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Sample records for adverse early life

  1. Cumulative early life adversity predicts longevity in wild baboons

    PubMed Central

    Tung, Jenny; Archie, Elizabeth A.; Altmann, Jeanne; Alberts, Susan C.

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  2. Cumulative early life adversity predicts longevity in wild baboons.

    PubMed

    Tung, Jenny; Archie, Elizabeth A; Altmann, Jeanne; Alberts, Susan C

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations.

  3. Cumulative early life adversity predicts longevity in wild baboons.

    PubMed

    Tung, Jenny; Archie, Elizabeth A; Altmann, Jeanne; Alberts, Susan C

    2016-01-01

    In humans and other animals, harsh circumstances in early life predict morbidity and mortality in adulthood. Multiple adverse conditions are thought to be especially toxic, but this hypothesis has rarely been tested in a prospective, longitudinal framework, especially in long-lived mammals. Here we use prospective data on 196 wild female baboons to show that cumulative early adversity predicts natural adult lifespan. Females who experience ≥3 sources of early adversity die a median of 10 years earlier than females who experience ≤1 adverse circumstances (median lifespan is 18.5 years). Females who experience the most adversity are also socially isolated in adulthood, suggesting that social processes partially explain the link between early adversity and adult survival. Our results provide powerful evidence for the developmental origins of health and disease and indicate that close ties between early adversity and survival arise even in the absence of health habit and health care-related explanations. PMID:27091302

  4. Early Life Adversity and Adult Biological Risk Profiles

    PubMed Central

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

    2015-01-01

    Objectives 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. Methods We analyzed data on 1,180 respondents from the biomarker subsample of the second wave of the National Survey of Midlife Development in the United States (MIDUS) study. ELA assessments were based on childhood socioeconomic disadvantage (i.e. on welfare, perceived low income, 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: education, social relationships, and health behaviors. Results Childhood socioeconomic adversity was associated with increased AL (B=0.094, SE=0.041) and physical abuse (B=0.263, SE=0.091), with non-significant associations for parental divorce and death. Adult education mediated the relationship between socioeconomic ELA and cumulative allostatic load to the point of non-significance, 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. Conclusions 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. PMID:25650548

  5. Children of Misfortune: Early Adversity and Cumulative Inequality in Perceived Life Trajectories1

    PubMed Central

    Schafer, Markus H.; Ferraro, Kenneth F.; Mustillo, Sarah A.

    2011-01-01

    Adversity early in life may alter pathways of aging, but what interpretive processes can soften the blow of early insults? Drawing from cumulative inequality theory, the authors analyze trajectories of life evaluations and then consider whether early adversity offsets favorable expectations for the future. Results reveal that early adversity contributes to more negative views of the past but rising expectations for the future. Early adversity also has enduring effects on life evaluations, offsetting the influence of buoyant expectations. The findings draw attention to the limits of human agency under the constraints of early adversity—a process described as biographical structuration. PMID:21648247

  6. 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

  7. Impact of early life adversity on EMG stress reactivity of the trapezius muscle.

    PubMed

    Luijcks, Rosan; Vossen, Catherine J; Roggeveen, Suzanne; van Os, Jim; Hermens, Hermie J; Lousberg, Richel

    2016-09-01

    Human and animal research indicates that exposure to early life adversity increases stress sensitivity later in life. While behavioral markers of adversity-induced stress sensitivity have been suggested, physiological markers remain to be elucidated. It is known that trapezius muscle activity increases during stressful situations. The present study examined to what degree early life adverse events experienced during early childhood (0-11 years) and adolescence (12-17 years) moderate experimentally induced electromyographic (EMG) stress activity of the trapezius muscles, in an experimental setting. In a general population sample (n = 115), an anticipatory stress effect was generated by presenting a single unpredictable and uncontrollable electrical painful stimulus at t = 3 minutes. Subjects were unaware of the precise moment of stimulus delivery and its intensity level. Linear and nonlinear time courses in EMG activity were modeled using multilevel analysis. The study protocol included 2 experimental sessions (t = 0 and t = 6 months) allowing for examination of reliability.Results show that EMG stress reactivity during the stress paradigm was consistently stronger in people with higher levels of early life adverse events; early childhood adversity had a stronger moderating effect than adolescent adversity. The impact of early life adversity on EMG stress reactivity may represent a reliable facet that can be used in both clinical and nonclinical studies. PMID:27684800

  8. Disproportionate Exposure to Early-Life Adversity and Sexual Orientation Disparities in Psychiatric Morbidity

    ERIC Educational Resources Information Center

    McLaughlin, Katie A.; Hatzenbuehler, Mark L.; Xuan, Ziming; Conron, Kerith J.

    2012-01-01

    Objectives: Lesbian, gay, and bisexual (LGB) populations exhibit elevated rates of psychiatric disorders compared to heterosexuals, and these disparities emerge early in the life course. We examined the role of exposure to early-life victimization and adversity--including physical and sexual abuse, homelessness, and intimate partner violence--in…

  9. Evaluation of hypothesized adverse outcome pathway linking thyroid peroxidase inhibition to 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...

  10. Broken or maladaptive? Altered trajectories in neuroinflammation and behavior after early life adversity

    PubMed Central

    Ganguly, Prabarna; Brenhouse, Heather C.

    2014-01-01

    Exposure to adversity and stress early in development yields vulnerability to mental illnesses throughout the lifespan. Growing evidence suggests that this vulnerability has mechanistic origins involving aberrant development of both neurocircuitry and neuro-immune activity. Here we review the current understanding of when and how stress exposure initiates neuroinflammatory events that interact with brain development. We first review how early life adversity has been associated with various psychopathologies, and how neuroinflammation plays a role in these pathologies. We then summarize data and resultant hypotheses describing how early life adversity may particularly alter neuro-immune development with psychiatric consequences. Finally, we review how sex differences contribute to individualistic vulnerabilities across the lifespan. We submit the importance of understanding how stress during early development might cause outright neural or glial damage, as well as experience-dependent plasticity that may insufficiently prepare an individual for sex-specific or life-stage specific challenges. PMID:25081071

  11. The long-term impact of early adversity on late-life psychiatric disorders.

    PubMed

    Gershon, Anda; Sudheimer, Keith; Tirouvanziam, Rabindra; Williams, Leanne M; O'Hara, Ruth

    2013-04-01

    Early adversity is a strong and enduring predictor of psychiatric disorders including mood disorders, anxiety disorders, substance abuse or dependence, and posttraumatic stress disorder. However, the mechanisms of this effect are not well understood. The purpose of this review is to summarize and integrate the current research knowledge pertaining to the long-term effects of early adversity on psychiatric disorders, particularly in late life. We explore definitional considerations including key dimensions of the experience such as type, severity, and timing of adversity relative to development. We then review the potential biological and environmental mediators and moderators of the relationships between early adversity and psychiatric disorders. We conclude with clinical implications, methodological challenges and suggestions for future research. PMID:23443532

  12. Early Life Adversity as a Risk Factor for Fibromyalgia in Later Life

    PubMed Central

    Low, Lucie A.; Schweinhardt, Petra

    2012-01-01

    The impact of early life events is increasingly becoming apparent, as studies investigate how early childhood can shape long-term physiology and behaviour. Fibromyalgia (FM), which is characterised by increased pain sensitivity and a number of affective co-morbidities, has an unclear etiology. This paper discusses risk factors from early life that may increase the occurrence or severity of FM in later life: pain experience during neonatal life causes long-lasting changes in nociceptive circuitry and increases pain sensitivity in the older organism; premature birth and related stressor exposure cause lasting changes in stress responsivity; maternal deprivation affects anxiety-like behaviours that may be partially mediated by epigenetic modulation of the genome—all these adult phenotypes are strikingly similar to symptoms displayed by FM sufferers. In addition, childhood trauma and exposure to substances of abuse may cause lasting changes in developing neurotransmitter and endocrine circuits that are linked to anxiety and stress responses. PMID:22110940

  13. General and specific effects of early-life psychosocial adversities on adolescent grey matter volume☆

    PubMed Central

    Walsh, Nicholas D.; Dalgleish, Tim; Lombardo, Michael V.; Dunn, Valerie J.; Van Harmelen, Anne-Laura; Ban, Maria; Goodyer, Ian M.

    2014-01-01

    Exposure to childhood adversities (CA) is associated with subsequent alterations in regional brain grey matter volume (GMV). Prior studies have focused mainly on severe neglect and maltreatment. The aim of this study was to determine in currently healthy adolescents if exposure to more common forms of CA results in reduced GMV. Effects on brain structure were investigated using voxel-based morphometry in a cross-sectional study of youth recruited from a population-based longitudinal cohort. 58 participants (mean age = 18.4) with (n = 27) or without (n = 31) CA exposure measured retrospectively from maternal interview were included in the study. Measures of recent negative life events (RNLE) recorded at 14 and 17 years, current depressive symptoms, gender, participant/parental psychiatric history, current family functioning perception and 5-HTTLPR genotype were covariates in analyses. A multivariate analysis of adversities demonstrated a general association with a widespread distributed neural network consisting of cortical midline, lateral frontal, temporal, limbic, and cerebellar regions. Univariate analyses showed more specific associations between adversity measures and regional GMV: CA specifically demonstrated reduced vermis GMV and past psychiatric history with reduced medial temporal lobe volume. In contrast RNLE aged 14 was associated with increased lateral cerebellar and anterior cingulate GMV. We conclude that exposure to moderate levels of childhood adversities occurring during childhood and early adolescence exerts effects on the developing adolescent brain. Reducing exposure to adverse social environments during early life may optimize typical brain development and reduce subsequent mental health risks in adult life. PMID:25061568

  14. Psychiatric symptoms in adolescents: FKBP5 genotype--early life adversity interaction effects.

    PubMed

    Comasco, Erika; Gustafsson, Per A; Sydsjö, Gunilla; Agnafors, Sara; Aho, Nikolas; Svedin, Carl Göran

    2015-12-01

    Psychiatric disorders are multi-factorial and their symptoms overlap. Constitutional and environmental factors influence each other, and this contributes to risk and resilience in mental ill-health. We investigated functional genetic variation of stress responsiveness, assessed as FKBP5 genotype, in relation to early life adversity and mental health in two samples of adolescents. One population-based sample of 909 12-year-old adolescents was assessed using the Life Incidence of Traumatic Events scale and the Strengths and Difficulties Questionnaire. One sample of 398 17-year-old adolescents, enriched for poly-victimized individuals (USSS), was assessed using the Juvenile Victimization Questionnaire and the Trauma Symptom Checklist for Children (TSCC). The FKBP5 rs1360780 and rs3800373 polymorphisms were genotyped using a fluorescence-based competitive allele-specific PCR. Most prominently among poly-victimized older male adolescents, the least common alleles of the polymorphisms, in interaction with adverse life events, were associated with psychiatric symptoms, after controlling for ethno-socio-economic factors. The interaction effect between rs3800373 and adverse life events on the TSCC sub-scales-anxiety, depression, anger, and dissociation-and with the rs1360780 on dissociation in the USSS cohort remained significant after Bonferroni correction. This pattern of association is in line with the findings of clinical and neuroimaging studies, and implies interactive effects of FKBP5 polymorphisms and early life environment on several psychiatric symptoms. These correlates add up to provide constructs that are relevant to several psychiatric symptoms, and to identify early predictors of mental ill-health.

  15. DNA methylation of BDNF as a biomarker of early-life adversity

    PubMed Central

    Kundakovic, Marija; Gudsnuk, Kathryn; Herbstman, Julie B.; Tang, Deliang; Perera, Frederica P.; Champagne, Frances A.

    2015-01-01

    Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue. In humans, although there is evidence for DNA methylation changes in the peripheral blood of psychiatric patients, a fundamental question remains as to whether epigenetic markers in the blood can predict epigenetic changes occurring in the brain. We used in utero bisphenol A (BPA) exposure as a model environmental exposure shown to disrupt neurodevelopment and exert long-term effects on behavior in animals and humans. We show that prenatal BPA induces lasting DNA methylation changes in the transcriptionally relevant region of the Bdnf gene in the hippocampus and blood of BALB/c mice and that these changes are consistent with BDNF changes in the cord blood of humans exposed to high maternal BPA levels in utero. Our data suggest that BDNF DNA methylation in the blood may be used as a predictor of brain BDNF DNA methylation and gene expression as well as behavioral vulnerability induced by early-life environmental exposure. Because BDNF expression and DNA methylation are altered in several psychiatric disorders that are associated with early-life adversity, including depression, schizophrenia, bipolar disorder, and autism, BDNF DNA methylation in the blood may represent a novel biomarker for the early detection of psychopathology. PMID:25385582

  16. 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.

  17. 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

  18. Effects of early-life adversity on white matter diffusivity changes in patients at risk for major depression

    PubMed Central

    Frodl, Thomas; Carballedo, Angela; Fagan, Andrew J.; Lisiecka, Danuta; Ferguson, Yolande; Meaney, James F.

    2012-01-01

    Background Relatives of patients with major depressive disorder (MDD) and people who experienced early-life adversity are at risk for MDD. The aim of our study was to investigate whether unaffected first-degree healthy relatives (UHRs) of patients with MDD show changes in white matter fibre connections compared with healthy controls and whether there are interactions between early-life adversity and these microstructural changes. Methods Unaffected, healthy first-degree relatives of patients with MDD and healthy controls without any family history for a psychiatric disease underwent high angular resolution diffusion imaging with 61 diffusion directions. Data were analyzed with tract-based spatial statistics, and findings were confirmed with tractography. Results Twenty-one UHRs and 24 controls participated in our study. The UHRs showed greater fractional anisotropy than controls in the body and splenium of the corpus callosum, inferior fronto-occipital fasciculus (IFO), left superior longitudinal fasciculus (SLF) and right fornix. The UHRs who experienced more early-life adversity had greater fractional anisotropy than those with less early-life adversity in the splenium of the corpus callosum, fornix, IFO and SLF; in controls, early-life adversity was found to be associated with decreased fractional anisotropy in these fibre tracts. Limitations Studying participants’ strategies for coping with early-life adversity would have been helpful. Crossing fibres in tracts are a general limitation of the method used. Conclusion Altogether, our findings provide evidence for greater fractional anisotropy in UHRs and for interaction between early-life adversity and family risk on white matter tracts involved in cognitive–emotional processes. Whether stronger neural fibre connections are associated with more resilience against depression needs to be addressed in future studies. PMID:22008179

  19. 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.

  20. 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. PMID:27286932

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

    PubMed

    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

  2. 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

  3. Genetic predisposition for high stress reactivity amplifies effects of early-life adversity.

    PubMed

    McIlwrick, Silja; Rechenberg, Alexandra; Matthes, Mariana; Burgstaller, Jessica; Schwarzbauer, Thomas; Chen, Alon; Touma, Chadi

    2016-08-01

    A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) axis and the experience of early-life adversity are both well-established risk factors for the development of affective disorders, such as major depression. However, little is known about the interaction of these two factors in shaping endophenotypes of the disease. Here, we studied the gene-environment interaction of a genetic predisposition for HPA axis dysregulation with early-life stress (ELS), assessing the short-, as well as the long-lasting consequences on emotional behavior, neuroendocrine functions and gene expression profiles. Three mouse lines, selectively bred for either high (HR), intermediate (IR), or low (LR) HPA axis reactivity, were exposed to one week of ELS using the limited nesting and bedding material paradigm. Measurements collected during or shortly after the ELS period showed that, regardless of genetic background, ELS exposure led to impaired weight gain and altered the animals' coping behavior under stressful conditions. However, only HR mice additionally showed significant changes in neuroendocrine stress responsiveness at a young age. Accordingly, adult HR mice also showed lasting consequences of ELS, including hyperactive stress-coping, HPA axis hyperreactivity, and gene expression changes in the Crh system, as well as downregulation of Fkbp5 in relevant brain regions. We suggest that the genetic predisposition for high stress reactivity interacts with ELS exposure by disturbing the suppression of corticosterone release during a critical period of brain development, thus exerting lasting programming effects on the HPA axis, presumably via epigenetic mechanisms. In concert, these changes lead to the emergence of important endophenotypes associated with affective disorders. PMID:27179233

  4. A mechanistic look at the effects of adversity early in life on cardiovascular disease risk during adulthood

    PubMed Central

    Loria, A. S.; Ho, D. H.; Pollock, J. S.

    2014-01-01

    Early origins of adult disease may be defined as adversity or challenges during early life that alter physiological responses and prime the organism to chronic disease in adult life. Adverse childhood experiences or early life stress (ELS) may be considered a silent independent risk factor capable of predicting future cardiovascular disease risk. Maternal separation (Mat-Sep) provides a suitable model to elucidate the underlying molecular mechanisms by which ELS increases the risk to develop cardiovascular disease in adulthood. The aim of this review is to describe the links between behavioural stress early in life and chronic cardiovascular disease risk in adulthood. We will discuss the following: (i) adult cardiovascular outcomes in humans subjected to ELS, (ii) Mat-Sep as an animal model of ELS as well as the limitations and advantages of this model in rodents and (iii) possible ELS-induced mechanisms that predispose individuals to greater cardiovascular risk. Overall, exposure to a behavioural stressor early in life sensitizes the response to a second stressor later in life, thus unmasking an exaggerated cardiovascular dysfunction that may influence quality of life and life expectancy in adulthood. PMID:24330084

  5. 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 ...

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

    PubMed Central

    Farr, Olivia M.; Ko, Byung-Joon; Joung, Kyoung Eun; Zaichenko, Lesya; Usher, Nicole; Tsoukas, Michael; Thakkar, Bindiya; Davis, Cynthia R.; Crowell, Judith A.; Mantzoros, Christos S.

    2015-01-01

    Background and Aims 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. Methods We analyzed data from a cross-sectional and a 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. Results 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, ICAM, and TNFRII were significantly increased with higher PTSD severity during a 2.5 year follow-up period. Conclusions Individuals with early life adversity and PTSD are at high risk and should be monitored carefully for obesity, insulin resistance, and cardiometabolic risk. PMID:25770759

  7. Depression among Black bisexual men with early and later life adversities.

    PubMed

    Allen, Vincent C; Myers, Hector F; Williams, John K

    2014-01-01

    This study examined the role of adulthood adversities in the relationship between childhood adversities and depression in 117 HIV-positive Black men who have sex with men and women (MSMW) and who have histories of childhood sexual abuse (CSA). Men were participants in the Enhanced Sexual Health Intervention for Men, a 6-session health intervention, and, at baseline, reported their experiences of CSA, childhood adversities, perceived discrimination, chronic stress, social support, and depressive symptoms. The relationship between childhood adversities, including CSA, and depression was mediated by experiences with racial and HIV discrimination, R² = .25, F(3, 112) = 12.67, p < .001, and chronic stress, R² = .17, F(3, 112) = 7.41, p < .001. Social support moderated the mediated effects of both racial and HIV discrimination, b = -.154, t(111) = -2.82, p < .01, and chronic stress, b = -.019, t(111) = -3.759, p < .01. Men's early adverse experiences were predictive of depression in adulthood; however, this relationship was largely affected by adulthood experiences, specifically discrimination, high chronic stress, and low social support. These findings illustrate pathways by which Black MSMW's early vulnerability for depression is either exacerbated or attenuated by their experiences as adults.

  8. Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function.

    PubMed

    Anacker, Christoph; O'Donnell, Kieran J; Meaney, Michael J

    2014-09-01

    We review studies with human and nonhuman species that examine the hypothesis that epigenetic mechanisms, particularly those affecting the expression of genes implicated in stress responses, mediate the association between early childhood adversity and later risk of depression. The resulting studies provide evidence consistent with the idea that social adversity, particularly that involving parent-offspring interactions, alters the epigenetic state and expression of a wide range of genes, the products of which regulate hypothalamic-pituitary-adrenal function. We also address the challenges for future studies, including that of the translation of epigenetic studies towards improvements in treatments.

  9. Effects of adverse early-life events on aggression and anti-social behaviours in animals and humans.

    PubMed

    Haller, J; Harold, G; Sandi, C; Neumann, I D

    2014-10-01

    We review the impact of early adversities on the development of violence and antisocial behaviour in humans, and present three aetiological animal models of escalated rodent aggression, each disentangling the consequences of one particular adverse early-life factor. A review of the human data, as well as those obtained with the animal models of repeated maternal separation, post-weaning social isolation and peripubertal stress, clearly shows that adverse developmental conditions strongly affect aggressive behaviour displayed in adulthood, the emotional responses to social challenges and the neuronal mechanisms activated by conflict. Although similarities between models are evident, important differences were also noted, demonstrating that the behavioural, emotional and neuronal consequences of early adversities are to a large extent dependent on aetiological factors. These findings support recent theories on human aggression, which suggest that particular developmental trajectories lead to specific forms of aggressive behaviour and brain dysfunctions. However, dissecting the roles of particular aetiological factors in humans is difficult because these occur in various combinations; in addition, the neuroscientific tools employed in humans still lack the depth of analysis of those used in animal research. We suggest that the analytical approach of the rodent models presented here may be successfully used to complement human findings and to develop integrative models of the complex relationship between early adversity, brain development and aggressive behaviour.

  10. 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

  11. Coupling of the HPA and HPG axes in the context of early life adversity in incarcerated male adolescents.

    PubMed

    Dismukes, Andrew R; Johnson, Megan M; Vitacco, Michael J; Iturri, Florencia; Shirtcliff, Elizabeth A

    2015-09-01

    The effects of early life adversity can be observed across the lifespan, and the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonadal (HPG) axes could be mechanistic intermediaries underlying this phenomenon. The current study examined 50 adolescent males aged 12-18 in a maximum-security correctional and treatment setting. Saliva samples were collected five times a day for 2 days and assayed for cortisol, testosterone, and DHEA. Youth completed semi-structured life stress interviews and self-reports of child maltreatment to index adversity. When youth had higher testosterone levels, they had higher cortisol and DHEA levels, indicating positive "coupling" of the HPA-HPG axes. In addition, children experiencing greater life adversity had tighter coupling of the HPA-HPG axes. Additional analyses hint that coupling may be driven largely by HPG axis functioning. Results indicate that positive coupling of the HPA-HPG axis is observed within incarcerated adolescents, especially for those with the greatest life stress.

  12. Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.

    PubMed

    Sachs, Benjamin D; Rodriguiz, Ramona M; Tran, Ha L; Iyer, Akshita; Wetsel, William C; Caron, Marc G

    2015-03-01

    Brain 5-HT deficiency has long been implicated in psychiatric disease, but the effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early life stress (ELS) has been suggested to contribute to adult psychopathology, but efforts to study the long-term consequences of ELS have been limited by a lack of appropriate preclinical models. Here, we evaluated the effects of 5-HT deficiency on several long-term cellular, molecular, and behavioral responses of mice to a new model of ELS that combines early-life maternal separation (MS) of pups and postpartum learned helplessness (LH) training in dams. Our data demonstrate that this paradigm (LH/MS) induces depressive-like behavior and impairs pup retrieval in dams. In addition, we show that brain 5-HT deficiency exacerbates anxiety-like behavior induced by LH/MS and blunts the effects of LH/MS on acoustic startle responses in adult offspring. Although the mechanisms underlying these effects remain unclear, following LH/MS, 5-HT-deficient animals had significantly less mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type animals. In addition, 5-HT-deficient mice exhibited reduced mRNA levels of the 5-HT2a receptor and p11 in the hippocampus regardless of stress. LH/MS decreased the number of doublecortin+ immature neurons in the hippocampus in both wild-type (WT) and 5-HT-deficient animals. Our data emphasize the importance of complex interactions between genetic factors and early life experience in mediating long-term changes in emotional behavior. These findings may have important implications for our understanding of the combinatorial roles of 5-HT deficiency, ELS, and postpartum depression in the development of neuropsychiatric disorders.

  13. Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience

    PubMed Central

    Sachs, Benjamin D.; Rodriguiz, Ramona M.; Tran, Ha L.; Iyer, Akshita; Wetsel, William C.

    2015-01-01

    Brain 5-HT deficiency has long been implicated in psychiatric disease, but the effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early life stress (ELS) has been suggested to contribute to adult psychopathology, but efforts to study the long-term consequences of ELS have been limited by a lack of appropriate preclinical models. Here, we evaluated the effects of 5-HT deficiency on several long-term cellular, molecular, and behavioral responses of mice to a new model of ELS that combines early-life maternal separation (MS) of pups and postpartum learned helplessness (LH) training in dams. Our data demonstrate that this paradigm (LH/MS) induces depressive-like behavior and impairs pup retrieval in dams. In addition, we show that brain 5-HT deficiency exacerbates anxiety-like behavior induced by LH/MS and blunts the effects of LH/MS on acoustic startle responses in adult offspring. Although the mechanisms underlying these effects remain unclear, following LH/MS, 5-HT-deficient animals had significantly less mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type animals. In addition, 5-HT-deficient mice exhibited reduced mRNA levels of the 5-HT2a receptor and p11 in the hippocampus regardless of stress. LH/MS decreased the number of doublecortin+ immature neurons in the hippocampus in both wild-type (WT) and 5-HT-deficient animals. Our data emphasize the importance of complex interactions between genetic factors and early life experience in mediating long-term changes in emotional behavior. These findings may have important implications for our understanding of the combinatorial roles of 5-HT deficiency, ELS, and postpartum depression on the development of neuropsychiatric disorders. PMID:25602134

  14. Early life adversity increases foraging and information gathering in European starlings, Sturnus vulgaris

    PubMed Central

    Andrews, Clare; Viviani, Jérémie; Egan, Emily; Bedford, Thomas; Brilot, Ben; Nettle, Daniel; Bateson, Melissa

    2015-01-01

    Animals can insure themselves against the risk of starvation associated with unpredictable food availability by storing energy reserves or gathering information about alternative food sources. The former strategy carries costs in terms of mass-dependent predation risk, while the latter trades off against foraging for food; both trade-offs may be influenced by an individual's developmental history. Here, we consider a possible role of early developmental experience in inducing different mass regulation and foraging strategies in European starlings. We measured the body mass, body condition, foraging effort, food consumption and contrafreeloading (foraging for food hidden in sand when equivalent food is freely available) of adult birds (≥10 months old) that had previously undergone a subtle early life manipulation of food competition (cross-fostering into the highest or lowest ranks in the brood size hierarchy when 2–12 days of age). We found that developmentally disadvantaged birds were fatter in adulthood and differed in foraging behaviour compared with their advantaged siblings. Disadvantaged birds were hyperphagic compared with advantaged birds, but only following a period of food deprivation, and also spent more time contrafreeloading. Advantaged birds experienced a trade-off between foraging success and time spent contrafreeloading, whereas disadvantaged birds faced no such trade-off, owing to their greater foraging efficiency. Thus, developmentally disadvantaged birds appeared to retain a phenotypic memory of increased nestling food competition, employing both energy storage and information-gathering insurance strategies to a greater extent than their advantaged siblings. Our results suggest that subtle early life disadvantage in the form of psychosocial stress and/or food insecurity can leave a lasting legacy on foraging behaviour and mass regulation even in the absence of food insufficiency during development or adulthood. PMID:26566292

  15. 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.

  16. The lasting impact of early-life adversity on individuals and their descendants: potential mechanisms and hope for intervention.

    PubMed

    Cowan, C S M; Callaghan, B L; Kan, J M; Richardson, R

    2016-01-01

    The adverse effects of early-life stress are pervasive, with well-established mental and physical health consequences for exposed individuals. The impact of early adverse experiences is also highly persistent, with documented increases in risk for mental illness across the life span that are accompanied by stable alterations in neural function and hormonal responses to stress. Here, we review some of these 'stress phenotypes', with a focus on intermediary factors that may signal risk for long-term mental health outcomes, such as altered development of the fear regulation system. Intriguingly, recent research suggests that such stress phenotypes may persist even beyond the life span of the individuals, with consequences for their offspring and grand-offspring. Phenotypic characteristics may be transmitted to future generations via either the matriline or the patriline, a phenomenon that has been demonstrated in both human and animal studies. In this review, we highlight behavioral and epigenetic factors that may contribute to this multigenerational transmission and discuss the potential of various treatment approaches that may halt the cycle of stress phenotypes. PMID:26482536

  17. Early Life Adverse Environmental Exposures Increase the Risk of Uterine Fibroid Development: Role of Epigenetic Regulation.

    PubMed

    Yang, Qiwei; Diamond, Michael P; Al-Hendy, Ayman

    2016-01-01

    Uterine Fibroids [UF(s), AKA: leiomyoma] are the most important benign neoplastic threat to women's health. They are the most common cause of hysterectomy imposing untold personal consequences and 100s of billions of healthcare dollars, worldwide. Currently, there is no long term effective FDA-approved medical treatment available, and surgery is the mainstay. The etiology of UFs is not fully understood. In this regard, we and others have recently reported that somatic mutations in the gene encoding the transcriptional mediator subunit Med12 are found to occur at a high frequency (∼85%) in UFs. UFs likely originate when a Med12 mutation occurs in a myometrial stem cell converting it into a tumor-forming stem cell leading to a clonal fibroid lesion. Although the molecular attributes underlying the mechanistic formation of UFs is largely unknown, a growing body of literature implicates unfavorable early life environmental exposures as potentially important contributors. Early life exposure to EDCs during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life. Neonatal exposure to the EDCs such as diethylstilbestrol (DES) and genistein during reproductive tract development has been shown to increase the incidence, multiplicity and overall size of UFs in the Eker rat model, concomitantly reprogramming estrogen-responsive gene expression. Importantly, EDC exposure represses enhancer of zeste 2 (EZH2) and reduces levels of histone 3 lysine 27 trimethylation (H3K27me3) repressive mark through Estrogen receptor/Phosphatidylinositide 3-kinases/Protein kinase B non-genomic signaling in the developing uterus. Considering the fact that distinct Mediator Complex Subunit 12 (Med12) mutations are detected in different fibroid lesions in the same uterus, the emergence of each Med12 mutation is likely an independent event in an altered myometrial stem cell. It is therefore possible that a chronic reduction in

  18. Early Life Adverse Environmental Exposures Increase the Risk of Uterine Fibroid Development: Role of Epigenetic Regulation

    PubMed Central

    Yang, Qiwei

    2016-01-01

    Uterine Fibroids [UF(s), AKA: leiomyoma] are the most important benign neoplastic threat to women’s health. They are the most common cause of hysterectomy imposing untold personal consequences and 100s of billions of healthcare dollars, worldwide. Currently, there is no long term effective FDA-approved medical treatment available, and surgery is the mainstay. The etiology of UFs is not fully understood. In this regard, we and others have recently reported that somatic mutations in the gene encoding the transcriptional mediator subunit Med12 are found to occur at a high frequency (∼85%) in UFs. UFs likely originate when a Med12 mutation occurs in a myometrial stem cell converting it into a tumor-forming stem cell leading to a clonal fibroid lesion. Although the molecular attributes underlying the mechanistic formation of UFs is largely unknown, a growing body of literature implicates unfavorable early life environmental exposures as potentially important contributors. Early life exposure to EDCs during sensitive windows of development can reprogram normal physiological responses and alter disease susceptibility later in life. Neonatal exposure to the EDCs such as diethylstilbestrol (DES) and genistein during reproductive tract development has been shown to increase the incidence, multiplicity and overall size of UFs in the Eker rat model, concomitantly reprogramming estrogen-responsive gene expression. Importantly, EDC exposure represses enhancer of zeste 2 (EZH2) and reduces levels of histone 3 lysine 27 trimethylation (H3K27me3) repressive mark through Estrogen receptor/Phosphatidylinositide 3-kinases/Protein kinase B non-genomic signaling in the developing uterus. Considering the fact that distinct Mediator Complex Subunit 12 (Med12) mutations are detected in different fibroid lesions in the same uterus, the emergence of each Med12 mutation is likely an independent event in an altered myometrial stem cell. It is therefore possible that a chronic reduction in

  19. A paradoxical association of an oxytocin receptor gene polymorphism: early-life adversity and vulnerability to depression.

    PubMed

    McQuaid, Robyn J; McInnis, Opal A; Stead, John D; Matheson, Kimberly; Anisman, Hymie

    2013-01-01

    Several prosocial behaviors may be influenced by the hormone oxytocin. In line with this perspective, the oxytocin receptor (OXTR) gene single nucleotide polymorphism (SNP), rs53576, has been associated with a broad range of social behaviors. In this regard, the G allele of the OXTR SNP has been accompanied by beneficial attributes such as increased empathy, optimism, and trust. In the current study among university students (N = 288), it was shown that early-life maltreatment was associated with depressive symptoms, and that the OXTR genotype moderated this relationship, such that under high levels of childhood maltreatment, only individuals with GG/GA genotype demonstrated increased depressive symptomatology compared to those with the AA genotype. In addition, the role of distrust in mediating the relation between childhood maltreatment and depression seemed to be more important among G allele carriers compared to individuals with the AA genotype. Thus, a breach in trust (i.e., in the case of early-life abuse or neglect) may have a more deleterious effect among G carriers, who have been characterized as more prosocial and attuned to social cues. The data suggested that G carriers of the OXTR might favor social sensitivity and thus might have been more vulnerable to the effects of early-life adversity. PMID:23898235

  20. Periconceptional nutrition and the early programming of a life of obesity or adversity.

    PubMed

    Zhang, S; Rattanatray, L; McMillen, I C; Suter, C M; Morrison, J L

    2011-07-01

    Women entering pregnancy with a high body weight and fat mass have babies at increased risk of becoming overweight or obese in childhood and later life. It is not known, whether exposure to a high level of maternal nutrition before pregnancy and exposure to a high transplacental nutrient supply in later pregnancy act through similar mechanisms to program later obesity. Using the pregnant sheep we have shown that maternal overnutrition in late pregnancy results in an upregulation of PPARγ activated genes in fetal visceral fat and a subsequent increase in the mass of subcutaneous fat in the postnatal lamb. Exposure to maternal overnutrition during the periconceptional period alone, however, results in an increase in total body fat mass in female lambs only with a dominant effect on visceral fat depots. Thus the early programming of later obesity may result from 'two hits', the first occurring as a result of maternal overnutrition during the periconceptional period and the second occurring as a result of increased fetal nutrition in late pregnancy. Whilst a short period of dietary restriction during the periconceptional period reverses the impact of periconceptional overnutrition on the programming of obesity, it also results in an increased lamb adrenal weight and cortisol stress response, together with changes in the epigenetic state of the insulin like growth factor 2 (IGF2) gene in the adrenal. Thus, not all of the effects of dietary restriction in overweight or obese mother in the periconceptional period may be beneficial in the longer term.

  1. Are Specific Early-Life Adversities Associated With Specific Symptoms of Psychosis?

    PubMed Central

    Wickham, Sophie; Bentall, Richard

    2016-01-01

    Abstract Epidemiological studies have suggested that there may be associations between specific adversities and specific psychotic symptoms. There is also evidence that beliefs about justice may play a role in paranoid symptoms. In this study, we determined whether these associations could be replicated in a patient sample and whether beliefs about a just world played a specific role in the relationship between adversity and paranoia. We examined associations between childhood trauma, belief in justice, and paranoia and hallucinatory experiences in 144 individuals: 72 individuals with a diagnosis of schizophrenia spectrum disorders and 72 comparison controls. There was a dose-response relationship between cumulative trauma and psychosis. When controlling for comorbidity between symptoms, childhood sexual abuse predicted hallucinatory experiences, and experiences of childhood emotional neglect predicted paranoia. The relationship between neglect and paranoia was mediated by a perception of personal injustice. The findings replicate in a patient sample previous observations from epidemiological research. PMID:27065105

  2. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    PubMed

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity. PMID:26260665

  3. Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

    PubMed

    Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

    2015-01-01

    Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

  4. Early life Adversity and Inflammation in African Americans and Whites in the Midlife in the United States Survey

    PubMed Central

    Slopen, Natalie; Lewis, Tené T.; Gruenewald, Tara L.; Mujahid, Mahasin S.; Ryff, Carol D.; Albert, Michelle A.; Williams, David R.

    2010-01-01

    Objectives We sought to determine whether early life adversity (ELA) was predictive of inflammatory markers, and to determine the consistency of these associations across racial groups. Methods We analyzed data from 177 African Americans and 822 Whites aged 35 to 86 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 CRP, IL-6, fibrinogen, E-selectin, and sICAM-1, independent of age, gender, and medications. We extended race-stratified models to test three potential mechanisms for the observed associations. Results Significant interactions between ELA and race were observed for all 5 biomarkers. Models stratified by race revealed that ELA predicted higher levels of log IL-6, fibrinogen, E-selectin, and sICAM-1 among African Americans (p-values <.05), but not among Whites. Some, but not all, of these associations were attenuated after adjustment for health behaviors and BMI, adult stressors, and depressive symptoms. Conclusions 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. PMID:20595419

  5. 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

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

    PubMed Central

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

    2015-01-01

    Background 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. Methods 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. Results 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. Limitations Attrition may have led to an underestimation of the direct and indirect effect sizes in the complete case analysis. Conclusions 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. PMID:26047304

  7. 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…

  8. Early life adversities and adolescent antisocial behavior: The role of cardiac autonomic nervous system reactivity in the TRAILS study.

    PubMed

    Sijtsema, J J; Van Roon, A M; Groot, P F C; Riese, H

    2015-09-01

    In the current study, the role of pre-ejection period (PEP) and respiratory sinus arrhythmia (RSA) was studied in the association between prior adversities and antisocial behavior in adolescence. PEP and RSA task reactivity and recovery to a public speaking task were assessed in adolescents from a longitudinal population-based study (N=624, Mage=16.14 years, 49.2% boys). Perinatal adversities were unrelated to antisocial behavior, but experiencing more stressful adversities between age 0 and 15 was associated with antisocial behavior at age 16 in boys with blunted PEP reactivity and smaller PEP differences from rest to recovery. Number of adversities between age 0 and 15 was associated with antisocial behavior in boys with blunted and girls with heightened RSA reactivity and larger PEP differences from rest to recovery. The association between prior adversities and antisocial behavior were small in effect size and depended upon sex and PEP and RSA reactivity and recovery.

  9. 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...

  10. Early adversity, neural development, and inflammation.

    PubMed

    Chiang, Jessica J; Taylor, Shelley E; Bower, Julienne E

    2015-12-01

    Early adversity is a risk factor for poor mental and physical health. Although altered neural development is believed to be one pathway linking early adversity to psychopathology, it has rarely been considered a pathway linking early adversity to poor physical health. However, this is a viable pathway because the central nervous system is known to interact with the immune system via the hypothalamic-pituitary-adrenal (HPA) axis and autonomic nervous system (ANS). In support of this pathway, early adversity has been linked to changes in neural development (particularly of the amygdala, hippocampus, and prefrontal cortex), HPA axis and ANS dysregulation, and higher levels of inflammation. Inflammation, in turn, can be detrimental to physical health when prolonged. In this review, we present these studies and consider how altered neural development may be a pathway by which early adversity increases inflammation and thus risk for adverse physical health outcomes.

  11. Early adversity, immunity and infectious disease.

    PubMed

    Avitsur, Ronit; Levy, Sigal; Goren, Naama; Grinshpahet, Rachel

    2015-01-01

    Complex interactions between biological, behavioral and environmental factors are involved in mediating individual differences in health and disease. In this review, we present evidence suggesting that increased vulnerability to infectious disease may be at least, in part, due to long-lasting effects of early life psychosocial adversities. Studies have shown that maternal psychosocial stress during pregnancy is associated with long lasting changes in immune function and disease resistance in the offspring. Studies further indicated that harsh environmental conditions during the neonatal period may also cause lasting changes in host response to infectious disease. Although the mechanisms involved in these effects have not been fully examined, several potential mediators have been described, including changes in the development of the offspring hypothalamic-pituitary-adrenal axis, alterations in epigenetic pathways, stress-related maternal health risk behavior and infection during pregnancy. Although there are ample literature indicating that perinatal psychosocial stress increases vulnerability to disease, other reports suggest that mild predictable stressors may benefit the organism and allow better coping with future stressors. Thus, understanding the possible consequences of perinatal adversities and the mechanisms that are involved in immune regulation is important for increasing awareness to the potential outcomes of early negative life events and providing insight into potential therapies to combat infection in vulnerable individuals.

  12. Dysfunctional Astrocytic and Synaptic Regulation of Hypothalamic Glutamatergic Transmission in a Mouse Model of Early-Life Adversity: Relevance to Neurosteroids and Programming of the Stress Response

    PubMed Central

    Gunn, Benjamin G.; Cunningham, Linda; Cooper, Michelle A.; Corteen, Nicole L.; Seifi, Mohsen; Swinny, Jerome D.; Lambert, Jeremy J.

    2013-01-01

    Adverse early-life experiences, such as poor maternal care, program an abnormal stress response that may involve an altered balance between excitatory and inhibitory signals. Here, we explored how early-life stress (ELS) affects excitatory and inhibitory transmission in corticotrophin-releasing factor (CRF)-expressing dorsal-medial (mpd) neurons of the neonatal mouse hypothalamus. We report that ELS associates with enhanced excitatory glutamatergic transmission that is manifested as an increased frequency of synaptic events and increased extrasynaptic conductance, with the latter associated with dysfunctional astrocytic regulation of glutamate levels. The neurosteroid 5α-pregnan-3α-ol-20-one (5α3α-THPROG) is an endogenous, positive modulator of GABAA receptors (GABAARs) that is abundant during brain development and rises rapidly during acute stress, thereby enhancing inhibition to curtail stress-induced activation of the hypothalamic-pituitary-adrenocortical axis. In control mpd neurons, 5α3α-THPROG potently suppressed neuronal discharge, but this action was greatly compromised by prior ELS exposure. This neurosteroid insensitivity did not primarily result from perturbations of GABAergic inhibition, but rather arose functionally from the increased excitatory drive onto mpd neurons. Previous reports indicated that mice (dams) lacking the GABAAR δ subunit (δ0/0) exhibit altered maternal behavior. Intriguingly, δ0/0 offspring showed some hallmarks of abnormal maternal care that were further exacerbated by ELS. Moreover, in common with ELS, mpd neurons of δ0/0 pups exhibited increased synaptic and extrasynaptic glutamatergic transmission and consequently a blunted neurosteroid suppression of neuronal firing. This study reveals that increased synaptic and tonic glutamatergic transmission may be a common maladaptation to ELS, leading to enhanced excitation of CRF-releasing neurons, and identifies neurosteroids as putative early regulators of the stress

  13. 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.

  14. 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...

  15. Early Life Stage Exposure to BDE-47 Causes Adverse Effects on Reproductive Success and Sexual Differentiation in Fathead Minnows (Pimephales promelas).

    PubMed

    Thornton, Leah M; Path, Elise M; Nystrom, Gunnar S; Venables, Barney J; Sellin Jeffries, Marlo K

    2016-07-19

    2,2',4,4'-Tetrabromodiphenyl ether (BDE-47), a compound manufactured for use as a flame retardant, is a ubiquitous environmental contaminant and suspected endocrine disruptor. Though several studies have explored the reproductive effects of BDE-47 in adult fish, there is a paucity of data regarding the reproductive effects of early life stage exposure. The goal of this study was to assess the reproductive effects of early life stage BDE-47 exposure in fathead minnows (Pimephales promelas). To achieve this, minnows were exposed to either a low (57.68 μg BDE-47/g Artemia) or high (392.59 μg BDE-47/g Artemia) dose of BDE-47 from fertilization to 34 days postfertilization (dpf) via a combination of maternal transfer and dietary exposure. Larvae were then raised on a clean diet until sexual maturity (∼184 dpf) when reproductive function was evaluated using a 21 day breeding study. Fish exposed to BDE-47 had significantly reduced clutch size and fecundity relative to controls. BDE-47 exposed groups also had female-biased sex ratios and exposed males had fewer tubercles. Overall, this study demonstrates that exposure to BDE-47 during early life stages can alter both sexual differentiation and reproductive function. PMID:27326452

  16. Do Specific Early-Life Adversities Lead to Specific Symptoms of Psychosis? A Study from the 2007 The Adult Psychiatric Morbidity Survey

    PubMed Central

    Bentall, Richard P.; Wickham, Sophie; Shevlin, Mark; Varese, Filippo

    2012-01-01

    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. PMID:22496540

  17. Early Childhood Adversity and Pregnancy Outcomes

    PubMed Central

    Smith, Megan V.; Gotman, Nathan; Yonkers, Kimberly A.

    2016-01-01

    Objectives To examine the association between adverse childhood experiences (ACEs) and pregnancy outcomes; to explore mediators of this association including psychiatric illness and health habits. Methods Exposure to ACEs was determined by the Early Trauma Inventory Self Report Short Form; psychiatric diagnoses were generated by the Composite International Diagnostic Interview administered in a cohort of 2303 pregnant women. Linear regression and structural equation modeling bootstrapping approaches tested for multiple mediators. Results Each additional ACE decreased birth weight by 16.33 g and decreased gestational age by 0.063. Smoking was the strongest mediator of the effect on gestational age. Conclusions ACEs have an enduring effect on maternal reproductive health, as manifested by mothers’ delivery of offspring that were of reduced birth weight and shorter gestational age. PMID:26762511

  18. Early Life Exposures and Cancer

    Cancer.gov

    Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

  19. Early adversity and mental health: linking extremely low birth weight, emotion regulation, and internalizing disorders.

    PubMed

    Waxman, Jordana; Van Lieshout, Ryan J; Schmidt, Louis A

    2014-01-01

    The experience of early adversity can increase one's risk of psychopathology later in life. Extremely low birth weight (ELBW) provides a unique model of early adversity that affords us the opportunity to understand how prenatal and early postnatal stressors can affect the development of emotional, biological, and behavioural systems. Since the neuroendocrine system and emotion regulation can both be negatively affected by exposure to early adversity, and dysregulation in these regulatory systems has been linked to various forms of psychopathology, it is possible that these systems could mediate and/or moderate associations between early adversity, specifically ELBW, and later internalizing disorders. In this review, we discuss evidence of an early programming hypothesis underlying psychopathology and the identification of neuroendocrine markers of early adversity that may mediate/moderate the development of psychopathology.

  20. Beneficial Effects of Highly Palatable Food on the Behavioral and Neural Adversities induced by Early Life Stress Experience in Female Rats.

    PubMed

    Kim, Jin Young; Lee, Jong-Ho; Kim, Doyun; Kim, Soung-Min; Koo, JaeHyung; Jahng, Jeong Won

    2015-01-01

    This study examined the effects of highly palatable food during adolescence on the psycho-emotional and neural disturbances caused by early life stress experience in female rats. Female Sprague-Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (MS) or left undisturbed (NH). Half of MS females received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28. Pups were subjected to the behavioral tests during young adulthood. The plasma corticosterone response to acute stress, ΔFosB and brain-derived neurotrophic factor (BDNF) levels in the brain regions were analyzed. Total caloric intake and body weight gain during the whole experimental period did not differ among the experimental groups. Cookie access during adolescence and youth improved anxiety-/depression-like behaviors by MS experience. ΔFosB expression was decreased, but BDNF was increased in the nucleus accumbens of MS females, and ΔFosB expression was normalized and BDNF was further increased following cookie access. Corticosterone response to acute stress was blunted by MS experience and cookie access did not improve it. Results suggest that cookie access during adolescence improves the psycho-emotional disturbances of MS females, and ΔFosB and/or BDNF expression in the nucleus accumbens may play a role in its underlying neural mechanisms. PMID:26327809

  1. Beneficial Effects of Highly Palatable Food on the Behavioral and Neural Adversities induced by Early Life Stress Experience in Female Rats

    PubMed Central

    Kim, Jin Young; Lee, Jong-Ho; Kim, Doyun; Kim, Soung-Min; Koo, JaeHyung; Jahng, Jeong Won

    2015-01-01

    This study examined the effects of highly palatable food during adolescence on the psycho-emotional and neural disturbances caused by early life stress experience in female rats. Female Sprague-Dawley pups were separated from dam for 3 h daily during the first two weeks of birth (MS) or left undisturbed (NH). Half of MS females received free access to chocolate cookies in addition to ad libitum chow from postnatal day 28. Pups were subjected to the behavioral tests during young adulthood. The plasma corticosterone response to acute stress, ΔFosB and brain-derived neurotrophic factor (BDNF) levels in the brain regions were analyzed. Total caloric intake and body weight gain during the whole experimental period did not differ among the experimental groups. Cookie access during adolescence and youth improved anxiety-/depression-like behaviors by MS experience. ΔFosB expression was decreased, but BDNF was increased in the nucleus accumbens of MS females, and ΔFosB expression was normalized and BDNF was further increased following cookie access. Corticosterone response to acute stress was blunted by MS experience and cookie access did not improve it. Results suggest that cookie access during adolescence improves the psycho-emotional disturbances of MS females, and ΔFosB and/or BDNF expression in the nucleus accumbens may play a role in its underlying neural mechanisms. PMID:26327809

  2. 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…

  3. Practitioner Review: Early Adversity and Developmental Disorders

    ERIC Educational Resources Information Center

    Taylor, Eric; Rogers, Jody Warner

    2005-01-01

    Background: Knowledge of genetic influences, on developmental disorders such as autism spectrum, attention deficit/hyperactivity disorder and learning disabilities, has increased the opportunities for understanding the influences of the early environment. Methods: This paper provides a selective, narrative review for clinicians of the effects of…

  4. Adversity Across the Life Course of Incarcerated Parents: Gender Differences

    PubMed Central

    Borja, Sharon; Nurius, Paula; Eddy, J. Mark

    2016-01-01

    More than half of the 1.6 million adults in U.S. prions are parents. Despite growing knowledge regarding the life course adversities of corrections-involved populations, less is known regarding incarcerated parents per se and the implications of cumulative adversities both on their needs and those of their children. Using a gender-balanced (41% minority) sample of incarcerated parents (N=357) from a randomized controlled trial of an in-prison parent training program, this study examines differences between incarcerated mothers and fathers in their exposures to adversities across the life course. Mothers and fathers shared similar patterns of adversity exposure in their families of origin, but differed in their experiences of juvenile justice and child welfare systems involvement, as well as in their adult experiences of victimization and related adult social and mental health outcomes. Implications for gender-responsive parent support and prevention programs for their children of incarcerated mothers and fathers are discussed. PMID:26998189

  5. 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. PMID:26303813

  6. Early adversity, hypocortisolism, and behavior problems at school entry: A study of internationally adopted children.

    PubMed

    Koss, Kalsea J; Mliner, Shanna B; Donzella, Bonny; Gunnar, Megan R

    2016-04-01

    The hypothalamic-pituitary-adrenal (HPA) axis is influenced by early life adversity; however, less is known about the potential for recovery following marked improvements in care. The present study examined longitudinal changes in children's cortisol reactivity in the laboratory (4 assessments over 2 years) after adoption. Post-institutionalized (N=65) and post-foster care children (N=49) demonstrated blunted reactivity relative to non-adopted peers (N=53). Furthermore, post-institutionalized children exhibited no evidence of expected adaptation to repeated sessions in the 2 years following adoption. As evidenced by blunted cortisol reactivity, flatter diurnal slope, and lower home morning cortisol, we found support for hypocortisolism among children experiencing adverse early care. Hypocortisolism served as a mediator between adversity and teacher-reported attention and externalizing problems during kindergarten. Early adversity appears to contribute to the down-regulation of the HPA axis under both basal and stress conditions. PMID:26773398

  7. Epigenomic Mechanisms of Early Adversity and HPA Dysfunction: Considerations for PTSD Research.

    PubMed

    McGowan, Patrick O

    2013-01-01

    Childhood adversity can have life-long consequences for the response to stressful events later in life. Abuse or severe neglect are well-known risk factors for post-traumatic stress disorder (PTSD), at least in part via changes in neural systems mediating the endocrine response to stress. Determining the biological signatures of risk for stress-related mental disorders such as PTSD is important for identifying homogenous subgroups and improving treatment options. This review will focus on epigenetic regulation in early life by adversity and parental care - prime mediators of offspring neurodevelopment - in order to address several questions: (1) what have studies of humans and analogous animal models taught us about molecular mechanisms underlying changes in stress-sensitive physiological systems in response to early life trauma? (2) What are the considerations for studies relating early adversity and PTSD risk, going forward? I will summarize studies in animals and humans that address the epigenetic response to early adversity in the brain and in peripheral tissues. In so doing, I will describe work on the glucocorticoid receptor and other well-characterized genes within the stress response pathway and then turn to genomic studies to illustrate the use of increasingly powerful high-throughput approaches to the study of epigenomic mechanisms. PMID:24133457

  8. Early adversity disrupts the adult use of aversive prediction errors to reduce fear in uncertainty

    PubMed Central

    Wright, Kristina M.; DiLeo, Alyssa; McDannald, Michael A.

    2015-01-01

    Early life adversity increases anxiety in adult rodents and primates, and increases the risk for developing post-traumatic disorder (PTSD) in humans. We hypothesized that early adversity impairs the use of learning signals -negative, aversive prediction errors–to reduce fear in uncertainty. To test this hypothesis, we gave adolescent rats a battery of adverse experiences then assessed adult performance in probabilistic Pavlovian fear conditioning and fear extinction. Rats were confronted with three cues associated with different probabilities of foot shock: one cue never predicted shock, another cue predicted shock with uncertainty, and a final cue always predicted shock. Control rats initially acquired fear to all cues, but rapidly reduced fear to the non-predictive and uncertain cues. Early adversity rats were slower to reduce fear to the non-predictive cue and never fully reduced fear to the uncertain cue. In extinction, all cues were presented in the absence of shock. Fear to the uncertain cue in discrimination, but not early adversity itself, predicted the reduction of fear in extinction. These results demonstrate early adversity impairs the use of negative aversive prediction errors to reduce fear, especially in situations of uncertainty. PMID:26379520

  9. 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.

  10. 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.

