Adverse Early Life Conditions Research Articles

Early life adversity and adult social relationships have independent effects on survival in a wild primate.

Adverse conditions in early life can have negative consequences for adult health and survival in humans and other animals. What variables mediate the relationship between early adversity and adult survival? Adult social environments represent one candidate: Early life adversity is linked to social adversity in adulthood, and social adversity in adulthood predicts survival outcomes. However, no study has prospectively linked early life adversity, adult social behavior, and adult survival to measure the extent to which adult social behavior mediates this relationship. We do so in a wild baboon population in Amboseli, Kenya. We find weak mediation and largely independent effects of early adversity and adult sociality on survival. Furthermore, strong social bonds and high social status in adulthood can buffer some negative effects of early adversity. These results support the idea that affiliative social behavior is subject to natural selection through its positive relationship with survival, and they highlight possible targets for intervention to improve human health and well-being.

Trends in inequality of opportunity in health over the life cycle: The role of early-life conditions

This paper explores the evolution of inequality of opportunity in the prevalence of chronic diseases along the life cycle and across different birth cohorts for individuals aged 50 or older and residing in 13 European countries. We adopt an ex-ante parametric approach and rely on the dissimilarity index as our reference inequality metric. In addition to a commonly used set of circumstances, we pay particular attention to the role of adverse early-life conditions, such as the experience of harm and the quality of the relationship with parents. In order to quantify the relative importance of each circumstance, we apply the Shapley inequality decomposition method. Our results suggest that inequality of opportunity in health is not stable over the life cycle - it is generally lower at younger ages and then monotonically increases. Moreover, it varies between different birth cohorts and is generally higher for younger individuals than for older age groups. Finally, the contribution of adverse early life conditions ranges between 25% and 45%, which is comparable to the share of socio-economic circumstances but significantly higher than the relative contribution of other demographic characteristics, especially at younger ages.

Early-Life Origins of Metabolic Syndrome: Mechanisms and Preventive Aspects.

One of the leading global public-health burdens is metabolic syndrome (MetS), despite the many advances in pharmacotherapies. MetS, now known as “developmental origins of health and disease” (DOHaD), can have its origins in early life. Offspring MetS can be programmed by various adverse early-life conditions, such as nutrition imbalance, maternal conditions or diseases, maternal chemical exposure, and medication use. Conversely, early interventions have shown potential to revoke programming processes to prevent MetS of developmental origins, namely reprogramming. In this review, we summarize what is currently known about adverse environmental insults implicated in MetS of developmental origins, including the fundamental underlying mechanisms. We also describe animal models that have been developed to study the developmental programming of MetS. This review extends previous research reviews by addressing implementation of reprogramming strategies to prevent the programming of MetS. These mechanism-targeted strategies include antioxidants, melatonin, resveratrol, probiotics/prebiotics, and amino acids. Much work remains to be accomplished to determine the insults that could induce MetS, to identify the mechanisms behind MetS programming, and to develop potential reprogramming strategies for clinical translation.

Population-level impact of adverse early life conditions on adult healthy life expectancy in low- and middle-income countries

Evidence from theories of Developmental Origins of Health and Disease (DOHaD) suggests that experiencing adverse early life conditions subsequently leads to detrimental adult health outcomes. The bulk of empirical DOHaD literature does not consider the nature and magnitude of the impact of adverse early life conditions at the population level. In particular, it ignores the distortion of age and cohort patterns of adult health and mortality and the increased load of chronic illness and disability that ensues. In this paper, we use a microsimulation model combined with empirical estimates of incidence and prevalence of obesity, type 2 diabetes, and associated disability in low- and middle-income countries to assess the magnitude of delayed effects on adult healthy life expectancy and on compression (or expansion) of morbidity at older ages. The main goal is to determine if, in what ways, and to what extent delayed effects due to early conditions can influence cohorts’ chronic illness and disability profiles.

