia M.

2016-01-01

Iron (Fe) deficiency increases risk for adverse health outcomes in humans; however little is known about the potential interaction with methylmercury (MeHg) exposure. Studies testing multiple stressor hypotheses are expensive and time consuming in mammalian model systems; therefore, determining relevance of alternative models is important. Daphnia pulex were fed standard or low-Fe diets of freshwater algae, Ankistrodesmus falcatus. MeHgCl (1600 ng/L) or vehicle was added to culture media for 24 h during early life, and the combinatorial effects of a low-Fe diet and MeHg exposure on lifespan, maturation time, and reproduction were evaluated. Lipid storage effects were measured using image analysis of Oil Red O staining and triacylglyceride quantification. Our results show a dose-dependent reduction in lifespan in D. pulex fed low Fe diets. Lipid analysis suggests an interactive effect of diet and MeHg exposure, with MeHg exposure increasing lipid storage in D. pulex fed a low-Fe diet. These findings suggest the effects of dietary iron intake and early life MeHg exposure in D. pulex may be mediated by changes in energetics that result in differential lipid storage. Therefore, lipid storage in D. pulex may be a useful screen for detecting long-term effects of multiple stressors early in life. PMID:26806633

Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level.

PubMed

Humphreys, Kathryn L; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A; Drury, Stacy S

2016-12-30

Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2-4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child's life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Accelerated telomere shortening: Tracking the lasting impact of early institutional care at the cellular level

PubMed Central

Humphreys, Kathryn L.; Esteves, Kyle; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A.; Drury, Stacy S.

2016-01-01

Studies examining the association between early adversity and longitudinal changes in telomere length within the same individual are rare, yet are likely to provide novel insight into the subsequent lasting effects of negative early experiences. We sought to examine the association between institutional care history and telomere shortening longitudinally across middle childhood and into adolescence. Buccal DNA was collected 2 to 4 times, between the ages of 6 and 15 years, in 79 children enrolled in the Bucharest Early Intervention Project (BEIP), a longitudinal study exploring the impact of early institutional rearing on child health and development. Children with a history of early institutional care (n=50) demonstrated significantly greater telomere shortening across middle childhood and adolescence compared to never institutionalized children (n=29). Among children with a history of institutional care, randomization to high quality foster care was not associated with differential telomere attrition across development. Cross-sectional analysis of children randomized to the care as usual group indicated shorter telomere length was associated with greater percent of the child’s life spent in institutional care up to age 8. These results suggest that early adverse care from severe psychosocial deprivation may be embedded at the molecular genetic level through accelerated telomere shortening. PMID:27677058

Height, education and later-life cognition in Latin America and the Caribbean.

PubMed

Maurer, Jürgen

2010-07-01

Building on previous evidence from the U.S., this study investigates the relationship between anthropometric markers (height and knee height), early-life conditions, education, and cognitive function in later life among urban elderly from Latin America and the Caribbean. I document a positive association between height and later-life cognitive function, which is larger for women than for men. This sex difference increases when I address potential feedback effects from mid- and later-life circumstances on stature by using knee height as an instrument for height. Specifically, while the estimates for women remain largely unchanged, I only find a diminished and statistically insignificant association between instrumented height and later-life cognition for men. This finding suggests that at least part of the association between height and later-life cognition among men may stem from common third factors that are correlated with both height and later-life cognition, such as adverse occupational exposures or health events during mid- and later life. Extended models that also include education further diminish the association between height and later-life cognition. Education displays strong positive gradients with the employed measures of childhood circumstances - including height - which points to education as a potential pathway linking early-life conditions and later-life cognitive function. 2010 Elsevier B.V. All rights reserved.

Mode of treatment affects quality of life in head and neck cancer survivors: Implications for holistic care.

PubMed

Bower, Wendy Fiona; Vlantis, Alexander Christopher; Chung, Tiffany M L; Van Hasselt, C Andrew

2010-10-01

As adverse effects of live-saving treatment are unavoidable surgeons have a duty to address physical changes and quality of life issues that matter to head and neck (H&N) cancer patients. We propose a tailored holistic care package. This study compared the quality of life of H&N cancer survivors managed with different approaches in the follow-up phase after initial treatment and identified factors adversely impacting quality of life parameters. H&N cancer patients studied: 1) surgery only, 2) radiotherapy only, 3) surgery and radiotherapy, and 4) any combination of surgery, chemotherapy or radiotherapy. Patients unable to communicate in Cantonese, with thyroid cancer or end-of-life disease were excluded. EORTC QLQ-H&N35 Cantonese version was administered at least 1 year after initial H&N cancer treatment. Quality of life impairment was worse in all of the domains for combination therapy versus monotherapy patients. Scores between surgery or radiotherapy-only patients were not significantly different. Radiotherapy preceding surgery impacted significantly more on speech than surgery before the radiotherapy. Patients with advanced disease had more impairment of quality of life in each domain than patients with early disease. Coughing, eating problems, sticky saliva, and difficulties with social contact were all significant predictors of problems associated with a dry mouth.

Interplay between childhood maltreatment, parental bonding, and gender effects: impact on quality of life.

PubMed

Rikhye, Kobita; Tyrka, Audrey R; Kelly, Megan M; Gagne, Gerard G; Mello, Andrea F; Mello, Marcelo F; Price, Lawrence H; Carpenter, Linda L

2008-01-01

The aim of this study was to examine associations between childhood adversity, parental bonding, gender, depressive symptoms, and quality of life in non-treatment-seeking adults from the community. Effects of differential parental rearing were compared in adults who reported a high degree of childhood maltreatment (n=72) and those who reported no significant adverse events in childhood (n=69). Subjects completed retrospective measures of childhood maltreatment and perceived parenting style, as well as measures of current depressive symptoms and quality of life. The subjects without childhood maltreatment were younger and endorsed less current depressive symptomatology than did subjects with childhood maltreatment. While the subjects without a history of maltreatment reported more "optimal" bonding experiences with their parents, the maltreatment group members were more likely to characterize their early parental bonding experiences in terms of "affectionless control" (p<.001 for both maternal and paternal parenting), "affectionate constraint" (p=.025 for maternal parenting and p=.004 for paternal parenting), or "weak or absent" bonding (p<.001 for both maternal and paternal parenting). Results of a multiple regression analysis revealed that overall quality of paternal care (p=.015) and current level of depressive symptoms (p<.001) were significant independent predictors of adult quality of life. Gender effects between subjects providing parental bonding data were limited to the group with childhood maltreatment. These findings extend previous work documenting a relationship between early life maltreatment and suboptimal parental bonding, suggesting gender-specific effects of maternal and paternal care. Effects of childhood maltreatment on quality of life in adulthood appear to be linked with the quality of childhood paternal care and the occurrence of depressive symptomatology in adulthood, suggesting possible targets for primary or secondary prevention.

Associations between parenting behavior and anxiety in a rodent model and a clinical sample: relationship to peripheral BDNF levels

PubMed Central

Dalle Molle, R; Portella, A K; Goldani, M Z; Kapczinski, F P; Leistner-Segala, S; Salum, G A; Manfro, G G; Silveira, P P

2012-01-01

Adverse early-life environment is associated with anxiety-like behaviors and disorders. Brain-derived neurotrophic factor (BDNF) is sensitive to this environment and could be a marker of underlying brain changes. We aimed at evaluating the development of anxiety-like behaviors in a rat model of early adversity, as well as the possible association with BDNF levels. Similar associations were investigated in a sample of adolescent humans. For the rat study, Wistar rat litters were divided into: early-life stress (ELS, limited access to nesting material) and control groups. Maternal behavior was observed from days 1 to 9 of life and, as adults, rats were subjected to behavioral testing and BDNF measurements in plasma, hippocampus, amygdala and periaqueductal gray. For the human study, 129 adolescents were evaluated for anxiety symptoms and perceived parental care. Serum BDNF levels and the Val66Met polymorphism of the BDNF gene were investigated. We found that ELS dams showed more pure contact, that is, contact with low care and high control, toward pups, and their adult offspring demonstrated higher anxiety-like behaviors and plasma BDNF. Also the pure contact correlated positively with adult peripheral BDNF. Similarly in humans, there was a positive correlation between maternal overprotection and serum BDNF only in Met carriers. We also found negative correlations between maternal warmth and separation anxiety, social phobia and school phobia. Finally, our translational approach revealed that ELS, mediated through variations in maternal care, is associated with anxiety in both rats and humans and increased peripheral BDNF may be marking these phenomena. PMID:23168995

The Economics and Psychology of Inequality and Human Development*

PubMed Central

Cunha, Flavio; Heckman, James J.

2009-01-01

Recent research on the economics of human development deepens understanding of the origins of inequality and excellence. It draws on and contributes to personality psychology and the psychology of human development. Inequalities in family environments and investments in children are substantial. They causally affect the development of capabilities. Both cognitive and noncognitive capabilities determine success in life but to varying degrees for different outcomes. An empirically determined technology of capability formation reveals that capabilities are self-productive and cross-fertilizing and can be enhanced by investment. Investments in capabilities are relatively more productive at some stages of a child’s life cycle than others. Optimal child investment strategies differ depending on target outcomes of interest and on the nature of adversity in a child’s early years. For some configurations of early disadvantage and for some desired outcomes, it is efficient to invest relatively more in the later years of childhood than in the early years. PMID:20209045

A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

PubMed

Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

Lethal effect of dehydroleucodine (DhL) on amphibian Bufo arenarum embryos.

PubMed

Moreno, Liliana Elizabeth; Juárez, Américo Osvaldo; Pelzer, Lilian Eugenia

2012-03-01

The dehydroleucodine is a sesquiterpene lactone isolated from Artemisia douglasiana Besser which is used in popular medicine. Toxicity tests using embryos of amphibian have been widely used in order to predict toxic effects of different compounds. However, to our knowledge, there are not studies focussed on the toxic effects of dehydroleucodine on Bufo arenarum, which is an anuran widely distributed in South America. The effect of dehydroleucodine on the survival of embryos was evaluated in an acute test during the early life stage of B. arenarum embryos. Lethality and the degree of adverse effects were dehydroleucodine dose-dependent. Overall, amphibian early life stages appeared to be more susceptible to the embryotoxicity associated with exposure to dehydroleucodine, especially at concentration greater that 3mM. This increased susceptibility may result from the relatively high rate of cellular differentiation and morphogenesis that occurs at this early stage of development. Copyright © 2012 Elsevier Ltd. All rights reserved.

Early-Life Antibiotic Exposure, Gut Microbiota Development, and Predisposition to Obesity.

PubMed

Azad, Meghan B; Moossavi, Shirin; Owora, Arthur; Sepehri, Shadi

2017-01-01

Antibiotics are often prescribed inappropriately to infants and young children, with potentially adverse effects on the developing gut microbiota and related metabolic processes. We review evidence from 17 epidemiologic studies suggesting that antibiotic exposure during critical periods of early development may influence weight gain and the development of obesity. Complementary research in both humans and rodents indicates that gut microbiota play a key role in this process, although further research is needed to confirm and characterize the causal mechanisms involved. Obesity is a complex and multifactorial condition; thus, a multipronged prevention strategy will be required to curb the current obesity epidemic. Evidence to date suggests this strategy should include the judicious use of antibiotics, especially in early life when the developing gut microbiota is particularly susceptible to perturbations with long-lasting implications for metabolic programming and obesity risk. © 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

Early-Life Adversity Interacts with FKBP5 Genotypes: Altered Working Memory and Cardiac Stress Reactivity in the Oklahoma Family Health Patterns Project.

PubMed

Lovallo, William R; Enoch, Mary-Anne; Acheson, Ashley; Cohoon, Andrew J; Sorocco, Kristen H; Hodgkinson, Colin A; Vincent, Andrea S; Goldman, David

2016-06-01

Exposure to stress during critical periods of development can have adverse effects on adult health behaviors, and genetic vulnerabilities may enhance these stress effects. We carried out an exploratory examination of psychological, physiological, and behavioral characteristics of 252 healthy young adults for the impact of early-life adversity (ELA) in relation to the G-to-A single nucleotide polymorphism (SNP), rs9296158, of the FKBP5 gene. FKBP5 is a molecular cochaperone that contributes to the functional status of the glucocorticoid receptor (GR) and to the quality of corticosteroid signaling. FKBP5 expression is upregulated by cortisol exposure during stressful episodes, with greater upregulation seen in A-allele carriers. As such, FKBP5 expression and GR function may be environmentally sensitive in A-allele carriers and therefore suitable for the study of gene-by-environment (G × E) interactions. Compared with FKBP5, GG homozygotes (N=118), A-allele carriers (N = 132) without psychiatric morbidity had progressively worse performance on the Stroop color-word task with increasing levels of ELA exposure (Genotype × ELA, F=5.14, P=0.007), indicating a G × E interaction on working memory in early adulthood. In addition, heart rate response to mental stress was diminished overall in AA/AG-allele carriers (F=5.15, P=0.024). Diminished working memory and attenuated autonomic responses to stress are both associated with risk for alcoholism and other substance use disorders. The present data suggest that FKBP5 in the GR pathway may be a point of vulnerability to ELA, as seen in this group of non-traumatized young adults. FKBP5 is accordingly a potential target for more extensive studies of the impact of ELA on health and health behaviors in adulthood.

Adverse childhood experience and asthma onset: a systematic review.

PubMed

Exley, Daniel; Norman, Alyson; Hyland, Michael

2015-06-01

Adverse childhood experiences such as abuse and neglect are associated with subsequent immune dysregulation. Some studies show an association between adverse childhood experiences and asthma onset, although significant disparity in results exists in the published literature. We aimed to review available studies employing a prospective design that investigates associations between adverse childhood experience and asthma. A search protocol was developed and studies were drawn from four electronic journal databases. Studies were selected in accordance with pre-set inclusion criteria and relevant data were extracted. 12 studies, assessing data from a total of 31 524 individuals, were identified that investigate the impact of a range of adverse childhood experiences on the likelihood of developing asthma. Evidence suggests that chronic stress exposure and maternal distress in pregnancy operate synergistically with known triggers such as traffic-related air pollution to increase asthma risk. Chronic stress in early life is associated with an increased risk of asthma onset. There is evidence that adverse childhood experience increases the impact of traffic-related air pollution and inconsistent evidence that adverse childhood experience has an independent effect on asthma onset. Copyright ©ERS 2015.

Relationship between breastfeeding and asthma prevalence in young children exposed to adverse childhood experiences.

PubMed

Abarca, Nancy E; Garro, Aris C; Pearlman, Deborah N

2018-03-13

To investigate if duration of supplemental breastfeeding is associated with a lower asthma risk and whether adverse childhood experiences (ACEs) early in life influence this relationship in children ages 3 to 5 years. Data were from the 2011-2012 National Survey of Children's Health, a nationally representative cross-sectional survey. Modified Poisson regression models were used to estimate incident risk ratios (IRR) for lifetime and current asthma in young children aged 3 to 5 years (n = 15,642). We tested for effect measure modification using stratified analyses. Exclusive breastfeeding for at least 6 months or supplemental breastfeeding for children ≥12 months significantly reduced the risk of lifetime asthma prevalence compared to never breastfed children (IRR 0.64; 95% CI: 0.46-0.88, p = 0.007; and IRR 0.68; 95% CI: 0.47-0.99, p = 0.044, respectively), adjusted for covariates. In stratified analyses, breastfeeding reduced the risk of lifetime asthma for children who experienced 1 ACE but not for children who experienced 2 or more ACEs. Exclusive breastfeeding for at least 6 months, with and without supplementation, appears to prevent asthma or delay its onset. The protective effect of breastfeeding was attenuated among children who experienced more than 2 ACEs. The known harmful effects that ACEs have on children's health may outweigh the benefits of breastfeeding in reducing the risk of a child developing asthma. Understanding how specific time periods in a child's life may be most affected by exposure to early life adversities, along with the protective effect of breastfeeding against asthma, are important areas of further study.

Genetically reduced FAAH activity may be a risk for the development of anxiety and depression in persons with repetitive childhood trauma.

PubMed

Lazary, Judit; Eszlari, Nora; Juhasz, Gabriella; Bagdy, Gyorgy

2016-06-01

Fatty acid amide hydrolase (FAAH) inhibitors are addressed for promising anxiolytics, but human studies on genetically reduced FAAH activity, stress and affective phenotypes are scarce. We investigated the effect of a functional polymorphism of FAAH (FAAH C385A or rs324420; low FAAH activity and high anandamide concentration are associated with the A allele) together with childhood adversity on the anxious and depressive phenotypes in 858 subjects from the general population. Phenotypes were measured by the Zung Self-Rating Depression Scale (ZSDS), the depression and anxiety subscales of the Brief Symptom Inventory (BSI-DEP, BSI-ANX) and the State-Trait Anxiety scales (STAI-S, STAI-T). Childhood Adversity Questionnaire (CHA) was used to assess early life traumas. Frequency of the A allele was greater among subjects with high ZSDS scores compared to the CC genotype. Furthermore, FAAH C385A and the CHA have shown a robust gene-environment interaction, namely, significantly higher anxiety and depression scores were exhibited by individuals carrying the A allele if they had high CHA scores compared to CC carriers. These data provided preliminary evidence that genetically reduced FAAH activity and repetitive stress in the childhood are associated with increased vulnerability for anxiety and depression in later life. Our results together with earlier experimental data suggest that permanently elevated anandamide level together with early life stress may cause a lifelong damage on stress response probably via the downregulation of CB1R during the neurodevelopment in the brain. It may also point to pharmacogenomic consequences, namely ineffectiveness or adverse effects of FAAH inhibitors in this subpopulation. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Strategies for Reversing the Effects of Metabolic Disorders Induced as a Consequence of Developmental Programming

PubMed Central

Vickers, M. H.; Sloboda, D. M.

2012-01-01

Obesity and the metabolic syndrome have reached epidemic proportions worldwide with far-reaching health care and economic implications. The rapid increase in the prevalence of these disorders suggests that environmental and behavioral influences, rather than genetic causes, are fueling the epidemic. The developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal, and early infant phases of life and the subsequent development of metabolic disorders in later life. In particular, the impact of poor maternal nutrition on susceptibility to later life metabolic disease in offspring is now well documented. Several studies have now shown, at least in experimental animal models, that some components of the metabolic syndrome, induced as a consequence of developmental programming, are potentially reversible by nutritional or targeted therapeutic interventions during windows of developmental plasticity. This review will focus on critical windows of development and possible therapeutic avenues that may reduce metabolic and obesogenic risk following an adverse early life environment. PMID:22783205

Antibiotic Use in Early Life, Rural Residence, and Allergic Diseases in Argentinean Children.

PubMed

Han, Yueh-Ying; Forno, Erick; Badellino, Héctor A; Celedón, Juan C

Little is known about differential effects of antibiotic use on allergic diseases in rural versus urban environments. To examine whether area of residence in the first year of life modifies the relation between antibiotic use in early life and allergic diseases during childhood. Cross-sectional study of allergic diseases in 1517 children (ages 6-7 years) attending 101 schools in urban and rural areas of San Francisco (Córdoba, Argentina). Current asthma, wheeze, and allergic rhinoconjunctivitis were defined on the basis of responses to a validated questionnaire from the International Study of Asthma and Allergies in Childhood. Multivariate logistic regression was used for the analysis of antibiotic use and allergic diseases. After adjustment for paracetamol use, bronchiolitis, and other covariates, antibiotic use in the first year of life was associated with increased odds of current wheeze (odds ratio [OR], 1.8; 95% CI, 1.3-2.6) and allergic rhinoconjunctivitis (OR, 1.9; 95% CI, 1.3-2.7). After stratification by area of residence, antibiotic use was associated with current wheeze (OR, 2.4; 95% CI, 1.5-4.0) and allergic rhinoconjunctivitis (OR, 2.1; 95% CI, 1.3-3.4) among children who lived in an urban area in their first year of life, but not among those who lived in a rural area in their first year of life. Early-life antibiotic use is associated with current wheeze and allergic rhinoconjunctivitis in Argentinean children who lived in urban areas during their first year of life. Exposure to a rural environment early in life may protect against the adverse effects of antibiotics on atopic diseases in children. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Adler's psychology (of use) today: personal history of traumatic life events as a self-handicapping strategy.

PubMed

DeGree, C E; Snyder, C R

1985-06-01

We investigated the hypothesis that the reporting of a history of traumatic life events may serve as a strategy to control attributions about performance in an evaluative setting (i.e., self-handicapping). Following from Alfred Adler's early theorization in the psychology of use, as well as more recent theory and research on self-handicapping, we predicted that individuals would emphasize the adversity of events and experiences in their background when an uncertain evaluation was expected and when a traumatic background would serve as a suitable excuse for potential failure. Results generally supported the hypothesized self-protective reporting of traumatic life events.

Childhood Poverty, Chronic Stress, and Young Adult Working Memory: The Protective Role of Self-Regulatory Capacity

ERIC Educational Resources Information Center

Evans, Gary W.; Fuller-Rowell, Thomas E.

2013-01-01

Prior research shows that childhood poverty as well as chronic stress can damage children's executive functioning (EF) capacities, including working memory. However, it is also clear that not all children suffer the same degree of adverse consequences from risk exposure. We show that chronic stress early in life (ages 9-13) links childhood…

Foster Care Placement, Poor Parenting, and Negative Outcomes among Homeless Young Adults

ERIC Educational Resources Information Center

Tyler, Kimberly A.; Melander, Lisa A.

2010-01-01

Although homeless youth with and without foster care histories both face adverse life circumstances, little is known about how these two groups compare in terms of their early histories and whether they face similar outcomes. As such, we compared those with and without a history of foster care placement to determine if the associations between a…

A Transagency Approach to Enabling Access to Parent-Based Intervention for Language Delay in Areas of Social Disadvantage: A Service Evaluation

ERIC Educational Resources Information Center

Gibbard, Deborah; Smith, Clare

2016-01-01

Primary language delay remains one of the most prevalent developmental delays in early childhood, particularly in disadvantaged areas. Previous research has established language difficulties and social disadvantage being particular risk factors for adverse outcomes later in life. To help prevent low educational achievement and poorer outcomes,…

Long-term effects of early life exposure to environmental estrogens on ovarian function: Role of epigenetics

PubMed Central

Cruz, Gonzalo; Foster, Warren; Paredes, Alfonso; Yi, Kun Don; Uzumcu, Mehmet

2014-01-01

Estrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is thought that developmental exposure to environmental estrogens can disrupt neural and reproductive tract development potentially resulting in long-term alterations in neurobehavior and reproductive function. Many chemicals have been shown to have estrogenic activity whereas others affect estrogen production and turnover resulting in disruption of estrogen signaling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on estrogen sensitive target tissues. Hence, alternative mechanisms are thought to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including estrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying disruption of ovarian follicular development. In addition, we discuss how exposure to environmental estrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. PMID:25040227

Long-term effects of early-life exposure to environmental oestrogens on ovarian function: role of epigenetics.

PubMed

Cruz, G; Foster, W; Paredes, A; Yi, K D; Uzumcu, M

2014-09-01

Oestrogens play an important role in development and function of the brain and reproductive tract. Accordingly, it is considered that developmental exposure to environmental oestrogens can disrupt neural and reproductive tract development, potentially resulting in long-term alterations in neurobehaviour and reproductive function. Many chemicals have been shown to have oestrogenic activity, whereas others affect oestrogen production and turnover, resulting in the disruption of oestrogen signalling pathways. However, these mechanisms and the concentrations required to induce these effects cannot account for the myriad adverse effects of environmental toxicants on oestrogen-sensitive target tissues. Hence, alternative mechanisms are assumed to underlie the adverse effects documented in experimental animal models and thus could be important to human health. In this review, the epigenetic regulation of gene expression is explored as a potential target of environmental toxicants including oestrogenic chemicals. We suggest that toxicant-induced changes in epigenetic signatures are important mechanisms underlying the disruption of ovarian follicular development. In addition, we discuss how exposure to environmental oestrogens during early life can alter gene expression through effects on epigenetic control potentially leading to permanent changes in ovarian physiology. © 2014 British Society for Neuroendocrinology.

[The outcomes of Adoption in the Case of the "British Chinese Adoption Study"].

PubMed

Rushton, Alan

2015-01-01

Practitioners can over-estimate the incidence of problems in adopted children and adults because they do not see those who make good psychological and social adjustments. Research into adoption outcomes can be hard to interpret without information about differing pre-adoption histories. Examples are given of research into three types of adoption: domestic infant adoption, adoptions from public care of maltreated children and international adoption of ex-orphanage children. Although negative outcomes are indisputably evident for some, recovery from adversity is more common than many would predict. It is important to recognize that subsequent nurturing in consistent and stimulating environments can build a platform for effective adaptations to challenges in the future. However, a proper understanding of the consequences of adoption has been limited by the fact that follow-up studies have rarely extended beyond adolescence and early adulthood. The British Chinese Adoption Study is a 50 year follow-up of orphanage girls internationally adopted into the United Kingdom, and is given as an example of good outcomes despite early years of adversity. Scores on mental health assessments were equivalent to the non-adopted, age-matched comparison group of UK women. Most of the women were rated as "good functioning" and educational achievements were many times higher than the comparison women. Life-long adverse effects are not inevitable following early adversity. Improved circumstances can promote recovery and good adult adjustment. Practice and research implications are discussed.

Adverse events arising from a palliative care survey.

PubMed

Braithwaite, M; Philip, J; Finlayson, F; Tranberg, H; Gold, M; Kotsimbos, T; Wilson, J

2009-10-01

Development of evidence-based practice requires investigation of the attitudes and needs of patients, families and healthcare professionals, particularly for sensitive subject areas. Cystic fibrosis (CF) is a recessively inherited life-limiting disorder resulting in early death. Patients with this condition generally expect that lung transplantation will be an available treatment option; however, this is uncertain. A dual approach to care that involves both preparing patients for transplant assessment, while simultaneously exploring acceptable palliative care options is needed. A survey amongst patients with CF, their families and health carers was conducted to understand their attitudes and needs in relation to end-of-life care. The survey encompassed five separate domains, with a total of 60 questions requiring approximately 20 min to complete. Of the 200 surveys sent to patients, 82 (41%) completed responses were received. The Institutional Ethics Committee received six complaints from families of seven patients (3.5% of those surveyed). This article explores the nature of the adverse responses to the survey. The majority of complaints were received from family members rather than from patients. Complaints described dissatisfaction with the topic, little warning about the study and felt it to be inappropriate for their family member's level of health. Survey instruments used to determine attitudes and needs in relation to end-of-life patient care are likely to elicit adverse responses that should be reported in a similar way to other investigational studies. Also arising from adverse responses and the complaint process, is the impact of criticism on study researchers.

Genetic and epigenetic associations of MAOA and NR3C1 with depression and childhood adversities.

PubMed

Melas, Philippe A; Wei, Yabin; Wong, Chloe C Y; Sjöholm, Louise K; Åberg, Elin; Mill, Jonathan; Schalling, Martin; Forsell, Yvonne; Lavebratt, Catharina

2013-08-01

Monoamine oxidase A (MAOA) harbours a polymorphic upstream variable-number tandem repeat (u-VNTR). The MAOA-L allele of the u-VNTR leads to decreased gene expression levels in vitro and has been found to increase the risk of conduct disorder in males with childhood adversities. Early-life adversities have been associated with hypermethylation of the glucocorticoid receptor (NR3C1). In this study, we first performed a genetic association analysis of the MAOA u-VNTR using individuals with depression (n = 392) and controls (n = 1276). Next, DNA methylation analyses of MAOA and NR3C1 were performed using saliva samples of depressed and control subgroups. Adult MAOA-L females with childhood adversities were found to have a higher risk of developing depression (p = 0.006) and overall MAOA methylation levels were decreased in depressed females compared to controls (mean depressed, 42% vs. mean controls, 44%; p = 0.04). One specific childhood adversity [early parental death (EPD)] was associated with hypermethylation of NR3C1 close to an NGFI-A binding site (mean EPD, 19% vs. mean non-EPD, 14%; p = 0.005). Regression analysis indicated that this association may be mediated by the MAOA-L allele (adjusted R² = 0.24, ANOVA: F = 23.48, p < 0.001). Conclusively: (1) depression in females may result from a gene × childhood-adversity interaction and/or a dysregulated epigenetic programming of MAOA; (2) childhood-adversity subtypes may differentially impact DNA methylation at NR3C1; (3) baseline MAOA-genotypic variations may affect the extent of NR3C1 methylation.

The influence of ethnicity and adverse life experiences during adolescence on young adult socioeconomic attainment: the moderating role of education.

PubMed

Wickrama, K A S; Simons, Leslie Gordon; Baltimore, Diana

2012-11-01

Previous research has documented that adverse life experiences during adolescence, particularly for ethnic minorities, have a long-term influence on income and asset attainment and that this relationship is largely mediated by educational achievement. We extend prior research by investigating three research questions. First, we investigate the extent to which community disadvantage, family factors and race/ethnicity each exert an independent influence on young adult socioeconomic attainment. Second, we examine whether youths' educational attainment mediates these independent influences on socioeconomic attainment. Third, we test whether educational attainment ameliorates the negative influences of disadvantaged community and family conditions and race/ethnicity on socioeconomic attainment. We address these questions using multilevel modeling with longitudinal, prospective data from Waves 1 and 4 of National Longitudinal Study of Adolescent Health, which has a nationally representative sample of adolescents (N = 13, 450; 53 % females). Regarding our first research question, our results indicated that African Americans, youth from disadvantaged communities, lower SES families achieve significantly lower levels of earnings, assets, and job quality during young adulthood. Second, we found that young adults' educational level only partially mediate the influences of family and race/ethnicity influences on young adults' socioeconomic attainment. Third, we found that young adults' educational level buffered the influence of early socioeconomic adversities and accentuated the positive influences of family resources. Findings highlight the importance of social context as well as educational opportunities during childhood and adolescence for economic stability in early adulthood.

Adverse early life environment increases hippocampal microglia abundance in conjunction with decreased neural stem cells in juvenile mice.

PubMed

Cohen, Susan; Ke, Xingrao; Liu, Qiuli; Fu, Qi; Majnik, Amber; Lane, Robert

2016-12-01

Adverse maternal lifestyle resulting in adverse early life environment (AELE) increases risks for neuropsychiatric disorders in offspring. Neuropsychiatric disorders are associated with impaired neurogenesis and neuro-inflammation in the hippocampus (HP). Microglia are neuro-inflammatory cells in the brain that regulate neurogenesis via toll-like receptors (TLR). TLR-9 is implicated in neurogenesis inhibition and is responsible for stress-related inflammatory responses. We hypothesized that AELE would increase microglia cell count and increase TLR-9 expression in juvenile mouse HP. These increases in microglia cell count and TLR-9 expression would be associated with decrease neural stem cell count and neuronal cell count. We developed a mouse model of AELE combining Western diet and a stress environment. Stress environment consisted of random change from embryonic day 13 (E13) to E17 as well as static change in maternal environment from E13 to postnatal day 21(P21). At P21, we measured hippocampal cell numbers of microglia, neural stem cell and neuron, as well as hippocampal TLR-9 expression. AELE significantly increased total microglia number and TLR-9 expression in the hippocampus. Concurrently, AELE significantly decreased neural stem cell and neuronal numbers. AELE increased the neuro-inflammatory cellular response in the juvenile HP. We speculate that increased neuro-inflammatory responses may contribute to impaired neurogenesis seen in this model. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Early life stress-induced alterations in rat brain structures measured with high resolution MRI.

PubMed

Sarabdjitsingh, R Angela; Loi, Manila; Joëls, Marian; Dijkhuizen, Rick M; van der Toorn, Annette

2017-01-01

Adverse experiences early in life impair cognitive function both in rodents and humans. In humans this increases the vulnerability to develop mental illnesses while in the rodent brain early life stress (ELS) abnormalities are associated with changes in synaptic plasticity, excitability and microstructure. Detailed information on the effects of ELS on rodent brain structural integrity at large and connectivity within the brain is currently lacking; this information is highly relevant for understanding the mechanism by which early life stress predisposes to mental illnesses. Here, we exposed rats to 24 hours of maternal deprivation (MD) at postnatal day 3, a paradigm known to increase corticosterone levels and thereby activate glucocorticoid receptors in the brain. Using structural magnetic resonance imaging we examined: i) volumetric changes and white/grey matter properties of the whole cerebrum and of specific brain areas; and ii) whether potential alterations could be normalized by blocking glucocorticoid receptors with mifepristone during the critical developmental window of early adolescence, i.e. between postnatal days 26 and 28. The results show that MD caused a volumetric reduction of the prefrontal cortex, particularly the ventromedial part, and the orbitofrontal cortex. Within the whole cerebrum, white (relative to grey) matter volume was decreased and region-specifically in prefrontal cortex and dorsomedial striatum following MD. A trend was found for the hippocampus. Grey matter fractions were not affected. Treatment with mifepristone did not normalize these changes. This study indicates that early life stress in rodents has long lasting consequences for the volume and structural integrity of the brain. However, changes were relatively modest and-unlike behavior- not mitigated by blockade of glucocorticoid receptors during a critical developmental period.