  11. 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. PMID:26568620

  12. 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

  13. The Early Years: "Life" Science

    ERIC Educational Resources Information Center

    Ashbrook, Peggy

    2013-01-01

    Talking about death as part of a life cycle is often ignored or spoken about in hushed tones in early childhood. Books with "life cycle" in the title often do not include the death of the living organism in the information about the cycle. The concept of a complete life cycle does not appear in "A Framework for K-12 Science…

  14. Shaping adult phenotypes through early life environments.

    PubMed

    Weaver, Ian C G

    2009-12-01

    A major question in the biology of stress and environmental adaptation concerns the neurobiological basis of how neuroendocrine systems governing physiological regulatory mechanisms essential for life (metabolism, immune response, organ function) become harmful. The current view is that a switch from protection to damage occurs when vulnerable phenotypes are exposed to adverse environmental conditions. In accordance with this theory, sequelae of early life social and environmental stressors, such as childhood abuse, neglect, poverty, and poor nutrition, have been associated with the emergence of mental and physical illness (i.e., anxiety, mood disorders, poor impulse control, psychosis, and drug abuse) and an increased risk of common metabolic and cardiovascular diseases later in life. Evidence from animal and human studies investigating the associations between early life experiences (including parent-infant bonding), hypothalamus-pituitary-adrenal axis activity, brain development, and health outcome provide important clues into the neurobiological mechanisms that mediate the contribution of stressful experiences to personality development and the manifestation of illness. This review summarizes our current molecular understanding of how early environment influences brain development in a manner that persists through life and highlights recent evidence from rodent studies suggesting that maternal care in the first week of postnatal life establishes diverse and stable phenotypes in the offspring through epigenetic modification of genes expressed in the brain that shape neuroendocrine and behavioral stress responsivity throughout life. PMID:19960543

  15. Shaping adult phenotypes through early life environments.

    PubMed

    Weaver, Ian C G

    2009-12-01

    A major question in the biology of stress and environmental adaptation concerns the neurobiological basis of how neuroendocrine systems governing physiological regulatory mechanisms essential for life (metabolism, immune response, organ function) become harmful. The current view is that a switch from protection to damage occurs when vulnerable phenotypes are exposed to adverse environmental conditions. In accordance with this theory, sequelae of early life social and environmental stressors, such as childhood abuse, neglect, poverty, and poor nutrition, have been associated with the emergence of mental and physical illness (i.e., anxiety, mood disorders, poor impulse control, psychosis, and drug abuse) and an increased risk of common metabolic and cardiovascular diseases later in life. Evidence from animal and human studies investigating the associations between early life experiences (including parent-infant bonding), hypothalamus-pituitary-adrenal axis activity, brain development, and health outcome provide important clues into the neurobiological mechanisms that mediate the contribution of stressful experiences to personality development and the manifestation of illness. This review summarizes our current molecular understanding of how early environment influences brain development in a manner that persists through life and highlights recent evidence from rodent studies suggesting that maternal care in the first week of postnatal life establishes diverse and stable phenotypes in the offspring through epigenetic modification of genes expressed in the brain that shape neuroendocrine and behavioral stress responsivity throughout life.

  16. 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. PMID:26990202

  17. Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment

    PubMed Central

    El Hajj, Nady; Schneider, Eberhard; Lehnen, Harald; Haaf, Thomas

    2014-01-01

    The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as ‘developmental origins of health and disease (DOHAD)’ or ‘Barker’ hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene–environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10–20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease. PMID:25187623

  18. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    PubMed

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention.

  19. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    PubMed

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention. PMID:27025444

  20. Mu opioid receptor polymorphism, early social adversity, and social traits.

    PubMed

    Carver, Charles S; Johnson, Sheri L; Kim, Youngmee

    2016-10-01

    A polymorphism in the mu opioid receptor gene OPRM1 (rs1799971) has been investigated for its role in sensitivity to social contexts. Evidence suggests that the G allele of this polymorphism is associated with higher levels of sensitivity. This study tested for main effects of the polymorphism and its interaction with a self-report measure of childhood adversity as an index of negative environment. Outcomes were several personality measures relevant to social connection. Significant interactions were obtained, such that the negative impact of childhood adversity on personality was greater among G carriers than among A homozygotes on measures of agreeableness, interdependence, anger proneness, hostility, authentic pride, life engagement, and an index of (mostly negative) feelings coloring one's world view. Findings support the role of OPRM1 in sensitivity to negative environments. Limitations are noted, including the lack of a measure of advantageous social environment to assess sensitivity to positive social contexts.

  1. Do social disadvantage and early family adversity affect the diurnal cortisol rhythm in infants? The Generation R Study.

    PubMed

    Saridjan, Nathalie S; Huizink, Anja C; Koetsier, Jitske A; Jaddoe, Vincent W; Mackenbach, Johan P; Hofman, Albert; Kirschbaum, Clemens; Verhulst, Frank C; Tiemeier, Henning

    2010-02-01

    Dysregulation of diurnal cortisol secretion patterns may explain the link between adversities early in life and later mental health problems. However, few studies have investigated the influence of social disadvantage and family adversity on the hypothalamic-pituitary-adrenal (HPA) axis early in life. In 366 infants aged 12-20 months from the Generation R Study, a population-based cohort from fetal life onwards, parents collected saliva samples from their infant at 5 moments over the course of 1 day. The area under the curve (AUC), the cortisol awakening response (CAR) and the diurnal cortisol slope were calculated as different composite measures of the diurnal cortisol rhythm. Information about social disadvantage and early adversity was collected using prenatal and postnatal questionnaires. We found that older infants showed lower AUC levels; moreover, infants with a positive CAR were significantly older. Both the AUC and the CAR were related to indicators of social disadvantage and early adversity. Infants of low income families, in comparison to high income families, showed higher AUC levels and a positive CAR. Infants of mothers who smoked during pregnancy were also significantly more likely to show a positive CAR. Furthermore, infants of mothers experiencing parenting stress showed higher AUC levels. The results of our study show that effects of social disadvantage and early adversity on the diurnal cortisol rhythm are already observable in infants. This may reflect the influence of early negative life events on early maturation of the HPA axis. PMID:20006614

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

    PubMed Central

    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 from a prospective longitudinal study of prenatal substance exposure (N = 860). Cortisol reactivity was assessed at age 11. Among African-Americans, prenatal substance exposure exerted an indirect effect through early adversity and cortisol reactivity to predict externalizing behavior, delinquency, and a positive student-teacher relationship at age 11. Decreased cortisol reactivity was related to maladaptive outcomes, and increased cortisol reactivity predicted better executive functioning and a more positive student-teacher relationship. PMID:25376131

  3. Home visiting and the biology of toxic stress: opportunities to address early childhood adversity.

    PubMed

    Garner, Andrew S

    2013-11-01

    Home visiting is an important mechanism for minimizing the lifelong effects of early childhood adversity. To do so, it must be informed by the biology of early brain and child development. Advances in neuroscience, epigenetics, and the physiology of stress are revealing the biological mechanisms underlying well-established associations between early childhood adversity and suboptimal life-course trajectories. Left unchecked, mediators of physiologic stress become toxic, alter both genome and brain, and lead to a vicious cycle of chronic stress. This so-called "toxic stress" results a wide array of behavioral attempts to blunt the stress response, a process known as "behavioral allostasis." Although behaviors like smoking, overeating, promiscuity, and substance abuse decrease stress transiently, over time they become maladaptive and result in the unhealthy lifestyles and noncommunicable diseases that are the leading causes of morbidity and mortality. The biology of toxic stress and the concept of behavioral allostasis shed new light on the developmental origins of lifelong disease and highlight opportunities for early intervention and prevention. Future efforts to minimize the effects of childhood adversity should focus on expanding the capacity of caregivers and communities to promote (1) the safe, stable, and nurturing relationships that buffer toxic stress, and (2) the rudimentary but foundational social-emotional, language, and cognitive skills needed to develop healthy, adaptive coping skills. Building these critical caregiver and community capacities will require a public health approach with unprecedented levels of collaboration and coordination between the healthcare, childcare, early education, early intervention, and home visiting sectors. PMID:24187125

  4. Gambling and Adverse Life Events Among Urban Adolescents

    PubMed Central

    Lee, Grace P.; Derevensky, Jeffrey L.; Ialongo, Nicholas S.; Martins, Silvia S.

    2011-01-01

    This study explored the cross sectional association between adverse life events and gambling in a sample of 515 urban adolescents (average age 17, 55% male, 88% African American). Approximately half of the sample had gambled in the past year (51%); 78% of the gamblers gambled monthly and 39% had a gambling-related problem. On the other hand, 88% of the sample had experienced at least one life event in the past year, and those experiencing events tended to live in more disadvantaged neighborhoods. The mere acknowledgement of experiencing a stressful life event in the past year (yes/no) was not associated with an increase in odds of being a gambler, with gambling more frequently, or with having a gambling problem. However, when the context of the event was considered, an association was found between directly experiencing threatening and deviant/violent types of events and frequent gambling (OR > 2). Additionally, the probability of being a gambler increased as the number of events experienced increased (aOR = 1.07, 95% CI = 1.01, 1.13, P = 0.013), but problems among gamblers were not associated with the number of events experienced (aOR = 1.01, 95% CI = 0.92, 1.11, P = 0.876). During adolescence, life events appear to be connected more with the frequency of gambling rather than with problems related to gambling. PMID:21614529

  5. Benefits of adversity?! How life history affects the behavioral profile of mice varying in serotonin transporter genotype

    PubMed Central

    Bodden, Carina; Richter, S. Helene; Schreiber, Rebecca S.; Kloke, Vanessa; Gerß, Joachim; Palme, Rupert; Lesch, Klaus-Peter; Lewejohann, Lars; Kaiser, Sylvia; Sachser, Norbert

    2015-01-01

    Behavioral profiles are influenced by both positive and negative experiences as well as the genetic disposition. Traditionally, accumulating adversity over lifetime is considered to predict increased anxiety-like behavior (“allostatic load”). The alternative “mismatch hypothesis” suggests increased levels of anxiety if the early environment differs from the later-life environment. Thus, there is a need for a whole-life history approach to gain a deeper understanding of how behavioral profiles are shaped. The aim of this study was to elucidate the effects of life history on the behavioral profile of mice varying in serotonin transporter (5-HTT) genotype, an established mouse model of increased anxiety-like behavior. For this purpose, mice grew up under either adverse or beneficial conditions during early phases of life. In adulthood, they were further subdivided so as to face a situation that either matched or mismatched the condition experienced so far, resulting in four different life histories. Subsequently, mice were tested for their anxiety-like and exploratory behavior. The main results were: (1) Life history profoundly modulated the behavioral profile. Surprisingly, mice that experienced early beneficial and later escapable adverse conditions showed less anxiety-like and more exploratory behavior compared to mice of other life histories. (2) Genotype significantly influenced the behavioral profile, with homozygous 5-HTT knockout mice displaying highest levels of anxiety-like and lowest levels of exploratory behavior. Our findings concerning life history indicate that the absence of adversity does not necessarily cause lower levels of anxiety than accumulating adversity. Rather, some adversity may be beneficial, particularly when following positive events. Altogether, we conclude that for an understanding of behavioral profiles, it is not sufficient to look at experiences during single phases of life, but the whole life history has to be considered

  6. Adverse life events and mental health in middle adolescence.

    PubMed

    Flouri, Eirini; Kallis, Constantinos

    2011-04-01

    This study's aim was to search for the appropriate functional form of the effect of proximal cumulative contextual risk (PCCR), measured with number of adverse life events experienced in the last 6 months, on adolescent psychopathology and prosocial behavior, measured with the Strengths and Difficulties Questionnaire. The study sample was 171 year ten (aged 14-15) adolescents from predominantly socio-economically disadvantaged families in the UK. Adjustment was made for parental education, and for child's age, gender, and academic achievement, which was measured with results in Standard Attainment Tests in English, mathematics and science taken in the previous year. PCCR predicted total difficulties, emotional symptoms, conduct problems and hyperactivity. The relationship between PCCR and total difficulties and emotional symptoms was non-quadratic; the PCCR/externalizing problems relationship was quadratic. The findings highlight the importance of considering both outcome specificity and non-linear patterns of associations when modelling cumulative contextual risk effects on adolescent psychopathology. PMID:20434208

  7. Duration of Early Adversity and Structural Brain Development in Post-Institutionalized Adolescents

    PubMed Central

    Hodel, Amanda S.; Hunt, Ruskin H.; Cowell, Raquel A.; Van Den Heuvel, Sara E.; Gunnar, Megan R.; Thomas, Kathleen M.

    2014-01-01

    For children reared in institutions for orphaned or abandoned children, multiple aspects of the early environment deviate from species-typical experiences, which may lead to alterations in neurobehavioral development. Although the effects of early deprivation and early life stress have been studied extensively in animal models, less is known about implications for human brain development. This structural neuroimaging study examined the long-term neural correlates of early adverse rearing environments in a large sample of 12–14 year old children (N = 110) who were internationally adopted from institutional care as young children (median age at adoption = 12 months) relative to a same age, comparison group reared with their biological families in the United States. History of institutional rearing was associated with broad changes in cortical volume even after controlling for variability in head size. Results suggested that prefrontal cortex was especially susceptible to early adversity, with significant reductions in volume (driven primarily by differences in surface area rather than cortical thickness) in post-institutionalized youth. Hippocampal volumes showed an association with duration of institutional care, with later-adopted children showing the smallest volumes relative to non-adopted controls. Larger amygdala volumes were not detected in this sample of post-institutionalized children. These data suggest that this temporally discrete period of early deprivation is associated with persisting alterations in brain morphology even years after exposure. Furthermore, these alterations are not completely ameliorated by subsequent environmental enrichment by early adolescence. PMID:25451478

  8. Duration of early adversity and structural brain development in post-institutionalized adolescents.

    PubMed

    Hodel, Amanda S; Hunt, Ruskin H; Cowell, Raquel A; Van Den Heuvel, Sara E; Gunnar, Megan R; Thomas, Kathleen M

    2015-01-15

    For children reared in institutions for orphaned or abandoned children, multiple aspects of the early environment deviate from species-typical experiences, which may lead to alterations in neurobehavioral development. Although the effects of early deprivation and early life stress have been studied extensively in animal models, less is known about implications for human brain development. This structural neuroimaging study examined the long-term neural correlates of early adverse rearing environments in a large sample of 12-14 year old children (N = 110) who were internationally adopted from institutional care as young children (median age at adoption = 12 months) relative to a same age, comparison group reared with their biological families in the United States. History of institutional rearing was associated with broad changes in cortical volume even after controlling for variability in head size. Results suggested that prefrontal cortex was especially susceptible to early adversity, with significant reductions in volume (driven primarily by differences in surface area rather than cortical thickness) in post-institutionalized youth. Hippocampal volumes showed an association with duration of institutional care, with later-adopted children showing the smallest volumes relative to non-adopted controls. Larger amygdala volumes were not detected in this sample of post-institutionalized children. These data suggest that this temporally discrete period of early deprivation is associated with persisting alterations in brain morphology even years after exposure. Furthermore, these alterations are not completely ameliorated by subsequent environmental enrichment by early adolescence. PMID:25451478

  9. 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.

  10. Ontogeny of Early Life Immunity

    PubMed Central

    Dowling, David J.; Levy, Ofer

    2014-01-01

    The human immune system is comprised of cellular and molecular components designed to coordinately prevent infection while avoiding potentially harmful inflammation and auto-immunity. Immunity varies with age, reflecting unique age-dependent challenges including fetal gestation, the neonatal phase and infancy. Herein, we review novel mechanistic insights into early life immunity, with emphasis on emerging models of human immune ontogeny, which may inform age-specific translational development of novel anti-infectives, immunomodulators and vaccines. PMID:24880460

  11. Survival of offspring who experience early parental death: early life conditions and later-life mortality.

    PubMed

    Smith, Ken R; Hanson, Heidi A; Norton, Maria C; Hollingshaus, Michael S; Mineau, Geraldine P

    2014-10-01

    We examine the influences of a set of early life conditions (ELCs) on all-cause and cause-specific mortality among elderly individuals, with special attention to one of the most dramatic early events in a child's, adolescent's, or even young adult's life, the death of a parent. The foremost question is, once controlling for prevailing (and potentially confounding) conditions early in life (family history of longevity, paternal characteristics (SES, age at time of birth, sibship size, and religious affiliation)), is a parental death associated with enduring mortality risks after age 65? The years following parental death may initiate new circumstances through which the adverse effects of paternal death operate. Here we consider the offspring's marital status (whether married; whether and when widowed), adult socioeconomic status, fertility, and later life health status. Adult health status is based on the Charlson Co-Morbidity Index, a construct that summarizes nearly all serious illnesses afflicting older individuals that relies on Medicare data. The data are based on linkages between the Utah Population Database and Medicare claims that hold medical diagnoses data. We show that offspring whose parents died when they were children, but especially when they were adolescents/young adults, have modest but significant mortality risks after age 65. What are striking are the weak mediating influences of later-life comorbidities, marital status, fertility and adult socioeconomic status since controls for these do little to alter the overall association. No beneficial effects of the surviving parent's remarriage were detected. Overall, we show the persistence of the effects of early life loss on later-life mortality and indicate the difficulties in addressing challenges at young ages.

  12. Palatable cafeteria diet ameliorates anxiety and depression-like symptoms following an adverse early environment.

    PubMed

    Maniam, Jayanthi; Morris, Margaret J

    2010-06-01

    Early trauma contributes to psychosocial disorders later in life. An adverse early environment induced by maternal separation (MS) is known to alter behavioural and stress responses in rats. Palatable food dampens stress responses. We investigated the influence of palatable cafeteria high-fat diet (HFD) on behavioural responses following MS or non-handling (NH), versus 15min brief separation. After littering, Sprague-Dawley rats were exposed to short separation, S15 (15min), prolonged separation, S180 (180min) daily from postnatal days 2 to 14 or were non-handled. Pups were assigned to HFD or chow at weaning. We assessed depression and anxiety-like behaviour with sucrose preference test (SPT) and elevated plus maze (EPM) respectively, and measured hypothalamic CRH and hippocampal glucocorticoid receptor (GR) expression. S180 rats showed increased anxiety-and depression-like behaviours, with increased plasma corticosterone, hypothalamic CRH, and reduced hippocampal GR expression versus S15 rats. Similar effects were observed across gender. These were normalized by provision of HFD, with greater beneficial effects in males. S15 showed no benefit of HFD. NH female rats had less adverse impacts; HFD had beneficial impact on behaviour in NH males. Thus behavioural deficits and gene expression changes induced by early life stress were ameliorated by HFD. These results highlight the important place of palatable food in reducing central stress responses supporting the therapeutic value of 'comfort food'.

  13. 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…

  14. Early Life Bereavement and Schizophrenia

    PubMed Central

    Liang, Hong; Olsen, Jørn; Yuan, Wei; Cnattingus, Sven; Vestergaard, Mogens; Obel, Carsten; Gissler, Mika; Li, Jiong

    2016-01-01

    Abstract We aimed to examine whether early life bereavement, as indicator of severe stress, was associated with an increased risk of schizophrenia later in life. Based on population registers, we established a cohort of all children born in Denmark (N = 1 686 416) and Sweden (N = 2 563 659) from 1973 to 1997. Children were categorized as exposed if they lost a first-degree relative during the first 18 years of life. Outcome is the first diagnosis of schizophrenia as either inpatient or outpatient. Log-linear Poisson regression models were used to estimate incidence rate ratios (IRRs). A total of 188,850 children (4.6%) experienced death of a first-degree relative from birth to 18 years of age. Compared with unexposed children, those exposed had overall a 39% higher risk of schizophrenia (= 1.39, 95% CI [confidence interval]: 1.32–1.47). The IRR was particularly high if the family member committed suicide (aIRR = 2.11, 95% CI: 1.90–2.34) or died due to an injury or accident (aIRR = 1.44, 95% CI: 1.27–1.63). The IRR of schizophrenia decreased with increasing child's age at bereavement (P < 0.0001). Children who experienced >1 death during the first 18 years of life (aIRR = 1.79, 95% CI: 1.46–2.19) had a higher risk than those with a single death (aIRR = 1.37, 95% CI: 1.30–1.45). The study suggested that exposure to death of a first-degree relative before 18 years was associated with an increased risk of schizophrenia in later life. The complex mechanisms behind these associations remain to be elucidated. PMID:26817875

  15. Naturalistic Rodent Models of Chronic Early-Life Stress

    PubMed Central

    Molet, Jenny; Maras, Pamela M.; Avishai-Eliner, Sarit

    2016-01-01

    A close association between early-life experience and cognitive and emotional outcomes is found in humans. In experimental models, early-life experience can directly influence a number of brain functions long-term. Specifically, and often in concert with genetic background, experience regulates structural and functional maturation of brain circuits and alters individual neuronal function via large-scale changes in gene expression. Because adverse experience during sensitive developmental periods is often associated with neuropsychiatric disease, there is an impetus to create realistic models of distinct early-life experiences. These can then be used to study causality between early-life experiential factors and cognitive and emotional outcomes, and to probe the underlying mechanisms. Although chronic early-life stress has been linked to the emergence of emotional and cognitive disorders later in life, most commonly used rodent models of involve daily maternal separation and hence intermittent early-life stress. We describe here a naturalistic and robust chronic early-life stress model that potently influences cognitive and emotional outcomes. Mice and rats undergoing this stress develop structural and functional deficits in a number of limbic-cortical circuits. Whereas overt pathological memory impairments appear during adulthood, emotional and cognitive vulnerabilities emerge already during adolescence. This naturalistic paradigm, widely adopted around the world, significantly enriches the repertoire of experimental tools available for the study of normal brain maturation and of cognitive and stress-related disorders including depression, autism, post-traumatic stress disorder, and dementia. PMID:24910169

  16. Genetic variation in oxytocin rs2740210 and early adversity associated with postpartum depression and breastfeeding duration.

    PubMed

    Jonas, W; Mileva-Seitz, V; Girard, A W; Bisceglia, R; Kennedy, J L; Sokolowski, M; Meaney, M J; Fleming, A S; Steiner, M

    2013-10-01

    Mothers vary in duration of breastfeeding. These individual differences are related to a variety of demographic and individual maternal factors including maternal hormones, mood and early experiences. However, little is known about the role of genetic factors. We studied single-nucleotide polymorphisms (SNPs) in the OXT peptide gene (rs2740210; rs4813627) and the OXT receptor gene (OXTR rs237885) in two samples of mothers from the Maternal adversity, Vulnerability and Neurodevelopment study (MAVAN), a multicenter (Hamilton and Montreal, Canada) study following mothers and their children from pregnancy until 7 years of age. Data from the Hamilton site was the primary sample (n = 201) and data from Montreal was the replication sample (n = 151). Breastfeeding duration, maternal mood (measured by the CES-D scale) and early life adversity (measured by the CTQ scale) were established during 12 months postpartum. In our primary sample, polymorphisms in OXT rs2740210, but not the other SNPs, interacted with early life adversity to predict variation in breastfeeding duration (overall F8,125  = 2.361, P = 0.021; interaction effect b = -8.12, t = -2.3, P = 0.023) and depression (overall F8,118  = 5.751, P ≤ 0.001; interaction effect b = 6.06, t = 3.13, P = 0.002). A moderated mediation model showed that higher levels of depression mediated the inverse relation of high levels of early life adversity to breastfeeding duration, but only in women possessing the CC genotype [effect a' = -3.3401, 95% confidence interval (CI) = -7.9466 to -0.0015] of the OXT SNP and not in women with the AA/AC genotype (a' = -1.2942, ns). The latter findings (moderated mediation model) were replicated in our Montreal sample (a' = -0.277, 95% CI = -0.7987 to -0.0348 for CC; a' = -0.1820, ns for AA/AC). PMID:23941164

  17. 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. PMID:22682911

  18. Predicting Later-Life Outcomes of Early-Life Exposures

    EPA Science Inventory

    Background: In utero exposure of the fetus to a stressor can lead to disease in later life. Epigenetic mechanisms are likely mediators of later-life expression of early-life events.Objectives: We examined the current state of understanding of later-life diseases resulting from ea...

  19. Early childhood adversity and later hypertension: Data from the World Mental Health Survey

    PubMed Central

    Stein, Dan J.; Scott, Kate; Haro Abad, Josep M.; Aguilar-Gaxiola, Sergio; Alonso, Jordi; Angermeyer, Matthias; Demytteneare, Koen; de Girolamo, Giovanni; Iwata, Noboru; Posada-Villa, José; Kovess, Viviane; Lara, Carmen; Ormel, Johan; Kessler, Ronald C.; Von Korff, Michael

    2012-01-01

    BACKGROUND Although many studies have indicated that psychosocial factors contribute to hypertension, and that early childhood adversity is associated with long-term adverse mental and physical health sequelae, the association between early adversity and later hypertension is not well studied. METHOD Data from 10 countries participating in the World Health Organization (WHO) World Mental Health (WHM) Surveys (N = 18,630) were analyzed to assess the relationship between childhood adversity and adult-onset hypertension, as ascertained by self-report. The potentially mediating effect of early-onset depression-anxiety disorders, as assessed by the WHM Survey version of the International Diagnostic Interview (WMH-CIDI), on the relationship between early adversity and hypertension was also examined. RESULTS Two or more early childhood adversities, as well as early-onset depression-anxiety, were significantly associated with hypertension. A range of specific childhood adversities, as well as early-onset social phobia and panic/agoraphobia, were significantly associated with hypertension. In multivariate analyses, the presence of 3 or more childhood adversities was associated with hypertension, even when early-onset depression-anxiety or current depression-anxiety was included in the model. CONCLUSIONS Although caution is required in the interpretation of self-report data on adult-onset hypertension, the results of this study further strengthen the evidence base regarding the role of psychosocial factors in the pathogenesis of hypertension. PMID:20196979

  20. 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.

  1. 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

  2. Early Adversity, Elevated Stress Physiology, Accelerated Sexual Maturation and Poor Health in Females

    PubMed Central

    Belsky, Jay; Ruttle, Paula L.; Boyce, W. Thomas; Armstrong, Jeffrey M.; Essex, Marilyn J.

    2015-01-01

    Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for increased probability of reproducing before dying via a process of accelerated reproductive maturation. Using data from 73 females, we test the following propositions using path analysis: (a) greater exposure to prenatal stress predicts greater maternal depression and negative parenting in infancy, (b) which predicts elevated basal cortisol at 4.5 years, (c) which predicts accelerated adrenarcheal development, (d) which predicts more physical and mental health problems at age 18. Results prove generally consistent with these propositions, including a direct link from cortisol to mental health problems. DOoHaD investigators should consider including early sexual maturation as a core component linking early adversity and stress physiology with poor health later in life in females. PMID:25915592

  3. Early adversity, elevated stress physiology, accelerated sexual maturation, and poor health in females.

    PubMed

    Belsky, Jay; Ruttle, Paula L; Boyce, W Thomas; Armstrong, Jeffrey M; Essex, Marilyn J

    2015-06-01

    Evolutionary-minded developmentalists studying predictive-adaptive-response processes linking childhood adversity with accelerated female reproductive development and health scientists investigating the developmental origins of health and disease (DOoHaD) may be tapping the same process, whereby longer-term health costs are traded off for increased probability of reproducing before dying via a process of accelerated reproductive maturation. Using data from 73 females, we test the following propositions using path analysis: (a) greater exposure to prenatal stress predicts greater maternal depression and negative parenting in infancy, (b) which predicts elevated basal cortisol at 4.5 years, (c) which predicts accelerated adrenarcheal development, (d) which predicts more physical and mental health problems at age 18. Results prove generally consistent with these propositions, including a direct link from cortisol to mental health problems. DOoHaD investigators should consider including early sexual maturation as a core component linking early adversity and stress physiology with poor health later in life in females.

  4. 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.

  5. Seeing Touches Early in Life.

    PubMed

    Addabbo, Margaret; Longhi, Elena; Bolognini, Nadia; Senna, Irene; Tagliabue, Paolo; Macchi Cassia, Viola; Turati, Chiara

    2015-01-01

    The sense of touch provides fundamental information about the surrounding world, and feedback about our own actions. Although touch is very important during the earliest stages of life, to date no study has investigated infants' abilities to process visual stimuli implying touch. This study explores the developmental origins of the ability to visually recognize touching gestures involving others. Looking times and orienting responses were measured in a visual preference task, in which participants were simultaneously presented with two videos depicting a touching and a no-touching gesture involving human body parts (face, hand) and/or an object (spoon). In Experiment 1, 2-day-old newborns and 3-month-old infants viewed two videos: in one video a moving hand touched a static face, in the other the moving hand stopped before touching it. Results showed that only 3-month-olds, but not newborns, differentiated the touching from the no-touching gesture, displaying a preference for the former over the latter. To test whether newborns could manifest a preferential visual response when the touched body part is different from the face, in Experiment 2 newborns were presented with touching/no-touching gestures in which a hand or an inanimate object-i.e., a spoon- moved towards a static hand. Newborns were able to discriminate a hand-to-hand touching gesture, but they did not manifest any preference for the object-to-hand touch. The present findings speak in favour of an early ability to visually recognize touching gestures involving the interaction between human body parts. PMID:26366563

  6. Cumulative experiences with life adversity: Identifying critical levels for targeting prevention efforts

    PubMed Central

    Mitchell, Kimberly J.; Tynes, Brendesha; Umaña-Taylor, Adriana J.; Williams, David

    2015-01-01

    This paper aims to assess the role of individual types and cumulative life adversity for understanding depressive symptomatology and aggressive behavior. Data were collected in 2011 as part of the Teen Life Online and in Schools Study from 916 ethnically-diverse students from 12 middle, K-8, 6-12 and high schools in the Midwest United States. Youth reported an average of 4.1 non-victimization adversities and chronic stressors in their lifetimes. There was a linear relationship between number of adversities and depression and aggression scores. Youth reporting the highest number of adversities (7 or more) had significantly higher depression and aggression scores than youth reporting any other number of adversities suggesting exposure at this level is a critical tipping point for mental health concerns. Findings underscore an urgent need to support youth as they attempt to negotiate, manage, and cope with adversity in their social worlds. PMID:26057876

  7. Cumulative experiences with life adversity: Identifying critical levels for targeting prevention efforts.

    PubMed

    Mitchell, Kimberly J; Tynes, Brendesha; Umaña-Taylor, Adriana J; Williams, David

    2015-08-01

    This paper aims to assess the role of individual types and cumulative life adversity for understanding depressive symptomatology and aggressive behavior. Data were collected in 2011 as part of the Teen Life Online and in Schools Study from 916 ethnically-diverse students from 12 middle, K-8, 6-12 and high schools in the Midwest United States. Youth reported an average of 4.1 non-victimization adversities and chronic stressors in their lifetimes. There was a linear relationship between number of adversities and depression and aggression scores. Youth reporting the highest number of adversities (7 or more) had significantly higher depression and aggression scores than youth reporting any other number of adversities suggesting exposure at this level is a critical tipping point for mental health concerns. Findings underscore an urgent need to support youth as they attempt to negotiate, manage, and cope with adversity in their social worlds.

  8. Social Involvement Modulates the Response to Novel and Adverse Life Events in Mice

    PubMed Central

    Colnaghi, Luca; Clemenza, Kelly; Groleau, Sarah E.; Weiss, Shira; Snyder, Anna M.; Lopez-Rosas, Mariana; Levine, Amir A.

    2016-01-01

    Epidemiological findings suggest that social involvement plays a major role in establishing resilience to adversity, however, the neurobiology by which social involvement confers protection is not well understood. Hypothesizing that social involvement confers resilience by changing the way adverse life events are encoded, we designed a series of behavioral tests in mice that utilize the presence or absence of conspecific cage mates in measuring response to novel and adverse events. We found that the presence of cage mates increased movement after exposure to a novel environment, increased time spent in the open arms of the elevated plus maze, and decreased freezing time after a foot shock as well as expedited fear extinction, therefore significantly changing the response to adversity. This is a first description of a mouse model for the effects of social involvement on adverse life events. Understanding how social involvement provides resilience to adversity may contribute to the future treatment and prevention of mental and physical illness. PMID:27632422

  9. Social Involvement Modulates the Response to Novel and Adverse Life Events in Mice.

    PubMed

    Colnaghi, Luca; Clemenza, Kelly; Groleau, Sarah E; Weiss, Shira; Snyder, Anna M; Lopez-Rosas, Mariana; Levine, Amir A

    2016-01-01

    Epidemiological findings suggest that social involvement plays a major role in establishing resilience to adversity, however, the neurobiology by which social involvement confers protection is not well understood. Hypothesizing that social involvement confers resilience by changing the way adverse life events are encoded, we designed a series of behavioral tests in mice that utilize the presence or absence of conspecific cage mates in measuring response to novel and adverse events. We found that the presence of cage mates increased movement after exposure to a novel environment, increased time spent in the open arms of the elevated plus maze, and decreased freezing time after a foot shock as well as expedited fear extinction, therefore significantly changing the response to adversity. This is a first description of a mouse model for the effects of social involvement on adverse life events. Understanding how social involvement provides resilience to adversity may contribute to the future treatment and prevention of mental and physical illness. PMID:27632422

  10. What a general paediatrician needs to know about early life programming.

    PubMed

    Williams, Thomas C; Drake, Amanda J

    2015-11-01

    The process whereby early exposure to an adverse environment has an influence on later life outcomes has been called 'early life programming'. While epidemiological evidence for this has been available for decades, only in recent years have the mechanisms, in particular epigenetic modifications, for this process begun to be elucidated. We discuss the evidence for early life programming, the possible mechanisms, how effects may be transmitted across generations, and conclude by looking at some examples relevant to general paediatrics.

  11. The Early History of Life

    NASA Astrophysics Data System (ADS)

    Nisbet, E. G.; Fowler, C. M. R.

    2003-12-01

    The youth of the Earth is strange to us. Many of the most fundamental constraints on life may have been different, especially the oxidation state of the surface. Should we suddenly land on its Hadean or early Archean surface by some sci-fi accident, we would not recognize our home. Above, the sky may have been green or some other unworldly color, and above that the weak young Sun might have been unrecognizable to someone trying to identify it from its spectrum. Below, seismology would show a hot, comparatively low-viscosity interior, possibly with a magma ocean in the deeper part of the upper mantle (Drake and Righter, 2002; Nisbet and Walker, 1982), and a core that, though present, was perhaps rather smaller than today. The continents may have been small islands in an icy sea, mostly frozen with some leads of open water, ( Sleep et al., 2001). Into these icy oceans, huge protruding Hawaii-like volcanoes would have poured out vast far-spreading floods of komatiite lavas in immense eruptions that may have created sudden local hypercane storms to disrupt the nearby icebergs. And meteorites would rain down.Or perhaps it was not so strange, nor so violent. The child is father to the man; young Earth was mother to Old Earth. Earth had hydrogen, silicate rock below and on the surface abundant carbon, which her ancient self retains today. Moreover, Earth was oxygen-rich, as today. Today, a tiny part of the oxygen is free, as air; then the oxygen would have been in the mantle while the surface oxygen was used to handcuff the hydrogen as dihydrogen monoxide. Oxygen dihydride is dense, unlikely to fly off to space, and at the poles, rock-forming. Of all the geochemical features that make Earth unique, the initial degassing (Genesis 2 : b) and then the sustained presence of liquid water is the defining oddity of this planet. Early Earth probably also kept much of its carbon, nitrogen, and sulfur as oxide or hydride. And, after the most cataclysmic events had passed, ˜4.5 Ga

  12. 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…

  13. Early Adverse Experiences and the Neurobiology of Facial Emotion Processing

    ERIC Educational Resources Information Center

    Moulson, Margaret C.; Fox, Nathan A.; Zeanah, Charles H.; Nelson, Charles A.

    2009-01-01

    To examine the neurobiological consequences of early institutionalization, the authors recorded event-related potentials (ERPs) from 3 groups of Romanian children--currently institutionalized, previously institutionalized but randomly assigned to foster care, and family-reared children--in response to pictures of happy, angry, fearful, and sad…

  14. Emotional Suppression Mediates the Relation Between Adverse Life Events and Adolescent Suicide: Implications for Prevention

    PubMed Central

    Kaplow, Julie B.; Gipson, Polly Y.; Horwitz, Adam G.; Burch, Bianca N.; King, Cheryl A.

    2016-01-01

    Suicidal ideation substantially increases the odds of future suicide attempts, and suicide is the second leading cause of death among adolescents. A history of adverse life events has been linked with future suicidal ideation and attempts, although studies examining potential mediating variables have been scarce. One probable mediating mechanism is how the individual copes with adverse life events. For example, certain coping strategies appear to be more problematic than others in increasing future psychopathology, and emotional suppression in particular has been associated with poor mental health outcomes in adults and children. However, no studies to date have examined the potential mediating role of emotional suppression in the relation between adverse life events and suicidal thoughts/behavior in adolescence. The goal of the current study was to examine emotional suppression as a mediator in the relation between childhood adversity and future suicidal thoughts/behaviors in youth. A total of 625 participants, aged 14–19 years, seeking ER services were administered measures assessing adverse life events, coping strategies, suicidal ideation in the last 2 weeks, and suicide attempts in the last month. The results suggest that emotional suppression mediates the relation between adversity and both (1) suicidal thoughts and (2) suicide attempts above and beyond demographic variables and depressive symptoms. This study has important implications for interventions aimed at preventing suicidal thoughts and behavior in adolescents with histories of adversity. PMID:23412949

  15. 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.

  16. 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...

  17. Neurobiology of early life stress: clinical studies.

    PubMed

    Heim, Christine; Nemeroff, Charles B

    2002-04-01

    A burgeoning number of clinical studies have evaluated the immediate and long-term neurobiological effects of early developmental stress, eg, child abuse and neglect or parental loss, in the past years. This review summarizes and discusses the available findings from neuroendocrine (hypothalamic-pituitary-adrenal axis, other neuroendocrine axes), neurochemical (catecholamines, serotonin, other neurotransmitters), psychophysiological (autonomic function, startle reactivity, brain electrical activity) and neuroimaging studies (brain structure, function) conducted in children or adults with a history of early life stress, with or without psychiatric disorders. Early developmental stress in humans appears to be associated with neurobiological alterations that are similar to many findings in animal models of early life stress, and likely represent the biological basis of an enhanced risk for psychopathology. Clinical studies are now beginning to explore potentially differential neurobiological effects of different types of early life stress and the existence of critical developmental periods, which may be sensitive to the neurobiological effects of specific stressors. In addition, the role of a multitude of moderating and mediating factors in the determination of individual vulnerability or resilience to the neurobiological effects of early life stress should be addressed. Findings from such studies may ultimately help to prevent the deleterious neurobiological and psychopathological consequences in the unacceptably high number of children exposed to early life stress in modern society. PMID:11953939

  18. Early life circumstances and their impact on menarche and menopause

    PubMed Central

    Mishra, Gita D; Cooper, Rachel; Tom, Sarah E; Kuh, Diana

    2012-01-01

    Ages at menarche and menopause have been shown to be associated with adverse health outcomes in later life. For example, earlier menarche and later menopause have been independently linked to higher risk of breast cancer. Earlier menarche may also be associated with an increased risk of endometrial cancer, menstrual problems and adult obesity. Given the associations of ages at menarche and menopause with future health outcomes, it is important to establish what factors across life, and generations, may influence these. This article examines the associations of early life factors, namely birthweight, bodyweight and growth during childhood, childhood socioeconomic circumstances and psychosocial factors with ages at menarche and menopause. It examines possible explanations of the associations found, including life history theory, and discusses areas for future research. PMID:19245355

  19. Suffering and compassion: The links among adverse life experiences, empathy, compassion, and prosocial behavior.

    PubMed

    Lim, Daniel; DeSteno, David

    2016-03-01

    Experiencing past adversity traditionally has been linked to negative life outcomes. However, emerging evidence suggests that heterogeneity exists with respect to links between adversity and resilience, with adversity often enhancing cooperation in the face of joint suffering. Here, the authors present 2 studies designed to examine if the severity of past adversity is associated with an enduring propensity for empathy-mediated compassion, and, if so, whether the resulting compassion directly is, in turn, linked to behavior meant to relieve the suffering of others. Using both MTurk and laboratory-based paradigms, the authors find that increasing severity of past adversity predicts increased empathy, which in turn, is linked to a stable tendency to feel compassion for others in need. In addition, they demonstrate that the resulting individual differences in compassion appear to engender behavioral responses meant to assist others (i.e., charitable giving, helping a stranger).

  20. Early adverse experience as a developmental risk factor for later psychopathology: evidence from rodent and primate models.

    PubMed

    Sánchez, M M; Ladd, C O; Plotsky, P M

    2001-01-01

    Increasing evidence supports the view that the interaction of perinatal exposure to adversity with individual genetic liabilities may increase an individual's vulnerability to the expression of psycho- and physiopathology throughout life. The early environment appears to program some aspects of neurobiological development and, in turn, behavioral, emotional, cognitive, and physiological development. Several rodent and primate models of early adverse experience have been analyzed in this review, including those that "model" maternal separation or loss, abuse or neglect, and social deprivation. Accumulating evidence shows that these early traumatic experiences are associated with long-term alterations in coping style, emotional and behavioral regulation. neuroendocrine responsiveness to stress, social "fitness,' cognitive function, brain morphology, neurochemistry, and expression levels of central nervous system genes that have been related to anxiety and mood disorders. Studies are underway to identify important aspects of adverse early experience, such as (a) the existence of "sensitive periods" during development associated with alterations in particular output systems. (b) the presence of "windows of opportunity" during which targeted interventions (e.g., nurturant parenting or supportive-enriching environment) may prevent or reverse dysfunction, (c) the identity of gene polymorphisms contributing to the individual's variability in vulnerability, and (d) a means to translate the timing of these developmental "sensitive periods" across species. PMID:11523842

  1. Association between Adverse Life Events and Addictive Behaviors among Male and Female Adolescents

    PubMed Central

    Lee, Grace P.; Storr, Carla L.; Ialongo, Nicholas S.; Martins, Silvia S.

    2012-01-01

    Background Adverse life events have been associated with gambling and substance use as they can serve as forms of escapism. Involvement in gambling and substance use can also place individuals in adversely stressful situations. Objectives To explore potential male-female differences in the association between addictive behavior and adverse life events among an urban cohort of adolescents. Methods The study sample comprised of 515 adolescent participants in a randomized prevention trial. With self-reported data, four addictive behavior groups were created: Non-Substance Users and Non-Gamblers, Substance Users Only, Gamblers Only, and Substance Users and Gamblers. Multinomial logistic regression analyses with interaction terms of sex and adverse life events were conducted. Results Adverse life events and engaging in at least one addictive behavior were common for both sexes. Substance Users and Gamblers had more than twice the likelihood of Non-Substance Users and Non-Gamblers to experience any event as well as events of various domains (i.e., relationship, violence, and instability). Neither relationship nor instability events’ associations with the co-occurrence of substance use and gambling significantly differed between sexes. Conversely, females exposed to violence events were significantly more likely than similarly exposed males to report the co-occurrence of substance use and gambling. Conclusion Findings from the current study prompt future studies to devote more attention to the development of effective programs that teach adaptive coping strategies to adolescents, particularly to females upon exposure to violence. PMID:23082829

  2. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking.

    PubMed

    Cornelius, Marie D; De Genna, Natacha M; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n=917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  3. Prenatal alcohol and other early childhood adverse exposures: Direct and indirect pathways to adolescent drinking

    PubMed Central

    Cornelius, Marie D.; De Genna, Natacha M.; Goldschmidt, Lidush; Larkby, Cynthia; Day, Nancy L.

    2016-01-01

    We examined direct and indirect pathways between adverse environmental exposures during gestation and childhood and drinking in mid-adolescence. Mothers and their offspring (n = 917 mother/child dyads) were followed prospectively from second trimester to a 16-year follow-up assessment. Interim assessments occurred at delivery, 6, 10, and 14 years. Adverse environmental factors included gestational exposures to alcohol, tobacco, and marijuana, exposures to childhood maltreatment and violence, maternal psychological symptoms, parenting practices, economic and home environments, and demographic characteristics of the mother and child. Indirect effects of early child behavioral characteristics including externalizing, internalizing activity, attention, and impulsivity were also examined. Polytomous logistic regression analyses were used to evaluate direct effects of adverse environmental exposures with level of adolescent drinking. Structural equation modeling (SEM) was applied to simultaneously estimate the relation between early adversity variables, childhood characteristics, and drinking level at age 16 while controlling for significant covariates. Level of drinking among the adolescent offspring was directly predicted by prenatal exposure to alcohol, less parental strictness, and exposures to maltreatment and violence during childhood. Whites and offspring with older mothers were more likely to drink at higher levels. There was a significant indirect effect between childhood exposure to violence and adolescent drinking via childhood externalizing behavior problems. All other hypothesized indirect pathways were not significant. Thus most of the early adversity measures directly predicted adolescent drinking and did not operate via childhood behavioral dysregulation characteristics. These results highlight the importance of adverse environmental exposures on pathways to adolescent drinking. PMID:26994529

  4. Early Gestational Weight Gain Rate and Adverse Pregnancy Outcomes in Korean Women.

    PubMed

    Cho, Eun-Hee; Hur, Junguk; Lee, Kyung-Ju

    2015-01-01

    During pregnancy, many women gain excessive weight, which is related to adverse maternal and neonatal outcomes. In this study, we evaluated whether rate of gestational weight gain (RGWG) in early, mid, and late pregnancy is strongly associated with adverse pregnancy outcomes. A retrospective chart review of 2,789 pregnant Korean women was performed. Weights were recorded at the first clinic visit, during the screening test for fetal anomaly, and during the 50g oral glucose challenge test and delivery, to represent early, mid, and late pregnancy, respectively. A multivariate logistic regression analysis was performed to examine the relationship between RGWG and adverse pregnancy outcomes. At early pregnancy, the RGWG was significantly associated with high risk of developing gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), large for gestational age (LGA) infants, macrosomia, and primary cesarean section (P-CS). The RGWG of mid pregnancy was not significantly associated with any adverse pregnancy outcomes. The RGWG at late pregnancy was significantly associated with a lower risk of developing GDM, preterm birth and P-CS, but with a higher risk of developing LGA infants and macrosomia. When the subjects were divided into three groups (Underweight, Normal, and Obese), based on pre-pregnancy body mass index (BMI), the relationship between early RGWG and adverse pregnancy outcomes was significantly different across the three BMI groups. At early pregnancy, RGWG was not significantly associated to adverse pregnancy outcomes for subjects in the Underweight group. In the Normal group, however, early RGWG was significantly associated with GDM, PIH, LGA infants, macrosomia, P-CS, and small for gestational weight (SGA) infants, whereas early RGWG was significantly associated with only a high risk of PIH in the Obese group. The results of our study suggest that early RGWG is significantly associated with various adverse pregnancy outcomes and that

  5. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function

    PubMed Central

    Hoeijmakers, Lianne; Lucassen, Paul J.; Korosi, Aniko

    2015-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity. PMID:25620909

  6. The interplay of early-life stress, nutrition, and immune activation programs adult hippocampal structure and function.

    PubMed

    Hoeijmakers, Lianne; Lucassen, Paul J; Korosi, Aniko

    2014-01-01

    Early-life adversity increases the vulnerability to develop psychopathologies and cognitive decline later in life. This association is supported by clinical and preclinical studies. Remarkably, experiences of stress during this sensitive period, in the form of abuse or neglect but also early malnutrition or an early immune challenge elicit very similar long-term effects on brain structure and function. During early-life, both exogenous factors like nutrition and maternal care, as well as endogenous modulators, including stress hormones and mediator of immunological activity affect brain development. The interplay of these key elements and their underlying molecular mechanisms are not fully understood. We discuss here the hypothesis that exposure to early-life adversity (specifically stress, under/malnutrition and infection) leads to life-long alterations in hippocampal-related cognitive functions, at least partly via changes in hippocampal neurogenesis. We further discuss how these different key elements of the early-life environment interact and affect one another and suggest that it is a synergistic action of these elements that shapes cognition throughout life. Finally, we consider different intervention studies aiming to prevent these early-life adversity induced consequences. The emerging evidence for the intriguing interplay of stress, nutrition, and immune activity in the early-life programming calls for a more in depth understanding of the interaction of these elements and the underlying mechanisms. This knowledge will help to develop intervention strategies that will converge on a more complete set of changes induced by early-life adversity.

  7. Parental responsiveness moderates the association between early-life stress and reduced telomere length.

    PubMed

    Asok, A; Bernard, K; Roth, T L; Rosen, J B; Dozier, M

    2013-08-01

    Early-life stress, such as maltreatment, institutionalization, and exposure to violence, is associated with accelerated telomere shortening. Telomere shortening may thus represent a biomarker of early adversity. Previous studies have suggested that responsive parenting may protect children from the negative biological and behavioral consequences of early adversity. This study examined the role of parental responsiveness in buffering children from telomere shortening following experiences of early-life stress. We found that high-risk children had significantly shorter telomeres than low-risk children, controlling for household income, birth weight, gender, and minority status. Further, parental responsiveness moderated the association between risk and telomere length, with more responsive parenting associated with longer telomeres only among high-risk children. These findings suggest that responsive parenting may have protective benefits on telomere shortening for young children exposed to early-life stress. Therefore, this study has important implications for early parenting interventions. PMID:23527512

  8. Early life programming and metabolic syndrome.

    PubMed

    Wang, Xiu-Min

    2013-02-01

    Metabolic syndrome (MS) has reached epidemic proportions worldwide among children. Early life "programming" is now thought to be important in the etiology of obesity, type 2 diabetes, cardiovascular disease and MS. Nutritional imbalance and exposures to endocrine disruptor chemicals during development can increase risk for MS later in life. Epigenetic marks may be reprogrammed in response to both stochastic and environmental stimuli, such as changes in diet and the in utero environment, therefore, determination of targets for early life effects on epigenetic gene regulation provides insight into the molecular mechanisms involved in the epigenetic transgenerational inheritance of a variety of adult onset disease phenotypes. The perinatal period is a crucial time of growth, development and physiological changes in mother and child, which provides a window of opportunity for early intervention that may induce beneficial physiological alternations.

  9. Antibiotics in early life and obesity

    PubMed Central

    Cox, Laura M.; Blaser, Martin J.

    2015-01-01

    The intestinal microbiota can influence host metabolism. When given early in life, agents that disrupt microbiota composition and consequently its metabolic activity, can influence body mass of the host by either promoting weight gain or stunting growth, which is consistent with effects of the microbiota on development. In this Perspective, we posit that microbiota disruptions in early-life can have long-lasting effects on body weight in adulthood. Furthermore, we examine the dichotomy between antibiotic-induced repressed or promoted growth and review the experimental and epidemiological evidence that supports these phenotypes. Considering the characteristics of the gut microbiota in early life as a distinct dimension of human growth and development, as well as comprehending its susceptibility to perturbation, will allow for increased understanding of human physiology and could lead to development of interventions to stem current epidemic diseases, such as obesity and types 1 and 2 diabetes mellitus. PMID:25488483

  10. Osteoporosis in survivors of early life starvation.

    PubMed

    Weisz, George M; Albury, William R

    2013-01-01

    The objective of this study was to provide evidence for the association of early life nutritional deprivation and adult osteoporosis, in order to suggest that a history of such deprivation may be an indicator of increased risk of osteoporosis in later life. The 'fetal programming' of a range of metabolic and cardiovascular disorders in adults was first proposed in the 1990s and more recently extended to disorders of bone metabolism. Localised famines during World War II left populations in whom the long-term effects of maternal, fetal and infantile nutritional deprivation were studied. These studies supported the original concept of 'fetal programming' but did not consider bone metabolism. The present paper offers clinical data from another cohort of World War II famine survivors - those from the Holocaust. The data presented here, specifically addressing the issue of osteoporosis, report on 11 Holocaust survivors in Australia (five females, six males) who were exposed to starvation in early life. The cases show, in addition to other metabolic disorders associated with early life starvation, various levels of osteoporosis, often with premature onset. The cohort studied is too small to support firm conclusions, but the evidence suggests that the risk of adult osteoporosis in both males and females is increased by severe starvation early in life - not just in the period from gestation to infancy but also in childhood and young adulthood. It is recommended that epidemiological research on this issue be undertaken, to assist planning for the future health needs of immigrants to Australia coming from famine affected backgrounds. Pending such research, it would be prudent for primary care health workers to be alert to the prima facie association between early life starvation and adult osteoporosis, and to take this factor into account along with other indicators when assessing a patient's risk of osteoporosis in later life.

  11. Magnetism and the putative early Martian life

    NASA Astrophysics Data System (ADS)

    Rochette, P.

    2001-08-01

    A short critical review is provided on three questions linking magnetism and the putative early Mars life. Was there a large internal Martian magnetic field, during which period, and is it a requisite for life? What is the origin of the paleomagnetic signal of Martian meteorites, including ALH84001? What is the present credibility of the case for fossil bacterial magnetite grains in ALH84001?