Morphological and physiological consequences of a dietary restriction during early life in bats

Abstract Early life adverse conditions can have major consequences on an individual’s life history traits. Oxidative stress has been hypothesized to be one main mechanism underlying the negative consequences of early life adverse conditions. To test this hypothesis, we restricted the food availability of Seba’s short-tailed bat (Carollia perspicillata) mothers of unweaned pups for 10 days, followed by ad libitum provisioning. We also had a control, unrestricted group. We explored the morphological consequences of dietary restriction during early life by measuring growth rate. We also measured four markers of blood oxidative balance during growth. We assessed the level of cortisol, and its inactive form cortisone, in the hair of the pups at the end of growth. Finally, we monitored survival during the first year. Food restriction triggered a slowdown in growth followed by catch-up growth when ad libitum feeding was restored which did not lead to full compensation in size or mass compared to control individuals. We found that higher growth rate was associated with elevated oxidative damage, suggesting an oxidative cost to growth. However, we found no clear evidence for physiological costs specific to the catch-up growth. Survival after a year was not impacted by the treatment, the oxidative balance or the level of glucocorticoids at the end of growth. In conclusion, our results show that individuals were able to efficiently mitigate the short-term consequences of adverse early life conditions. However, consequences might arise in the long-term, and could impact reproductive success or lifespan.

Prevalence and determinants of type 2 diabetes among lean African migrants and non-migrants: the RODAM study.

BackgroundExposure to adverse conditions earlier in life-course can predispose to type 2 diabetes in adulthood, irrespective of body mass index (BMI). However, the burden of type 2 diabetes in lean Africans is not well understood despite higher exposure to adverse early life conditions. Mirroring ongoing epidemiological transition, we assessed the burden and determinants of type 2 diabetes in a homogenous group of lean Ghanaians residing in rural and urban Ghana, and as migrants in Europe.MethodsBaseline data from 2179 RODAM study participants with BMI<25kg/m2 (25-70 years) were analyzed. Prevalence and determinants of type 2 diabetes were estimated using logistic regression analysis. Adjustments were made for socio-demographic and lifestyle factors, use of anti-diabetic medication and optimal blood glucose control.ResultsPrevalence of type 2 diabetes in rural, urban and migrant lean participants were 3.5%, 8.9% and 7.5% respectively, representing 55.4%, 35.6%, 13.2% of all participants with type 2 diabetes. Compared with lean rural participants, the odds of type 2 diabetes were higher in lean urban participants (adjusted OR = 8.81, 95% CI = 6.56-11.06), followed by migrants (5.27, 95% CI = 3.51-6.91). Irrespective of site, determinants of type 2 diabetes in lean participants include; presence of hypertension, physical inactivity, hypercholesterolemia and age (>45 years).ConclusionsOur study shows a high prevalence of type 2 diabetes among lean African populations in different geographical settings. Future studies are needed in-order to examine how contextual differences are related to the pathophysiology of type 2 diabetes in lean individuals.

Gabrysch and van Ewijk Respond to "Detrimental Consequences of Adverse Early-Life Conditions" and "Ramadan, Pregnancy, Nutrition, and Epidemiology".

Gabrysch and van Ewijk Respond to "Detrimental Consequences of Adverse Early-Life Conditions" and "Ramadan, Pregnancy, Nutrition, and Epidemiology".

Invited Commentary: A Matter of Survival-The Detrimental Consequences of Adverse Early-Life Conditions.

Studies across different species have shown that moderate dietary restriction is associated with a longer life span. Surprisingly, however, when diet is restricted in prenatal life, the effect is completely the opposite. Animal studies and human epidemiologic data have shown that undernutrition in utero negatively affects health in later life and reduces life span considerably. In this issue of the Journal, Schoeps et al. (Am J Epidemiol. 2018;187(10):2085-2092) provide new evidence that variations in nutritional conditions during pregnancy relate to the future health of the unborn child. In a detailed analysis of data from Muslim and non-Muslim pregnant women in Burkina Faso, they showed that the occurrence of Ramadan in early life was strongly associated with mortality rates among children under 5 years of age. Mortality rates were highest when Ramadan had occurred in the preconception period or during the first trimester. That nutritional conditions in early life can have such profound consequences for child mortality is both astonishing and extremely relevant from a public health perspective.