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed

Buchhorn, Reiner; Meint, Sebastian; Willaschek, Christian

2016-01-01

Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children-allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)-have the highest risk for 'stress diseases' such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children.

The Impact of Early Life Stress on Growth and Cardiovascular Risk: A Possible Example for Autonomic Imprinting?

PubMed Central

Buchhorn, Reiner; Meint, Sebastian

2016-01-01

Introduction Early life stress is imprinting regulatory properties with life-long consequences. We investigated heart rate variability in a group of small children with height below the third percentile, who experienced an episode of early life stress due to heart failure or intra uterine growth retardation. These children appear to develop autonomic dysfunction in later life. Results Compared to the healthy control group heart rate variability (HRV) is reduced on average in a group of 101 children with short stature. Low HRV correlates to groups of children born small for gestational age (SGA), children with cardiac growth failure and children with congenital syndromes, but not to those with constitutional growth delay (CGD), who had normal HRV. Reduced HRV indicated by lower RMSSD and High Frequency (HF)-Power is indicating reduced vagal activity as a sign of autonomic imbalance. Conclusion It is not short stature itself, but rather the underlying diseases that are the cause for reduced HRV in children with height below the third percentile. These high risk children—allocated in the groups with an adverse autonomic imprinting in utero or infancy (SGA, congenital heart disease and congenital syndromes)—have the highest risk for ‘stress diseases’ such as cardiovascular disease in later life. The incidence of attention deficit disorder is remarkably high in our group of short children. PMID:27861527

Rare and very rare adverse effects of clozapine

PubMed Central

De Fazio, Pasquale; Gaetano, Raffaele; Caroleo, Mariarita; Cerminara, Gregorio; Maida, Francesca; Bruno, Antonio; Muscatello, Maria Rosaria; Moreno, Maria Jose Jaén; Russo, Emilio; Segura-García, Cristina

2015-01-01

Clozapine (CLZ) is the drug of choice for the treatment of resistant schizophrenia; however, its suitable use is limited by the complex adverse effects’ profile. The best-described adverse effects in the literature are represented by agranulocytosis, myocarditis, sedation, weight gain, hypotension, and drooling; nevertheless, there are other known adverse effects that psychiatrists should readily recognize and manage. This review covers the “rare” and “very rare” known adverse effects of CLZ, which have been accurately described in literature. An extensive search on the basis of predefined criteria was made using CLZ and its combination with adverse effects as keywords in electronic databases. Data show the association between the use of CLZ and uncommon adverse effects, including ischemic colitis, paralytic ileus, hematemesis, gastroesophageal reflux disease, priapism, urinary incontinence, pityriasis rosea, intertriginous erythema, pulmonary thromboembolism, pseudo-pheochromocytoma, periorbital edema, and parotitis, which are influenced by other variables including age, early diagnosis, and previous/current pharmacological therapies. Some of these adverse effects, although unpredictable, are often manageable if promptly recognized and treated. Others are serious and potentially life-threatening. However, an adequate knowledge of the drug, clinical vigilance, and rapid intervention can drastically reduce the morbidity and mortality related to CLZ treatment. PMID:26273202

Early Life Stress and Inflammatory Mechanisms of Fatigue in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

PubMed Central

Cho, Hyong Jin; Bower, Julienne E.; Kiefe, Catarina I.; Seeman, Teresa E.; Irwin, Michael R.

2012-01-01

Fatigue is highly prevalent and causes serious disruption in quality of life. Although cross-sectional studies suggest childhood adversity is associated with adulthood fatigue, longitudinal evidence of this relationship and its specific biological mechanisms have not been established. This longitudinal study examined the association between early life stress and adulthood fatigue and tested whether this association was mediated by low-grade systemic inflammation as indexed by circulating C-reactive protein (CRP) and interleukin-6 (IL-6). In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based longitudinal study conducted in 4 US cities, early life stress was retrospectively assessed in 2716 African-American and white adults using the Risky Families Questionnaire at Year 15 examination (2000–2001, ages 33–45 years). Fatigue as indexed by a loss of subjective vitality using the Vitality Subscale of the 12-item Short Form Health Survey was assessed at both Years 15 and 20. While CRP was measured at both Years 15 and 20, IL-6 was measured only at Year 20. Early life stress assessed at Year 15 was associated with adulthood fatigue at Year 20 after adjustment for sociodemographic characteristics, body-mass index, medication use, medical comorbidity, smoking, alcohol consumption, physical activity, current stress, pain, sleep disturbance as well as Year 15 fatigue (adjusted beta 0.047, P=0.007). However, neither CRP nor IL-6 was a significant mediator of this association. In summary, early life stress assessed in adulthood was associated with fatigue 5 years later, but this association was not mediated by low-grade systemic inflammation. PMID:22554493

Early life stress and inflammatory mechanisms of fatigue in the Coronary Artery Risk Development in Young Adults (CARDIA) study.

PubMed

Cho, Hyong Jin; Bower, Julienne E; Kiefe, Catarina I; Seeman, Teresa E; Irwin, Michael R

2012-08-01

Fatigue is highly prevalent and causes serious disruption in quality of life. Although cross-sectional studies suggest childhood adversity is associated with adulthood fatigue, longitudinal evidence of this relationship and its specific biological mechanisms have not been established. This longitudinal study examined the association between early life stress and adulthood fatigue and tested whether this association was mediated by low-grade systemic inflammation as indexed by circulating C-reactive protein (CRP) and interleukin-6 (IL-6). In the Coronary Artery Risk Development in Young Adults (CARDIA) study, a population-based longitudinal study conducted in 4 US cities, early life stress was retrospectively assessed in 2716 African-American and white adults using the Risky Families Questionnaire at Year 15 examination (2000-2001, ages 33-45 years). Fatigue as indexed by a loss of subjective vitality using the Vitality Subscale of the 12-item Short Form Health Survey was assessed at both Years 15 and 20. While CRP was measured at both Years 15 and 20, IL-6 was measured only at Year 20. Early life stress assessed at Year 15 was associated with adulthood fatigue at Year 20 after adjustment for sociodemographic characteristics, body-mass index, medication use, medical comorbidity, smoking, alcohol consumption, physical activity, current stress, pain, sleep disturbance as well as Year 15 fatigue (adjusted beta 0.047, P=0.007). However, neither CRP nor IL-6 was a significant mediator of this association. In summary, early life stress assessed in adulthood was associated with fatigue 5 years later, but this association was not mediated by low-grade systemic inflammation. Copyright © 2012 Elsevier Inc. All rights reserved.

Disturbance of the gut microbiota in early-life selectively affects visceral pain in adulthood without impacting cognitive or anxiety-related behaviors in male rats.

PubMed

O'Mahony, S M; Felice, V D; Nally, K; Savignac, H M; Claesson, M J; Scully, P; Woznicki, J; Hyland, N P; Shanahan, F; Quigley, E M; Marchesi, J R; O'Toole, P W; Dinan, T G; Cryan, J F

2014-09-26

Disruption of bacterial colonization during the early postnatal period is increasingly being linked to adverse health outcomes. Indeed, there is a growing appreciation that the gut microbiota plays a role in neurodevelopment. However, there is a paucity of information on the consequences of early-life manipulations of the gut microbiota on behavior. To this end we administered an antibiotic (vancomycin) from postnatal days 4-13 to male rat pups and assessed behavioral and physiological measures across all aspects of the brain-gut axis. In addition, we sought to confirm and expand the effects of early-life antibiotic treatment using a different antibiotic strategy (a cocktail of pimaricin, bacitracin, neomycin; orally) during the same time period in both female and male rat pups. Vancomycin significantly altered the microbiota, which was restored to control levels by 8 weeks of age. Notably, vancomycin-treated animals displayed visceral hypersensitivity in adulthood without any significant effect on anxiety responses as assessed in the elevated plus maze or open field tests. Moreover, cognitive performance in the Morris water maze was not affected by early-life dysbiosis. Immune and stress-related physiological responses were equally unaffected. The early-life antibiotic-induced visceral hypersensitivity was also observed in male rats given the antibiotic cocktail. Both treatments did not alter visceral pain perception in female rats. Changes in visceral pain perception in males were paralleled by distinct decreases in the transient receptor potential cation channel subfamily V member 1, the α-2A adrenergic receptor and cholecystokinin B receptor. In conclusion, a temporary disruption of the gut microbiota in early-life results in very specific and long-lasting changes in visceral sensitivity in male rats, a hallmark of stress-related functional disorders of the brain-gut axis such as irritable bowel disorder. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Individual differences in early adolescents' latent trait cortisol (LTC): Relation to early adversity.

PubMed

Stroud, Catherine B; Chen, Frances R; Doane, Leah D; Granger, Douglas A

2016-09-01

Substantial evidence suggests that youth who experience early adversity exhibit alterations in hypothalamic pituitary adrenal (HPA) axis functioning, thereby increasing risk for negative health outcomes. However, few studies have explored whether early adversity alters enduring trait indicators of HPA axis activity. Using objective contextual stress interviews with adolescents and their mothers to assess early adversity, we examined the cumulative impact of nine types of early adversity on early adolescents girls' latent trait cortisol (LTC). Adolescents (n = 122; M age = 12.39 years) provided salivary cortisol samples three times a day (waking, 30 min post-waking, and bedtime) over 3 days. Latent state-trait modeling indicated that the waking and 30 min post-waking samples contributed to a LTC factor. Moreover, greater early adversity was associated with a lower LTC level. Implications of LTC for future research examining the impact of early adversity on HPA axis functioning are discussed. © 2016 Wiley Periodicals, Inc. Dev Psychobiol 58:700-713, 2016. © 2016 Wiley Periodicals, Inc.

Blunted Diurnal Cortisol Activity in Healthy Adults with Childhood Adversity.

PubMed

Kuras, Yuliya I; Assaf, Naomi; Thoma, Myriam V; Gianferante, Danielle; Hanlin, Luke; Chen, Xuejie; Fiksdal, Alexander; Rohleder, Nicolas

2017-01-01

Childhood adversity, such as neglect, or physical, emotional, or sexual abuse, is prevalent in the U.S. and worldwide, and connected to an elevated incidence of disease in adulthood. A pathway in this relationship might be altered hypothalamic-pituitary-adrenal (HPA) axis functioning, as a result of differential hippocampal development in early life. A blunted diurnal cortisol slope is a precursor for many disorders. While studies have focused on HPA reactivity in relation to childhood adversity, there has been markedly less research on basal HPA functioning in those with low-to-moderate adversity. Based on previous research, we hypothesized that adults with low-to-moderate childhood adversity would have altered HPA axis functioning, as evidenced by a blunted diurnal cortisol slope and altered cortisol awakening response (CAR). Healthy adults aged 18-65 ( n = 61 adults; 31 males and 30 females) completed the Childhood Trauma Questionnaire. Participants provided at-home saliva samples on two consecutive days at wake-up, and 30 min, 1, 4, 9, and 13 h later; samples were averaged over the 2 days. We found that low-to-moderate childhood adversity predicted lower morning cortisol (β = -0.34, p = 0.007, R 2 = 0.21), as well as a blunted cortisol slope (β = 2.97, p = 0.004, R 2 = 0.22), but found no association with CAR (β = 0.19, p = 0.14, R 2 = 0.12). Overall, we found that in healthy participants, low-to-moderate adversity in childhood is associated with altered basal HPA activity in adulthood. Our findings indicate that even low levels of childhood adversity may predispose individuals to disease associated with HPA dysregulation in later life.

The moderating impact of childhood adversity profiles and conflict on psychological health and suicidal behaviour in the Northern Ireland population.

PubMed

McLafferty, Margaret; O'Neill, Siobhan; Murphy, Sam; Armour, Cherie; Ferry, Finola; Bunting, Brendan

2018-04-01

Childhood adversities are key etiological factors in the onset and persistence of psychopathology. In Northern Ireland the Troubles also impacted on the population's psychological health. This study used data from the Northern Ireland Study of Health and Stress a collaborative epidemiological study which used the WMH-CIDI to assess mental health disorders in a nationally representative sample (Part 2, n = 1986). The aims of the study were to assess co-occurrences of childhood adversities and investigate the impact of adversity profiles and conflict experience on psychopathology and suicidal behaviour. Latent Class Analysis uncovered 3 discrete childhood adversity profiles, a low, medium, and high risk class. Individuals from higher risk adversity profiles displayed significantly increased odds of having psychological problems, with conflict exposure also impacting on psychopathology. However, the study revealed that the impact of conflict exposure on suicidal behaviour was moderated by latent class membership and that some adversity may actually be protective. The findings highlight the need to consider that, while adversity can have a negative impact on psychopathology, a lack of adversity early in life may hinder some people from developing adequate coping strategies. Further research is required to identify adversity patterns and other interacting factors that are protective. Copyright © 2018 Elsevier B.V. All rights reserved.

Childhood Adversity and Epigenetic Regulation of Glucocorticoid Signaling Genes: Associations in Children and Adults

PubMed Central

Tyrka, Audrey R.; Ridout, Kathryn K.; Parade, Stephanie H.

2017-01-01

Early childhood experiences have lasting effects on development, including the risk for psychiatric disorders. Research examining the biologic underpinnings of these associations has revealed the impact of childhood maltreatment on the physiologic stress response and activity of the hypothalamic pituitary adrenal (HPA) axis. A growing body of literature supports the hypothesis that environmental exposures mediate their biological effects via epigenetic mechanisms. Methylation, which is thought to be the most stable form of epigenetic change, is a likely mechanism by which early life exposures has lasting effects. In this review, we present recent evidence related to epigenetic regulation of genes involved in HPA axis regulation, namely the glucocorticoid receptor gene (NR3C1) and FK506 binding protein 51 (FKBP5), after childhood adversity and associations with risk for psychiatric disorders. Implications for the development of interventions and future research are discussed. PMID:27691985

Interplay between childhood maltreatment, parental bonding, and gender effects: Impact on quality of life☆

PubMed Central

Rikhye, Kobita; Tyrka, Audrey R.; Kelly, Megan M.; Gagne, Gerard G.; Mello, Andrea F.; Mello, Marcelo F.; Price, Lawrence H.

2015-01-01

Objective The aim of this study was to examine associations between childhood adversity, parental bonding, gender, depressive symptoms, and quality of life in non-treatment-seeking adults from the community. Method Effects of differential parental rearing were compared in adults who reported a high degree of childhood maltreatment (n = 72) and those who reported no significant adverse events in childhood (n = 69). Subjects completed retrospective measures of childhood maltreatment and perceived parenting style, as well as measures of current depressive symptoms and quality of life. Results The subjects without childhood maltreatment were younger and endorsed less current depressive symptomatology than did subjects with childhood maltreatment. While the subjects without a history of maltreatment reported more “optimal” bonding experiences with their parents, the maltreatment group members were more likely to characterize their early parental bonding experiences in terms of “affectionless control” (p < .001 for both maternal and paternal parenting), “affectionate constraint” (p = .025 for maternal parenting and p = .004 for paternal parenting), or “weak or absent” bonding (p < .001 for both maternal and paternal parenting). Results of a multiple regression analysis revealed that overall quality of paternal care (p = .015) and current level of depressive symptoms (p < .001) were significant independent predictors of adult quality of life. Gender effects between subjects providing parental bonding data were limited to the group with childhood maltreatment. Conclusion These findings extend previous work documenting a relationship between early life maltreatment and suboptimal parental bonding, suggesting gender-specific effects of maternal and paternal care. Effects of childhood maltreatment on quality of life in adulthood appear to be linked with the quality of childhood paternal care and the occurrence of depressive symptomatology in adulthood, suggesting possible targets for primary or secondary prevention. PMID:18082260

Childhood adversity, recent life stressors and suicidal behavior in Chinese college students.

PubMed

You, Zhiqi; Chen, Mingxi; Yang, Sen; Zhou, Zongkui; Qin, Ping

2014-01-01

Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population.

Comparing the impact of personal and parental risk factors, and parental lifespan on all-cause mortality and cardiovascular disease: findings from the Midspan Family cohort study.

PubMed

Hart, Carole; McCartney, Gerry; Gruer, Laurence; Watt, Graham

2015-10-01

We aimed to identify which personal and parental factors best explained all-cause mortality and cardiovascular disease (CVD). In 1996, data were collected on 2338 adult offspring of the participants in the 1972-1976 Renfrew and Paisley prospective cohort study. Recorded risk factors were assigned to 5 groups: mid-life biological and behavioural (BB), mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan. Participants were followed up for mortality and hospital admissions to the end of 2011. Cox proportional hazards models were used to analyse how well each group explained all-cause mortality or CVD. Akaike's Information Criterion (AIC), a measure of goodness-of-fit, identified the most important groups. For all-cause mortality (1997 participants with complete data, 111 deaths), decreases in AIC from the null model (adjusting for age and sex) to models including mid-life BB, mid-life socioeconomic, parental BB, early-life socioeconomic and parental lifespan were 55.8, 21.6, 10.3, 7.3 and 5.9, respectively. For the CVD models (1736 participants, 276 with CVD), decreases were 37.8, 3.7, 6.7, 17.3 and 0.4. Mid-life BB factors were the most important for both all-cause mortality and CVD; mid-life socioeconomic factors were important for all-cause mortality, and early-life socioeconomic factors were important for CVD. Parental lifespan was the weakest factor. As mid-life BB risk factors best explained all-cause mortality and CVD, continued action to reduce these is warranted. Targeting adverse socioeconomic factors in mid-life and early life may contribute to reducing all-cause mortality and CVD risk, respectively. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Developmental toxicity of PAH mixtures in fish early life stages. Part II: adverse effects in Japanese medaka.

PubMed

Le Bihanic, Florane; Clérandeau, Christelle; Le Menach, Karyn; Morin, Bénédicte; Budzinski, Hélène; Cousin, Xavier; Cachot, Jérôme

2014-12-01

In aquatic environments, polycyclic aromatic hydrocarbons (PAHs) mostly occur as complex mixtures, for which risk assessment remains problematic. To better understand the effects of PAH mixture toxicity on fish early life stages, this study compared the developmental toxicity of three PAH complex mixtures. These mixtures were extracted from a PAH-contaminated sediment (Seine estuary, France) and two oils (Arabian Light and Erika). For each fraction, artificial sediment was spiked at three different environmental concentrations roughly equivalent to 0.5, 4, and 10 μg total PAH g(-1) dw. Japanese medaka embryos were incubated on these PAH-spiked sediments throughout their development, right up until hatching. Several endpoints were recorded at different developmental stages, including acute endpoints, morphological abnormalities, larvae locomotion, and genotoxicity (comet and micronucleus assays). The three PAH fractions delayed hatching, induced developmental abnormalities, disrupted larvae swimming activity, and damaged DNA at environmental concentrations. Differences in toxicity levels, likely related to differences in PAH proportions, were highlighted between fractions. The Arabian Light and Erika petrogenic fractions, containing a high proportion of alkylated PAHs and low molecular weight PAHs, were more toxic to Japanese medaka early life stages than the pyrolytic fraction. This was not supported by the toxic equivalency approach, which appeared unsuitable for assessing the toxicity of the three PAH fractions to fish early life stages. This study highlights the potential risks posed by environmental mixtures of alkylated and low molecular weight PAHs to early stages of fish development.

Maternal determinants of renal mass and function in the fetus and neonate.

PubMed

Brophy, Patrick

2017-04-01

The impact of adverse maternal and early gestational issues, ranging from maternal-fetal interactions all the way through to premature birth, are recognized as having influence on the subsequent development of chronic diseases later in life. The development of chronic kidney disease (CKD) as a direct result of early life renal injury or a sequela of diseases such as hypertension or diabetes is a good model example of the potential impact that early life events may have on renal development and lifelong function. The global monetary and human resource cost of CKD is exorbitant. Socio-economic factors, along with other factors (genetic and environmental) may significantly influence the timing and display of phenotypic expression in fetuses and neonates at risk for developing CKD, yet very few of these factors are studied or well understood. In general our focus has been directed at treatment once CKD is established. This strategy has been and remains short-sighted and costly. Earlier understanding of the intrauterine determinants of renal mass development (i.e. environmental "biomes", poor maternal-fetal health, socio-economic factors impacting early life events, diet, access to value based health care and educational opportunities on disease evolution) may allow us an opportunity for earlier intervention. This article aims to provide some foundation for improved understanding of the maternal determinants of renal mass and function in the fetus and neonate. Copyright © 2017 Elsevier Ltd. All rights reserved.

Does life-course socioeconomic position influence racial inequalities in the occurrence of uterine leiomyoma? Evidence from the Pró-Saúde Study.

PubMed

Boclin, Karine de Limas Irio; Faerstein, Eduardo; Szklo, Moyses

2014-02-01

We aimed to investigate whether life-course socioeconomic position mediates the association between skin color/race and occurrence of uterine leiomyomas. We analyzed 1,475 female civil servants with baseline data (1999-2001) of the Pró-Saúde Study in Rio de Janeiro State, Brazil. Life-course socioeconomic position was determined by parental education (early life socioeconomic position), participant education (socioeconomic position in early adulthood) and their combination (cumulative socioeconomic position). Gynecological/breast exams and health insurance status were considered markers of access to health care. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using Cox proportional hazards models. Compared with white women, black and parda ("brown") women had higher risk of reporting uterine leiomyomas, respectively HR: 1.6, 95%CI: 1.2-2.1; HR: 1.4, 95%CI: 0.8-2.5. Estimates were virtually identical in models including different variables related to life-course socioeconomic position. This study corroborated previous evidence of higher uterine leiomyomas risk in women with darker skin color, and further suggest that life-course socioeconomic position adversity does not influence this association.

Gender differences in the pathway from adverse life events to adolescent emotional and behavioural problems via negative cognitive errors.

PubMed

Flouri, Eirini; Panourgia, Constantina

2011-06-01

The aim of this study was to test for gender differences in how negative cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and personalizing) mediate the association between adverse life events and adolescents' emotional and behavioural problems (measured with the Strengths and Difficulties Questionnaire). The sample consisted of 202 boys and 227 girls (aged 11-15 years) from three state secondary schools in disadvantaged areas in one county in the South East of England. Control variables were age, ethnicity, special educational needs, exclusion history, family structure, family socio-economic disadvantage, and verbal cognitive ability. Adverse life events were measured with Tiet et al.'s (1998) Adverse Life Events Scale. For both genders, we assumed a pathway from adverse life events to emotional and behavioural problems via cognitive errors. We found no gender differences in life adversity, cognitive errors, total difficulties, peer problems, or hyperactivity. In both boys and girls, even after adjustment for controls, cognitive errors were related to total difficulties and emotional symptoms, and life adversity was related to total difficulties and conduct problems. The life adversity/conduct problems association was not explained by negative cognitive errors in either gender. However, we found gender differences in how adversity and cognitive errors produced hyperactivity and internalizing problems. In particular, life adversity was not related, after adjustment for controls, to hyperactivity in girls and to peer problems and emotional symptoms in boys. Cognitive errors fully mediated the effect of life adversity on hyperactivity in boys and on peer and emotional problems in girls.

The Consequences of Contact with the Criminal Justice System for Health in the Transition to Adulthood

PubMed Central

Esposito, Michael H.; Lee, Hedwig; Hicken, Margret T.; Porter, Lauren C.; Herting, Jerald R.

2017-01-01

A rapidly growing literature has documented the adverse social, economic and, recently, health impacts of experiencing incarceration in the United States. Despite the insights that this work has provided in consistently documenting the deleterious effects of incarceration, little is known about the specific timing of criminal justice contact and early health consequences during the transition from adolescence to adulthood—a critical period in the life course, particularly for the development of poor health. Previous literature on the role of incarceration has also been hampered by the difficulties of parsing out the influence that incarceration exerts on health from the social and economic confounding forces that are linked to both criminal justice contact and health. This paper addresses these two gaps in the literature by examining the association between incarceration and health in the United States during the transition to adulthood, and by using an analytic approach that better isolates the association of incarceration with health from the multitude of confounders which could be alternatively driving this association. In this endeavor, we make use of variable-rich data from The National Longitudinal Study of Adolescent to Adult Health (n = 10,785) and a non-parametric Bayesian machine learning technique- Bayesian Additive Regression Trees. Our results suggest that the experience of incarceration at this stage of the life course increases the probability of depression, adversely affects the perception of general health status, but has no effect on the probability of developing hypertension in early adulthood. These findings signal that incarceration in emerging adulthood is an important stressor that can have immediate implications for mental and general health in early adulthood, and may help to explain long lasting implications incarceration has for health across the life course. PMID:28781613

Proinflammatory T Cell Status Associated with Early Life Adversity.

PubMed

Elwenspoek, Martha M C; Hengesch, Xenia; Leenen, Fleur A D; Schritz, Anna; Sias, Krystel; Schaan, Violetta K; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Schächinger, Hartmut; Vögele, Claus; Turner, Jonathan D; Muller, Claude P

2017-12-15

Early life adversity (ELA) has been associated with an increased risk for diseases in which the immune system plays a critical role. The ELA immune phenotype is characterized by inflammation, impaired cellular immunity, and immunosenescence. However, data on cell-specific immune effects are largely absent. Additionally, stress systems and health behaviors are altered in ELA, which may contribute to the generation of the ELA immune phenotype. The present investigation tested cell-specific immune differences in relationship to the ELA immune phenotype, altered stress parameters, and health behaviors in individuals with ELA ( n = 42) and those without a history of ELA (control, n = 73). Relative number and activation status (CD25, CD69, HLA-DR, CD11a, CD11b) of monocytes, NK cells, B cells, T cells, and their main subsets were assessed by flow cytometry. ELA was associated with significantly reduced numbers of CD69 + CD8 + T cells ( p = 0.022), increased numbers of HLA-DR + CD4 and HLA-DR + CD8 T cells ( p < 0.001), as well as increased numbers of CD25 + CD8 + T cells ( p = 0.036). ELA also showed a trend toward higher numbers of CCR4 + CXCR3 - CCR6 + CD4 T cells. Taken together, our data suggest an elevated state of immune activation in ELA, in which particularly T cells are affected. Although several aspects of the ELA immune phenotype were related to increased activation markers, neither stress nor health-risk behaviors explained the observed group differences. Thus, the state of immune activation in ELA does not seem to be secondary to alterations in the stress system or health-risk behaviors, but rather a primary effect of early life programming on immune cells. Copyright © 2017 by The American Association of Immunologists, Inc.

Pregnancy And Neonatal Diabetes Outcomes in Remote Australia (PANDORA) Study.

PubMed

Maple-Brown, Louise J; Brown, Alex; Lee, I-Lynn; Connors, Christine; Oats, Jeremy; McIntyre, Harold D; Whitbread, Cherie; Moore, Elizabeth; Longmore, Danielle; Dent, Glynis; Corpus, Sumaria; Kirkwood, Marie; Svenson, Stacey; van Dokkum, Paula; Chitturi, Sridhar; Thomas, Sujatha; Eades, Sandra; Stone, Monique; Harris, Mark; Inglis, Chrissie; Dempsey, Karen; Dowden, Michelle; Lynch, Michael; Boyle, Jacqueline; Sayers, Sue; Shaw, Jonathan; Zimmet, Paul; O'Dea, Kerin

2013-12-01

Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal post-partum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring.

A Biographic Comparison Tracing the Origin of Their Ideas of Jean Piaget and Lev Vygotsky.

ERIC Educational Resources Information Center

Pass, Susan

This paper compares the early life, background, and education of Jean Piaget and Lev Vygotsky. It makes the case that an adaptation of the curve developed by C. Quigley can be used to trace the motivations of both Piaget and Vygotsky in creating their respective theories. The analysis also reveals the adversity that each man faced. Although they…

Prospective Assessment of Neurocognition in Future Gulf-deployed and Gulf-nondeployed Military Personnel: A Pilot Study

DTIC Science & Technology

2007-02-01

increased emotional distress but with advantaged simple reactiontime. Unit cohesion buffers the adverse effects of early life events on PTSD prior to...motor speed), and emotional (e.g., mood) behaviors thought to reflect neural integrity. Unresolved issues include whether subjective...including neurobehavioral and emotional functioning, (b) examine the impact of deployment-related stress and environmental exposures on

Effect of Socioeconomic Status (SES) Disparity on Neural Development in Female African-American Infants at Age 1 Month

ERIC Educational Resources Information Center

Betancourt, Laura M.; Avants, Brian; Farah, Martha J.; Brodsky, Nancy L.; Wu, Jue; Ashtari, Manzar; Hurt, Hallam

2016-01-01

There is increasing interest in both the cumulative and long-term impact of early life adversity on brain structure and function, especially as the brain is both highly vulnerable and highly adaptive during childhood. Relationships between SES and neural development have been shown in children older than age 2 years. Less is known regarding the…

The Role of Maternal Adverse Childhood Experiences and Race in Intergenerational High-Risk Smoking Behaviors.

PubMed

Pear, Veronica A; Petito, Lucia C; Abrams, Barbara

2017-05-01

A history of adversity in childhood is associated with cigarette smoking in adulthood, but there is less evidence for prenatal and next-generation offspring smoking. We investigated the association between maternal history of childhood adversity, pregnancy smoking, and early initiation of smoking in offspring, overall and by maternal race/ethnicity. Data on maternal childhood exposure to physical abuse, household alcohol abuse, and household mental illness, prenatal smoking behaviors, and offspring age of smoking initiation were analyzed from the US National Longitudinal Survey of Youth 1979 (NLSY79, n = 2999 mothers) and the NLSY79 Children and Young Adults Survey (NLSYCYA, n = 6596 children). Adjusted risk ratios were estimated using log-linear regression models. We assessed multiplicative interaction by race/ethnicity for all associations and a three-way interaction by maternal exposure to adversity and race/ethnicity for the association between prenatal and child smoking. Maternal exposure to childhood physical abuse was significantly associated with 39% and 20% increased risks of prenatal smoking and child smoking, respectively. Household alcohol abuse was associated with significantly increased risks of 20% for prenatal smoking and 17% for child smoking. The prenatal smoking-child smoking relationship was modified by maternal exposure to household alcohol abuse and race. There were increased risks for Hispanic and white/other mothers as compared to the lowest risk group: black mothers who did not experience childhood household alcohol abuse. Mothers in this national sample who experienced adversity in childhood are more likely to smoke during pregnancy and their offspring are more likely to initiate smoking before age 18. Findings varied by type of adversity and race/ethnicity. These findings support the importance of a life-course approach to understanding prenatal and intergenerational smoking, and suggest that maternal early-life history is a potentially important risk factor that could be targeted with screening and interventions to reduce smoking in pregnant women and their children. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Life expectancy in elderly patients following burns injury.

PubMed

Sepehripour, Sarvnaz; Duggineni, Sirisha; Shahsavari, Somaya; Dheansa, Baljit

2018-05-18

Burn injuries commonly occur in vulnerable age and social groups. Previous research has shown that frailty may represent a more important marker of adverse outcome in healthcare rather than chronological age (Roberts et al., 2012). In this paper we determined the relationship between burn injury, frailty, co-morbidities and long-term survival. Retrospective data collection from patients aged 75 with burns injuries, treated and discharged at Queen Victoria Hospital. The Clinical Frailty Scale (Rockwood et al., 2005) was used to calculate frailty at the time of admission. The expected mortality age (life expectancy) of deceased patients was obtained from two survival predictors. The data shows a statistically significant correlation between frailty score and complications and a statistically significant correlation between total body surface area percentage and complications. No significant difference was found between expected and observed age of death or life expectancy amongst the deceased (p value of 0.109). Based on the data from our unit, sustaining a burn as an elderly person does not reduce life expectancy. Medical and surgical complications, immediate, early and late, although higher with greater frailty and TBSA of burn, but do not adversely affect survival in this population. Copyright © 2018 Elsevier Ltd. All rights reserved.

Social isolation mediated anxiety like behavior is associated with enhanced expression and regulation of BDNF in the female mouse brain.