  12. Profiles of family-focused adverse experiences through childhood and early adolescence: The ROOTS project a community investigation of adolescent mental health

    PubMed Central

    2011-01-01

    Background Adverse family experiences in early life are associated with subsequent psychopathology. This study adds to the growing body of work exploring the nature and associations between adverse experiences over the childhood years. Methods Primary carers of 1143 randomly recruited 14-year olds in Cambridgeshire and Suffolk, UK were interviewed using the Cambridge Early Experiences Interview (CAMEEI) to assess family-focused adversities. Adversities were recorded retrospectively in three time periods (early and later childhood and early adolescence). Latent Class Analysis (LCA) grouped individuals into adversity classes for each time period and longitudinally. Adolescents were interviewed to generate lifetime DSM-IV diagnoses using the K-SADS-PL. The associations between adversity class and diagnoses were explored. Results LCA generated a 4-class model for each time period and longitudinally. In early childhood 69% were allocated to a low adversity class; a moderate adversity class (19%) showed elevated rates of family loss, mild or moderate family discord, financial difficulties, maternal psychiatric illness and higher risk for paternal atypical parenting; a severe class (6%) experienced higher rates on all indicators and almost exclusively accounted for incidents of child abuse; a fourth class, characterised by atypical parenting from both parents, accounted for the remaining 7%. Class membership was fairly stable (~ 55%) over time with escape from any adversity by 14 years being uncommon. Compared to those in the low class, the odds ratio for reported psychopathology in adolescents in the severe class ranged from 8 for disruptive behaviour disorders through to 4.8 for depressions and 2.0 for anxiety disorders. Only in the low adversity class did significantly more females than males report psychopathology. Conclusions Family adversities in the early years occur as multiple rather than single experiences. Although some children escape adversity, for many this

  13. Therapist Adversity and the Life of the Therapist: Perspectives from Miriam Greenspan

    ERIC Educational Resources Information Center

    Comstock, Dana L.

    2008-01-01

    Painful situations arise during the education and careers of counselors and therapists. Most theoretical orientations fail to address how clinicians are to handle their live adversity during the course of their work with clients. In fact, irrespective of the theoretical orientation, most clinicians are given the directive to "check your own life"…

  14. The International Society for Developmental Psychobiology Sackler Symposium: Early adversity and the maturation of emotion circuits - a cross-species analysis

    PubMed Central

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

    2016-01-01

    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 4 different research laboratories, using 3 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 behaviour with the caregiver, and emotional reactions to the world. These results provide insight into mechanisms responsible for caregiver induced mental health trajectory alterations. PMID:25290865

  15. 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.

  16. 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.

  17. EARLY CRANIOFACIAL DEVELOPMENT: LIFE AMONG THE SIGNALS

    EPA Science Inventory

    Early Craniofacial Development: Life Among the Signals. Sid Hunter and Keith Ward. Reproductive Toxicology Division, NHEERL, US EPA, RTP, NC, 27711

    Haloacetic acids (HAA) are chemicals formed during drinking water disinfection and present in finished tap water. Exposure o...

  18. 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. PMID:22201148

  19. 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.

  20. Development of Life on Early Mars

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2009-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution encompassed conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water- as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at 3.9 Gy, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H20, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 My?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve). The commonly stated requirement that life would need hundreds of millions of year to get started is only an assumption; we know of no evidence that requires such a long interval for the development of life, if the proper habitable

  1. Life insurance and breast cancer risk assessment: adverse selection, genetic testing decisions, and discrimination.

    PubMed

    Armstrong, Katrina; Weber, Barbara; FitzGerald, Genevieve; Hershey, John C; Pauly, Mark V; Lemaire, Jean; Subramanian, Krupa; Asch, David A

    2003-07-30

    Life insurance industry access to genetic information is controversial. Consumer groups argue that access will increase discrimination in life insurance premiums and discourage individuals from undergoing genetic testing that may provide health benefits. Conversely, life insurers argue that without access to risk information available to individuals, they face substantial financial risk from adverse selection. Given this controversy, we conducted a retrospective cohort study to evaluate the impact of breast cancer risk information on life insurance purchasing, the impact of concerns about life insurance discrimination on use of BRCA1/2 testing, and the incidence of life insurance discrimination following participation in breast cancer risk assessment and BRCA1/2 testing. Study participants were 636 women who participated in genetic counseling and/or genetic testing at a University based clinic offering breast cancer risk assessment, genetic counseling, and BRCA1/2 testing between January 1995 and May 2000. Twenty-seven women (4%) had increased and six (1%) had decreased their life insurance since participation in breast cancer risk assessment. The decision to increase life insurance coverage was associated with predicted breast cancer risk (adjusted OR 1.03 for each 1% absolute increase in risk, 95% CI 1.01-1.10) and being found to carry a mutation in BRCA1/2 (OR 5.10, 95% CI 1.90-13.66). Concern about life insurance discrimination was inversely associated with the decision to undergo BRCA1/2 testing (RR 0.67, 95% CI 0.52-0.85). No respondent reported having life insurance denied or canceled. In this cohort of women, these results indicate that information about increased breast cancer risk is associated with increase in life insurance purchasing, raising the possibility of adverse selection. Although fear of insurance discrimination is associated with the decision not to undergo BRCA1/2 testing, there was no evidence of actual insurance discrimination from BRCA1

  2. Impact of early adversity on glucocorticoid regulation and later mental disorders.

    PubMed

    Strüber, Nicole; Strüber, Daniel; Roth, Gerhard

    2014-01-01

    Early adverse experiences such as abuse or neglect can influence brain development and consequently bring forth a predisposition toward mental and behavioral disorders. Many authors suggest that long-term changes in the functionality of the HPA axis might be involved in mediating this relationship. The direction of change and its consequences have not been clarified though: Do early adverse experiences yield a stable glucocorticoid hyperfunction or a long-term glucocorticoid hypofunction, and how is this change of functionality associated with mental or behavioral disorders? This review summarizes correlative findings and illustrates inconsistencies of current research literature. It focuses on the specific neurochemical milieu accompanying early adverse experiences and discusses possible interactions of the glucocorticoid system with oxytocin and components of the serotonergic system. On the basis of this physiological view, a novel two-pathway model is presented, according to which specific early experiences are associated with characteristic early changes in the functionality of these systems and result in a predisposition to distinct mental and behavioral disorders. PMID:24216122

  3. 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

  4. Evaluation of whole mount in situ hybridization as a tool for pathway-based toxicological research in early-life stage fathead minnows (poster)

    EPA Science Inventory

    Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

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

    EPA Science Inventory

    Early-life stage fish can be more sensitive to chemical exposure than mature, adult fish. Therefore, defining adverse outcome pathways (AOPs) relevant to early-life stages is critical for linking perturbations of key events during fish development to potential adverse outcomes of...

  6. Early evolution without a tree of life

    PubMed Central

    2011-01-01

    Life is a chemical reaction. Three major transitions in early evolution are considered without recourse to a tree of life. The origin of prokaryotes required a steady supply of energy and electrons, probably in the form of molecular hydrogen stemming from serpentinization. Microbial genome evolution is not a treelike process because of lateral gene transfer and the endosymbiotic origins of organelles. The lack of true intermediates in the prokaryote-to-eukaryote transition has a bioenergetic cause. This article was reviewed by Dan Graur, W. Ford Doolittle, Eugene V. Koonin and Christophe Malaterre. PMID:21714942

  7. Effects of early adversity on young children's diurnal cortisol rhythms and externalizing behavior.

    PubMed

    Bernard, Kristin; Zwerling, Jordana; Dozier, Mary

    2015-12-01

    Early adversity is associated with biological and behavioral dysregulation in early childhood. We examined whether early adversity (i.e., poverty and involvement with child protective services [CPS]) had an indirect effect on externalizing behavior through HPA axis dysregulation, specifically blunted diurnal cortisol patterns. Participants included 94 children between the ages of 3.94 and 6.52 years old, who had a history of CPS involvement (n = 53) or no history of CPS involvement (n = 41). Cortisol samples were collected at wake-up and bedtime across 3 days, and parent-reported externalizing behavior was assessed using the Child Behavior Checklist. Results showed that history of CPS involvement and poverty were associated with blunted cortisol patterns, which in turn led to elevated externalizing behavior. The indirect effect of CPS involvement on externalizing behavior through blunted cortisol was significant, whereas the indirect effect of poverty on externalizing behavior was nonsignificant. Findings add to our understanding of neurobiological mechanisms linking early adversity to psychopathology. PMID:26289841

  8. Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

    PubMed

    Zilioli, Samuele; Slatcher, Richard B; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

    2016-09-01

    Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span.

  9. Childhood Adversity, Self-Esteem, and Diurnal Cortisol Profiles Across the Life Span.

    PubMed

    Zilioli, Samuele; Slatcher, Richard B; Chi, Peilian; Li, Xiaoming; Zhao, Junfeng; Zhao, Guoxiang

    2016-09-01

    Childhood adversity is associated with poor health outcomes in adulthood; the hypothalamic-pituitary-adrenal (HPA) axis has been proposed as a crucial biological intermediary of these long-term effects. Here, we tested whether childhood adversity was associated with diurnal cortisol parameters and whether this link was partially explained by self-esteem. In both adults and youths, childhood adversity was associated with lower levels of cortisol at awakening, and this association was partially driven by low self-esteem. Further, we found a significant indirect pathway through which greater adversity during childhood was linked to a flatter cortisol slope via self-esteem. Finally, youths who had a caregiver with high self-esteem experienced a steeper decline in cortisol throughout the day compared with youths whose caregiver reported low self-esteem. We conclude that self-esteem is a plausible psychological mechanism through which childhood adversity may get embedded in the activity of the HPA axis across the life span. PMID:27481911

  10. DNA memories of early social life.

    PubMed

    Hoffmann, A; Spengler, D

    2014-04-01

    The foundations of brain architecture are established early in life through a continuous series of dynamic interactions in which environmental conditions and personal experiences have a significant impact on how genetic predispositions are expressed. New scientific research shows that early social experiences can actually influence how genes are expressed. Thus, the old-school concepts that genes are "chiseled in stone" or that they alone determine development have been disproven. The discovery of the epigenome provides an explanation, at the molecular level, for why and how early positive and negative social experiences give rise to a biological memory that can have lifelong impacts. Signatures associated with the epigenome can be temporary or permanent, affect multiple organ systems, and increase the risk not only for poor physical and mental health outcomes but also for impairments in future learning capacity and behavior. Here, we focus on recent evidence for a role of epigenetic DNA modifications as a potential mechanism that explains how early social life experiences become embedded in the circuitry of the developing brain and are associated with lifelong consequences.

  11. Examining the Relationships Between Prenatal Methamphetamine Exposure, Early Adversity, and Child Neurobehavioral Disinhibition

    PubMed Central

    Abar, Beau; LaGasse, Linda L.; Newman, Elana; Smith, Lynne M; Huestis, Marilyn; Neal, Charles; DeRauf, Chris; Shah, Rizwan; Arria, Amelia; Grotta, Sheri Della; Dansereau, Lynne M.; Lester, Barry M.

    2013-01-01

    Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother–infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed. PMID:23067308

  12. Examining the relationships between prenatal methamphetamine exposure, early adversity, and child neurobehavioral disinhibition.

    PubMed

    Abar, Beau; LaGasse, Linda L; Derauf, Chris; Newman, Elana; Shah, Rizwan; Smith, Lynne M; Arria, Amelia; Huestis, Marilyn; Della Grotta, Sheri; Dansereau, Lynne M; Neal, Charles; Lester, Barry M

    2013-09-01

    Methamphetamine use is a growing problem among pregnant women in the United States. Many negative consequences of methamphetamine use have been documented for the users, but little research has examined the long-term association between prenatal methamphetamine exposure (PME) and childhood outcomes. The current study examined the extent to which PME was predictive of childhood neurobehavioral disinhibition (ND), as well as the extent to which early adversity mediated this relationship. A sample of 320 mother-infant dyads (162 PME) was followed from birth through 6.5 years of age. ND was conceptualized as a two factor model consisting of deficits in (a) behavioral and emotional control, and (b) executive function. PME was associated with behavioral and emotional control at 5 years, which was associated with executive function deficits at 6.5 years. Early adversity (birth through year 3) significantly mediated the relationship between PME and ND. Associations with previous research and implications for prevention are discussed. PMID:23067308

  13. 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...

  14. 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. PMID:22528370

  15. 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.

  16. 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…

  17. 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

    2016-01-01

    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. PMID:27121911

  18. Histone Modifications in a Mouse Model of Early Adversities and Panic Disorder: Role for Asic1 and Neurodevelopmental Genes

    PubMed Central

    Cittaro, Davide; Lampis, Valentina; Luchetti, Alessandra; Coccurello, Roberto; Guffanti, Alessandro; Felsani, Armando; Moles, Anna; Stupka, Elia; D’ Amato, Francesca R.; Battaglia, Marco

    2016-01-01

    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. PMID:27121911

  19. Early life recorded in archean pillow lavas.

    PubMed

    Furnes, Harald; Banerjee, Neil R; Muehlenbachs, Karlis; Staudigel, Hubert; de Wit, Maarten

    2004-04-23

    Pillow lava rims from the Mesoarchean Barberton Greenstone Belt in South Africa contain micrometer-scale mineralized tubes that provide evidence of submarine microbial activity during the early history of Earth. The tubes formed during microbial etching of glass along fractures, as seen in pillow lavas from recent oceanic crust. The margins of the tubes contain organic carbon, and many of the pillow rims exhibit isotopically light bulk-rock carbonate delta13C values, supporting their biogenic origin. Overlapping metamorphic and magmatic dates from the pillow lavas suggest that microbial life colonized these subaqueous volcanic rocks soon after their eruption almost 3.5 billion years ago. PMID:15105498

  20. Early life recorded in archean pillow lavas.

    PubMed

    Furnes, Harald; Banerjee, Neil R; Muehlenbachs, Karlis; Staudigel, Hubert; de Wit, Maarten

    2004-04-23

    Pillow lava rims from the Mesoarchean Barberton Greenstone Belt in South Africa contain micrometer-scale mineralized tubes that provide evidence of submarine microbial activity during the early history of Earth. The tubes formed during microbial etching of glass along fractures, as seen in pillow lavas from recent oceanic crust. The margins of the tubes contain organic carbon, and many of the pillow rims exhibit isotopically light bulk-rock carbonate delta13C values, supporting their biogenic origin. Overlapping metamorphic and magmatic dates from the pillow lavas suggest that microbial life colonized these subaqueous volcanic rocks soon after their eruption almost 3.5 billion years ago.

  1. Cumulative childhood adversity, educational attainment, and active life expectancy among U.S. adults.

    PubMed

    Montez, Jennifer Karas; Hayward, Mark D

    2014-04-01

    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.

  2. 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

  3. Childhood Adversity and Neural Development: Deprivation and Threat as Distinct Dimensions of Early Experience

    PubMed Central

    McLaughlin, Katie A.; Sheridan, Margaret A.; Lambert, Hilary K.

    2014-01-01

    A growing body of research has examined the impact of childhood adversity on neural structure and function. Advances in our understanding of the neurodevelopmental consequences of adverse early environments require the identification of dimensions of environmental experience that influence neural development differently and mechanisms other than the frequently-invoked stress pathways. We propose a novel conceptual framework that differentiates between deprivation (absence of expected environmental inputs and complexity) and threat (presence of experiences that represent a threat to one’s physical integrity) and make predictions grounded in basic neuroscience principles about their distinct effects on neural development. We review animal research on fear learning and sensory deprivation as well as human research on childhood adversity and neural development to support these predictions. We argue that these previously undifferentiated dimensions of experience exert strong and distinct influences on neural development that cannot be fully explained by prevailing models focusing only on stress pathways. Our aim is not to exhaustively review existing evidence on childhood adversity and neural development, but to provide a novel framework to guide future research. PMID:25454359

  4. Childhood adversity and neural development: deprivation and threat as distinct dimensions of early experience.

    PubMed

    McLaughlin, Katie A; Sheridan, Margaret A; Lambert, Hilary K

    2014-11-01

    A growing body of research has examined the impact of childhood adversity on neural structure and function. Advances in our understanding of the neurodevelopmental consequences of adverse early environments require the identification of dimensions of environmental experience that influence neural development differently and mechanisms other than the frequently-invoked stress pathways. We propose a novel conceptual framework that differentiates between deprivation (absence of expected environmental inputs and complexity) and threat (presence of experiences that represent a threat to one's physical integrity) and make predictions grounded in basic neuroscience principles about their distinct effects on neural development. We review animal research on fear learning and sensory deprivation as well as human research on childhood adversity and neural development to support these predictions. We argue that these previously undifferentiated dimensions of experience exert strong and distinct influences on neural development that cannot be fully explained by prevailing models focusing only on stress pathways. Our aim is not to exhaustively review existing evidence on childhood adversity and neural development, but to provide a novel framework to guide future research.

  5. Early Palliative Care Improves Patients' Quality of Life

    MedlinePlus

    ... fullstory_160885.html Early Palliative Care Improves Patients' Quality of Life Also increases chances of having end-of-life ... incurable cancer helps patients cope and improves their quality of life, a new study shows. It also leads to ...

  6. 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

  7. The early Earth atmosphere and early life catalysts.

    PubMed

    Ramírez Jiménez, Sandra Ignacia

    2014-01-01

    Homochirality is a property of living systems on Earth. The time, the place, and the way in which it appeared are uncertain. In a prebiotic scenario two situations are of interest: either an initial small bias for handedness of some biomolecules arouse and progressed with life, or an initial slight excess led to the actual complete dominance of the known chiral molecules. A definitive answer can probably never be given, neither from the fields of physics and chemistry nor biology. Some arguments can be advanced to understand if homochirality is necessary for the initiation of a prebiotic homochiral polymer chemistry, if this homochirality is suggesting a unique origin of life, or if a chiral template such as a mineral surface is always required to result in an enantiomeric excess. A general description of the early Earth scenario will be presented in this chapter, followed by a general description of some clays, and their role as substrates to allow the concentration and amplification of some of the building blocks of life.

  8. Predicting adverse obstetric outcome after early pregnancy events and complications: a review.

    PubMed

    van Oppenraaij, R H F; Jauniaux, E; Christiansen, O B; Horcajadas, J A; Farquharson, R G; Exalto, N

    2009-01-01

    BACKGROUND The aim was to evaluate the impact of early pregnancy events and complications as predictors of adverse obstetric outcome. METHODS We conducted a literature review on the impact of first trimester complications in previous and index pregnancies using Medline and Cochrane databases covering the period 1980-2008. RESULTS Clinically relevant associations of adverse outcome in the subsequent pregnancy with an odds ratio (OR) > 2.0 after complications in a previous pregnancy are the risk of perinatal death after a single previous miscarriage, the risk of very preterm delivery (VPTD) after two or more miscarriages, the risk of placenta praevia, premature preterm rupture of membranes, VPTD and low birthweight (LBW) after recurrent miscarriage and the risk of VPTD after two or more termination of pregnancy. Clinically relevant associations of adverse obstetric outcome in the ongoing pregnancy with an OR > 2.0 after complications in the index pregnancy are the risk of LBW and very low birthweight (VLBW) after a threatened miscarriage, the risk of pregnancy-induced hypertension, pre-eclampsia, placental abruption, preterm delivery (PTD), small for gestational age and low 5-min Apgar score after detection of an intrauterine haematoma, the risk of VPTD and intrauterine growth restriction after a crown-rump length discrepancy, the risk of VPTD, LBW and VLBW after a vanishing twin phenomenon and the risk of PTD, LBW and low 5-min Apgar score in a pregnancy complicated by severe hyperemesis gravidarum. CONCLUSIONS Data from our literature review indicate, by finding significant associations, that specific early pregnancy events and complications are predictors for subsequent adverse obstetric and perinatal outcome. Though, some of these associations are based on limited or small uncontrolled studies. Larger population-based controlled studies are needed to confirm these findings. Nevertheless, identification of these risks will improve obstetric care. PMID:19270317

  9. 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

  10. Incidence and management of life-threatening adverse events during cardiac catheterization for congenital heart disease.

    PubMed

    Lin, C Huie; Hegde, Sanjeet; Marshall, Audrey C; Porras, Diego; Gauvreau, Kimberlee; Balzer, David T; Beekman, Robert H; Torres, Alejandro; Vincent, Julie A; Moore, John W; Holzer, Ralf; Armsby, Laurie; Bergersen, Lisa

    2014-01-01

    Continued advancements in congenital cardiac catheterization and interventions have resulted in increased patient and procedural complexity. Anticipation of life-threatening events and required rescue measures is a critical component to preprocedural preparation. We sought to determine the incidence and nature of life-threatening adverse events in congenital and pediatric cardiac catheterization, risk factors, and resources necessary to anticipate and manage events. Data from 8905 cases performed at the 8 participating institutions of the Congenital Cardiac Catheterization Project on Outcomes were captured between 2007 and 2010 [median 1,095/site (range 133-3,802)]. The incidence of all life-threatening events was 2.1 % [95 % confidence interval (CI) 1.8-2.4 %], whereas mortality was 0.28 % (95 % CI 0.18-0.41 %). Fifty-seven life-threatening events required cardiopulmonary resuscitation, whereas 9 % required extracorporeal membrane oxygenation. Use of a risk adjustment model showed that age <1 year [odd ratio (OR) 1.9, 95 % CI 1.4-2.7, p < 0.001], hemodynamic vulnerability (OR 1.6, 95 % CI 1.1-2.3, p < 0.01), and procedure risk (category 3: OR 2.3, 95 % CI 1.3-4.1; category 4: OR 4.2, 95 % CI 2.4-7.4) were predictors of life-threatening events. Using this model, standardized life-threatening event ratios were calculated, thus showing that one institution had a life-threatening event rate greater than expected. Congenital cardiac catheterization and intervention can be performed safely with a low rate of life-threatening events and mortality; preprocedural evaluation of risk may optimize preparation of emergency rescue and bailout procedures. Risk predictors (age < 1, hemodynamic vulnerability, and procedure risk category) can enhance preprocedural patient risk stratification and planning.

  11. Early Adolescent Affect Predicts Later Life Outcomes

    PubMed Central

    Kansky, Jessica; Allen, Joseph P.; Diener, Ed

    2016-01-01

    Background Subjective well-being as a predictor for later behavior and health has highlighted its relationship to health, work performance, and social relationships. However, the majority of such studies neglect the developmental nature of well-being in contributing to important changes across the transition to adulthood. Methods To examine the potential role of subjective well-being as a long-term predictor of critical life outcomes, we examined indicators of positive and negative affect at age 14 as a predictor of relationship, adjustment, self worth, and career outcomes a decade later at ages 23 to 25, controlling for family income and gender. We utilized multi-informant methods including reports from the target participant, close friends, and romantic partners in a demographically diverse community sample of 184 participants. Results Early adolescent positive affect predicted less relationship problems (less self-reported and partner-reported conflict, greater friendship attachment as rated by close peers), healthy adjustment to adulthood (lower levels of depression, anxiety, and loneliness). It also predicted positive work functioning (higher levels of career satisfaction and job competence) and increased self-worth. Negative affect did not significantly predict any of these important life outcomes. In addition to predicting desirable mean levels of later outcomes, early positive affect predicted beneficial changes across time in many outcomes. Conclusions The findings extend early research on the beneficial outcomes of subjective well-being by having an earlier assessment of well-being, including informant reports in measuring a large variety of outcome variables, and by extending the findings to a lower socioeconomic group of a diverse and younger sample. The results highlight the importance of considering positive affect as an important component of subjective well-being distinct from negative affect. PMID:27075545

  12. Early-life origin of adult insomnia: does prenatal-early-life stress play a role?

    PubMed

    Palagini, Laura; Drake, Christopher L; Gehrman, Philip; Meerlo, Peter; Riemann, Dieter

    2015-04-01

    Insomnia is very common in the adult population and it includes a wide spectrum of sequelae, that is, neuroendocrine and cardiovascular alterations as well as psychiatric and neurodegenerative disorders. According to the conceptualization of insomnia in the context of the 3-P model, the importance of predisposing, precipitating, and perpetuating factors has been stressed. Predisposing factors are present before insomnia is manifested and they are hypothesized to interact with precipitating factors, such as environmental stressful events, contributing to the onset of insomnia. Understanding the early-life origins of insomnia may be particularly useful in order to prevent and treat this costly phenomenon. Based on recent evidence, prenatal-early-life stress exposure results in a series of responses that involve the stress system in the child and could persist into adulthood. This may encompass an activation of the hypothalamic-pituitary-adrenal axis accompanied by long-lasting modifications in stress reactivity. Furthermore, early-life stress exposure might play an important role in predisposing to a vulnerability to hyperarousal reactions to negative life events in the adult contributing to the development of chronic insomnia. Epigenetic mechanisms may also be involved in the development of maladaptive stress responses in the newborn, ultimately predisposing to develop a variety of (psycho-) pathological states in adult life.

  13. Assessing adverse experiences from infancy through early childhood in home visiting programs.

    PubMed

    McKelvey, Lorraine M; Whiteside-Mansell, Leanne; Conners-Burrow, Nicola A; Swindle, Taren; Fitzgerald, Shalese

    2016-01-01

    The general aim of early intervention and home visiting programs is to support families to minimize Adverse Childhood Experiences (ACEs). However, assessing children's exposure to these risks is complicated because parents serve as the conduit for both measurement and intervention. The primary aims of the study were to develop an assessment of children's exposure to ACEs and to examine concurrently measured parental child abuse and neglect potential and child social-emotional functioning. Home visiting programs in a southern state implemented the Family Map Inventories (FMI) as comprehensive family assessment and child screenings (N=1,282) within one month of enrollment. Children (M=33 months of age, SD=20) were exposed at rates of 27% to one, 18% to two, 11% to three, and 12% to four or more FMI-ACEs. FMI-ACEs were associated with increased parental beliefs and behaviors associated with child abuse and neglect. FMI-ACEs also significantly predicted the likelihood of the child having at-risk social-emotional development; children with 4 or more FMI-ACEs were over 6 times more likely than those with none to have at-risk scores. The findings add to our understanding of the negative impact of trauma on children and families. Assessing these risks as they occur in a family-friendly manner provides a platform for early intervention programs to work with families to increase family strengths and reduce the impacts of adverse experiences for their children.

  14. Assessing adverse experiences from infancy through early childhood in home visiting programs.

    PubMed

    McKelvey, Lorraine M; Whiteside-Mansell, Leanne; Conners-Burrow, Nicola A; Swindle, Taren; Fitzgerald, Shalese

    2016-01-01

    The general aim of early intervention and home visiting programs is to support families to minimize Adverse Childhood Experiences (ACEs). However, assessing children's exposure to these risks is complicated because parents serve as the conduit for both measurement and intervention. The primary aims of the study were to develop an assessment of children's exposure to ACEs and to examine concurrently measured parental child abuse and neglect potential and child social-emotional functioning. Home visiting programs in a southern state implemented the Family Map Inventories (FMI) as comprehensive family assessment and child screenings (N=1,282) within one month of enrollment. Children (M=33 months of age, SD=20) were exposed at rates of 27% to one, 18% to two, 11% to three, and 12% to four or more FMI-ACEs. FMI-ACEs were associated with increased parental beliefs and behaviors associated with child abuse and neglect. FMI-ACEs also significantly predicted the likelihood of the child having at-risk social-emotional development; children with 4 or more FMI-ACEs were over 6 times more likely than those with none to have at-risk scores. The findings add to our understanding of the negative impact of trauma on children and families. Assessing these risks as they occur in a family-friendly manner provides a platform for early intervention programs to work with families to increase family strengths and reduce the impacts of adverse experiences for their children. PMID:26455263

  15. Cortical Reorganization following Injury Early in Life

    PubMed Central

    Artzi, Moran; Shiran, Shelly Irene; Weinstein, Maya; Myers, Vicki; Tarrasch, Ricardo; Schertz, Mitchell; Fattal-Valevski, Aviva; Miller, Elka; Gordon, Andrew M.; Green, Dido; Ben Bashat, Dafna

    2016-01-01

    The brain has a remarkable capacity for reorganization following injury, especially during the first years of life. Knowledge of structural reorganization and its consequences following perinatal injury is sparse. Here we studied changes in brain tissue volume, morphology, perfusion, and integrity in children with hemiplegia compared to typically developing children, using MRI. Children with hemiplegia demonstrated reduced total cerebral volume, with increased cerebrospinal fluid (CSF) and reduced total white matter volumes, with no differences in total gray matter volume, compared to typically developing children. An increase in cortical thickness at the hemisphere contralateral to the lesion (CLH) was detected in motor and language areas, which may reflect compensation for the gray matter loss in the lesion area or retention of ipsilateral pathways. In addition, reduced cortical thickness, perfusion, and surface area were detected in limbic areas. Increased CSF volume and precentral cortical thickness and reduced white matter volume were correlated with worse motor performance. Brain reorganization of the gray matter within the CLH, while not necessarily indicating better outcome, is suggested as a response to neuronal deficits following injury early in life. PMID:27298741

  16. Life course adversity in the lives of formerly homeless persons with serious mental illness: context and meaning.

    PubMed

    Padgett, Deborah K; Smith, Bikki Tran; Henwood, Benjamin F; Tiderington, Emmy

    2012-07-01

    This qualitative study assessed the frequency and subjective meaning of adverse experiences using case study analyses of interviews with 38 formerly homeless adults with co-occurring serious mental illness (SMI) and substance abuse histories. Adverse life events were inventoried using an adaptation of Lloyd and Turner's (2008) 41-item checklist. Participants averaged 8.8 adverse events, with approximately one-third having experienced incarceration (37%), suicidality (32%), abandonment by one or both parents (30%), and death of their mother (34%). Cross-case analyses yielded 3 themes: social losses because of death and estrangement; the significance of chronic stressors as well as acute events; and the cumulative lifetime nature of adversity. Findings suggest that life course experiences of trauma and loss have a cumulative influence in the lives of this population in addition and in relation to SMI, substance abuse, and homelessness. In this context, the mental health recovery movement should address prior adverse experiences beyond comorbid diagnoses in this population.

  17. The role of nonverbal cognitive ability in the association of adverse life events with dysfunctional attitudes and hopelessness in adolescence.

    PubMed

    Flouri, Eirini; Panourgia, Constantina

    2012-10-01

    The aim of this study was to test whether nonverbal cognitive ability buffers the effect of life stress (number of adverse life events in the last year) on diatheses for depression. It was expected that, as problem-solving aptitude, nonverbal cognitive ability would moderate the effect of life stress on those diatheses (such as dysfunctional attitudes) that are depressogenic because they represent deficits in information-processing or problem-solving skills, but not on diatheses (such as hopelessness) that are depressogenic because they represent deficits in motivation or effort to apply problem-solving skills. The sample included 558 10- to 19-year-olds from a state secondary school in London. Nonverbal cognitive ability was negatively associated with both dysfunctional attitudes and hopelessness. As expected, nonverbal cognitive ability moderated the association between life adversity and dysfunctional attitudes. However, hopelessness was not related to life stress, and therefore, there was no life stress effect for nonverbal cognitive ability to moderate. This study adds to knowledge about the association between problem-solving ability and depressogenic diatheses. By identifying life stress as a risk factor for dysfunctional attitudes but not hopelessness, it highlights the importance of considering outcome specificity in models predicting adolescent outcomes from adverse life events. Importantly for practice, it suggests that an emphasis on recent life adversity will likely underestimate the true level of hopelessness among adolescents.

  18. The relationship between early-life environment, the epigenome and the microbiota.

    PubMed

    Majnik, Amber V; Lane, Robert H

    2015-10-01

    Children exposed to early-life adversity carry a greater risk of poor health and disease into adulthood. This increased disease risk is shadowed by changes in the epigenome. Epigenetics can change gene expression to modify disease risk; unfortunately, how epigenetics are changed by the environment is unclear. It is known that the environment modifies the microbiota, and recent data indicate that the microbiota and the epigenome interact and respond to each other. Specifically, the microbiome may alter the epigenome through the production of metabolites. Investigating the relationship between the microbiome and the epigenome may provide novel understanding of the impact of early-life environment on long-term health.

  19. The Prevalence of Childhood Adversity among Healthcare Workers and Its Relationship to Adult Life Events, Distress and Impairment

    ERIC Educational Resources Information Center

    Maunder, Robert G.; Peladeau, Nathalie; Savage, Diane; Lancee, William J.

    2010-01-01

    Objective: We investigated the prevalence of childhood adversity among healthcare workers and if such experiences affect responses to adult life stress. Methods: A secondary analysis was conducted of a 2003 study of 176 hospital-based healthcare workers, which surveyed lifetime traumatic events, recent life events, psychological distress, coping,…

  20. Adverse childhood events: incarceration of household members and health-related quality of life in adulthood

    PubMed Central

    Gjelsvik, Annie; Dumont, Dora M.; Nunn, Amy; Rosen, David L.

    2016-01-01

    Background Incarceration of a household member has been associated with adverse outcomes for child well-being. Methods We assessed the association between childhood exposure to the incarceration of a household member and adult health-related quality of life (HRQOL) in the 2009/2010 Behavioral Risk Factor Surveillance System controlling for age, race/ethnicity, education, and additional adverse childhood experiences. Results Adults who lived in childhood with an incarcerated household member had higher risk of poor HRQOL compared with adults who had not (adjusted relative risk [ARR] 1.18; 95% CI 1.07, 1.31). Among Black adults the association was strongest with the physical health component of HRQOL (ARR 1.58 [95% CI 1.18, 2.12]); among White adults, the association was strongest with the mental health component of HRQOL (ARR 1.29, [95% CI 1.07–1.54]). Conclusions Living with an incarcerated household member during childhood is associated with higher risk of poor HRQOL during adulthood, suggesting that the collateral damages of incarceration for children are long-term. PMID:25130232

  1. 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

  2. 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

  3. Altered GABA Signaling in Early Life Epilepsies

    PubMed Central

    Briggs, Stephen W.; Galanopoulou, Aristea S.

    2011-01-01

    The incidence of seizures is particularly high in the early ages of life. The immaturity of inhibitory systems, such as GABA, during normal brain development and its further dysregulation under pathological conditions that predispose to seizures have been speculated to play a major role in facilitating seizures. Seizures can further impair or disrupt GABAA signaling by reshuffling the subunit composition of its receptors or causing aberrant reappearance of depolarizing or hyperpolarizing GABAA receptor currents. Such effects may not result in epileptogenesis as frequently as they do in adults. Given the central role of GABAA signaling in brain function and development, perturbation of its physiological role may interfere with neuronal morphology, differentiation, and connectivity, manifesting as cognitive or neurodevelopmental deficits. The current GABAergic antiepileptic drugs, while often effective for adults, are not always capable of stopping seizures and preventing their sequelae in neonates. Recent studies have explored the therapeutic potential of chloride cotransporter inhibitors, such as bumetanide, as adjunctive therapies of neonatal seizures. However, more needs to be known so as to develop therapies capable of stopping seizures while preserving the age- and sex-appropriate development of the brain. PMID:21826277

  4. Early-life conditions and age at first pregnancy in British women.

    PubMed

    Nettle, Daniel; Coall, David A; Dickins, Thomas E

    2011-06-01

    There is growing evidence that the reproductive schedules of female mammals can be affected by conditions experienced during early development, with low parental investment leading to accelerated life-history strategies in the offspring. In humans, the relationships between early-life conditions and timing of puberty are well studied, but much less attention has been paid to reproductive behaviour. Here, we investigate associations between early-life conditions and age at first pregnancy (AFP) in a large, longitudinally studied cohort of British women (n = 4553). Low birthweight for gestational age, short duration of breastfeeding, separation from mother in childhood, frequent family residential moves and lack of paternal involvement are all independently associated with earlier first pregnancy. Apart from that of birthweight, the effects are robust to adjustment for family socioeconomic position (SEP) and the cohort member's mother's age at her birth. The association between childhood SEP and AFP is partially mediated by early-life conditions, and the association between early-life conditions and AFP is partially mediated by emotional and behavioural problems in childhood. The overall relationship between early-life adversities and AFP appears to be approximately additive.

  5. Early life triclocarban exposure during lactation affects neonate rat survival.

    PubMed

    Kennedy, Rebekah C M; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A; Hu, Pan; Bae, Jiyoung; Gee, Nancy A; Lasley, Bill L; Zhao, Ling; Chen, Jiangang

    2015-01-01

    Triclocarban (3,4,4'-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure.

  6. Early Life Triclocarban Exposure During Lactation Affects Neonate Rat Survival

    PubMed Central

    Kennedy, Rebekah C. M.; Menn, Fu-Min; Healy, Laura; Fecteau, Kellie A.; Hu, Pan; Bae, Jiyoung; Gee, Nancy A.; Lasley, Bill L.; Zhao, Ling

    2015-01-01

    Triclocarban (3,4,4′-trichlorocarbanilide; TCC), an antimicrobial used in bar soaps, affects endocrine function in vitro and in vivo. This study investigates whether TCC exposure during early life affects the trajectory of fetal and/or neonatal development. Sprague Dawley rats were provided control, 0.2% weight/weight (w/w), or 0.5% w/w TCC-supplemented chow through a series of 3 experiments that limited exposure to critical growth periods: gestation, gestation and lactation, or lactation only (cross-fostering) to determine the susceptible windows of exposure for developmental consequences. Reduced offspring survival occurred when offspring were exposed to TCC at concentrations of 0.2% w/w and 0.5% w/w during lactation, in which only 13% of offspring raised by 0.2% w/w TCC dams survived beyond weaning and no offspring raised by 0.5% w/w TCC dams survived to this period. In utero exposure status had no effect on survival, as all pups nursed by control dams survived regardless of their in utero exposure status. Microscopic evaluation of dam mammary tissue revealed involution to be a secondary outcome of TCC exposure rather than a primary effect of compound administration. The average concentration of TCC in the milk was almost 4 times that of the corresponding maternal serum levels. The results demonstrate that gestational TCC exposure does not affect the ability of dams to carry offspring to term but TCC exposure during lactation has adverse consequences on the survival of offspring although the mechanism of reduced survival is currently unknown. This information highlights the importance of evaluating the safety of TCC application in personal care products and the impacts during early life exposure. PMID:24803507

  7. Mgat5 modulates the effect of early life stress on adult behavior and physical health in mice.

    PubMed

    Feldcamp, Laura; Doucet, Jean-Sebastien; Pawling, Judy; Fadel, Marc P; Fletcher, Paul J; Maunder, Robert; Dennis, James W; Wong, Albert H C

    2016-10-01

    Psychosocial adversity in early life increases the likelihood of mental and physical illness, but the underlying mechanisms are poorly understood. Mgat5 is an N-acetylglucosaminyltransferase in the Golgi pathway that remodels the N-glycans of glycoproteins at the cell surface. Mice lacking Mgat5 display conditional phenotypes in behaviour, immunity, metabolism, aging and cancer susceptibility. Here we investigated potential gene-environment interactions between Mgat5 and early life adversity on behaviour and physiological measures of physical health. Mgat5(-/-) mutant and Mgat5(+/+) wild-type C57Bl/6 littermates were subject to maternal separation or foster rearing as an early life stressor, in comparison to control mice reared normally. We found an interaction between Mgat5 genotype and maternal rearing condition in which Mgat5(-/-) mice subjected to early life stress had lower glucose levels and higher bone density. Mgat5(-/-) genotype was also associated with less immobility in the forced swim test and greater sucrose consumption, consistent with a less depression-like phenotype. Cortical neuron dendrite spine density and branching was altered by Mgat5 deletion as well. In general, Mgat5 genotype affects both behaviour and physical outcomes in response to early life stress, suggesting some shared pathways for both in this model. These results provide a starting point for studying the mechanisms by which protein N-glycosylation mediates the effects of early life adversity. PMID:27329152

  8. Circulating Endothelial Cells and Endothelial Function predict Major Adverse Cardiac Events and Early Adverse Left Ventricular Remodeling in Patients with ST-Segment Elevation Myocardial Infarction

    PubMed Central

    Magdy, Abdel Hamid; Bakhoum, Sameh; Sharaf, Yasser; Sabry, Dina; El-Gengehe, Ahmed T; Abdel-Latif, Ahmed

    2016-01-01

    Endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) are mobilized from the bone marrow and increase in the early phase after ST-elevation myocardial infarction (STEMI). The aim of this study was to assess the prognostic significance of CECs and indices of endothelial dysfunction in patients with STEMI. In 78 patients with acute STEMI, characterization of CD34+/VEGFR2+ CECs, and indices of endothelial damage/dysfunction such as brachial artery flow mediated dilatation (FMD) were determined. Blood samples for CECs assessment and quantification were obtained within 24 hours of admission and FMD was assessed during the index hospitalization. At 30 days follow up, the primary composite end point of major cardiac adverse events (MACE) consisting of all-cause mortality, recurrent non-fatal MI, or heart failure and the secondary endpoint of early adverse left ventricular (LV) remodeling were analyzed. The 17 patients (22%) who developed MACE had significantly higher CEC level (P = 0.004), vWF level (P =0.028), and significantly lower FMD (P = 0.006) compared to the remaining patients. Logistic regression analysis showed that CECs level and LV ejection fraction were independent predictors of MACE. The areas under the receiver operating characteristic curves (ROC) for CEC level, FMD, and the logistic model with both markers were 0.73, 0.75, and 0.82 respectively for prediction of the MACE. The 16 patients who developed the secondary endpoint had significantly higher CEC level compared to remaining patients (p =0.038). In conclusion, increased circulating endothelial cells and endothelial dysfunction predicted the occurrence of major adverse cardiac events and adverse cardiac remodeling in patients with STEMI. PMID:26864952

  9. Early-Life Origins of Life-Cycle Well-Being: Research and Policy Implications

    ERIC Educational Resources Information Center

    Currie, Janet; Rossin-Slater, Maya

    2015-01-01

    Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population…

  10. 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. PMID:14702025

  11. Understanding the potency of stressful early life experiences on brain and body function.

    PubMed

    McEwen, Bruce S

    2008-10-01

    Early life experiences have powerful effects on the brain and body lasting throughout the entire life span and influencing brain function, behavior, and the risk for a number of systemic and mental disorders. Animal models of early life adversity are providing mechanistic insights, including glimpses into the fascinating world that is now called "epigenetics" as well as the role of naturally occurring alleles of a number of genes. These studies also provide insights into the adaptive value as well as the negative consequences, of early life stress, exposure to novelty, and poor-quality vs good-quality maternal care. Animal models begin to provide a mechanistic basis for understanding how brain development and physiological functioning is affected in children exposed to early life abuse and neglect, where there is a burgeoning literature on the consequences for physical health and emotional and cognitive development. An important goal is to identify interventions that are likely to be most effective in early life and some guidelines are provided. PMID:18803958

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

    PubMed

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

    2015-01-01

    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.

  13. 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

  14. 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-...

  15. The Role of Prenatal Substance Exposure and Early Adversity on Parasympathetic Functioning from 3 to 6 Years of Age

    PubMed Central

    Abar, Beau; Sheinkopf, Stephen; Lester, Barry; Lagasse, Linda; Seifer, Ronald; Shankaran, Seetha; Bada-Ellzey, Henrietta; Bauer, Charles; Whitaker, Toni; Hinckley, Matt; Hammond, Jane; Higgins, Rosemary

    2014-01-01

    We employed latent growth curve analysis to examine trajectories of respiratory sinus arrhythmia (RSA) from 3 to 6 years among children with varying levels of prenatal substance exposure and early adversity. Data were drawn from a prospective longitudinal study of prenatal substance exposure that included 1,121 participants. Baseline RSA and RSA reactivity to an attention-demanding task were assessed at 3, 4, 5, and 6 years. Overall, there were significant individual differences in the trajectories of RSA reactivity, but not baseline RSA, across development. Greater levels of prenatal substance exposure, and less exposure to early adversity, were associated with increased RSA reactivity at 3 years, but by 6 years, both were associated with greater RSA reactivity. Prenatal substance exposure had an indirect influence through early adversity on growth in RSA reactivity. Results are in support of and contribute to the framework of allostatic load. PMID:24002807

  16. Life adversity is associated with smoking relapse after a quit attempt.

    PubMed

    Lemieux, Andrine; Olson, Leif; Nakajima, Motohiro; Schulberg, Lauren; al'Absi, Mustafa

    2016-09-01

    Multiple cross-sectional studies have linked adverse childhood events and adult adversities to current smoking, lifetime smoking, and former smoking. To date, however, there have been no direct observational studies assessing the influence of adversities on smoking relapse. We prospectively followed 123 participants, 86 of whom were habitual smokers, from pre-quit ad libitum smoking to four weeks post-quit. Thirty-seven non-smokers were also tested in parallel as a comparison group. Subjects provided biological samples for confirmation of abstinence status and self-report history of adversities such as abuse, neglect, family dysfunction, incarceration, and child-parent separation. They also completed mood and smoking withdrawal symptom measures. The results indicated that within non-smokers and smokers who relapsed within the first month of a quit attempt, but not abstainers, females had significantly higher adversity scores than males. Cigarette craving, which was independent from depressive affect, increased for low adversity participants, but not those with no adversity nor high adversity. These results demonstrate that sex and relapse status interact to predict adversity and that craving for nicotine may be an important additional mediator of relapse. These results add further support to the previous cross-sectional evidence of an adversity and smoking relationship. Further studies to clarify how adversity complicates smoking cessation and impacts smoking behaviors are warranted. PMID:27100471

  17. Toxicity of TFM lampricide to early life stages of walleye

    USGS Publications Warehouse

    Seelye, J.G.; Marking, L.L.; King, E.L.; Hanson, L.H.; Bills, T.D.

    1987-01-01

    The authors studied the effects of the lampricide 3-trifluoromethyl-4-nitrophenol (TFM) on gametes, newly fertilized eggs, eyed eggs, larvae, and swim-up fry of the walleye Stizostedion vitreum . When gametes from sexually mature walleyes were stripped into solutions of TFM, no effects were observed during the fertilization process at concentrations up to 3.0 mg/L - three times the concentration lethal to 99.9% of larval sea lampreys Petromyzon marinus held 12 h (LC99.9) under the same test conditions. Newly fertilized eggs likewise were unaffected during water hardening by concentrations of TFM that were lethal to sea lamprey ammocoetes. Eyed eggs, sac fry, and swim-up fry yielded LC25 values that were 2.5 to 5 times greater than the 12-h LC99.9 for sea lamprey ammocoetes. The data thus indicated that all of the early life stages of walleyes tested were considerably more resistant than sea lamprey ammocoetes to TFM, and that it is unlikely they would be adversely affected by standard stream treatments to kill sea lamprey ammocoetes.

  18. Alteration of somatosensory response in adulthood by early life stress.

    PubMed

    Takatsuru, Yusuke; Koibuchi, Noriyuki

    2015-01-01

    Early life stress is well-known as a critical risk factor for mental and cognitive disorders in adulthood. Such disorders are accompanied by altered neuro- (synapto-) genesis and gene expression. Because psychosomatic disorders induced by early life stress (e.g., physical and/or sexual abuse, and neglect) have become a socio-economic problem, it is very important to clarify the mechanisms underlying these changes. However, despite of intensive clinical and animal studies, such mechanisms have not yet been clarified. Although the disturbance of glucocorticoid and glutamate homeostasis by stress has been well-documented, it has not yet been clarified whether such disturbance by early life stress persists for life. Furthermore, since previous studies have focused on the detection of changes in specific brain regions, such as the hippocampus and prefrontal cortex, it has not been clarified whether early life stress induced changes in the sensory/motor system. Thus, in this review, we introduce recent studies on functional/structural changes in the somatosensory cortex induced by early life stress. We believe that this review provides new insights into the functional alteration of the somatosensory system induced by early life stress. Such information may have clinical relevance in terms of providing effective therapeutic interventions to early life stressed individuals. PMID:26041988

  19. Limitations of toxicity characterization in life cycle assessment: Can adverse outcome pathways provide a new foundation?

    PubMed

    Gust, Kurt A; Collier, Zachary A; Mayo, Michael L; Stanley, Jacob K; Gong, Ping; Chappell, Mark A

    2016-07-01

    Life cycle assessment (LCA) has considerable merit for holistic evaluation of product planning, development, production, and disposal, with the inherent benefit of providing a forecast of potential health and environmental impacts. However, a technical review of current life cycle impact assessment (LCIA) methods revealed limitations within the biological effects assessment protocols, including: simplistic assessment approaches and models; an inability to integrate emerging types of toxicity data; a reliance on linear impact assessment models; a lack of methods to mitigate uncertainty; and no explicit consideration of effects in species of concern. The purpose of the current study is to demonstrate that a new concept in toxicological and regulatory assessment, the adverse outcome pathway (AOP), has many useful attributes of potential use to ameliorate many of these problems, to expand data utility and model robustness, and to enable more accurate and defensible biological effects assessments within LCIA. Background, context, and examples have been provided to demonstrate these potential benefits. We additionally propose that these benefits can be most effectively realized through development of quantitative AOPs (qAOPs) crafted to meet the needs of the LCIA framework. As a means to stimulate qAOP research and development in support of LCIA, we propose 3 conceptual classes of qAOP, each with unique inherent attributes for supporting LCIA: 1) mechanistic, including computational toxicology models; 2) probabilistic, including Bayesian networks and supervised machine learning models; and 3) weight of evidence, including models built using decision-analytic methods. Overall, we have highlighted a number of potential applications of qAOPs that can refine and add value to LCIA. As the AOP concept and support framework matures, we see the potential for qAOPs to serve a foundational role for next-generation effects characterization within LCIA. Integr Environ Assess Manag

  20. Pathways from Early Childhood Adversity to Later Adult Drug Use and Psychological Distress: A Prospective Study of a Cohort of African Americans.

    PubMed

    Fothergill, Kate; Ensminger, Margaret E; Doherty, Elaine E; Juon, Hee-Soon; Green, Kerry M

    2016-06-01

    Drawing on the life course perspective, this research addresses the direct and indirect pathways between childhood adversity and midlife psychological distress and drug use across a majority of the life span in an African American cohort (N = 1,242) followed from age 6 to 42 (1966 to 2002). Results from structural equation models highlight the impact of low childhood socioeconomic status (SES), poor maternal mental health, and the role of first-grade maladaptation in launching a trajectory of social maladaptation from age 6 to 42. Specifically, for men, we found a direct pathway from early low SES to drug use in mid adulthood and an indirect pathway to psychological distress through first-grade maladaptation and adolescent poor mental health. For females, early SES affected first-grade maladaptation and low school bonds, which then predicted later drug use. PMID:27284077

  1. The longitudinal study of rat hippocampus influenced by stress: early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats.

    PubMed

    Jin, Fengkui; Li, Lei; Shi, Mei; Li, Zhenzi; Zhou, Jinghua; Chen, Li

    2013-06-01

    Epidemiologic studies indicate that early adverse experience is related to learning disabilities in adults, but the neurobiological mechanisms have not yet been identified. We used longitudinal animal experiments to test the hypothesis that early life stress enhances hippocampal vulnerability and working memory deficit in adult rats. The expression of Synaptophysin (SYN) and apoptosis (Apo) in hippocampal CA3 and dentate gyrus (DG) regions were examined to evaluate the effects of environmental factors on the hippocampus. The working memory errors via radial 8-arm maze were studied to evaluate the long-term effect of early stress on rats' spatial learning ability. Our results indicated that chronic restraint stress in early life and forced cold water swimming stress in adulthood reduced SYN expression and increased Apo levels in rat hippocampus, but the hippocampal damage tended to recover when rats returned to a non-stress environment. In addition, when the rats were exposed to forced cold water swimming stress during adulthood, SYN expression (CA3 and DG regions) and Apo levels (CA3 region) in rat hippocampus showed statistical difference between early restraint stress group and non-early restraint stress group (rats exposed to stress in adulthood only). One month after the two groups of rats returned to non-stress environment, this difference of SYN expression (CA3 and DG regions) and working memory deficit between the two groups was still statistically significant. Our study findings suggested that early adverse experience enhances hippocampal vulnerability and working memory deficit in adult rats, and reduces structural plasticity of hippocampus.

  2. Life-threatening adverse events following therapeutic opioid administration in adults: Is pharmacogenetic analysis useful?

    PubMed Central

    Madadi, Parvaz; Sistonen, Johanna; Silverman, Gregory; Gladdy, Rebecca; Ross, Colin J; Carleton, Bruce C; Carvalho, Jose C; Hayden, Michael R; Koren, Gideon

    2013-01-01

    BACKGROUND: Systemic approaches are needed to understand how variations in the genes associated with opioid pharmacokinetics and response can be used to predict patient outcome. The application of pharmacogenetic analysis to two cases of life-threatening opioid-induced respiratory depression is presented. The usefulness of genotyping in the context of these cases is discussed. METHODS: A panel of 20 functional candidate polymorphisms in genes involved in the opioid biotransformation pathway (CYP2D6, UGT2B7, ABCB1, OPRM1, COMT) were genotyped in these two patients using commercially available genotyping assays. RESULTS: In case 1, the patient experienced adverse outcomes when administered codeine and morphine, but not hydromorphone. Genetic test results suggested that this differential response may be due to an inherent propensity to generate active metabolites from both codeine and morphine. These active metabolites are not generated with hydromorphone. In case 2, the patient experienced severe respiratory depression during postoperative recovery following standard doses of morphine. The patient was found to carry genetic variations that result in decreased morphine efflux transporter activity at the blood-brain barrier and increased sensitivity to opioids. CONCLUSIONS: Knowledge of the relative contribution of pharmacogenetic biomarkers and their influence on opioid response are continually evolving. Pharmacogenetic analysis, together with clinical history, has the potential to provide mechanistic insight into severe respiratory depressive events in patients who receive opioids at therapeutic doses. PMID:23748253

  3. Gene-environment interplay in Drosophila melanogaster: chronic food deprivation in early life affects adult exploratory and fitness traits.

    PubMed

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

    2012-10-16

    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.

  4. The Influence of Ethnicity and Adverse Life Experiences during Adolescence on Young Adult Socioeconomic Attainment: The Moderating Role of Education

    ERIC Educational Resources Information Center

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

    2012-01-01

    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…

  5. Effects of early life stress on brain activity: implications from maternal separation model in rodents.

    PubMed

    Nishi, Mayumi; Horii-Hayashi, Noriko; Sasagawa, Takayo; Matsunaga, Wataru

    2013-01-15

    Adverse experiences in early life can affect the formation of neuronal circuits during postnatal development and exert long-lasting influences on neural function. Many studies have shown that daily repeated maternal separation (RMS), an animal model of early life stress, can modulate the hypothalamic-pituitary-adrenal axis (HPA-axis) and can affect subsequent brain function and emotional behavior during adulthood. However, the molecular basis of the long-lasting effects of early life stress on brain function has not been completely elucidated. In this mini-review, we introduce various cases of maternal separation in rodents and illustrate the alterations in HPA-axis activity by focusing on corticosterone (CORT), an end-product of the HPA-axis in rodents. We then present the characterization of the brain regions affected by various patterns of MS, including RMS and single time maternal separation (SMS) at various stages before weaning, by investigating c-Fos expression, a biological marker of neuronal activity. These CORT and c-Fos studies suggest that repeated early life stress may affect neuronal function in region- and temporal-specific manners, indicating a critical period for habituation to early life stress. Furthermore, we introduce changes in behavioral aspects and gene expression in adult mice exposed to RMS.