An adverse early life environment can enhance stress resilience in adulthood

Chronic stress is a major risk factor for depression. Interestingly, not all individuals develop psychopathology after chronic stress exposure. In contrast to the prevailing view that stress effects are cumulative and increase stress vulnerability throughout life, the match/mismatch hypothesis of psychiatric disorders. The match/mismatch hypothesis proposes that individuals who experience moderate levels of early life psychosocial stress can acquire resilience to renewed stress exposure later in life. Here, we have tested this hypothesis by comparing the developmental effects of 2 opposite early life conditions, when followed by 2 opposite adult environments. Male Balb/c mice were exposed to either adverse early life conditions (limited nesting and bedding material) or a supportive rearing environment (early handling). At adulthood, the animals of each group were either housed with an ovariectomized female (supportive environment) or underwent chronic social defeat stress (socially adverse environment) for 3 weeks. At the end of the adult manipulations, all of the animals were returned to standard housing conditions. Then, we compared the neuroendocrine, behavioral and molecular effects of the interaction between early and adult environment. Our study shows that early life adversity does not necessarily result in increased vulnerability to stress. Specific endophenotypes, like hypothalamic-pituitary-adrenal axis activity, anxiety-related behavior and glucocorticoid receptor expression levels in the hippocampus were not significantly altered when adversity is experienced during early life and in adulthood, and are mainly affected by either early life or adult life adversity alone. Overall our data support the notion that being raised in a stressful environment prepares the offspring to better cope with a challenging adult environment and emphasize the role of early life experiences in shaping adult responsiveness to stress.

Maternal Separation Impairs Cocaine-Induced Behavioural Sensitization in Adolescent Mice.

Adverse early-life conditions induce persistent disturbances that give rise to negative emotional states. Therefore, early life stress confers increased vulnerability to substance use disorders, mainly during adolescence as the brain is still developing. In this study, we investigated the consequences of maternal separation, a model of maternal neglect, on the psychotropic effects of cocaine and the neuroplasticity of the dopaminergic system. Our results show that mice exposed to maternal separation displayed attenuated behavioural sensitization, while no changes were found in the rewarding effects of cocaine in the conditioned place preference paradigm and in the reinforcing effects of cocaine in the self-administration paradigm. The evaluation of neuroplasticity in the striatal dopaminergic pathways revealed that mice exposed to maternal separation exhibited decreased protein expression levels of D2 receptors and increased levels of the transcriptional factor Nurr1. Furthermore, animals exposed to maternal separation and treated with cocaine exhibited increased DA turnover and protein expression levels of DAT and D2R, while decreased Nurr1 and Pitx3 protein expression levels were observed when compared with saline-treated mice. Taken together, our data demonstrate that maternal separation caused an impairment of cocaine-induced behavioural sensitization possibly due to a dysfunction of the dopaminergic system, a dysfunction that has been proposed as a factor of vulnerability for developing substance use disorders.