PubMed

Kumari, Anita; Singh, Padmanabh; Baghel, Meghraj Singh; Thakur, M K

2016-05-01

Adverse early life experience is prominent risk factors for numerous psychiatric illnesses, including mood and anxiety disorders. It imposes serious long-term costs on the individual as well as health and social systems. Hence, developing therapies that prevent the long-term consequences of early life stress is of utmost importance, and necessitates a better understanding of the mechanisms by which early life stress triggers long-lasting alterations in gene expression and behavior. Post-weaning isolation rearing of rodents models the behavioral consequences of adverse early life experiences in humans and it is reported to cause anxiety like behavior which is more common in case of females. Therefore, in the present study, we have studied the impact of social isolation of young female mice for 8weeks on the anxiety like behavior and the underlying molecular mechanism. Elevated plus maze and open field test revealed that social isolation caused anxiety like behavior. BDNF, a well-known molecule implicated in the anxiety like behavior, was up-regulated both at the message and protein level in cerebral cortex by social isolation. CREB-1 and CBP, which play a crucial role in BDNF transcription, were up-regulated at mRNA level in cerebral cortex by social isolation. HDAC-2, which negatively regulates BDNF expression, was down-regulated at mRNA and protein level in cerebral cortex by social isolation. Furthermore, BDNF acts in concert with Limk-1, miRNA-132 and miRNA-134 for the regulation of structural and morphological plasticity. Social isolation resulted in up-regulation of Limk-1 mRNA and miRNA-132 expression in the cerebral cortex. MiRNA-134, which inhibits the translation of Limk-1, was decreased in cerebral cortex by social isolation. Taken together, our study suggests that social isolation mediated anxiety like behavior is associated with up-regulation of BDNF expression and concomitant increase in the expression of CBP, CREB-1, Limk-1 and miRNA-132, and decrease in the expression of HDAC-2 and miRNA-134 in the cerebral cortex. Copyright © 2016. Published by Elsevier Inc.

Developmental origins of adult health and disease: the role of periconceptional and foetal nutrition.

PubMed

McMillen, I Caroline; MacLaughlin, Severence M; Muhlhausler, Beverly S; Gentili, Sheridan; Duffield, Jaime L; Morrison, Janna L

2008-02-01

The 'developmental origins of adult health and disease' hypothesis stated that environmental factors, particularly maternal undernutrition, act in early life to programme the risks for adverse health outcomes, such as cardiovascular disease, obesity and the metabolic syndrome in adult life. Early physiological tradeoffs, including activation of the foetal hypothalamo-pituitary-adrenal (HPA) axis, confer an early fitness advantage such as foetal survival, while incurring delayed health costs. We review the evidence that such tradeoffs are anticipated from conception and that the periconceptional nutritional environment can programme the developmental trajectory of the stress axis and the systems that maintain and regulate arterial blood pressure. There is also evidence that restriction of placental growth and function, results in an increased dependence of the maintenance of arterial blood pressure on the sequential recruitment of the sympathetic nervous system and HPA axis. While the 'early origins of adult disease' hypothesis has focussed on the impact of maternal undernutrition, an increase in maternal nutritional intake and in maternal body mass intake has become more prevalent in developed countries. Exposure to overnutrition in foetal life results in a series of central and peripheral neuroendocrine responses that in turn programme development of the fat cell and of the central appetite regulatory system. While the physiological responses to foetal undernutrition result in the physiological trade off between foetal survival and poor health outcomes that emerge after reproductive senescence, exposure to early overnutrition results in poor health outcomes that emerge in childhood and adolescence. Thus, the effects of early overnutrition can directly impact on reproductive fitness and on the health of the next generation. In this context, the physiological responses to relative overnutrition in early life may directly contribute to an intergenerational cycle of obesity.

Childhood Adversity, Recent Life Stressors and Suicidal Behavior in Chinese College Students

PubMed Central

You, Zhiqi; Chen, Mingxi; Yang, Sen; Zhou, Zongkui; Qin, Ping

2014-01-01

Background Although the independent effects of childhood adversities and of recent negative events on suicidality have been well-documented, the combinative role of childhood and recent adversities on risk for suicidality is still underexplored, especially in the context of Chinese culture and in consideration of specific types of negative events. Method 5989 students, randomly sampled from six universities in central China, completed the online survey for this study. Suicidal behavior, life adversity during childhood and stressful events in recent school life were assessed with designed questionnaires. Results Students experiencing recent stressful life events more often reported an experience of life adversity during childhood. While recent stressful life events and childhood life adversity both were associated with an increased risk for suicidal behavior, the two exposures presented conjunctively and acted interactively to increase the risk. There was noticeable variation of effects associated with specific childhood life adversities, and sexual abuse, poor parental relationship, divorce of parents and loss of a parent were among the adversities associated with the highest increased risk. Recent conflicts with classmates, poor school performance and rupture of romantic relationships were the recent school life stressors associated with the highest increased risk. Conclusions Childhood adversity and recent school life stressors had a combinative role in predicting suicidality of young people studying in Chinese colleges. Unhappy family life during childhood and recent interpersonal conflicts in school were the most important predictors of suicidality in this population. PMID:24681891

Growth outcome: nutritionist perspective.

PubMed

Agostoni, Carlo; Fattore, Giovanni

2013-01-01

Increasing evidence points to a fundamental role of early nutrition on rates of growth and development, and later health. We may identify three major fields of scientific interest and clinical application. (1) In developing countries poor growth is associated with greater risk of morbidity and mortality from infectious diseases, mainly lower respiratory infections and diarrhea. In these settings, failure to promote compensatory growth may have negative short-term consequences, and the nutritionist's task is the primary prevention of nutrient deficiencies to promote the full expression of the individual genetic potential, while allowing for recovery of early secondary functional deficiencies. (2) A second challenge for nutritionists is represented by the approach to growth impairments in rare disorders, ranging from congenital disorders to chronic infections. Most disorders are favorably influenced by improved nutritional status and better growth, and patients may satisfactorily reach adolescence, pubertal and reproductive age, up to ageing. Even for the less positive conditions, an improvement in the quality of life for families is in any case a rewarding aim. (3) A third challenge is represented by the definition of the role of nutrition on growth in physiological conditions for all individuals. Concern has been raised about the potential adverse long-term consequences of accelerated child growth rates, possibly resulting in a predisposition to develop non-communicable chronic diseases in the adult age. Accordingly, this hypothesis might explain the benefits of breastfeeding in terms of slower early growth, and the fetal origins hypothesis in terms of adverse postnatal catch-up growth in infants born small. Therefore, growth as viewed by a pediatric nutritionist perspective is a complex matter, ranging from the early stages of intrauterine development up to adult ages and ageing processes. Cost/benefit analyses of interventions on growth such as cost per DALYs (disability-adjusted life years) or QALYs (quality-adjusted life years) should be expanded on population basis and extended also to congenital and invalidating disorders to identify the most effective and economic sustainable strategies of action. Copyright © 2013 S. Karger AG, Basel.

Altered fetal skeletal muscle nutrient metabolism following an adverse in utero environment and the modulation of later life insulin sensitivity.

PubMed

Dunlop, Kristyn; Cedrone, Megan; Staples, James F; Regnault, Timothy R H

2015-02-12

The importance of the in utero environment as a contributor to later life metabolic disease has been demonstrated in both human and animal studies. In this review, we consider how disruption of normal fetal growth may impact skeletal muscle metabolic development, ultimately leading to insulin resistance and decreased insulin sensitivity, a key precursor to later life metabolic disease. In cases of intrauterine growth restriction (IUGR) associated with hypoxia, where the fetus fails to reach its full growth potential, low birth weight (LBW) is often the outcome, and early in postnatal life, LBW individuals display modifications in the insulin-signaling pathway, a critical precursor to insulin resistance. In this review, we will present literature detailing the classical development of insulin resistance in IUGR, but also discuss how this impaired development, when challenged with a postnatal Western diet, may potentially contribute to the development of later life insulin resistance. Considering the important role of the skeletal muscle in insulin resistance pathogenesis, understanding the in utero programmed origins of skeletal muscle deficiencies in insulin sensitivity and how they may interact with an adverse postnatal environment, is an important step in highlighting potential therapeutic options for LBW offspring born of pregnancies characterized by placental insufficiency.

Life-Stage Physiologically-Based Pharmacokinetic (PBPK) ...

EPA Pesticide Factsheets

This presentation discusses methods used to extrapolate from in vitro high-throughput screening (HTS) toxicity data for an endocrine pathway to in vivo for early life stages in humans, and the use of a life stage PBPK model to address rapidly changing physiological parameters. Adverse outcome pathways (AOPs), in this case endocrine disruption during development, provide a biologically-based framework for linking molecular initiating events triggered by chemical exposures to key events leading to adverse outcomes. The application of AOPs to human health risk assessment requires extrapolation of in vitro HTS toxicity data to in vivo exposures (IVIVE) in humans, which can be achieved through the use of a PBPK/PD model. Exposure scenarios for chemicals in the PBPK/PD model will consider both placental and lactational transfer of chemicals, with a focus on age dependent dosimetry during fetal development and after birth for a nursing infant. This talk proposes a universal life-stage computational model that incorporates changing physiological parameters to link environmental exposures to in vitro levels of HTS assays related to a developmental toxicological AOP for vascular disruption. In vitro toxicity endpoints discussed are based on two mechanisms: 1) Fetal vascular disruption, and 2) Neurodevelopmental toxicity induced by altering thyroid hormone levels in neonates via inhibition of thyroperoxidase in the thyroid gland. Application of our Life-stage computati

Poverty, Stress, and Brain Development: New Directions for Prevention and Intervention.

PubMed

Blair, Clancy; Raver, C Cybele

2016-04-01

We review some of the growing evidence of the costs of poverty to children's neuroendocrine function, early brain development, and cognitive ability. We underscore the importance of addressing the negative consequences of poverty-related adversity early in children's lives, given evidence supporting the plasticity of executive functions and associated physiologic processes in response to early intervention and the importance of higher order cognitive functions for success in school and in life. Finally, we highlight some new directions for prevention and intervention that are rapidly emerging at the intersection of developmental science, pediatrics, child psychology and psychiatry, and public policy. Copyright © 2016 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

[Early transjugular intrahepatic portosystemic shunt: When, how and in whom?].

PubMed

Ruiz-Blard, Esteban; Baiges, Anna; Turon, Fanny; Hernández-Gea, Virginia; García-Pagán, Juan Carlos

2016-01-01

Early TIPS is basically a new application of an old concept. This intervention used to be a useful rescue therapy when other interventions failed but has now become a primary intervention in patients with variceal bleeding and risk factors for poor prognosis. This technique has also been proven to control bleeding and has a definite survival advantage at 6 weeks and 1 year over standard therapy with vasoactive drugs and endoscopy, without increasing the rate of adverse events. In well-trained hands and with appropriate candidate selection, early TIPS is a safe, life-saving and evidenced-based procedure. Copyright © 2015 Elsevier España, S.L.U. y AEEH y AEG. All rights reserved.

The Neurobiology of Intervention and Prevention in Early Adversity.

PubMed

Fisher, Philip A; Beauchamp, Kate G; Roos, Leslie E; Noll, Laura K; Flannery, Jessica; Delker, Brianna C

2016-01-01

Early adverse experiences are well understood to affect development and well-being, placing individuals at risk for negative physical and mental health outcomes. A growing literature documents the effects of adversity on developing neurobiological systems. Fewer studies have examined stress neurobiology to understand how to mitigate the effects of early adversity. This review summarizes the research on three neurobiological systems relevant to interventions for populations experiencing high levels of early adversity: the hypothalamic-adrenal-pituitary axis, the prefrontal cortex regions involved in executive functioning, and the system involved in threat detection and response, particularly the amygdala. Also discussed is the emerging field of epigenetics and related interventions to mitigate early adversity. Further emphasized is the need for intervention research to integrate knowledge about the neurobiological effects of prenatal stressors (e.g., drug use, alcohol exposure) and early adversity. The review concludes with a discussion of the implications of this research topic for clinical psychology practice and public policy.

OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

PubMed

Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

2017-10-01

Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC = differentiated thyroid cancer; LASA = linear analog self-assessment; PR = partial response; QOL = quality of life; RAI = radioactive iodine; RAIR = RAI-resistant; RECIST = Response Evaluation Criteria In Solid Tumors; Tg = thyroglobulin; VEGFR = vascular endothelial growth factor receptor.

Evidence supporting the match/mismatch hypothesis of psychiatric disorders.

PubMed

Santarelli, Sara; Lesuis, Sylvie L; Wang, Xiao-Dong; Wagner, Klaus V; Hartmann, Jakob; Labermaier, Christiana; Scharf, Sebastian H; Müller, Marianne B; Holsboer, Florian; Schmidt, Mathias V

2014-06-01

Chronic stress is one of the predominant environmental risk factors for a number of psychiatric disorders, particularly for major depression. Different hypotheses have been formulated to address the interaction between early and adult chronic stress in psychiatric disease vulnerability. The match/mismatch hypothesis of psychiatric disease states that the early life environment shapes coping strategies in a manner that enables individuals to optimally face similar environments later in life. We tested this hypothesis in female Balb/c mice that underwent either stress or enrichment early in life and were in adulthood further subdivided in single or group housed, in order to provide aversive or positive adult environments, respectively. We studied the effects of the environmental manipulation on anxiety-like, depressive-like and sociability behaviors and gene expression profiles. We show that continuous exposure to adverse environments (matched condition) is not necessarily resulting in an opposite phenotype compared to a continuous supportive environment (matched condition). Rather, animals with mismatched environmental conditions behaved differently from animals with matched environments on anxious, social and depressive like phenotypes. These results further support the match/mismatch hypothesis and illustrate how mild or moderate aversive conditions during development can shape an individual to be optimally adapted to similar conditions later in life. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Review of clinical and laboratory experiences with molindone hydrochloride.

PubMed

Claghorn, J L

1985-08-01

The literature concerning the pharmacokinetics, pharmacodynamics, receptor physiology, and clinical use of molindone is reviewed. Unanswered questions about the drug are addressed. Although molindone is reputed to have a short half-life (1.5 hours), clinical observations report a prolonged effect from a once-daily dose. Early in treatment, some patients show intolerance due to akathisia or extrapyramidal symptoms. This may be withdrawal dyskinesia due to discontinuation of another drug or an early adverse effect of molindone. Different effects on dopamine receptors have been described, but the significance of these properties for the development of tardive dyskinesia remains unclear.

The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

PubMed

Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

2016-01-01

Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p < 0.001). No interaction effect was found for the BDNF pathway with life stress in the associations with chronic pain presence and severity. This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

Adversity and psychosis: a 10-year prospective study investigating synergism between early and recent adversity in psychosis.

PubMed

Lataster, J; Myin-Germeys, I; Lieb, R; Wittchen, H-U; van Os, J

2012-05-01

Recent studies have suggested that early adverse events, such as childhood trauma, may promote enduring liability for psychosis whereas more recent adverse events may act as precipitants. Examination of these environmental dynamics, however, requires prospective studies in large samples. This study examines whether the association between recent adverse events and psychosis is moderated by exposure to early adversity. A random regional representative population sample of 3021 adolescents and young adults in Munich, Germany, was assessed three times over a period of up to 10 years, collecting information on sociodemographic factors, environmental exposures, and measures of psychopathology and associated clinical relevance. Evidence of statistical non-additivity between early adversity (two levels) and more recent adversity (four levels) was assessed in models of psychotic symptoms. Analyses were a priori corrected for age, gender, cannabis use, and urbanicity. Early and recent adversity were associated with each other (RR = 1.32, 95% CI 1.06-1.66; P = 0.014) and displayed statistical non-additivity at the highest level of exposure to recent adversity (χ(2) = 4.59; P = 0.032). The findings suggest that early adversity may impact on later expression of psychosis either by increasing exposure to later adversity and/or by rendering individuals more sensitive to later adversity if it is severe. © 2011 John Wiley & Sons A/S.

Social influences on bipolar affective disorders.

PubMed

Ramana, R; Bebbington, P

1995-07-01

The impact of psychosocial adversity on the onset and course of bipolar disorder has been assessed in studies that have relied on methods of eliciting life event histories and evaluating family atmosphere. The results of life event studies have been inconsistent, perhaps because the relationship between bipolar disorder and major stress is only pronounced in first or early episodes. If this is so, this phenomenon itself invites explanation, whether in social or biological terms. The two studies to data of family atmosphere suggest an association between high expressed emotion and relapse. The relationship between psychosocial stress and bipolar disorder requires further and more detailed research.

The natural history of substance use disorders.

PubMed

Sarvet, Aaron L; Hasin, Deborah

2016-07-01

Illicit drugs, alcohol, and tobacco use disorders contribute substantially to the global burden of disease. Knowledge about the major elements of the natural history of substance use disorders (incidence, remission, persistence, and relapse) is crucial to a broader understanding of the course and outcomes of substance use disorders. Prospective cohort studies in nonclinical samples indicate that externalizing psychopathology in earlier life, including early disordered substance use, delinquency, and personality disorders, are related to substance use disorders later in life and chronic course. Externalizing psychopathology may be initiated by early adverse experiences, for example, childhood maltreatment and stressful life events. After controlling for confounders, 'age at first use' as a causal factor for alcohol use disorder later in life and the 'drug substitution' hypothesis are not supported in general population data. Future research should focus on elaborating the causal framework that leads to the development and persistence of severe substance use disorders, with an emphasis on identifying modifiable factors for intervention by policy makers or health professionals. More research is needed on the natural history of substance use disorders in low-income and middle-income countries.

Putting the Barker Theory into the Future: Time to Act on Preventing Pediatric Obesity.

PubMed

Pietrobelli, Angelo; Agosti, Massimo; Zuccotti, Gianvincenzo

2016-11-17

Growth and development are key characteristics of childhood and sensitive markers of health and adequate nutrition. The first 1000 days of life-conception through 24 months of age-represent a fundamental period for development and thus the prevention of childhood obesity and its adverse consequences is mandatory. There are many growth drivers during this complex phase of life, such as nutrition, genetic and epigenetic factors, and hormonal regulation. The challenge thus involves maximizing the potential for normal growth without increasing the risk of associated disorders. The Mediterranean Nutrition Group (MeNu Group), a group of researchers of the Mediterranean Region, in this Special Issue titled "Prevent Obesity in the First 1000 Days", presented results that advanced the science of obesity risk factors in early life, coming both from animal model studies and studies in humans. In the future, early-life intervention designs for the prevention of pediatric obesity will need to look at different strategies, and the MeNu Group is available for guidance regarding an appropriate conceptual framework to accomplish either prevention or treatment strategies to tackle pediatric obesity.

Re-experiencing Violence across the Life Course: Histories of Childhood Maltreatment and Elder Abuse Victimization.

PubMed

Kong, Jooyoung; Easton, Scott D

2018-03-26

This study primarily examines the associations between histories of childhood maltreatment (i.e., neglect, emotional, physical, and sexual abuse) and elder abuse victimization and explores whether gender moderates the associations. We conducted a secondary data analysis of 5,968 older adults (mean age = 71 years) based on data from the Wisconsin Longitudinal Study (2010-2011). Using retrospective self-reports of childhood and current (past 12 months) victimization experiences, logistic regression analyses were conducted to estimate the effects of early-life adversities on the likelihood of elder abuse victimization. Results indicate that childhood emotional abuse and childhood sexual abuse were associated with greater risk of being abused as older adults, after controlling for childhood and adult background factors. We also found that the effect of childhood sexual abuse on elder abuse victimization was weaker for women than men. Findings suggest that the phenomenon of revictimization may occur not only in early and middle adulthood, but also in late life. To advance our understanding of victimization across the life course, future research on root causes of elder abuse should include histories of child abuse.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress.

PubMed

Engert, Veronika; Efanov, Simona I; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C

2010-11-01

In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic-pituitary-adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group.

Perceived early-life maternal care and the cortisol response to repeated psychosocial stress

PubMed Central

Engert, Veronika; Efanov, Simona I.; Dedovic, Katarina; Duchesne, Annie; Dagher, Alain; Pruessner, Jens C.

2010-01-01

Background In the past decade, a body of animal and human research has revealed a profound influence of early-life experiences, ranging from variations in parenting behaviour to severe adversity, on hypothalamic–pituitary–adrenal axis regulation in adulthood. In our own previous studies, we have shown how variations in early-life parental care influence the development of the hippocampus and modify the cortisol awakening response. Methods In the present study, we investigated the influence of early-life maternal care on cortisol, heart rate and subjective psychological responses to the repeated administration of a psychosocial laboratory stressor in a population of 63 healthy young adults. Low, medium and high early-life maternal care groups were identified using the Parental Bonding Instrument. Results Controlling for the effect of sex, we found an inverted u-shaped relation between increasing levels of maternal care and cortisol stress responsivity. Specifically, overall and stress-induced cortisol levels went from below normal in the low maternal care, to normal in the medium care, back to below normal in the high maternal care groups. We found no group differences with respect to heart rate and subjective psychological stress measures. Whereas low and high maternal care groups exhibited similarly low endocrine stress responses, their psychological profiles were opposed with increased levels of depression and anxiety and decreased self-esteem in the low care group. Limitations Sex was unequally distributed among maternal care groups, whereby the number of men with low maternal care was too small to allow introducing sex as a second between-group variable. Conclusion We discuss the potential significance of this dissociation between endocrine and psychological parameters with respect to stress vulnerability and resistance for each maternal care group. PMID:20964960

Does early-life income inequality predict self-reported health in later life? Evidence from the United States.

PubMed

Lillard, Dean R; Burkhauser, Richard V; Hahn, Markus H; Wilkins, Roger

2015-03-01

We investigate the association between adult health and the income inequality they experienced as children up to 80 years earlier. Our inequality data track shares of national income held by top percentiles from 1913 to 2009. We average those data over the same early-life years and merge them to individual data from the Panel Study of Income Dynamics data for 1984-2009. Controlling for demographic and economic factors, we find both men and women are statistically more likely to report poorer health if income was more unequally distributed during the first years of their lives. The association is robust to alternative specifications of income inequality and time trends and remains significant even when we control for differences in overall childhood health. Our results constitute prima facie evidence that adults' health may be adversely affected by the income inequality they experienced as children. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-Term Mortality Consequences of Childhood Family Context in Liaoning, China, 1749-1909

PubMed Central

Campbell, Cameron Dougall; Lee, James Z

2009-01-01

We examine the effects on adult and old age mortality of childhood living arrangements and other aspects of family context in early life. We focus on features of family context that have already been shown to be associated with infant or child mortality in historical and developing country populations. We apply discrete-time event-history analysis to longitudinal, individual-level household register data for a rural population in northeast China from the eighteenth and nineteenth centuries. Loss of a mother in childhood, a short preceding birth interval, and high maternal age were all associated with elevated mortality risks later in life. Such effects persist in a model with fixed effects that account for unobserved characteristics of the community and household. An important implication of these results is that in high mortality populations, features of early life family context that are associated with elevated infant and child mortality may also predict adverse mortality outcomes in adulthood. PMID:19278765

Developmental programming of cardiovascular disease by prenatal hypoxia.

PubMed

Giussani, D A; Davidge, S T

2013-10-01

It is now recognized that the quality of the fetal environment during early development is important in programming cardiovascular health and disease in later life. Fetal hypoxia is one of the most common consequences of complicated pregnancies worldwide. However, in contrast to the extensive research effort on pregnancy affected by maternal nutrition or maternal stress, the contribution of pregnancy affected by fetal chronic hypoxia to developmental programming is only recently becoming delineated and established. This review discusses the increasing body of evidence supporting the programming of cardiac susceptibility to ischaemia and reperfusion (I/R) injury, of endothelial dysfunction in peripheral resistance circulations, and of indices of the metabolic syndrome in adult offspring of hypoxic pregnancy. An additional focus of the review is the identification of plausible mechanisms and the implementation of maternal and early life interventions to protect against adverse programming.

Early nutrition programming of long-term health.

PubMed

Koletzko, Berthold; Brands, Brigitte; Poston, Lucilla; Godfrey, Keith; Demmelmair, Hans

2012-08-01

Increasing evidence from the EU Project EARNEST and many other investigators demonstrates that early nutrition and lifestyle have long-term effects on later health and the risk of common non-communicable diseases (known as 'developmental programming'). Because of the increasing public health importance and the transgenerational nature of the problem, obesity and associated disorders are the focus of the new EU funded project 'EarlyNutrition'. Currently, three key hypotheses have been defined: the fuel mediated 'in utero' hypothesis suggests that intrauterine exposure to an excess of fuels, most notably glucose, causes permanent changes of the fetus that lead to obesity in postnatal life; the accelerated postnatal weight gain hypothesis proposes an association between rapid weight gain in infancy and an increased risk of later obesity and adverse outcomes; and the mismatch hypothesis suggests that experiencing a developmental 'mismatch' between a sub-optimal perinatal and an obesogenic childhood environment is related to a particular predisposition to obesity and corresponding co-morbidities. Using existing cohort studies, ongoing and novel intervention studies and a basic science programme to investigate those key hypotheses, project EarlyNutrition will provide the scientific foundations for evidence-based recommendations for optimal nutrition considering long-term health outcomes, with a focus on obesity and related disorders. Scientific and technical expertise in placental biology, epigenetics and metabolomics will provide understanding at the cellular and molecular level of the relationships between early life nutritional status and the risk of later adiposity. This will help refine strategies for intervention in early life to prevent obesity.

Individual differences in early adolescents' latent trait cortisol: Interaction of early adversity and 5-HTTLPR.

PubMed

Chen, Frances R; Stroud, Catherine B; Vrshek-Schallhorn, Suzanne; Doane, Leah D; Granger, Douglas A

2017-10-01

The present study aimed to examine the interaction of 5-HTTLPR and early adversity on trait-like levels of cortisol. A community sample of 117 early adolescent girls (M age=12.39years) provided DNA samples for 5-HTTLPR genotyping, and saliva samples for assessing cortisol 3 times a day (waking, 30min post-waking, and bedtime) over a three-day period. Latent trait cortisol (LTC) was modeled using the first 2 samples of each day. Early adversity was assessed with objective contextual stress interviews with adolescents and their mothers. A significant 5-HTTLPR×early adversity interaction indicated that greater early adversity was associated with lower LTC levels, but only among individuals with either L/L or S/L genotype. Findings suggest that serotonergic genetic variation may influence the impact of early adversity on individual differences in HPA-axis regulation. Future research should explore whether this interaction contributes to the development of psychopathology through HPA axis functioning. Copyright © 2017 Elsevier B.V. All rights reserved.

Early life adversity and inflammation in African Americans and whites in the midlife in the United States survey.

PubMed

Slopen, Natalie; Lewis, Tené T; Gruenewald, Tara L; Mujahid, Mahasin S; Ryff, Carol D; Albert, Michelle A; Williams, David R

2010-09-01

To determine whether early life adversity (ELA) was predictive of inflammatory markers and to determine the consistency of these associations across racial groups. We analyzed data from 177 African Americans and 822 whites aged 35 to 86 years from two preliminary subsamples of the Midlife in the United States biomarker study. ELA was measured via retrospective self-report. We used multivariate linear regression models to examine the associations between ELA and C-reactive protein, interleukin-6, fibrinogen, endothelial leukocyte adhesion molecule-1, and soluble intercellular adhesion molecule-1, independent of age, gender, and medications. We extended race-stratified models to test three potential mechanisms for the observed associations. Significant interactions between ELA and race were observed for all five biomarkers. Models stratified by race revealed that ELA predicted higher levels of log interleukin-6, fibrinogen, endothelial leukocyte adhesion molecule-1, and soluble intercellular adhesion molecule-1 among African Americans (p < .05), but not among whites. Some, but not all, of these associations were attenuated after adjustment for health behaviors and body mass index, adult stressors, and depressive symptoms. ELA was predictive of high concentrations of inflammatory markers at midlife for African Americans, but not whites. This pattern may be explained by an accelerated course of age-related disease development for African Americans.

An exploration of addiction in adults experiencing early-life stress: a metasynthesis 1

PubMed Central

Teixeira, Carla Araujo Bastos; Lasiuk, Gerri; Barton, Sylvia; Fernandes, Maria Neyrian de Fatima; Gherardi-Donato, Edilaine Cristina da Silva

2017-01-01

ABSTRACT Objective: to review and synthesize qualitative research on the links between early-life stress and addiction behaviours in adulthood. Method: metasynthesis to review qualitative research findings based on procedures that outline how to identify themes or constructs across studies in a specific area. Comprehensive searches of multiple electronic databases were performed. The initial search yielded 1050 articles and the titles and abstracts were screened for inclusion based on predetermined criteria. Thirty-eight full text, peer-reviewed articles were retrieved and assessed by three independent reviewers. Twelve articles were eligible for full review and appraised using the Critical Appraisal Skills Programme (CASP) tools. Results: the findings revealed that clear associations exist between early-life stress and addictive behaviours in adulthood, such as between trauma in childhood, violence, and addictive behaviours. A common theme in the findings indicates that participants turn to addictive substances as a way of strategically coping with stressful childhood experiences, regardless of the harmful side effects or detrimental social outcomes. Conclusion: it can be inferred that addiction may be viewed as a way to deal with adversity in childhood and that there is an interrelationship between addiction, domestic violence and crime. PMID:29020127

Soy consumption and histopathologic markers in breast tissue using tissue microarrays.

PubMed

Maskarinec, Gertraud; Erber, Eva; Verheus, Martijn; Hernandez, Brenda Y; Killeen, Jeffrey; Cashin, Suzanne; Cline, J Mark

2009-01-01

This study examined the relation of soy intake with hormonal and proliferation markers in benign and malignant breast tissue using tissue microarrays (TMAs). TMAs with up to 4 malignant and 4 benign tissue samples for 268 breast cancer cases were constructed. Soy intake in early life and in adulthood was assessed by questionnaire. The TMAs were stained for estrogen receptor (ER) alpha, ERbeta, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2/neu), proliferating cell nuclear antigen (PCNA), and Ki-67 using standard immunohistochemical methods. Logistic regression was applied for statistical analysis. A higher percentage of women showed positive marker expression in malignant than in benign tissue. With one exception, HER2/neu, no significant associations between soy intake and pathologic markers were observed. Early life soy intake was associated with lower HER2/neu and PCNA staining of malignant tissue. In benign tissue, early life soy intake showed higher ER and PR expression, but no difference in proliferation markers. The results of this investigation provide some assurance that soy intake does not adversely affect markers of proliferation. TMAs were shown to be a useful tool for epidemiologic research.

Greater Caregiving Risk, Better Infant Memory Performance?

PubMed

Rifkin-Graboi, Anne; Quan, Jeffry; Richmond, Jenny; Goh, Shaun Kok Yew; Sim, Lit Wee; Chong, Yap Seng; Francois-Bureau, Jean; Chen, Helen; Qiu, Anqi

2018-04-16

Poor early life care often relates to cognitive difficulties. However, newer work suggests that in early-life, adversity may associate with enhanced or accelerated neurodevelopment. We examine associations between postnatal caregiving risks (i.e., higher self-reported postnatal-anxiety and lower observed maternal sensitivity) and infant relational memory (i.e. via deferred imitation and relational binding). Using subsamples of 67-181 infants (aged 433-477 post-conceptual days, or roughly five to seven months since birth) taking part in the GUSTO study, we found such postnatal caregiving risk significantly predictive of "better" performance on a relational binding task following a brief delay, after Bonferroni adjustments. Subsequent analyses suggest that the association between memory and these risks may specifically be apparent amongst infants spending at least 50% of their waking hours in the presence of their mothers. Our findings echo neuroimaging research concerning similar risk exposure and larger infant hippocampal volume, and likewise underscore the importance of considering developmental context in understanding early life experience. With this in mind, these findings caution against the use of cognitive outcomes as indices of experienced risk. This article is protected by copyright. All rights reserved. © 2018 Wiley Periodicals, Inc.

Brain metabolic alterations in mice subjected to postnatal traumatic stress and in their offspring.

PubMed

Gapp, Katharina; Corcoba, Alberto; van Steenwyk, Gretchen; Mansuy, Isabelle M; Duarte, João Mn

2017-07-01

Adverse environmental and social conditions early in life have a strong impact on health. They are major risk factors for mental diseases in adulthood and, in some cases, their effects can be transmitted across generations. The consequences of detrimental stress conditions on brain metabolism across generations are not well known. Using high-field (14.1 T) magnetic resonance spectroscopy, we investigated the neurochemical profile of adult male mice exposed to traumatic stress in early postnatal life and of their offspring, and of undisturbed control mice. We found that, relative to controls, early life stress-exposed mice have metabolic alterations consistent with neuronal dysfunction, including reduced concentration of N-acetylaspartate, glutamate and γ-aminobutyrate, in the prefrontal cortex in basal conditions. Their offspring have normal neurochemical profiles in basal conditions. Remarkably, when challenged by an acute cold swim stress, the offspring has attenuated metabolic responses in the prefrontal cortex, hippocampus and striatum. In particular, the expected stress-induced reduction in the concentration of N-acetylaspartate, a putative marker of neuronal health, was prevented in the cortex and hippocampus. These findings suggest that paternal trauma can confer beneficial brain metabolism adaptations to acute stress in the offspring.

Distinct contributions of adverse childhood experiences and resilience resources: a cohort analysis of adult physical and mental health.