  6. Understanding the potency of stressful early life experiences on brain and body function

    PubMed Central

    McEwen, Bruce S.

    2008-01-01

    Early life experiences have powerful effects on the brain and body lasting throughout the entire lifespan and influencing brain function, behavior and the risk for a number of systemic and mental disorders. Animal models of early life adversity are providing mechanistic insights, including glimpses into the fascinating world that is now called “epigenetics” as well as the role of naturally occurring alleles of a number of genes. These studies also provide insights into the adaptive value, as well as the negative consequences, of early life stress, exposure to novelty, and poor vs good quality maternal care. Animal models begin to provide a mechanistic basis for understanding how brain development and physiological functioning is affected in children exposed to early life abuse and neglect, where there is a burgeoning literature on the consequences for physical health and emotional and cognitive development. An important goal is to identify interventions that are likely to be most effective in early life and some guidelines are provided. PMID:18803958

  7. Early earth: Arsenic and primordial life

    NASA Astrophysics Data System (ADS)

    Kulp, Thomas R.

    2014-11-01

    Some modern microorganisms derive energy from the oxidation and reduction of arsenic. The association of arsenic with organic cellular remains in 2.7-billion-year-old stromatolites hints at arsenic-based metabolisms at the dawn of life.

  8. The early evolution of life: solution to Darwin's dilemma

    NASA Technical Reports Server (NTRS)

    Schopf, J. W.

    1994-01-01

    Recent studies of Precambrian fossils indicate that life on Earth originated earlier than assumed, microscopic life was prevalent in the Precambrian Eon, the tempo and mode of evolution during the Precambrian period were different from other periods, and that only the Precambrian fossil record can be used as evidence of early life. Implications for future research include directing the search for the origin of life away from the geological record, modification of hypotheses about molecular change, use of Precambrian microfossils in dating younger geological units, and progress in defining the nature of major events in early evolution.

  9. The Impact of Postnatal Depression and Associated Adversity on Early Mother-Infant Interactions and Later Infant Outcome.

    ERIC Educational Resources Information Center

    Murray, Lynne; And Others

    1996-01-01

    Examined the impact of maternal depression and adversity on mother-infant face-to-face interactions at 2 months, and on subsequent infant cognitive development and attachment. Disturbances in early mother-infant interactions were found to be predictive of poorer infant cognitive outcomes at 18 months. (MDM)

  10. Self-Focused and Other-Focused Resiliency: Plausible Mechanisms Linking Early Family Adversity to Health Problems in College Women

    ERIC Educational Resources Information Center

    Coleman, Sulamunn R. M.; Zawadzki, Matthew J.; Heron, Kristin E.; Vartanian, Lenny R.; Smyth, Joshua M.

    2016-01-01

    Objectives: This study examined whether self-focused and other-focused resiliency help explain how early family adversity relates to perceived stress, subjective health, and health behaviors in college women. Participants: Female students (N = 795) participated between October 2009 and May 2010. Methods: Participants completed self-report measures…

  11. Cumulative Effects of Prenatal Substance Exposure and Early Adversity on Foster Children's HPA-Axis Reactivity during a Psychosocial Stressor

    ERIC Educational Resources Information Center

    Fisher, Philip A.; Kim, Hyoun K.; Bruce, Jacqueline; Pears, Katherine C.

    2012-01-01

    Dysregulated hypothalamic-pituitary-adrenocortical (HPA) axis stress response has been reported among individuals with prenatal substance exposure and those with early adversity exposure. However, few researchers have examined the combined effects of these risk factors. Patterns of HPA reactivity among maltreated foster children with and without…

  12. 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

  13. Early-life stress interactions with the epigenome: potential mechanisms driving vulnerability toward psychiatric illness.

    PubMed

    Lewis, Candace R; Olive, M Foster

    2014-09-01

    Throughout the 20th century a body of literature concerning the long-lasting effects of the early environment was produced. Adverse experiences in early life, or early-life stress (ELS), is associated with a higher risk of developing various psychiatric illnesses. The mechanisms driving the complex interplay between ELS and adult phenotype has baffled many investigators for decades. Over the last decade, the new field of neuroepigenetics has emerged as one possible mechanism by which ELS can have far-reaching effects on adult phenotype, behavior, and risk for psychiatric illness. Here we review two commonly investigated epigenetic mechanisms, histone modifications and DNA methylation, and the emerging field of neuroepigenetics as they relate to ELS. We discuss the current animal literature demonstrating ELS-induced epigenetic modulation of gene expression that results in altered adult phenotypes. We also briefly discuss other areas in which neuroepigenetics has emerged as a potential mechanism underlying environmental and genetic interactions.

  14. Impact of Adverse Childhood Experiences on Psychotic-Like Symptoms and Stress Reactivity in Daily Life in Nonclinical Young Adults

    PubMed Central

    Ballespí, Sergi; Mitjavila, Mercè; Myin-Germeys, Inez; Kwapil, Thomas R.; Barrantes-Vidal, Neus

    2016-01-01

    Background There is increasing interest in elucidating the association of different childhood adversities with psychosis-spectrum symptoms as well as the mechanistic processes involved. This study used experience sampling methodology to examine (i) associations of a range of childhood adversities with psychosis symptom domains in daily life; (ii) whether associations of abuse and neglect with symptoms are consistent across self-report and interview methods of trauma assessment; and (iii) the role of different adversities in moderating affective, psychotic-like, and paranoid reactivity to situational and social stressors. Method A total of 206 nonclinical young adults were administered self-report and interview measures to assess childhood abuse, neglect, bullying, losses, and general traumatic events. Participants received personal digital assistants that signaled them randomly eight times daily for one week to complete questionnaires about current experiences, including symptoms, affect, and stress. Results Self-reported and interview-based abuse and neglect were associated with psychotic-like and paranoid symptoms, whereas only self-reported neglect was associated with negative-like symptoms. Bullying was associated with psychotic-like symptoms. Losses and general traumatic events were not directly associated with any of the symptom domains. All the childhood adversities were associated with stress reactivity in daily life. Interpersonal adversities (abuse, neglect, bullying, and losses) moderated psychotic-like and/or paranoid reactivity to situational and social stressors, whereas general traumatic events moderated psychotic-like reactivity to situational stress. Also, different interpersonal adversities exacerbated psychotic-like and/or paranoid symptoms in response to distinct social stressors. Discussion The present study provides a unique examination of how childhood adversities impact the expression of spectrum symptoms in the real world and lends support

  15. Conway's Game of Life: Early Personal Recollections

    NASA Astrophysics Data System (ADS)

    Wainwright, Robert

    When the October 1970 issue of Scientific American arrived, I had no idea the extent to which Martin Gardner's article in that issue would affect my life. As long as I can remember, my custom would be to seek out the Mathematical Games column in search for Gardner's latest topic with the usual reader challenges. My first reaction to that particular article introducing a new pastime titled "The fantastic combinations of John Conway's new solitaire game 'life''' was only mildly interesting. A couple of days later, still curious about the outcome of random patterns, I located an old checkerboard and a small jarful of pennies to investigate this new game.

  16. Early life stress in fathers improves behavioural flexibility in their offspring.

    PubMed

    Gapp, Katharina; Soldado-Magraner, Saray; Alvarez-Sánchez, María; Bohacek, Johannes; Vernaz, Gregoire; Shu, Huan; Franklin, Tamara B; Wolfer, David; Mansuy, Isabelle M

    2014-01-01

    Traumatic experiences in childhood can alter behavioural responses and increase the risk for psychopathologies across life, not only in the exposed individuals but also in their progeny. In some conditions, such experiences can however be beneficial and facilitate the appraisal of adverse environments later in life. Here we expose newborn mice to unpredictable maternal separation combined with unpredictable maternal stress (MSUS) for 2 weeks and assess the impact on behaviour in the offspring when adult. We show that MSUS in male mice favours goal-directed behaviours and behavioural flexibility in the adult offspring. This effect is accompanied by epigenetic changes involving histone post-translational modifications at the mineralocorticoid receptor (MR) gene and decreased MR expression in the hippocampus. Mimicking these changes pharmacologically in vivo reproduces the behavioural phenotype. These findings highlight the beneficial impact that early adverse experiences can have in adulthood, and the implication of epigenetic modes of gene regulation. PMID:25405779

  17. The positive and negative consequences of stressors during early life

    PubMed Central

    Monaghan, Pat; Haussmann, Mark F.

    2015-01-01

    We discuss the long-term effects of stress exposure in pre- and early postnal life. We present an evolutionary framework within which such effects can be viewed, and describe how the outcomes might vary with species life histories. We focus on stressors that induce increases in glucocorticoid hormones and discuss the advantages of an experimental approach. We describe a number of studies demonstrating how exposure to these hormones in early life can influence stress responsiveness and have substantial long-term, negative consequences for adult longevity. We also describe how early life exposure to mild levels of stressors can have beneficial effects on resilience to stress in later life, and discuss how the balance of costs and benefits is likely dependent on the nature of the adult environment. PMID:26385447

  18. Pleiotropy and life history evolution in Drosophila melanogaster: uncoupling life span and early fecundity.

    PubMed

    Khazaeli, Aziz A; Curtsinger, James W

    2013-05-01

    Populations of Drosophila melanogaster that have been artificially selected for late age of reproduction evolve longer life spans and, in some cases, reduced early fecundity. The negative correlation is widely interpreted as evidence of antagonistic pleiotropy. Here, we show that the correlation breaks down in recombinant genomes. A major quantitative trait locus that increases adult life span by 20% has no detectable effect on early fecundity. Several recombinant genotypes are superflies, exhibiting both elevated early fecundity and long life. The genetic correlation of early fecundity and life span is not different from zero, while the midlife fecundity correlation is positive and statistically significant, suggesting age-specific adaptation. The results are not consistent with a dominant role for negative pleiotropy, but can be understood in terms of a mixture of pleiotropic and recombining nonpleiotropic elements. Life span and early fecundity can be genetically uncoupled.

  19. Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: A cohort study of an urban, minority sample in the U.S.

    PubMed Central

    Topitzes, J.; Reynolds, A.J.

    2014-01-01

    Research has shown that adverse childhood experiences (ACEs) increase the risk of poor health-related outcomes in later life. Less is known about the consequences of ACEs in early adulthood or among diverse samples. Therefore, we investigated the impacts of differential exposure to ACEs on an urban, minority sample of young adults. Health, mental health, and substance use outcomes were examined alone and in aggregate. Potential moderating effects of sex were also explored. Data were derived from the Chicago Longitudinal Study, a panel investigation of individuals who were born in 1979 or 1980. Main-effect analyses were conducted with multivariate logistic and OLS regression. Sex differences were explored with stratified analysis, followed by tests of interaction effects with the full sample. Results confirmed that there was a robust association between ACEs and poor outcomes in early adulthood. Greater levels of adversity were associated with poorer self-rated health and life satisfaction, as well as more frequent depressive symptoms, anxiety, tobacco use, alcohol use, and marijuana use. Cumulative adversity also was associated with cumulative effects across domains. For instance, compared to individuals without an ACE, individuals exposed to multiple ACEs were more likely to have three or more poor outcomes (OR range = 2.75–10.15) and four or more poor outcomes (OR range = 3.93–15.18). No significant differences between males and females were detected. Given that the consequences of ACEs in early adulthood may lead to later morbidity and mortality, increased investment in programs and policies that prevent ACEs and ameliorate their impacts is warranted. PMID:23978575

  20. Impacts of adverse childhood experiences on health, mental health, and substance use in early adulthood: a cohort study of an urban, minority sample in the U.S.

    PubMed

    Mersky, J P; Topitzes, J; Reynolds, A J

    2013-11-01

    Research has shown that adverse childhood experiences (ACEs) increase the risk of poor health-related outcomes in later life. Less is known about the consequences of ACEs in early adulthood or among diverse samples. Therefore, we investigated the impacts of differential exposure to ACEs on an urban, minority sample of young adults. Health, mental health, and substance use outcomes were examined alone and in aggregate. Potential moderating effects of sex were also explored. Data were derived from the Chicago Longitudinal Study, a panel investigation of individuals who were born in 1979 or 1980. Main-effect analyses were conducted with multivariate logistic and OLS regression. Sex differences were explored with stratified analysis, followed by tests of interaction effects with the full sample. Results confirmed that there was a robust association between ACEs and poor outcomes in early adulthood. Greater levels of adversity were associated with poorer self-rated health and life satisfaction, as well as more frequent depressive symptoms, anxiety, tobacco use, alcohol use, and marijuana use. Cumulative adversity also was associated with cumulative effects across domains. For instance, compared to individuals without an ACE, individuals exposed to multiple ACEs were more likely to have three or more poor outcomes (OR range=2.75-10.15) and four or more poor outcomes (OR range=3.93-15.18). No significant differences between males and females were detected. Given that the consequences of ACEs in early adulthood may lead to later morbidity and mortality, increased investment in programs and policies that prevent ACEs and ameliorate their impacts is warranted.

  1. Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.

    PubMed

    Grassi-Oliveira, Rodrigo; Honeycutt, Jennifer A; Holland, Freedom H; Ganguly, Prabarna; Brenhouse, Heather C

    2016-09-01

    Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population.

  2. Cognitive impairment effects of early life stress in adolescents can be predicted with early biomarkers: Impacts of sex, experience, and cytokines.

    PubMed

    Grassi-Oliveira, Rodrigo; Honeycutt, Jennifer A; Holland, Freedom H; Ganguly, Prabarna; Brenhouse, Heather C

    2016-09-01

    Childhood adversity increases vulnerability to psychiatric disorders that emerge in adolescence, in a sex-dependent manner. Early adversity modeled in rodents with maternal separation (MS) affects cognition and medial prefrontal cortex (mPFC) circuitry. Humans and animals exposed to early life adversity also display heightened circulating inflammatory cytokines, however the predictive relationship of these early measures with later behavioral deficits is unknown. Here, male and female rats were exposed to MS or control rearing during the postnatal period (P2-21). Blood samples were taken at distinct developmental time points for analysis of the pro-inflammatory cytokine IL-1β and the anti-inflammatory cytokines IL-4, and IL-10, followed by win-shift cognitive testing and analysis of mPFC parvalbumin (PVB) immunofluorescent interneurons in adolescence. Regression analyses were conducted to explore the relationship between early cytokines and adolescent behavioral measures. We observed sex- and age-dependent effects of MS on circulating cytokines. MS also yielded adolescent decreases in mPFC PVB and cognitive deficits, which were predicted by early cytokine expression in a sex- and experience-dependent manner. Taken together, the present data reveals that circulating cytokines and PVB levels are predictive of adolescent cognitive deficits, and therefore provide compelling evidence for a putative role of early biomarkers in mediating MS-induced behavioral dysfunction. Importantly, predictive relationships often depended on sex and on MS history, suggesting that early life experiences may yield individualistic mechanisms of vulnerability compared to the general population. PMID:27235636

  3. Examining Resilience of Quality of Life in the Face of Health-Related and Psychosocial Adversity at Older Ages: What Is "Right" about the Way We Age?

    ERIC Educational Resources Information Center

    Hildon, Zoe; Montgomery, Scott M.; Blane, David; Wiggins, Richard D.; Netuveli, Gopalakrishnan

    2010-01-01

    Purpose: This article examines resilience at older ages, focusing on the relationships between quality of life (qol) and adversity. Our objectives are to identify (a) the basis of adversity, (b) the characteristics of resilient individuals, and (c) the attributes that attenuate the full impact of adversity. Design and Methods: Resilience is…

  4. Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions.

    PubMed

    Stamoulis, Catherine; Vanderwert, Ross E; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2015-12-01

    Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1-3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross

  5. Early Psychosocial Neglect Adversely Impacts Developmental Trajectories of Brain Oscillations and Their Interactions.

    PubMed

    Stamoulis, Catherine; Vanderwert, Ross E; Zeanah, Charles H; Fox, Nathan A; Nelson, Charles A

    2015-12-01

    Rhythmicity is a fundamental property of neural activity at multiple spatiotemporal scales, and associated oscillations represent a critical mechanism for communication and transmission of information across brain regions. During development, these oscillations evolve dynamically as a function of neural maturation and may be modulated by early experiences, positive and/or negative. This study investigated the impact of psychosocial deprivation associated with institutional rearing in early life and the effects of subsequent foster care intervention on developmental trajectories of neural oscillations and their cross-frequency correlations. Longitudinally acquired nontask EEGs from three cohorts of children from the Bucharest Early Intervention Project were analyzed. These included abandoned children initially reared in institutions and subsequently randomized to be placed in foster care or receive care as usual (prolonged institutional rearing) and a group of never-institutionalized children. Oscillation trajectories were estimated from 42 to 96 months, that is, 1-3 years after all children in the intervention arm of the study had been placed in foster care. Significant differences between groups were estimated for the amplitude trajectories of cognitive-related gamma, beta, alpha, and theta oscillations. Similar differences were identified as a function of time spent in institutions, suggesting that increased time spent in psychosocial neglect may have profound and widespread effects on brain activity. Significant group differences in cross-frequency coupling were estimated longitudinally between gamma and lower frequencies as well as alpha and lower frequencies. Lower cross-gamma coupling was estimated at 96 months in the group of children that remained in institutions at that age compared to the other two groups, suggesting potentially impaired communication between local and long-distance brain networks in these children. In contrast, higher cross

  6. Endocrine Disruptors and the Breast: Early Life Effects and Later Life Disease

    PubMed Central

    Macon, Madisa B.

    2013-01-01

    Breast cancer risk has both heritable and environment/lifestyle components. The heritable component is a small contribution (5–27 %), leaving the majority of risk to environment (e.g., applied chemicals, food residues, occupational hazards, pharmaceuticals, stress) and lifestyle (e.g., physical activity, cosmetics, water source, alcohol, smoking). However, these factors are not well-defined, primarily due to the enormous number of factors to be considered. In both humans and rodent models, environmental factors that act as endocrine disrupting compounds (EDCs) have been shown to disrupt normal mammary development and lead to adverse lifelong consequences, especially when exposures occur during early life. EDCs can act directly or indirectly on mammary tissue to increase sensitivity to chemical carcinogens or enhance development of hyperplasia, beaded ducts, or tumors. Protective effects have also been reported. The mechanisms for these changes are not well understood. Environmental agents may also act as carcinogens in adult rodent models, directly causing or promoting tumor development, typically in more than one organ. Many of the environmental agents that act as EDCs and are known to affect the breast are discussed. Understanding the mechanism(s) of action for these compounds will be critical to prevent their effects on the breast in the future. PMID:23417729

  7. Early-life origins of life-cycle well-being: research and policy implications.

    PubMed

    Currie, Janet; Rossin-Slater, Maya

    2015-01-01

    Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the life cycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socioeconomic status. However, there is some variation in the degree to which current policies in the United States are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early-childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited. PMID:25558491

  8. Early-life origins of life-cycle well-being: research and policy implications.

    PubMed

    Currie, Janet; Rossin-Slater, Maya

    2015-01-01

    Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the life cycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the life cycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socioeconomic status. However, there is some variation in the degree to which current policies in the United States are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early-childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited.

  9. Early Life Crises of Habitable Planets

    SciTech Connect

    Pierrehumbert, Raymond

    2006-02-08

    There are a number of crises that a potentially habitable planet must avoid or surmount if its potential is to be realized. These include the runaway greenhouse, loss of atmosphere by chemical or physical processes, and long-lasting global glaciation. In this lecture I will present research on the climate dynamics governing such processes, with particular emphasis on the lessons to be learned from the cases of Early Mars and the Neoproterozoic Snowball Earth.

  10. Early Life Crises of Habitable Planets

    ScienceCinema

    Pierrehumbert, Raymond [University of Chicago, Chicago, Illinois, United States

    2016-07-12

    There are a number of crises that a potentially habitable planet must avoid or surmount if its potential is to be realized. These include the runaway greenhouse, loss of atmosphere by chemical or physical processes, and long-lasting global glaciation. In this lecture I will present research on the climate dynamics governing such processes, with particular emphasis on the lessons to be learned from the cases of Early Mars and the Neoproterozoic Snowball Earth.

  11. Paraoxonase-1 and Early-Life Environmental Exposures.

    PubMed

    Marsillach, Judit; Costa, Lucio G; Furlong, Clement E

    2016-01-01

    Acute and chronic exposures to widely used organophosphorus (OP) insecticides are common. Children's detoxification mechanisms are not well developed until several years after birth. The increased cases of neurodevelopmental disorders in children, together with their increased susceptibility to OP neurotoxicity cannot be explained by genetic factors alone but could be related to gene-environment interactions. Paraoxonase-1 (PON1) is an enzyme that can detoxify OPs but its catalytic efficiency for hydrolysis to certain OPs is modulated by the Q192R polymorphism. Studies with animals have provided important information on the role of PON1 in protecting against gestational and postnatal toxicity to OPs. The PON1Q192 allele is less efficient in hydrolyzing certain OPs than the PON1R192 allele. Maternal PON1 status (PON1 activity levels, the most important measurement, and functional Q192R phenotype) modulates the detrimental effects of exposure to the OP chlorpyrifos oxon on fetal brain gene expression and biomarkers of exposure. Epidemiologic studies suggest that children from mothers with lower PON1 status who were in contact with OPs during pregnancy tend to show smaller head circumference at birth and adverse effects in cognitive function during childhood. Infants and children are vulnerable to OP toxicity. The detrimental consequences of OPs on neurodevelopment can lead to future generations with permanent cognitive problems and susceptibility to develop neurodegenerative diseases. Improved methods using mass spectrometry to monitor OP-adducted biomarker proteins are needed and will be extremely helpful in early life biomonitoring, while measurement of PON1 status as a biomarker of susceptibility will help identify mothers and children highly sensitive to OPs. The use of adductomics instead of enzymatic activity assays for biomonitoring OP exposures have proved to provide several advantages, including the use of dried blood spots, which would facilitate monitoring

  12. Iron Deficiency Anemia Coexists with Cancer Related Anemia and Adversely Impacts Quality of Life

    PubMed Central

    Kanuri, Giridhar; Sawhney, Ritica; Varghese, Jeeva; Britto, Madonna; Shet, Arun

    2016-01-01

    Cancer related anemia (CRA) adversely affects patient Quality of Life (QoL) and overall survival. We prospectively studied the prevalence, etiology and the impact of anemia on QoL in 218 Indian cancer patients attending a tertiary referral hospital. The study used the sTfR/log Ferritin index to detect iron deficiency anemia and assessed patient QoL using the Functional Assessment of Cancer Therapy-Anemia (FACT-An) tool, standardized for language. Mean patient age was 51±13 years and 60% were female. The prevalence of cancer related anemia in this setting was 64% (n = 139). As expected, plasma ferritin did not differ significantly between anemic (n = 121) and non-anemic cancer patients (n = 73). In contrast, plasma sTfR levels were significantly higher in anemic cancer patients compared to non-anemic cancer patients (31 nmol/L vs. 24 nmol/L, p = 0.002). Among anemic cancer patients, using the sTfR/log Ferritin index, we found that 60% (n = 83) had iron deficiency anemia (IDA). Interestingly, plasma sTfR levels were significantly higher in cancer patients with CRA+IDA (n = 83) compared with patients having CRA (n = 38) alone (39 nmol/L vs. 20 nmol/L, p<0.001). There was a significant linear correlation between Hb and QoL (Spearman ρ = 0.21; p = 0.001) and multivariate regression analysis revealed that every gram rise in Hb was accompanied by a 3.1 unit increase in the QoL score (95% CI = 0.19–5.33; p = 0.003). The high prevalence of anemia in cancer patients, a major portion of which is due to iron deficiency anemia, the availability of sensitive and specific biomarkers of iron status to detect IDA superimposed on anemia of inflammation, suggests an urgent need to diagnose and treat such patients. Despite the potential negative consequences of increasing metabolically available plasma iron in cancer, our clinical data suggest that detecting and treating IDA in anemic cancer patients will have important consequences to their QoL and overall survival. Clinical

  13. Early life stress sensitizes rats to angiotensin II-induced hypertension and vascular inflammation in adult life.

    PubMed

    Loria, Analia S; Pollock, David M; Pollock, Jennifer S

    2010-02-01

    Maternal separation during early life is an established chronic behavioral model of early life stress in rats. It is known that perinatal adverse environments increase activity of the renin-angiotensin (Ang) system, specifically Ang II, in adulthood. The aim of this study was to investigate whether the effects of early life stress augment the sensitivity of the Ang II pathway. Using Wistar Kyoto rats, the maternal separation (MS) protocol was performed by separating approximately half of the male pups from their mother 3 h/d from days 2 to 14 of life. Pups remaining with the mother at all times were used as controls. Maternal separation did not influence the plasma basal parameters, such as blood glucose, insulin, Ang II, Ang 1-7 and plasma renin activity. Furthermore, body weight, blood pressure, and heart rate were similar in MS and control rats. The acute pressor response to Ang II was not different in anesthetized MS and control rats. However, the chronic infusion of Ang II (65 ng/min SC) elicited an exaggerated hypertensive response in MS compared with control rats (P<0.05). Surprisingly, HR was dramatically increased during the second week of Ang II infusion in MS compared with control rats (P<0.05). This enhanced Ang II sensitivity was accompanied by a greater vascular inflammatory response in MS versus control rats. Chronic Ang II infusion increased vascular wall structure in both groups similarly. These data indicate that early life stress sensitizes rats to an increased hemodynamic and inflammatory response during Ang II-induced hypertension.

  14. The Peroxy Challenge to Early Life

    NASA Astrophysics Data System (ADS)

    Rothschild, L. J.; Freund, F. T.; Gosling, P.

    2002-12-01

    The development of aerobic metabolism was one of the most important breakthroughs in evolution. But the early Earth was anaerobic, with most researchers today attributing the build-up of free O2 to oxygenic photosynthesizers. This reasoning is problematic because photosynthesis invariably produces oxygen radicals as by-products or intermediates. Known collectively as reactive oxygen species, ROS, these radicals damage DNA, damage membranes, and inactivate essential enzymes. In addition, molecular data on the evolution of cytochrome oxidase suggest that early organisms must have "learned" to detoxify ROS prior to the evolution of aerobic metabolism and oxygenic photosynthesis. A possible way out of this dilemma comes from a study of igneous and high-grade metamorphic rocks, which indicates that a small but significant fraction of the oxygen anions in their minerals exists in the 1- state, forming peroxy links of the type O3Si-OO-SiO3 (J. Geodynamics 33, 543-570, 2002). Water hydrolyzes these peroxy links to hydrogen peroxide, H2O2. As a result, microorganisms that attach themselves to mineral grains will be exposed to a constant trickle of ROS from the production of H2O2. We propose the following scenario: Though the overall conditions on the early Earth were anaerobic, conditions at microsites were not. The hydrolysis of peroxy links in minerals to hydrogen peroxide at the rock-water interface was biochemically challenging for any microbes living in intimate contact with rock surfaces. The generation of ROS placed the microbes under evolutionary stress to develop biochemical defenses against the potentially lethal effects of ROS radicals. Only after these enzymatic defenses were in place, oxygenic photosynthesizers were able to develop and increase the O2 partial pressure in the Earth's atmosphere to a high level.

  15. Reduced cortical thickness in veterans exposed to early life trauma.

    PubMed

    Corbo, Vincent; Salat, David H; Amick, Melissa M; Leritz, Elizabeth C; Milberg, William P; McGlinchey, Regina E

    2014-08-30

    Studies have shown that early life trauma may influence neural development and increase the risk of developing psychological disorders in adulthood. We used magnetic resonance imaging to examine the impact of early life trauma on the relationship between current posttraumatic stress disorder (PTSD) symptoms and cortical thickness/subcortical volumes in a sample of deployed personnel from Operation Enduring Freedom/Operation Iraqi Freedom. A group of 108 service members enrolled in the Translational Research Center for Traumatic Brain Injury and Stress Disorders (TRACTS) were divided into those with interpersonal early life trauma (EL-Trauma+) and Control (without interpersonal early life trauma) groups based on the Traumatic Life Events Questionnaire. PTSD symptoms were assessed using the Clinician-Administered PTSD Scale. Cortical thickness and subcortical volumes were analyzed using the FreeSurfer image analysis package. Thickness of the paracentral and posterior cingulate regions was positively associated with PTSD severity in the EL-Trauma+ group and negatively in the Control group. In the EL-Trauma+ group, both the right amygdala and the left hippocampus were positively associated with PTSD severity. This study illustrates a possible influence of early life trauma on the vulnerability of specific brain regions to stress. Changes in neural morphometry may provide information about the emergence and maintenance of symptoms in individuals with PTSD.

  16. Nutrient Intakes in Early Life and Risk of Obesity.

    PubMed

    Rolland-Cachera, Marie Françoise; Akrout, Mouna; Péneau, Sandrine

    2016-06-06

    There is increasing evidence that environmental factors in early life predict later health. The early adiposity rebound recorded in most obese subjects suggests that factors promoting body fat development have operated in the first years of life. Birth weight, growth velocity and body mass index (BMI) trajectories seem to be highly sensitive to the environmental conditions present during pregnancy and in early life ("The first 1000 days"). Particularly, nutritional exposure can have a long-term effect on health in adulthood. The high protein-low fat diet often recorded in young children may have contributed to the rapid rise of childhood obesity prevalence during the last decades. Metabolic programming by early nutrition could explain the development of later obesity and adult diseases.

  17. Nutrient Intakes in Early Life and Risk of Obesity

    PubMed Central

    Rolland-Cachera, Marie Françoise; Akrout, Mouna; Péneau, Sandrine

    2016-01-01

    There is increasing evidence that environmental factors in early life predict later health. The early adiposity rebound recorded in most obese subjects suggests that factors promoting body fat development have operated in the first years of life. Birth weight, growth velocity and body mass index (BMI) trajectories seem to be highly sensitive to the environmental conditions present during pregnancy and in early life (“The first 1000 days”). Particularly, nutritional exposure can have a long-term effect on health in adulthood. The high protein-low fat diet often recorded in young children may have contributed to the rapid rise of childhood obesity prevalence during the last decades. Metabolic programming by early nutrition could explain the development of later obesity and adult diseases. PMID:27275827

  18. Sorafenib in hepatocellular carcinoma: prospective study on adverse events, quality of life, and related feasibility under daily conditions.

    PubMed

    Brunocilla, Paola Rita; Brunello, Franco; Carucci, Patrizia; Gaia, Silvia; Rolle, Emanuela; Cantamessa, Alessandro; Castiglione, Anna; Ciccone, Giovannino; Rizzetto, Mario

    2013-03-01

    Sorafenib is an oral multikinase inhibitor approved for the treatment of hepatocellular carcinoma (HCC). In two randomized trials, sorafenib was reported to be safe without a significant impact on quality of life (QoL). The aim of this study was to evaluate the occurrence of adverse events, QoL variations, and treatment discontinuations in HCC patients treated with sorafenib. Between November 2009 and March 2011, all patients evaluated as suitable for sorafenib treatment were enrolled. Every patient was invited to complete the Functional Assessment of Cancer Therapy-Hepatobiliary Questionnaire before starting therapy, at week 1, and at months 1 and 2. QoL scores were analyzed by the Wilcoxon matched-pairs test. Side effects were classified according to the Common Terminology Criteria for Adverse Events v.3.0. Thirty-six patients were enrolled. The cumulative incidence of therapy discontinuation for drug-related adverse events was 33 % (95 % confidence interval, 20.2-49.7). The most common adverse event was fatigue (66.7 %). The worst score decrease was detected from baseline to week 1 in physical well-being, with a median reduction of -8.3 (range -60.1 to 17.9; P = 0.0003). Treatment withdrawal from adverse events was higher than previously reported, significant QoL decrease occurred, and estimated feasibility was 66.7 %.

  19. Early life stress produces compulsive-like, but not impulsive, behavior in females.

    PubMed

    Brydges, Nichola M; Holmes, Megan C; Harris, Anjanette P; Cardinal, Rudolf N; Hall, Jeremy

    2015-06-01

    Adverse experiences during childhood are associated with the development of psychiatric disorders later in life. In particular, childhood abuse and neglect are risk factors for addictive disorders, such as substance misuse and pathological gambling. Impulsivity and compulsivity are key features of these disorders. Therefore, we investigated whether childhood adversity might increase vulnerability for addictive disorders through promotion of compulsive and impulsive behaviors. Rats were exposed to a brief, variable childhood or prepubertal stress protocol (Postnatal Days 25-27), and their behavior in a delay discounting task was compared with that of control animals in adulthood. Prepubertal stress produced compulsive-type behavior in females. Specifically, stressed females displayed inappropriate responses during a choice phase of the task, perseverating with nosepoke responding instead of choosing between 2 levers. Stressed females also showed learning impairments during task training. However, prepubertal stress was not associated with the development of impulsive behavior, as rates of delay discounting were not affected in either sex. Childhood adversity may contribute to the establishment and maintenance of addictive disorders by increasing perseveration in females. Perseverative behavior may therefore provide a viable therapeutic target for preventing the development of addictive disorders in individuals exposed to childhood adversity. These effects were not seen in males, highlighting sex differences in response to early life stress. PMID:26030429

  20. Adverse effects of ocean acidification on early development of squid (Doryteuthis pealeii).

    PubMed

    Kaplan, Maxwell B; Mooney, T Aran; McCorkle, Daniel C; Cohen, Anne L

    2013-01-01

    Anthropogenic carbon dioxide (CO2) is being absorbed into the ocean, altering seawater chemistry, with potentially negative impacts on a wide range of marine organisms. The early life stages of invertebrates with internal and external aragonite structures may be particularly vulnerable to this ocean acidification. Impacts to cephalopods, which form aragonite cuttlebones and statoliths, are of concern because of the central role they play in many ocean ecosystems and because of their importance to global fisheries. Atlantic longfin squid (Doryteuthis pealeii), an ecologically and economically valuable taxon, were reared from eggs to hatchlings (paralarvae) under ambient and elevated CO2 concentrations in replicated experimental trials. Animals raised under elevated pCO2 demonstrated significant developmental changes including increased time to hatching and shorter mantle lengths, although differences were small. Aragonite statoliths, critical for balance and detecting movement, had significantly reduced surface area and were abnormally shaped with increased porosity and altered crystal structure in elevated pCO2-reared paralarvae. These developmental and physiological effects could alter squid paralarvae behavior and survival in the wild, directly and indirectly impacting marine food webs and commercial fisheries.

  1. Adverse Effects of Ocean Acidification on Early Development of Squid (Doryteuthis pealeii)

    PubMed Central

    Kaplan, Maxwell B.; Mooney, T. Aran; McCorkle, Daniel C.; Cohen, Anne L.

    2013-01-01

    Anthropogenic carbon dioxide (CO2) is being absorbed into the ocean, altering seawater chemistry, with potentially negative impacts on a wide range of marine organisms. The early life stages of invertebrates with internal and external aragonite structures may be particularly vulnerable to this ocean acidification. Impacts to cephalopods, which form aragonite cuttlebones and statoliths, are of concern because of the central role they play in many ocean ecosystems and because of their importance to global fisheries. Atlantic longfin squid (Doryteuthis pealeii), an ecologically and economically valuable taxon, were reared from eggs to hatchlings (paralarvae) under ambient and elevated CO2 concentrations in replicated experimental trials. Animals raised under elevated pCO2 demonstrated significant developmental changes including increased time to hatching and shorter mantle lengths, although differences were small. Aragonite statoliths, critical for balance and detecting movement, had significantly reduced surface area and were abnormally shaped with increased porosity and altered crystal structure in elevated pCO2-reared paralarvae. These developmental and physiological effects could alter squid paralarvae behavior and survival in the wild, directly and indirectly impacting marine food webs and commercial fisheries. PMID:23741298

  2. Sepsis After Cardiac Surgery Early in Infancy and Adverse 4.5-Year Neurocognitive Outcomes

    PubMed Central

    Sidhu, Naveen; Joffe, Ari R; Doughty, Paul; Vatanpour, Shabnam; Dinu, Irina; Alton, Gwen; Acton, Bryan; Robertson, Charlene M T

    2015-01-01

    Background We aimed to determine whether sepsis is associated with neurocognitive outcomes 4.5 years after congenital heart disease surgery in early infancy. Methods and Results A secondary analysis from a prospective inception cohort included all children having congenital heart disease surgery done at ≤6 weeks of age with cardiopulmonary bypass at the Western Canadian referral center from 1996 to 2009. Follow-up at the referral center determined the primary outcomes at 4.5 years with full-scale, performance, and verbal intelligence quotients on the Wechsler Preschool and Primary Scale of Intelligence. Perioperative variables were collected prospectively, and confirmation of blood culture–positive sepsis was done retrospectively. Multiple linear regression models for neurocognitive outcomes and multiple Cox proportional hazards regression for mortality were determined. Sepsis occurred in 97 of 502 patients (19%) overall and in 76 of 396 survivors (19%) with 4.5-year follow-up. By 4.5 years, there were 91 (18%) deaths, and 396 of 411 survivors (96%) had follow-up completed. Extracorporeal membrane oxygenation was associated with worse scores on all neurocognitive outcomes on multivariable regression; the association between extracorporeal membrane oxygenation and full-scale intelligence quotient had a regression coefficient of −13.6 (95% CI −21.3 to −5.9; P =0.001). Sepsis perioperatively was associated with performance and verbal intelligence quotients, with a trend for full-scale intelligence quotient (P =0.058) on multivariable regression. The regression coefficient for sepsis was strongest for performance intelligence quotient (−5.31; 95% CI −9.84 to −0.78; P =0.022). Sepsis was not but extracorporeal membrane oxygenation was associated with mortality by 4.5 years. Conclusions Perioperative sepsis and extracorporeal membrane oxygenation were associated with adverse neurocognitive outcomes on multivariable regression. Quality improvement to

  3. The Intestinal Microbiome in Early Life: Health and Disease

    PubMed Central

    Arrieta, Marie-Claire; Stiemsma, Leah T.; Amenyogbe, Nelly; Brown, Eric M.; Finlay, Brett

    2014-01-01

    Human microbial colonization begins at birth and continues to develop and modulate in species abundance for about 3 years, until the microbiota becomes adult-like. During the same time period, children experience significant developmental changes that influence their health status as well as their immune system. An ever-expanding number of articles associate several diseases with early-life imbalances of the gut microbiota, also referred to as gut microbial dysbiosis. Whether early-life dysbiosis precedes and plays a role in disease pathogenesis, or simply originates from the disease process itself is a question that is beginning to be answered in a few diseases, including IBD, obesity, and asthma. This review describes the gut microbiome structure and function during the formative first years of life, as well as the environmental factors that determine its composition. It also aims to discuss the recent advances in understanding the role of the early-life gut microbiota in the development of immune-mediated, metabolic, and neurological diseases. A greater understanding of how the early-life gut microbiota impacts our immune development could potentially lead to novel microbial-derived therapies that target disease prevention at an early age. PMID:25250028

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

    PubMed

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

    2015-01-01

    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.

  5. 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

  6. Whole cow's milk in early life.

    PubMed

    Thorsdottir, Inga; Thorisdottir, Asa V

    2011-01-01

    Cow's milk is a major food for young children. Whole cow's milk is known to be detrimental to infants, mainly due to its low iron content. The negative association with iron status led to recommending the introduction of formula feeding in infancy during the weaning period or when breastfeeding ceased. More recently, the literature suggests that consuming whole cow's milk in infancy has unfortunate effects on growth, especially weight acceleration and development of overweight in childhood. These issues are discussed in the following chapter. Other suggested reasons for the avoidance of whole cow's milk in infancy are touched upon, such as milk protein allergy and high renal solute load. The hypothesis about early cow's milk introduction in the pathology of certain diseases, mainly through the peptide β-casomorphin-7, is briefly reviewed, showing that there is no clear evidence for the suggested associations. The chapter gives a recent example of introducing formula at 6 months of age instead of whole cow's milk in infants' diet in Iceland. Several aspects of consuming whole cow's milk in infancy can be found in recent reviews. PMID:21335988

  7. Nutrition and brain development in early life.

    PubMed

    Prado, Elizabeth L; Dewey, Kathryn G

    2014-04-01

    Presented here is an overview of the pathway from early nutrient deficiency to long-term brain function, cognition, and productivity, focusing on research from low- and middle-income countries. Animal models have demonstrated the importance of adequate nutrition for the neurodevelopmental processes that occur rapidly during pregnancy and infancy, such as neuron proliferation and myelination. However, several factors influence whether nutrient deficiencies during this period cause permanent cognitive deficits in human populations, including the child's interaction with the environment, the timing and degree of nutrient deficiency, and the possibility of recovery. These factors should be taken into account in the design and interpretation of future research. Certain types of nutritional deficiency clearly impair brain development, including severe acute malnutrition, chronic undernutrition, iron deficiency, and iodine deficiency. While strategies such as salt iodization and micronutrient powders have been shown to improve these conditions, direct evidence of their impact on brain development is scarce. Other strategies also require further research, including supplementation with iron and other micronutrients, essential fatty acids, and fortified food supplements during pregnancy and infancy.

  8. Inborn Stress Reactivity Shapes Adult Behavioral Consequences of Early-Life Maternal Separation Stress

    PubMed Central

    Rana, Samir; Pugh, Phyllis C.; Jackson, Nateka; Clinton, Sarah M.; Kerman, Ilan A.

    2015-01-01

    Early-life experience strongly impacts neurodevelopment and stress susceptibility in adulthood. Maternal separation (MS), an established model of early-life adversity, has been shown to negatively impact behavioral and endocrine responses to stress in adulthood. However, the impact of MS in rats with heightened inborn stress susceptibility has not been fully explored. To address this issue we conducted MS in Wistar-Kyoto (WKY) rats, an animal model of comorbid depression and anxiety, and Wistar rats, which share a similar genetic background with WKYs. WKY and Wistar pups experienced either 180-min daily MS or 15-min separation (neonatal handling) during the first two postnatal weeks, and were tested for depressive- and anxiety- like behaviors in adulthood. Exposure to early-life MS in WKY rats decreased anxiety- and depressive- like behaviors, leading to increased exploration on the open field test (OFT), enhanced social interaction, and diminished immobility on the forced swim test. MS had an opposite effect in Wistar offspring, leading to enhanced anxiety-like behaviors, such as reduced OFT exploration and decreased social interaction. These findings are consistent with the match/mismatch theory of disease and the predictive adaptive response, which suggest that early life stress exposure can confer adaptive value in later life within certain individuals. Our data supports this theory, showing that early-life MS has positive and perhaps adaptive effects within stress-vulnerable WKY offspring. Future studies will be required to elucidate the neurobiological underpinnings of contrasting behavioral effects of MS on WKY vs. Wistar offspring. PMID:25451726

  9. Factors in Early-Life Programming of Reproductive Fitness.

    PubMed

    Sominsky, Luba; Fuller, Erin A; Hodgson, Deborah M

    2015-01-01

    Fertility rates have been declining worldwide, with a growing number of young women suffering from infertility. Infectious and inflammatory diseases are important causes of infertility, and recent evidence points to the critical role of the early-life microbial environment in developmental programming of adult reproductive fitness. Our laboratory and others have demonstrated that acute exposure to an immunological challenge early in life has a profound and prolonged impact on male and female reproductive development. This review presents evidence that perinatal exposure to immunological challenge by a bacterial endotoxin, lipopolysaccharide, acts at all levels of the hypothalamic-pituitary-gonadal axis, resulting in long-lasting changes in reproductive function, suggesting that disposition to infertility may begin early in life.

  10. Commentary: On the Importance of Early Life Cognitive Abilities in Shaping Later Life Outcomes.

    PubMed

    Hofer, Scott M; Clouston, Sean

    2014-01-01

    Early life cognitive ability is likely to be dynamically related to life course factors including educational attainment, occupational outcomes, health behaviors, activities, health, and subsequent cognitive health. Disentangling the selective and causal processes contributing to cognitive functioning across the lifespan is challenging and requires long-term investments in longitudinal data. We discuss results from several analyses using data from the Individual Development and Adaptation longitudinal research program (Bergman, 2000; Magnusson, 1988) that provide fresh insights into the relation of early life cognition, particularly high levels of cognitive capabilities, to educational achievement, emotional adjustment, and career success. These papers and the longitudinal data provide a remarkable window into the development and impacts of cognition, and high cognitive functioning, on a variety of important life outcomes that we hope will continue to inform us about additional outcomes in middle life, transition to retirement, and cognition and health in later years and to robustly examine how the early years matter across the whole lifespan.

  11. Dopamine D4 receptor exon III polymorphism, adverse life events and personality traits in a nonclinical German adult sample.

    PubMed

    Reiner, Iris; Spangler, Gottfried

    2011-01-01

    Personality and temperament embrace a wide area of both psychological and behavioral processes which are also based on disposition. A functional polymorphism in exon III of the dopamine D4 receptor gene (DRD4) has been a highly suspect genetic marker for personality in spite of ambiguous results. The present study aimed to further elucidate the relationship between DRD4, negative life events and personality in a representative nonclinical sample. Hundred sixty-seven Germans completed the NEO Five-Factor Inventory, the Tridimensional Personality Questionnaire and the California Adult Q-Sort. A factor analysis revealed 3 factors: emotional stability, social orientation and impulsivity. DNA from buccal cells was genotyped for the DRD4 variable-number tandem-repeat exon III polymorphism with respect to presence versus absence of the DRD4 7-repeat allele. Adverse life events were assessed by means of the Adverse Life Events Scale. Men carrying the DRD4 7-repeat allele were more impulsive than those without. Male 7-repeat carriers were more emotionally instable than others, but only when they experienced a large amount of negative life events. No genotype-personality relationships were found for women. The results indicate gender-specific influences of the DRD4 gene on human behavior and invite researchers to further investigate gene-environment correlations on personality traits.

  12. The diversity of early Life on Earth : implications for life on Mars

    NASA Astrophysics Data System (ADS)

    Westall, F.; Southam, G.

    Although the locations where the earliest traces of life can be studied are few and far between (Isua, 3.8 Ga; Pilbara and Barberton, 3.5-3.3 Ga), the life that existed in the Early Archaean life has left a wealth of testimony. Structural and chemical fossils found in Early Arcahean `habitats' demonstrate that the biosphere was already in an advanced evolutionary state, i.e., much of the strata preserved from this period appears to have been colonised by morphologically and biochemically diverse bacteria. The Early-Mid Archaean microorganisms were morphologically similar to modern organisms and behaved in the same way, building colonies, biofilms and mats and interacting directly with their immediate substrate and with each other (in consortia). Their metabolic processes included chemolithotrophy, possibly methanogenesis and possibly anoxygenic photosynthesis. Early life was diverse and included thermophilic, acid-tolerant, halo-tolerant to halophilic, and radiation resistant species. With one exception, the traces of early life are subtle, on the scale of tens to hundreds of µm although, where environmental conditions were stable and quiet enough for their development, microbial mats on sediment surfaces could contribute to the formation of stromatolites of about 10 cm in height. The diversity, relative level of evolution and widespread distribution of life by 3.5 Ga implies that it must have evolved much earlier, possibly even before or during the period of late heavy bombardment). However, no record of its appearance and early evolution remains on Earth. Given the conditions on early Mars were generally similar to those on early Earth, i.e., habitable, the Southern Highlands of Mars could potentially host this missing record. Life on early Mars would probably have been similarly subtle in its expression, although there is a possibility of "stumbling" across small macroscopic stromatolites. If life still exists on the planet today, it's in the subsurface and its

  13. 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

  14. Epigenetic Vestiges of Early Developmental Adversity: Childhood Stress Exposure and DNA Methylation in Adolescence

    ERIC Educational Resources Information Center

    Essex, Marilyn J.; Boyce, W. Thomas; Hertzman, Clyde; Lam, Lucia L.; Armstrong, Jeffrey M.; Neumann, Sarah M. A.; Kobor, Michael S.

    2013-01-01

    Fifteen-year-old adolescents (N = 109) in a longitudinal study of child development were recruited to examine differences in DNA methylation in relation to parent reports of adversity during the adolescents' infancy and preschool periods. Microarray technology applied to 28,000 cytosine-guanine dinucleotide sites within DNA derived from buccal…

  15. The origin and early evolution of life on earth

    NASA Technical Reports Server (NTRS)

    Oro, J.; Miller, Stanley L.; Lazcano, Antonio

    1990-01-01

    Results of the studies that have provided insights into the cosmic and primitive earth environments are reviewed with emphasis on those environments in which life is thought to have originated. The evidence bearing on the antiquity of life on the earth and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar-system bodies such as comets, dark asteroids, and carbonaceous chondrites are assessed. The environmental models of the Hadean and early Archean earth are discussed, as well as the prebiotic formation of organic monomers and polymers essential to life. The processes that may have led to the appearance in the Archean of the first cells are considered, and possible effects of these processes on the early steps of biological evolution are analyzed. The significance of these results to the study of the distribution of life in the universe is evaluated.

  16. Early Earth and early life: an extreme environment and extremophiles - application to the search for life on Mars

    NASA Astrophysics Data System (ADS)

    Westall, Frances; Brack, André; Barbier, Bernard; Bertrand, Marylène; Chabin, A.

    2002-11-01

    The early Earth was an extreme environment compared to the present day Earth: oceans with probably higher salinity and lower Ph, evaporitic conditions in the littoral environment, temperatures 70-80°C, little or no O2 in the atmosphere, pervasive volcanism and hydrothermal activity, and peak bolide activity between 4.0-3.85 b.y. ago. The oldest fossil evidence from 3.45 b.y. old sediments shows that life was widespread and thriving in and around hydrothermal vents and in evaporitic, littoral environments, exposed to high UV radiation. Given these conditions, life must have been extremophile by definition. Although there are strong dissimilarities between the geological evolution of early Mars and early Earth, from a microbial point of view, the environmental conditions on both planets were very similar, although the wider range in temperatures on Mars may have made a wider diversity possible. Early Earth and early life therefore represent an excellent analogue for the study of potential early Martian life.

  17. Early-life course socioeconomic factors and chronic kidney disease.

    PubMed

    Brophy, Patrick D; Shoham, David A; Charlton, Jennifer R; Carmody, J Bryan; Reidy, Kimberly J; Harshman, Lyndsay; Segar, Jeffrey; Askenazi, David

    2015-01-01

    Kidney failure or ESRD affects approximately 650,000 Americans, whereas the number with earlier stages of CKD is much higher. Although CKD and ESRD are usually associated with adulthood, it is likely that the initial stages of CKD begin early in life. Many of these pathways are associated with low birth weight and disadvantaged socioeconomic status (SES) in childhood, translating childhood risk into later-life CKD and kidney failure. Social factors are thought to be fundamental causes of disease. Although the relationship between adult SES and CKD has been well established, the role of early childhood SES for CKD risk remains obscure. This review provides a rationale for examining the association between early-life SES and CKD. By collecting data on early-life SES and CKD, the interaction with other periods in the life course could also be studied, allowing for examination of whether SES trajectories (eg, poverty followed by affluence) or cumulative burden (eg, poverty at multiple time points) are more relevant to lifetime CKD risk.

  18. Can environmental conditions experienced in early life influence future generations?

    PubMed Central

    Burton, Tim; Metcalfe, Neil B.

    2014-01-01

    The consequences of early developmental conditions for performance in later life are now subjected to convergent interest from many different biological sub-disciplines. However, striking data, largely from the biomedical literature, show that environmental effects experienced even before conception can be transmissible to subsequent generations. Here, we review the growing evidence from natural systems for these cross-generational effects of early life conditions, showing that they can be generated by diverse environmental stressors, affect offspring in many ways and can be transmitted directly or indirectly by both parental lines for several generations. In doing so, we emphasize why early life might be so sensitive to the transmission of environmentally induced effects across generations. We also summarize recent theoretical advancements within the field of developmental plasticity, and discuss how parents might assemble different ‘internal’ and ‘external’ cues, even from the earliest stages of life, to instruct their investment decisions in offspring. In doing so, we provide a preliminary framework within the context of adaptive plasticity for understanding inter-generational phenomena that arise from early life conditions. PMID:24807254

  19. 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

  20. Research Note: Are Life-Course-Persistent Offenders at Risk for Adverse Health Outcomes?

    ERIC Educational Resources Information Center

    Piquero, Alex R.; Daigle, Leah E.; Gibson, Chris; Piquero, Nicole Leeper; Tibbetts, Stephen G.