PubMed

Logan-Greene, Patricia; Green, Sara; Nurius, Paula S; Longhi, Dario

2014-01-01

Although evidence is rapidly amassing as to the damaging potential of early life adversities on physical and mental health, as yet few investigations provide comparative snapshots of these patterns across adulthood. This population-based study addresses this gap, examining the relationship of adverse childhood experiences (ACEs) to physical and mental health within a representative sample (n = 19,333) of adults, comparing the prevalence and explanatory strength of ACEs among four birth cohorts spanning ages 18-79. This assessment accounts for demographic and socioeconomic factors, as well as both direct and moderating effects of resilience resources (social/emotional support, life satisfaction, and sleep quality). Findings demonstrate (1) increasing trends of reported ACEs across younger cohorts, including time period shifts such as more prevalent family incarceration, substance abuse, and divorce, (2) significant bivariate as well as independent associations of ACEs with poor health within every cohort, controlling for multiple covariates (increasing trends in older age for physical health), and (3) robust patterns wherein resilience resources moderated ACEs, indicating buffering pathways that sustained into old age. Theoretical and practice implications for health professionals are discussed.

Childhood Exposure to Adversity and Risk of Substance-Use Disorder in Two American Indian Populations: The Meditational Role of Early Substance-Use Initiation*

PubMed Central

Whitesell, Nancy Rumbaugh; Beals, Janette; Mitchell, Christina M.; Manson, Spero M.; Turner, R. Jay

2009-01-01

Objective: We examined the relationship of childhood exposure to adversity and risk of substance-use disorder in two culturally distinct American Indian reservation communities, exploring both the role of early initiation of substance use in mediating this relationship and variation in risk across types of adversity exposure. Method: The American Indian Service Utilization, Psychiatric Epidemiology, Risk and Protective Factors Project provided data from 2,927 American Indians on the occurrence and age at onset of adversities, substance use, and substance-use-disorder symptoms. Results: The risk of substance-use disorder associated with early adversity was explained partially by early initiation of substance use. Three types of adversity (major childhood events, traumas, and witnessed violence) were associated with early onset of substance use and increased risk of substance-use disorder. Gender and tribe were also related to variation in both early substance use and substance-use disorder. Conclusions: Early exposure to adverse events was associated with early substance use and the subsequent development of substance-use disorders among American Indians. Public health initiatives targeting substance use and substance-use disorders in American Indian communities should include efforts to help children in these communities cope with adversities they encounter. PMID:19895776

Adverse Childhood Experiences and the Health of University Students in Eight Provinces of Vietnam.

PubMed

Tran, Quynh Anh; Dunne, Michael P; Vo, Thang Van; Luu, Ngoc Hoat

2015-11-01

Recent systematic reviews have emphasized the need for more research into the health and social impacts of adverse childhood experiences (ACEs) in the Asia-Pacific region. This cross-sectional study was conducted with 2099 young adult students in 8 medical universities throughout Vietnam. An anonymous, self-report questionnaire included the World Health Organization ACE-International Questionnaire and standardized measures of mental and physical health. Three quarters (76%) of the students reported at least one exposure to ACEs; 21% had 4 or more ACEs. The most commonly reported adversities were emotional abuse, physical abuse, and witnessing a household member being treated violently (42.3%, 39.9%, and 34.6%, respectively). Co-occurrence of ACEs had dose-response relationships with poor mental health, suicidal ideation, and low physical health-related quality of life. This first multisite study of ACEs among Vietnamese university students provided evidence that childhood adversity is common and is significantly linked with impaired health and well-being into the early adult years. © 2015 APJPH.

Early intake of long-chain polyunsaturated fatty acids preserves brain structure and function in diet-induced obesity.

PubMed

Arnoldussen, Ilse A C; Zerbi, Valerio; Wiesmann, Maximilian; Noordman, Rikko H J; Bolijn, Simone; Mutsaers, Martina P C; Dederen, Pieter J W C; Kleemann, Robert; Kooistra, Teake; van Tol, Eric A F; Gross, Gabriele; Schoemaker, Marieke H; Heerschap, Arend; Wielinga, Peter Y; Kiliaan, Amanda J

2016-04-01

Worldwide, the incidence of obesity is increasing at an alarming rate, and the number of children with obesity is especially worrisome. These developments raise concerns about the physical, psychosocial and cognitive consequences of obesity. It was shown that early dietary intake of arachidonic acid (ARA) and docosahexaenoic acid (DHA) can reduce the detrimental effects of later obesogenic feeding on lipid metabolism and adipogenesis in an animal model of mild obesity. In the present study, the effects of early dietary ARA and DHA on cognition and brain structure were examined in mildly obesogenic ApoE*3Leiden mouse model. We used cognitive tests and neuroimaging during early and later life. During their early development after weaning (4-13weeks of age), mice were fed a chow diet or ARA and DHA diet for 8 weeks and then switched to a high-fat and high-carbohydrate (HFHC) diet for 12weeks (14-26weeks of age). An HFHC-diet led to increased energy storage in white adipose tissue, increased cholesterol levels, decreased triglycerides levels, increased cerebral blood flow and decreased functional connectivity between brain regions as well as cerebrovascular and gray matter integrity. ARA and DHA intake reduced the HFHC-diet-induced increase in body weight, attenuated plasma triglycerides levels and improved cerebrovasculature, gray matter integrity and functional connectivity in later life. In conclusion, an HFHC diet causes adverse structural brain and metabolic adaptations, most of which can be averted by dietary ARA and DHA intake early in life supporting metabolic flexibility and cerebral integrity later in life. Copyright © 2016 Elsevier Inc. All rights reserved.

The Association Between Maternal Early Life Forced Sexual Intercourse and Offspring Birth Weight: The Role of Socioeconomic Status.

PubMed

Gavin, Amelia R; Morris, Julia

2017-05-01

This study utilizes a life-course framework to investigate whether maternal early life forced sexual intercourse operates in conjunction with health behaviors during adolescence, young adulthood, and the prenatal period to influence offspring birth weight. Using data from the 1994-2009 National Longitudinal Study of Adolescent Health (Add Health), we examined whether early life forced sexual intercourse predicted offspring birth weight through a mediated pathway, including depressive symptoms, substance use, and prenatal cigarette smoking. We stratify our analysis by socioeconomic status (SES) to determine whether the proposed pathways operate similarly, or differently, according to SES. Our findings suggest that the pathways through which forced sexual intercourse affects offspring birth weight differ by SES. Among middle-to-high SES women, we found a mediated pathway linking forced sexual intercourse to offspring birth weight with prenatal cigarette smoking predicting lower offspring birth weight. Among low SES women, however, we did not find a mediated pathway linking forced sexual intercourse to birth weight. Findings suggest that prenatal cigarette smoking was not a mechanism of influence in the pathway between maternal early life forced sexual intercourse and offspring birth weight for low SES women. Our findings suggest that forced sexual intercourse may influence infant birth weight in the next generation. Infants born with a low birth weight are at increased risk for a myriad of adverse outcomes across the life-course. Study results suggest the importance of interventions designed to reduce behavioral risks and to support health promoting behaviors among survivors in the short term, in an effort to prevent long-term consequences among later-born offspring.

Childhood adversity, early-onset depressive/anxiety disorders, and adult-onset asthma.

PubMed

Scott, Kate M; Von Korff, Michael; Alonso, Jordi; Angermeyer, Matthias C; Benjet, Corina; Bruffaerts, Ronny; de Girolamo, Giovanni; Haro, Josep Maria; Kessler, Ronald C; Kovess, Viviane; Ono, Yutaka; Ormel, Johan; Posada-Villa, José

2008-11-01

To investigate a) whether childhood adversity predicts adult-onset asthma; b) whether early-onset depressive/anxiety disorders predict adult-onset asthma; and c) whether childhood adversity and early-onset depressive/anxiety disorders predict adult-onset asthma independently of each other. Previous research has suggested, but not established, that childhood adversity may predict adult-onset asthma and, moreover, that the association between mental disorders and asthma may be a function of shared risk factors, such as childhood adversity. Ten cross-sectional population surveys of household-residing adults (>18 years, n = 18,303) assessed mental disorders with the Composite International Diagnostic Interview (CIDI 3.0) as part of the World Mental Health surveys. Assessment of a range of childhood family adversities was included. Asthma was ascertained by self-report of lifetime diagnosis and age of diagnosis. Survival analyses calculated hazard ratios (HRs) for risk of adult-onset (>age 20 years) asthma as a function of number and type of childhood adversities and early-onset (

Persistent carry-over effects of planktonic exposure to ocean acidification in the Olympia oyster.

PubMed

Hettinger, Annaliese; Sanford, Eric; Hill, Tessa M; Russell, Ann D; Sato, Kirk N S; Hoey, Jennifer; Forsch, Margaux; Page, Heather N; Gaylord, Brian

2012-12-01

Predicting impacts of global environmental change is challenging due to the complex life cycles that characterize many terrestrial and aquatic taxa. Different life stages often interact with the physical environment in distinct ways, and a growing body of work suggests that stresses experienced during one life stage can "carry over" to influence subsequent stages. Assessments of population responses to environmental perturbation must therefore consider how effects might propagate across life-history transitions. We investigated consequences of ocean acidification (decreased pH and carbonate saturation) for early life stages of the Olympia oyster (Ostrea lurida), a foundation species in estuaries along the Pacific coast of North America. We reared oysters at three levels of seawater pH, including a control (8.0) and two additional levels (7.9 and 7.8). Oysters were cultured through their planktonic larval period to metamorphosis and into early juvenile life. Larvae reared under pH 7.8 exhibited a 15% decrease in larval shell growth rate, and a 7% decrease in shell area at settlement, compared to larvae reared under control conditions. Impacts were even more pronounced a week after settlement, with juveniles that had been reared as larvae under reduced pH exhibiting a 41% decrease in shell growth rate. Importantly, the latter effect arose regardless of the pH level the oysters experienced as juveniles, indicating a strong carry-over effect from the larval phase. Adverse impacts of early exposure to low pH persisted for at least 1.5 months after juveniles were transferred to a common environment. Overall, our results suggest that a stringent focus on a single phase of the life cycle (e.g., one perceived as the "weakest link") may neglect critical impacts that can be transferred across life stages in taxa with complex life histories.

Early Adverse Caregiving Experiences and Preschoolers' Current Attachment Affect Brain Responses during Facial Familiarity Processing: An ERP Study.

PubMed

Kungl, Melanie T; Bovenschen, Ina; Spangler, Gottfried

2017-01-01

When being placed into more benign environments like foster care, children from adverse rearing backgrounds are capable of forming attachment relationships to new caregivers within the first year of placement, while certain problematic social behaviors appear to be more persistent. Assuming that early averse experiences shape neural circuits underlying social behavior, neurophysiological studies on individual differences in early social-information processing have great informative value. More precisely, ERP studies have repeatedly shown face processing to be sensitive to experience especially regarding the caregiving background. However, studies on effects of early adverse caregiving experiences are restricted to children with a history of institutionalization. Also, no study has investigated effects of attachment security as a marker of the quality of the caregiver-child relationship. Thus, the current study asks how adverse caregiving experiences and attachment security to (new) caregivers affect early- and mid-latency ERPs sensitive to facial familiarity processing. Therefore, pre-school aged foster children during their second year within the foster home were compared to an age matched control group. Attachment was assessed using the AQS and neurophysiological data was collected during a passive viewing task presenting (foster) mother and stranger faces. Foster children were comparable to the control group with regard to attachment security. On a neurophysiological level, however, the foster group showed dampened N170 amplitudes for both face types. In both foster and control children, dampened N170 amplitudes were also found for stranger as compared to (foster) mother faces, and, for insecurely attached children as compared to securely attached children. This neural pattern may be viewed as a result of poorer social interactions earlier in life. Still, there was no effect on P1 amplitudes. Indicating heightened attentional processing, Nc amplitude responses to stranger faces were found to be enhanced in foster as compared to control children. Also, insecurely attached children allocated more attentional resources for the neural processing of mother faces. The study further confirms that early brain development is highly sensitive to the quality of caregiving. The findings are also relevant from a developmental perspective as miswiring of neural circuits may possibly play a critical role in children's psycho-social adjustment.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection.

PubMed

Elwenspoek, Martha M C; Sias, Krystel; Hengesch, Xenia; Schaan, Violetta K; Leenen, Fleur A D; Adams, Philipp; Mériaux, Sophie B; Schmitz, Stephanie; Bonnemberger, Fanny; Ewen, Anouk; Schächinger, Hartmut; Vögele, Claus; Muller, Claude P; Turner, Jonathan D

2017-01-01

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n  = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n  = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57 + ) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts.

T Cell Immunosenescence after Early Life Adversity: Association with Cytomegalovirus Infection

PubMed Central

Elwenspoek, Martha M. C.; Sias, Krystel; Hengesch, Xenia; Schaan, Violetta K.; Leenen, Fleur A. D.; Adams, Philipp; Mériaux, Sophie B.; Schmitz, Stephanie; Bonnemberger, Fanny; Ewen, Anouk; Schächinger, Hartmut; Vögele, Claus; Muller, Claude P.; Turner, Jonathan D.

2017-01-01

Early life adversity (ELA) increases the risk for multiple age-related diseases, such as diabetes type 2 and cardiovascular disease. As prevalence is high, ELA poses a major and global public health problem. Immunosenescence, or aging of the immune system, has been proposed to underlie the association between ELA and long-term health consequences. However, it is unclear what drives ELA-associated immunosenescence and which cells are primarily affected. We investigated different biomarkers of immunosenescence in a healthy subset of the EpiPath cohort. Participants were either parent-reared (Ctrl, n = 59) or had experienced separation from their parents in early childhood and were subsequently adopted (ELA, n = 18). No difference was observed in telomere length or in methylation levels of age-related CpGs in whole blood, containing a heterogeneous mixture of immune cells. However, when specifically investigating T cells, we found a higher expression of senescence markers (CD57) in ELA. In addition, senescent T cells (CD57+) in ELA had an increased cytolytic potential compared to senescent cells in controls. With a mediation analysis we demonstrated that cytomegalovirus (CMV) infection, which is an important driving force of immunosenescence, largely accounted for elevated CD57 expression observed in ELA. Leukocyte telomere length may obscure cell-specific immunosenescence; here, we demonstrated that the use of cell surface markers of senescence can be more informative. Our data suggest that ELA may increase the risk of CMV infection in early childhood, thereby mediating the effect of ELA on T cell-specific immunosenescence. Thus, future studies should include CMV as a confounder or selectively investigate CMV seronegative cohorts. PMID:29089944

Early complications, pain, and quality of life after reconstructive surgery for abdominal rectus muscle diastasis: a 3-month follow-up.

PubMed

Emanuelsson, P; Gunnarsson, U; Strigård, K; Stark, B

2014-08-01

The aim of this study was to evaluate early complications following retromuscular mesh repair with those after dual layer suture of the anterior rectus sheath in a randomised controlled clinical trial for abdominal rectus muscle diastasis (ARD). Patients with an ARD wider than 3 cm and clinical symptoms related to the ARD were included in a prospective randomised study. They were assigned to either retromuscular inset of a lightweight polypropylene mesh or to dual closure of the anterior rectus fascia using Quill self-locking technology. All patients completed a validated questionnaire for pain assessment (Ventral Hernia Pain Questionnaire, VHPQ) and for quality of life (SF36) prior to and 3 months after surgery. The most frequently seen adverse event was minor wound infection. Of the patients, 14/57 had a superficial wound infection; five related to Quill and nine to mesh repair. No deep wound infections were reported. Patient rating for subjective muscular improvement postoperatively was better in the mesh technique group with a mean of 6.9 (range 0-10) compared to a mean of 4.8 (range 0-10) in the Quill group (p=0.01). The pre- and post-operative SF36 scores improved in both groups. There was no significant difference between the two surgical techniques in terms of early complications and perceived pain at the 3-month follow-up. Both techniques may be considered equally reliable for ARD repair in terms of adverse outcomes during the early postoperative phase, even though patients operated with a mesh experienced better improvement in muscular strength. ClinicalTrial.gov: 2009/227-31/3/PE/96. Copyright © 2014 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Early origins of inflammation: An examination of prenatal and childhood social adversity in a prospective cohort study.

PubMed

Slopen, Natalie; Loucks, Eric B; Appleton, Allison A; Kawachi, Ichiro; Kubzansky, Laura D; Non, Amy L; Buka, Stephen; Gilman, Stephen E

2015-01-01

Children exposed to social adversity carry a greater risk of poor physical and mental health into adulthood. This increased risk is thought to be due, in part, to inflammatory processes associated with early adversity that contribute to the etiology of many adult illnesses. The current study asks whether aspects of the prenatal social environment are associated with levels of inflammation in adulthood, and whether prenatal and childhood adversity both contribute to adult inflammation. We examined associations of prenatal and childhood adversity assessed through direct interviews of participants in the Collaborative Perinatal Project between 1959 and 1974 with blood levels of C-reactive protein in 355 offspring interviewed in adulthood (mean age=42.2 years). Linear and quantile regression models were used to estimate the effects of prenatal adversity and childhood adversity on adult inflammation, adjusting for age, sex, and race and other potential confounders. In separate linear regression models, high levels of prenatal and childhood adversity were associated with higher CRP in adulthood. When prenatal and childhood adversity were analyzed together, our results support the presence of an effect of prenatal adversity on (log) CRP level in adulthood (β=0.73, 95% CI: 0.26, 1.20) that is independent of childhood adversity and potential confounding factors including maternal health conditions reported during pregnancy. Supplemental analyses revealed similar findings using quantile regression models and logistic regression models that used a clinically-relevant CRP threshold (>3mg/L). In a fully-adjusted model that included childhood adversity, high prenatal adversity was associated with a 3-fold elevated odds (95% CI: 1.15, 8.02) of having a CRP level in adulthood that indicates high risk of cardiovascular disease. Social adversity during the prenatal period is a risk factor for elevated inflammation in adulthood independent of adversities during childhood. This evidence is consistent with studies demonstrating that adverse exposures in the maternal environment during gestation have lasting effects on development of the immune system. If these results reflect causal associations, they suggest that interventions to improve the social and environmental conditions of pregnancy would promote health over the life course. It remains necessary to identify the mechanisms that link maternal conditions during pregnancy to the development of fetal immune and other systems involved in adaptation to environmental stressors. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term changes in cognitive bias and coping response as a result of chronic unpredictable stress during adolescence.

PubMed

Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

2013-01-01

Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. Aversive experiences during this time might, therefore, be expected to generate long-term consequences for the adult phenotype. Here we investigated the long-term effects of exposure to chronic unpredictable stress during adolescence on adult decision-making, coping response, cognitive bias, and exploratory behavior in rats. Rats exposed to chronic unpredictable stress (e.g., isolation, crowding, cage tilt) were compared to control animals that were maintained in standard, predictable conditions throughout development. Unpredictable stress during adolescence resulted in a suite of long-term behavioral and cognitive changes including a negative cognitive bias [F (1, 12) = 5.000, P < 0.05], altered coping response [T (1, 14) = 2.216, P = 0.04], and accelerated decision-making [T (1, 14) = 3.245, P = 0.01]. Exposure to chronic stress during adolescence also caused a short-term increase in boldness behaviors; in a novel object test 15 days after the last stressor, animals exposed to chronic unpredictable stress had decreased latencies to leave a familiar shelter and approach a novel object [T (1, 14) = 2.240, P = 0.04; T (1, 14) = 2.419, P = 0.03, respectively]. The results showed that stress during adolescence has long-term impacts on behavior and cognition that affect the interpretation of ambiguous stimuli, behavioral response to adverse events, and how animals make decisions.

High novelty-seeking rats are resilient to negative physiological effects of the early life stress.

PubMed

Clinton, Sarah M; Watson, Stanley J; Akil, Huda

2014-01-01

Exposure to early life stress dramatically impacts adult behavior, physiology, and neuroendocrine function. Using rats bred for novelty-seeking differences and known to display divergent anxiety, depression, and stress vulnerability, we examined the interaction between early life adversity and genetic predisposition for high- versus low-emotional reactivity. Thus, bred Low Novelty Responder (bLR) rats, which naturally exhibit high anxiety- and depression-like behavior, and bred High Novelty Responder (bHR) rats, which show low anxiety/depression together with elevated aggression, impulsivity, and addictive behavior, were subjected to daily 3 h maternal separation (MS) stress postnatal days 1-14. We hypothesized that MS stress would differentially impact adult bHR/bLR behavior, physiology (stress-induced defecation), and neuroendocrine reactivity. While MS stress did not impact bHR and bLR anxiety-like behavior in the open field test and elevated plus maze, it exacerbated bLRs' already high physiological response to stress - stress-induced defecation. In both tests, MS bLR adult offspring showed exaggerated stress-induced defecation compared to bLR controls while bHR offspring were unaffected. MS also selectively impacted bLRs' (but not bHRs') neuroendocrine stress reactivity, producing an exaggerated corticosterone acute stress response in MS bLR versus control bLR rats. These findings highlight how genetic predisposition shapes individuals' response to early life stress. Future work will explore neural mechanisms underlying the distinct behavioral and neuroendocrine consequences of MS in bHR/bLR animals.

Interactions between Early Life Stress, Nucleus Accumbens MeCP2 Expression, and Methamphetamine Self-Administration in Male Rats

PubMed Central

Lewis, Candace R; Bastle, Ryan M; Manning, Tawny B; Himes, Sarah M; Fennig, Paulette; Conrad, Phoebe R; Colwell, Jenna; Pagni, Broc A; Hess, Lyndsay A; Matekel, Caitlin G; Newbern, Jason M; Olive, M Foster

2016-01-01

Early life stress (ELS) is highly related to the development of psychiatric illnesses in adulthood, including substance use disorders. A recent body of literature suggests that long-lasting changes in the epigenome may be a mechanism by which experiences early in life can alter neurobiological and behavioral phenotypes in adulthood. In this study, we replicate our previous findings that ELS, in the form of prolonged maternal separation, increases adult methamphetamine self-administration (SA) in male rats as compared with handled controls. In addition, we show new evidence that both ELS and methamphetamine SA alter the expression of the epigenetic regulator methyl CpG-binding protein 2 (MeCP2) in key brain reward regions, particularly in the nucleus accumbens (NAc) core. In turn, viral-mediated knockdown of MeCP2 expression in the NAc core reduces methamphetamine SA, as well as saccharin intake. Furthermore, NAc core MeCP2 knockdown reduces methamphetamine, but not saccharin, SA on a progressive ratio schedule of reinforcement. These data suggest that NAc core MeCP2 may be recruited by both ELS and methamphetamine SA and promote the development of certain aspects of drug abuse-related behavior. Taken together, functional interactions between ELS, methamphetamine SA, and the expression of MeCP2 in the NAc may represent novel mechanisms that can ultimately be targeted for intervention in individuals with adverse early life experiences who are at risk for developing substance use disorders. PMID:27312406

INVESTIGATING ALTERNATIVES TO THE FISH EARLY-LIFE STAGE TEST: A STRATEGY FOR DISCOVERING AND ANNOTATING ADVERSE OUTCOME PATHWAYS FOR EARLY FISH DEVELOPMENT

PubMed Central

Villeneuve, Daniel; Volz, David C; Embry, Michelle R; Ankley, Gerald T; Belanger, Scott E; Léonard, Marc; Schirmer, Kristin; Tanguay, Robert; Truong, Lisa; Wehmas, Leah

2014-01-01

The fish early-life stage (FELS) test (Organisation for Economic Co-operation and Development [OECD] test guideline 210) is the primary test used internationally to estimate chronic fish toxicity in support of ecological risk assessments and chemical management programs. As part of an ongoing effort to develop efficient and cost-effective alternatives to the FELS test, there is a need to identify and describe potential adverse outcome pathways (AOPs) relevant to FELS toxicity. To support this endeavor, the authors outline and illustrate an overall strategy for the discovery and annotation of FELS AOPs. Key events represented by major developmental landmarks were organized into a preliminary conceptual model of fish development. Using swim bladder inflation as an example, a weight-of-evidence–based approach was used to support linkage of key molecular initiating events to adverse phenotypic outcomes and reduced young-of-year survival. Based on an iterative approach, the feasibility of using key events as the foundation for expanding a network of plausible linkages and AOP knowledge was explored and, in the process, important knowledge gaps were identified. Given the scope and scale of the task, prioritization of AOP development was recommended and key research objectives were defined relative to factors such as current animal-use restrictions in the European Union and increased demands for fish toxicity data in chemical management programs globally. The example and strategy described are intended to guide collective efforts to define FELS-related AOPs and develop resource-efficient predictive assays that address the toxicological domain of the OECD 210 test. Environ Toxicol Chem 2014;33:158–169. © 2013 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals, Inc. on behalf of SETAC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. PMID:24115264

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

PubMed Central

Unternaehrer, Eva; Bolten, Margarete; Nast, Irina; Staehli, Simon; Meyer, Andrea H.; Dempster, Emma; Hellhammer, Dirk H.; Lieb, Roselind

2016-01-01

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007–10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1–3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment. PMID:27107296

Milk--the promoter of chronic Western diseases.

PubMed

Melnik, Bodo C

2009-06-01

Common chronic diseases of Western societies, such as coronary heart disease, diabetes mellitus, cancer, hypertension, obesity, dementia, and allergic diseases are significantly influenced by dietary habits. Cow's milk and dairy products are nutritional staples in most Western societies. Milk and dairy product consumption is recommended by most nutritional societies because of their beneficial effects for calcium uptake and bone mineralization and as a source of valuable protein. However, the adverse long-term effects of milk and milk protein consumption on human health have been neglected. A hypothesis is presented, showing for the first time that milk protein consumption is an essential adverse environmental factor promoting most chronic diseases of Western societies. Milk protein consumption induces postprandial hyperinsulinaemia and shifts the growth hormone/insulin-like growth factor-1 (IGF-1) axis to permanently increased IGF-1 serum levels. Insulin/IGF-1 signalling is involved in the regulation of fetal growth, T-cell maturation in the thymus, linear growth, pathogenesis of acne, atherosclerosis, diabetes mellitus, obesity, cancer and neurodegenerative diseases, thus affecting most chronic diseases of Western societies. Of special concern is the possibility that milk intake during pregnancy adversely affects the early fetal programming of the IGF-1 axis which will influence health risks later in life. An accumulated body of evidence for the adverse effects of cow's milk consumption from fetal life to childhood, adolescence, adulthood and senescence will be provided which strengthens the presented hypothesis.

Social Origins of Developmental Risk for Mental and Physical Illness.

PubMed

Cameron, Judy L; Eagleson, Kathie L; Fox, Nathan A; Hensch, Takao K; Levitt, Pat

2017-11-08

Adversity in early childhood exerts an enduring impact on mental and physical health, academic achievement, lifetime productivity, and the probability of interfacing with the criminal justice system. More science is needed to understand how the brain is affected by early life stress (ELS), which produces excessive activation of stress response systems broadly throughout the child's body (toxic stress). Our research examines the importance of sex, timing and type of stress exposure, and critical periods for intervention in various brain systems across species. Neglect (the absence of sensitive and responsive caregiving) or disrupted interaction with offspring induces robust, lasting consequences in mice, monkeys, and humans. Complementary assessment of internalizing disorders and brain imaging in children suggests that early adversity can interfere with white matter development in key brain regions, which may increase risk for emotional difficulties in the long term. Neural circuits that are most plastic during ELS exposure in monkeys sustain the greatest change in gene expression, offering a mechanism whereby stress timing might lead to markedly different long-term behaviors. Rodent models reveal that disrupted maternal-infant interactions yield metabolic and behavioral outcomes often differing by sex. Moreover, ELS may further accelerate or delay critical periods of development, which reflect GABA circuit maturation, BDNF, and circadian Clock genes. Such factors are associated with several mental disorders and may contribute to a premature closure of plastic windows for intervention following ELS. Together, complementary cross-species studies are elucidating principles of adaptation to adversity in early childhood with molecular, cellular, and whole organism resolution. Copyright © 2017 the authors 0270-6474/17/3710783-09$15.00/0.

More than jobs and houses: mental health, quality of life and the perceptions of locality in an area undergoing urban regeneration.

PubMed

Rogers, Anne; Huxley, Peter; Evans, Sherrill; Gately, Claire

2008-05-01

Urban regeneration initiatives are considered to be one means of making a contribution to improving people's quality of life and mental health. This paper considers the relationship between lay perceptions of locality adversity, mental health and social capital in an area undergoing urban regeneration. Using qualitative methods as part of a larger multi-method study, perceptions of material, and non-material aspects of the locality and the way in which people vulnerable to mental health problems coped with living in adversity were identified as being more highly valued than intended or actual changes to structural elements such as the provision of housing or employment. Themes derived from narrative accounts included concerns about the absence of social control in the locality, the reputation of the area, a lack of faith in local agencies to make changes considered important to local residents, a reliance on personal coping strategies to manage adversity and perceived threats to mental health which reinforced a sense of social isolation. We suggest these elements are implicated in restricting opportunities and enhancing feelings of 'entrapment' contributing to low levels of local collective efficacy. The gap between social capital capacity at an individual level and links with collective community resources may in part have accounted for the absence of improvements in mental health during the early life of the urban regeneration initiative. In order to enhance quality of life or mental health, agencies involved in urban initiatives need as a basic minimum to promote security, increase leisure opportunities, and improve the image of the locality.

Exercise deficit disorder in youth: play now or pay later.

PubMed

Faigenbaum, Avery D; Myer, Gregory D

2012-01-01

Although the benefits of regular physical activity are widely acknowledged, recent epidemiological findings indicate that a growing number of youth are not as active as they should be. The impact of a sedentary lifestyle during childhood and adolescence on lifelong pathological processes and associated health care costs has created a need for immediate action to manage, if not prevent, unhealthy behaviors during this vulnerable period of life. The concept of identifying children with exercise deficit disorder early in life and prescribing effective exercise interventions to prevent the cascade of adverse health outcomes later in life is needed to raise public awareness, focus on primary prevention, and impact the collective behaviors of health care providers, government officials, school administrators, public health agencies, and insurance companies.

School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5 Year Follow-Up From The Infant Development, Environment, and Lifestyle (IDEAL) Study

PubMed Central

Eze, Nwando; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Arria, Amelia; Huestis, Marilyn A.; Della Grotta, Sheri A; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

2016-01-01

Objective To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years, and the extent to which early adversity mediated this relationship. Study design The multicenter, longitudinal IDEAL study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n= 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5 year follow-up, 290 children with complete Child Behavior Checklist (CBCL) data and an early adversity index score were available for analysis (n=146 exposed). Results PME was significantly associated with an increased early adversity index score (P<0.001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P<0.05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant. Conclusion Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems. PMID:26781836

School-Aged Outcomes following Prenatal Methamphetamine Exposure: 7.5-Year Follow-Up from the Infant Development, Environment, and Lifestyle Study.

PubMed

Eze, Nwando; Smith, Lynne M; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Arria, Amelia; Huestis, Marilyn A; Della Grotta, Sheri A; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

2016-03-01

To assess the relationship between prenatal methamphetamine exposure (PME) and behavior problems at age 7.5 years and the extent to which early adversity mediated this relationship. The multicenter, longitudinal Infant Development, Environment, and Lifestyle study enrolled 412 mother-infant pairs at 4 sites. Methamphetamine-exposed participants (n = 204) were identified by self-report and/or gas chromatography/mass spectrometry confirmation of amphetamine and metabolites in infant meconium. Matched participants (n = 208) denied methamphetamine use and had a negative meconium screen. At the 7.5-year follow-up, 290 children with complete Child Behavior Checklist data and an early adversity index score were available for analysis (n = 146 exposed). PME was significantly associated with an increased early adversity index score (P < .001) and with increased externalizing, rule-breaking behavior, and aggressive behavior (P < .05). Early adversity was also associated with higher externalizing behavior scores. Early adversity significantly mediated the relationship between PME and behavioral problems. After adjusting the mediation model for sex, prenatal tobacco, alcohol, and marijuana exposures, and study site, the association of PME with early adversity remained significant. Though PME is associated with behavioral problems, early adversity may be a strong determinant of behavioral outcome for children exposed to methamphetamine in utero. Early adversity significantly mediated the relationship between PME and behavioral problems. Copyright © 2016 Elsevier Inc. All rights reserved.

Ambient and household air pollution: complex triggers of disease

PubMed Central

Farmer, Stephen A.; Nelin, Timothy D.; Falvo, Michael J.

2014-01-01

Concentrations of outdoor air pollution are on the rise, particularly due to rapid urbanization worldwide. Alternatively, poor ventilation, cigarette smoke, and other toxic chemicals contribute to rising concentrations of indoor air pollution. The World Health Organization recently reported that deaths attributable to indoor and outdoor air pollutant exposure are more than double what was originally documented. Epidemiological, clinical, and animal data have demonstrated a clear connection between rising concentrations of air pollution (both indoor and outdoor) and a host of adverse health effects. During the past five years, animal, clinical, and epidemiological studies have explored the adverse health effects associated with exposure to both indoor and outdoor air pollutants throughout the various stages of life. This review provides a summary of the detrimental effects of air pollution through examination of current animal, clinical, and epidemiological studies and exposure during three different periods: maternal (in utero), early life, and adulthood. Additionally, we recommend future lines of research while suggesting conceivable strategies to curb exposure to indoor and outdoor air pollutants. PMID:24929855

Novel adverse outcome pathways revealed by chemical genetics in a developing marine fish

PubMed Central

Sørhus, Elin; Incardona, John P; Furmanek, Tomasz; Goetz, Giles W; Scholz, Nathaniel L; Meier, Sonnich; Edvardsen, Rolf B; Jentoft, Sissel

2017-01-01

Crude oil spills are a worldwide ocean conservation threat. Fish are particularly vulnerable to the oiling of spawning habitats, and crude oil causes severe abnormalities in embryos and larvae. However, the underlying mechanisms for these developmental defects are not well understood. Here, we explore the transcriptional basis for four discrete crude oil injury phenotypes in the early life stages of the commercially important Atlantic haddock (Melanogrammus aeglefinus). These include defects in (1) cardiac form and function, (2) craniofacial development, (3) ionoregulation and fluid balance, and (4) cholesterol synthesis and homeostasis. Our findings suggest a key role for intracellular calcium cycling and excitation-transcription coupling in the dysregulation of heart and jaw morphogenesis. Moreover, the disruption of ionoregulatory pathways sheds new light on buoyancy control in marine fish embryos. Overall, our chemical-genetic approach identifies initiating events for distinct adverse outcome pathways and novel roles for individual genes in fundamental developmental processes. DOI: http://dx.doi.org/10.7554/eLife.20707.001 PMID:28117666

Effects of a Therapeutic Intervention for Foster Preschoolers on Diurnal Cortisol Activity

PubMed Central

Fisher, Philip A.; Stoolmiller, Mike; Gunnar, Megan R.; Burraston, Bert O.

2007-01-01

Atypical diurnal patterns of hypothalamic-pituitary-adrenal (HPA) axis activity have been observed samples of individuals following early life adversity. A characteristic pattern arising from disrupted caregiving is a low early morning cortisol level that changes little from morning to evening. Less well understood is the plasticity of the HPA axis in response to subsequent supportive caregiving environments. Monthly early morning and evening cortisol levels were assessed over 12 months in a sample of 3- to 6-year-old foster children enrolled in a randomized trial of a family-based therapeutic intervention (N = 117; intervention condition n = 57; regular foster care condition n = 60), and a community comparison group of same-aged, nonmaltreated children from low-income families (n = 60). Latent growth analyses revealed stable and typical diurnal (morning-to-evening) cortisol activity among community comparison children. Foster children in the intervention condition exhibited cortisol activity that became comparable to the comparison group children over the course of the study. In contrast, children in regular foster care condition exhibited increasingly flattened morning-to-evening cortisol activity over the course of the study. In sum, improvements in caregiving following early adversity appear to have the potential to reverse or prevent disruptions in HPA axis functioning. PMID:17656028

Cancer in working-age is not associated with childhood adversities.

PubMed

Korpimäki, Sonja K; Sumanen, Markku P T; Sillanmäki, Lauri H; Mattila, Kari J

2010-05-01

Early life events are studied as potential causes of cancer. The objective here was to study childhood adversities in the etiology of cancer. The material comprised a population based random sample of 25 898 individuals among the Finnish working-aged population. In 1998 they were requested through six questions in a postal questionnaire to recall their childhood adversities. The cases consisted of people with cancer diagnosed 2000-2006 and registered in the Finnish Cancer Registry (n = 384). The rest of the sample consisted of cancer-free controls. The most common adversities were prolonged financial difficulties, serious conflicts in the family and someone in the family having been seriously or chronically ill. The cancer patients reported more prolonged financial difficulties and someone seriously or chronically ill in the family. They reported less parental divorce than the controls. The associations were not statistically significant after adjusting for age, sex, education, and health behaviour. Nor was there a significant difference in the total number of childhood adversities between the study group and the controls. On the whole, these cancer patients had not experienced more childhood adversities than the controls. According to our findings, there is no cause to attribute development of cancer in working age to childhood adversities. This information may also give relief to other family members.

Distinguishing among weapons offenders, drug offenders, and weapons and drug offenders based on childhood predictors and adolescent correlates.

PubMed

Stephens, Skye; Day, David M

2013-07-01

Weapons and drug offences incur a large cost to society and tend to be strongly associated. Improved understanding of their antecedents could inform targeted early intervention and prevention programmes. This study aimed to examine differences in criminal careers, childhood predictors and adolescent correlates among weapons-only offenders, drugs-only offenders and a versatile group of weapons + drugs offenders. We conducted a longitudinal records study of 455 young Canadians charged with drug and/or weapons offences who started their offending in late childhood/early adolescence. Consistent with expectation, differences emerged in their criminal careers as the versatile group had a longer criminal career and desisted from offending at a later age than weapons-only offenders. Against prediction, weapons-only offenders experienced the greatest number of childhood predictors and adolescent correlates. The three offending groups could be differentiated on offending trajectories and developmental factors.In making links between past events and later behaviour, life-course criminology may inform development of effective early intervention and prevention strategies.As weapons-only offenders experience the greatest level of adversity in childhood and adolescence, they may benefit most (of these three groups) from early intervention and prevention programmes.A reduction in weapon carrying and use might be achieved by early identification of children risk factors (e.g. family adversity) and appropriate intervention. Copyright © 2013 John Wiley & Sons, Ltd.

Early Life Exposure to Fructose and Offspring Phenotype: Implications for Long Term Metabolic Homeostasis

PubMed Central

Sloboda, Deborah M.; Li, Minglan; Patel, Rachna; Clayton, Zoe E.; Yap, Cassandra; Vickers, Mark H.

2014-01-01

The consumption of artificially sweetened processed foods, particularly high in fructose or high fructose corn syrup, has increased significantly in the past few decades. As such, interest into the long term outcomes of consuming high levels of fructose has increased significantly, particularly when the exposure is early in life. Epidemiological and experimental evidence has linked fructose consumption to the metabolic syndrome and associated comorbidities—implicating fructose as a potential factor in the obesity epidemic. Yet, despite the widespread consumption of fructose-containing foods and beverages and the rising incidence of maternal obesity, little attention has been paid to the possible adverse effects of maternal fructose consumption on the developing fetus and long term effects on offspring. In this paper we review studies investigating the effects of fructose intake on metabolic outcomes in both mother and offspring using human and experimental studies. PMID:24864200

Early life stage (ELS) toxicity of sucralose to fathead minnows, Pimephales promelas.

PubMed

Stoddard, K I; Huggett, D B

2014-10-01

Sucralose, an intense artificial sweetener, has been detected in wastewater and surface waters at concentrations ranging from ng/L to low µg/L. Although over a hundred studies have been conducted to evaluate the safety of sucralose for human consumption, few studies have focused on the chronic ecotoxicological effects of this compound in fish. As a remedy to this data gap, an early-life stage toxicity test was conducted to assess the effects of sucralose on hatching, survival, and growth of fathead minnows (Pimephales promelas). Hatching, survival, and growth were unaffected by 98 mg/L of sucralose. The Lowest-Observed-Effect Concentration (LOEC) and the No-Observed-Effect Concentration (NOEC) for fathead minnows determined by this study are >98 and 98 mg/L, respectively. The results from this study suggest that the concentrations of sucralose detected in the environment are well below those required to cause adverse effects to developing aquatic organisms.

Developmental programming of the metabolic syndrome - critical windows for intervention

PubMed Central

Vickers, Mark H

2011-01-01

Metabolic disease results from a complex interaction of many factors, including genetic, physiological, behavioral and environmental influences. The recent rate at which these diseases have increased suggests that environmental and behavioral influences, rather than genetic causes, are fuelling the present epidemic. In this context, the developmental origins of health and disease hypothesis has highlighted the link between the periconceptual, fetal and early infant phases of life and the subsequent development of adult obesity and the metabolic syndrome. Although the mechanisms are yet to be fully elucidated, this programming was generally considered an irreversible change in developmental trajectory. Recent work in animal models suggests that developmental programming of metabolic disorders is potentially reversible by nutritional or targeted therapeutic interventions during the period of developmental plasticity. This review will discuss critical windows of developmental plasticity and possible avenues to ameliorate the development of postnatal metabolic disorders following an adverse early life environment. PMID:21954418

Advancing Early Childhood Development: from Science to Scale 1

PubMed Central

Black, Maureen M; Walker, Susan P; Fernald, Lia C H; Andersen, Christopher T; DiGirolamo, Ann M; Lu, Chunling; McCoy, Dana C; Fink, Günther; Shawar, Yusra R; Shiffman, Prof Jeremy; Devercelli, Amanda E; Wodon, Quentin T; Vargas-Barón, Emily; Grantham-McGregor, Sally

2018-01-01

Early childhood development programmes vary in coordination and quality, with inadequate and inequitable access, especially for children younger than 3 years. New estimates, based on proxy measures of stunting and poverty, indicate that 250 million children (43%) younger than 5 years in low-income and middle-income countries are at risk of not reaching their developmental potential. There is therefore an urgent need to increase multisectoral coverage of quality programming that incorporates health, nutrition, security and safety, responsive caregiving, and early learning. Equitable early childhood policies and programmes are crucial for meeting Sustainable Development Goals, and for children to develop the intellectual skills, creativity, and wellbeing required to become healthy and productive adults. In this paper, the first in a three part Series on early childhood development, we examine recent scientific progress and global commitments to early childhood development. Research, programmes, and policies have advanced substantially since 2000, with new neuroscientific evidence linking early adversity and nurturing care with brain development and function throughout the life course. PMID:27717614

Infant Parasympathetic and Sympathetic Activity during Baseline, Stress and Recovery: Interactions with Prenatal Adversity Predict Physical Aggression in Toddlerhood.

PubMed

Suurland, J; van der Heijden, K B; Huijbregts, S C J; van Goozen, S H M; Swaab, H

2018-05-01

Exposure to prenatal adversity is associated with aggression later in life. Individual differences in autonomic nervous system (ANS) functioning, specifically nonreciprocal activation of the parasympathetic (PNS) and sympathetic (SNS) nervous systems, increase susceptibility to aggression, especially in the context of adversity. Previous work examining interactions between early adversity and ANS functioning in infancy is scarce and has not examined interaction between PNS and SNS. This study examined whether the PNS and SNS moderate the relation between cumulative prenatal risk and early physical aggression in 124 children (57% male). Cumulative risk (e.g., maternal psychiatric disorder, substance (ab)use, and social adversity) was assessed during pregnancy. Parasympathetic respiratory sinus arrhythmia (RSA) and sympathetic pre-ejection period (PEP) at baseline, in response to and during recovery from emotional challenge were measured at 6 months. Physical aggression and non-physical aggression/oppositional behavior were measured at 30 months. The results showed that cumulative prenatal risk predicted elevated physical aggression and non-physical aggression/oppositional behavior in toddlerhood; however, the effects on physical aggression were moderated by PNS and SNS functioning. Specifically, the effects of cumulative risk on physical aggression were particularly evident in children characterized by low baseline PNS activity and/or by nonreciprocal activity of the PNS and SNS, characterized by decreased activity (i.e., coinhibition) or increased activity (i.e., coactivation) of both systems at baseline and/or in response to emotional challenge. These findings extend our understanding of the interaction between perinatal risk and infant ANS functioning on developmental outcome.

The specificity of childhood adversities and negative life events across the life span to anxiety and depressive disorders.

PubMed

Spinhoven, Philip; Elzinga, Bernet M; Hovens, Jacqueline G F M; Roelofs, Karin; Zitman, Frans G; van Oppen, Patricia; Penninx, Brenda W J H

2010-10-01

Although several studies have shown that life adversities play an important role in the etiology and maintenance of both depressive and anxiety disorders, little is known about the relative specificity of several types of life adversities to different forms of depressive and anxiety disorder and the concurrent role of neuroticism. Few studies have investigated whether clustering of life adversities or comorbidity of psychiatric disorders critically influence these relationships. Using data from the Netherlands Study of Depression and Anxiety (NESDA), we analyzed the association of childhood adversities and negative life experiences across the lifespan with lifetime DSM-IV-based diagnoses of depression or anxiety among 2288 participants with at least one affective disorder. Controlling for comorbidity and clustering of adversities the association of childhood adversity with affective disorders was greater than that of negative life events across the life span with affective disorders. Among childhood adversities, emotional neglect was specifically associated with depressive disorder, dysthymia, and social phobia. Persons with a history of emotional neglect and sexual abuse were more likely to develop more than one lifetime affective disorder. Neuroticism and current affective disorder did not affect the adversity-disorder relationships found. Using a retrospective study design, causal interpretations of the relationships found are not warranted. Emotional neglect seems to be differentially related to depression, dysthymia and social phobia. This knowledge may help to reduce underestimation of the impact of emotional abuse and lead to better recognition and treatment to prevent long-term disorders. Copyright 2010 Elsevier B.V. All rights reserved.

5HTT genotype moderates the influence of early institutional deprivation on emotional problems in adolescence: evidence from the English and Romanian Adoptee (ERA) study.

PubMed

Kumsta, Robert; Stevens, Suzanne; Brookes, Keeley; Schlotz, Wolff; Castle, Jenny; Beckett, Celia; Kreppner, Jana; Rutter, Michael; Sonuga-Barke, Edmund

2010-07-01

A common polymorphism in the serotonin transporter gene (SLC6A4, 5HTT) has been repeatedly shown to moderate the influence of childhood adversity and stressful life events on the development of psychopathology. Using data from the English and Romanian Adoptee Study, a prospective-longitudinal study of individuals (n = 125) exposed to severe early institutional deprivation (ID), we tested whether the effect of ID on adolescent emotional problems is moderated by 5HTT genotype and stressful life events in adolescence. Emotional problems were assessed using questionnaire data (age 11), and on the basis of the CAPA diagnostic interview (age 15). Additionally, the number of stressful life events was measured. There was a significant effect for genotype (p = .003) and a gene x environment interaction (p = .008) that was independent of age at testing. Carriers of the s/l and s/s genotype who experienced severe ID showed the highest emotional problem scores, while l/l homozygotes in the severe ID group showed the lowest overall levels. Furthermore, s/s carriers in the severe ID group who experienced a high number of stressful life events between 11 and 15 years had the largest increases in emotional problem scores, while a low number of stressful life events was associated with the largest decrease (4-way interaction: p = .05). The effects of severe early ID on emotional problems in adolescence are moderated by 5HTT genotype, and influenced by stressful life events in adolescence.

Kindergarten stressors and cumulative adrenocortical activation: the "first straws" of allostatic load?

PubMed

Bush, Nicole R; Obradović, Jelena; Adler, Nancy; Boyce, W Thomas

2011-11-01

Using an ethnically diverse longitudinal sample of 338 kindergarten children, this study examined the effects of cumulative contextual stressors on children's developing hypothalamic-pituitary-adrenocortical (HPA) axis regulation as an early life indicator of allostatic load. Chronic HPA axis regulation was assessed using cumulative, multiday measures of cortisol in both the fall and spring seasons of the kindergarten year. Hierarchical linear regression analyses revealed that contextual stressors related to ethnic minority status, socioeconomic status, and family adversity each uniquely predicted children's daily HPA activity and that some of those associations were curvilinear in conformation. Results showed that the quadratic, U-shaped influences of family socioeconomic status and family adversity operate in different directions to predict children's HPA axis regulation. Results further suggested that these associations differ for White and ethnic minority children. In total, this study revealed that early childhood experiences contribute to shifts in one of the principal neurobiological systems thought to generate allostatic load, confirming the importance of early prevention and intervention efforts. Moreover, findings suggested that analyses of allostatic load and developmental theories accounting for its accrual would benefit from an inclusion of curvilinear associations in tested predictive models.

Childhood physical abuse predicts stressor-evoked activity within central visceral control regions

PubMed Central

Sheu, Lei K.; Midei, Aimee J.; Gianaros, Peter J.

2015-01-01

Early life experience differentially shapes later stress reactivity, as evidenced by both animal and human studies. However, early experience-related changes in the function of central visceral neural circuits that control stress responses have not been well characterized, particularly in humans. The paraventricular nucleus of the hypothalamus (PVN), bed nucleus of the stria terminalis (BNST), amygdala (Amyg) and subgenual anterior cingulate cortex (sgACC) form a core visceral stress-responsive circuit. The goal of this study is to examine how childhood emotional and physical abuse relates to adulthood stressor-evoked activity within these visceral brain regions. To evoke acute states of mental stress, participants (n = 155) performed functional magnetic resonance imaging (fMRI)-adapted versions of the multi-source interference task (MSIT) and the Stroop task with simultaneous monitoring of mean arterial pressure (MAP) and heart rate. Regression analyses revealed that childhood physical abuse correlated positively with stressor-evoked changes in MAP, and negatively with unbiased, a priori extractions of fMRI blood-oxygen level-dependent signal change values within the sgACC, BNST, PVN and Amyg (n = 138). Abuse-related changes in the function of visceral neural circuits may reflect neurobiological vulnerability to adverse health outcomes conferred by early adversity. PMID:24847113

Quality of life in children with adverse drug reactions: a narrative and systematic review.

PubMed

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-10-01

Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn's disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. © 2014 The British Pharmacological Society.

Testing an integral conceptual model of frailty.

PubMed

Gobbens, Robbert J; van Assen, Marcel A; Luijkx, Katrien G; Schols, Jos M

2012-09-01

This paper is a report of a study conducted to test three hypotheses derived from an integral conceptual model of frailty.   The integral model of frailty describes the pathway from life-course determinants to frailty to adverse outcomes. The model assumes that life-course determinants and the three domains of frailty (physical, psychological, social) affect adverse outcomes, the effect of disease(s) on adverse outcomes is mediated by frailty, and the effect of frailty on adverse outcomes depends on the life-course determinants. In June 2008 a questionnaire was sent to a sample of community-dwelling people, aged 75 years and older (n = 213). Life-course determinants and frailty were assessed using the Tilburg frailty indicator. Adverse outcomes were measured using the Groningen activity restriction scale, the WHOQOL-BREF and questions regarding healthcare utilization. The effect of seven self-reported chronic diseases was examined. Life-course determinants, chronic disease(s), and frailty together explain a moderate to large part of the variance of the seven continuous adverse outcomes (26-57%). All these predictors together explained a significant part of each of the five dichotomous adverse outcomes. The effect of chronic disease(s) on all 12 adverse outcomes was mediated at least partly by frailty. The effect of frailty domains on adverse outcomes did not depend on life-course determinants. Our finding that the adverse outcomes are differently and uniquely affected by the three domains of frailty (physical, psychological, social), and life-course determinants and disease(s), emphasizes the importance of an integral conceptual model of frailty. © 2011 Blackwell Publishing Ltd.

Quality of life in children with adverse drug reactions: a narrative and systematic review

PubMed Central

Del Pozzo-Magaña, Blanca R; Rieder, Michael J; Lazo-Langner, Alejandro

2015-01-01

Aims Adverse drug reactions are a common problem affecting adults and children. The economic impact of the adverse drug reactions has been widely evaluated; however, studies of the impact on the quality of life of children with adverse drug reactions are scarce. The aim was to evaluate studies assessing the health-related quality of life of children with adverse drug reactions. Methods We conducted a systematic review that included the following electronic databases: MEDLINE, EMBASE and the Cochrane Library (including the Cochrane Database of Systematic Reviews, the Database of Abstracts of Reviews of Effects, the Cochrane Controlled Trials Register and the Health Technology Assessment Databases). Results Nine studies were included. Four of the studies were conducted in children with epilepsy; the rest of them involved children with chronic viral hepatitis, Crohn’s disease, paediatric cancer and multiple adverse drug reactions compared with healthy children. Based on their findings, authors of all studies concluded that adverse drug reactions had a negative impact on the quality of life of children. No meta-analysis was conducted given the heterogeneous nature of the studies. Conclusions To date, there is no specific instrument that measures quality of life of children with adverse drug reactions, and the information available is poor and variable. In general, adverse drug reactions have a negative impact on the quality of life of affected children. For those interested in this area, more work needs to be done to improve tools that help to evaluate efficiently the health-related quality of life of children with adverse drug reactions and chronic diseases. PMID:24833305

The association of adverse childhood experiences with mid-life depressive symptoms and quality of life among incarcerated males: exploring multiple mediation.

PubMed

Skarupski, Kimberly A; Parisi, Jeanine M; Thorpe, Roland; Tanner, Elizabeth; Gross, Deborah

2016-01-01

To explore the association of experiencing death, trauma, and abuse during childhood with depressive symptoms and quality of life at mid-life among incarcerated men and to understand how current social support and coping strategies mediate the impact of childhood trauma histories on mental health. Study participants were 192 male inmates in a maximum security prison. Participants completed measures of adverse childhood experiences related to death, trauma, and abuse, and depressive symptoms and quality of life. Data were analyzed using multiple mediation modeling. Men who reported having experienced adverse childhood experiences reported more depressive symptoms and lower quality of life than their counterparts. The results showed that in models both unadjusted and adjusted for age, race, education, number of years served, and whether the inmate had a life sentence, the association between adverse childhood experiences and quality of life were partially explained by the total of the indirect effects (point estimate = -.5052; CI.95 = -1.0364, -.0429 and point estimate = -.7792; CI.95 = -1.6369, -.0381), primarily via social support. However, the associations between adverse childhood experiences and depressive symptoms were not explained by social support and coping. Adverse childhood experiences are associated with deleterious mental health effects in later life. Social support and coping partially mediate the association between adverse childhood experiences and quality of life. The high prevalence of childhood trauma among aging prison inmates warrants attention to increasing social support mechanisms to improve mental health.

Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression.

PubMed

Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

2016-05-03

Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors-overall trauma 'load' and specific type of abuse-on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes after 8 weeks of antidepressants, across the three treatment arms. In addition, the abuses occurring between ages 4 and 7 years differentially predicted the poorest outcome following the treatment with sertraline. Specific types of early-life trauma, particularly physical, emotional and sexual abuse, especially when occurring at ⩽7 years of age are important moderators of subsequent response to antidepressant therapy for MDD.

Childhood trauma predicts antidepressant response in adults with major depression: data from the randomized international study to predict optimized treatment for depression

PubMed Central

Williams, L M; Debattista, C; Duchemin, A-M; Schatzberg, A F; Nemeroff, C B

2016-01-01

Few reliable predictors indicate which depressed individuals respond to antidepressants. Several studies suggest that a history of early-life trauma predicts poorer response to antidepressant therapy but results are variable and limited in adults. The major goal of the present study was to evaluate the role of early-life trauma in predicting acute response outcomes to antidepressants in a large sample of well-characterized patients with major depressive disorder (MDD). The international Study to Predict Optimized Treatment for Depression (iSPOT-D) is a randomized clinical trial with enrollment from December 2008 to January 2012 at eight academic and nine private clinical settings in five countries. Patients (n=1008) meeting DSM-IV criteria for MDD and 336 matched healthy controls comprised the study sample. Six participants withdrew due to serious adverse events. Randomization was to 8 weeks of treatment with escitalopram, sertraline or venlafaxine with dosage adjusted by the participant's treating clinician per routine clinical practice. Exposure to 18 types of traumatic events before the age of 18 was assessed using the Early-Life Stress Questionnaire. Impact of early-life stressors—overall trauma ‘load' and specific type of abuse—on treatment outcomes measures: response: (⩾50% improvement on the 17-item Hamilton Rating Scale for Depression, HRSD17 or on the 16-item Quick Inventory of Depressive Symptomatology—Self-Rated, QIDS_SR16) and remission (score ⩽7 on the HRSD17 and ⩽5 on the QIDS_SR16). Trauma prevalence in MDD was compared with controls. Depressed participants were significantly more likely to report early-life stress than controls; 62.5% of MDD participants reported more than two traumatic events compared with 28.4% of controls. The higher rate of early-life trauma was most apparent for experiences of interpersonal violation (emotional, sexual and physical abuses). Abuse and notably abuse occurring at ⩽7 years of age predicted poorer outcomes after 8 weeks of antidepressants, across the three treatment arms. In addition, the abuses occurring between ages 4 and 7 years differentially predicted the poorest outcome following the treatment with sertraline. Specific types of early-life trauma, particularly physical, emotional and sexual abuse, especially when occurring at ⩽7 years of age are important moderators of subsequent response to antidepressant therapy for MDD. PMID:27138798

Drug use during early pregnancy: cross-sectional analysis from the Childbirth and Health Study in Primary Care in Iceland.

PubMed

Axelsdottir, Thury O; Sigurdsson, Emil L; Gudmundsdottir, Anna M; Kristjansdottir, Hildur; Sigurdsson, Johann A

2014-09-01

To analyse drug use in early pregnancy with special focus on socio-demographic factors associated with psychotropic and analgesic drug use. Cross-sectional study. A total of 1765 women were invited via their local health care centres, and 1111 participated at 11-16 weeks of pregnancy by filling out a postal questionnaire concerning socio-demographic and obstetric background, stressful life events, and drug use. Drug use prior to and early on in pregnancy, socio-demographic factors, smoking, and adverse life events were investigated. Drug categories screened for were psychotropics (collective term for antidepressants, relaxants, and sleep medication), analgesics, hormones, nicotine, vitamins/minerals, and homeopathic medicine. Drug use from the aforementioned drug categories, excluding vitamins/minerals and homeopathic medicine, was reduced by 18% during early pregnancy, compared with six months prior to conception (49% vs. 60%). Psychotropic drug use during early pregnancy was associated with elementary maternal education (p < 0.5), being unemployed (p < 0.001), being single/divorced/separated (p < 0.01), smoking prior to or during pregnancy (p < 0.01), forced to change job/move house (p < 0.001), and psychotropic drug use six months prior to pregnancy (p < 0.001). No items on the stressful life events scale were associated with increased analgesic use, which increased only with multiparity. Use of analgesics and psychotropic drugs seems common in pregnancy. Our results indicate that lack of a support network, stressful life events, and lower status in society may predispose women to more drug use. GPs and midwives responsible for maternity care could take this into account when evaluating risk and gain for women and foetuses in the primary care setting.

The effect of early-life stress and chronic high-sucrose diet on metabolic outcomes in female rats.

PubMed

Maniam, Jayanthi; Antoniadis, Christopher P; Morris, Margaret J

2015-01-01

Early-life stress affects metabolic outcomes and choice of diet influences the development of metabolic disease. Here we tested the hypothesis that chronic sugar intake exacerbates metabolic deficits induced by early-life stress. Early-life stress was induced in Sprague-Dawley rats using limited nesting material in early lactation (LN, postnatal days 2-9), and siblings were given chow alone or with additional sucrose post weaning (n = 9-17 per group). Female control and LN siblings had unlimited access to either chow plus water, or chow and water plus 25% sucrose solution (Sucrose), from 3-15 weeks of age. Weekly body weight and food intake were measured. Glucose and insulin tolerance were tested at 13 and 14 weeks of age, respectively. Rats were killed at 15 weeks. Hepatic triglyceride and markers of lipid synthesis - fatty acid synthase, acetyl-CoA carboxylase alpha and oxidation - and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (Pgc-1α) were examined. Mediators of hepatic glucocorticoid metabolism, specifically 11-beta hydroxysteroid dehydrogenase-1 (11βHSD-1), 5-α reductase, and glucocorticoid and mineralocorticoid receptor mRNAs were also measured. Sucrose increased caloric intake in both groups, but overall energy intake was not altered by LN exposure. LN exposure had no further impact on sucrose-induced glucose intolerance and increased plasma and liver triglycerides. Hepatic markers of fat synthesis and oxidation were concomitantly activated and 11βHSD-1 mRNA expression was increased by 53% in LN-Sucrose versus Con-Sucrose rats. Adiposity was increased by 26% in LN-Sucrose versus Con-Sucrose rats. Thus, LN exposure had minimal adverse metabolic effects despite high-sugar diet postweaning.

Unhealthy lifestyle in early psychoses: the role of life stress and the hypothalamic-pituitary-adrenal axis.

PubMed

Manzanares, Núria; Monseny, Rosa; Ortega, Laura; Montalvo, Itziar; Franch, Joan; Gutiérrez-Zotes, Alfonso; Reynolds, Rebecca M; Walker, Brian R; Vilella, Elisabet; Labad, Javier

2014-01-01

An unhealthy lifestyle is thought to contribute to the metabolic syndrome in subjects with psychoses. In the present study we aimed to study whether life stress or cortisol measures may influence dietary patterns in subjects with early stages of psychoses. We studied 81 subjects with early psychoses (65 subjects with a psychotic disorder [PD] and <5 years of illness; 16 subjects at risk for psychosis [high-risk, HR]) and a control group of 25 healthy subjects (HS). Dietary habits were examined by a dietician, who registered food intake (24h recall). Physical activity was assessed by validated questionnaire. Life stress was assessed with Holmes-Rahe Social Readjustment Scale. Fasting morning salivary and plasma cortisol levels were determined. We found that PD and HR reported an unhealthier lifestyle with more smoking, reduced physical activity and poorer dietary habits. HR reported increased intake of calories and saturated fatty acids and reduced protein consumption, when compared to HS. Life stress was a predictor of these adverse behaviours, although we found opposite associations in HR and PD. Life stress was associated with increased intake of refined sugar in PD and decreased intake in HR and HS. Salivary cortisol was related to increased intake of saturated fat only in HR subjects, but cortisol levels in plasma or saliva were not associated with other dietary habits or obesity measures (BMI, waist circumference). Our study suggests that unhealthy diet in early psychoses is influenced by stress, but our data do not support this effect being mediated by hypercortisolism. Future preventive interventions in psychosis may target dietary habits, particularly for those who are at risk for psychosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Life-course determinants of bone mass in young adults from a transitional rural community in India: the Andhra Pradesh Children and Parents Study (APCAPS).

PubMed

Matsuzaki, Mika; Kuper, Hannah; Kulkarni, Bharati; Radhakrishna, K V; Viljakainen, Heli; Taylor, Amy E; Sullivan, Ruth; Bowen, Liza; Tobias, Jon H; Ploubidis, George B; Wells, Jonathan C; Prabhakaran, Dorairaj; Davey Smith, George; Ebrahim, Shah; Ben-Shlomo, Yoav; Kinra, Sanjay

2014-06-01

Undernutrition and physical inactivity are both associated with lower bone mass. This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development. This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987-1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009-2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18-23 y). Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm²; lumbar spine: 0.86 (women), 0.93 (men) g/cm²]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories. Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage.

Life-course determinants of bone mass in young adults from a transitional rural community in India: the Andhra Pradesh Children and Parents Study (APCAPS)123

PubMed Central

Matsuzaki, Mika; Kuper, Hannah; Kulkarni, Bharati; Radhakrishna, KV; Viljakainen, Heli; Taylor, Amy E; Sullivan, Ruth; Bowen, Liza; Tobias, Jon H; Ploubidis, George B; Wells, Jonathan C; Prabhakaran, Dorairaj; Davey Smith, George; Ebrahim, Shah; Ben-Shlomo, Yoav; Kinra, Sanjay

2014-01-01

Background: Undernutrition and physical inactivity are both associated with lower bone mass. Objective: This study aimed to investigate the combined effects of early-life undernutrition and urbanized lifestyles in later life on bone mass accrual in young adults from a rural community in India that is undergoing rapid socioeconomic development. Design: This was a prospective cohort study of participants of the Hyderabad Nutrition Trial (1987–1990), which offered balanced protein-calorie supplementation to pregnant women and preschool children younger than 6 y in the intervention villages. The 2009–2010 follow-up study collected data on current anthropometric measures, bone mineral density (BMD) measured by dual-energy X-ray absorptiometry, blood samples, diet, physical activity, and living standards of the trial participants (n = 1446, aged 18–23 y). Results: Participants were generally lean and had low BMD [mean hip BMD: 0.83 (women), 0.95 (men) g/cm2; lumbar spine: 0.86 (women), 0.93 (men) g/cm2]. In models adjusted for current risk factors, no strong evidence of a positive association was found between BMD and early-life supplementation. On the other hand, current lean mass and weight-bearing physical activity were positively associated with BMD. No strong evidence of an association was found between BMD and current serum 25-hydroxyvitamin D or dietary intake of calcium, protein, or calories. Conclusions: Current lean mass and weight-bearing physical activity were more important determinants of bone mass than was early-life undernutrition in this population. In transitional rural communities from low-income countries, promotion of physical activity may help to mitigate any potential adverse effects of early nutritional disadvantage. PMID:24695898

Early-Life Exposure to Perfluoroalkyl Substances and Childhood Metabolic Function.