    2007-01-01

    Moffitt's developmental taxonomy of adolescence-limited and life-course-persistent offenders has received much empirical attention, with researchers focusing on the etiology and trajectory of offending between the two groups. Recently, Moffitt articulated a new hypothesis that has yet to be empirically assessed--that life-course-persistent…

  1. Adverse Life Events, Coping and Internalizing and Externalizing Behaviors in Urban African American Youth

    ERIC Educational Resources Information Center

    Sanchez, Yadira M.; Lambert, Sharon F.; Cooley-Strickland, Michele

    2013-01-01

    African American youth residing in low income urban neighborhoods are at increased risk of experiencing negative life events in multiple domains, increasing their risk for internalizing and externalizing behaviors. However, little is known about youth's differential responses to life event stress, or protective processes and coping strategies for…

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

    PubMed

    Wallace, J G; Gohir, W; Sloboda, D M

    2016-02-01

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

  3. Interaction between sex and early-life stress: influence on epileptogenesis and epilepsy comorbidities.

    PubMed

    Jones, Nigel C; O'Brien, Terence J; Carmant, Lionel

    2014-12-01

    Epilepsy is a common brain disorder which is characterised by recurring seizures. In addition to suffering from the constant stress of living with this neurological condition, patients also frequently experience comorbid psychiatric and cognitive disorders which significantly impact their quality of life. There is growing appreciation that stress, in particular occurring in early life, can negatively impact brain development, creating an enduring vulnerability to develop epilepsy. This aligns with the solid connections between early life environments and the development of psychiatric conditions, promoting the possibility that adverse early life events could represent a common risk factor for the later development of both epilepsy and comorbid psychiatric disorders. The influence of sex has been little studied, but recent research points to potential important interactions, particularly with regard to effects mediated by HPA axis programming. Understanding these interactions, and the underlying molecular mechanisms, will provide important new insights into the causation of both epilepsy and of psychiatric disorders, and potentially open up novel avenues for treatment.

  4. Club foot, an adverse outcome of early amniocentesis: disruption or deformation?

    PubMed Central

    Farrell, S; Summers, A; Dallaire, L; Singer, J; Johnson, J.; Wilson, R

    1999-01-01

    An association between the occurrence of club foot and early amniocentesis has been reported. The largest of these randomised studies was the Canadian Early and Mid-Trimester Amniocentesis Trial. Data describing the neonatal outcome, focusing on this association, are presented. Possible mechanisms for the association and the implications for the development of club foot are discussed.


Keywords: amniocentesis; early amniocentesis; club foot PMID:10544229

  5. Severe early life stress hampers spatial learning and neurogenesis, but improves hippocampal synaptic plasticity and emotional learning under high-stress conditions in adulthood.

    PubMed

    Oomen, Charlotte A; Soeters, Heleen; Audureau, Nathalie; Vermunt, Lisa; van Hasselt, Felisa N; Manders, Erik M M; Joëls, Marian; Lucassen, Paul J; Krugers, Harm

    2010-05-12

    Early life stress increases the risk for developing stress-related pathologies later in life. Recent studies in rats suggest that mild early life stress, rather than being overall unfavorable, may program the hippocampus such that it is optimally adapted to a stressful context later in life. Here, we tested whether this principle of "adaptive programming" also holds under severely adverse early life conditions, i.e., 24 h of maternal deprivation (MD), a model for maternal neglect. In young adult male rats subjected to MD on postnatal day 3, we observed reduced levels of adult hippocampal neurogenesis as measured by cell proliferation, cell survival, and neuronal differentiation. Also, mature dentate granule cells showed a change in their dendritic morphology that was most noticeable in the proximal part of the dendritic tree. Lasting structural changes due to MD were paralleled by impaired water maze acquisition but did not affect long-term potentiation in the dentate gyrus. Importantly, in the presence of high levels of the stress hormone corticosterone, even long-term potentiation in the dentate gyrus of MD animals was facilitated. In addition to this, contextual learning in a high-stress environment was enhanced in MD rats. These morphological, electrophysiological, and behavioral observations show that even a severely adverse early life environment does not evolve into overall impaired hippocampal functionality later in life. Rather, adversity early in life can prepare the organism to perform optimally under conditions associated with high corticosteroid levels in adulthood.

  6. Do early life factors affect the development of knee osteoarthritis in later life: a narrative review.

    PubMed

    Antony, Benny; Jones, Graeme; Jin, Xingzhong; Ding, Changhai

    2016-01-01

    Osteoarthritis (OA) mainly affects older populations; however, it is possible that early life factors contribute to the development of OA in later life. The aim of this review is to describe the association between childhood or early adulthood risk factors and knee pain, structural imaging markers and development of knee OA in later life. A narrative overview of the literature synthesising the findings of literature retrieved from searches of computerised databases and manual searches was conducted. We found that only a few studies have explored the long-term effect of childhood or early adulthood risk factors on the markers of joint health that predispose people to OA or joint symptoms. High body mass index (BMI) and/or overweight status from childhood to adulthood were independently related to knee pain and OA in later life. The findings regarding the association between strenuous physical activity and knee structures in young adults are still conflicting. However, a favourable effect of moderate physical activity and fitness on knee structures is reported. Childhood physical activity and performance measures had independent beneficial effects on knee structures including knee cartilage in children and young adults. Anterior knee pain syndrome in adolescence could lead to the development of patellofemoral knee OA in the late 40s. Furthermore, weak evidence suggests that childhood malalignment, socioeconomic status and physical abuse are associated with OA in later life. The available evidence suggests that early life intervention may prevent OA in later life. PMID:27623622

  7. Attic still life southsoutheast looking northnorthwest. Shows an early toilet, ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Attic still life south-southeast looking north-northwest. Shows an early toilet, what is possibly the original front door, and a lead lined reservoir. Also shows the attic framing. - Samuel P. Grindle House, 13 School Street, Castine, Hancock County, ME

  8. Aim for the Inner Life: Teaching Early Teens.

    ERIC Educational Resources Information Center

    Regelski, Thomas A.

    1979-01-01

    Music study should be construed primarily as an experience of its feeling content. Taught so, it can reach for the inner core of the early adolescent, to pierce that sometimes hard outer surface that protects the vulnerable inner life. Attempts to intellectualize music with young teens are doomed. (Author/SJL)

  9. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  10. Early-Life Determinants of Children's Creativity: The Rorschach Perspective.

    ERIC Educational Resources Information Center

    Peske, Patric O.

    Using Rorschach inkblots, the author sought investigation and disclosure of early-life determinants of young children's creativity as influenced by home and school environmental experiences. Significant and empirically defined characterological features of children and adults in their lives and children's Rorschach and other examination findings,…

  11. Family Quality of Life Following Early Identification of Deafness

    ERIC Educational Resources Information Center

    Jackson, Carla W.; Wegner, Jane R.; Turnbull, Ann P.

    2010-01-01

    Purpose: Family members' perceptions of their quality of life were examined following early identification of deafness in children. Method: A questionnaire was used to solicit ratings of satisfaction from the family members of 207 children who were deaf and younger than 6 years of age. Results: Results indicated that families were generally…

  12. Early Stages of the Evolution of Life: a Cybernetic Approach

    NASA Astrophysics Data System (ADS)

    Melkikh, Alexey V.; Seleznev, Vladimir D.

    2008-08-01

    Early stages of the evolution of life are considered in terms of control theory. A model is proposed for the transport of substances in a protocell possessing the property of robustness with regard to changes in the environmental concentration of a substance.

  13. TOXICITY OF AHR AGONISTS TO FISH EARLY LIFE STAGES

    EPA Science Inventory

    Fish early life stages are exceptionally sensitive to the lethal toxicity of chemicals that act as arylhydrocarbon receptor (AhR) agonists. Toxicity characterizations based on 2,3,7,8-tetrachlorodibenzo-p-dioxin, generally the most potent AhR agonist, support the toxicity equiva...

  14. Child Development, Early Childhood Education and Family Life: A Bibliography.

    ERIC Educational Resources Information Center

    Reardon, Beverly, Comp.

    This bibliographical listing of approximately 2500 books on child development, early childhood education and family life was compiled as a resource for parents and students. Books are listed alphabetically by author and are grouped according to the following categories: child development; observation of children; adolescence; language…

  15. [Early life opportunities for promotion of children health].

    PubMed

    Tao, Fangbiao

    2016-02-01

    This editorial highlights some of the emerging threats and risks to children health, including birth defects, psychological behavioral problems, neurodevelopmental disorders and health risk behaviors, which will continue to have increased impact on healthy growth and development. Mounting evidence has confirmed the adverse effects of environmental exposure during preconception and pregnancy on children's health, which suggests that one of the best investments we can make to achieve lasting progress in global health is the prevention of children's health problems during the first thousand days of life and beyond. PMID:26926715

  16. Bottom of the Heap: Having Heavier Competitors Accelerates Early-Life Telomere Loss in the European Starling, Sturnus vulgaris

    PubMed Central

    Nettle, Daniel; Monaghan, Pat; Boner, Winnie; Gillespie, Robert; Bateson, Melissa

    2013-01-01

    Early-life adversity is associated with poorer health and survival in adulthood in humans and other animals. One pathway by which early-life environmental stressors could affect the adult phenotype is via effects on telomere dynamics. Several studies have shown that early-life adversity is associated with relatively short telomeres, but these are often cross-sectional and usually correlational in design. Here, we present a novel experimental system for studying the relationship between early-life adversity and telomere dynamics using a wild bird, the European starling (Sturnus vulgaris). We used cross-fostering to experimentally assign sibling chicks to either small or large broods for twelve days of the growth period. We measured telomere length in red blood cells using quantitative PCR near the beginning of the experimental manipulation (4 days old), at the end of the experimental manipulation (15 days old), and once the birds were independent (55 days old). Being in a larger brood slowed growth and retarded wing development and the timing of fledging. We found no evidence that overall brood size affected telomere dynamics. However, the greater the number of competitors above the focal bird in the within-brood size hierarchy, the greater was the telomere loss during the period of the experimental manipulation. The number of competitors below the focal in the hierarchy had no effect. The effect of heavier competitors was still evident when we controlled for the weight of the focal bird at the end of the manipulation, suggesting it was not due to retarded growth per se. Moreover, the impact of early competition on telomeres was still evident at independence, suggesting persistence beyond early life. Our study provides experimental support for the hypothesis that social stress, in this case induced by the presence of a greater number of dominant competitors, accelerates the rate of telomere loss. PMID:24386235

  17. Bottom of the heap: having heavier competitors accelerates early-life telomere loss in the European starling, Sturnus vulgaris.

    PubMed

    Nettle, Daniel; Monaghan, Pat; Boner, Winnie; Gillespie, Robert; Bateson, Melissa

    2013-01-01

    Early-life adversity is associated with poorer health and survival in adulthood in humans and other animals. One pathway by which early-life environmental stressors could affect the adult phenotype is via effects on telomere dynamics. Several studies have shown that early-life adversity is associated with relatively short telomeres, but these are often cross-sectional and usually correlational in design. Here, we present a novel experimental system for studying the relationship between early-life adversity and telomere dynamics using a wild bird, the European starling (Sturnus vulgaris). We used cross-fostering to experimentally assign sibling chicks to either small or large broods for twelve days of the growth period. We measured telomere length in red blood cells using quantitative PCR near the beginning of the experimental manipulation (4 days old), at the end of the experimental manipulation (15 days old), and once the birds were independent (55 days old). Being in a larger brood slowed growth and retarded wing development and the timing of fledging. We found no evidence that overall brood size affected telomere dynamics. However, the greater the number of competitors above the focal bird in the within-brood size hierarchy, the greater was the telomere loss during the period of the experimental manipulation. The number of competitors below the focal in the hierarchy had no effect. The effect of heavier competitors was still evident when we controlled for the weight of the focal bird at the end of the manipulation, suggesting it was not due to retarded growth per se. Moreover, the impact of early competition on telomeres was still evident at independence, suggesting persistence beyond early life. Our study provides experimental support for the hypothesis that social stress, in this case induced by the presence of a greater number of dominant competitors, accelerates the rate of telomere loss.

  18. Bottom of the heap: having heavier competitors accelerates early-life telomere loss in the European starling, Sturnus vulgaris.

    PubMed

    Nettle, Daniel; Monaghan, Pat; Boner, Winnie; Gillespie, Robert; Bateson, Melissa

    2013-01-01

    Early-life adversity is associated with poorer health and survival in adulthood in humans and other animals. One pathway by which early-life environmental stressors could affect the adult phenotype is via effects on telomere dynamics. Several studies have shown that early-life adversity is associated with relatively short telomeres, but these are often cross-sectional and usually correlational in design. Here, we present a novel experimental system for studying the relationship between early-life adversity and telomere dynamics using a wild bird, the European starling (Sturnus vulgaris). We used cross-fostering to experimentally assign sibling chicks to either small or large broods for twelve days of the growth period. We measured telomere length in red blood cells using quantitative PCR near the beginning of the experimental manipulation (4 days old), at the end of the experimental manipulation (15 days old), and once the birds were independent (55 days old). Being in a larger brood slowed growth and retarded wing development and the timing of fledging. We found no evidence that overall brood size affected telomere dynamics. However, the greater the number of competitors above the focal bird in the within-brood size hierarchy, the greater was the telomere loss during the period of the experimental manipulation. The number of competitors below the focal in the hierarchy had no effect. The effect of heavier competitors was still evident when we controlled for the weight of the focal bird at the end of the manipulation, suggesting it was not due to retarded growth per se. Moreover, the impact of early competition on telomeres was still evident at independence, suggesting persistence beyond early life. Our study provides experimental support for the hypothesis that social stress, in this case induced by the presence of a greater number of dominant competitors, accelerates the rate of telomere loss. PMID:24386235

  19. Hypomagnesemia as a potentially life-threatening adverse effect of omeprazole

    PubMed Central

    Hansen, Bent-Are; Bruserud, Øyvind

    2016-01-01

    Hypomagnesemia can be caused by a wide range of diseases (e.g. gastrointestinal disorders, kidney diseases or endocrine disorders), but it can also be a side effect of several drugs. It can be asymptomatic or cause many different clinical symptoms, and the clinical manifestations mainly depend on the rate of development rather than the actual serum magnesium concentration. We here present a 40-year-old female patient with Torsade de pointes ventricular tachycardia and cardiac arrest caused by severe hypomagnesemia as an adverse effect of the proton pump inhibitor omeprazole. PMID:27471598

  20. A Protocolised Once a Day Modified Early Warning Score (MEWS) Measurement Is an Appropriate Screening Tool for Major Adverse Events in a General Hospital Population

    PubMed Central

    Ludikhuize, Jeroen; Kramer, Mark H. H.

    2016-01-01

    Background The Modified Early Warning Score (MEWS) was developed to timely recognise clinically deteriorating hospitalised patients. However, the ability of the MEWS in predicting serious adverse events (SAEs) in a general hospital population has not been examined prospectively. The aims were to (1) analyse protocol adherence to a MEWS protocol in a real-life setting and (2) to determine the predictive value of protocolised daily MEWS measurement on SAEs: death, cardiac arrests, ICU-admissions and readmissions. Methods All adult patients admitted to 6 hospital wards in October and November 2015 were included. MEWS were checked each morning by the research team. For each critical score (MEWS ≥ 3), the clinical staff was inquired about the actions performed. 30-day follow-up for SAEs was performed to compare between patients with and without a critical score. Results 1053 patients with 3673 vital parameter measurements were included, 200 (19.0%) had a critical score. The protocol adherence was 89.0%. 18.2% of MEWS were calculated wrongly. Patients with critical scores had significant higher rates of unplanned ICU admissions [7.0% vs 1.3%, p < 0.001], in-hospital mortality [6.0% vs 0.8%, p < 0.001], 30-day readmission rates [18.6% vs 10.8%, p < 0.05], and a longer length of stay [15.65 (SD: 15.7 days) vs 6.09 (SD: 6.9), p < 0.001]. Specificity of MEWS related to composite adverse events was 83% with a negative predicting value of 98.1%. Conclusions Protocol adherence was high, even though one-third of the critical scores were calculated wrongly. Patients with a MEWS ≥ 3 experienced significantly more adverse events. The negative predictive value of early morning MEWS < 3 was 98.1%, indicating the reliability of this score as a screening tool. PMID:27494719

  1. Early life stress and blood pressure levels in late adulthood.

    PubMed

    Alastalo, H; Räikkönen, K; Pesonen, A-K; Osmond, C; Barker, D J P; Heinonen, K; Kajantie, E; Eriksson, J G

    2013-02-01

    Severe stress experienced in early life may have long-term consequences on adult physiological functions. We studied the long-term effects of separation on blood pressure levels in non-obese subjects who were separated temporarily in childhood from their parents during World War II (WWII). The original clinical study cohort consists of people born during 1934-1944 in Helsinki, Finland. This substudy includes 1361 non-obese subjects (body mass index <30 kg m(-2)). Of these, 192 (14.1%) had been evacuated abroad during WWII. The remaining subjects served as controls. Blood pressure levels and use of blood pressure medication were studied. The separated subjects had significantly higher systolic blood pressure values than the non-separated (148.6+21.5 vs 142.2+19.6 mm Hg, P<0.0001) in adult life. Those subjects separated in early childhood had markedly higher systolic and diastolic blood pressure values in adult life compared with the non-separated (154.6 vs 142.5 mm Hg; 95% confidence interval (CI) 2.6-14.7; P<0.005 and 90.8 vs 87.7 mm Hg; 95% CI 1.0-7.3; P<0.02, respectively). Systolic blood pressure was also higher in the group separated for a duration of <1 year (151.7 vs 142.2 mm Hg; 95% CI 0.0-12.4; P<0.05) compared with the non-separated. Besides being separated, age at separation and duration of separation also influenced blood pressure levels in adult life. This could be due to early hormonal and metabolic programming, during plastic periods in early life, influencing blood pressure levels in adult life.

  2. Chronic family adversity and early child behavior problems: a longitudinal study of low income families.

    PubMed

    Shaw, D S; Vondra, J I; Hommerding, K D; Keenan, K; Dunn, M

    1994-09-01

    A beginning step in the prevention of child psychopathology is the identification of conditions associated with a disproportionately high incidence of behavior problems. Rutter and colleagues (British Journal of Psychiatry, 1975, 126, 493-509) have reported a dramatic increase in the probability of child adjustment difficulties as a function of multiple family stressors. However, few investigators have tested this association beginning in infancy. The present investigation examines this relationship at the ages of 1 and 2 with behavioral adjustment at age 3 among 100 low-income families. Broad support was found for the family adversity hypothesis, though sex differences were evident regarding individual correlates of problem behavior.

  3. Early Mars: A Warm Wet Niche for Life

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.

    2010-01-01

    Exploration of Mars has begun to unveil the history of the planet. Combinations of remote sensing, in situ compositional measurements and photographic observations have shown Mars had a dynamic and active geologic evolution. Mars geologic evolution had conditions that were suitable for supporting life. A habitable planet must have water, carbon and energy sources along with a dynamic geologic past. Mars meets all of these requirements. The first 600 Ma of Martian history were ripe for life to develop because of the abundance of: (i) Water-as shown by carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001, well-dated at approx.3.9 Ga, (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, active volcanism continuing throughout Martian history, and continuing impact processes, (iii) Carbon, water and a likely thicker atmosphere from extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic patterns in the crust [1]. The question arises: "Why would life not develop from these favorable conditions on Mars in its first 600 Ma?" During this period, environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would favor the formation of early life. (Even if life developed elsewhere on Earth, Venus, or on other bodies-it was transported to Mars where surface conditions were suitable for life to evolve)

  4. Cumulative trauma, adversity and grief symptoms associated with fronto-temporal regions in life-course persistent delinquent boys.

    PubMed

    Lansing, Amy E; Virk, Agam; Notestine, Randy; Plante, Wendy Y; Fennema-Notestine, Christine

    2016-08-30

    Delinquent youth have substantial trauma exposure, with life-course persistent delinquents [LCPD] demonstrating notably elevated cross-diagnostic psychopathology and cognitive deficits. Because adolescents remain in the midst of brain and neurocognitive development, tailored interventions are key to improving functional outcomes. This structural magnetic resonance imaging study compared neuroanatomical profiles of 23 LCPD and 20 matched control adolescent boys. LCPD youth had smaller overall gray matter, and left hippocampal, volumes alongside less cortical surface area and folding within the left pars opercularis and supramarginal cortex. LCPD youth had more adversity-related exposures, and their higher Cumulative Trauma, Adversity and Grief [C-TAG] symptoms were associated with less surface area and folding in the pars opercularis and lingual gyrus. Neuroanatomical differences between LCPD and control youth overlap with data from both maltreatment and antisocial literatures. The affected left frontal regions also share connections to language- and executive-related functions, aligning well with LCPD youths' cognitive and behavioral difficulties. These data also dovetail with research suggesting the possibility of neurodevelopmental delays or disruptions related to cumulative adversity burden. Thus, concurrent treatment of LCPD youths' C-TAG symptoms and, cognitive deficits with overlapping neuroanatomical bases, may be most effective in improving outcomes and optimizing neurodevelopmental trajectories. PMID:27388804

  5. 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.

  6. 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

    2016-04-01

    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

  7. 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

  8. 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.

  9. Adverse Life Events and Psychopathology and Prosocial Behavior in Late Adolescence: Testing the Timing, Specificity, Accumulation, Gradient, and Moderation of Contextual Risk

    ERIC Educational Resources Information Center

    Flouri, Eirini; Kallis, Constantinos

    2007-01-01

    A study examines the role of contextual risk in psychopathology and prosocial behavior in adolescents. The results show that risk accumulation matters instead of specificity and that the number of adverse life events is nonmultiplicative with psychopathology.

  10. DNA methylation: the pivotal interaction between early-life nutrition and glucose metabolism in later life.

    PubMed

    Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao

    2014-12-14

    Traditionally, it has been widely acknowledged that genes together with adult lifestyle factors determine the risk of developing some metabolic diseases such as insulin resistance, obesity and diabetes mellitus in later life. However, there is now substantial evidence that prenatal and early-postnatal nutrition play a critical role in determining susceptibility to these diseases in later life. Maternal nutrition has historically been a key determinant for offspring health, and gestation is the critical time window that can affect the growth and development of offspring. The Developmental Origins of Health and Disease (DOHaD) hypothesis proposes that exposures during early life play a critical role in determining the risk of developing metabolic diseases in adulthood. Currently, there are substantial epidemiological studies and experimental animal models that have demonstrated that nutritional disturbances during the critical periods of early-life development can significantly have an impact on the predisposition to developing some metabolic diseases in later life. The hypothesis that epigenetic mechanisms may link imbalanced early-life nutrition with altered disease risk has been widely accepted in recent years. Epigenetics can be defined as the study of heritable changes in gene expression that do not involve alterations in the DNA sequence. Epigenetic processes play a significant role in regulating tissue-specific gene expression, and hence alterations in these processes may induce long-term changes in gene function and metabolism that persist throughout the life course. The present review focuses on how nutrition in early life can alter the epigenome, produce different phenotypes and alter disease susceptibilities, especially for impaired glucose metabolism.

  11. Right hepatic lobe donation adversely affects donor life insurability up to one year after donation.

    PubMed

    Nissing, Matthew H; Hayashi, Paul H

    2005-07-01

    There are no data regarding hepatic lobe donation effects on donor life insurability. Two investigators called 10 agents of 10 different large life insurance companies. One investigator gave a fictitious profile: Caucasian man, 33 years old, nonsmoker, without medical problems (control profile [CP]). The other investigator used the same profile with a history of uncomplicated right lobe donation 12 months earlier (donor profile [DP]). Investigators asked for premium quotes on a $100,000 term life policy. No medical testing or record review was allowed. Investigators were blinded to the results of each other's calls. Agents were unaware of the study. We documented underwriting decisions, premiums quoted, stipulations, number of phone calls, and phone time. All 10 companies would pursue underwriting CP at their lowest, "preferred" rate. Five would do the same for DP. Two might underwrite DP at a more expensive "standard" rate, but a "preferred" rate would be less likely. One would underwrite DP at the "standard" rate; one would not underwrite DP. One agent did not return follow-up calls (DP insurability < CP, P = 0.04). Mean quoted premiums were lower for CP vs. DP ($189/yr. vs. $202/yr., P = 0.56). Median number of phone calls required was 1 for CP and 3 for DP (P = 0.01). Mean telephone minutes were 4.2 for CP and 8.0 for DP (P = 0.004). In conclusion, right hepatic lobe donation decreases life insurability 1 year after uncomplicated donation. Donors can expect some increased difficulty obtaining life insurance, but they should find a company willing to pursue underwriting. The premium paid may be slightly higher.

  12. Early life developmental effects of marine persistent organic pollutants on the sea urchin Psammechinus miliaris.

    PubMed

    Anselmo, Henrique M R; Koerting, Lina; Devito, Sarah; van den Berg, Johannes H J; Dubbeldam, Marco; Kwadijk, Christiaan; Murk, Albertinka J

    2011-11-01

    A new 16-day echinoid early life stage (ELS) bioassay was developed to allow for prolonged observation of possible adverse effects during embryogenesis and larval development of the sea urchin Psammechinus miliaris. Subsequently, the newly developed bioassay was applied to study the effects of key marine persistent organic pollutants (POPs). Mortality, morphological abnormalities and larval development stages were quantified at specific time points during the 16-day experimental period. In contrast to amphibians and fish, P. miliaris early life development was not sensitive to dioxin-like toxicity in the prolonged early life stage test. Triclosan (TCS) levels higher than 500 nM were acutely toxic during embryo development. Morphological abnormalities were induced at concentrations higher than 50 nM hexabromocyclododecane (HBCD) and 1000 nM tetrabromobisphenol A (TBBPA). Larval development was delayed above 25 nM HBCD and 500 nM TBBPA. Heptadecafluorooctane sulfonic acid (PFOS) exposure slightly accelerated larval development at 9 days post-fertilization (dpf). However, the accelerated development was no longer observed at the end of the test period (16 dpf). The newly developed 16-day echinoid ELS bioassay proved to be sensitive to toxic effects of POPs that can be monitored for individual echinoid larvae. The most sensitive and dose related endpoint was the number of developmental penalty points. By manipulation of the housing conditions, the reproductive season could be extended from 3 to 9 months per year and the ELS experiments could be performed in artificial sea water as well.

  13. Early-Life Exposure to Clostridium leptum Causes Pulmonary Immunosuppression

    PubMed Central

    Huang, Fei; Qiao, Hong-mei; Yin, Jia-ning; Gao, Yang; Ju, Yang-hua; Li, Ya-nan

    2015-01-01

    Introduction Low Clostridium leptum levels are a risk factor for the development of asthma. C. leptum deficiency exacerbates asthma; however, the impact of early-life C. leptum exposure on cesarean-delivered mice remains unclear. This study is to determine the effects of early-life C. leptum exposure on asthma development in infant mice. Methods We exposed infant mice to C. leptum (fed-CL) and then induced asthma using the allergen ovalbumin (OVA). Results Fed-CL increased regulatory T (Treg) cells in cesarean-delivered mice compared with vaginally delivered mice. Compared with OVA-exposed mice, mice exposed to C. leptum + OVA did not develop the typical asthma phenotype, which includes airway hyper-responsiveness, cell infiltration, and T helper cell subset (Th1, Th2, Th9, Th17) inflammation. Early-life C. leptum exposure induced an immunosuppressive environment in the lung concurrent with increased Treg cells, resulting in the inhibition of Th1, Th2, Th9, and Th17 cell responses. Conclusion These findings demonstrate a mechanism whereby C. leptum exposure modulates adaptive immunity and leads to failure to develop asthma upon OVA sensitization later in life. PMID:26565810

  14. Diversity of the Human Skin Microbiome Early in Life

    PubMed Central

    Capone, Kimberly A; Dowd, Scot E; Stamatas, Georgios N; Nikolovski, Janeta

    2011-01-01

    Within days after birth, rapid surface colonization of infant skin coincides with significant functional changes. Gradual maturation of skin function, structure, and composition continues throughout the first years of life. Recent reports have revealed topographical and temporal variations in the adult skin microbiome. Here we address the question of how the human skin microbiome develops early in life. We show that the composition of cutaneous microbial communities evolves over the first year of life, showing increasing diversity with age. Although early colonization is dominated by Staphylococci, their significant decline contributes to increased population evenness by the end of the first year. Similar to what has been shown in adults, the composition of infant skin microflora appears to be site specific. In contrast to adults, we find that Firmicutes predominate on infant skin. Timely and proper establishment of healthy skin microbiome during this early period might have a pivotal role in denying access to potentially infectious microbes and could affect microbiome composition and stability extending into adulthood. Bacterial communities contribute to the establishment of cutaneous homeostasis and modulate inflammatory responses. Early microbial colonization is therefore expected to critically affect the development of the skin immune function. PMID:21697884

  15. Exposure to early adversity: Points of cross-species translation that can lead to improved understanding of depression.

    PubMed

    Andersen, Susan L

    2015-05-01

    The relationship between developmental exposure to adversity and affective disorders is reviewed. Adversity discussed herein includes physical and sexual abuse, neglect, or loss of a caregiver in humans. While these stressors can occur at any point during development, the unique temporal relationship to specific depressive symptoms was the focus of discussion. Further influences of stress exposure during sensitive periods can vary by gender and duration of abuse as well. Data from animal studies are presented to provide greater translational and causal understanding of how sensitive periods, different types of psychosocial stressors, and sex interact to produce depressive-like behaviors. Findings from maternal separation, isolation rearing, chronic variable stress, and peer-peer rearing paradigms clarify interpretation about how various depressive behaviors are influenced by age of exposure. Depressive behaviors are broken down into the following categories: mood and affect, anhedonia, energy, working memory, sleep-wake, appetite changes, suicide, and general malaise. Cross-species evidence from humans, nonhuman primates, rats, and mice within each of these categories is discussed. In conclusion, sensitive periods for affective-related behaviors (anxiety, mood, and controllability) occur earlier in life, while other aspects of depression are associated with adversity later during adolescence. PMID:25997766

  16. Long-term impact of early life events on physiology and behaviour.

    PubMed

    Boersma, G J; Bale, T L; Casanello, P; Lara, H E; Lucion, A B; Suchecki, D; Tamashiro, K L

    2014-09-01

    This review discusses the effects of stress and nutrition throughout development and summarises studies investigating how exposure to stress or alterations in nutrition during the pre-conception, prenatal and early postnatal periods can affect the long-term health of an individual. In general, the data presented here suggest that that anything signalling potential adverse conditions later in life, such as high levels of stress or low levels of food availability, will lead to alterations in the offspring, possibly of an epigenetic nature, preparing the offspring for these conditions later in life. However, when similar environmental conditions are not met in adulthood, these alterations may have maladaptive consequences, resulting in obesity and heightened stress sensitivity. The data also suggest that the mechanism underlying these adult phenotypes might be dependent on the type and the timing of exposure.

  17. The origin and early evolution of life on Earth.

    PubMed

    Oró, J; Miller, S L; Lazcano, A

    1990-01-01

    We do not have a detailed knowledge of the processes that led to the appearance of life on Earth. In this review we bring together some of the most important results that have provided insights into the cosmic and primitive Earth environments, particularly those environments in which life is thought to have originated. To do so, we first discuss the evidence bearing on the antiquity of life on our planet and the prebiotic significance of organic compounds found in interstellar clouds and in primitive solar system bodies such as comets, dark asteroids, and carbonaceous chondrites. This is followed by a discussion on the environmental models of the Hadean and early Archean Earth, as well as on the prebiotic formation of organic monomers and polymers essential to life. We then consider the processes that may have led to the appearance in the Archean of the first cells, and how these processes may have affected the early steps of biological evolution. Finally, the significance of these results to the study of the distribution of life in the Universe is discussed.

  18. Mechanisms of early life programming: current knowledge and future directions.

    PubMed

    Tarry-Adkins, Jane L; Ozanne, Susan E

    2011-12-01

    It has been >20 y since epidemiologic studies showed a relation between patterns of early growth and subsequent risk of diseases, such as type 2 diabetes, cardiovascular disease, and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, and animal models have provided strong evidence that the early environment, including early nutrition, plays an important role in mediating these relations. The concept of early life programming is therefore widely accepted. However, the mechanisms by which a phenomenon that occurs in early life can have long-term effects on the function of a cell and therefore on the metabolism of an organism many years later are only starting to emerge. These mechanisms include 1) permanent structural changes in an organ resulting from suboptimal concentrations of an important factor during a critical period of development, eg, the permanent reduction in β cell mass in the endocrine pancreas; 2) persistent alterations in epigenetic modifications (eg, DNA methylation and histone modifications) that lead to changes in gene expression (eg, several transcription factors are susceptible to programmed changes in gene expression through such mechanisms); and 3) permanent effects on the regulation of cellular aging (eg, increases in oxidative stress that lead to macromolecular damage, including that to DNA and specifically to telomeres, can contribute to such effects). Further understanding of such processes will enable the development of preventive and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease. PMID:21543536

  19. Mechanisms of early life programming: current knowledge and future directions.

    PubMed

    Tarry-Adkins, Jane L; Ozanne, Susan E

    2011-12-01

    It has been >20 y since epidemiologic studies showed a relation between patterns of early growth and subsequent risk of diseases, such as type 2 diabetes, cardiovascular disease, and the metabolic syndrome. Studies of identical twins, individuals who were in utero during periods of famine, and animal models have provided strong evidence that the early environment, including early nutrition, plays an important role in mediating these relations. The concept of early life programming is therefore widely accepted. However, the mechanisms by which a phenomenon that occurs in early life can have long-term effects on the function of a cell and therefore on the metabolism of an organism many years later are only starting to emerge. These mechanisms include 1) permanent structural changes in an organ resulting from suboptimal concentrations of an important factor during a critical period of development, eg, the permanent reduction in β cell mass in the endocrine pancreas; 2) persistent alterations in epigenetic modifications (eg, DNA methylation and histone modifications) that lead to changes in gene expression (eg, several transcription factors are susceptible to programmed changes in gene expression through such mechanisms); and 3) permanent effects on the regulation of cellular aging (eg, increases in oxidative stress that lead to macromolecular damage, including that to DNA and specifically to telomeres, can contribute to such effects). Further understanding of such processes will enable the development of preventive and intervention strategies to combat the burden of common diseases such as type 2 diabetes and cardiovascular disease.

  20. Searching for Life on Early Mars: Lessons from the Pilbara

    NASA Technical Reports Server (NTRS)

    Clarke, J. D. A.; Stoker, C. R.

    2016-01-01

    Stromatolites in the Pilbara region of Western Australia constitute the earliest outcrop-scale evidence of life on Earth (Figure 1). The stromatolites in the 3.4 Ga Strelley Pool Formation (SPF) provide an important analog for searching for fossil evidence of early life on Mars, as Noachian aged sediments on Mars were formed under similar environmental conditions. Stromatolites represent possibly the best evidence that could be collected by a rover because they form recognizable macroscopic structures and are often associated with chemical and microscopic evidence.

  1. Reproductive and early life stages pathology - Histopathology workshop report

    USGS Publications Warehouse

    Bruno, D.W.; Nowak, B.; Elliott, D.G.

    2006-01-01

    Pathology occurring during reproduction and larval development represents an important part of the life cycle of fish, and the diseases that affect eggs and larvae often result in significant losses. However, mortality during this period is frequently ignored or poorly researched as the temptation is to replace the losses rather than investigate the causes. A histopathology workshop organised at the newly refurnished laboratory within the Danish Veterinary School was an opportunity to discuss the pathology of selected diseases associated with Reproductive and Early Life Stages Pathology. Several people also kindly provided reference slides.

  2. The Confluence of Adverse Early Experience and Puberty on the Cortisol Awakening Response

    ERIC Educational Resources Information Center

    Quevedo, Karina; Johnson, Anna E.; Loman, Michelle L.; LaFavor, Theresa L.; Gunnar, Megan

    2012-01-01

    Associations between early deprivation/neglect in the form of institutional care with the cortisol awakening response (CAR) were examined as a function of pubertal status among 12- and 13-year-old postinstitutionalized youth. CARs indexed hypothalamic-pituitary-adrenocortical reactivity. Postinstitutionalized youth were compared to youth adopted…

  3. Radiation Therapy Overcomes Adverse Prognostic Role of Cyclooxygenase-2 Expression on Reed-Sternberg Cells in Early Hodgkin Lymphoma

    SciTech Connect

    Mestre, Francisco; Gutiérrez, Antonio; Rodriguez, Jose; Ramos, Rafael; Garcia, Juan Fernando; Martinez-Serra, Jordi; Casasus, Marta; Nicolau, Cristina; Bento, Leyre; Herraez, Ines; Lopez-Perezagua, Paloma; Daumal, Jaime; Besalduch, Joan

    2015-05-01

    Purpose: To analyze the role of radiation therapy (RT) on the adverse prognostic influence of cyclooxygenase-2 (COX-2) expression on Reed-Sternberg (RS) cells, in the setting of early Hodgkin lymphoma (HL) treated with ABVD (adriamycin, vinblastine, bleomycin, dacarbazine). Methods and Materials: In the present study we retrospectively investigated the prognostic value of COX-2 expression in a large (n=143), uniformly treated early HL population from the Spanish Network of HL using tissue microarrays. Univariate and multivariate analyses were done, including the most recognized clinical variables and the potential role of administration of adjuvant RT. Results: Median age was 31 years; the expression of COX-2 defined a subgroup with significantly worse prognosis. Considering COX-2{sup +} patients, those who received RT had significantly better 5-year progression-free survival (PFS) (80% vs 54% if no RT; P=.008). In contrast, COX-2{sup −} patients only had a modest, nonsignificant benefit from RT in terms of 5-year PFS (90% vs 79%; P=.13). When we compared the outcome of patients receiving RT considering the expression of COX-2 on RS cells, we found a nonsignificant 10% difference in terms of PFS between COX-2{sup +} and COX-2{sup −} patients (P=.09), whereas the difference between the 2 groups was important (25%) in patients not receiving RT (P=.04). Conclusions: Cyclooxygenase-2 RS cell expression is an adverse independent prognostic factor in early HL. Radiation therapy overcomes the worse prognosis associated with COX-2 expression on RS cells, acting in a chemotherapy-independent way. Cyclooxygenase-2 RS cell expression may be useful for determining patient candidates with early HL to receive consolidation with RT.

  4. Conditions on Early Mars Might Have Fostered Rapid and Early Development of Life

    NASA Technical Reports Server (NTRS)

    Gibson, Everett K.; McKay, David S.; Thomas-Keprta, Kathie L.; Clemett, Simon J.; Wentworth, Susan J.

    2007-01-01

    The exploration of Mars during the past decades has begun to unveil the history of the planet. The combinations of remote sensing, in situ geochemical compositional measurements and photographic observations from both above and on the surface have shown Mars to have a dynamic and active geologic evolution. Mars geologic evolution clearly had conditions that were suitable for supporting life. For a planet to be able to be habitable, it must have water, carbon sources, energy sources and a dynamic geologic past. Mars meets all of these requirements. The first 600 My of Martian history were ripe for life to develop because of the abundance of (i) Water-carved canyons and oceans or lakes with the early presence of near surface water shown by precipitated carbonates in ALH84001 well-dated at approx.3.9 Gy., (ii) Energy from the original accretional processes, a molten core which generated a strong magnetic field leaving a permanent record in the early crust, early active volcanism continuing throughout Martian history, and, and continuing impact processes, (iii) Carbon and water from possibly extensive volcanic outgassing (i.e. H2O, CO2, CH4, CO, O2, N2, H2S, SO2, etc.) and (iv) some crustal tectonics as revealed by faulting and possible plate movement reflected by the magnetic pattern in the crust. The question arises: "Why would life not evolve from these favorable conditions on early Mars in its first 600 My?" During this period, it seems likely that environmental near-surface conditions on Mars were more favorable to life than at any later time. Standing bodies of water, precipitation and flowing surface water, and possibly abundant hydrothermal energy would all favor the formation of early life. Even if life developed elsewhere (on Earth, Venus, or on other solar systems) and was transported to Mars, the surface conditions were likely very hospitable for that introduced life to multiply and evolve.

  5. Human heterophilic antibodies against equine immunoglobulins: assessment of their role in the early adverse reactions to antivenom administration.

    PubMed

    León, Guillermo; Segura, Alvaro; Herrera, María; Otero, Rafael; França, Francisco Oscar de Siqueira; Barbaro, Katia Cristina; Cardoso, João Luiz Costa; Wen, Fan Hui; de Medeiros, Carlos Roberto; Prado, José Carlos Lopes; Malaque, Ceila María Sant'Ana; Lomonte, Bruno; Gutiérrez, José María

    2008-11-01

    The presence of human heterophilic antibodies against horse immunoglobulins (HHA-HI) was determined by ELISA in sera from healthy volunteers and from patients who received equine antivenom for therapy of snake bite envenoming. These patients were selected from two independent clinical studies: one in Colombia in which patients received antivenom constituted by whole IgG (n=25); and the other in Brazil where an antivenom constituted by F(ab')(2) fragments was administered (n=31). Results show that healthy volunteers have antibodies, mainly of the IgG class, able to react with whole equine IgG. Additionally, patients have IgG antibodies that react both with whole equine IgG and F(ab')(2) fragments. In both clinical studies, no significant differences were observed in the HHA-HI titres between the patients who presented early adverse (anaphylactoid) reactions and those who did not develop them. In addition, no variation in titre was observed in samples collected before and after antivenom administration. These results do not support the hypothesis that the incidence of early adverse reactions to antivenom administration correlates with the titre of HHA-HI in the serum of patients. Nevertheless, participation of these antibodies as part of a multifactorial pathogenic mechanism associated with these reactions cannot be ruled out. PMID:18561967

  6. Early life stress, the development of aggression and neuroendocrine and neurobiological correlates: what can we learn from animal models?

    PubMed

    Veenema, Alexa H

    2009-10-01

    Early life stress (child and adolescent abuse, neglect and trauma) induces robust alterations in emotional and social functioning resulting in enhanced risk for the development of psychopathologies such as mood and aggressive disorders. Here, an overview is given on recent findings in primate and rodent models of early life stress, demonstrating that chronic deprivation of early maternal care as well as chronic deprivation of early physical interactions with peers are profound risk factors for the development of inappropriate aggressive behaviors. Alterations in the hypothalamic-pituitary-adrenocortical (HPA), vasopressin and serotonin systems and their relevance for the regulation of aggression are discussed. Data suggest that social deprivation-induced inappropriate forms of aggression are associated with high or low HPA axis (re)activity and a generally lower functioning of the serotonin system in adulthood. Moreover, genetic and epigenetic modifications in HPA and serotonin systems influence the outcome of early life stress and may even moderate adverse effects of early social deprivation on aggression. A more comprehensive study of aggression, neuroendocrine, neurobiological and (epi)genetic correlates of early life stress using animal models is necessary to provide a better understanding of the invasive aggressive deficits observed in humans exposed to child maltreatment. PMID:19341763

  7. Early spontaneous multiple fetal pregnancy reduction is associated with adverse perinatal outcomes in in vitro fertilization cycles.

    PubMed

    Petrini, Allison C; Pereira, Nigel; Lekovich, Jovana P; Elias, Rony T; Spandorfer, Steven D

    2016-07-01

    The primary objective of this study is to investigate whether early spontaneous multiple fetal pregnancy reduction, also known as vanishing twin syndrome, is associated with adverse perinatal outcomes in fresh in vitro fertilization cycles. This is a retrospective cohort study of women with live singleton births with and without an early vanishing twin after fresh in vitro fertilization. Characteristics compared included incidence of preterm birth, overall birth weight, overall low birth weight, overall very low birth weight, and term low birth weight. In all, 4049 patients with live singleton births were included-853 and 3196 with and without a vanishing twin, respectively. The vanishing twin group had a lower overall birth weight compared to those without (3279.5 ± 369.9 vs 3368.6 ± 567.5 g; p < 0.01). Early vanishing twin was also associated with an increased odds of overall low birth weight (odds ratio: 1.75; 95% confidence interval: 1.36-2.25; p < 0.01) and increased odds of term low birth weight (odds ratio: 3.44; 95% confidence interval: 2.14-5.53; p < 0.01). Our study suggests that early vanishing twin is associated with lower overall birth weight and higher odds of overall low birth weight and term low birth weight in live singleton births after fresh in vitro fertilization. PMID:27638897

  8. Psychosocial problems of donor heart recipients adversely affecting quality of life.

    PubMed

    Bunzel, B; Wollenek, G; Grundböck, A

    1992-10-01

    Heart transplantation has become an accepted therapy for patients suffering from terminal heart disease for whom neither standard forms of medication nor the usual surgery are of any benefit. Although results regarding postoperative quantity and quality of life are encouraging, it must not be overlooked that the patient and his family face, and have to overcome, profound psychosocial problems. The main stressors were identified in interviews with 47 heart transplant patients. The main preoperative problems were: the way of being informed about the diagnosis, the waiting period for transplantation, anguishing doubts about the decision to have a transplant, being a body without heart ('zombie'), guilt and shame regarding the donor, the reactions of others. Postoperatively the patients have to cope with: re-entering social systems, reactions of friends, neighbours and colleagues, rejection episodes, death of a fellow patient, the need to redesign family life. All the problems reported by the patients interviewed are discussed regarding their psychosocial implications, and hints are given on how to minimize them. PMID:1299462

  9. Plate tectonics, surface mineralogy, and the early evolution of life

    NASA Astrophysics Data System (ADS)

    Parnell, J.

    2004-04-01

    In addition to the accepted roles of plate tectonics in regulating planetary habitability through the composition of the atmosphere and temperature, and creating continents to enhance land-based evolution and biodiversity, it has a hitherto unexplored role in influencing surface mineralogy with possible implications for early evolution. Plate tectonics creates continents through the accretion of buoyant granitic crust. Erosion of the granites yields specific minerals including quartz, radioactive (uranium-, thorium-bearing) phases and phosphates, which could play a role in early evolution. Radioactive grains could help to concentrate carbon and increase its complexity through irradiation-induced polymerization at the prebiotic stage, and possibly influence mutation rates once life was established. Weathering of phosphate minerals was an important source of phosphorus for the biochemistry that is essential to life. Quartz-rich sands provide a translucent refuge for early photosynthesizers below the harmful effects of ultra-violet irradiation at the surface. Uranium is also important to the development of nuclear power in an advanced civilization. The mineralogy that engenders these processes is distinct from that to be expected on a planet without plate tectonics, where volcanogenic sediments would predominate, and further emphasizes the importance of plate tectonics to the evolution of life.

  10. Epigenetic changes in early life and future risk of obesity.

    PubMed

    Lillycrop, K A; Burdge, G C

    2011-01-01

    The rapid increase in incidence of obesity over the past two decades cannot be explained solely by genetic and adult lifestyle factors. There is now considerable evidence that the fetal and early postnatal environments also strongly influence the risk of developing obesity in later life. Initially, human studies showed that low birth weight was associated with an increased risk of obesity but increasingly there is evidence that overnutrition in the early life can also increase susceptibility to future obesity. These findings have now been replicated in animal models, which have shown that both maternal under- and overnutrition can induce persistent changes in gene expression and metabolism. The mechanism by which the maternal nutritional environment induces such changes is beginning to be understood and involves the altered epigenetic regulation of specific genes. In this review, we discuss the recent evidence that shows that early-life environment can induce altered epigenetic regulation leading to the induction of an altered phenotype. The demonstration of a role for altered epigenetic regulation of genes in the developmental induction of obesity opens the possibility that interventions, either through nutrition or specific drugs, may modify long-term obesity risk and combat this rapid rise in obesity.

  11. Life Stress Impairs Self-Control in Early Adolescence

    PubMed Central

    Duckworth, Angela L.; Kim, Betty; Tsukayama, Eli

    2013-01-01

    The importance of self-control to a wide range of developmental outcomes prompted the current investigation of negative life events and self-control in early adolescence. In three prospective, longitudinal studies, negative life events reported by the mother (in Study 1) or child (in Studies 2 and 3) predicted rank-order decreases in self-control over time. In all studies, self-control was measured at two different time points using questionnaires completed by three separate raters, including a classroom teacher who knew the child well and two other raters (parents, caregivers, and/or the child himself/herself). Psychological distress measured in Studies 2 and 3 mediated the deleterious effects of negative life events on self-control. These findings extend prior experimental laboratory research documenting the acute effects of stress on self-control. PMID:23443890

  12. Inter-generational social mobility following early life stress.

    PubMed

    Pesonen, Anu-Katriina; Räikkönen, Katri; Kajantie, Eero; Heinonen, Kati; Osmond, Clive; Barker, David J P; Forsén, Tom; Eriksson, Johan G

    2011-06-01

    INTRODUCTION. Socio-economic position (SEP) is a powerful source of health inequality. Less is known of early life conditions that may determine the course of adult SEP. We tested if early life stress (ELS) due to a separation from the parents during World War II predicts adult SEP, trajectories of incomes across the entire working career, and inter-generational social mobility. MATERIALS AND METHODS. Participants (n = 10,702) were from the Helsinki Birth Cohort Study 1934-44. Compared to the non-separated, the separated individuals attained a lower SEP in adulthood. The separated whose fathers were manual workers were less likely to be upwardly mobile from paternal occupation category to higher categories of own occupation, education, and incomes. The separated whose fathers had junior and senior clerical occupations were more likely to be downwardly mobile. Comparison of trajectories of incomes across adulthood showed that the difference between the separated and the non-separated grew larger across time, such that among the separated the incomes decreased. CONCLUSIONS. This life-course study shows that severe ELS due to a separation from parents in childhood is associated with socio-economic disadvantage in adult life. Even high initial SEP in childhood may not protect from the negative effects of ELS. PMID:21366512

  13. Life history and the early origins of health differentials.

    PubMed

    Worthman, Carol M; Kuzara, Jennifer

    2005-01-01

    Current epidemiologic models concerning the fetal origins of later health risk are evaluated from the perspectives of evolutionary and developmental biology. Claims of adaptive value for and biological status of fetal programming are critically examined. Life history theory is applied to identify key trade-offs in adaptive strategies that constrain developmental design to use information from the environment to guide ontogeny and establish cost-benefit trade-offs that weigh early survival advantage against remote or unlikely future costs. Expectable environments of evolutionary adaptedness, particularly of gestation, are characterized and their impact on human adaptive design discussed. The roles of neuroendocrine mechanisms in scaffolding life course development, negotiating ongoing cost-benefit trade-offs, and mediating their long-term impacts on function and health are reviewed in detail. Overviews of gestational biology and the postnatal physiologic, cognitive-affective, and behavioral effects of gestational stress identify a shared central role for the hypothalamic-pituitary-adrenal (HPA) axis. Rather than merely mediating stress responses, the axis emerges an agent of resource allocation that draws a common thread among conditions of gestation, postnatal environments, and functional and health-related outcomes. The preponderance of evolutionary and developmental analysis identifies environments as agents on both sides of the health risk equation, by influencing vulnerabilities and capacities established in early and later life course development, and determining exposures and demands encountered over the life course. PMID:15611966

  14. Inter-generational social mobility following early life stress.

    PubMed

    Pesonen, Anu-Katriina; Räikkönen, Katri; Kajantie, Eero; Heinonen, Kati; Osmond, Clive; Barker, David J P; Forsén, Tom; Eriksson, Johan G

    2011-06-01

    INTRODUCTION. Socio-economic position (SEP) is a powerful source of health inequality. Less is known of early life conditions that may determine the course of adult SEP. We tested if early life stress (ELS) due to a separation from the parents during World War II predicts adult SEP, trajectories of incomes across the entire working career, and inter-generational social mobility. MATERIALS AND METHODS. Participants (n = 10,702) were from the Helsinki Birth Cohort Study 1934-44. Compared to the non-separated, the separated individuals attained a lower SEP in adulthood. The separated whose fathers were manual workers were less likely to be upwardly mobile from paternal occupation category to higher categories of own occupation, education, and incomes. The separated whose fathers had junior and senior clerical occupations were more likely to be downwardly mobile. Comparison of trajectories of incomes across adulthood showed that the difference between the separated and the non-separated grew larger across time, such that among the separated the incomes decreased. CONCLUSIONS. This life-course study shows that severe ELS due to a separation from parents in childhood is associated with socio-economic disadvantage in adult life. Even high initial SEP in childhood may not protect from the negative effects of ELS.

  15. Epigenetic mechanisms elicited by nutrition in early life.

    PubMed

    Canani, Roberto Berni; Costanzo, Margherita Di; Leone, Ludovica; Bedogni, Giorgio; Brambilla, Paolo; Cianfarani, Stefano; Nobili, Valerio; Pietrobelli, Angelo; Agostoni, Carlo

    2011-12-01

    A growing number of studies focusing on the developmental origin of health and disease hypothesis have identified links among early nutrition, epigenetic processes and diseases also in later life. Different epigenetic mechanisms are elicited by dietary factors in early critical developmental ages that are able to affect the susceptibility to several diseases in adulthood. The studies here reviewed suggest that maternal and neonatal diet may have long-lasting effects in the development of non-communicable chronic adulthood diseases, in particular the components of the so-called metabolic syndrome, such as insulin resistance, type 2 diabetes, obesity, dyslipidaemia, hypertension, and CVD. Both maternal under- and over-nutrition may regulate the expression of genes involved in lipid and carbohydrate metabolism. Early postnatal nutrition may also represent a vital determinant of adult health by making an impact on the development and function of gut microbiota. An inadequate gut microbiota composition and function in early life seems to account for the deviant programming of later immunity and overall health status. In this regard probiotics, which have the potential to restore the intestinal microbiota balance, may be effective in preventing the development of chronic immune-mediated diseases. More recently, the epigenetic mechanisms elicited by probiotics through the production of SCFA are hypothesised to be the key to understand how they mediate their numerous health-promoting effects from the gut to the peripheral tissues.

  16. Early Life on Earth: the Ancient Fossil Record

    NASA Astrophysics Data System (ADS)

    Westall, F.