PubMed

Fleisch, Abby F; Rifas-Shiman, Sheryl L; Mora, Ana M; Calafat, Antonia M; Ye, Xiaoyun; Luttmann-Gibson, Heike; Gillman, Matthew W; Oken, Emily; Sagiv, Sharon K

2017-03-01

Perfluoroalkyl substances (PFASs) are synthetic chemicals that may persist in the environment and in humans. There is a possible association between early-life PFAS exposure and metabolic dysfunction in later life, but data are limited. We studied 665 mother-child pairs in Project Viva, a Boston, Massachusetts-area cohort recruited 1999-2002. We quantified concentrations of PFASs [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluorodecanoate (PFDeA)] in maternal plasma collected at the first prenatal visit (median, 9.6 weeks gestation) and in child plasma from the mid-childhood research visit (median, 7.7 years). We assessed leptin, adiponectin, and homeostatic model assessment of insulin resistance (HOMA-IR) in mid-childhood. We fit covariate-adjusted linear regression models and conducted stratified analyses by child sex. Children with higher PFAS concentrations had lower HOMA-IR [e.g., -10.1% (95% CI: -17.3, -2.3) per interquartile range increment in PFOA]. This inverse association between child PFAS and HOMA-IR was more pronounced in females [e.g., PFOA: -15.6% (95% CI: -25.4, -4.6) vs. -6.1% (95% CI: -16.2, 5.2) for males]. Child PFAS plasma concentrations were not associated with leptin or adiponectin. Prenatal PFAS plasma concentrations were not associated with leptin, adiponectin, or HOMA-IR in offspring. We found no evidence for an adverse effect of early-life PFAS exposure on metabolic function in mid-childhood. In fact, children with higher PFAS concentrations had lower insulin resistance. Citation: Fleisch AF, Rifas-Shiman SL, Mora AM, Calafat AM, Ye X, Luttmann-Gibson H, Gillman MW, Oken E, Sagiv SK. 2017. Early-life exposure to perfluoroalkyl substances and childhood metabolic function. Environ Health Perspect 125:481-487; http://dx.doi.org/10.1289/EHP303.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem.

PubMed

Kabiru, Caroline W; Elung'ata, Patricia; Mojola, Sanyu A; Beguy, Donatien

2014-01-01

Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? We used cross-sectional data from 3,064 males and females aged 12-19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries.

Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes.

PubMed

Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D' Amato, Francesca R; Battaglia, Marco

2016-04-28

Hyperventilation following transient, CO2-induced acidosis is ubiquitous in mammals and heritable. In humans, respiratory and emotional hypersensitivity to CO2 marks separation anxiety and panic disorders, and is enhanced by early-life adversities. Mice exposed to the repeated cross-fostering paradigm (RCF) of interference with maternal environment show heightened separation anxiety and hyperventilation to 6% CO2-enriched air. Gene-environment interactions affect CO2 hypersensitivity in both humans and mice. We therefore hypothesised that epigenetic modifications and increased expression of genes involved in pH-detection could explain these relationships. Medullae oblongata of RCF- and normally-reared female outbred mice were assessed by ChIP-seq for H3Ac, H3K4me3, H3K27me3 histone modifications, and by SAGE for differential gene expression. Integration of multiple experiments by network analysis revealed an active component of 148 genes pointing to the mTOR signalling pathway and nociception. Among these genes, Asic1 showed heightened mRNA expression, coherent with RCF-mice's respiratory hypersensitivity to CO2 and altered nociception. Functional enrichment and mRNA transcript analyses yielded a consistent picture of enhancement for several genes affecting chemoception, neurodevelopment, and emotionality. Particularly, results with Asic1 support recent human findings with panic and CO2 responses, and provide new perspectives on how early adversities and genes interplay to affect key components of panic and related disorders.

Adverse Childhood Experiences and Adult Well-Being in a Low-income, Urban Cohort.

PubMed

Giovanelli, Alison; Reynolds, Arthur J; Mondi, Christina F; Ou, Suh-Ruu

2016-04-01

This study tests the association between adverse childhood experiences (ACEs) and multidimensional well-being in early adulthood for a low-income, urban cohort, and whether a preschool preventive intervention moderates this association. Follow-up data were analyzed for 1202 low-income, minority participants in the Chicago Longitudinal Study, a prospective investigation of the impact of early experiences on life-course well-being. Born between 1979 and 1980 in high-poverty neighborhoods, individuals retrospectively reported ACEs from birth to adolescence, except in cases of child abuse and neglect. Nearly two-thirds of the study sample experienced ≥1 ACEs by age 18. After controlling for demographic factors and early intervention status, individuals reporting ACEs were significantly more likely to exhibit poor outcomes than those with no ACEs. Those with ≥4 ACEs had significantly reduced likelihood of high school graduation (odds ratio [OR] = 0.37; P < .001), increased risk for depression (OR = 3.9; P < .001), health compromising behaviors (OR = 4.5; P < .001), juvenile arrest (OR = 3.1; P < .001), and felony charges (OR = 2.8; P < .001). They were also less likely to hold skilled jobs (OR = 0.50; P = .001) and to go further in school even for adversity measured by age 5. ACEs consistently predicted a diverse set of adult outcomes in a high-risk, economically disadvantaged sample. Effective and widely available preventive interventions are needed to counteract the long-term consequences of ACEs. Copyright © 2016 by the American Academy of Pediatrics.

Life adverse experiences in relation with obesity and binge eating disorder: A systematic review

PubMed Central

Palmisano, Giovanni Luca; Innamorati, Marco; Vanderlinden, Johan

2016-01-01

Background and aims Several studies report a positive association between adverse life experiences and adult obesity. Despite the high comorbidity between binge eating disorder (BED) and obesity, few authors have studied the link between trauma and BED. In this review the association between exposure to adverse life experiences and a risk for the development of obesity and BED in adulthood is explored. Methods Based on a scientific literature review in Medline, PubMed and PsycInfo databases, the results of 70 studies (N = 306,583 participants) were evaluated including 53 studies on relationship between adverse life experiences and obesity, 7 studies on post-traumatic stress disorder (PTSD) symptoms in relation to obesity, and 10 studies on the association between adverse life experiences and BED. In addition, mediating factors between the association of adverse life experiences, obesity and BED were examined. Results The majority of studies (87%) report that adverse life experiences are a risk factor for developing obesity and BED. More precisely a positive association between traumatic experiences and obesity and PTSD and obesity were found, respectively, in 85% and 86% of studies. Finally, the great majority of studies (90%) between trauma and the development of BED in adulthood strongly support this association. Meanwhile, different factors mediating between the trauma and obesity link were identified. Discussion and conclusions Although research data show a strong association between life adverse experiences and the development of obesity and BED, more research is needed to explain this association. PMID:28092189

Integrative medicine: Breaking down silos of knowledge and practice an epigenetic approach.

PubMed

McEwen, Bruce S

2017-04-01

The future of medicine is discussed in the context of epigenetic influences during the entire life course and the lived experiences of each person, avoiding as much as possible the "medicalization" of the individual and taking a more humanistic view. The reciprocal communication between brain and body via the neuroendocrine, autonomic, metabolic and immune systems and the plasticity of brain architecture provide the basis for devising better "top down" interventions that engage the whole person in working towards his or her welfare. The life course perspective emphasizes the importance of intervening early in life to prevent adverse early life experiences, including the effects of poverty, that can have lifelong consequences, referred to as "biological embedding". In the spirit of integrative, humanistic medicine, treatments that "open windows of plasticity" allow targeted behavioral interventions to redirect brain and body functions and behavior in healthier directions. Policies of government and the private sector, particularly at the local, community level, can create a supporting environment for such interventions. See "Common Ground for Health: Personalized, Precision and Social Medicine McEwen & Getz - https://www.youtube.com/watch?v=IRy_uUWyrEw. Copyright © 2017. Published by Elsevier Inc.

Validation of DSM-5 age-of-onset criterion of attention deficit/hyperactivity disorder (ADHD) in adults: Comparison of life quality, functional impairment, and family function.

PubMed

Lin, Yu-Ju; Lo, Kuan-Wu; Yang, Li-Kuang; Gau, Susan Shur-Fen

2015-12-01

The newly published Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) elevates the threshold of the ADHD age-of-onset criterion from 7 to 12 years. This study evaluated the quality of life and functional impairment of adults with ADHD who had symptoms onset by or after 7 years and examined the mediation effect of family function and anxiety/depression symptoms between ADHD diagnosis and quality of life and functional impairment. We assessed 189 adults with ADHD and 153 non-ADHD controls by psychiatric interview and self-administered reports on the Adult ADHD Quality of Life Scale, Weiss Functional Impairment Rating Scale, Family APGAR, and Adult Self Report Inventory-4. The ADHD group was divided into early-onset ADHD (onset <7 years, n=147) and late-onset ADHD (onset between 7 and 12 years, n=42). The mediation analysis was conducted to verify the mediating factors from ADHD to functional impairment and quality of life. The late-onset ADHD had more severe functional impairment at work and poorer family support than early-onset ADHD while they had comparable impairment at other domains. Less perceived family support and current anxiety/depressive symptoms partially mediated the link between ADHD diagnosis and quality of life/functional impairment both in early- and late-onset ADHD. Our data support decreased quality of life and increased functional impairment in adult ADHD, regardless of age of onset, and these adverse outcomes may be mediated by family support and anxiety/depression at adulthood. Our findings also imply that the new DSM-5 ADHD criteria do not over-include individuals without impairment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cognitive Impairment as a Mediator in the Developmental Pathway from Infant Malnutrition to Adolescent Depressive Symptoms in Barbadian Youth

PubMed Central

Waber, Deborah P.; Eaglesfield, David; Fitzmaurice, Garrett M.; Bryce, Cyralene; Harrison, Robert H.; Galler, Janina R.

2011-01-01

Background Depressive symptoms are elevated in adolescents who experienced significant malnutrition early in life. Early malnutrition can also have a significant impact on cognitive functioning, presumably due to the adverse impact of the malnutrition on the very young brain. In the context of a developmental cascade model, we tested the hypothesis that the association between early malnutrition and adolescent depressive symptoms is mediated by the cognitive impairment that ensues from the malnutrition. Method We evaluated Barbadian youth (N=57) hospitalized for moderate to severe protein-energy malnutrition in the first year of life and healthy controls (N=60) longitudinally. The primary hypothesis was tested by multiple regression models. Results After adjusting for covariates, early malnutrition predicted both cognitive functioning in childhood (IQ, p<0.001; attention problems, p<.01; Common Entrance Examination, p<0.01) and adolescent depressive symptoms (p<0.05). Childhood cognitive functioning mediated the association between early malnutrition and depressive symptoms in adolescence (p<0.001). Maternal depressive symptoms were a significant but independent predictor of adolescent depressive symptoms (p<0.05). Conclusions Cognitive compromise in childhood accounts indirectly for elevated depressive symptoms in previously malnourished adolescents, consistent with a developmental cascade model. The direct link between malnutrition and depressive symptoms in adolescence is small. PMID:21285893

Close Friends' Psychopathology as a Pathway From Early Adversity to Young Adulthood Depressive Symptoms.

PubMed

Raposa, Elizabeth B; Hammen, Constance L; Brennan, Patricia A

2015-01-01

Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults' close friends' psychological symptoms and the impact of these close friendships on later depressive symptoms. A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants' mothers provided contemporaneous information about adversity exposure up to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20s. Youth also nominated a best friend to complete questionnaires about his or her own psychopathology at age 20. Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends' psychopathology predicted target youth depressive symptoms 2 to 5 years later. Results indicate that early adversity continues to affect social functioning throughout young adulthood and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity.

Close Friends’ Psychopathology as a Pathway from Early Adversity to Young Adulthood Depressive Symptoms

PubMed Central

Raposa, Elizabeth; Hammen, Constance; Brennan, Patricia

2014-01-01

Objective Past research has highlighted the negative impact of early adverse experiences on childhood social functioning, including friendship selection, and later mental health. The current study explored the long-term effects of early adversity on young adults’ close friends’ psychological symptoms, and the impact of these close friendships on later depressive symptoms. Method A prospective longitudinal design was used to examine 816 youth from a large community-based sample, who were followed from birth through age 25. Participants’ mothers provided contemporaneous information about adversity exposure prior to age 5, and participants completed questionnaires about their own depressive symptoms at age 20 and in their early 20’s. Youth also nominated a best friend to complete questionnaires about their own psychopathology at age 20. Results Individuals who experienced more early adversity by age 5 had best friends with higher rates of psychopathology at age 20. Moreover, best friends’ psychopathology predicted target youth depressive symptoms two to five years later. Conclusions Results indicate that early adversity continues to affect social functioning throughout young adulthood, and that best friendships marked by elevated psychopathology in turn negatively affect mental health. Findings have implications for clinical interventions designed to prevent the development of depressive symptoms in youth who have been exposed to early adversity. PMID:24871609

Whole cow's milk in infancy.

PubMed

Leung, Alexander Kc; Sauve, Reginald S

2003-09-01

Early introduction of whole cow's milk may lead to iron deficiency anemia. From a nutritional point of view, it is best to delay the introduction of whole cow's milk until the infant is one year old. While there is no evidence to suggest adverse clinical sequelae associated with the increased renal solute load in healthy infants, feeding with whole cow's milk would narrow the margin of safety in situations that may lead to dehydration. Early exposure to cow's milk proteins increases the risk of developing allergy to milk proteins. Because of the possible association between early exposure to cow's milk proteins and risk for type 1 diabetes mellitus, breast-feeding and avoidance of commercially available cow's milk and products containing intact cow's milk protein during the first year of life are strongly encouraged in families with a strong history of insulin dependent diabetes mellitus. The authors suggest that the optimal food in infancy is human breast milk. If human milk is not available, it is preferred that iron-fortified formulas rather than whole cow's milk be used during the first year of life.

Early Development of the Gut Microbiota and Immune Health

PubMed Central

Francino, M. Pilar

2014-01-01

In recent years, the increase in human microbiome research brought about by the rapidly evolving “omic” technologies has established that the balance among the microbial groups present in the human gut, and their multipronged interactions with the host, are crucial for health. On the other hand, epidemiological and experimental support has also grown for the ‘early programming hypothesis’, according to which factors that act in utero and early in life program the risks for adverse health outcomes later on. The microbiota of the gut develops during infancy, in close interaction with immune development, and with extensive variability across individuals. It follows that the specific process of gut colonization and the microbe-host interactions established in an individual during this period have the potential to represent main determinants of life-long propensity to immune disease. Although much remains to be learnt on the progression of events by which the gut microbiota becomes established and initiates its intimate relationships with the host, and on the long-term repercussions of this process, recent works have advanced significatively in this direction. PMID:25438024

Developmental origins of cardiovascular disease: Impact of early life stress in humans and rodents.

PubMed

Murphy, M O; Cohn, D M; Loria, A S

2017-03-01

The Developmental Origins of Health and Disease (DOHaD) hypothesizes that environmental insults during childhood programs the individual to develop chronic disease in adulthood. Emerging epidemiological data strongly supports that early life stress (ELS) given by the exposure to adverse childhood experiences is regarded as an independent risk factor capable of predicting future risk of cardiovascular disease. Experimental animal models utilizing chronic behavioral stress during postnatal life, specifically maternal separation (MatSep) provides a suitable tool to elucidate molecular mechanisms by which ELS increases the risk to develop cardiovascular disease, including hypertension. The purpose of this review is to highlight current epidemiological studies linking ELS to the development of cardiovascular disease and to discuss the potential molecular mechanisms identified from animal studies. Overall, this review reveals the need for future investigations to further clarify the molecular mechanisms of ELS in order to develop more personalized therapeutics to mitigate the long-term consequences of chronic behavioral stress including cardiovascular and heart disease in adulthood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Complex Living Conditions Impair Behavioral Inhibition but Improve Attention in Rats

PubMed Central

van der Veen, Rixt; Kentrop, Jiska; van der Tas, Liza; Loi, Manila; van IJzendoorn, Marinus H.; Bakermans-Kranenburg, Marian J.; Joëls, Marian

2015-01-01

Rapid adaptation to changes, while maintaining a certain level of behavioral inhibition is an important feature in every day functioning. How environmental context and challenges in life can impact on the development of this quality is still unknown. In the present study, we examined the effect of a complex rearing environment during adolescence on attention and behavioral inhibition in adult male rats. We also tested whether these effects were affected by an adverse early life challenge, maternal deprivation (MD). We found that animals that were raised in large, two floor MarlauTM cages, together with 10 conspecifics, showed improved attention, but impaired behavioral inhibition in the 5-choice serial reaction time task. The early life challenge of 24 h MD on postnatal day 3 led to a decline in bodyweight during adolescence, but did not by itself influence responses in the 5-choice task in adulthood, nor did it moderate the effects of complex housing. Our data suggest that a complex rearing environment leads to a faster adaptation to changes in the environment, but at the cost of lower behavioral inhibition. PMID:26733839

Effects of stress and social support on mothers and premature and full-term infants.

PubMed

Crnic, K A; Greenberg, M T; Ragozin, A S; Robinson, N M; Basham, R B

1983-02-01

This study examined the relationships of stress and social support to maternal attitudes and early mother-infant interactive behavior. 52 mother-premature infant pairs and 53 mother-full-term infant pairs were seen for structured home interviews at 1 month, and behavioral interactions at 4 months. Maternal life stress, social support, life satisfaction, and satisfaction with parenting were assessed at the 1-month home visit. Although no group differences were found, both stress and support significantly predicted maternal attitudes at 1 month and interactive behavior at 4 months when data were pooled. Mothers with greater stress were less positive in their attitudes and behavior, while mothers with greater support were significantly more positive. Intimate support proved to have the most general positive effects. Additionally, social support moderated the adverse effects of stress on mother's life satisfaction and on several behavioral variables. Maternal social support was further found to have several significant effects on infant interactive behavior. Results are discussed in terms of the ecological significance of social support to parenting and infants' early development.

Neonatal Lipopolysaccharide Exposure Gender-Dependently Increases Heart Susceptibility to Ischemia/Reperfusion Injury in Male Rats.

PubMed

Zhang, Peng; Lv, Juanxiu; Li, Yong; Zhang, Lubo; Xiao, Daliao

2017-01-01

Background: Adverse stress exposure during the early neonatal period has been shown to cause aberrant development, resulting in an increased risk of adult disease. We tested the hypothesis that neonatal exposure to lipopolysaccharide (LPS) does not alter heart function at rest condition but causes heart dysfunction under stress stimulation later in life. Methods: Saline control or LPS were administered to neonatal rats via intraperitoneal injection. Experiments were conducted in 6 week-old male and female rats. Isolated hearts were perfused in a Langendorff preparation. Results: Neonatal LPS exposure exhibited no effects on the body weight of the developing rats, but induced decreases in the left ventricle (LV) to the body weight ratio in male rats. Neonatal LPS exposure showed no effects on the baseline heart function determined by in vivo and ex vivo experiments, but caused decreases in the post-ischemic recovery of the LV function in male but not female rats. Neonatal LPS-mediated LV dysfunction was associated with an increase in myocardial infarct size and the LDH release in the male rats. Conclusion: The present study provides novel evidence that neonatal immune challenges could induce gender-dependent long-term effects on cardiac development and heart function, which reinforces the notion that adverse stress exposure during the early neonatal period can aggravate heart functions and the development of a heart ischemia-sensitive phenotype later in life.

Early-life school, neighborhood, and family influences on adult health: a multilevel cross-classified analysis of the Aberdeen children of the 1950s study.

PubMed

Dundas, Ruth; Leyland, Alastair H; Macintyre, Sally

2014-07-15

Lifetime exposures to adverse social environments influence adult health, as do exposures in early life. It is usual to examine the influences of school on teenage health and of adult area of residence on adult health. We examined the combined long-term association of the school attended, as well as the area of residence in childhood, with adult health. A total of 6,285 children from Aberdeen, Scotland, who were aged 5-12 years in 1962, were followed up at a mean age of 47 years in 2001. Cross-classified multilevel logistic regression was used to estimate the associations of family, school, and area of residence with self-reported adult health and mental health, adjusting for childhood family-, school-, and neighborhood-level factors, as well as current adult occupational position. Low early-life social position (as determined by the father's occupational level) was associated with poor adult self-rated health but not poor mental health. There were small contextual associations between childhood school environment (median odds ratio = 1.08) and neighborhood environment (median odds ratio = 1.05) and adult self-rated health. The share of the total variance in health at the family level was 10.1% compared with 89.6% at the individual level. Both socioeconomic context and composition in early life appear to have an influence on adult health, even after adjustment for current occupational position. © The Author 2014. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health.

Pregnancy and Neonatal Diabetes Outcomes in Remote Australia (PANDORA) study

PubMed Central

2013-01-01

Background Diabetes in pregnancy carries an increased risk of adverse pregnancy outcomes for both the mother and foetus, but it also provides an excellent early opportunity for intervention in the life course for both mother and baby. In the context of the escalating epidemic of chronic diseases among Indigenous Australians, it is vital that this risk is reduced as early as possible in the life course of the individual. The aims of the PANDORA Study are to: (i) accurately assess rates of diabetes in pregnancy in the Northern Territory (NT) of Australia, where 38% of babies are born to Indigenous mothers; (ii) assess demographic, clinical, biochemical, anthropometric, socioeconomic and early life development factors that may contribute to key maternal and neonatal birth outcomes associated with diabetes in pregnancy; and (iii) monitor relevant post-partum clinical outcomes for both the mothers and their babies. Methods/Design Eligible participants are all NT women with diabetes in pregnancy aged 16 years and over. Information collected includes: standard antenatal clinical information, diagnosis and management of diabetes in pregnancy, socio-economic status, standard clinical birth information (delivery, gestational age, birth weight, adverse antenatal and birth outcomes). Cord blood is collected at the time of delivery and detailed neonatal anthropometric measurements performed within 72 hours of birth. Information will also be collected regarding maternal post-partum glucose tolerance and cardio-metabolic risk factor status, breastfeeding and growth of the baby up to 2 years post-partum in the first instance. Discussion This study will accurately document rates and outcomes of diabetes in pregnancy in the NT of Australia, including the high-risk Indigenous Australian population. The results of this study should contribute to policy and clinical guidelines with the goal of reducing the future risk of obesity and diabetes in both mothers and their offspring. PMID:24289168

Adverse Life Experience and Psychological Distress in Adolescence: Moderating and Mediating Effects of Emotion Regulation and Rumination.

PubMed

Boyes, Mark E; Hasking, Penelope A; Martin, Graham

2016-10-01

The current study tested whether emotion regulation and rumination moderated and/or mediated the relationship between accumulated adverse life experience and psychological distress in adolescence. In class, Australian high school students (n = 2637, 12-18 years, 68% female) from 41 schools completed well-validated measures of adverse life experience, emotion regulation, rumination and psychological distress, and were followed up 1 year later (n = 1973, 75% retention rate). Adjusting for age, gender and baseline psychological distress, adverse life experience predicted psychological distress 1 year later. Expressive suppression and rumination were positively associated with psychological distress. Cognitive reappraisal was negatively associated with psychological distress and moderated the relationship between adverse life experience and psychological distress. This relationship was also partially mediated by cognitive reappraisal, expressive suppression and rumination. Promoting cognitive reappraisal and minimizing expressive suppression and rumination may be useful strategies to improve mental health for adolescents who have experienced adverse life events. Future research should examine whether adolescents who have experienced adverse life events can be trained in effective emotion regulation strategies and whether this training can prevent development of psychological maladjustment. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Do cognitive distortions explain the longitudinal relationship between life adversity and emotional and behavioural problems in secondary school children?

PubMed Central

Comoretto, Amanda

2017-01-01

Abstract Research has shown that children exposed to life adversity are at higher risk of negative developmental outcomes than those enduring lower stress levels. Life adversity can lead, among other things, to emotional and behavioural problems. Several factors have been studied to explain this relationship, with several investigators underlining the role of thought structures such as cognitive distortions, which refer to negatively biased information‐processing of external events. This can help explain why some individuals characterised by adverse personal life stories interpret ambiguous events in a negatively biased way. This study was aimed at assessing the mediating role of cognitive distortions in the longitudinal relationship between life adversity and two dimensions of psychopathology, namely, emotional and behavioural problems in 247 secondary school children attending three state secondary schools in one county in the South East of England. An increase in life adversity was associated with an increase in cognitive distortions, which was in turn related to a higher number of symptoms reflecting behavioural issues. In terms of practical applications, an effort to protect children from further exposure to adverse life events could represent a step forward to prevent the development of future behavioural problems in at‐risk children. PMID:28198138

Early Life Adversity during the Infant Sensitive Period for Attachment:, Programming of Behavioral Neurobiology of Threat Processing and Social Behavior

PubMed Central

Opendak, Maya; Gould, Elizabeth; Sullivan, Regina

2017-01-01

Animals, including humans, require a highly coordinated and flexible system of social behavior and threat evaluation. However, trauma can disrupt this system, with the amygdala implicated as a mediator of these impairments in behavior. Recent evidence has further highlighted the context of infant trauma as a critical variable in determining its immediate and enduring consequences, with trauma experienced from an attachment figure, such as occurs in cases of caregiver-child maltreatment, as particularly detrimental. This review focuses on the unique role of caregiver presence during early-life trauma in programming deficits in social behavior and threat processing. Using data primarily from rodent models, we describe the interaction between trauma and attachment during a sensitive period in early life, which highlights the role of the caregiver’s presence in engagement of attachment brain circuitry and suppressing threat processing by the amygdala. These data suggest that trauma experienced directly from an abusive caregiver and trauma experienced in the presence of caregiver cues produce similar neurobehavioral deficits, which are unique from those resulting from trauma alone. We go on to integrate this information into social experience throughout the lifespan, including consequences for complex scenarios, such as dominance hierarchy formation and maintenance. PMID:28254197

FERTILITY INTENTIONS AND EARLY LIFE HEALTH STRESS AMONG WOMEN IN EIGHT INDIAN CITIES: TESTING THE REPRODUCTIVE ACCELERATION HYPOTHESIS.

PubMed

Kulathinal, Sangita; Säävälä, Minna

2015-09-01

In life history theory, early life adversity is associated with an accelerated reproductive tempo. In harsh and unpredictable conditions in developing societies fertility is generally higher and the reproductive tempo faster than in more secure environments. This paper examines whether differences in female anthropometry, particularly adult height, are associated with fertility intentions of women in urban environments in India. The study population consists of women aged 15-29 (N=4485) in slums and non-slums of eight Indian cities in the National Family Health Survey (NFHS) of 2005-2006. Adult height is taken as a proxy for early childhood health and nutritional condition. Fertility intentions are examined by using two variables: the desire to have a child or another child, and to have it relatively soon, as indicative of accelerated reproductive scheduling. Evidence supporting the acceleration hypothesis is found in two urban frames out of 26 examined in a two-staged multinomial logistic model. In three cases, the relationship between fertility intentions and height is the opposite than expected by the acceleration hypothesis: taller women have a higher predictive probability of desiring a(nother) child and/or narrower birth spacing. Potential explanations for the partly contradictory relationship between the childhood health indicator and fertility intentions are discussed.

The long arm of community: the influence of childhood community contexts across the early life course.

PubMed

Wickrama, K A S; Noh, Samuel

2010-08-01

This study examines the longitudinal effects of childhood community contexts on young adult outcomes. The study uses a sample of 14,000 adolescents (52% female) derived from the 1990 US Census and the National Longitudinal Study of Adolescent Health (Addhealth). The study examines whether community and family environments exert separate and/or joint long-term influences on young adult achievement and depression. We found both direct and indirect long-term influences of childhood community adversity on young adult educational attainment. The indirect influences of childhood community adversity operated through family and individual-level factors. The long-term influence of childhood community adversity on young adult depression was only indirect. Overall, community influences on young adult achievement outcomes were mediated by family context and by the adolescents' adjustments and transitions, including adolescent depression, school adjustment, and disruptive transitional events. The moderating effect of childhood community adversity suggests that the protective effects of family resources on young adult outcomes dissipate significantly in extremely adverse neighborhoods. The findings demonstrate the importance of integrating multiple theoretical perspectives for longitudinal research to capture pathways of community influence on adolescent developmental and young adulthood outcomes.

Adverse Childhood Experiences and Suicide Attempts: The Mediating Influence of Personality Development and Problem Behaviors.

PubMed

Perez, Nicholas M; Jennings, Wesley G; Piquero, Alex R; Baglivio, Michael T

2016-08-01

Adverse childhood experiences, comprised of forms of maltreatment and certain dysfunctional household environments, can affect the development of a child in a variety of different ways. This multitude of developmental changes may subsequently produce compounding harmful effects on the child's life and increase acutely maladaptive outcomes, including adolescent suicidal behavior. This study uses data collected from 2007 to 2012 for 64,329 Florida Department of Juvenile Justice youth (21.67 % female, 42.88 % African American, and 15.37 % Hispanic) to examine the direct and indirect effects of adverse childhood experiences on suicide attempts. Using a generalized structural equation model, the effects of adverse childhood experience scores are estimated on suicidal behavior through pathways of certain aspects of a child's personality development (aggression and impulsivity), as well as adolescent problem behaviors (school difficulties and substance abuse). The results show that a large proportion of the relationship between childhood adversity and suicide is mediated by the aforementioned individual characteristics, specifically through the youth's maladaptive personality development. These results suggest that, if identified early enough, the developmental issues for these youth could potentially be addressed in order to thwart potential suicidal behavior.

Mental disorders and subsequent educational attainment in a US national sample.

PubMed

Breslau, Joshua; Lane, Michael; Sampson, Nancy; Kessler, Ronald C

2008-07-01

As part of a larger investigation of the adverse effects of mental disorders on role functioning, we examined the associations of early-onset mental disorders with subsequent educational attainment in a large nationally representative survey of the US adult population. Diagnoses and age of onset for each of 17 DSM-IV disorders were assessed through retrospective self-report with the fully structured WHO Composite International Diagnostic Instrument (CIDI). Survival analysis was used to examine the associations between early-onset DSM-IV/CIDI disorders and subsequent termination of schooling with controls for socio-demographic characteristics and childhood adversities (i.e. childhood traumatic events, childhood neglect, parental mental illness, family disruption, and low parental educational attainment). Mental disorders were found to be significantly associated with termination of schooling prior to completion of each of four educational milestones (primary school graduation, high school graduation, college entry, college graduation), with odds ratios in the range of 1.3-7.0. The proportion of school terminations attributable to mental disorders was largest for high school graduation (10.2%) but also meaningful for primary school graduation (3.8%), college entry (4.4%) and college graduation (2.6%). These results add to a growing body of evidence documenting a wide variety of adverse life course effects of mental disorders.

Fusion of nonclinical and clinical data to predict human drug safety.

PubMed

Johnson, Dale E

2013-03-01

Adverse drug reactions continue to be a major cause of morbidity in both patients receiving therapeutics and in drug R&D programs. Predicting and possibly eliminating these adverse events remains a high priority in industry, government agencies and healthcare systems. With small molecule candidates, the fusion of nonclinical and clinical data is essential in establishing an overall system that creates a true translational science approach. Several new advances are taking place that attempt to create a 'patient context' mechanism early in drug research and development and ultimately into the marketplace. This 'life-cycle' approach has as its core the development of human-oriented, nonclinical end points and the incorporation of clinical knowledge at the drug design stage. The next 5 years should witness an explosion of what the author views as druggable and safe chemical space, pharmacosafety molecular targets and the most important aspect, an understanding of unique susceptibilities in patients developing adverse drug reactions. Our current knowledge of clinical safety relies completely on pharmacovigilance data from approved and marketed drugs, with a few exceptions of drugs failing in clinical trials. Massive data repositories now and soon to be available via cloud computing should stimulate a major effort in expanding our view of clinical drug safety and its incorporation into early drug research and development.

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study

PubMed Central

Hakulinen, Christian; Pulkki-Råback, Laura; Elovainio, Marko; Kubzansky, Laura D.; Jokela, Markus; Hintsanen, Mirka; Juonala, Markus; Kivimäki, Mika; Josefsson, Kim; Hutri-Kähönen, Nina; Kähönen, Mika; Viikari, Jorma; Keltikangas-Järvinen, Liisa; Raitakari, Olli T

2015-01-01

Objective Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity as well as having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Methods Participants were 2265 men and women (age range: 24-39 years in 2001) from the on-going Cardiovascular Risk in Young Finns study whose carotid IMT were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life-events, parental health behavior family, socioeconomic status, and childhood emotional environment). Results The cumulative risk score was associated with higher IMT in 2007 (b=.004; se=.001; p<.001) and increased IMT progression from 2001 to 2007 (b=.003; se=.001; p=.001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life-events was associated with higher IMT in 2001 (b=.007; se=.003; p=.016) and poorer parental health behavior predicted higher IMT in 2007 (b=.004; se=.002; p=.031) after adjustment for age, sex and childhood cardiovascular risk factors. Conclusions Early life psychosocial environment influences cardiovascular risk later in life and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood. PMID:26809108

Childhood Psychosocial Cumulative Risks and Carotid Intima-Media Thickness in Adulthood: The Cardiovascular Risk in Young Finns Study.