    2004-07-01

    The evidence for early life and its initial evolution on Earth is lin= ked intimately with the geological evolution of the early Earth. The environment of the early Earth would be considered extreme by modern standards: hot (50-80=B0C), volcanically and hydrothermally active, a= noxic, high UV flux, and a high flux of extraterrestrial impacts. Habitats = for life were more limited until continent-building processes resulted in= the formation of stable cratons with wide, shallow, continental platforms= in the Mid-Late Archaean. Unfortunately there are no records of the first appearance of life and the earliest isotopic indications of the exist= ence of organisms fractionating carbon in ~3.8 Ga rocks from the Isua greenst= one belt in Greenland are tenuous. Well-preserved microfossils and micro= bial mats (in the form of tabular and domical stromatolites) occur in 3.5-= 3.3 Ga, Early Archaean, sedimentary formations from the Barberton (South Afri= ca) and Pilbara (Australia) greenstone belts. They document life forms that = show a relatively advanced level of evolution. Microfossil morphology inclu= des filamentous, coccoid, rod and vibroid shapes. Colonial microorganism= s formed biofilms and microbial mats at the surfaces of volcaniclastic = and chemical sediments, some of which created (small) macroscopic microbi= alites such as stromatolites. Anoxygenic photosynthesis may already have developed. Carbon, nitrogen and sulphur isotopes ratios are in the r= ange of those for organisms with anaerobic metabolisms, such as methanogenesi= s, sulphate reduction and photosynthesis. Life was apparently distribute= d widely in shallow-water to littoral environments, including exposed, evaporitic basins and regions of hydrothermal activity. Biomass in t= he early Archaean was restricted owing to the limited amount of energy t= hat could be produced by anaerobic metabolisms. Microfossils resembling o= xygenic photosynthesisers, such as cyanobacteria, probably first occurred in

  17. Lack of Emotional Support from Parents Early in Life and Alcohol Abuse Later in Life

    ERIC Educational Resources Information Center

    Shaw, Benjamin A.

    2006-01-01

    The purpose of this study is to examine the association between lacking emotional support from parents early in life and adult alcohol abuse. A series of logistic regression models were run with data collected from a nationally representative sample of over 2,500 adults ages 25-74. The findings reveal a linear relationship between level of…

  18. Early Childhood Education Teachers: Life History, Life Course, and the Problem of Family-Work Balance

    ERIC Educational Resources Information Center

    Bullough, Robert V., Jr.

    2016-01-01

    In contrast to the wider education literature, rather little is known about the lives of early childhood education (ECE) teachers and the impact of those lives on their practice. Drawing on surveys completed by Head Start assistant and lead teachers, teacher lifelines, and interviews, and through the lens of life-course theory, the author portrays…

  19. Early adversity and combat exposure interact to influence anterior cingulate cortex volume in combat veterans☆

    PubMed Central

    Woodward, Steven H.; Kuo, Janice R.; Schaer, Marie; Kaloupek, Danny G.; Eliez, Stephan

    2013-01-01

    Objective Childhood and combat trauma have been observed to interact to influence amygdala volume in a sample of U.S. military veterans with and without PTSD. This interaction was assessed in a second, functionally-related fear system component, the pregenual and dorsal anterior cingulate cortex, using the same sample and modeling approach. Method Anterior cingulate cortical tissues (gray + white matter) were manually-delineated in 1.5 T MR images in 87 U.S. military veterans of the Vietnam and Persian Gulf wars. Hierarchical multiple regression modeling was used to assess associations between anterior cingulate volume and the following predictors, trauma prior to age 13, combat exposure, the interaction of early trauma and combat exposure, and PTSD diagnosis. Results As previously observed in the amygdala, unique variance in anterior cingulate cortical volume was associated with both the diagnosis of PTSD and with the interaction of childhood and combat trauma. The pattern of the latter interaction indicated that veterans with childhood trauma exhibited a significant inverse linear relationship between combat trauma and anterior cingulate volume while those without childhood trauma did not. Such associations were not observed in hippocampal or total cerebral tissue volumes. Conclusions In the dorsal anterior cingulate cortex, as in the amygdala, early trauma may confer excess sensitivity to later combat trauma. PMID:24179818

  20. Skeletal adverse effects with aromatase inhibitors in early breast cancer: evidence to date and clinical guidance

    PubMed Central

    Servitja, Sonia; Martos, Tamara; Rodriguez Sanz, Maria; Garcia-Giralt, Natalia; Prieto-Alhambra, Daniel; Garrigos, Laia; Nogues, Xavier

    2015-01-01

    Aromatase inhibitors (AIs) are routinely used in the adjuvant treatment of women with hormone receptor-positive early breast cancer. Patients who receive AIs have an increased risk of bone loss and arthralgia compared with those treated with tamoxifen. In addition to the effects of AIs, the population of women with early breast cancer has a high prevalence of 25-hydroxyvitamin D (25(OH)D) insufficiency. In our experience 88% of patients had concentrations lower than 30 ng/ml. Vitamin D supplementation should be adapted to the baseline concentration. Another relevant finding in our research program was the close relationship between 25(OH)D levels and intensity of AI-related arthralgia (AIrA). A target concentration of 40 ng/ml 25(OH)D may prevent development of AIrA. We also demonstrate that AIrA is genetically determined: single nucleotide polymorphisms located in genes encoding key factors for the metabolism of estrogens and vitamin D (CYP17A1, VDR, and CYP27B1) are associated with self-reported arthralgia during AI therapy. We recommend establishing an individualized protocol of bone-health surveillance based on baseline and evolutionary clinical variables. PMID:26327926

  1. Adverse Life Events and Emotional and Behavioral Problems in Adolescence: The Role of Non-Verbal Cognitive Ability and Negative Cognitive Errors

    ERIC Educational Resources Information Center

    Flouri, Eirini; Panourgia, Constantina

    2011-01-01

    The aim of this study was to test whether negative cognitive errors (overgeneralizing, catastrophizing, selective abstraction, and personalizing) mediate the moderator effect of non-verbal cognitive ability on the association between adverse life events (life stress) and emotional and behavioral problems in adolescence. The sample consisted of 430…

  2. 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

  3. Early life exposures and risk of atopy among Danish children.

    PubMed

    Thomsen, Simon F; Ulrik, Charlotte S; Porsbjerg, Celeste; Backer, Vibeke

    2006-01-01

    A large proportion of atopy develops in childhood and early life exposures are suspected to play a considerable role in the inception. The aim of this study was to examine the association between early life exposures and development of atopic disease in children. We performed a case-cohort study of a random population-based sample of children (n = 480) 7-17 years of age, living in urban Copenhagen, Denmark. Information on breast-feeding, supplementation, wheezy bronchitis, use of antibiotics, and parental smoking during pregnancy and in early life was obtained retrospectively by questionnaire. Skin test reactivity to 10 common aeroallergens was measured using standard techniques. Atopic disease was defined as a history of hayfever and/or asthma concomitantly with a positive skin-prick test. Logistic regression showed that parental atopy (odds ratio [OR] = 1.98; 95% confidence interval [CI], 1.12, 3.49; p = 0.019) and wheezy bronchitis before the age of 2 years (OR = 3.13; 95% CI, 1.63, 6.01; p < 0.001) were predictors of atopic disease, the latter especially when predisposition to atopy was present (OR = 8.63; 95% CI, 3.64, 20.44; p < 0.001). Duration of breast-feeding was longer in subjects with atopic heredity (p = 0.017), whereas smoking exposure during pregnancy (p = 0.019) and in the 1st year of life (p = 0.018) was less prevalent. Wheezy bronchitis was equally frequent among subjects with and without atopic predisposition (p = 0.893). Wheezy bronchitis before the age of 2 years seems to be independent of familial predisposition to atopic disease and significantly increases the likelihood for development of atopy in genetically susceptible individuals. Parental knowledge of atopic heredity significantly influences smoking and breast-feeding habits.

  4. In utero arsenic exposure in mice and early life susceptibility to cancer.

    PubMed

    Garry, Michael R; Santamaria, Annette B; Williams, Amy L; DeSesso, John M

    2015-10-01

    In its review of the U.S. Environmental Protection Agency's toxicological review of inorganic arsenic (iAs), the National Academy of Sciences identified carcinogenic endpoints among the highest priority health effects of concern and stated the need to consider evidence that early life exposures may increase the risk of adverse health effects. Recent studies in mice suggest that in utero exposure to arsenic increases susceptibility to cancer later in life. These data are striking in light of the general lack of evidence for carcinogenicity in rodents exposed to iAs. To evaluate the transplacental carcinogenic potential of iAs, a detailed analysis of the toxicology literature evaluating the role of in utero arsenic exposure in carcinogenesis was conducted. Bladder, lung, and skin tumors, which are the tumor types most consistently reported in humans exposed to high arsenic levels, were not consistently increased in mouse studies. There was also a lack of concordance across studies for other tumor types not typically reported in humans. Therefore, we considered methodological and other critical issues that may have contributed to variable results and we suggest additional studies to address these issues. It was concluded that the available data do not provide evidence of a causal link between in utero arsenic exposure and cancer or indicate early life-stage susceptibility to arsenic-induced cancer, particularly at environmentally relevant doses.

  5. Urinary catheterization may not adversely impact quality of life in multiple sclerosis patients.

    PubMed

    James, Rebecca; Frasure, Heidi E; Mahajan, Sangeeta T

    2014-01-01

    Background. Multiple sclerosis (MS) healthcare providers (HCP) have undergone considerable educational efforts regarding the importance of evaluating and treating pelvic floor disorders, specifically, urinary dysfunction. However, limited data are available to determine the impact of catheterization on patient quality of life (QoL). Objectives. To describe the use of urinary catheterization among MS patients and determine the differences between those who report positive versus negative impact of this treatment on QoL. Methods. Patients were queried as part of the 2010 North American Research Committee On Multiple Sclerosis survey; topics included 1) urinary/bladder, bowel, or sexual problems; 2) current urine leakage; 3) current catheter use; 4) catheterizing and QoL. Results. Respondents with current urine leakage were 5143 (54.7%), of which 1201 reported current catheter use (12.8%). The types of catheters (intermittent self-catheterization and Foley catheter (indwelling and suprapubic)) did not differ significantly. Of the current catheter users, 304 (25.35%) respondents reported catheterization negatively impacting QoL, 629 (52.4%) reported a positive impact on QoL, and 223 (18.6%) reported neutral QoL. Conclusions. A large proportion of catheterized MS patients report negative or positive changes in QoL associated with urinary catheterization. Urinary catheterization does not appear to have a universally negative impact on patient QoL. PMID:25006498

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

    PubMed Central

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

    2015-01-01

    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. PMID:26049556

  7. TGFB1 Single Nucleotide Polymorphisms Are Associated With Adverse Quality of Life in Prostate Cancer Patients Treated With Radiotherapy

    SciTech Connect

    Peters, Christopher A. Stock, Richard G.; Cesaretti, Jamie A.; Atencio, David P.; Peters, Sheila B.A.; Burri, Ryan J.; Stone, Nelson N.; Ostrer, Harry; Rosenstein, Barry S.

    2008-03-01

    Purpose: To investigate whether the presence of single nucleotide polymorphisms (SNPs) located within TGFB1 might be predictive for the development of adverse quality-of-life outcomes in prostate cancer patients treated with radiotherapy. Methods and Materials: A total of 141 prostate cancer patients treated with radiotherapy were screened for SNPs in TGFB1 using DNA sequencing. Three quality-of-life outcomes were investigated: (1) prospective decline in erectile function, (2) urinary quality of life, and (3) rectal bleeding. Median follow-up was 51.3 months (range, 12-138 months; SD, 24.4 months). Results: Those patients who possessed either the T/T genotype at position -509, the C/C genotype at position 869 (pro/pro, codon 10) or the G/C genotype at position 915 (arg/pro, codon 25) were significantly associated with the development of a decline in erectile function compared with those who did not have these genotypes: 56% (9 of 16) vs. 24% (11 of 45) (p = 0.02). In addition, patients with the -509 T/T genotype had a significantly increased risk of developing late rectal bleeding compared with those who had either the C/T or C/C genotype at this position: 55% (6 of 11) vs. 26% (34 of 130) (p = 0.05). Conclusions: Possession of certain TGFB1 genotypes is associated with the development of both erectile dysfunction and late rectal bleeding in patients treated with radiotherapy for prostate cancer. Therefore, identification of patients harboring these genotypes may represent a means to predict which men are most likely to suffer from poor quality-of-life outcomes after radiotherapy for prostate cancer.

  8. Early-life experience, epigenetics, and the developing brain.

    PubMed

    Kundakovic, Marija; Champagne, Frances A

    2015-01-01

    Development is a dynamic process that involves interplay between genes and the environment. In mammals, the quality of the postnatal environment is shaped by parent-offspring interactions that promote growth and survival and can lead to divergent developmental trajectories with implications for later-life neurobiological and behavioral characteristics. Emerging evidence suggests that epigenetic factors (ie, DNA methylation, posttranslational histone modifications, and small non-coding RNAs) may have a critical role in these parental care effects. Although this evidence is drawn primarily from rodent studies, there is increasing support for these effects in humans. Through these molecular mechanisms, variation in risk of psychopathology may emerge, particularly as a consequence of early-life neglect and abuse. Here we will highlight evidence of dynamic epigenetic changes in the developing brain in response to variation in the quality of postnatal parent-offspring interactions. The recruitment of epigenetic pathways for the biological embedding of early-life experience may also have transgenerational consequences and we will describe and contrast two routes through which this transmission can occur: experience dependent vs germline inheritance. Finally, we will speculate regarding the future directions of epigenetic research and how it can help us gain a better understanding of the developmental origins of psychiatric dysfunction. PMID:24917200

  9. Differential Susceptibility to Early Literacy Intervention in Children with Mild Perinatal Adversities: Short- and Long-Term Effects of a Randomized Control Trial

    ERIC Educational Resources Information Center

    Van der Kooy-Hofland, Verna A. C.; Van der Kooy, Jacoba; Bus, Adriana G.; van IJzendoorn, Marinus H.; Bonsel, Gouke J.

    2012-01-01

    In a randomized control trial, the authors tested whether short- and long-term effects of an early literacy intervention are moderated by mild perinatal adversities in accordance with differential susceptibility theory. One-hundred 5-year-old children (58% male) who scored at or below the 30th percentile on early literacy measures were randomized…

  10. Biomarkers as tracers for life on early earth and Mars

    NASA Technical Reports Server (NTRS)

    Simoneit, B. R.; Summons, R. E.; Jahnke, L. L.

    1998-01-01

    Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.

  11. Biomarkers as tracers for life on early earth and Mars.

    PubMed

    Simoneit, B R; Summons, R E; Jahnke, L L

    1998-10-01

    Biomarkers in geological samples are products derived from biochemical (natural product) precursors by reductive and oxidative processes (e.g., cholestanes from cholesterol). Generally, lipids, pigments and biomembranes are preserved best over longer geological times and labile compounds such as amino acids, sugars, etc. are useful biomarkers for recent times. Thus, the detailed characterization of biomarker compositions permits the assessment of the major contributing species of extinct and/or extant life. In the case of the early Earth, work has progressed to elucidate molecular structure and carbon isotropic signals preserved in ancient sedimentary rocks. In addition, the combination of bacterial biochemistry with the organic geochemistry of contemporary and ancient hydrothermal ecosystems permits the modeling of the nature, behavior and preservation potential of primitive microbial communities. This approach uses combined molecular and isotopic analyses to characterize lipids produced by cultured bacteria (representative of ancient strains) and to test a variety of culture conditions which affect their biosynthesis. On considering Mars, the biomarkers from lipids and biopolymers would be expected to be preserved best if life flourished there during its early history (3.5-4 x 10(9) yr ago). Both oxidized and reduced products would be expected. This is based on the inferred occurrence of hydrothermal activity during that time with the concomitant preservation of biochemically-derived organic matter. Both known biomarkers (i.e., as elucidated for early terrestrial samples and for primitive terrestrial microbiota) and novel, potentially unknown compounds should be characterized.

  12. Early Local Recurrence Presents Adverse Effect on Outcomes of Primary Breast Sarcoma

    PubMed Central

    Hu, Qun-Chao; Mei, Xin; Feng, Yan; Ma, Jin-Li; Yang, Zhao-Zhi; Shao, Zhi-Min; Yu, Xiao-Li; Guo, Xiao-Mao

    2016-01-01

    Abstract Primary breast sarcomas (PBSs) are spectrum heterogeneous sarcomas in breast and the optimal treatment for them is still under discussion. Our study was to investigate clinical characteristics and identify potential prognostic factors for this rare malignancy. The authors retrospectively reviewed 38 patients with PBSs between October 2000 and February 2014 in FuDan University Shanghai Cancer Center. Local control rate and overall survival (OS) were determined by Kaplan–Meier actuarial method. Univariate analysis and Cox proportional hazards model were applied to identify potential prognostic factors. With median follow-up of 40.19 months, 14 patients (14/38) were found with local recurrence. Extensive operation like mastectomy was not superior to local resection (P = 0.167). Three-year recurrence-free survival and OS rate were 61.9% and 89%, respectively. Larger tumor size and local recurrence were indicated as unfavorable prognostic factors in univariate analysis. Cox model identified narrow interval of recurrence free survival as an unfavorable factor (P = 0.048). Surgery remains crucial treatment for PBSs. Mastectomy, however, is not routinely necessary if clear margin could be achieved by local excision. Early recurrence indicates a poor OS. PMID:26735546

  13. High dose ursodeoxycholic acid increases risk of adverse outcomes in patients with early stage primary sclerosing cholangitis

    PubMed Central

    Imam, Mohamad H.; Sinakos, Emmanouil; Gossard, Andrea A.; Kowdley, Kris V.; Luketic, Velimir A. C.; Harrison, M. Edwyn; McCashland, Timothy; Befeler, Alex S.; Harnois, Denise; Jorgensen, Roberta; Petz, Jan; Keach, Jill; DeCook, Alisha C.; Enders, Felicity; Lindor, Keith D.

    2013-01-01

    Background Ursodeoxycholic acid (UDCA) in a dose of 28–30 mg/kg/day increases the likelihood of clinical deterioration of primary sclerosing cholangitis (PSC) patients. Aim Our aim was to compare the risk of adverse clinical endpoints in patients with varying disease status. Methods We reviewed records from patients previously enrolled in a study evaluating the effects of high-dose (28–30 mg/kg/day) UDCA in PSC. Patients were grouped according to treatment (UDCA vs. placebo) and baseline disease status (histologic stage of PSC, total serum bilirubin). Development of clinical endpoints including death, liver transplantation, cirrhosis, esophageal varices and cholangiocarcinoma was sought. Results One hundred fifty patients were included of which 49 patients developed endpoints. There was an increased development of endpoints amongst patients using UDCA vs. placebo (14 vs. 4, p = 0.0151) with early histologic disease (stage 1–2, n = 88) but not with late stage (stage 3–4, n = 62) disease (17 vs. 14, p = 0.2031). Occurrence of clinical endpoints was also higher in patients receiving UDCA vs. placebo (16 vs. 2, p = 0.0008) with normal bilirubin levels (total bilirubin ≤ 1.0 mg/dl) but not in patients with elevated bilirubin levels (15 vs. 16, p = 0.6018). Among patients not reaching endpoints 31.68% had normalization of their alkaline phosphatase levels as compared to 14.29% in patients who reached endpoints (p = 0.073). Conclusion The increased risk of adverse events with UDCA treatment as compared to placebo is only apparent in patients with early histologic stage disease or normal total bilirubin. PMID:21957881

  14. The composition of the gut microbiota throughout life, with an emphasis on early life

    PubMed Central

    Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R. Paul; Kober, Olivia I.; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C.; Marchesi, Julian R.; Collado, Maria Carmen

    2015-01-01

    The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3–5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health. PMID:25651996

  15. The composition of the gut microbiota throughout life, with an emphasis on early life.

    PubMed

    Rodríguez, Juan Miguel; Murphy, Kiera; Stanton, Catherine; Ross, R Paul; Kober, Olivia I; Juge, Nathalie; Avershina, Ekaterina; Rudi, Knut; Narbad, Arjan; Jenmalm, Maria C; Marchesi, Julian R; Collado, Maria Carmen

    2015-01-01

    The intestinal microbiota has become a relevant aspect of human health. Microbial colonization runs in parallel with immune system maturation and plays a role in intestinal physiology and regulation. Increasing evidence on early microbial contact suggest that human intestinal microbiota is seeded before birth. Maternal microbiota forms the first microbial inoculum, and from birth, the microbial diversity increases and converges toward an adult-like microbiota by the end of the first 3-5 years of life. Perinatal factors such as mode of delivery, diet, genetics, and intestinal mucin glycosylation all contribute to influence microbial colonization. Once established, the composition of the gut microbiota is relatively stable throughout adult life, but can be altered as a result of bacterial infections, antibiotic treatment, lifestyle, surgical, and a long-term change in diet. Shifts in this complex microbial system have been reported to increase the risk of disease. Therefore, an adequate establishment of microbiota and its maintenance throughout life would reduce the risk of disease in early and late life. This review discusses recent studies on the early colonization and factors influencing this process which impact on health.

  16. Early life stress and hippocampal neurogenesis in the neonate: sexual dimorphism, long term consequences and possible mediators

    PubMed Central

    Lajud, Naima; Torner, Luz

    2015-01-01

    Adverse early life experience decreases adult hippocampal neurogenesis and results in increased vulnerability to neuropsychiatric disorders. Despite that the effects of postnatal stress on neurogenesis have been widely studied in adult individuals, few efforts have been done to evaluate its immediate effects on the developing hippocampus. Moreover, it is not clear whether postnatal stress causes a differential impact in hippocampus development in male and female neonates that could be related to emotional deficits in adulthood. It has been proposed that the long term effects of early stress exposure rise from a persistent HPA axis activation during sensitive time windows; nevertheless the exact mechanisms and mediators remain unknown. Here, we summarize the immediate and late effects of early life stress on hippocampal neurogenesis in male and female rat pups, compare its later consequences in emotionality, and highlight some relevant mediator peptides that could be potentially involved in programming. PMID:25741234

  17. Early life stress and hippocampal neurogenesis in the neonate: sexual dimorphism, long term consequences and possible mediators.

    PubMed

    Lajud, Naima; Torner, Luz

    2015-01-01

    Adverse early life experience decreases adult hippocampal neurogenesis and results in increased vulnerability to neuropsychiatric disorders. Despite that the effects of postnatal stress on neurogenesis have been widely studied in adult individuals, few efforts have been done to evaluate its immediate effects on the developing hippocampus. Moreover, it is not clear whether postnatal stress causes a differential impact in hippocampus development in male and female neonates that could be related to emotional deficits in adulthood. It has been proposed that the long term effects of early stress exposure rise from a persistent HPA axis activation during sensitive time windows; nevertheless the exact mechanisms and mediators remain unknown. Here, we summarize the immediate and late effects of early life stress on hippocampal neurogenesis in male and female rat pups, compare its later consequences in emotionality, and highlight some relevant mediator peptides that could be potentially involved in programming.

  18. The potential adverse effect of energy drinks on executive functions in early adolescence

    PubMed Central

    Van Batenburg-Eddes, Tamara; Lee, Nikki C.; Weeda, Wouter D.; Krabbendam, Lydia; Huizinga, Mariette

    2014-01-01

    Introduction: Manufacturers of energy drinks (EDs) claim their products improve cognitive performance. Young adolescents are in a critical developmental phase. The impact of ED intake on their development is not yet clear. Therefore, we studied the associations of both caffeine intake and ED consumption with executive functions (EFs), and the role of pubertal status and sleeping problems. Methods: A sample of 509 participants (mean age: 13.1 years, SD 0.85; age range: 11–16 years) participated in the study. The level of pubertal development was classified in five pubertal status categories. Participants were asked to report their caffeine (for example coffee) and ED consumption for each day of the week. In addition, they indicated sleep quality by reporting problems falling asleep or waking up and/or interrupted sleep. EFs were assessed by self- and parent reports of the Behavior Rating Inventory of Executive Function (BRIEF). Results: Consuming on average one or more ED(s) a day was associated with more problems in self-reported behavior regulation and metacognition, and with more problems in parent-reported metacognition. Only high caffeine consumption (two or more cups a day) was associated with parent-reported problems with metacognition. The sum of caffeine and ED use was associated with a higher amount of problems with self-reported metacognition and parent reported behavior regulation. The effect estimates for the association between caffeine and ED use combined and EFs did not exceed those of EDs or caffeine separately. Adjusting for pubertal status, gender, educational level, number of sleeping problems and hours of sleep did not change the effect estimates substantially. Conclusion: The observed associations between ED consumption and EFs suggest that regular consumption of EDs—even in moderate amounts—may have a negative impact on daily life behaviors related to EF in young adolescents. PMID:24904473

  19. LIFE: The Case for Early Commercialization of Fusion Energy

    SciTech Connect

    Anklam, T; Simon, A J; Powers, S; Meier, W R

    2010-11-30

    This paper presents the case for early commercialization of laser inertial fusion energy (LIFE). Results taken from systems modeling of the US electrical generating enterprise quantify the benefits of fusion energy in terms of carbon emission, nuclear waste and plutonium production avoidance. Sensitivity of benefits-gained to timing of market-entry is presented. These results show the importance of achieving market entry in the 2030 time frame. Economic modeling results show that fusion energy can be competitive with other low-carbon energy sources. The paper concludes with a description of the LIFE commercialization path. It proposes constructing a demonstration facility capable of continuous fusion operations within 10 to 15 years. This facility will qualify the processes and materials needed for a commercial fusion power plant.

  20. Philosophical Approaches towards Sciences of Life in Early Cybernetics

    NASA Astrophysics Data System (ADS)

    Montagnini, Leone

    2008-07-01

    The article focuses on the different conceptual and philosophical approaches towards the sciences of life operating in the backstage of Early Cybernetics. After a short reconstruction of the main steps characterizing the origins of Cybernetics, from 1940 until 1948, the paper examines the complementary conceptual views between Norbert Wiener and John von Neumann, as a "fuzzy thinking" versus a "logical thinking", and the marked difference between the "methodological individualism" shared by both of them versus the "methodological collectivism" of most of the numerous scientists of life and society attending the Macy Conferences on Cybernetics. The main thesis sustained here is that these different approaches, quite invisible to the participants, were different, maybe even opposite, but they could provoke clashes, as well as cooperate in a synergic way.

  1. The future is now: early life events preset adult behaviour.

    PubMed

    Patchev, A V; Rodrigues, A J; Sousa, N; Spengler, D; Almeida, O F X

    2014-01-01

    To consider the evidence that human and animal behaviours are epigenetically programmed by lifetime experiences. Extensive PubMed searches were carried out to gain a broad view of the topic, in particular from the perspective of human psychopathologies such as mood and anxiety disorders. The selected literature cited is complemented by previously unpublished data from the authors' laboratories. Evidence that physiological and behavioural functions are particularly sensitive to the programming effects of environmental factors such as stress and nutrition during early life, and perhaps at later stages of life, is reviewed and extended. Definition of stimulus- and function-specific critical periods of programmability together with deeper understanding of the molecular basis of epigenetic regulation will deliver greater appreciation of the full potential of the brain's plasticity while providing evidence-based social, psychological and pharmacological interventions to promote lifetime well-being.

  2. Early Life Circumstances as Contributors to HIV Infection

    PubMed Central

    Siegel, Karolynn; Lekas, Helen-Maria; Ramjohn, Destiny; Schrimshaw, Eric W.; VanDevanter, Nancy

    2015-01-01

    Adolescents may come from family settings that heighten their vulnerability to early sexual initiation, promiscuity and sexual exploitation. To illuminate how this may occur, we present a set of five representative cases of HIV-infected females from a sample of 26 adolescent and young adult HIV-infected females (ages 16–24) enrolled in a study about the adaptive challenges people their age faced living with the disease. Study participants were recruited from five New York City adolescent HIV clinics that provided comprehensive specialty medical and supportive ancillary social services to adolescents and young adults with HIV. Study participants completed a battery of standardizes measures, using ACASI, and participated in a semi-structured in-depth interview. Using the qualitative interview data, we illustrate how early life and family circumstances including neglectful or dysfunctional parenting (e.g., low parental supervision), sexual abuse, and unstable housing placed these young women on a risk trajectory for HIV infection. PMID:25397349

  3. Possible sequelae of trauma and somatic disorder in early life.

    PubMed

    Weinberger, J L; Kantor, M

    All children experience trauma. The age, state of development and constitutional factors will determine whether some children will have a traumatic effect. Trauma occurring before the age of three, at a time when the ego has not developed its synthetic and integrative functions, may be reproduced in later life as an isolated symptom, by selected sensations involved in a sensory imprint or screen sensation of the trauma as a simple recording. After the age of three, under the influence of a more mature ego, excessive traumatic stimuli will be integrated and elaborated in symptom formations as phobias or other conditions and extended as part of the total personality. Recurrence in later life is triggered by events related not only to the original experience, but also to the content of its elaboration. The earlier in life the trauma occurs, the more likely that somatic imprints of primitive physiological symptoms would result as an archaic, biological defense or screen sensations. Recurrent sensory imprints or screens may appear as organic illness or functional somatic symptoms. Diagnostically, a detailed early life history is necessary to uncover the presence of a sensory screen memory of a trauma and so avoid diagnostic medical search for organic causation. Case material illustrating the two groups are presented. Indications for psychoanalysis and for supportive psychotherapy are discussed from our theoretical framework as well as from the literature. PMID:1052208

  4. In vivo research using early life stage models.

    PubMed

    Seabra, Rita; Bhogal, Nirmala

    2010-01-01

    Scientists, for a variety of reasons, need to carry out in vivo research. Since experiments that require the use of adult animals pose various logistical, economical and ethical issues, the use of embryonic and larval forms of some organisms are potentially attractive alternatives. Early life stages are appealing because, in general, large numbers of individuals can be maintained in relatively simple housing, minimising costs, and their use involves fewer legal formalities. With this succinct review, we aim to provide an overview of different biological issues that have been successfully explored with the help of eggs, embryos and larvae from the frog, zebrafish and chicken.

  5. Early-Life Origins of the Race Gap in Men's Mortality

    ERIC Educational Resources Information Center

    Warner, David F.; Hayward, Mark D.

    2006-01-01

    Using a life course framework, we examine the early life origins of the race gap in men's all-cause mortality. Using the National Longitudinal Survey of Older Men (1966-1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life…

  6. Early life exposure to fructose and offspring phenotype: implications for long term metabolic homeostasis.

    PubMed

    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.

  7. 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. PMID:25120258

  8. Early life exposure to fructose and offspring phenotype: implications for long term metabolic homeostasis.

    PubMed

    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

  9. Evidence on early-life income and late-life health from America's Dust Bowl era.

    PubMed

    Cutler, David M; Miller, Grant; Norton, Douglas M

    2007-08-14

    In recent decades, elderly Americans have enjoyed enormous gains in longevity and reductions in disability. The causes of this progress remain unclear, however. This paper investigates the role of fetal programming, exploring how economic progress early in the 20th century might be related to declining disability today. Specifically, we match sudden unexpected economic changes experienced in utero in America's Dust Bowl during the Great Depression to unusually detailed individual-level information about old-age disability and chronic disease. We are unable to detect any meaningful relationship between early life factors and outcomes in later life. We conclude that, if such a relationship exists in the United States, it is most likely not a quantitatively important explanation for declining disability today.

  10. Evidence on early-life income and late-life health from America's Dust Bowl era.

    PubMed

    Cutler, David M; Miller, Grant; Norton, Douglas M

    2007-08-14

    In recent decades, elderly Americans have enjoyed enormous gains in longevity and reductions in disability. The causes of this progress remain unclear, however. This paper investigates the role of fetal programming, exploring how economic progress early in the 20th century might be related to declining disability today. Specifically, we match sudden unexpected economic changes experienced in utero in America's Dust Bowl during the Great Depression to unusually detailed individual-level information about old-age disability and chronic disease. We are unable to detect any meaningful relationship between early life factors and outcomes in later life. We conclude that, if such a relationship exists in the United States, it is most likely not a quantitatively important explanation for declining disability today. PMID:17686988

  11. Could the early environment of Mars have supported the development of life?

    NASA Technical Reports Server (NTRS)

    Mckay, Christopher P.; Stoker, Carol R.

    1990-01-01

    The environment of Mars and its correlation to the origin of life on earth are examined. Evidence of liquid water and nitrogen on early Mars is discussed. The similarities between the early Mars and early earth environments are described.

  12. Early life mortality and height in Indian states

    PubMed Central

    Coffey, Diane

    2014-01-01

    Height is a marker for health, cognitive ability and economic productivity. Recent research on the determinants of height suggests that postneonatal mortality predicts height because it is a measure of the early life disease environment to which a cohort is exposed. This article advances the literature on the determinants of height by examining the role of early life mortality, including neonatal mortality, in India, a large developing country with a very short population. It uses state level variation in neonatal mortality, postneonatal mortality, and pre-adult mortality to predict the heights of adults born between 1970 and 1983, and neonatal and postneonatal mortality to predict the heights of children born between 1995 and 2005. In contrast to what is found in the literature on developed countries, I find that state level variation in neonatal mortality is a strong predictor of adult and child heights. This may be due to state level variation in, and overall poor levels of, pre-natal nutrition in India. PMID:25499239

  13. Early Life Manipulations Alter Learning and Memory in Rats

    PubMed Central

    Kosten, Therese A; Kim, Jeansok J; Lee, Hongjoo J.

    2012-01-01

    Much research shows early life manipulations have enduring behavioral, neural, and hormonal effects. However, findings of learning and memory performance vary widely across studies. We reviewed studies in which pre-weaning rat pups were exposed to stressors and tested on learning and memory tasks in adulthood. Tasks were classified as aversive conditioning, inhibitory learning, or spatial/relational memory. Variables of duration, type, and timing of neonatal manipulation and sex and strain of animals were examined to determine if any predict enhanced or impaired performance. Brief separations enhanced and prolonged separations impaired performance on spatial/relational tasks. Performance was impaired in aversive conditioning and enhanced in inhibitory learning tasks regardless of manipulation duration. Opposing effects on performance for spatial/relational memory also depended upon timing of manipulation. Enhanced performance was likely if the manipulation occurred during postnatal week 3 but performance was impaired if it was confined to the first two postnatal weeks. Thus, the relationship between early life experiences and adulthood learning and memory performance is multifaceted and decidedly task-dependent. PMID:22819985

  14. Effects of hydroelectric turbine passage on fish early life stages

    SciTech Connect

    Cada, G.F.

    1991-01-01

    Turbine-passage mortality has been studied extensively for juveniles and adults of migratory fish species, but few studies have directly quantified mortality of fish eggs and larvae. An analysis of literature relating to component stresses of turbine passage (i.e., pressure changes, blade contact, and shear) indicates that mortality of early life stages of fish would be relatively low at low-head, bulb turbine installations. The shear forces and pressure regimes normally experienced are insufficient to cause high mortality rates. The probability of contact with turbine blades is related to the size of the fish; less than 5% of entrained ichthyoplankton would be killed by the blades in a bulb turbine. Other sources of mortality (e.g., cavitation and entrainment of fish acclimated to deep water) are controlled by operation of the facility and thus are mitigable. Because turbine-passage mortality among fish early life stages can be very difficult to estimate directly, it may be more fruitful to base the need for mitigation at any given site on detailed knowledge of turbine characteristics and the susceptibility of the fish community to entrainment. 7 refs., 1 fig.

  15. Early Life Experiences and Exercise Associate with Canine Anxieties

    PubMed Central

    Tiira, Katriina; Lohi, Hannes

    2015-01-01

    Personality and anxiety disorders across species are affected by genetic and environmental factors. Shyness-boldness personality continuum exists across species, including the domestic dog, with a large within- and across-breed variation. Domestic dogs are also diagnosed for several anxiety-related behavioral conditions, such as generalized anxiety disorders, phobias, and separation anxiety. Genetic and environmental factors contributing to personality and anxiety are largely unknown. We collected questionnaire data from a Finnish family dog population (N = 3264) in order to study the associating environmental factors for canine fearfulness, noise sensitivity, and separation anxiety. Early life experiences and exercise were found to associate with anxiety prevalence. We found that fearful dogs had less socialization experiences (p = 0.002) and lower quality of maternal care (p < 0.0001) during puppyhood. Surprisingly, the largest environmental factor associating with noise sensitivity (p < 0.0001) and separation anxiety (p = 0.007) was the amount of daily exercise; dogs with noise sensitivity and separation anxiety had less daily exercise. Our findings suggest that dogs share many of the same environmental factors that contribute to anxiety in other species as well, such as humans and rodents. Our study highlights the importance of early life experiences, especially the quality of maternal care and daily exercise for the welfare and management of the dogs, and reveals important confounding factors to be considered in the genetic characterization of canine anxiety. PMID:26528555

  16. Atrazine and malathion shorten the maturation process of Xenopus laevis oocytes and have an adverse effect on early embryo development.

    PubMed

    Ji, Qichao; Lee, Jessica; Lin, Yu-Huey; Jing, Guihua; Tsai, L Jillianne; Chen, Andrew; Hetrick, Lindsay; Jocoy, Dylan; Liu, Junjun

    2016-04-01

    The use of pesticides has a negative impact on the environment. Amphibians have long been regarded as indicator species to pollutants due to their permeable skin and sensitivity to the environment. Studies have shown that population declines of some amphibians are directly linked with exposure to agricultural contaminants. In the past, much of the studies have focused on the toxic effect of contaminants on larvae (tadpoles), juvenile and adult frogs. However, due to the nature of their life cycle, amphibian eggs and early embryos are especially susceptible to the contaminants, and any alteration during the early reproductive stages may have a profound effect on the health and population of amphibians. In this study, we analyzed the effect of atrazine and malathion, two commonly used pesticides, on Xenopus laevis oocyte maturation and early embryogenesis. We found that both atrazine and malathion shortened the frog oocyte maturation process and resulted in reduced Emi2 levels at cytostatic factor-mediated metaphase arrest, and a high level of Emi2 is critically important for oocyte maturation. Furthermore, frog embryos fertilized under the influence of atrazine and/or malathion displayed a higher rate of abnormal division that eventually led to embryo death during early embryogenesis. PMID:26686575

  17. Atrazine and malathion shorten the maturation process of Xenopus laevis oocytes and have an adverse effect on early embryo development.

    PubMed

    Ji, Qichao; Lee, Jessica; Lin, Yu-Huey; Jing, Guihua; Tsai, L Jillianne; Chen, Andrew; Hetrick, Lindsay; Jocoy, Dylan; Liu, Junjun

    2016-04-01

    The use of pesticides has a negative impact on the environment. Amphibians have long been regarded as indicator species to pollutants due to their permeable skin and sensitivity to the environment. Studies have shown that population declines of some amphibians are directly linked with exposure to agricultural contaminants. In the past, much of the studies have focused on the toxic effect of contaminants on larvae (tadpoles), juvenile and adult frogs. However, due to the nature of their life cycle, amphibian eggs and early embryos are especially susceptible to the contaminants, and any alteration during the early reproductive stages may have a profound effect on the health and population of amphibians. In this study, we analyzed the effect of atrazine and malathion, two commonly used pesticides, on Xenopus laevis oocyte maturation and early embryogenesis. We found that both atrazine and malathion shortened the frog oocyte maturation process and resulted in reduced Emi2 levels at cytostatic factor-mediated metaphase arrest, and a high level of Emi2 is critically important for oocyte maturation. Furthermore, frog embryos fertilized under the influence of atrazine and/or malathion displayed a higher rate of abnormal division that eventually led to embryo death during early embryogenesis.

  18. 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.

  19. Maternal and genetic factors determine early life telomere length

    PubMed Central

    Asghar, Muhammad; Bensch, Staffan; Tarka, Maja; Hansson, Bengt; Hasselquist, Dennis

    2015-01-01

    In a broad range of species—including humans—it has been demonstrated that telomere length declines throughout life and that it may be involved in cell and organismal senescence. This potential link to ageing and thus to fitness has triggered recent interest in understanding how variation in telomere length is inherited and maintained. However, previous studies suffer from two main drawbacks that limit the possibility of understanding the relative importance of genetic, parental and environmental influences on telomere length variation. These studies have been based on (i) telomere lengths measured at different time points in different individuals, despite the fact that telomere length changes over life, and (ii) parent–offspring regression techniques, which do not enable differentiation between genetic and parental components of inheritance. To overcome these drawbacks, in our study of a songbird, the great reed warbler, we have analysed telomere length measured early in life in both parents and offspring and applied statistical models (so-called ‘animal models') that are based on long-term pedigree data. Our results showed a significant heritability of telomere length on the maternal but not on the paternal side, and that the mother's age was positively correlated with their offspring's telomere length. Furthermore, the pedigree-based analyses revealed a significant heritability and an equally large maternal effect. Our study demonstrates strong maternal influence on telomere length and future studies now need to elucidate possible underlying factors, including which types of maternal effects are involved. PMID:25621325

  20. Sugar Consumption Produces Effects Similar to Early Life Stress Exposure on Hippocampal Markers of Neurogenesis and Stress Response

    PubMed Central

    Maniam, Jayanthi; Antoniadis, Christopher P.; Youngson, Neil A.; Sinha, Jitendra K.; Morris, Margaret J.

    2016-01-01

    Adverse early life experience is a known risk factor for psychiatric disorders. It is also known that stress influences food preference. We were interested in exploring whether the choice of diet following early life stress exerts long-lasting molecular changes in the brain, particularly the hippocampus, a region critically involved in stress regulation and behavioral outcomes. Here, we examined the impact of early life stress induced by limited nesting material (LN) and chronic sucrose availability post-weaning on an array of hippocampal genes related to plasticity, neurogenesis, stress and inflammatory responses and mitochondrial biogenesis. To examine mechanisms underlying the impact of LN and sugar intake on hippocampal gene expression, we investigated the role of DNA methylation. As females are more likely to experience adverse life events, we studied female Sprague-Dawley rats. After mating LN was imposed from days 2 to 9 postpartum. From 3 to 15 weeks of age, female Control and LN siblings had unlimited to access to either chow and water, or chow, water and 25% sucrose solution. LN markedly reduced glucocorticoid receptor (GR) and neurogenic differentiation 1 (Neurod1) mRNA, markers involved in stress and hippocampal plasticity respectively, by more than 40%, with a similar effect of sugar intake in control rats. However, no further impact was observed in LN rats consuming sugar. Hippocampal Akt3 mRNA expression was similarly affected by LN and sucrose consumption. Interestingly, DNA methylation across 4 CpG sites of the GR and Neurod1 promoters was similar in LN and control rats. In summary, early life stress and post-weaning sugar intake produced long-term effects on hippocampal GR and Neurod1 expression. Moreover we found no evidence of altered promoter DNA methylation. We demonstrate for the first time that chronic sucrose consumption alone produces similar detrimental effects on the expression of hippocampal genes as LN exposure. PMID:26834554

  1. Adverse childhood experiences, mental health, and quality of life of Chilean girls placed in foster care: An exploratory study.

    PubMed

    Seiler, Annina; Kohler, Stefanie; Ruf-Leuschner, Martina; Landolt, Markus A

    2016-03-01

    In Latin America, little research has been conducted regarding exposure to adverse childhood experiences (ACEs), mental health, and health-related quality of life (HRQoL) among foster children. This study examined the association between ACEs and mental health, posttraumatic stress disorder (PTSD), and HRQoL in Chilean foster girls relative to age-matched Chilean family girls. Data were obtained from 27 Chilean foster girls and 27 Chilean girls ages 6 to 17 years living in family homes. Standardized self- and proxy-report measures were used. Foster girls reported more ACEs than controls in terms of familial and nonfamilial sexual abuse and both emotional and physical neglect. Girls living in foster care had a significantly higher rate of PTSD, displayed greater behavioral and emotional problems, and reported a lower HRQoL. Analysis confirmed the well-known cumulative risk hypothesis by demonstrating a significant positive association between the number of ACEs and PTSD symptom severity and a significant negative association with HRQoL. Chilean foster girls endured more ACEs that impair mental health and HRQoL than age-matched peers living with their families. These findings have implications for out-of-home care services in Latin America, highlighting the need to implement not only appropriate trauma-focused treatments but also appropriate prevention strategies.

  2. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood.

    PubMed

    Chen, E; Miller, G E; Kobor, M S; Cole, S W

    2011-07-01

    The notion that family support may buffer individuals under adversity from poor outcomes has been theorized to have important implications for mental and physical health, but little is known about the biological mechanisms that explain these links. We hypothesized that adults who grew up in low socioeconomic status (SES) households but who experienced high levels of maternal warmth would be protected from the pro-inflammatory states typically associated with low SES. A total of 53 healthy adults (aged 25-40 years) low in SES early in life were assessed on markers of immune activation and systemic inflammation. Genome-wide transcriptional profiling also was conducted. Low early-life SES individuals who had mothers, who expressed high warmth toward them, exhibited less Toll-like receptor-stimulated production of interleukin 6, and reduced bioinformatic indications of pro-inflammatory transcription factor activity (NF-κB) and immune activating transcription factor activity (AP-1) compared to those who were low in SES early in life but experienced low maternal warmth. To the extent that such effects are causal, they suggest the possibility that the detrimental immunologic effects of low early-life SES environments may be partly diminished through supportive family climates. PMID:20479762

  3. Maternal warmth buffers the effects of low early-life socioeconomic status on pro-inflammatory signaling in adulthood.

    PubMed

    Chen, E; Miller, G E; Kobor, M S; Cole, S W

    2011-07-01

    The notion that family support may buffer individuals under adversity from poor outcomes has been theorized to have important implications for mental and physical health, but little is known about the biological mechanisms that explain these links. We hypothesized that adults who grew up in low socioeconomic status (SES) households but who experienced high levels of maternal warmth would be protected from the pro-inflammatory states typically associated with low SES. A total of 53 healthy adults (aged 25-40 years) low in SES early in life were assessed on markers of immune activation and systemic inflammation. Genome-wide transcriptional profiling also was conducted. Low early-life SES individuals who had mothers, who expressed high warmth toward them, exhibited less Toll-like receptor-stimulated production of interleukin 6, and reduced bioinformatic indications of pro-inflammatory transcription factor activity (NF-κB) and immune activating transcription factor activity (AP-1) compared to those who were low in SES early in life but experienced low maternal warmth. To the extent that such effects are causal, they suggest the possibility that the detrimental immunologic effects of low early-life SES environments may be partly diminished through supportive family climates.

  4. Early Life on Earth and the Search for Extraterrestrial Biosignatures

    NASA Technical Reports Server (NTRS)

    Oehler, Dorothy Z.; House, Christopher

    2014-01-01

    In the last 2 years, scientists within the ARES Directorate at JSC have applied the technology of Secondary Ion Mass Spectrometry (SIMS) to individual organic structures preserved in Archean (approximately 3 billion years old) sediments on Earth. These organic structures are among the oldest on Earth that may be microfossils - structurally preserved remnants of ancient microbes. The SIMS work was done to determine the microfossils' stable carbon isotopic composition (delta C-13 values). This is the first time that such ancient, potential microfossils have been successfully analyzed for their individual delta C-13 values. The results support the interpretation that these structures are remnants of early life on Earth and that they may represent planktonic organisms that were widely distributed in the Earth's earliest oceans. This study has been accepted for publication in the journal Geology.

  5. Diffusion tensor imaging for understanding brain development in early life.

    PubMed

    Qiu, Anqi; Mori, Susumu; Miller, Michael I

    2015-01-01

    The human brain rapidly develops during the final weeks of gestation and in the first two years following birth. Diffusion tensor imaging (DTI) is a unique in vivo imaging technique that allows three-dimensional visualization of the white matter anatomy in the brain. It has been considered to be a valuable tool for studying brain development in early life. In this review, we first introduce the DTI technique. We then review DTI findings on white matter development at the fetal stage and in infancy as well as DTI applications for understanding neurocognitive development and brain abnormalities in preterm infants. Finally, we discuss limitations of DTI and potential valuable imaging techniques for studying white matter myelination.

  6. Mineral remains of early life on Earth? On Mars?

    USGS Publications Warehouse

    Iberall, Robbins E.; Iberall, A.S.

    1991-01-01

    The oldest sedimentary rocks on Earth, the 3.8-Ga Isua Iron-Formation in southwestern Greenland, are metamorphosed past the point where organic-walled fossils would remain. Acid residues and thin sections of these rocks reveal ferric microstructures that have filamentous, hollow rod, and spherical shapes not characteristic of crystalline minerals. Instead, they resemble ferric-coated remains of bacteria. Because there are no earlier sedimentary rocks to study on Earth, it may be necessary to expand the search elsewhere in the solar system for clues to any biotic precursors or other types of early life. A study of morphologies of iron oxide minerals collected in the southern highlands during a Mars sample return mission may therefore help to fill in important gaps in the history of Earth's earliest biosphere. -from Authors

  7. Early Life Nutrition and Energy Balance Disorders in Offspring in Later Life

    PubMed Central

    Reynolds, Clare M.; Gray, Clint; Li, Minglan; Segovia, Stephanie A.; Vickers, Mark H.

    2015-01-01

    The global pandemic of obesity and type 2 diabetes is often causally linked to changes in diet and lifestyle; namely increased intake of calorically dense foods and concomitant reductions in physical activity. Epidemiological studies in humans and controlled animal intervention studies have now shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. The mechanisms by which early environmental insults can have long-term effects on offspring remain poorly defined. However there is evidence from intervention studies which indicate altered wiring of the hypothalamic circuits that regulate energy balance and epigenetic effects including altered DNA methylation of key adipokines including leptin. Studies that elucidate the mechanisms behind these associations will have a positive impact on the health of future populations and adopting a life course perspective will allow identification of phenotype and markers of risk earlier, with the possibility of nutritional and other lifestyle interventions that have obvious implications for prevention of non-communicable diseases. PMID:26402696

  8. Early Life Nutrition and Energy Balance Disorders in Offspring in Later Life.

    PubMed

    Reynolds, Clare M; Gray, Clint; Li, Minglan; Segovia, Stephanie A; Vickers, Mark H

    2015-09-21

    The global pandemic of obesity and type 2 diabetes is often causally linked to changes in diet and lifestyle; namely increased intake of calorically dense foods and concomitant reductions in physical activity. Epidemiological studies in humans and controlled animal intervention studies have now shown that nutritional programming in early periods of life is a phenomenon that affects metabolic and physiological functions throughout life. This link is conceptualised as the developmental programming hypothesis whereby environmental influences during critical periods of developmental plasticity can elicit lifelong effects on the health and well-being of the offspring. The mechanisms by which early environmental insults can have long-term effects on offspring remain poorly defined. However there is evidence from intervention studies which indicate altered wiring of the hypothalamic circuits that regulate energy balance and epigenetic effects including altered DNA methylation of key adipokines including leptin. Studies that elucidate the mechanisms behind these associations will have a positive impact on the health of future populations and adopting a life course perspective will allow identification of phenotype and markers of risk earlier, with the possibility of nutritional and other lifestyle interventions that have obvious implications for prevention of non-communicable diseases.

  9. Indirect comparisons of adverse events and dropout rates in early Parkinson's disease trials of pramipexole, ropinirole, and rasagiline.

    PubMed

    Zagmutt, Francisco J; Tarrants, Marcy L

    2012-07-01

    The comparative safety profiles of monotherapeutic treatments for Parkinson's disease (PD) can provide valuable therapeutic information. The objective of this study was to perform an indirect comparison of Adverse Events (AEs) and Dropout Rates (DRs) among clinical trials of pramipexole, ropinirole, and rasagiline. Outcomes analyzed included DRs, total AEs, and AE categories: Cognitive (CG), Gastrointestinal (GI), and Sleep/Fatigue (SF). The odds-ratio (OR) and Credible Interval (CrI) of outcomes between products using placebo as common comparator was calculated using indirect meta-analytical methods. AEs incidences for subjects receiving rasagiline were not significantly different from placebo, whereas DRs were significantly lower than for placebo (OR = 0.55; 95% CrI = 0.34-0.88). Patients receiving pramipexole or ropinirole had higher incidence of all AEs and DRs than patients taking rasagiline, except for the nonsignificant incidence of CG for ropinirole vs. rasagiline (1.76; 0.69-4.70). The incidence of GI (2.11; 1.13-4.06) and SF (2.75; 1.42-5.47) was significantly higher for ropinirole than for pramipexole, whereas the incidence of CG was significantly lower for ropinirole than for pramipexole (0.22; 0.07-0.69). Findings suggest that subjects with early PD treated with rasagiline have fewer AEs and DRs than those treated with pramipexole or ropinirole. GI and SF AEs were highest for subjects treated with ropinirole, while individuals treated with pramipexole exhibited the highest incidence of cognitive AEs.

  10. Early-Life Stress and Neurometabolites of the Hippocampus

    PubMed Central

    Coplan, Jeremy D.; Mathew, Sanjay J.; Abdallah, Chadi G.; Mao, Xiangling; Kral, John G.; Smith, Eric L. P.; Rosenblum, Leonard A.; Perera, Tarique D.; Dwork, Andrew J.; Hof, Patrick R.; Gorman, Jack M.; Shungu, Dikoma C.

    2010-01-01

    We tested the hypothesis that early life stress would persistently compromise neuronal viability of the hippocampus of the grown nonhuman primate. Neuronal viability was assessed through ascertainment of N-acetyl aspartate (NAA) – an amino acid considered reflective of neuronal density/functional integrity – using in vivo proton magnetic resonance spectroscopic imaging (MRSI). The subjects reported herein represent a re-analysis of a sample of nineteen adult male bonnet macaques that had been reared in infancy under induced stress by maternal variable foraging demand (VFD) (N = 10) or control rearing conditions (N = 9). The MRSI spectral readings were recorded using a GE 1.5 Tesla machine under anesthesia. Relative NAA values were derived using NAA as numerator and both choline (Cho) or creatine (Cr) as denominators. Left medial temporal lobe (MTL) NAA/Cho but not NAA/Cr was decreased in VFD subjects versus controls. An MTL NAA/Cho ratio deficit remained significant when controlling for multiple confounding variables. Regression analyses suggested that the NAA/Choline finding was due to independently low left NAA and high left choline. Right MTL showed no rearing effects for NAA, but right NAA was positively related to body mass, irrespective of denominator. The current data indicate that decreased left MTL NAA/Cho may reflect low neuronal viability of the hippocampus following early life stress in VFD-reared versus normally-reared subjects. Given the importance of the hippocampus in stress-mediated toxicity, validation of these data using absolute quantification is suggested and correlative neurohistological studies of hippocampus are warranted. PMID:20713023

  11. Intravenous administration of equine-derived whole IgG antivenom does not induce early adverse reactions in non-envenomed horses and cows.