PubMed

Hakulinen, Christian; Pulkki-Råback, Laura; Elovainio, Marko; Kubzansky, Laura D; Jokela, Markus; Hintsanen, Mirka; Juonala, Markus; Kivimäki, Mika; Josefsson, Kim; Hutri-Kähönen, Nina; Kähönen, Mika; Viikari, Jorma; Keltikangas-Järvinen, Liisa; Raitakari, Olli T

2016-01-01

Adverse experiences in childhood may influence cardiovascular risk in adulthood. We examined the prospective associations between types of psychosocial adversity and having multiple adversities (e.g., cumulative risk) with carotid intima-media thickness (IMT) and its progression among young adults. Higher cumulative risk score in childhood was expected to be associated with higher IMT and its progression. Participants were 2265 men and women (age range, 24-39 years in 2001) from the ongoing Cardiovascular Risk in Young Finns study whose carotid IMTs were measured in 2001 and 2007. A cumulative psychosocial risk score, assessed at the study baseline in 1980, was derived from four separate aspects of the childhood environment that may impose risk (childhood stressful life events, parental health behavior family, socioeconomic status, and childhood emotional environment). The cumulative risk score was associated with higher IMT in 2007 (b = 0.004, standard error [SE] = 0.001, p < .001) and increased IMT progression from 2001 to 2007 (b = 0.003, SE = 0.001, p = .001). The associations were robust to adjustment for conventional cardiovascular risk factors in childhood and adulthood, including adulthood health behavior, adulthood socioeconomic status, and depressive symptoms. Among the individual childhood psychosocial risk categories, having more stressful life events was associated with higher IMT in 2001 (b = 0.007, SE = 0.003, p = .016) and poorer parental health behavior predicted higher IMT in 2007 (b = 0.004, SE = 0.002, p = .031) after adjustment for age, sex, and childhood cardiovascular risk factors. Early life psychosocial environment influences cardiovascular risk later in life, and considering cumulative childhood risk factors may be more informative than individual factors in predicting progression of preclinical atherosclerosis in adulthood.

Adversity in childhood and measures of aging in midlife: Findings from a cohort of british women.

PubMed

Anderson, Emma L; Heron, Jon; Ben-Shlomo, Yoav; Kuh, Diana; Cooper, Rachel; Lawlor, Debbie A; Fraser, Abigail; Howe, Laura D

2017-09-01

Very few studies have assessed whether socioeconomic and psychosocial adversity during childhood are associated with objective measures of aging later in life. We assessed associations of socioeconomic position (SEP) and total psychosocial adversity during childhood, with objectively measured cognitive and physical capability in women during midlife. Adverse childhood experiences were retrospectively reported at mean ages 28-30 years in women from the Avon Longitudinal Study of Parents And Children (N = 2,221). We investigated associations of childhood SEP and total psychosocial adversity, with composite measures of cognitive and physical capability at mean age 51 years. There was evidence that, compared with participants whose fathers had professional occupations, participants whose fathers had managerial/technical, skilled nonmanual, skilled manual, and partly or unskilled manual occupations had, on average, lower physical and cognitive capability. There was a clear trend for increasing magnitudes of association with lowering childhood SEP. There was also evidence that greater total psychosocial adversity in childhood was associated with lower physical capability. Total psychosocial adversity in childhood was not associated with cognitive capability. Lower SEP in childhood is detrimental to cognitive and physical capability in midlife, at least in part, independently of subsequent SEP in adulthood. Greater psychosocial adversity in childhood is associated with poorer physical capability, independently of social disadvantage in childhood. Our findings highlight the need for interventions to both identify and support children experiencing socioeconomic or psychosocial of adversity as early as possible. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Adversity in Childhood and Measures of Aging in Midlife: Findings From a Cohort of British Women

PubMed Central

2017-01-01

Very few studies have assessed whether socioeconomic and psychosocial adversity during childhood are associated with objective measures of aging later in life. We assessed associations of socioeconomic position (SEP) and total psychosocial adversity during childhood, with objectively measured cognitive and physical capability in women during midlife. Adverse childhood experiences were retrospectively reported at mean ages 28–30 years in women from the Avon Longitudinal Study of Parents And Children (N = 2,221). We investigated associations of childhood SEP and total psychosocial adversity, with composite measures of cognitive and physical capability at mean age 51 years. There was evidence that, compared with participants whose fathers had professional occupations, participants whose fathers had managerial/technical, skilled nonmanual, skilled manual, and partly or unskilled manual occupations had, on average, lower physical and cognitive capability. There was a clear trend for increasing magnitudes of association with lowering childhood SEP. There was also evidence that greater total psychosocial adversity in childhood was associated with lower physical capability. Total psychosocial adversity in childhood was not associated with cognitive capability. Lower SEP in childhood is detrimental to cognitive and physical capability in midlife, at least in part, independently of subsequent SEP in adulthood. Greater psychosocial adversity in childhood is associated with poorer physical capability, independently of social disadvantage in childhood. Our findings highlight the need for interventions to both identify and support children experiencing socioeconomic or psychosocial of adversity as early as possible. PMID:28891666

Adult attachment as mediator between recollections of childhood and satisfaction with life.

PubMed

Hinnen, Chris; Sanderman, Robbert; Sprangers, Mirjam A G

2009-01-01

In accordance with attachment theory, the present study investigates whether internal working models of attachment mediated the association between childhood memories and satisfaction about life in adulthood. A convenient sample of 437 participants completed questionnaires assessing a broad range of childhood memories, working models of attachment and life satisfaction. After controlling for demographics, relational status and living condition, Baron and Kenny's mediation criteria were met for the association between memories about childhood, adult attachment and life satisfaction. That is, family warmth and harmony and parental support were associated with attachment security while parental rejection and adverse childhood events (e.g., abuse, parental psychopathology) were associated with an insecure attachment style. More securely attached individuals were in turn more satisfied about their current life than insecurely attached individuals. Sobel test confirmed these findings. These finding are in accordance with attachment theory and highlight the importance of this theory for understanding how early childhood experiences may impact adult life.

Adverse life events and health: a population study in Hong Kong.

PubMed

Karatzias, Thanos; Yan, Elsie; Jowett, Sally

2015-02-01

Although the effects of adverse life events on mental health have been well documented in the literature, there has never been a population based study that investigated systematically the association between history of adverse life events and physical health (objective and subjective) in adults. Cross-sectional, face-to-face household population based survey of adults (18+) in Hong Kong (N=1147). Participants were asked if they had a diagnosis of six health conditions including hypertension, heart disease, arthritis, diabetes, eyesight degeneration, and hearing loss. They were also asked if they had experienced five adverse life events including death of a partner or spouse, abuse, natural disaster, life threatening illness or injury, and family disruption. Interviews also included the Short-Form 12 Health Survey (SFHS-12) and the short version of the Centre for Epidemiologic Studies Depression Scale (CES-D). Overall, results indicate that specific adverse life events may be associated with specific health conditions. However, all tested life events were associated with subjective physical and mental health. Death of partner or parent and life threatening illness or injury were found to have the strongest association with physical health problems. A dose-response relationship between adverse life events and physical health in general was evident but more so for heart disease and eyesight degeneration. Considering the high prevalence of traumatic events and how common the conditions associated with such events are in the general population, screening for adverse life events as part of comprehensive assessment will allow a deeper understanding of patients' needs. Copyright © 2014 Elsevier Inc. All rights reserved.

Lifecourse adversity and physical performance across countries among men and women aged 65-74.

PubMed

Sousa, Ana Carolina Patrício de Albuquerque; Guerra, Ricardo Oliveira; Thanh Tu, Mai; Phillips, Susan P; Guralnik, Jack M; Zunzunegui, Maria-Victoria

2014-01-01

This study examines the associations between lifecourse adversity and physical performance in old age in different societies of North and South America and Europe. We used data from the baseline survey of the International Study of Mobility in Aging, conducted in: Kingston (Canada), Saint-Hyacinthe (Canada), Natal (Brazil), Manizales (Colombia) and Tirana (Albania). The study population was composed of community dwelling people between 65 and 74 years of age, recruiting 200 men and 200 women at each site. Physical Performance was assessed with the Short Physical Performance Battery (SPPB). Economic and social adversity was estimated from childhood adverse events, low education, semi-skilled occupations during adulthood and living alone and insufficient income in old age. A total of 1995 people were assessed. Low physical performance was associated with childhood social and economic adversity, semi-skilled occupations, living alone and insufficient income. Physical performance was lower in participants living in Colombia, Brazil and Albania than in Canada counterparts, despite adjustment for lifecourse adversity, age and sex. We show evidence of the early origins of social and economic inequalities in physical performance during old age in distinct populations and for the independent and cumulative disadvantage of low socioeconomic status during adulthood and poverty and living alone in later life.

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation.

PubMed

Unternaehrer, Eva; Bolten, Margarete; Nast, Irina; Staehli, Simon; Meyer, Andrea H; Dempster, Emma; Hellhammer, Dirk H; Lieb, Roselind; Meinlschmidt, Gunther

2016-09-01

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment. © The Author (2016). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Early deprivation disruption of associative learning is a developmental pathway to depression and social problems.

PubMed

Sheridan, Margaret A; McLaughlin, Katie A; Winter, Warren; Fox, Nathan; Zeanah, Charles; Nelson, Charles A

2018-06-07

Exposure to psychosocial deprivation is associated with elevations in numerous forms of impairment throughout the life-course. Disruptions in associative learning may be a key mechanism through which adversity, particularly psychosocial deprivation, increases risk for impairment. Existing data consistent with this claim come entirely from correlational studies. Here, we present the first experimental evidence relating psychosocial deprivation and disruptions in multiple forms of associative learning. Using data from the Bucharest Early Intervention Project, we demonstrate that randomized placement into a family caregiving environment during the infant/toddler period as compared to prolonged institutional care normalizes two forms of associative learning in early adolescence: reward responsivity and implicit motor learning. These forms of associative learning significantly mediate the effect of institutional rearing on depressive symptoms and peer relationships. In sum, we provide evidence for a novel pathway linking early experience to psychopathology and peer relationships through basic associative learning mechanisms.

Early (< 8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants.

PubMed

Doyle, Lex W; Cheong, Jeanie L; Ehrenkranz, Richard A; Halliday, Henry L

2017-10-24

Bronchopulmonary dysplasia remains a major problem in neonatal intensive care units. Persistent inflammation in the lungs is the most likely underlying pathogenesis. Corticosteroids have been used to prevent or treat bronchopulmonary dysplasia because of their potent anti-inflammatory effects. To examine the relative benefits and adverse effects of systemic postnatal corticosteroids commenced within the first seven days of life for preterm infants at risk of developing bronchopulmonary dysplasia. For the 2017 update, we used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 1); MEDLINE via PubMed (January 2013 to 21 February 2017); Embase (January 2013 to 21 February 2017); and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 2013 to 21 February 2017). We also searched clinical trials databases, conference proceedings, and reference lists of retrieved articles for randomised controlled trials (RCTs) and quasi-randomised trials. For this review, we selected RCTs examining systemic postnatal corticosteroid treatment within the first seven days of life (early) in high-risk preterm infants. Most studies evaluated the use of dexamethasone, but we also included studies that assessed hydrocortisone, even when used primarily for management of hypotension. We used the GRADE approach to assess the quality of evidence.We extracted and analysed data regarding clinical outcomes that included mortality, bronchopulmonary dysplasia, death or bronchopulmonary dysplasia, failure to extubate, complications during primary hospitalisation, and long-term health outcomes. We included 32 RCTs enrolling a total of 4395 participants. The overall risk of bias of included studies was probably low, as all were RCTs, and most trials used rigorous methods. Investigators reported significant benefits for the following outcomes overall: lower rates of failure to extubate, decreased risks of bronchopulmonary dysplasia both at 28 days of life and at 36 weeks' postmenstrual age, death or bronchopulmonary dysplasia at 28 days of life and at 36 weeks' postmenstrual age, patent ductus arteriosus, and retinopathy of prematurity (ROP), including severe ROP. Researchers found no significant differences in rates of neonatal or subsequent mortality; they noted that gastrointestinal bleeding and intestinal perforation were important adverse effects, and that risks of hyperglycaemia, hypertension, hypertrophic cardiomyopathy, and growth failure were increased. The 13 trials that reported late outcomes described several adverse neurological effects at follow-up examination, including cerebral palsy. However, study authors indicated that major neurosensory disability was not significantly increased, either overall in the eight studies for which this outcome could be determined, or in the two individual studies in which rates of cerebral palsy or abnormal neurological examination were significantly increased. Moreover, data show that rates of the combined outcomes of death or cerebral palsy, or of death or major neurosensory disability, were not significantly increased. Two-thirds of studies used dexamethasone (n = 21). Subgroup analyses by type of corticosteroid revealed that most of the beneficial and harmful effects of treatment were attributable to dexamethasone. However, as with dexamethasone, hydrocortisone was associated with reduced rates of patent ductus arteriosus, mortality, and the combined outcome of mortality or chronic lung disease, but with increased occurrence of intestinal perforation. Results showed that hydrocortisone was not associated with obvious longer-term problems.Use of the GRADE approach revealed that the quality of evidence was high for the major outcomes considered, but review authors downgraded quality one level for several outcomes (mortality at latest age, bronchopulmonary dysplasia at 36 weeks, and death or bronchopulmonary dysplasia at 36 weeks) because of weak evidence of publication bias or moderate heterogeneity (death or cerebral palsy). Benefits of early postnatal corticosteroid treatment (≤ 7 days), particularly dexamethasone, may not outweigh adverse effects associated with this treatment. Although early corticosteroid treatment facilitates extubation and reduces risk of bronchopulmonary dysplasia and patent ductus arteriosus, it causes short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy, and growth failure. Long-term follow-up studies report increased risk of abnormal findings on neurological examination and increased risk of cerebral palsy. However, the methodological quality of studies examining long-term outcomes is limited in some cases: Surviving children have been assessed predominantly before school age; no study has been sufficiently powered to detect important adverse long-term neurosensory outcomes; and no study has been designed with survival free of adverse long-term neurodevelopmental disability as the primary outcome. There is a compelling need for long-term follow-up and reporting of late outcomes, especially neurological and developmental outcomes, among surviving infants who participated in all randomised trials of early postnatal corticosteroid treatment. Hydrocortisone reduced rates of patent ductus arteriosus, of mortality, and of the combined outcome of mortality or bronchopulmonary dysplasia, without causing any obvious long-term harm. However, gastrointestinal perforation was more frequent in the hydrocortisone group. Longer-term follow-up into late childhood is vital for assessment of important effects or other effects that cannot be assessed in early childhood, such as effects of early hydrocortisone treatment on higher-order neurological functions, including cognitive function, academic performance, behaviour, mental health, and motor function. Further randomised controlled trials of early hydrocortisone should include longer-term survival free of neurodevelopmental disability as the main outcome.

Mindfulness as a mediator of the association between adverse childhood experiences and alcohol use and consequences.

PubMed

Brett, Emma I; Espeleta, Hannah C; Lopez, Susanna V; Leavens, Eleanor L S; Leffingwell, Thad R

2018-09-01

One-third of college students report past-year heavy episodic drinking, making college student alcohol use an important area for continued research. Research has consistently linked early experiences of adversity to problematic substance use in adolescence and adulthood. Given the negative health consequences associated with heavy episodic drinking, it is imperative to identify mechanisms that contribute to this relation. Low levels of mindfulness have been linked to early adversity as well as impulsivity and alcohol use, therefore, the current study aims to examine the mediating role of mindfulness in the relation between early adversity and current alcohol use and consequences. Undergraduate students (N = 385) at a Midwestern university completed an online questionnaire assessing experiences of childhood adversity, trait mindfulness, and current alcohol use and related consequences. Results indicated that increased adverse experiences and lower levels of mindfulness predicted both increased alcohol consumption and consequences (ps < 0.025), with mindfulness mediating the relationships. Mindfulness is a predictor of alcohol outcomes and appears to mediate the relation between early adversity and alcohol use and consequences. Findings suggest that students with a history of adversity are more likely to exhibit lower levels of mindfulness, which may lead to an increase in alcohol consumption and consequences in early adulthood. Targeted alcohol intervention efforts that incorporate mindfulness skills may be particularly beneficial for those who have experienced early adversity. Copyright © 2018. Published by Elsevier Ltd.

The early life nutritional environment and early life stress as potential pathways towards the metabolic syndrome in mid-life? A lifecourse analysis using the 1958 British Birth cohort.

PubMed

Delpierre, C; Fantin, R; Barboza-Solis, C; Lepage, B; Darnaudéry, M; Kelly-Irving, M

2016-08-18

Lifecourse studies suggest that the metabolic syndrome (MetS) may be rooted in the early life environment. This study aims to examine the pathways linking early nutritional and psychosocial exposures and the presence of MetS in midlife. Data are from the National Child Development Study including individuals born during 1 week in 1958 in Great Britain and followed-up until now. MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III classification. Mother's pre-pregnancy body mass index (BMI) was used as a proxy of the early nutritional environment and Adverse Childhood Experiences (ACE) as a proxy for early psychosocial stress. Socioeconomic characteristics, pregnancy and birth conditions were extracted as potential confounders. Adult health behaviors, BMI, socioeconomic environment and psychological state were considered as mediating variables. Multivariate models were performed by including variables sequentially taking a lifecourse approach. 37.5 % of men and 19.8 % of women had MetS. Participants with an obese/overweight mother presented a higher risk of MetS than those whose mother had a normal pre-pregnancy BMI. Men exposed to two ACE or more, and women exposed to one ACE, were more at risk of MetS compared to unexposed individuals. After including confounders and mediators, mother's pre-pregnancy BMI was still associated with MetS in midlife but the association was weakened after including participant's adult BMI. ACE was no longer associated with MetS after including confounders in models. The early nutritional environment, represented by mother's pre-pregnancy BMI, was associated with the risk of MetS in midlife. An important mechanism involves a mother-to-child BMI transmission, independent of birth or perinatal conditions, socioeconomic characteristics and health behaviors over the lifecourse. However this mechanism is not sufficient for explaining the influence of mother's pre-pregnancy BMI which implies the need to further explore other mechanisms in particular the role of genetics and early nutritional environment. ACE is not independently associated with MetS. However, other early life stressful events such as emergency caesarean deliveries and poor socioeconomic status during childhood may contribute as determinants of MetS.

Adverse life events and delinquent behavior among Kenyan adolescents: a cross-sectional study on the protective role of parental monitoring, religiosity, and self-esteem

PubMed Central

2014-01-01

Background Past research provides strong evidence that adverse life events heighten the risk of delinquent behavior among adolescents. Urban informal (slum) settlements in sub-Saharan Africa are marked by extreme adversity. However, the prevalence and consequences of adverse life events as well as protective factors that can mitigate the effects of exposure to these events in slum settlements is largely understudied. We examine two research questions. First, are adverse life events experienced at the individual and household level associated with a higher likelihood of delinquent behavior among adolescents living in two slums in Nairobi, Kenya? Second, are parental monitoring, religiosity, and self-esteem protective against delinquency in a context of high adversity? Methods We used cross-sectional data from 3,064 males and females aged 12–19 years who participated in the Transitions to Adulthood Study. We examined the extent to which a composite index of adverse life events was associated with delinquent behavior (measured using a composite index derived from nine items). We also examined the direct and moderating effects of three protective factors: parental monitoring, religiosity, and self-esteem. Results Fifty-four percent of adolescents reported at least one adverse life event, while 18% reported three or more adverse events. For both males and females, adversity was positively and significantly associated with delinquency in bivariate and multivariate models. Negative associations were observed between the protective factors and delinquency. Significant adverse events × protective factor interaction terms were observed for parental monitoring (females and males), religiosity (males), and self-esteem (females). Conclusions Similar to research in high income countries, adverse life events are associated with an increased likelihood of delinquent behavior among adolescents living in urban slums in Kenya, a low-income country. However, parental monitoring, religiosity, and self-esteem may moderate the effect of adversity on delinquent behavior and pinpoint possible avenues to develop interventions to reduce delinquency in resource-poor settings in low and middle income countries. PMID:25210535

Interactions Between Depression and Lower Urinary Tract Symptoms: The Role of Adverse Life Events and Inflammatory Mechanisms. Results From the European Male Ageing Study.

PubMed

Castellini, Giovanni; Wu, Frederick C W; Finn, Joseph D; OʼNeill, Terrence W; Lean, Michael E J; Pendleton, Neil; Rastrelli, Giulia; Rutter, Martin K; Gacci, Mauro; Ricca, Valdo; Maggi, Mario

2016-01-01

Depression and lower urinary tract symptoms (LUTSs) have been found to co-occur among aging men. The present study attempted to clarify the nature of this relationship, considering adverse life events as potential moderators and the inflammation as an underlying biological mechanism. The relationship between depression and LUTS was evaluated using data from the European Male Ageing Study, the largest multicenter population-based study of aging in European men. The sample included 3369 men who were assessed by means of several self-reported questionnaires, including the Beck Depression Inventory-II, the International Prostate Symptom Score, and the Adverse Life Events Scale. Participants were asked to provide information regarding general health and life-style, and medical comorbidities. Biological measures including prostate-specific antigen, testosterone, and C-reactive protein were measured. LUTS and depressive symptoms were correlated (R = 0.32, β = .10, p < .001), even after adjusting for life-style, psychological, and medical variables. A history of adverse life events was associated with both higher LUTS and Beck Depression Inventory scores. Furthermore, adverse life events moderated the LUTS-depression association (F = 22.62, b = 0.061, p < .001), which increased as a function of the number of life events. C-reactive protein was found to mediate the LUTS-depression association. This mediation effect was moderated by number of adverse life events. Participants with a history of adverse life events represent a vulnerable population in whom the association between somatic and depressive symptoms is stronger. One of the biological mechanisms underlying this association could be an activation of the central inflammatory signaling pathways.

Novel coronary heart disease risk factors at 60–64 years and life course socioeconomic position: The 1946 British birth cohort

PubMed Central

Jones, Rebecca; Hardy, Rebecca; Sattar, Naveed; Deanfield, John E.; Hughes, Alun; Kuh, Diana; Murray, Emily T.; Whincup, Peter H.; Thomas, Claudia

2015-01-01

Social disadvantage across the life course is associated with a greater risk of coronary heart disease (CHD) and with established CHD risk factors, but less is known about whether novel CHD risk factors show the same patterns. The Medical Research Council National Survey of Health and Development was used to investigate associations between occupational socioeconomic position during childhood, early adulthood and middle age and markers of inflammation (C-reactive protein, interleukin-6), endothelial function (E-selectin, tissue-plasminogen activator), adipocyte function (leptin, adiponectin) and pancreatic beta cell function (proinsulin) measured at 60–64 years. Life course models representing sensitive periods, accumulation of risk and social mobility were compared with a saturated model to ascertain the nature of the relationship between social class across the life course and each of these novel CHD risk factors. For interleukin-6 and leptin, low childhood socioeconomic position alone was associated with high risk factor levels at 60–64 years, while for C-reactive protein and proinsulin, cumulative effects of low socioeconomic position in both childhood and early adulthood were associated with higher (adverse) risk factor levels at 60–64 years. No associations were observed between socioeconomic position at any life period with either endothelial marker or adiponectin. Associations for C-reactive protein, interleukin-6, leptin and proinsulin were reduced considerably by adjustment for body mass index and, to a lesser extent, cigarette smoking. In conclusion, socioeconomic position in early life is an important determinant of several novel CHD risk factors. Body mass index may be an important mediator of these relationships. PMID:25437893

Adverse events and the relation with quality of life in adults with intellectual disability and challenging behaviour using psychotropic drugs.

PubMed

Scheifes, Arlette; Walraven, Sanne; Stolker, Joost Jan; Nijman, Henk L I; Egberts, Toine C G; Heerdink, Eibert R

2016-01-01

Psychotropic drugs are prescribed to approximately 30-40% of adults with intellectual disability (ID) and challenging behaviour, despite the limited evidence of effectiveness and the potential of adverse events. To assess the prevalence of adverse events in association with psychotropic drug use in adults with ID and challenging behaviour and to examine the relation of these adverse events with the person's quality of life. The presence of adverse events was measured with a questionnaire that had to be filled in by the physicians of the participants. Movement disorders were measured separately with a standardised protocol. The strength of the association between adverse events and Intellectual Disability Quality of Life-16 (IDQOL-16), and daily functioning was investigated using linear regression analyses, taking into account the severity of disease (CGI-S) as potential confounder. Virtually all of 103 adults with ID and challenging behaviour had at least one adverse event (84.4%) and almost half had ≥3 adverse events (45.6%) across different subclasses. Using psychotropic drugs increased the prevalence of adverse events significantly. Respectively 13% of the patients without psychotropic drugs and 61% of the patients with ≥2 psychotropic drugs had ≥3 adverse events. Having adverse events had a significantly negative influence on the quality of life. A large majority of all patients had at least one adverse event associated with psychotropic drug use. More attention is needed for these adverse events and their negative influence on the quality of life of these patients, taking into account the lack of evidence of effectiveness of psychotropic drugs for challenging behaviour. Copyright © 2015. Published by Elsevier Ltd.

The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles.

PubMed

Barrett, C E; Arambula, S E; Young, L J

2015-07-21

Genes and social experiences interact to create variation in social behavior and vulnerability to develop disorders of the social domain. Socially monogamous prairie voles display remarkable diversity in neuropeptide receptor systems and social behavior. Here, we examine the interaction of early-life adversity and brain oxytocin receptor (OTR) density on adult social attachment in female prairie voles. First, pups were isolated for 3 h per day, or unmanipulated, from postnatal day 1-14. Adult subjects were tested on the partner preference (PP) test to assess social attachment and OTR density in the brain was quantified. Neonatal social isolation impaired female PP formation, without affecting OTR density. Accumbal OTR density was, however, positively correlated with the percent of time spent huddling with the partner in neonatally isolated females. Females with high accumbal OTR binding were resilient to neonatal isolation. These results are consistent with the hypothesis that parental nurturing shapes neural systems underlying social relationships by enhancing striatal OTR signaling. Thus, we next determined whether early touch, mimicking parental licking and grooming, stimulates hypothalamic OT neuron activity. Tactile stimulation induced immediate-early gene activity in OT neurons in neonates. Finally, we investigated whether pharmacologically potentiating OT release using a melanocortin 3/4 agonist, melanotan-II (10 mg kg(-1) subcutaneously), would mitigate the social isolation-induced impairments in attachment behavior. Neonatal melanotan-II administration buffered against the effects of early isolation on partner preference formation. Thus, variation in accumbal OTR density and early OT release induced by parental nurturing may moderate susceptibility to early adverse experiences, including neglect.

Effects of Hurricane Katrina and Other Adverse Life Events on Adolescent Female Offenders: A Test of General Strain Theory

PubMed Central

Robertson, Angela R.; Stein, Judith A.; Schaefer-Rohleder, Lacey

2011-01-01

This study tested Agnew’s General Strain Theory (GST) by examining the roles of anger, anxiety, and maladaptive coping in mediating the relationship between strain and three outcomes (serious delinquency, minor delinquency, and continued involvement in the juvenile justice system) among adolescent female offenders (N = 261). Strains consisted of adverse life events and exposure to Hurricane Katrina. Greater exposure to Hurricane Katrina was directly related to serious delinquency and maladaptive coping. Hurricane Katrina also had an indirect effect on minor delinquency and Post–Katrina juvenile justice involvement mediated through maladaptive coping. Adverse life events were associated with increased anger, anxiety, and maladaptive coping. Anger mediated the relationship between adverse life events and serious delinquency. Anxiety mediated the relationship between adverse life events and minor delinquency. Maladaptive coping strategies were associated with minor delinquency and juvenile justice involvement. Findings lend support to GST. PMID:21572904

The interaction of early life experiences with COMT val158met affects anxiety sensitivity.

PubMed

Baumann, C; Klauke, B; Weber, H; Domschke, K; Zwanzger, P; Pauli, P; Deckert, J; Reif, A

2013-11-01

The pathogenesis of anxiety disorders is considered to be multifactorial with a complex interaction of genetic factors and individual environmental factors. Therefore, the aim of this study was to examine gene-by-environment interactions of the genes coding for catechol-O-methyltransferase (COMT) and monoamine oxidase A (MAOA) with life events on measures related to anxiety. A sample of healthy subjects (N = 782; thereof 531 women; mean age M = 24.79, SD = 6.02) was genotyped for COMT rs4680 and MAOA-uVNTR (upstream variable number of tandem repeats), and was assessed for childhood adversities [Childhood Trauma Questionnaire (CTQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] and anxious apprehension [Penn State Worry Questionnaire (PSWQ)]. Main and interaction effects of genotype, environment and gender on measures related to anxiety were assessed by means of regression analyses. Association analysis showed no main gene effect on either questionnaire score. A significant interactive effect of childhood adversities and COMT genotype was observed: Homozygosity for the low-active met allele and high CTQ scores was associated with a significant increment of explained ASI variance [R(2) = 0.040, false discovery rate (FDR) corrected P = 0.04]. A borderline interactive effect with respect to MAOA-uVNTR was restricted to the male subgroup. Carriers of the low-active MAOA allele who reported more aversive experiences in childhood exhibited a trend for enhanced anxious apprehension (R(2) = 0.077, FDR corrected P = 0.10). Early aversive life experiences therefore might increase the vulnerability to anxiety disorders in the presence of homozygosity for the COMT 158met allele or low-active MAOA-uVNTR alleles. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of Type 2 diabetes mellitus.

PubMed Central

Holness, M J; Langdown, M L; Sugden, M C

2000-01-01

There is increasing epidemiological evidence in humans which associates low birthweight with later metabolic disorders, including insulin resistance and glucose intolerance. There is evidence that nutritional and hormonal factors (e.g. maternal protein restriction, exposure to excess maternal glucocorticoids) markedly influence intra-uterine growth and development. A picture is also emerging of the biochemical and physiological mechanisms that may underlie these effects. This review focuses on recent research directed towards understanding the molecular basis of the relationship between indices of poor early growth and the subsequent development of glucose intolerance and Type 2 diabetes mellitus using animal models that attempt to recreate the process of programming via an adverse intra-uterine or neonatal environment. Emphasis is on the chain of events and potential mechanisms by which adverse adaptations affect pancreatic-beta-cell insulin secretion and the sensitivity to insulin of key metabolic processes, including hepatic glucose production, skeletal-muscle glucose disposal and adipose-tissue lipolysis. Unravelling the molecular details involved in metabolic programming may provide new insights into the pathogenesis of impaired glucoregulation and Type 2 diabetes. PMID:10903125

Behavioral, emotional and neurobiological determinants of coronary heart disease risk in women☆

PubMed Central

Vaccarino, Viola; Bremner, J. Douglas

2016-01-01

Women have more of the stress-related behavioral profile that has been linked to cardiovascular disease than men. For example, women double the rates of stress-related mental disorders such as depression and posttraumatic stress disorder (PTSD) than men, and have higher rates of exposure to adversity early in life. This profile may increase women's long-term risk of cardiometabolic conditions linked to stress, especially coronary heart disease (CHD). In addition to having a higher prevalence of psychosocial stress-ors, women may be more vulnerable to the adverse effects of these stressors on CHD, perhaps through altered neurobiological physiology. Emerging data suggest that young women are disproportionally susceptible to the adverse effects of stress on the risk of cardiovascular disease, both in terms of initiating the disease as well as worsening the prognosis in women who have already exhibited symptoms of the disease. Women's potential vulnerability to psychosocial stress could also help explain their higher propensity toward abnormal coronary vasomotion and microvascular disease compared with men. PMID:27496672

Developmental Programming of Cardiovascular Disease Following Intrauterine Growth Restriction: Findings Utilising A Rat Model of Maternal Protein Restriction

PubMed Central

Zohdi, Vladislava; Lim, Kyungjoon; Pearson, James T.; Black, M. Jane

2014-01-01

Over recent years, studies have demonstrated links between risk of cardiovascular disease in adulthood and adverse events that occurred very early in life during fetal development. The concept that there are embryonic and fetal adaptive responses to a sub-optimal intrauterine environment often brought about by poor maternal diet that result in permanent adverse consequences to life-long health is consistent with the definition of “programming”. The purpose of this review is to provide an overview of the current knowledge of the effects of intrauterine growth restriction (IUGR) on long-term cardiac structure and function, with particular emphasis on the effects of maternal protein restriction. Much of our recent knowledge has been derived from animal models. We review the current literature of one of the most commonly used models of IUGR (maternal protein restriction in rats), in relation to birth weight and postnatal growth, blood pressure and cardiac structure and function. In doing so, we highlight the complexity of developmental programming, with regards to timing, degree of severity of the insult, genotype and the subsequent postnatal phenotype. PMID:25551250

The CREST-E study of creatine for Huntington disease

PubMed Central

Schifitto, Giovanni; Oakes, David; Bredlau, Amy-Lee; Meyers, Catherine M.; Nahin, Richard; Rosas, Herminia Diana

2017-01-01

Objective: To investigate whether creatine administration could slow progressive functional decline in adults with early symptoms of Huntington disease. Methods: We conducted a multicenter, randomized, double-blind, placebo-controlled study of up to 40 g daily of creatine monohydrate in participants with stage I and II HD treated for up to 48 months. The primary outcome measure was the rate of change in total functional capacity (TFC) between baseline and end of follow-up. Secondary outcome measures included changes in additional clinical scores, tolerability, and quality of life. Safety was assessed by adverse events and laboratory studies. Results: At 46 sites in North America, Australia, and New Zealand, 553 participants were randomized to creatine (275) or placebo (278). The trial was designed to enroll 650 patients, but was halted for futility after the first interim analysis. The estimated rates of decline in the primary outcome measure (TFC) were 0.82 points per year for participants on creatine, 0.70 points per year for participants on placebo, favoring placebo (nominal 95% confidence limits −0.11 to 0.35). Adverse events, mainly gastrointestinal, were significantly more common in participants on creatine. Serious adverse events, including deaths, were more frequent in the placebo group. Subgroup analysis suggested that men and women may respond differently to creatine treatment. Conclusions: Our data do not support the use of creatine treatment for delaying functional decline in early manifest HD. Clinicaltrials.gov identifier: NCT00712426. Classification of evidence: This study provides Class II evidence that for patients with early symptomatic HD, creatine monohydrate is not beneficial for slowing functional decline. PMID:28701493

Positive Adjustment Among American Repatriated Prisoners of the Vietnam War: Modeling the Long-Term Effects of Captivity.

PubMed

King, Daniel W; King, Lynda A; Park, Crystal L; Lee, Lewina O; Kaiser, Anica Pless; Spiro, Avron; Moore, Jeffrey L; Kaloupek, Danny G; Keane, Terence M

2015-11-01

A longitudinal lifespan model of factors contributing to later-life positive adjustment was tested on 567 American repatriated prisoners from the Vietnam War. This model encompassed demographics at time of capture and attributes assessed after return to the U.S. (reports of torture and mental distress) and approximately 3 decades later (later-life stressors, perceived social support, positive appraisal of military experiences, and positive adjustment). Age and education at time of capture and physical torture were associated with repatriation mental distress, which directly predicted poorer adjustment 30 years later. Physical torture also had a salutary effect, enhancing later-life positive appraisals of military experiences. Later-life events were directly and indirectly (through concerns about retirement) associated with positive adjustment. Results suggest that the personal resources of older age and more education and early-life adverse experiences can have cascading effects over the lifespan to impact well-being in both positive and negative ways.

Positive Adjustment Among American Repatriated Prisoners of the Vietnam War: Modeling the Long-Term Effects of Captivity

PubMed Central

King, Daniel W.; King, Lynda A.; Park, Crystal L.; Lee, Lewina O.; Kaiser, Anica Pless; Spiro, Avron; Moore, Jeffrey L.; Kaloupek, Danny G.; Keane, Terence M.

2015-01-01

A longitudinal lifespan model of factors contributing to later-life positive adjustment was tested on 567 American repatriated prisoners from the Vietnam War. This model encompassed demographics at time of capture and attributes assessed after return to the U.S. (reports of torture and mental distress) and approximately 3 decades later (later-life stressors, perceived social support, positive appraisal of military experiences, and positive adjustment). Age and education at time of capture and physical torture were associated with repatriation mental distress, which directly predicted poorer adjustment 30 years later. Physical torture also had a salutary effect, enhancing later-life positive appraisals of military experiences. Later-life events were directly and indirectly (through concerns about retirement) associated with positive adjustment. Results suggest that the personal resources of older age and more education and early-life adverse experiences can have cascading effects over the lifespan to impact well-being in both positive and negative ways. PMID:26693100

Adversity, time, and well-being: A longitudinal analysis of time perspective in adulthood.

PubMed

Holman, E Alison; Silver, Roxane Cohen; Mogle, Jacqueline A; Scott, Stacey B

2016-09-01

Despite the prominence of time in influential aging theories and the ubiquity of stress across the life span, research addressing how time perspective (TP) and adversity are associated with well-being across adulthood is rare. Examining the role of TP in coping with life events over the life span would be best accomplished after large-scale population-based exposure to a specific event, with repeated assessments to examine within- and between-person differences over time. A national sample aged 18-91 years (N = 722, M = 49.4 years) was followed for 3 years after the September 11, 2001 (9/11) terrorist attacks. Respondents completed assessments of 9/11-related television (TV) exposure 9-21 days after the attacks, temporal disintegration 2 months post-9/11, and TP, ongoing stress, and well-being at 12, 24, and 36 months post-9/11. Results provided support for measurement invariance of TP across time and across age. Early 9/11-related TV exposure was significantly associated with greater temporal disintegration. Temporal disintegration and ongoing stress, in turn, were associated with between- and within-person variation in past TP. This effect was qualified by an age interaction that indicated a stronger relationship between ongoing stress and past TP for younger compared with older adults. Past and future TP were significantly and independently related to individual differences and within-person variation in psychological well-being, regardless of age. Future work should incorporate adversity as an important correlate of TP across adulthood. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Air pollution-induced placental epigenetic alterations in early life: a candidate miRNA approach

PubMed Central

Tsamou, Maria; Vrijens, Karen; Madhloum, Narjes; Lefebvre, Wouter; Vanpoucke, Charlotte; Nawrot, Tim S

2018-01-01

ABSTRACT Particulate matter (PM) exposure during in utero life may entail adverse health outcomes in later-life. Air pollution's adverse effects are known to alter gene expression profiles, which can be regulated by microRNAs (miRNAs). We investigate the potential influence of air pollution exposure in prenatal life on placental miRNA expression. Within the framework of the ENVIRONAGE birth cohort, we measured the expression of six candidate miRNAs in placental tissue from 210 mother-newborn pairs by qRT-PCR. Trimester-specific PM2.5 exposure levels were estimated for each mother's home address using a spatiotemporal model. Multiple regression models were used to study miRNA expression and in utero exposure to PM2.5 over various time windows during pregnancy. The placental expression of miR-21 (−33.7%, 95% CI: −53.2 to −6.2, P = 0.022), miR-146a (−30.9%, 95% CI: −48.0 to −8.1, P = 0.012) and miR-222 (−25.4%, 95% CI: −43.0 to −2.4, P = 0.034) was inversely associated with PM2.5 exposure during the 2nd trimester of pregnancy, while placental expression of miR-20a and miR-21 was positively associated with 1st trimester exposure. Tumor suppressor phosphatase and tensin homolog (PTEN) was identified as a common target of the miRNAs significantly associated with PM exposure. Placental PTEN expression was strongly and positively associated (+59.6% per 5 µg/m³ increment, 95% CI: 26.9 to 100.7, P < 0.0001) with 3rd trimester PM2.5 exposure. Further research is required to establish the role these early miRNA and mRNA expression changes might play in PM-induced health effects. We provide molecular evidence showing that in utero PM2.5 exposure affects miRNAs expression as well as its downstream target PTEN. PMID:27104955

Childhood Social Disadvantage, Cardiometabolic Risk, and Chronic Disease in Adulthood

PubMed Central

Non, Amy L.; Rewak, Marissa; Kawachi, Ichiro; Gilman, Stephen E.; Loucks, Eric B.; Appleton, Allison A.; Román, Jorge C.; Buka, Stephen L.; Kubzansky, Laura D.

2014-01-01

Adverse social environments in early life are hypothesized to become biologically embedded during the first few years of life, with potentially far-reaching implications for health across the life course. Using prospective data from a subset of a US birth cohort, the Collaborative Perinatal Project, started in 1959–1966 (n = 566), we examined associations of social disadvantage assessed in childhood with cardiometabolic function and chronic disease status more than 40 years later (in 2005–2007). Social disadvantage was measured with an index that combined information on adverse socioeconomic and family stability factors experienced between birth and age 7 years. Cardiometabolic risk (CMR) was assessed by combining information from 8 CMR biomarkers; an index of chronic disease status was derived by assessing 8 chronic diseases. Poisson models were used to investigate associations between social disadvantage and CMR or chronic disease scores while adjusting for childhood covariates and potential pathway variables. A high level of social disadvantage was significantly associated with both higher CMR (incident rate ratio = 1.69, 95% confidence interval: 1.19, 2.39) and with a higher number of chronic diseases (incident rate ratio = 1.39, 95% confidence interval: 1.00, 1.92) in minimally adjusted models. Associations with CMR persisted even after accounting for childhood and adult covariates. PMID:24970845

AMP-Activated Protein Kinase as a Reprogramming Strategy for Hypertension and Kidney Disease of Developmental Origin.

PubMed

Tain, You-Lin; Hsu, Chien-Ning

2018-06-12

Suboptimal early-life conditions affect the developing kidney, resulting in long-term programming effects, namely renal programming. Adverse renal programming increases the risk for developing hypertension and kidney disease in adulthood. Conversely, reprogramming is a strategy aimed at reversing the programming processes in early life. AMP-activated protein kinase (AMPK) plays a key role in normal renal physiology and the pathogenesis of hypertension and kidney disease. This review discusses the regulation of AMPK in the kidney and provides hypothetical mechanisms linking AMPK to renal programming. This will be followed by studies targeting AMPK activators like metformin, resveratrol, thiazolidinediones, and polyphenols as reprogramming strategies to prevent hypertension and kidney disease. Further studies that broaden our understanding of AMPK isoform- and tissue-specific effects on renal programming are needed to ultimately develop reprogramming strategies. Despite the fact that animal models have provided interesting results with regard to reprogramming strategies targeting AMPK signaling to protect against hypertension and kidney disease with developmental origins, these results await further clinical translation.

Small body size in an insect shifts development, prior to adult eclosion, towards early reproduction

PubMed Central

Thorne, Ashley D; Pexton, John J; Dytham, Calvin; Mayhew, Peter J

2006-01-01

Life-history theory has suggested that individual body size can strongly affect the allocation of resources to reproduction and away from other traits such as survival. In many insects, adults eclose with a proportion of their potential lifetime egg production that is already mature (the ovigeny index). We establish for the solitary parasitoid wasp Aphaereta genevensis that the ovigeny index decreases with adult body size, despite both initial egg load and potential lifetime fecundity increasing with body size. This outcome is predicted by adaptive models and is the first unequivocal intraspecific demonstration. Evidence suggests that a high ovigeny index carries a cost of reduced longevity in insects. Our results therefore contribute to the emerging evidence that small body size can favour a developmental shift in juveniles that favours early reproduction, but which has adverse late-life consequences. These findings are likely to have important implications for developmental biologists and population biologists. PMID:16600887

Heavy Rare Earth Elements Affect Sphaerechinus granularis Sea Urchin Early Life Stages by Multiple Toxicity Endpoints.

PubMed

Gravina, Maria; Pagano, Giovanni; Oral, Rahime; Guida, Marco; Toscanesi, Maria; Siciliano, Antonietta; Di Nunzio, Aldo; Burić, Petra; Lyons, Daniel M; Thomas, Philippe J; Trifuoggi, Marco

2018-05-01

Heavy rare earth elements (HREEs) were tested for adverse effects to early life stages of the sea urchin Sphaerechinus granularis. Embryos were exposed to analytically measured HREE concentrations ranging from 10 -7 to 10 -5  M. No significant developmental defect (DD) increases were observed in embryos exposed to 10 -7  M HREEs, whereas 10 -5  M HREEs resulted in significant DD increase up to 96% for HoCl 3 versus 14% in controls. Embryos exposed to 10 -6  M HREEs showed the highest DD frequency in embryos exposed to 10 -6  M DyCl 3 and HoCl 3 . Cytogenetic analysis of HREE-exposed embryos revealed a significant decrease in mitotic activity, with increased mitotic aberrations. When S. granularis sperm were exposed to HREEs, the offspring of sperm exposed to 10 -5  M GdCl 3 and LuCl 3 showed significant DD increases. The results warrant investigations on HREEs in other test systems, and on REE-containing complex mixtures.

Epigenetic and Neural Circuitry Landscape of Psychotherapeutic Interventions

PubMed Central

2017-01-01

The science behind psychotherapy has garnered considerable interest, as objective measures are being developed to map the patient's subjective change over the course of treatment. Prenatal and early life influences have a lasting impact on how genes are expressed and the manner in which neural circuits are consolidated. Transgenerationally transmitted epigenetic markers as well as templates of enhanced thought flexibility versus evasion can be passed down from parent to child. This influences gene expression/repression (impacting neuroplasticity) and kindling of neurocircuitry which can perpetuate maladaptive cognitive processing seen in a number of psychiatric conditions. Importantly, genetic factors and the compounding effects of early life adversity do not inexorably lead to certain fated outcomes. The concepts of vulnerability and resilience are becoming more integrated into the framework of “differential susceptibility,” speaking to how corrective environmental factors may promote epigenetic change and reconfigure neural templates, allowing for symptomatic improvement. Psychotherapy is one such factor, and this review will focus on our current knowledge of its epigenetic and neurocircuitry impact. PMID:29226124

Impact of adverse life events on individuals with low and high schizotypy in a nonpatient sample.

PubMed

Kocsis-Bogár, Krisztina; Miklósi, Mónika; Forintos, Dóra Perczel

2013-03-01

The aims of this study were to gain a better understanding of adverse life events connected with the development of schizotypal personality traits and, also, to examine whether subclinical schizotypy has a relationship with vulnerability to traumatic intrusions and avoidance. In a cross-sectional design, 198 undergraduate students completed the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), the Impact of Event Scale (IES), and Paykel's Life Events Scale, together with other relevant scales. The number of adverse life events was significantly related to overall schizotypy measured by O-LIFE scores and positive schizotypy measured by the Unusual Experiences (UnEx) subscale. The subjective severity of life events was significantly related to Cognitive Disorganization (CogDis). Measures of positive schizotypy (UnEx and CogDis) were significantly related to the scores on the IES and on the intrusion and avoidance subscales, too. Adverse life events are associated with schizotypal personality traits, which contribute to a tendency for traumatic intrusions, even in a nonpatient sample.

Early childhood predictors of early onset of smoking: a birth prospective study.

PubMed

Hayatbakhsh, Reza; Mamun, Abdullah A; Williams, Gail M; O'Callaghan, Michael J; Najman, Jake M

2013-10-01

Early onset of smoking is associated with subsequent abuse of other substances and development of negative health outcomes. This study aimed to examine early life predictors of onset of smoking in an Australian young cohort. Data were from the Mater Hospital and University of Queensland Study of Pregnancy (MUSP), a population-based prospective birth cohort study (1981-2012). The present study is based on a cohort of 3714 young adults who self-reported smoking status and age of onset of smoking at the 21-year follow-up. Of these, data were available for 3039 on early childhood factors collected between the baseline and 14-year follow-up of the study. Of 3714 young adults, 49.6% (49.9% males and 49.3% females) reported having ever smoked cigarettes. For those who had ever smoked, mean and median ages at first smoke were 15.5 and 16.0years, respectively. In multivariate Cox proportional hazard analysis mother's education, change in maternal marital status, maternal cigarette smoking and alcohol consumption, maternal depression and child externalizing when the child was 5years statistically significantly predicted early onset of smoking. The data suggest that individuals exposed to personal and environmental risk factors during the early stage of childhood are at increased risk of initiation to cigarette smoking at an earlier age. Identification of the pathways of association between these early life factors and initiation to cigarette smoking may help reduce risk of tobacco smoking in adolescents and its adverse consequences. Copyright © 2013 Elsevier Ltd. All rights reserved.

Early menarche and childhood adversities in a nationally representative sample.

PubMed

Henrichs, Kimberly L; McCauley, Heather L; Miller, Elizabeth; Styne, Dennis M; Saito, Naomi; Breslau, Joshua

2014-01-01

Epidemiological evidence suggests that early menarche, defined as onset of menses at age 11 or earlier, has increased in prevalence in recent birth cohorts and is associated with multiple poor medical and mental health outcomes in adulthood. There is evidence that childhood adversities occurring prior to menarche contribute to early menarche. Data collected in face-to-face interviews with a nationally representative sample of women age 18 and over (N = 3288), as part of the National Comorbidity Survey-Replication, were analyzed. Associations between pre-menarchal childhood adversities and menarche at age 11 or earlier were estimated in discrete time survival models with statistical adjustment for age at interview, ethnicity, and body mass index. Adversities investigated included physical abuse, sexual abuse, neglect, biological father absence from the home, other parent loss, parent mental illness, parent substance abuse, parent criminality, inter-parental violence, serious physical illness in childhood, and family economic adversity. Mean age at menarche varied across decadal birth cohorts (χ(2)₍₄₎ = 21.41, p < .001) ranging from a high of 12.9 years in the oldest cohort (age 59 or older at the time of interview) to a low of 12.4 in the second youngest cohort (age 28-37). Childhood adversities were also more common in younger than older cohorts. Of the 11 childhood adversities, 5 were associated with menarche at age 11 or earlier, with OR of 1.3 or greater. Each of these five adversities is associated with a 26% increase in the odds of early menarche (OR = 1.26, 95% CI 1.14-1.39). The relationship between childhood sexual abuse and early menarche was sustained after adjustment for co-occurring adversities. (OR = 1.77, 95% CI 1.21-2.6). Evidence from this study is consistent with hypothesized physiological effects of early childhood family environment on endocrine development. Childhood sexual abuse is the adversity most strongly associated with early menarche. However, because of the complex way that childhood adversities cluster within families, the more generalized influence of highly dysfunctional family environments cannot be ruled out.

Roles of attachment and self-esteem: impact of early life stress on depressive symptoms among Japanese institutionalized children.

PubMed

Suzuki, Hanako; Tomoda, Akemi

2015-02-05

Although exposure to early life stress is known to affect mental health, the underlying mechanisms of its impacts on depressive symptoms among institutionalized children and adolescents have been little studied. To investigate the role of attachment and self-esteem in association with adverse childhood experiences (ACEs) and depressive symptoms, 342 children (149 boys, 193 girls; age range 9-18 years old, mean age = 13.5 ± 2.4) living in residential foster care facilities in Japan completed questionnaires related to internal working models, self-esteem, and depressive symptoms. Their care workers completed questionnaires on ACEs. Structural equation modeling (SEM) was created and the goodness of fit was examined (CMIN = 129.223, df = 1.360, GFI = .959, AGFI = .936, CFI = .939, RMSEA = .033). Maltreatment negatively predicted scores on secure attachment, but positively predicted scores on avoidant and ambivalent attachment. The secure attachment score negatively predicted depressive symptoms. The ambivalent attachment score positively predicted depressive symptoms both directly and through self-esteem, whereas the avoidant attachment score positively predicted depressive symptoms only directly. Maltreatment neither directly predicts self-esteem nor depressive symptoms, and parental illness/death and parental sociopathic behaviors did not predict any variables. Results show that the adversity of child maltreatment affects depression through attachment styles and low self-esteem among institutionalized children. Implications of child maltreatment and recommendations for child welfare services and clinical interventions for institutionalized children are discussed.

Early Life Experiences and Telomere Length in Adult Rhesus Monkeys: An Exploratory Study

PubMed Central

Schneper, Lisa M.; Brooks-Gunn, Jeanne; Notterman, Daniel A.; Suomi, Stephen J.

2016-01-01

Objective Child rearing environments have been associated with morbidity in adult rhesus monkeys. We examine whether such links are also seen with leukocyte telomere length. Methods To determine telomere length in leukocytes, blood was collected from 11 adult females aged seven to ten years who had been exposed to different rearing environments between birth and seven months. Four had been reared with their mothers in typical social groups comprised of other females, their offspring, and 1–2 adult males. The other seven had been reared in either small groups of peers or in individual cages with extensive peer interaction daily. After seven months, all shared a common environment. Results Telomere lengths were longer for those adults who had been reared with their mothers in social groups (median = 16.0 kb, interquartile range = 16.5–15.4) than for those who were reared without their mothers (median = 14.0 kb, interquartile range = 14.3–12.7; 2.2 kb/telomere difference, p<0.027). Conclusions This observation adds to emerging knowledge about early adverse child rearing conditions and their potential for influencing later morbidity. As newborns were randomly assigned to the mother or other rearing conditions, the findings are not confounded by other conditions that co-occur with adverse child rearing environments in humans (e.g., prenatal stress, nutrition and health as well as postnatal nutrition and negative life experiences over and above rearing conditions). PMID:27763985

Epigenetic and epistatic interactions between serotonin transporter and brain-derived neurotrophic factor genetic polymorphism: insights in depression.

PubMed

Ignácio, Z M; Réus, G Z; Abelaira, H M; Quevedo, J

2014-09-05

Epidemiological studies have shown significant results in the interaction between the functions of brain-derived neurotrophic factor (BDNF) and 5-HT in mood disorders, such as major depressive disorder (MDD). The latest research has provided convincing evidence that gene transcription of these molecules is a target for epigenetic changes, triggered by stressful stimuli that starts in early childhood and continues throughout life, which are subsequently translated into structural and functional phenotypes culminating in depressive disorders. The short variants of 5-HTTLPR and BDNF-Met are seen as forms which are predisposed to epigenetic aberrations, which leads individuals to a susceptibility to environmental adversities, especially when subjected to stress in early life. Moreover, the polymorphic variants also feature epistatic interactions in directing the functional mechanisms elicited by stress and underlying the onset of depressive disorders. Also emphasized are works which show some mediators between stress and epigenetic changes of the 5-HTT and BDNF genes, such as the hypothalamic-pituitary-adrenal (HPA) axis and the cAMP response element-binding protein (CREB), which is a cellular transcription factor. Both the HPA axis and CREB are also involved in epistatic interactions between polymorphic variants of 5-HTTLPR and Val66Met. This review highlights some research studying changes in the epigenetic patterns intrinsic to genes of 5-HTT and BDNF, which are related to lifelong environmental adversities, which in turn increases the risks of developing MDD. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Do specific early-life adversities lead to specific symptoms of psychosis? A study from the 2007 the Adult Psychiatric Morbidity Survey.

PubMed

Bentall, Richard P; Wickham, Sophie; Shevlin, Mark; Varese, Filippo

2012-06-01

Previous studies have reported associations between childhood adversities, eg, loss of a parent, being raised in institutional care, sexual and other kinds of abuse by adults and bullying by peers, and psychosis in adulthood. However, the mechanisms by which these adversities lead to psychotic experiences are poorly understood. From models of the psychological processes involved in positive symptoms, it was predicted that childhood sexual abuse would be specifically associated with auditory hallucinations in adulthood, and that disruption of early attachment relations and more chronic forms of victimization such as bullying would be specifically associated with paranoid ideation. We therefore examined the associations between sexual trauma, physical abuse, bullying, and being brought up in institutional or local authority care and reports of auditory hallucinations and paranoid beliefs in the 2007 Adult Psychiatric Morbidity Survey. All simple associations between childhood adversities and the two symptom types were significant. Childhood rape was associated only with hallucinations (OR 8.9, CI = 1.86-42.44) once co-occurring paranoia was controlled for. Being brought up in institutional care (OR = 11.08, CI = 3.26-37.62) was specifically associated with paranoia once comorbid hallucinations had been controlled for. For each symptom, dose-response relationships were observed between the number of childhood traumas and the risk of the symptom. The specific associations observed are consistent with current psychological theories about the origins of hallucinations and paranoia. Further research is required to study the psychological and biological mediators of these associations.

The presence of MWCNTs reduces developmental toxicity of PFOS in early life stage of zebrafish.

PubMed

Wang, Shutao; Zhuang, Changlu; Du, Jia; Wu, Chuan; You, Hong

2017-03-01

Both carbon nanotubes (CNTs) and perfluorooctane sulfonate (PFOS) are used widely. There is considerable concern regarding their ecotoxicity. CNTs might interact with PFOS in water and result in different impacts compared with those after single exposures. To our knowledge, the developmental toxicity of PFOS in the presence of multi-walled carbon nanotubes (MWCNTs) in the early life stage of zebrafish (from 3 h post fertilization (hpf) to 96 hpf) was investigated for the first time in this study. The embryos and larvae were exposed to PFOS (0.2, 0.4, 0.8, and 1.6 mg/L), MWCNTs (50 mg/L), and a mixture of both. Compared with PFOS exposure, the adverse effects induced by PFOS on the hatching rate of zebrafish embryos and the heart rate and body length of zebrafish larvae were reduced in the presence of MWCNTs, and mortality and malformation were also alleviated. In addition, zebrafish larvae exposed to PFOS showed decreased activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as decreased levels of reactive oxygen species and malondialdehyde, in the presence of MWCNTs, indicating that oxidative stress and lipid peroxidation was relieved. Thus, the presence of MWCNTs reduces the developmental toxicity of PFOS in the early life stage of zebrafish. Copyright © 2016 Elsevier Ltd. All rights reserved.

Relationship between early-life stress load and sleep in psychiatric outpatients: a sleep diary and actigraphy study.

PubMed

Schäfer, Valérie; Bader, Klaus

2013-08-01

The present study aimed to investigate whether stress experienced early in life is associated with actigraphic and subjective sleep measures in a sample of adult psychiatric outpatients. A total of 48 psychiatric outpatients completed self-report questionnaires assessing current depression, current anxiety symptoms and stress load during childhood (before the age of 13 years), adolescence (between the age of 13 and 18 years) and adulthood (between the age of 19 and current age). Sleep-related activity was measured using 24-h wrist actigraphy over a 7-day period at home, during which participants also kept a sleep diary. High stress load in childhood, but not in adolescence, was associated with shortened actigraphically assessed total sleep time, prolonged sleep onset latency, decreased sleep efficiency and an increased number of body movements in sleep, even after accounting for the effects of later occurring stress and psychopathological symptoms such as depression and anxiety scores. Unexpectedly, no significant associations between early-life stress load and subjective sleep measures were found. Results are consistent with findings from previous studies indicating an association between childhood adversities and higher levels of nocturnal activity. The findings suggest that high stress load during childhood might be a vulnerability factor for sleep continuity problems in adulthood. Copyright © 2012 John Wiley & Sons, Ltd.

Early life status epilepticus and stress have distinct and sex-specific effects on learning, subsequent seizure outcomes, including anticonvulsant response to phenobarbital.

PubMed

Akman, Ozlem; Moshé, Solomon L; Galanopoulou, Aristea S

2015-02-01

Neonatal status epilepticus (SE) is often associated with adverse cognitive and epilepsy outcomes. We investigate the effects of three episodes of kainic acid-induced SE (3KA-SE) and maternal separation in immature rats on subsequent learning, seizure susceptibility, and consequences, and the anticonvulsant effects of phenobarbital, according to sex, type, and age at early life (EL) event. 3KA-SE or maternal separation was induced on postnatal days (PN) 4-6 or 14-16. Rats were tested on Barnes maze (PN16-19), or lithium-pilocarpine SE (PN19) or flurothyl seizures (PN32). The anticonvulsant effects of phenobarbital (20 or 40 mg/kg/rat, intraperitoneally) pretreatment were tested on flurothyl seizures. FluoroJadeB staining assessed hippocampal injury. 3KA-SE or separation on PN4-6 caused more transient learning delays in males and did not alter lithium-pilocarpine SE latencies, but aggravated its outcomes in females. Anticonvulsant effects of phenobarbital were preserved and potentiated in specific groups depending on sex, type, and age at EL event. Early life 3KA-SE and maternal separation cause more but transient cognitive deficits in males but aggravate the consequences of subsequent lithium-pilocarpine SE in females. In contrast, on flurothyl seizures, EL events showed either beneficial or no effect, depending on gender, type, and age at EL events. © 2014 John Wiley & Sons Ltd.

Childhood abuse and psychotic experiences - evidence for mediation by adulthood adverse life events.

PubMed

Bhavsar, V; Boydell, J; McGuire, P; Harris, V; Hotopf, M; Hatch, S L; MacCabe, J H; Morgan, C

2017-10-09

We have previously reported an association between childhood abuse and psychotic experiences (PEs) in survey data from South East London. Childhood abuse is related to subsequent adulthood adversity, which could form one pathway to PEs. We aimed to investigate evidence of mediation of the association between childhood abuse and PEs by adverse life events. Data were analysed from the South East London Community Health Study (SELCoH, n = 1698). Estimates of the total effects on PEs of any physical or sexual abuse while growing up were partitioned into direct (i.e. unmediated) and indirect (total and specific) effects, mediated via violent and non-violent life events. There was strong statistical evidence for direct (OR 1.58, 95% CI: 1.19-2.1) and indirect (OR 1.51, 95% CI: 1.32-1.72) effects of childhood abuse on PEs after adjustment for potential confounders, indicating partial mediation of this effect via violent and non-violent life events. An estimated 47% of the total effect of abuse on PEs was mediated via adulthood adverse life events, of which violent life events made up 33% and non-violent life events the remaining 14%. The association between childhood abuse and PEs is partly mediated through the experience of adverse life events in adulthood. There is some evidence that a larger proportion of this effect was mediated through violent life events than non-violent life events.

A prospective observational study to examine the relationship between quality of life and adverse events of first-line chemotherapy plus cetuximab in patients with KRAS wild-type unresectable metastatic colorectal cancer: QUACK Trial.

PubMed

Ooki, Akira; Ando, Masahiko; Sakamoto, Junichi; Sato, Atushi; Fujii, Hirofumi; Yamaguchi, Kensei

2014-04-01

We have planned a multicentre prospective study to examine the relative impact of the efficacy and adverse events of cetuximab plus first-line chemotherapy on the quality of life in Japanese patients with KRAS wild-type unresectable colorectal cancer. The Dermatology Life Quality Index and the European Organization for Research Treatment of Cancer Quality of Life Questionnaire Core 30 will be used to assess dermatology-specific and health-related quality of life. The severity of adverse events will be assessed by using the National Cancer Institute Common Terminology Criteria for adverse Events ver. 4.0. The endpoints will be the following associations: adverse events, including skin toxicity and quality of life; efficacy and skin toxicity; efficacy and quality of life; and skin-related quality of life and health-related quality of life. A total of 140 patients are considered to be appropriate for inclusion in this study. The results of this study will provide more information to both patients and physicians regarding the practical use of cetuximab and its impact on quality of life in patients with unresectable colorectal cancer in Japan. This study was registered at the University Hospital Medical Information Network Clinical Trial Registry as UMIN000010985.

Early Elevations of the Complement Activation Fragment C3a and Adverse Pregnancy Outcomes

PubMed Central

Lynch, Anne M.; Gibbs, Ronald S.; Murphy, James R.; Giclas, Patricia C.; Salmon, Jane E.; Holers, V. Michael

2016-01-01

OBJECTIVE To estimate whether elevations of complement C3a early in pregnancy are predictive of the subsequent development of adverse pregnancy outcomes. METHODS A plasma sample was obtained from each enrolled pregnant woman before 20 weeks of gestation. The cohort (n=1,002) was evaluated for the development of adverse pregnancy outcomes defined as hypertensive diseases of pregnancy (gestational hypertension or preeclampsia), preterm birth (before 37 weeks of gestation), premature rupture of the membranes, pregnancy loss (during the embryonic and fetal period), intrauterine growth restriction, and the composite outcome of any adverse outcome. RESULTS One or more adverse pregnancy outcomes occurred in 211 (21%) of the cohort. The mean levels (ng/mL) of C3a in early pregnancy were significantly (P=<.001) higher among women with one or more adverse outcomes (858±435) compared with women with an uncomplicated pregnancy (741±407). Adjusted for parity and prepregnancy body mass index, women with levels of C3a in the upper quartile in early pregnancy were three times more likely to have an adverse outcome later in pregnancy compared with women in the lowest quartile (95% confidence interval, 1.8–4.8; P<.001). The link between early elevated C3a levels and adverse pregnancy outcomes was driven primarily by individual significant (P<.05) associations of C3a with hypertensive diseases of pregnancy, preterm birth, and premature rupture of the membranes. CONCLUSION Elevated C3a as early as the first trimester of pregnancy is an independent predictive factor for adverse pregnancy outcomes, suggesting that complement-related inflammatory events in pregnancy contribute to the subsequent development of poor outcomes at later stages of pregnancy. PMID:21173647