    PubMed

    Estrada, Ricardo; Herrera, María; Segura, Alvaro; Araya, Javier; Boschini, Carlos; Gutiérrez, José María; León, Guillermo

    2010-11-01

    Administration of antivenoms to treat snakebite envenomings has the potential risk of inducing early adverse reactions. The mechanisms involved in these reactions are unclear. In this study, polyspecific antivenom consisting of whole IgG purified from equine plasma by caprylic acid precipitation was administered intravenously to non-envenomed horses (n = 47) and cows (n = 20) at a dose of 0.4 mL/kg. It has been reported that, in humans, this formulation (administered at a dose of 0.4 mL/kg) induces mild noticeable early adverse reactions, such as fever, vomiting, diarrhea, urticaria, generalized rash, tachypnea or tachycardia, in about 15-20% of the patients. Unexpectedly, none of the animals receiving antivenom in our study showed any evidence of early adverse reaction. Moreover, no late adverse reactions, i.e. serum sickness, were observed during 40 days after antivenom administration. Unlike studies performed in envenomed humans, our present results were obtained in a group of non-envenomed individuals. It is concluded that, in addition to the physicochemical characteristics of the formulation, other unknown factors must determine the occurrence of adverse reactions in snakebite envenomed humans treated with equine-derived antivenoms.

  12. Predicting Negative Life Outcomes from Early Aggressive-Disruptive Behavior Trajectories: Gender Differences in Maladaptation across Life Domains

    ERIC Educational Resources Information Center

    Bradshaw, Catherine P.; Schaeffer, Cindy M.; Petras, Hanno; Ialongo, Nicholas

    2010-01-01

    Transactional theories of development suggest that displaying high levels of antisocial behavior early in life and persistently over time causes disruption in multiple life domains, which in turn places individuals at risk for negative life outcomes. We used longitudinal data from 1,137 primarily African American urban youth (49.1% female) to…

  13. Influence of Serotonin Transporter Gene Polymorphisms and Adverse Life Events on Depressive Symptoms in the Elderly: A Population-Based Study

    PubMed Central

    Davin, Annalisa; Monti, Maria Cristina; Polito, Letizia; Vaccaro, Roberta; Abbondanza, Simona; Gnesi, Marco; Villani, Simona; Guaita, Antonio

    2015-01-01

    Background Depression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear. Methods We evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from “InveCe.Ab”, a population-based study of 1321 subjects aged 70–74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms–a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms–and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors. Results Two hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S′S′ carriers showed an increased risk of depressive symptoms (ORadj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (ORadj = 2.49, p < .001), age (ORadj = 1.19, p = .007), a history of depression (ORadj = 4.73, p < .001), and comorbidity (ORadj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L′L′ carriers, while antidepressant intake was directly related to GDS≥5 in the L′S′ carriers (ORadj = 2.46, p = .036) and borderline significant in the S′S′ carriers (ORadj = 2.41, p = .081). Discussion The S′S′ genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S′S′ genotype, compared with the environment

  14. Early life stress affects limited regional brain activity in depression.

    PubMed

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-05-03

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients.

  15. Early life stress affects limited regional brain activity in depression

    PubMed Central

    Du, Lian; Wang, Jingjie; Meng, Ben; Yong, Na; Yang, Xiangying; Huang, Qingling; Zhang, Yan; Yang, Lingling; Qu, Yuan; Chen, Zhu; Li, Yongmei; Lv, Fajin; Hu, Hua

    2016-01-01

    Early life stress (ELS) can alter brain function and increases the risk of major depressive disorder (MDD) in later life. This study investigated whether ELS contributes to differences in regional brain activity between MDD patients and healthy controls (HC), as measured by amplitude of low-frequency fluctuation (ALFF)/fractional (f)ALFF. Eighteen first-episode, treatment-naïve MDD patients and HC were assessed with the Childhood Trauma Questionnaire and resting-state functional magnetic resonance imaging. We compared ALFF/fALFF between MDD patients and HC, with or without controlling for ELS, and determined whether ELS level was correlated with regional brain activity in each group. After regressing out ELS, we found that ALFF increased in bilateral amygdala and left orbital/cerebellum, while fALFF decreased in left inferior temporal and right middle frontal gyri in MDD patients relative to controls. ELS positively correlated with regional activity in the left cerebellum in MDD and in the right post-central/inferior temporal/superior frontal cingulate, inferior frontal gyrus and bilateral cerebellum in HC. Our findings indicate that there is only very limited region showing correlation between ELS and brain activity in MDD, while diverse areas in HC, suggesting ELS has few impacts on MDD patients. PMID:27138376

  16. Neuroanatomical changes in a mouse model of early life neglect.

    PubMed

    Duque, Alvaro; Coman, Daniel; Carlyle, Becky C; Bordner, Kelly A; George, Elizabeth D; Papademetris, Xenophon; Hyder, Fahmeed; Simen, Arthur A

    2012-04-01

    Using a novel mouse model of early life neglect and abuse (ENA) based on maternal separation with early weaning, George et al. (BMC Neurosci 11:123, 2010) demonstrated behavioral abnormalities in adult mice, and Bordner et al. (Front Psychiatry 2(18):1-18, 2011) described concomitant changes in mRNA and protein expression. Using the same model, here we report neuroanatomical changes that include smaller brain size and abnormal inter-hemispheric asymmetry, decreases in cortical thickness, abnormalities in subcortical structures, and white matter disorganization and atrophy most severely affecting the left hemisphere. Because of the similarities between the neuroanatomical changes observed in our mouse model and those described in human survivors of ENA, this novel animal model is potentially useful for studies of human ENA too costly or cumbersome to be carried out in primates. Moreover, our current knowledge of the mouse genome makes this model particularly suited for targeted anatomical, molecular, and pharmacological experimentation not yet possible in other species. PMID:21984312

  17. The Human Microbiome. Early Life Determinant of Health Outcomes

    PubMed Central

    2014-01-01

    The development of new technologies to isolate and identify microbial genomes has markedly increased our understanding of the role of microbiomes in health and disease. The idea, first proposed as part of the hygiene hypothesis, that environmental microbes influence the developmental trajectories of the immune system in early life, has now been considerably extended and refined. The abundant microbiota present in mucosal surfaces, especially the gut, is actively selected by the host through complex receptor systems that respond differentially depending on the molecular patterns presented to mucosal cells. Germ-free mice are more likely to develop allergic airway inflammation and show alterations in normal motor control and anxiety. These effects can be reversed by neonatal microbial recolonization but remain unchanged if recolonization occurs in adults. What emerges from these recent studies is the discovery of a complex, major early environmental determinant of lifetime human phenotypes. To change the natural course of asthma, obesity, and other chronic inflammatory conditions, active manipulation of the extensive bacterial, phage, and fungal metagenomes present in mucosal surfaces may be required, specifically during the developing years. Domesticating the human microbiome and adapting it to our health needs may be a challenge akin to, but far more complex than, the one faced by humanity when a few dozen species of plants and animals were domesticated during the transition between hunter-gatherer and sedentary societies after the end of the Pleistocene era. PMID:24437411

  18. Early life perfluorooctanesulphonic acid (PFOS) exposure impairs zebrafish organogenesis

    PubMed Central

    Chen, Jiangfei; Tanguay, Robert L.; Tal, Tamara L.; Bai, Chenglian; Tilton, Susan C.; Jin, Daqing; Yang, Dongren; Huang, Changjiang; Dong, Qiaoxiang

    2014-01-01

    As a persistent organic contaminant, perfluorooctanesulphonic acid (PFOS) has been widely detected in the environment, wildlife, and humans. The present study revealed that zebrafish embryos exposed to 16 µM PFOS during a sensitive window of 48–96 hour post-fertilization (hpf) disrupted larval morphology at 120 hpf. Malformed zebrafish larvae were characterized by uninflated swim bladder, less developed gut, and curved spine. Histological and ultrastructural examination of PFOS-exposed larvae showed structural alterations in swim bladder and gut. Whole genome microarray was used to identify the early transcripts dysregulated following exposure to 16 µM PFOS at 96 hpf. In total, 1,278 transcripts were significantly misexpressed (p < 0.05) and 211 genes were changed at least two-fold upon PFOS exposure in comparison to the vehicle exposed control group. A PFOS-induced network of perturbed transcripts relating to swim bladder and gut development revealed that misexpression of genes were involved in organogenesis. Taken together, early life stage exposure to PFOS perturbs various molecular pathways potentially resulting in observed defects in swim bladder and gut development. PMID:24667235

  19. Early life stress and novelty seeking behavior in adolescent monkeys.

    PubMed

    Parker, Karen J; Rainwater, Kimberly L; Buckmaster, Christine L; Schatzberg, Alan F; Lindley, Steven E; Lyons, David M

    2007-08-01

    Recent evidence suggests that early exposure to mild stress promotes the development of novelty seeking behavior. Here we test this hypothesis in squirrel monkeys and investigate whether novelty seeking behavior is associated with differences in cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5HIAA), the dopamine metabolite homovanillic acid (HVA), the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethylene glycol (MHPG), and the neuropeptide corticotrophin-releasing factor (CRF). Monkeys were randomized early in life to either mild intermittent stress (IS) or no stress (NS) conditions, and subsequently presented with opportunities to interact with a familiar or novel object in a test box that was connected to each monkey's home cage. To further minimize the potentially stressful nature of the test situation, monkeys were acclimated to the test procedures prior to study initiation. Post-test plasma levels of cortisol in IS and NS monkeys did not differ significantly from baseline levels measured in undisturbed conditions. During testing, more IS than NS monkeys voluntarily left the home cage, and IS monkeys spent more time in the test box compared to NS monkeys. More IS than NS monkeys engaged in object exploration in the test box, and IS monkeys preferred to interact with the novel vs. familiar object. Novelty seeking was not associated with differences in 5HIAA, HVA, MHPG, or CRF, but correlated with differences in object exploration observed in a different test situation at an earlier age. These trait-like differences in novelty seeking appear to reflect mild early stress-induced adaptations that enhance curiosity and resilience. PMID:17604913

  20. Hydrogen, nitrogen, and life on the early Earth

    NASA Astrophysics Data System (ADS)

    Wordsworth, Robin; Pierrehumbert, Raymond

    2013-04-01

    In Earth's Hadean and Archean eras, the Sun was 20-40 % fainter than it is today, but there is no evidence for widespread long-term glaciation. An enhanced greenhouse effect via increased CO2 levels is perhaps the simplest solution to the problem, but observational and theoretical studies both suggest only moderately elevated atmospheric CO2 at this time. Other phenomena such as CO2 / H2O line broadening via increased atmospheric N2 and a lower planetary albedo have been proposed, but are probably insufficient to explain the necessary warming alone. Recently, we have suggested that increased hydrogen and nitrogen levels on the early Earth may have played a role in warming through H2-N2 collision-induced absorption (CIA). This process is well-known on Titan, where it dominates infra-red absorption across large regions of the spectrum. Broadening of the absorption bands at higher temperatures means that H2-N2 CIA can block the critical 800-1200 cm-1 water vapour 'window', allowing mean surface temperatures up to 280 K with only ~20-80 × PAL CO2 under a solar flux 75 % of that today. Here we present our modeling results and discuss their potential relevance to climate in the Archean and Hadean. We consider the evidence for and against high H2 levels on the early Earth and the main challenges in constraining outgassing and rates of hydrogen escape to space. We discuss the effects an H2-rich atmosphere might have had on the early development of life, including its possible demise at the hands of the methanogens. Finally, we speculate on the possible importance of the H2-N2 warming mechanism for Earth-like rocky planets around other stars.

  1. The effect of early-life education on later-life mortality.

    PubMed

    Black, Dan A; Hsu, Yu-Chieh; Taylor, Lowell J

    2015-12-01

    Many studies link cross-state variation in compulsory schooling laws to early-life educational attainment, thereby providing a plausible way to investigate the causal impact of education on various lifetime outcomes. We use this strategy to estimate the effect of education on older-age mortality of individuals born in the early twentieth century U.S. Our key innovation is to combine U.S. Census data and the complete Vital Statistics records to form precise mortality estimates by sex, birth cohort, and birth state. In turn we find that virtually all of the variation in these mortality rates is captured by cohort effects and state effects alone, making it impossible to reliably tease out any additional impact due to changing educational attainment induced by state-level changes in compulsory schooling.

  2. The die is cast - Arsenic exposure in early life and disease susceptibility

    EPA Science Inventory

    Abstract Early life exposure to arsenic in humans and mice produces similar patterns of disease in later life. Given the long interval between exposure and effect, epigenetic effects of early life exposure to arsenic may account for development and progression of disease in bo...

  3. Accounting Early for Life Long Learning: The AcE Project.

    ERIC Educational Resources Information Center

    University Coll. Worcester (England). Centre for Research in Early Childhood Education.

    Building upon the work of the Effective Early Learning (EEL) Project in raising the quality of early learning for young children in the United Kingdom, the 3-year Accounting Early for Life Long Learning Project (AcE Project) focuses on enhancing in 3- to 6-year-olds those attitudes and dispositions that are important to life-long learning. This…

  4. Delinquency and Recidivism: A Multicohort, Matched-Control Study of the Role of Early Adverse Experiences, Mental Health Problems, and Disabilities

    ERIC Educational Resources Information Center

    Barrett, David E.; Katsiyannis, Antonis; Zhang, Dalun; Zhang, Dake

    2014-01-01

    The authors examined the role of early adverse experiences, mental health problems, and disabilities in the prediction of juvenile delinquency and recidivism, using a matched-control group design. The delinquent group comprised 99,602 youth, born between 1981 and 1988, whose cases had been processed by the South Carolina Department of Juvenile…

  5. 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. PMID:24118915

  6. 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.

  7. Prevention and early intervention for depression in adolescence and early adult life.

    PubMed

    Harrington, R; Clark, A

    1998-01-01

    Over the past decade there has been increasing interest in the possibility that early intervention might prevent mental disorders later in life. Indeed, in the United Kingdom the Department of Health recommends that health promotion should be one of the main functions of child mental health services, a suggestion that has been endorsed by professional bodies. It is easy to see why both purchasers and providers of mental health services would be interested in prevention, but will preventive interventions work in practice? This paper discusses the possibility of preventing depressive disorder in late adolescence and early adult life by intervening in childhood and early adolescence. The paper begins with a description of the phenomenology of depression and its risk factors. It then goes on to describe a framework of prevention and within this framework explores whether there is an adequate knowledge base. The general perspective that is presented is one of cautious scepticism. It is argued that difficulties in defining depression and identifying risk factors that can easily be remedied make it unlikely that within the foreseeable future primary prevention programmes will prove to be more effective than treatment and rehabilitation of affected individuals. The possibility that preventive programmes could do harm will also be discussed. The paper concludes with some proposals about appropriate targets for prevention. It is suggested that apart from a few policy areas where there are some relatively harmless measures that could protect from later depression, a balanced preventive programme will give higher priority to treatment services than to those concerned with early intervention.

  8. 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).…

  9. Illinois Early Learning Project Tip Sheets: Parenting and Family Life.

    ERIC Educational Resources Information Center

    2003

    The Illinois Early Learning Project (IEL) is funded by the Illinois State Board of Education to provide information resources on early learning and training related to implementing the Illinois Early Learning Standards for parents and for early childhood personnel in all settings. The IEL tip sheets offer suggestions to parents and early childhood…

  10. Early life disadvantage strengthens flight performance trade-offs in European starlings, Sturnus vulgaris

    PubMed Central

    O'Hagan, Daniel; Andrews, Clare P.; Bedford, Thomas; Bateson, Melissa; Nettle, Daniel

    2015-01-01

    Developmental stress has been shown to affect adult flight performance in birds, with both negative and positive effects reported in the literature. Previous studies have used developmental manipulations that had substantial effects on patterns of growth. They have also examined mean levels of flight performance per individual, rather than investigating how developmental stress might alter trade-offs between different components of flight performance. We recorded multiple components of escape flight performance in 20 adult European starlings previously subjected to a manipulation likely to have altered levels of developmental stress. Siblings had been cross-fostered to nests where they were either slightly larger (advantaged treatment) or slightly smaller (disadvantaged treatment) than their competitors. The manipulation had no detectable effect on growth. However, developmental treatment affected performance in escape flights a year later by strengthening the trade-offs between different flight parameters. Disadvantaged birds faced a steeper trade-off between take-off speed and take-off angle, and a steeper trade-off between take-off angle and total time in flight, than advantaged birds. The results suggest that even subtle early life adversity that has no obvious effect on growth or size can leave a lasting legacy in the form of constraints on locomotor performance later in life. PMID:25843958

  11. Early life maternal separation stress augmentation of limbic epileptogenesis: the role of corticosterone and HPA axis programming.

    PubMed

    Koe, Amelia S; Salzberg, Michael R; Morris, Margaret J; O'Brien, Terence J; Jones, Nigel C

    2014-04-01

    Early life stress causes long-lasting effects on the limbic system that may be relevant to the development of mesial temporal lobe epilepsy (MTLE) and its associated psychopathology. Recent studies in rats suggest that maternal separation (MS), a model of early life stress, confers enduring vulnerability to amygdala kindling limbic epileptogenesis. However, the mechanisms underlying this remain unknown. Here, we tested whether hypothalamic-pituitary-adrenal (HPA) axis hyper-reactivity induced by MS - specifically the excessive secretion of corticosterone following a seizure - was involved in this vulnerability. In adult female rats subjected to MS from postnatal days 2-14, seizure-induced corticosterone responses were significantly augmented and prolonged for at least two hours post-seizure, compared to control early-handled (EH) rats. This was accompanied by reduced seizure threshold (p<0.05) and increased vulnerability to the kindling-induced progression of seizure duration (p<0.05) in MS rats. Pre-seizure treatment with the corticosterone synthesis inhibitor, metyrapone (MET) (50mg/kgsc) effectively blocked seizure-induced corticosterone responses. When delivered throughout kindling, MET treatment also reversed the MS-induced reduction in seizure threshold and the lengthened seizure duration back to levels of EH rats. These observations suggest that adverse early life environments induce a vulnerability to kindling epileptogenesis mediated by HPA axis hyper-reactivity, which could have relevance for the pathogenesis of MTLE.

  12. Effects of Mixture of Pharmaceuticals on Early Life Stages of Tench (Tinca tinca)

    PubMed Central

    Stancova, Vlasta; Plhalova, Lucie; Bartoskova, Marta; Zivna, Dana; Prokes, Miroslav; Marsalek, Petr; Blahova, Jana; Skoric, Misa; Svobodova, Zdenka

    2014-01-01

    Ubiquitous occurrence of pharmaceuticals in aquatic environment results in concern about potential adverse the effects on nontarget organisms. In water, drugs are present in complex mixtures, in which complicated interactions affect toxicity of single components. The purpose of this study was to examine effect of 35-day-long exposure to mixture of ibuprofen, diclofenac, and carbamazepine on the mortality, growth, early ontogeny, and histopathological changes in tench (Tinca tinca). Early life stage toxicity test was carried out using a modified protocol according to OECD guideline 210. Exposure to mixture of pharmaceuticals at concentration of 60 μg·L−1 for each substance was associated with significant increase in mortality, as well as significant increase in growth and elevated incidence of malformations. Any of the tested concentrations resulted in histopathological changes of liver, kidney, skin, or gill. After fourteen days of exposure there was short-term delay of development related to increased concentrations of pharmaceuticals in the mixture (2, 20, and 60 μg·L−1). Environmentally relevant concentrations (0.02; and 0.2 μg·L−1) used in this experiment did not result in toxic impairment of tench. PMID:24772417

  13. Early life stage toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in zebrafish (Danio rerio)

    SciTech Connect

    Henry, T.R.; Hornung, M.W.; Abnet, C.C.; Peterson, R.E.

    1995-12-31

    TCDD and related compounds cause toxicity in fish early life stages, characterized by edema, regional ischemia, craniofacial malformations, growth retardation and mortality. Determining the mechanism of these effects requires understanding normal early life stage development, which has been studied extensively in the zebrafish. Establishing zebrafish as a model for TCDD developmental toxicity requires demonstration that TCDD adversely affects zebrafish early life stages. Toxicity of TCDD to zebrafish early life stages was characterized by exposing newly fertilized eggs for 1 hr to water containing acetone or graded concentrations of [{sup 3}H]-TCDD and observed for signs of toxicity at 12 hr intervals for 240 hr post fertilization (hpf). TCDD did not increase embryo mortality during the egg stage (0--48 hpf) nor did it affect the time to hatching (48--96 hpf). At the highest TCDD egg doses (4.5--6.5 ng/g) the earliest sign of toxicity was pericardial edema (72 hpf) followed by the onset of yolk sac edema (96 hpf) onset of mortality (132 hpf). At lower egg doses the same effects were seen but after a longer delay period. Other signs of toxicity included craniofacial malformations, cranial edema and loss of swimming activity prior to death. To determine the dose-response relationship for pericardial and yolk sac edema and larval mortality the cumulative incidence of each effect was determined at 240 hpf. The ED{sub 50}s (95% fiducial limits) for pericardial edema and yolk sac edema were 2.1 6 (1.82--2.48) and 2.43 (2.12--2.72) ng TCDD/g egg, respectively. The LD{sub 50} was 2.45 (1.94--2.89) ng TCDD/g egg. In conclusion, the signs of TCDD early life stage toxicity in zebrafish are essentially identical to those in other fish species, however, larger egg doses of TCDD are required to elicit the effects.

  14. Early life trauma predicts self-reported levels of depressive and anxiety symptoms in nonclinical community adults: relative contributions of early life stressor types and adult trauma exposure.

    PubMed

    Chu, Denise A; Williams, Leanne M; Harris, Anthony W F; Bryant, Richard A; Gatt, Justine M

    2013-01-01

    Exposure to early life trauma is a known risk factor for depression and anxiety disorders in adulthood. This study aimed to evaluate the relative contributions of early life versus adult trauma in predicting levels of depressive and anxiety symptoms in nonclinical community adults. 1209 nonclinical community adults (18-70 years; 45% male) were assessed for mental health status, early life stressors, lifetime trauma exposure, and self-reported levels of depressive and anxiety symptoms. A subset of the full sample subjected to group comparisons (n = 1088) indicated that early life stressor exposure primarily accounted for significantly higher depressive and anxiety symptom scores when compared against adults reporting to be free of childhood stressor or adult trauma exposure. Subsequent hierarchical multiple regression analyses of this subset using five distinct early life stressor types, namely 'Interpersonal violation', 'Family breakup', 'Disasters/war', 'Familial health trauma/death' and 'Personal health trauma' derived from principal component analysis of a wide range of self-reported early stressor events in the full sample, showed childhood 'Interpersonal violation' differentially predicted higher self-reported depressive and anxiety symptom scores in both males and females. Adult trauma exposure did not significantly predict these symptom scores. These findings underline the relative importance of exposure to 'interpersonal violation' relative to other types of early life stressors and adult trauma in the risk of depressive and anxiety symptoms in nonclinical community adults.

  15. Nutritional influences in early life upon obesity and body proportions.

    PubMed

    Jackson, A A; Langley-Evans, S C; McCarthy, H D

    1996-01-01

    Close relationships exist between patterns of intra-uterine growth and the risk of ischaemic heart disease, hypertension, diabetes, insulin-resistance syndrome, obesity and some cancers later in life. Earlier studies placed emphasis on low birth weight and reduced growth, but it is now clear that disproportions in early growth are of great importance. Disproportion may be identified as disproportions of fetal and placental growth (and the risk of high blood pressure), or in head circumference, length and weight. It is hypothesized that the availability of nutrients at different times during gestation, by interacting with the maternal and fetal hormonal profile, predisposes to different patterns of growth. The same interaction programmes critical metabolic functions and determines the metabolic capacity at all later ages. People who were exposed to severe undernutrition during the Dutch hunger winter showed increased adiposity if the exposure was during early pregnancy, but decreased adiposity if the exposure was during late pregnancy. In men born in the UK, those with evidence of retarded fetal growth had significantly greater waist/hip circumference ratios for any given body mass index (the ratio fell with increasing weight at one year of age). In Mexican-Americans and non-Hispanic Caucasian Americans, people in the lowest third of birth weight had more truncal fat than those in the highest third. Offspring of rats exposed to marginally reduced protein intakes during pregnancy manifest a similar pattern of growth and metabolic change to that seen in humans, with perturbations of appetite and body fat patterning. Studies in rats suggest that programming of the hypothalamus, especially the hypothalamic-pituitary-adrenal axis might be the mechanism through which these changes are brought about. PMID:9017278

  16. Early life events influence whole-of-life metabolic health via gut microflora and gut permeability.

    PubMed

    Kerr, Caroline A; Grice, Desma M; Tran, Cuong D; Bauer, Denis C; Li, Dongmei; Hendry, Phil; Hannan, Garry N

    2015-01-01

    The capacity of our gut microbial communities to maintain a stable and balanced state, termed 'resilience', in spite of perturbations is vital to our achieving and maintaining optimal health. A loss of microbial resilience is observed in a number of diseases including obesity, diabetes and metabolic syndrome. There are large gaps in our understanding of why an individual's co-evolved microflora consortium fail to develop resilience thereby establishing a trajectory towards poor metabolic health. This review examines the connections between the developing gut microbiota and intestinal barrier function in the neonate, infant and during the first years of life. We propose that the effects of early life events on the gut microflora and permeability, whilst it is in a dynamic and vulnerable state, are fundamental in shaping the microbial consortia's resilience and that it is the maintenance of resilience that is pivotal for metabolic health throughout life. We review the literature supporting this concept suggesting new potential research directions aimed at developing a greater understanding of the longitudinal effects of the gut microflora on metabolic health and potential interventions to recalibrate the 'at risk' infant gut microflora in the direction of enhanced metabolic health.

  17. Early Life Stress as an Influence on Limbic Epilepsy: An Hypothesis Whose Time has Come?

    PubMed Central

    Koe, Amelia S.; Jones, Nigel C.; Salzberg, Michael R.

    2009-01-01

    The pathogenesis of mesial temporal lobe epilepsy (MTLE), the most prevalent form of refractory focal epilepsy in adults, is thought to begin in early life, even though seizures may not commence until adolescence or adulthood. Amongst the range of early life factors implicated in MTLE causation (febrile seizures, traumatic brain injury, etc.), stress may be one important contributor. Early life stress is an a priori agent deserving study because of the large amount of neuroscientific data showing enduring effects on structure and function in hippocampus and amygdala, the key structures involved in MTLE. An emerging body of evidence directly tests hypotheses concerning early life stress and limbic epilepsy: early life stressors, such as maternal separation, have been shown to aggravate epileptogenesis in both status epilepticus and kindling models of limbic epilepsy. In addition to elucidating its influence on limbic epileptogenesis itself, the study of early life stress has the potential to shed light on the psychiatric disorder that accompanies MTLE. For many years, psychiatric comorbidity was viewed as an effect of epilepsy, mediated psychologically and/or neurobiologically. An alternative – or complementary – perspective is that of shared causation. Early life stress, implicated in the pathogenesis of several psychiatric disorders, may be one such causal factor. This paper aims to critically review the body of experimental evidence linking early life stress and epilepsy; to discuss the direct studies examining early life stress effects in current models of limbic seizures/epilepsy; and to suggest priorities for future research. PMID:19838325

  18. Impact of early vs. late childhood early life stress on brain morphometrics.

    PubMed

    Baker, Laurie M; Williams, Leanne M; Korgaonkar, Mayuresh S; Cohen, Ronald A; Heaps, Jodi M; Paul, Robert H

    2013-06-01

    Previous studies of early life trauma suggest that in addition to its emotional impact, exposure to early life stress (ELS) is associated with alterations in brain structure. However, little attention has been devoted to the relationship between emotional processing and brain integrity as a function of age of ELS onset. In the present study we examined whether ELS onset in older ages of youth rather than younger ages is associated with smaller limbic and basal ganglia volumes as measured by magnetic resonance imaging (MRI). We hypothesized that later age of manifestation during youth is associated with smaller volumetric morphology in limbic and basal ganglia volumes in adulthood. A total of 173 individuals were divided into three groups based on the age of self-reported ELS. The three groups included individuals only experiencing early childhood ELS (1 month-7 years, n = 38), those only experiencing later childhood ELS (8 years -17 years, n = 59), and those who have not experienced ELS (n = 76). Anterior cingulate cortex (ACC), hippocampus, amygdala, insula and caudate volumes were measured using a T1-weighted MRI. Analyses confirmed that later childhood ELS was associated with volumetric reductions in the ACC and insula volumes, while ELS experienced between the ages of 1 month and 7 years was not associated with lower brain volumes in these regions. The results may reflect the influence of more fully developed emotional processing of ELS on the developing brain and reinforce a body of research implicating both the ACC and insula in neuropsychiatric disorders and emotional regulation.

  19. Life and the solar uv environment on the early Earth

    NASA Astrophysics Data System (ADS)

    Bérces, A.; Kovács, G.; Rontó, G.; Lammer, H.; Kargl, G.; Kömle, N.; Bauer, S.

    2003-04-01

    The solar UV radiation environment on planetary surfaces and within their atmospheres is of importance in a wide range of scientific disciplines. Solar UV radiation is the driving force of chemical and organic evolution and serves also as a constraint in biological evolution. Studies of the solar UV environment of the early Earth 2.0 Gyr to 3.8 Gyr ago suggest that the terrestrial atmosphere was essentially anoxic, resulting in an ozone column abundance insufficient for protecting the planetary surface in the UV-B and the UV-C ranges. Since, short wavelength solar UV radiation in the UV-B ind UV-C range penetrated through the unprotected atmosphere to the surface on early Earth, associated biological consequences may be expected. For DNA-based terrestrial solar UV dosimetry, bacteriophage T7, isolated phage-DNA ind polycrystalline Uracil samples have been used. The effect of solar UV radiation can be measured by detecting the biological-structural consequences of the damage induced by UV photons. We show model calculations for the Biological Effective Dose (BED) rate of Uracil and bacteriophage T7, for various ozone concentrations representing early atmospheric conditions on Earth up to a UV protecting ozone layer comparable to present times. Further, we discuss experimental data which show the photo-reverse effect of Uracil molecules caused by short UV wavelengths. These photoreversion effect highly depend on the wavelength of the radiation. Shorter wavelength UV radiation of about 200 nm is strongly effective in monomerisation, while the longer wavelengths prefer the production of dimerisation. We could demonstrate experimentally, for the case of an Uracil thin-layer that the photo-reaction process of the nucleotides can be both, dimerization and the reverse process: monomerization. These results are important for the study of solar UV exposure on organisms in the terrestrial environment more than 2 Gyr ago where Earth had no UV protecting ozone layer as well as

  20. Telomeres, early-life stress and mental illness.

    PubMed

    Ridout, Samuel J; Ridout, Kathryn K; Kao, Hung-Teh; Carpenter, Linda L; Philip, Noah S; Tyrka, Audrey R; Price, Lawrence H

    2015-01-01

    Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying stress-response biomarker that crosses the brain/body distinction that is often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine for the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches.

  1. Telomeres, Early-Life Stress and Mental Illness

    PubMed Central

    Ridout, Samuel J.; Ridout, Kathryn K.; Kao, Hung-Teh; Carpenter, Linda L.; Philip, Noah S.; Tyrka, Audrey R.; Price, Lawrence H.

    2015-01-01

    Telomeres are structures of tandem TTAGGG repeats at the ends of chromosomes which preserve the encoding DNA by serving as a disposable brake to terminate DNA duplication during chromosome replication. In this process, the telomere itself shortens with each cell division, and can consequently be thought of as a cellular “clock” reflecting the age of a cell and the time until senescence. Telomere shortening, and changes in levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress [ELS]), and perhaps in association with some psychiatric disorders. These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying biomarker of stress response that crosses the brain/body distinction often made in medicine. Prospective studies will help to clarify whether this biomarker has broad utility in psychiatry and medicine in the evaluation of responses to psychosocial stressors. The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches. PMID:25832516

  2. Nephron number and its determinants in early life: a primer.

    PubMed

    Charlton, Jennifer R; Springsteen, Caleb H; Carmody, J Bryan

    2014-12-01

    Although there is wide variation, humans possess on average 900,000 nephrons per kidney. So far as is known, nephrons cannot regenerate; therefore, an individual's nephron endowment has profound implications in determining his or her long-term risk of developing chronic kidney disease. Most of the variability in human nephron number is determined early in life. Nephrogenesis is a complex and carefully orchestrated process that occurs during a narrow time window until 36 weeks gestation in humans, and disruption of any part of this sequence may lead to reduced nephron number. In utero, genetic abnormalities, toxic insults, and nutritional deficiencies can each alter final nephron number. Infants born prematurely must continue nephrogenesis in an ex utero environment where there may be multiple threats to successful nephrogenesis. Once the nephron endowment is determined, postnatal factors (such as acute kidney injury or chronic illnesses) can only decrease nephron number. Current techniques for estimating nephron number require an invasive procedure or complete destruction of the tissue, making noninvasive means for counting nephron surgently needed. A better understanding of nephron number and its determinants, particularly during growth and maturation, could allow the development of therapies to support, prolong, or resume nephrogenesis.

  3. Life satisfaction and maladaptive behaviors in early adolescents.

    PubMed

    Lyons, Michael D; Otis, Kristin L; Huebner, E Scott; Hills, Kimberly J

    2014-12-01

    This study explored the directionality of the relations between global life satisfaction (LS) and internalizing and externalizing behaviors using a sample of regular education students who were initially enrolled in Grade 7 (n = 470). Self-report measures of internalizing and externalizing behaviors and LS were administered on 2 occasions, 6 months apart, to students from a Southeastern U.S. middle school. Short-term longitudinal analyses revealed that neither externalizing behaviors nor internalizing behaviors at Time 1 predicted LS at Time 2. However, LS at Time 1 predicted externalizing behaviors at Time 2. LS at Time 1 also predicted internalizing behaviors at Time 2, but the results were moderated by student gender. At higher levels of LS, boys reported lower levels of internalizing behaviors at Time 2. The overall results suggested that lower levels of LS are an antecedent of increased maladaptive behaviors among early adolescents. Alternatively, higher levels of LS may be a protective factor against subsequent externalizing behaviors among boys and girls and internalizing behaviors among boys. Furthermore, the results provide further support for the discriminant validity of positive and negative measures of mental health and suggest that LS measures may provide useful information for comprehensive adolescent health screening and monitoring systems.

  4. Chronic effects of acetone on the fathead minnow (Pimephales promelas) during early life-stage development

    SciTech Connect

    Mank, M.; Swigert, J.

    1995-12-31

    A 28-day post-hatch early life-stage development toxicity test was conducted to determine the chronic effects of acetone on the fathead minnow (Pimephales promelas). In this study, less than 24-hour old fathead minnow embryos were exposed to 0.25, 0.50, 1.0, 2.0, and 4.0 mL acetone/L and a negative control for a 4-day pre-hatch period and 28 days following hatch. During the pre-hatch period, no adverse effects on embryo survival or hatching success were observed in any of the treatment groups tested when compared to the negative control. From completion of matching to test termination, fathead minnows exposed to 4.0 mL acetone/L, experienced reduced survival, a statistically significant reduction in growth and impairment of critical behavioral functions when compared to the negative control group. Growth of fathead minnows exposed to 2.0 mL acetone/L also experienced a statistically significant effect upon growth when compared to the negative control, however, survival and behavior were not affected during the post-hatch period. Survival, growth, and behavior of fathead minnows exposed to 0.25, 0.50, and 1.0 mL acetone/L from hatching to test termination was comparable to the control group. The no observed effect concentration (NOEC) for fathead minnows exposed to acetone during early life-stage development was 1.0 mL acetone/L, and the lowest observed effect concentration (LOEC) was 2.0 mL acetone/L. The maximum acceptable toxicant concentration (MATC) was calculated to be 1.4 mL acetone/L.

  5. 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

  6. Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

    PubMed

    Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

    2016-10-01

    Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age.

  7. Early life socioeconomic position and immune response to persistent infections among elderly Latinos.

    PubMed

    Meier, Helen C S; Haan, Mary N; Mendes de Leon, Carlos F; Simanek, Amanda M; Dowd, Jennifer B; Aiello, Allison E

    2016-10-01

    Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T. gondii, H. pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age. PMID:27543684

  8. Impact of nutrition since early life on cardiovascular prevention

    PubMed Central

    2012-01-01

    The cardiovascular disease represents the leading cause of morbidity and mortality in Western countries and it is related to the atherosclerotic process. Cardiovascular disease risk factors, such as dyslipidemia, hypertension, insulin resistance, obesity, accelerate the atherosclerotic process which begins in childhood and progresses throughout the life span. The cardiovascular disease risk factor detection and management through prevention delays the atherosclerotic progression towards clinical cardiovascular disease. Dietary habits, from prenatal nutrition, breastfeeding, complementary feeding to childhood and adolescence nutrition play a basic role for this topic. The metabolic and neuroendocrine environment of the fetus is fundamental in the body’s “metabolic programming”. Further several studies have demonstrated the beneficial effects of breastfeeding on cardiovascular risk factors reduction. Moreover the introduction of complementary foods represents another important step, with particular regard to protein intake. An adequate distribution between macronutrients (lipids, proteins and carbohydrates) is required for correct growth development from infancy throughout adolescence and for prevention of several cardiovascular disease risk determinants in adulthood. The purpose of this review is to examine the impact of nutrition since early life on disease. La malattia cardiovascolare rappresenta la principale causa di morbilità e mortalità dei paesi occidentali ed è correlata a degenerazione vascolare aterosclerotica. I fattori di rischio cardiovascolari quali dislipidemia, ipertensione, insulino resistenza e obesità accelerano tale processo il cui esordio è noto sin dell’età pediatrica ed evolve nel corso della vita. L’individuazione e la cura dei fattori di rischio cardiovascolari mediante la prevenzione dei fattori causali ritardano la progressione dell’aterosclerosi e l’insorgenza dei sintomi cardiovascolari. La nutrizione svolge un ruolo

  9. Early life exposure to air pollution induces adult cardiac dysfunction.

    PubMed

    Gorr, Matthew W; Velten, Markus; Nelin, Timothy D; Youtz, Dane J; Sun, Qinghua; Wold, Loren E

    2014-11-01

    Exposure to ambient air pollution contributes to the progression of cardiovascular disease, particularly in susceptible populations. The objective of the present study was to determine whether early life exposure to air pollution causes persistent cardiovascular consequences measured at adulthood. Pregnant FVB mice were exposed to filtered (FA) or concentrated ambient particulate matter (PM2.5) during gestation and nursing. Mice were exposed to PM2.5 at an average concentration of 51.69 μg/m(3) from the Columbus, OH region for 6 h/day, 7 days/wk in utero until weaning at 3 wk of age. Birth weight was reduced in PM2.5 pups compared with FA (1.36 ± 0.12 g FA, n = 42 mice; 1.30 ± 0.15 g PM2.5, n = 67 P = 0.012). At adulthood, mice exposed to perinatal PM2.5 had reduced left ventricular fractional shortening compared with FA-exposed mice (43.6 ± 2.1% FA, 33.2 ± 1.6% PM2.5, P = 0.001) with greater left ventricular end systolic diameter. Pressure-volume loops showed reduced ejection fraction (79.1 ± 3.5% FA, 35.5 ± 9.5% PM2.5, P = 0.005), increased end-systolic volume (10.4 ± 2.5 μl FA, 39.5 ± 3.8 μl PM2.5, P = 0.001), and reduced dP/dt maximum (11,605 ± 200 μl/s FA, 9,569 ± 800 μl/s PM2.5, P = 0.05) and minimum (-9,203 ± 235 μl/s FA, -7,045 ± 189 μl/s PM2.5, P = 0.0005) in PM2.5-exposed mice. Isolated cardiomyocytes from the hearts of PM2.5-exposed mice had reduced peak shortening (%PS, 8.53 ± 2.82% FA, 6.82 ± 2.04% PM2.5, P = 0.003), slower calcium reuptake (τ, 0.22 ± 0.09 s FA, 0.26 ± 0.07 s PM2.5, P = 0.048), and reduced response to β-adrenergic stimulation compared with cardiomyocytes isolated from mice that were exposed to FA. Histological analyses revealed greater picro-sirius red-positive-stained areas in the PM2.5 vs. FA group, indicative of increased collagen deposition. We concluded that these data demonstrate the detrimental role of early life exposure to ambient particulate air pollution in programming of adult cardiovascular

  10. A novel passive dosing system for determining the toxicity of phenanthrene to early life stages of zebrafish.

    PubMed

    Butler, Josh D; Parkerton, Thomas F; Letinski, Daniel J; Bragin, Gail E; Lampi, Mark A; Cooper, Keith R

    2013-10-01

    Reliable experimental early life stage chronic toxicity data for fish are limited and further data are needed for polyaromatic hydrocarbons to establish environmental quality objectives and compare with toxicity model predictions. Efforts are underway to develop a zebrafish embryo toxicity test guideline to reduce, refine and replace the use of vertebrates in animal testing. An adaptation of this method which includes embryo lethal and sub-lethal developmental endpoints after a 5-day exposure as well as larval survival and growth endpoints during a subsequent 25-day test period is described using phenanthrene as a model test substance. To deliver well controlled exposure concentrations, a passive dosing system consisting of silicone coated vials and silicone O-rings was employed. Acute results indicated that edema and spinal curvature were the most sensitive sub-lethal effects observed and in many cases preceded observed mortality. The 30-day LC/EC10 for larval survival and growth was 40 and 67 μg/L respectively. Concentrations shown to cause adverse effects in this study are in the range of previous studies that have investigated the chronic effects of phenanthrene on fish. Further, results indicate that predicted water quality objectives for phenanthrene derived using the target lipid model are protective of early life stage effects on zebrafish. Based on these results the predicted water quality objectives for phenanthrene derived using the target lipid model (10 μg/L) would be protective of early life stage effects on zebrafish. PMID:23872248

  11. Evaluation for Early Life Stage Fall Chinook Salmon Exposed to Hexavalent Chromium from a Contaminated Groundwater Source

    SciTech Connect

    Patton, Gregory W.; Dauble, Dennis D.; McKinstry, Craig A.

    2007-09-01

    We conducted a laboratory evaluation to assess the risk to early life stage (i.e., eyed egg to swim up) fall Chinook salmon (Oncorhynchus tshawytscha) for exposure to hexavalent chromium from a contaminated groundwater source. Local populations of fall Chinook salmon were exposed to Hanford Site source groundwater that was diluted with Columbia River water. Specific endpoints included survival, development rate, and growth. Tissue burdens of fish were also measured to estimate uptake and elimination rates of chromium. Survival, development, and growth of early life stage fall Chinook salmon were not adversely affected by extended exposures (i.e., 98 day) to hexavalent chromium ranging from 0.79 to 260 μg/L. Survival for all treatment levels and controls exceeded 98% at termination of the test. In addition, there were no differences among the mean lengths and weights of fish among all treatment groups. Whole-body concentrations of chromium in early life stage fall Chinook salmon had a typical dose-response pattern; i.e., those subjected to highest exposure concentrations and longest exposure intervals had higher tissue concentrations. Given the spatial extent of chromium concentrations at the Hanford Site, and the dynamics of the groundwater - river water interface, the current cleanup criterion of 10 µg/L chromium appear adequate to protect fall Chinook salmon populations.

  12. Do minimum wages improve early life health? Evidence from developing countries.

    PubMed

    Majid, Muhammad Farhan; Mendoza Rodríguez, José M; Harper, Sam; Frank, John; Nandi, Arijit

    2016-06-01

    The impact of legislated minimum wages on the early-life health of children living in low and middle-income countries has not been examined. For our analyses, we used data from the Demographic and Household Surveys (DHS) from 57 countries conducted between 1999 and 2013. Our analyses focus on height-for-age z scores (HAZ) for children under 5 years of age who were surveyed as part of the DHS. To identify the causal effect of minimum wages, we utilized plausibly exogenous variation in the legislated minimum wages during each child's year of birth, the identifying assumption being that mothers do not time their births around changes in the minimum wage. As a sensitivity exercise, we also made within family comparisons (mother fixed effect models). Our final analysis on 49 countries reveal that a 1% increase in minimum wages was associated with 0.1% (95% CI = -0.2, 0) decrease in HAZ scores. Adverse effects of an increase in the minimum wage were observed among girls and for children of fathers who were less than 35 years old, mothers aged 20-29, parents who were married, parents who were less educated, and parents involved in manual work. We also explored heterogeneity by region and GDP per capita at baseline (1999). Adverse effects were concentrated in lower-income countries and were most pronounced in South Asia. By contrast, increases in the minimum wage improved children's HAZ in Latin America, and among children of parents working in a skilled sector. Our findings are inconsistent with the hypothesis that increases in the minimum wage unconditionally improve child health in lower-income countries, and highlight heterogeneity in the impact of minimum wages around the globe. Future work should involve country and occupation specific studies which can explore not only different outcomes such as infant mortality rates, but also explore the role of parental investments in shaping these effects. PMID:27132065

  13. Do minimum wages improve early life health? Evidence from developing countries.

    PubMed

    Majid, Muhammad Farhan; Mendoza Rodríguez, José M; Harper, Sam; Frank, John; Nandi, Arijit

    2016-06-01

    The impact of legislated minimum wages on the early-life health of children living in low and middle-income countries has not been examined. For our analyses, we used data from the Demographic and Household Surveys (DHS) from 57 countries conducted between 1999 and 2013. Our analyses focus on height-for-age z scores (HAZ) for children under 5 years of age who were surveyed as part of the DHS. To identify the causal effect of minimum wages, we utilized plausibly exogenous variation in the legislated minimum wages during each child's year of birth, the identifying assumption being that mothers do not time their births around changes in the minimum wage. As a sensitivity exercise, we also made within family comparisons (mother fixed effect models). Our final analysis on 49 countries reveal that a 1% increase in minimum wages was associated with 0.1% (95% CI = -0.2, 0) decrease in HAZ scores. Adverse effects of an increase in the minimum wage were observed among girls and for children of fathers who were less than 35 years old, mothers aged 20-29, parents who were married, parents who were less educated, and parents involved in manual work. We also explored heterogeneity by region and GDP per capita at baseline (1999). Adverse effects were concentrated in lower-income countries and were most pronounced in South Asia. By contrast, increases in the minimum wage improved children's HAZ in Latin America, and among children of parents working in a skilled sector. Our findings are inconsistent with the hypothesis that increases in the minimum wage unconditionally improve child health in lower-income countries, and highlight heterogeneity in the impact of minimum wages around the globe. Future work should involve country and occupation specific studies which can explore not only different outcomes such as infant mortality rates, but also explore the role of parental investments in shaping these effects.

  14. Learning about Life and Death in Early Childhood

    ERIC Educational Resources Information Center

    Slaughter, Virginia; Lyons, Michelle

    2003-01-01

    Inagaki and Hatano (2002) have argued that young children initially understand biological phenomena in terms of vitalism, a mode of construal in which "life" or "life-force" is the central causal-explanatory concept. This study investigated the development of vitalistic reasoning in young children's concepts of life, the human body and death.…

  15. Early Quality of Life in Patients with Localized Prostate Carcinoma

    PubMed Central

    Eton, David T.; Lepore, Stephen J.; Helgeson, Vicki S.

    2008-01-01

    BACKGROUND Men with localized prostate carcinoma are faced with important treatment decisions, and quality of life (QoL) information has become a crucial element of decision making. The first objective of this study was to compare the early, health-related QoL (HRQoL) of men with localized prostate carcinoma who were treated with radical prostatectomy, external beam radiotherapy, or brachytherapy. A second objective was to identify demographic and psychosocial variables that predict HRQoL. METHODS Two-hundred fifty-six men with localized prostate carcinoma were interviewed within 7 weeks of treatment initiation. The interview included measures of prostate-specific HRQoL (the University of California—Los Angeles Prostate Cancer Index), general HRQoL (the SF-36), and psychosocial variables. RESULTS After adjusting for covariates, treatment group differences were found for both prostate specific HRQoL and general HRQoL. Men who underwent prostatectomy reported more urinary and sexual problems and more general physical dysfunction compared with men who were treated with either form of radiation therapy. Men who were treated with brachytherapy reported the fewest problems in sexual function and the least general physical dysfunction. Few treatment group differences were found in mental functioning. Both demographic factors and psychosocial factors predicted HRQoL. Older men and African-American men reported more physical problems than younger men and Caucasian men, respectively. A supportive social environment, high self-efficacy, and high self-esteem were predictive of better HRQoL. CONCLUSIONS Shortly after undergoing treatment for localized prostate carcinoma, men who underwent radical prostatectomy, older men, and African-American men are at heightened risk for experiencing prostate-specific and general deficits in HRQoL. Having psychosocial resources from which to draw may enhance HRQoL. PMID:11745222

  16. Early Life Factors and Risk of Childhood Rhabdomyosarcoma

    PubMed Central

    Shrestha, Anshu; Ritz, Beate; Ognjanovic, Simona; Lombardi, Christina A.; Wilhelm, Michelle; Heck, Julia E.

    2013-01-01

    Although little is known about etiology of childhood rhabdomyosarcoma (RMS), early life factors are suspected in the etiology. We explored this hypothesis using linked data from the California Cancer Registry and the California birth rolls. Incident cases were 359 children <6-year-old (218 embryonal, 81 alveolar, 60 others) diagnosed in 1988–2008. Controls (205, 173), frequency matched on birth year (1986–2007), were randomly selected from the birth rolls. We examined association of birth characteristics such as birth weight, size for gestational age, and timing of prenatal care with all-type RMS, embryonal, and alveolar subtypes. Crude and adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated using logistic regression. In contrast to a previous study, we observed statistically non-significant association for embryonal subtype among high birth weight (4000–5250 g) children for term births [OR (95% CI): 1.28 (0.85, 1.92)] and all births adjusted for gestational age [OR (95% CI): 1.21 (0.81, 1.81)]. On the other hand, statistically significant 1.7-fold increased risk of alveolar subtype (95% CI: 1.02, 2.87) was observed among children with late or no prenatal care and a 1.3-fold increased risk of all RMS subtypes among children of fathers ≥35 years old at child birth (95% CI: 1.00, 1.75), independent of all covariates. Our finding of positive association on male sex for all RMS types is consistent with previous studies. While we did not find a convincingly positive association between high birth weight and RMS, our findings on prenatal care supports the hypothesis that prenatal environment modifies risk for childhood RMS. PMID:24350186

  17. FKBP5 polymorphisms moderate the influence of adverse life events on the risk of anxiety and depressive disorders in preschool children.

    PubMed

    Scheuer, Sandra; Ising, Marcus; Uhr, Manfred; Otto, Yvonne; von Klitzing, Kai; Klein, Annette Maria

    2016-01-01

    FKBP5 is thought to be involved in the pathogenesis of stress-related disorders. Studies have shown that FKBP5 genotypes moderate the risk of post-traumatic stress disorder and depression in traumatized adults. We aimed to replicate this finding in a sample of preschool children. Parents of preschoolers (N = 186) were interviewed using the Preschool Age Psychiatric Assessment (PAPA) to evaluate the presence of anxiety and depressive disorders and to quantify the child's exposure to adverse events. All FKBP5 polymorphisms showed significant interactions with mild to moderate life events, but not with severe life events, in predicting the risk of anxiety and/or depressive disorders (p = 0.003-0.019). Children who experienced a high number of mild to moderate life events had a higher risk of developing an anxiety and/or depressive disorder if they were carriers of the minor allele compared to major allele homozygotes. Results indicate that genetic variation in FKBP5 influences the risk of anxiety and/or depressive disorders in preschool age by altering the sensitivity to the deleterious effects of mild to moderate adverse events. In case of severe life events, the FKBP5 genotype does not seem to play a role, suggesting that severe life events might influence directly the risk of anxiety and/or depressive disorders independent of an FKBP5 genotype-dependent vulnerability.

  18. Life Satisfaction in Early Adolescence: Personal, Neighborhood, School, Family, and Peer Influences

    ERIC Educational Resources Information Center

    Oberle, Eva; Schonert-Reichl, Kimberly A.; Zumbo, Bruno D.

    2011-01-01

    Drawing from an ecological assets framework as well as research and theory on positive youth development, this study examined the relationship of early adolescents' satisfaction with life to trait optimism and assets representing the social contexts in which early adolescents spend most of their time. Self-reports of satisfaction with life,…

  19. Trans-Agency Early-Life Exposures and Cancer Working Group

    Cancer.gov

    The Trans-Agency Early-Life Exposures and Cancer Working Group promotes integration of early-life events and exposures into public health cancer research, control, prevention, and policy strategies to reduce the cancer burden in the United States and globally.

  20. Application of Diversity Indices to Quantify Early Life-History Diversity for Chinook Salmon

    SciTech Connect

    Johnson, Gary E.; Sather, Nichole K.; Skalski, John R.; Teel, David

    2014-03-01

    We developed an index of early life history diversity (ELHD) for Pacific salmon (Oncorhynchus spp.) Early life history diversity is the variation in morphological and behavioral traits expressed within and among populations by individual juvenile salmon during their downstream migration. A standard quantitative method does not exist for this prominent concept in salmon biology.

  1. Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico.

    PubMed

    DeGraff, Deborah S; Wong, Rebeca

    2014-04-01

    This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth.

  2. Modeling old-age wealth with endogenous early-life outcomes: The case of Mexico

    PubMed Central

    DeGraff, Deborah S.; Wong, Rebeca

    2014-01-01

    This paper contributes to the literature on the life course and aging by examining the association between early-life outcomes and late-life well being, using data from the Mexican Health and Aging Study. Empirical research in this area has been challenged by the potential endogeneity of the early-life outcomes of interest, an issue which most studies ignore or downplay. Our contribution takes two forms: (1) we examine in detail the potential importance of two key life-cycle outcomes, age at marriage (a measure of family formation) and years of educational attainment (a measure of human capital investment) for old-age wealth, and (2) we illustrate the empirical value of past context variables that could help model the association between early-life outcomes and late-life well being. Our illustrative approach, matching macro-level historical policy and census variables to individual records to use as instruments in modeling the endogeneity of early-life behaviors, yields a statistically identified two-stage model of old-age wealth with minimum bias. We use simulations to show that the results for the model of wealth in old age are meaningfully different when comparing the approach that accounts for endogeneity with an approach that assumes exogeneity of early-life outcomes. Furthermore, our results suggest that in the Mexican case, models which ignore the potential endogeneity of early-life outcomes are likely to under-estimate the effects of such variables on old-age wealth. PMID:25170434

  3. Low-grade disease activity in early life precedes childhood asthma and allergy.

    PubMed

    Chawes, Bo Lund Krogsgaard

    2016-08-01

    neonates is associated with wheezing and asthma proneness, but it is unknown if such host factor also confers a risk of acute bronchiolitis, which is considered an index event of asthma persisting into school age. In paper VI, we investigated neonatal forced flow, volume, and responsiveness to methacholine in relation to occurrence of acute severe bronchiolitis at age 0-2 years. Children developing bronchiolitis had a 2.5-fold increased bronchial responsiveness as neonates (VI) suggesting a preexisting joint propensity of the airways to react adversely to common respiratory viruses and to develop asthma. This finding proposes airway hyperresponsiveness as yet another marker of low-grade disease activity among asymptomatic neonates on a trajectory towards childhood asthma. In paper VII, we examined whether neonates with impaired pulmonary capacity also had signs of systemic inflammation prior to clinical symptoms. Reduced FEV0.5 was significantly associated with elevated serum hs-CRP and other blood inflammatory markers (VII) suggesting presence of systemic low-grade inflammation from the beginning of life. Chronic low-grade inflammation is a common nominator of virtually all the major non-communicable welfare diseases (NCDs) of modernity whereof asthma and allergies are the earliest debuting disorders. The novel finding of systemic low-grade inflammation among neonates at increased risk of asthma and allergy, therefore implies that exploring the origins of asthma and allergy may also unravel disease mechanisms involved in other NCDs. In conclusion, the series of papers presented in this thesis (I-VII) evidence the presence of a pre-symptomatic disease process measurable in several body compartments, which supports the notion of low-grade disease activity in early life as a generic trait among neonates developing asthma and allergy. This hypothesis piggybacking on single biomarker assessments could be enforced and refined by applying novel global omics approaches. In

  4. 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...

  5. How emotional abilities modulate the influence of early life stress on hippocampal functioning

    PubMed Central

    Alkan Härtwig, Elif; Koelsch, Stefan; Heekeren, Hauke R.; Heuser, Isabella; Bajbouj, Malek

    2014-01-01

    Early life stress (ELS) is known to have considerable influence on brain development, mental health and affective functioning. Previous investigations have shown that alexithymia, a prevalent personality trait associated with difficulties experiencing and verbalizing emotions, is particularly related to ELS. The aim of the present study was to investigate how neural correlates of emotional experiences in alexithymia are altered in the presence and absence of ELS. Therefore, 50 healthy individuals with different levels of alexithymia were matched regarding ELS and investigated with respect to neural correlates of audio-visually induced emotional experiences via functional magnetic resonance imaging. The main finding was that ELS modulated hippocampal responses to pleasant (>neutral) stimuli in high-alexithymic individuals, whereas there was no such modulation in low-alexithymic individuals matched for ELS. Behavioral and psychophysiological results followed a similar pattern. When considered independent of ELS, alexithymia was associated with decreased responses in insula (pleasant > neutral) and temporal pole (unpleasant > neutral). Our results show that the influence of ELS on emotional brain responses seems to be modulated by an individual’s degree of alexithymia. Potentially, protective and adverse effects of emotional abilities on brain responses to emotional experiences are discussed. PMID:23685776

  6. Effect of chronic copper and pentachlorophenol exposure to early life stages of Xenopus laevis

    SciTech Connect

    Fort, D.J.; Stover, E.L.

    1995-12-31

    An evaluation of the effects of low-level copper and pentachlorophenol exposure on various early life stages of the South African clawed frog, Xenopus laevis was performed using stage-specific and long-term continuous exposures. Stage-specific exposure experiments were conducted such that separate subsets of embryos and larvae from the same clutch were exposed to two toxicants, copper and pentachlorophenol, from 0 d to 4 d (standard Frog Embryo Teratagenesis Assay Xenopus [FETAX]), 4 d to 8 d, 8 d to 12 d, and 12 d to 16 d. Results from two separate concentration-response experiments indicated that sensitivity to either toxicant increased in each successive time period. Continuous exposure studies conducted for 60 to 75 days indicated that copper, but not pentachlorophenol induced reduction deficiency malformations of the hind limb at concentrations as low as 0.05 mg/L. Pentachlorophenol concentrations as low as 0.5/{micro}g/L inhibited tail resorption. However, copper did not adversely affect the process of tail resorption. These results indicated that studies evaluating longer-term developmental processes are important in ecological hazard evaluation.

  7. Life, Labor, and, Song in New England during the Early Republic.

    ERIC Educational Resources Information Center

    Scott, John W., Ed.; Scott, John A., Ed.

    1998-01-01

    Singing the tunes in this collection will help students understand many of the realities of life during the early years of the United States. From hearth and home to the perils of the sea, and from factory life to Presidential elections, this journal offers a selection of 19 songs to introduce the life and labor of New England people during the…

  8. Conditions for the emergence of life on the early Earth: summary and reflections

    PubMed Central

    Jortner, Joshua

    2006-01-01

    This review attempts to situate the emergence of life on the early Earth within the scientific issues of the operational and mechanistic description of life, the conditions and constraints of prebiotic chemistry, together with bottom-up molecular fabrication and biomolecular nanofabrication and top-down miniaturization approaches to the origin of terrestrial life. PMID:17008225

  9. Early life origins of metabolic disease: Developmental programming of hypothalamic pathways controlling energy homeostasis.

    PubMed

    Dearden, Laura; Ozanne, Susan E

    2015-10-01

    A wealth of animal and human studies demonstrate that perinatal exposure to adverse metabolic conditions - be it maternal obesity, diabetes or under-nutrition - results in predisposition of offspring to develop obesity later in life. This mechanism is a contributing factor to the exponential rise in obesity rates. Increased weight gain in offspring exposed to maternal obesity is usually associated with hyperphagia, implicating altered central regulation of energy homeostasis as an underlying cause. Perinatal development of the hypothalamus (a brain region key to metabolic regulation) is plastic and sensitive to metabolic signals during this critical time window. Recent research in non-human primate and rodent models has demonstrated that exposure to adverse maternal environments impairs the development of hypothalamic structure and consequently function, potentially underpinning metabolic phenotypes in later life. This review summarizes our current knowledge of how adverse perinatal environments program hypothalamic development and explores the mechanisms that could mediate these effects.

  10. Early-Life State-of-Residence Characteristics and Later Life Hypertension, Diabetes, and Ischemic Heart Disease

    PubMed Central

    Eisen, Ellen A.; Modrek, Sepideh; Mokyr Horner, Elizabeth; Goldstein, Benjamin; Costello, Sadie; Cantley, Linda F.; Slade, Martin D.; Cullen, Mark R.

    2015-01-01

    Objectives. We examined how state characteristics in early life are associated with individual chronic disease later in life. Methods. We assessed early-life state of residence using the first 3 digits of social security numbers from blue- and white-collar workers from a US manufacturing company. Longitudinal data were available from 1997 to 2012, with 305 936 person-years of observation. Disease was assessed using medical claims. We modeled associations using pooled logistic regression with inverse probability of censoring weights. Results. We found small but statistically significant associations between early-state-of-residence characteristics and later life hypertension, diabetes, and ischemic heart disease. The most consistent associations were with income inequality, percentage non-White, and education. These associations were similar after statistically controlling for individual socioeconomic and demographic characteristics and current state characteristics. Conclusions. Characteristics of the state in which an individual lives early in life are associated with prevalence of chronic disease later in life, with a strength of association equivalent to genetic associations found for these same health outcomes. PMID:26066927

  11. The Role of Eye Movement Desensitization and Reprocessing (EMDR) Therapy in Medicine: Addressing the Psychological and Physical Symptoms Stemming from Adverse Life Experiences

    PubMed Central

    Shapiro, Francine

    2014-01-01

    Background: A substantial body of research shows that adverse life experiences contribute to both psychological and biomedical pathology. Eye movement desensitization and reprocessing (EMDR) therapy is an empirically validated treatment for trauma, including such negative life experiences as commonly present in medical practice. The positive therapeutic outcomes rapidly achieved without homework or detailed description of the disturbing event offer the medical community an efficient treatment approach with a wide range of applications. Methods: All randomized studies and significant clinical reports related to EMDR therapy for treating the experiential basis of both psychological and somatic disorders are reviewed. Also reviewed are the recent studies evaluating the eye movement component of the therapy, which has been posited to contribute to the rapid improvement attributable to EMDR treatment. Results: Twenty-four randomized controlled trials support the positive effects of EMDR therapy in the treatment of emotional trauma and other adverse life experiences relevant to clinical practice. Seven of 10 studies reported EMDR therapy to be more rapid and/or more effective than trauma-focused cognitive behavioral therapy. Twelve randomized studies of the eye movement component noted rapid decreases in negative emotions and/or vividness of disturbing images, with an additional 8 reporting a variety of other memory effects. Numerous other evaluations document that EMDR therapy provides relief from a variety of somatic complaints. Conclusion: EMDR therapy provides physicians and other clinicians with an efficient approach to address psychological and physiologic symptoms stemming from adverse life experiences. Clinicians should therefore evaluate patients for experiential contributors to clinical manifestations. PMID:24626074

  12. Early Memories as a Guide to Client Movement through Life.

    ERIC Educational Resources Information Center

    Slavik, Steve

    1991-01-01

    Outlines the theory of the significance of early memories used as a projective tool by Adlerian psychologists. Describes a procedure for elicitation and interpretation of early memories and provides several examples of their use in an encouraging therapeutic context. Attempts to show effectiveness of this technique in assessing client issues and…

  13. Transgenerational Effects of Early Life Starvation on Growth, Reproduction, and Stress Resistance in Caenorhabditis elegans

    PubMed Central

    Jobson, Meghan A.; Jordan, James M.; Sandrof, Moses A.; Hibshman, Jonathan D.; Lennox, Ashley L.; Baugh, L. Ryan

    2015-01-01

    Starvation during early development can have lasting effects that influence organismal fitness and disease risk. We characterized the long-term phenotypic consequences of starvation during early larval development in Caenorhabditis elegans to determine potential fitness effects and develop it as a model for mechanistic studies. We varied the amount of time that larvae were developmentally arrested by starvation after hatching (“L1 arrest”). Worms recovering from extended starvation grew slowly, taking longer to become reproductive, and were smaller as adults. Fecundity was also reduced, with the smallest individuals most severely affected. Feeding behavior was impaired, possibly contributing to deficits in growth and reproduction. Previously starved larvae were more sensitive to subsequent starvation, suggesting decreased fitness even in poor conditions. We discovered that smaller larvae are more resistant to heat, but this correlation does not require passage through L1 arrest. The progeny of starved animals were also adversely affected: Embryo quality was diminished, incidence of males was increased, progeny were smaller, and their brood size was reduced. However, the progeny and grandprogeny of starved larvae were more resistant to starvation. In addition, the progeny, grandprogeny, and great-grandprogeny were more resistant to heat, suggesting epigenetic inheritance of acquired resistance to starvation and heat. Notably, such resistance was inherited exclusively from individuals most severely affected by starvation in the first generation, suggesting an evolutionary bet-hedging strategy. In summary, our results demonstrate that starvation affects a variety of life-history traits in the exposed animals and their descendants, some presumably reflecting fitness costs but others potentially adaptive. PMID:26187123

  14. 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…

  15. Early feeding and early life housing conditions influence the response towards a noninfectious lung challenge in broilers.

    PubMed

    Simon, K; de Vries Reilingh, G; Bolhuis, J E; Kemp, B; Lammers, A

    2015-09-01

    Early life conditions such as feed and water availability immediately post hatch (PH) and housing conditions may influence immune development and therefore immune reactivity later in life. The current study addressed the consequences of a combination of these 2 early life conditions for immune reactivity, i.e., the specific antibody response towards a non-infectious lung challenge. Broiler chicks received feed and water either immediately p.h. or with a 72 h delay and were either reared in a floor or a cage system. At 4 weeks of age, chicks received either an intra-tracheally administered Escherichia coli lipopolysaccharide (LPS)/Human Serum Albumin (HUSA) challenge or a placebo, and antibody titers were measured up to day 14 after administration of the challenge. Chicks housed on the floor and which had a delayed access to feed p.h. showed the highest antibody titers against HuSA. These chicks also showed the strongest sickness response and poorest performance in response to the challenge, indicating that chicks with delayed access to feed might be more sensitive to an environment with higher antigenic pressure. In conclusion, results from the present study show that early life feeding strategy and housing conditions influence a chick's response to an immune challenge later in life. These 2 early life factors should therefore be taken into account when striving for a balance between disease resistance and performance in poultry.

  16. Life history plasticity of a tropical seabird in response to El Niño anomalies during early life.

    PubMed

    Ancona, Sergio; Drummond, Hugh

    2013-01-01

    Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO) experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability) in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life.

  17. Life History Plasticity of a Tropical Seabird in Response to El Niño Anomalies during Early Life

    PubMed Central

    Ancona, Sergio; Drummond, Hugh

    2013-01-01

    Food shortage and other challenges associated with El Niño Southern Oscillation (ENSO) experienced early in life may have long-term impacts on life history traits, but these potential impacts remain virtually unexplored. By monitoring 2556 blue-footed boobies from 11 cohorts, we showed that birds facing warm water ENSO conditions (and probably low food availability) in the natal year were underweight at fledging, recruited earlier and bred less frequently, but showed no deficit in longevity or breeding success over the first 10 years. Life history impacts of ENSO were substantial when experienced in the prenatal year, the natal year, or the second year of life, and absent when experienced in the third year of life, implying that harsh conditions have greater effects when experienced earlier in life. Sexual differences in impacts depended on the age when warm water conditions were experienced: pre-natal and natal experience, respectively, induced early recruitment and influenced the relationship between age and laying date only in females, whereas second year experience reduced total breeding success only of males. Most surprising were positive transgenerational impacts in females: daughters of females that experienced ENSO conditions in their natal year showed improved breeding success. Developmental plasticity of boobies thus enables them to largely neutralize potential long-term impacts of harsh climatic conditions experienced early in life. PMID:24023760

  18. FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

    PubMed

    Lieberman, Richard; Armeli, Stephen; Scott, Denise M; Kranzler, Henry R; Tennen, Howard; Covault, Jonathan

    2016-09-01

    Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc. PMID:27196697

  19. FKBP5 genotype interacts with early life trauma to predict heavy drinking in college students.

    PubMed

    Lieberman, Richard; Armeli, Stephen; Scott, Denise M; Kranzler, Henry R; Tennen, Howard; Covault, Jonathan

    2016-09-01

    Alcohol use disorder (AUD) is debilitating and costly. Identification and better understanding of risk factors influencing the development of AUD remain a research priority. Although early life exposure to trauma increases the risk of adulthood psychiatric disorders, including AUD, many individuals exposed to early life trauma do not develop psychopathology. Underlying genetic factors may contribute to differential sensitivity to trauma experienced in childhood. The hypothalamic-pituitary-adrenal (HPA) axis is susceptible to long-lasting changes in function following childhood trauma. Functional genetic variation within FKBP5, a gene encoding a modulator of HPA axis function, is associated with the development of psychiatric symptoms in adulthood, particularly among individuals exposed to trauma early in life. In the current study, we examined interactions between self-reported early life trauma, past-year life stress, past-year trauma, and a single nucleotide polymorphism (rs1360780) in FKBP5 on heavy alcohol consumption in a sample of 1,845 college students from two university settings. Although we found no effect of early life trauma on heavy drinking in rs1360780*T-allele carriers, rs1360780*C homozygotes exposed to early life trauma had a lower probability of heavy drinking compared to rs1360780*C homozygotes not exposed to early life trauma (P < 0.01). The absence of an interaction between either current life stress or past-year trauma, and FKBP5 genotype on heavy drinking suggests that there exists a developmental period of susceptibility to stress that is moderated by FKBP5 genotype. These findings implicate interactive effects of early life trauma and FKBP5 genetic variation on heavy drinking. © 2016 Wiley Periodicals, Inc.

  20. Serotonin Transporter Expression is Predicted by Early Life Stress and is Associated with Disinhibited Behavior in Infant Rhesus Macaques

    PubMed Central

    Kinnally, E. L.; Tarara, E. R.; Mason, W.A.; Mendoza, S.P.; Abel, K.; Lyons, L.A.; Capitanio, John P.

    2009-01-01

    Serotonin transporter (5-HTT) expression patterns may contribute to the risk for adverse psychological outcomes following early life stress. The present study investigated whether two types of early life stress, maternal and social aggression, and the serotonin transporter gene promoter polymorphism (rh5-HTTLPR) predicted lower post-stressor PBMC 5-HTT expression in infant rhesus macaques. We further probed the relationships among these factors and infant behavioral disinhibition within a stressful situation. Fifty-three infants residing with mothers in large, complex social groups were observed over the first 12 postnatal weeks, during which time the rate of aggression received by the infant from their mothers and social group members was recorded. At 90- 120 days of age, infants underwent a 25-hour maternal separation/biobehavioral assessment, which included standardized behavioral assessments and blood sampling. Infants' rh5-HTTLPR genotypes were determined, and infant 5-HTT expression was quantified from PBMCs collected eight hours after separation. Receipt of aggression from the mother, but not from social group members, was associated with lower post-stressor 5-HTT expression. Lower post-stressor 5-HTT expression, but not receipt of aggression, was associated with disinhibited behavior during assessment. Rh5-HTTLPR genotype was unrelated to any measure. We conclude that 5-HTT regulation is linked with specific, presumably stressful early experiences in infant rhesus macaques. Further, 5-HTT expression may be a better predictor of behavioral disinhibition than genotype or experiences, presumably via parallel processes that operate in the brain. PMID:19817873

  1. Sociodemographic Risk, Developmental Competence, and PTSD Symptoms in Young Children Exposed to Interpersonal Trauma in Early Life

    PubMed Central

    Enlow, Michelle Bosquet; Blood, Emily; Egeland, Byron

    2014-01-01

    Children under age six years are disproportionately exposed to interpersonal trauma, including maltreatment and witnessing intimate partner violence (IPV), and may be particularly susceptible to negative sequelae. However, young children have generally been neglected from trauma research; thus, little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed prospectively from birth to 1st grade via home and laboratory observations, record reviews, and maternal and teacher interviews. Greater trauma exposure and sociodemographic risk and lower developmental competence predicted more severe PTSD symptoms. Developmental competence partially mediated the association between exposures and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a) exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and child mental health. PMID:24490247

  2. Sociodemographic risk, developmental competence, and PTSD symptoms in young children exposed to interpersonal trauma in early life.

    PubMed

    Enlow, Michelle Bosquet; Blood, Emily; Egeland, Byron

    2013-12-01

    Young children are disproportionately exposed to interpersonal trauma (maltreatment, witnessing intimate partner violence [IPV]) and appear particularly susceptible to negative sequelae. Little is known about the factors influencing vulnerability to traumatic stress responses and other negative outcomes in early life. This study examined associations among interpersonal trauma exposure, sociodemographic risk, developmental competence, and posttraumatic stress disorder (PTSD) symptoms in 200 children assessed from birth to first grade via standardized observations, record reviews, and maternal and teacher interviews. More severe PTSD symptoms were predicted by greater trauma exposure (r = .43), greater sociodemographic risk (r = .22), and lower developmental competence (rs=−.31 and −.54 for preschool and school-age developmental competence, respectively). Developmental competence partially mediated the association between trauma exposure and symptoms. Trauma exposure fully mediated the association between sociodemographic risk and symptoms. Neither sociodemographic risk nor developmental competence moderated trauma exposure effects on symptoms. The findings suggest that (a)exposure to maltreatment and IPV has additive effects on posttraumatic stress risk in early life, (b) associations between sociodemographic adversity and poor mental health may be attributable to increased trauma exposure in disadvantaged populations, and (c) early exposures have a negative cascade effect on developmental competence and mental health.

  3. Searching for Life: Early Earth, Mars and Beyond

    NASA Technical Reports Server (NTRS)

    DesMarais, David J.; Chang, Sherwood (Technical Monitor)

    1996-01-01

    We might be entering a golden age for exploring life throughout time and space. Rapid gene sequencing will better define our most distant ancestors. The earliest geologic evidence of life is now 3.8 billion years old. Organic matter and submicron-sized morphologies have been preserved in the martian crust for billions of years. Several new missions to Mars are planned, with a high priority on the search for life, past or present. The recent discovery of large extrasolar planets has heightened interest in spacecraft to detect small, earth-like planets. A recent workshop discussed strategies for life detection on such planets. There is much to anticipate in the near future.

  4. PROSTATE CANCER: IS IT TIME TO EXPAND THE RESEARCH FOCUS TO EARLY-LIFE EXPOSURES?

    PubMed Central

    Sutcliffe, Siobhan; Colditz, Graham A.

    2013-01-01

    Preface Although the contribution of lifestyle and environment (non-genetic factors) to prostate carcinogenesis is indicated by international variation in prostate cancer occurrence and migration studies, no conclusive modifiable risk factors have been identified to date. One possible reason for this may be the dearth of epidemiological research on exposures experienced early-in-life when the immature prostate may be more susceptible to carcinogenic exposures. Herein, we motivate the study of early-life exposures, describe the small body of early-life research and its associated challenges, and point towards solutions for future research. PMID:23363989

  5. Rate of growth in early life: a predictor of later health?

    PubMed

    Rolland-Cachera, Marie François

    2005-01-01

    The purpose of this review is to describe the studies which investigate the association between early growth pattern and future metabolic risks. Childhood obesity is increasing but other growth parameters are also changing. There is a trend of earlier maturation and increasing height. The increase in height from one generation to the next occurs mainly in the first years of life. Rapid growth in early life (rapid weight and length gain, early adiposity rebound) is associated with various health risks in later life (obesity, cancer, cardiovascular diseases, diabetes). Pattern of growth rather than absolute level of fatness seams to be of most importance.

  6. Early life characteristics and late life burden of cerebral small vessel disease in the Lothian Birth Cohort 1936

    PubMed Central

    Field, Thalia S.; Doubal, Fergus N.; Johnson, Wendy; Backhouse, Ellen; McHutchison, Caroline; Cox, Simon; Corley, Janie; Pattie, Alison; Gow, Alan J.; Shenkin, Susan; Cvoro, Vera; Morris, Zoe; Staals, Julie; Bastin, Mark; Deary, Ian J.; Wardlaw, Joanna M.

    2016-01-01

    It is unknown whether relations between early-life factors and overall health in later life apply to burden of cerebral small vessel disease (cSVD), a major cause of stroke and dementia. We explored relations between early-life factors and cSVD in the Lothian Birth Cohort, a healthy aging cohort. Participants were recruited at age 70 (N = 1091); most had completed a test of cognitive ability at age 11 as part of the Scottish Mental Survey of 1947. Of those, 700 participants had brain MRI that could be rated for cSVD conducted at age 73. Presence of lacunes, white matter hyperintensities, microbleeds, and perivascular spaces were summed in a score of 0-4 representing all MRI cSVD features. We tested associations with early-life factors using multivariate logistic regression. Greater SVD score was significantly associated with lower age-11 IQ (OR higher SVD score per SD age-11 IQ = .78, 95%CI 0.65-.95, p=.01). The associations between SVD score and own job class (OR higher job class, .64 95%CI .43-.95, p=.03), age-11 deprivation index (OR per point deprivation score, 1.08, 95%CI 1.00-1.17, p=.04), and education (OR some qualifying education, .60 95%CI .37-.98, p=.04) trended towards significance (p<.05 for all) but did not meet thresholds for multiple testing. No early-life factor was significantly associated with any one individual score component. Early-life factors may contribute to age-73 burden of cSVD. These relations, and the potential for early social interventions to improve brain health, deserve further study. PMID:27652981

  7. 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.

  8. Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders.

    PubMed

    Tyrka, A R; Parade, S H; Welch, E S; Ridout, K K; Price, L H; Marsit, C; Philip, N S; Carpenter, L L

    2016-01-01

    Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic-pituitary-adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene.

  9. Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders.

    PubMed

    Tyrka, A R; Parade, S H; Welch, E S; Ridout, K K; Price, L H; Marsit, C; Philip, N S; Carpenter, L L

    2016-01-01

    Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic-pituitary-adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene. PMID

  10. Methylation of the leukocyte glucocorticoid receptor gene promoter in adults: associations with early adversity and depressive, anxiety and substance-use disorders

    PubMed Central

    Tyrka, A R; Parade, S H; Welch, E S; Ridout, K K; Price, L H; Marsit, C; Philip, N S; Carpenter, L L

    2016-01-01

    Early adversity increases risk for developing psychopathology. Epigenetic modification of stress reactivity genes is a likely mechanism contributing to this risk. The glucocorticoid receptor (GR) gene is of particular interest because of the regulatory role of the GR in hypothalamic–pituitary–adrenal (HPA) axis function. Mounting evidence suggests that early adversity is associated with GR promoter methylation and gene expression. Few studies have examined links between GR promoter methylation and psychopathology, and findings to date have been mixed. Healthy adult participants (N=340) who were free of psychotropic medications reported on their childhood experiences of maltreatment and parental death and desertion. Lifetime depressive and anxiety disorders and past substance-use disorders were assessed using the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Methylation of exon 1F of the GR gene (NR3C1) was examined in leukocyte DNA via pyrosequencing. On a separate day, a subset of the participants (n=231) completed the dexamethasone/corticotropin-releasing hormone (Dex/CRH) test. Childhood adversity and a history of past substance-use disorder and current or past depressive or anxiety disorders were associated with lower levels of NR3C1 promoter methylation across the region as a whole and at individual CpG sites (P<0.05). The number of adversities was negatively associated with NR3C1 methylation in participants with no lifetime disorder (P=0.018), but not in those with a lifetime disorder. GR promoter methylation was linked to altered cortisol responses to the Dex/CRH test (P<0.05). This study presents evidence of reduced methylation of NR3C1 in association with childhood maltreatment and depressive, anxiety and substance-use disorders in adults. This finding stands in contrast to our prior work, but is consistent with emerging findings, suggesting complexity in the regulation of this gene. PMID

  11. 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. PMID:26365331

  12. 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.

  13. Early-life Origins of Lifecycle Well-being: Research and Policy Implications

    PubMed Central

    Currie, Janet; Rossin-Slater, Maya

    2016-01-01

    Mounting evidence across different disciplines suggests that early-life conditions can have consequences on individual outcomes throughout the lifecycle. Relative to other developed countries, the United States fares poorly on standard indicators of early-life health, and this disadvantage may have profound consequences not only for population well-being, but also for economic growth and competitiveness in a global economy. In this paper, we first discuss the research on the strength of the link between early-life health and adult outcomes, and then provide an evidence-based review of the effectiveness of existing U.S. policies targeting the early-life environment. We conclude that there is a robust and economically meaningful relationship between early-life conditions and well-being throughout the lifecycle, as measured by adult health, educational attainment, labor market attachment, and other indicators of socio-economic status. However, there is some variation in the degree to which current policies in the U.S. are effective in improving early-life conditions. Among existing programs, some of the most effective are the Special Supplemental Program for Women, Infants, and Children (WIC), home visiting with nurse practitioners, and high-quality, center-based early childhood care and education. In contrast, the evidence on other policies such as prenatal care and family leave is more mixed and limited. PMID:25558491

  14. Protein needs early in life and long-term health.

    PubMed

    Michaelsen, Kim F; Greer, Frank R

    2014-03-01

    The objective of this review was to summarize selected health aspects of protein intake during the first 2 y of life. During this period there is a marked increase in protein intake from an intake of ∼ 5% of energy from protein (PE%) in an exclusively breastfed infant to ∼ 15 PE% when complementary foods have been introduced. At this age, mean protein intake is ∼ 3 times as high as the physiologic requirement, but some children receive 4-5 times their physiologic requirement. Protein from cow milk constitutes a main part of protein intake in toddlers and seems to have a specific effect on insulin-like growth factor I concentrations and growth. Meat has a high protein content, but the small amounts of meat needed to ensure good iron status have less impact on total protein intake. The difference in protein intake between breastfed and formula-fed infants is likely to play a role in the difference between breastfed and formula-fed infants. There is emerging evidence that high protein intake during the first 2 y of life is a risk factor for later development of overweight and obesity. It therefore seems prudent to avoid a high protein intake during the first 2 y of life. This could be accomplished by decreasing the upper allowable limit of the protein content of infant formulas for the first year of life and limiting the intake of cow milk in the second year of life. PMID:24452233

  15. Quantifying Cost Risk Early in the Life Cycle

    SciTech Connect

    B. Mar

    2004-11-04

    A new method for analyzing life cycle cost risk on large programs is presented that responds to an increased emphasis on improving sustainability for long-term programs. This method provides better long-term risk assessment and risk management techniques. It combines standard Monte Carlo analysis of risk drivers and a new data-driven method developed by the BMDO. The approach permits quantification of risks throughout the entire life cycle without resorting to difficult to support subjective methods. The BMDO methodology is shown to be relatively straightforward to apply to a specific component or process within a project using standard technical risk assessment methods. The total impact on system is obtained using the program WBS, which allows for the capture of correlated risks shared by multiple WBS items. Once the correlations and individual component risks are captured, a Monte Carlo simulation can be run using a modeling tool such as ANALYTICA to produce the overall life cycle cost risk.

  16. Nonmarine stromatolites and the search for early life on Mars

    NASA Technical Reports Server (NTRS)

    Awramik, S. M.

    1991-01-01

    The available evidence permits one to conclude that streams flowed and lakes developed on Mars sometime in the remote past. The lessons learned from the Earth's earliest fossil record suggest that stromatolites might have formed on Mars, speculating that: (1) biopoesis occurred on Mars during its earliest history; (2) life evolved and diversified; (3) life inhabited aqueous environments; and (4) sunlight was an important environmental resource. The most likely place to find stromatolites and possibly microbial fossils on Mars would be in ancient lake and stream deposits. If thermal spring deposits can be identified, then they too are sites for biogeological investigations. Other aspects of this study are presented.

  17. Physical Environmental Adversity and the Protective Role of Maternal Monitoring in Relation to Early Child Conduct Problems.

    PubMed

    Supplee, Lauren H; Unikel, Emily B; Shaw, Daniel S

    2007-01-01

    Research on the development of externalizing behaviors during early childhood has focused on child and parenting factors. Fewer studies have investigated effects of aversive features of the micro-level physical environment, such as overcrowding and chaos in the home, and the macro-level environment, such as neighborhood quality. This study extends research on physical environmental factors by examining their association with children's early externalizing behaviors, and exploring how maternal monitoring may serve as a protective factor in such contexts. 120 male toddlers at high risk for developing early externalizing behaviors were followed from ages 2 to 5 years. Direct longitudinal associations were found for micro-level environmental factors beginning at age 2 and for neighborhood risk beginning at age 3. Maternal monitoring served as a protective factor for child externalizing behaviors in the context of neighborhood risk. Implications for prevention research and the development of early externalizing behaviors are discussed.

  18. Examination of age-related epigenetic changes following early-life exposure to dichloroacetic acid

    EPA Science Inventory

    Recent studies have shown that transient early-life exposure to dichloroacetic acid (DCA), a pyruvate analog and metabolic reprogramming agent, increases liver cancer incidence in older mice. This carcinogenic effect is not associated with direct mutagenicity, persistent cytotoxi...

  19. Weighing Evidence from Mendelian Randomization-Early-Life Obesity as a Causal Factor in Multiple Sclerosis?

    PubMed

    Ascherio, Alberto; Munger, Kassandra L

    2016-06-01

    In this Perspective, Alberto Ascherio and Kassandra Munger discuss the implications of Richards and colleagues' study exploring the role of early-life obesity in risk of multiple sclerosis. PMID:27351631

  20. Long-term effects of early life stress exposure: Role of epigenetic mechanisms.

    PubMed

    Silberman, Dafne M; Acosta, Gabriela B; Zorrilla Zubilete, María A

    2016-07-01

    Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress during the first years of life has been shown to have profound effects on the growth and development of an adult individual. There are evidences demonstrating that stressful experiences during gestation or in early life can lead to enhanced susceptibility to mental disorders. Early-life stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and the associated neurochemical reactions following glucocorticoid release are accompanied by a rapid physiological response. An excessive response may affect the developing brain resulting in neurobehavioral and neurochemical changes later in life. This article reviews the data from experimental studies aimed to investigate hormonal, functional, molecular and epigenetic mechanisms involved in the stress response during early-life programming. We think these studies might prove useful for the identification of novel pharmacological targets for more effective treatments of mental disorders.

  1. Long-term effects of early life stress exposure: Role of epigenetic mechanisms.

    PubMed

    Silberman, Dafne M; Acosta, Gabriela B; Zorrilla Zubilete, María A

    2016-07-01

    Stress is an adaptive response to demands of the environment and thus essential for survival. Exposure to stress during the first years of life has been shown to have profound effects on the growth and development of an adult individual. There are evidences demonstrating that stressful experiences during gestation or in early life can lead to enhanced susceptibility to mental disorders. Early-life stress triggers hypothalamic-pituitary-adrenocortical (HPA) axis activation and the associated neurochemical reactions following glucocorticoid release are accompanied by a rapid physiological response. An excessive response may affect the developing brain resulting in neurobehavioral and neurochemical changes later in life. This article reviews the data from experimental studies aimed to investigate hormonal, functional, molecular and epigenetic mechanisms involved in the stress response during early-life programming. We think these studies might prove useful for the identification of novel pharmacological targets for more effective treatments of mental disorders. PMID:26774789

  2. Life Satisfaction and Maladaptive Behaviors in Early Adolescents

    ERIC Educational Resources Information Center

    Lyons, Michael D.; Otis, Kristin L.; Huebner, E. Scott; Hills, Kimberly J.

    2014-01-01

    This study explored the directionality of the relations between global life satisfaction (LS) and internalizing and externalizing behaviors using a sample of regular education students who were initially enrolled in Grade 7 ("n" = 470). Self-report measures of internalizing and externalizing behaviors and LS were administered on 2…

  3. Effect of ocean warming and acidification on the early life stages of subtropical Acropora spicifera

    NASA Astrophysics Data System (ADS)

    Foster, T.; Gilmour, J. P.; Chua, C. M.; Falter, J. L.; McCulloch, M. T.

    2015-12-01

    This study investigated the impacts of acidified seawater ( pCO2 ~ 900 μatm) and elevated water temperature (+3 °C) on the early life history stages of Acropora spicifera from the subtropical Houtman Abrolhos Islands (28°S) in Western Australia. Settlement rates were unaffected by high temperature (27 °C, ~250 μatm), high pCO2 (24 °C, ~900 μatm), or a combination of both high temperature and high pCO2 treatments (27 °C, ~900 μatm). There were also no significant differences in rates of post-settlement survival after 4 weeks of exposure between any of the treatments, with survival ranging from 60 to 70 % regardless of treatment. Similarly, calcification, as determined by the skeletal weight of recruits, was unaffected by an increase in water temperature under both ambient and high pCO2 conditions. In contrast, high pCO2 significantly reduced early skeletal development, with mean skeletal weight in the high pCO2 and combined treatments reduced by 60 and 48 %, respectively, compared to control weights. Elevated temperature appeared to have a partially mitigative effect on calcification under high pCO2; however, this effect was not significant. Our results show that rates of settlement, post-settlement survival, and calcification in subtropical corals are relatively resilient to increases in temperature. This is in marked contrast to the sensitivity to temperature reported for the majority of tropical larvae and recruits in the literature. The subtropical corals in this study appear able to withstand an increase in temperature of 3 °C above ambient, indicating that they may have a wider thermal tolerance range and may not be adversely affected by initial increases in water temperature from subtropical 24 to 27 °C. However, the reduction in skeletal weight with high pCO2 indicates that early skeletal formation will be highly vulnerable to the changes in ocean pCO2 expected to occur over the twenty-first century, with implications for their longer-term growth

  4. Patterns of Reef Ecosystem Recovery Indicate That Adverse Early Triassic Ocean Conditions Extended into Middle Triassic Time

    NASA Astrophysics Data System (ADS)

    Kelley, B. M.; Yu, M.; Lehrmann, D. J.; Jost, A. B.; Lau, K. V.; Li, X.; Schaal, E. K.; Payne, J.

    2013-12-01

    The pattern of reef ecosystem recovery from the end-Permian extinction is poorly constrained due to the limited stratigraphic, spatial, and geographic range of reef buildups in Early Triassic and Anisian (early Middle Triassic) strata. In this study, we combined field studies and petrographic analysis to examine the pattern of reef evolution in latest Permian to Late Triassic carbonate platforms in the Nanpanjiang Basin of South China, an area of extensive shallow-water carbonate deposition in the tropical eastern Tethys. We find that early Mesozoic reef recovery in the eastern Tethys was a five-step process: (1) in the immediate aftermath of extinction, calcimicrobial biostromes (P/T boundary microbialites) developed in shallow-water platform settings; (2) in late Induan time, biohermal stromatolites developed in platform interior settings; (3) in latest Spathian time, large-scale Tubiphytes, microbial, and cement reefs lacking skeletal metazoans initiated on the margins and steep upper slopes of carbonate platforms, signaling the return of reefs to platform-margin settings; (4) in the Aegean or Bithynian (early Anisian), diminutive (mm-scale) calcareous sponges and calcareous algae appeared in the Tubiphytes reef, marking the reappearance of skeletal metazoans and calcareous algae to reefs in the eastern Tethys; and (5) in the late Anisian, the appearance of scleractinian corals coincided with increased abundance, size, and diversity of metazoan and algal reef builders. Early Mesozoic reefs of the eastern Tethys were dominated by microbes, Tubiphytes, and early-marine cements until the late Anisian, several million years into the Middle Triassic. The appearance of small metazoan buildups in Early Triassic strata in other parts of the world indicates that potential reef-building organisms were present much earlier. The limited stratigraphic range of those buildups, however, reinforces the interpretation that episodic environmental disturbances such as euxinia

  5. The OBELIX project: early life exposure to endocrine disruptors and obesity.

    PubMed

    Legler, Juliette; Hamers, Timo; van Eck van der Sluijs-van de Bor, Margot; Schoeters, Greet; van der Ven, Leo; Eggesbo, Merete; Koppe, Janna; Feinberg, Max; Trnovec, Tomas

    2011-12-01

    The hypothesis of whether early life exposure (both pre- and early postnatal) to endocrine-disrupting chemicals (EDCs) may be a risk factor for obesity and related metabolic diseases later in life will be tested in the European research project OBELIX (OBesogenic Endocrine disrupting chemicals: LInking prenatal eXposure to the development of obesity later in life). OBELIX is a 4-y project that started in May 2009 and which has the following 5 main objectives: 1) to assess early life exposure in humans to major classes of EDCs identified as potential inducers of obesity (ie, dioxin-like compounds, non-dioxin-like polychlorinated biphenyls, organochlorine pesticides, brominated flame retardants, phthalates, and perfluorinated compounds) by using mother-child cohorts from 4 European regions with different food-contaminant exposure patterns; 2) to relate early life exposure to EDCs with clinical markers, novel biomarkers, and health-effect data related to obesity; 3) to perform hazard characterization of early life exposure to EDCs for the development of obesity later in life by using a mouse model; 4) to determine mechanisms of action of obesogenic EDCs on developmental programming with in vivo and in vitro genomics and epigenetic analyses; and 5) to perform risk assessments of prenatal exposure to obesogenic EDCs in food by integrating maternal exposure through food-contaminant exposure and health-effect data in children and hazard data in animal studies.

  6. Early-late life trade-offs and the evolution of ageing in the wild

    PubMed Central

    Lemaître, Jean-François; Berger, Vérane; Bonenfant, Christophe; Douhard, Mathieu; Gamelon, Marlène; Plard, Floriane; Gaillard, Jean-Michel

    2015-01-01

    Empirical evidence for declines in fitness components (survival and reproductive performance) with age has recently accumulated in wild populations, highlighting that the process of senescence is nearly ubiquitous in the living world. Senescence patterns are highly variable among species and current evolutionary theories of ageing propose that such variation can be accounted for by differences in allocation to growth and reproduction during early life. Here, we compiled 26 studies of free-ranging vertebrate populations that explicitly tested for a trade-off between performance in early and late life. Our review brings overall support for the presence of early-late life trade-offs, suggesting that the limitation of available resources leads individuals to trade somatic maintenance later in life for high allocation to reproduction early in life. We discuss our results in the light of two closely related theories of ageing—the disposable soma and the antagonistic pleiotropy theories—and propose that the principle of energy allocation roots the ageing process in the evolution of life-history strategies. Finally, we outline research topics that should be investigated in future studies, including the importance of natal environmental conditions in the study of trade-offs between early- and late-life performance and the evolution of sex-differences in ageing patterns. PMID:25833848

  7. Early-late life trade-offs and the evolution of ageing in the wild.

    PubMed

    Lemaître, Jean-François; Berger, Vérane; Bonenfant, Christophe; Douhard, Mathieu; Gamelon, Marlène; Plard, Floriane; Gaillard, Jean-Michel

    2015-05-01

    Empirical evidence for declines in fitness components (survival and reproductive performance) with age has recently accumulated in wild populations, highlighting that the process of senescence is nearly ubiquitous in the living world. Senescence patterns are highly variable among species and current evolutionary theories of ageing propose that such variation can be accounted for by differences in allocation to growth and reproduction during early life. Here, we compiled 26 studies of free-ranging vertebrate populations that explicitly tested for a trade-off between performance in early and late life. Our review brings overall support for the presence of early-late life trade-offs, suggesting that the limitation of available resources leads individuals to trade somatic maintenance later in life for high allocation to reproduction early in life. We discuss our results in the light of two closely related theories of ageing-the disposable soma and the antagonistic pleiotropy theories-and propose that the principle of energy allocation roots the ageing process in the evolution of life-history strategies. Finally, we outline research topics that should be investigated in future studies, including the importance of natal environmental conditions in the study of trade-offs between early- and late-life performance and the evolution of sex-differences in ageing patterns.

  8. Predicting negative life outcomes from early aggressive-disruptive behavior trajectories: gender differences in maladaptation across life domains.

    PubMed

    Bradshaw, Catherine P; Schaeffer, Cindy M; Petras, Hanno; Ialongo, Nicholas

    2010-08-01

    Transactional theories of development suggest that displaying high levels of antisocial behavior early in life and persistently over time causes disruption in multiple life domains, which in turn places individuals at risk for negative life outcomes. We used longitudinal data from 1,137 primarily African American urban youth (49.1% female) to determine whether different trajectories of aggressive and disruptive behavior problems were associated with a range of negative life outcomes in young adulthood. General growth mixture modeling was used to classify the youths' patterns of aggressive-disruptive behavior across elementary school. These trajectories were then used to predict early sexual activity, early pregnancy, school dropout, unemployment, and drug abuse in young adulthood. The trajectories predicted the number but not type of negative life outcomes experienced. Girls with the chronic high aggression-disruption (CHAD) pattern experienced more negative outcomes than girls with consistently moderate levels, who were at greater risk than nonaggressive-nondisruptive girls. Boys with CHAD and boys with an increasing pattern had equal levels of risk for experiencing negative outcomes. The findings are consistent with transactional models of development and have implications for preventive interventions.

  9. Man-Made Closed Ecological Systems as Model of Natural Ecosystems and as Means to Provide High Quality of Human Life in Adverse Environment

    NASA Technical Reports Server (NTRS)

    Gitelson, I. I.; Harper, Lynn (Technical Monitor)

    1994-01-01

    For its more than thirty year long history, the experimental creation of closed ecological systems has from its very sources been distinctly and strongly motivated by the development of human life-support systems for space. As the trend developed its fundamental significance and broad opportunities of terrestrial applications of the technologies under development were coming to the foreground. Nowadays, it can be argued that development of closed ecosystems is experimental foundation of a new branch of ecology biospherics, the goal of which is to comprehend the regularities of existence of the biosphere as a unique in the Universe (in that part of it that we know, at least) closed ecosystem. Closed technologies can be implemented in life-support systems under adverse conditions of life on the Earth - in Arctic and Antarctic latitudes, deserts, high mountains or deep in the ocean, as well as under the conditions of polluted water and air. In space where the environment is hostile for life all around the cell of life should be sealed and the life-support system as close to the ideally closed cyclic turnover of the matter as possible. Under terrestrial conditions designers should strive for maximum closure of the limiting factor: water - in deserts, oxygen - in high mountains, energy - in polar latitudes, etc. Essential closure of a life-support systems withstands also pollution of the environment by the wastes of human vital activity. This is of particular importance for the quarantine of visited planets, and on the Earth under the conditions of deficient heat in high latitudes and water in and areas. The report describes experimental ecosystem 'BIOS' and exohabitats being designed on its basis, which are adapted to various conditions, described capacities of the Center for Closed Ecosystems in Drasnoyarsk for international collaboration in research and education in this field.

  10. Alternatives to the fish early life-stage test: Developing a conceptual model for early fish development

    EPA Science Inventory

    Chronic fish toxicity is a key parameter for hazard classification and environmental risk assessment of chemicals, and the OECD 210 fish early life-stage (FELS) test is the primary guideline test used for various international regulatory programs. There exists a need to develop ...

  11. 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.…

  12. Family-based risk factors for non-suicidal self-injury: Considering influences of maltreatment, adverse family-life experiences, and parent-child relational risk.

    PubMed

    Martin, Jodi; Bureau, Jean-François; Yurkowski, Kim; Fournier, Tania Renaud; Lafontaine, Marie-France; Cloutier, Paula

    2016-06-01

    The current investigation addressed the potential for unique influences of perceived childhood maltreatment, adverse family-life events, and parent-child relational trauma on the lifetime occurrence and addictive features of non-suicidal self-injury (NSSI). Participants included 957 undergraduate students (747 females; M = 20.14 years, SD = 3.88) who completed online questionnaires regarding the key variables under study. Although self-injuring youth reported more experiences with each family-based risk factor, different patterns of association were found when lifetime engagement in NSSI or its addictive features were under study. Perceived parent-child relational trauma was uniquely linked with NSSI behavior after accounting for perceived childhood maltreatment; adverse family-life events had an additional unique association. In contrast, perceived paternal maltreatment was uniquely related with NSSI's addictive features. Findings underline the importance of studying inter-related family-based risk factors of NSSI simultaneously for a comprehensive understanding of familial correlates of NSSI behavior and its underlying features.

  13. Pricing life insurance contracts with early exercise features

    NASA Astrophysics Data System (ADS)

    Bacinello, Anna Rita; Biffis, Enrico; Millossovich, Pietro

    2009-11-01

    In this paper we describe an algorithm based on the Least Squares Monte Carlo method to price life insurance contracts embedding American options. We focus on equity-linked contracts with surrender options and terminal guarantees on benefits payable upon death, survival and surrender. The framework allows for randomness in mortality as well as stochastic volatility and jumps in financial risk factors. We provide numerical experiments demonstrating the performance of the algorithm in the context of multiple risk factors and exercise dates.

  14. Mental Health Problems in Early Childhood Can Impair Learning and Behavior for Life. Working Paper #6

    ERIC Educational Resources Information Center

    National Scientific Council on the Developing Child, 2008

    2008-01-01

    Significant mental health problems can and do occur in young children. In some cases, these problems can have serious consequences for early learning, social competence, and lifelong health. Furthermore, the foundations of many mental health problems that endure through adulthood are established early in life through the interaction of genetic…

  15. Developmental exposure to organophosphate flame retardants elicits overt toxicity and alters behavior in early life stage zebrafish (Danio rerio).

    PubMed

    Dishaw, Laura V; Hunter, Deborah L; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M

    2014-12-01

    Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish.

  16. Developmental Exposure to Organophosphate Flame Retardants Elicits Overt Toxicity and Alters Behavior in Early Life Stage Zebrafish (Danio rerio)

    PubMed Central

    Dishaw, Laura V.; Hunter, Deborah L.; Padnos, Beth; Padilla, Stephanie; Stapleton, Heather M.

    2014-01-01

    Organophosphate flame retardants (OPFRs) are common replacements for the phased-out polybrominated diphenyl ethers (PBDEs) and have been detected at high concentrations in environmental samples. OPFRs are structurally similar to organophosphate pesticides and may adversely affect the developing nervous system. This study evaluated the overt toxicity, uptake, and neurobehavioral effects of tris (1,3-dichloro-2-propyl) phosphate (TDCPP), tris (2-chloroethyl) phosphate (TCEP), tris (1-chloro-2-propyl) phosphate (TCPP), and tris (2,3-dibromopropyl) phosphate (TDBPP) in early life stage zebrafish. Chlorpyrifos was used as a positive control. For overt toxicity and neurobehavioral assessments, zebrafish were exposed from 0 to 5 days postfertilization (dpf). Hatching, death, or malformations were evaluated daily. Teratogenic effects were scored by visual examination on 6 dpf. To evaluate uptake and metabolism, zebrafish were exposed to 1 µM of each organophosphate (OP) flame retardant and collected on 1 and 5 dpf to monitor accumulation. Larval swimming activity was measured in 6 dpf larvae to evaluate neurobehavioral effects of exposures below the acute toxicity threshold. TDBPP elicited the greatest toxicity at >1 µM. TDCPP and chlorpyrifos were overtly toxic at concentrations ≥10 µM, TCEP, and TCPP were not overtly toxic at the doses tested. Tissue concentrations increased with increasing hydrophobicity of the parent chemical after 24 h exposures. TDCPP and TDBPP and their respective metabolites were detected in embryos on 5 dpf. For all chemicals tested, developmental exposures that were not overtly toxic significantly altered larval swimming activity. These data indicate that OPFRs adversely affect development of early life stage zebrafish. PMID:25239634

  17. [Adverse Sensory Input of Childhood Maltreatment Modified by Early Experience Ascertaining the Neural Basis of Neurodevelopmental and Attachment Disorders].

    PubMed

    Tomoda, Akemi

    2015-01-01

    Childhood maltreatment, which markedly increases the risk of psychopathology such as depression, PTSD, and reduced cognitive abilities, is associated with structural and functional brain differences. Our earlier studies elucidated potential discernible effects on the brain morphology of childhood maltreatment on the gray matter volume or cortical thickness. Further, our preliminary studies revealed a significantly reduced gray matter volume (GMV) in the left primary visual cortex (Brodmann area 17) in the reactive attachment disorder (RAD) group compared to the typically developed group. These visual cortex GMV abnormalities may also be associated with such visual stimulus-induced emotion regulation impairments of RAD, leading to an increase in the risk of future psychopathology. Brain regions that process and convey the adverse sensory input of the abuse might be modified specifically by such experiences, particularly in subjects exposed to a single type of maltreatment. Thus, exposure to multiple types of maltreatment is more commonly associated with morphological alterations in corticolimbic regions. PMID:26901893

  18. Similar causes of various reproductive disorders in early life

    PubMed Central

    Svechnikov, Konstantin; Stukenborg, Jan-Bernd; Savchuck, Iuliia; Söder, Olle

    2014-01-01

    During the past few decades, scientific evidence has been accumulated concerning the possible adverse effects of the exposure to environmental chemicals on the well-being of wildlife and human populations. One large and growing group of such compounds of anthropogenic or natural origin is referred to as endocrine-disrupting chemicals (EDCs), due to their deleterious action on the endocrine system. This concern was first focused on the control of reproductive function particularly in males, but has later been expanded to include all possible endocrine functions. The present review describes the underlying physiology behind the cascade of developmental events that occur during sexual differentiation of males and the specific role of androgen in the masculinization process and proper organogenesis of the external male genitalia. The impact of the genetic background, environmental exposures and lifestyle factors in the etiology of hypospadias, cryptorchidism and testicular cancer are reviewed and the possible role of EDCs in the development of these reproductive disorders is discussed critically. Finally, the possible direct and programming effects of exposures in utero to widely use therapeutic compounds, environmental estrogens and other chemicals on the incidence of reproductive abnormalities and poor semen quality in humans are also highlighted. PMID:24369133

  19. The science of early adversity: is there a role for large institutions in the care of vulnerable children?

    PubMed

    Berens, Anne E; Nelson, Charles A

    2015-07-25

    It has been more than 80 years since researchers in child psychiatry first documented developmental delays among children separated from family environments and placed in orphanages or other institutions. Informed by such findings, global conventions, including the 1989 UN Convention on the Rights of the Child, assert a child's right to care within a family-like environment that offers individualised support. Nevertheless, an estimated 8 million children are presently growing up in congregate care institutions. Common reasons for institutionalisation include orphaning, abandonment due to poverty, abuse in families of origin, disability, and mental illness. Although the practice remains widespread, a robust body of scientific work suggests that institutionalisation in early childhood can incur developmental damage across diverse domains. Specific deficits have been documented in areas including physical growth, cognitive function, neurodevelopment, and social-psychological health. Effects seem most pronounced when children have least access to individualised caregiving, and when deprivation coincides with early developmental sensitive periods. Offering hope, early interventions that place institutionalised children into families have afforded substantial recovery. The strength of scientific evidence imparts urgency to efforts to achieve deinstitutionalisation in global child protection sectors, and to intervene early for individual children experiencing deprivation. PMID:25638660