Impact of Child Neglect and Abuse on Adult Mental Health

Child neglect and abuse is a public health priority. Adverse conditions in early life are associated with higher risk of mental disorders. Family conditions and quality of parenting have a significant impact on risk of mental and physical health. Children's exposure to neglect, direct physical and psychological abuse, and growing up in families with domestic violence was particularly damagin. The current review covers four aspects, namely, (i) prevalence of child neglect and abuse in South Asian Association Regional Cooperation (SAARC) countries; (ii) evidence of the lifetime impact of child neglect and abuse on the mental health in the general population and in specific population groups; (iii) the biological changes due to the impact of child neglect and abuse; and (iv) implications of the findings for research and interventions at the level of children, families and community. There is poor documentation of child neglect and abuse. A recent Tata Institute of Social Sciences (TISS) and Action Aid study (2014) in Mumbai city’ covered over 37,059 children, of whom 728 were studied in depth. Torture, beating, forced starving and sexual abuse were observed or heard by (among the) children. Threats from police, theft, hurt, displacement, kidnapping and ghosts were perceived mostly at nights, especially in the sleeping places. In total, 44% had observed abuse, which included torture, beating, forced starving and sexual abuse. In an another report, ‘The Republic's Lost Children’, it was reported that 38% were forced into sex trade; 23% forced into domestic servitude; 4% routed to work at hotels or hospitals; and 3% at the sweetmeat and garment units. The evidence of the long-lasting effects of ‘child neglect and abuse’ are increased rates of mental disorders. Physically abused, emotionally abused and neglected individuals have a higher risk, two to three times, of developing depressive disorders than non-abused individuals. Children with a history of bullying, 40–50 years later, had an increased risk for depression and suicidal thoughts and were likely to have lack of social relationships, lower educational levels and also more likely to be unemployed and earning less. Other significant associations between childhood adversities are occurrence of first-onset and recurrent mania, fatigue syndromes, adult violent offending, and criminality. There is growing evidence of the mediation of the effects of child neglect and abuse are biologically based with associated changes at the level of stress response, changes in brain structures, inflammatory response and neurocognitive functions. There is need for interventions at many levels, starting from documenting the problem, the longitudinal study of neglected children, interventions to remedy the disadvantages at the level of individual children, their families, communities and government policies. This is an urgent need in the SAARC countries.

Variation in adult body mass of roe deer: early environmental conditions influence early and late body growth of females

There is increasing evidence that environmental conditions experienced early in life can markedly affect an organism's life history, but the pathways by which early environment influences adult phenotype are poorly known. We used long-term data from two roe deer (Capreolus capreolus) populations (Chizé and Trois-Fontaines, France) to investigate the direct and indirect (operating through fawn body mass) effects of environmental conditions during early life on adult body mass. We found that environmental conditions (population size and spring temperatures) around birth influenced body mass of adult females through both direct and indirect effects in both populations. The occurrence of direct effects means that, for a given fawn body mass, adult female mass decreases with adverse conditions in early life. In contrast, we found no evidence for direct effects of early-life conditions on adult body mass of males, suggesting the existence of sex-specific long-term responses of body mass to stressful early conditions. Our results provide evidence that early environmental conditions influence the adult phenotype through persistent effects over the body development in wild mammal populations.

Stress: A Possible Link between Genetics, Epigenetics, and Childhood Asthma

Stress: A Possible Link between Genetics, Epigenetics, and Childhood Asthma

P.2.019 The mismatch hypothesis: a new way of linking early experiences and adult environment to vulnerability to stress

Purpose of the study: Chronic stress is considered one of the main risk factors for depression. Interestingly, not all individuals develop psychopathology after chronic stress. In contrast to the prevailing view that stress effects are cumulative and increase stress vulnerability later in life, the recently formulated mismatch hypothesis proposes that individuals experiencing high levels of psychosocial stress early in life are programmed for dealing with high psychosocial stress and are therefore resilient to high stress levels in later life [1]. We here test this hypothesis by comparing the developmental effects of two different early life conditions, when tested under two opposite adult environments. Methods used: We used female BALB/c mice that underwent either adverse early life conditions (limited nesting material) or a supportive environment (early handling) from PND2 to PND9. At weaning, the animals of each group were assigned to either group housing (supportive environment) or single housing (social deprivation, adverse environment). At adulthood, we compared the molecular and the behavioural effects of the interaction between early and adult environment, in particular on anxiety like and depressive like behaviour.

An unbalanced maternal diet in pregnancy associates with offspring epigenetic changes in genes controlling glucocorticoid action and foetal growth.

In epidemiological studies, adverse early-life conditions associate with subsequent cardiometabolic disease. Hypothesized causes include maternal malnutrition, foetal glucocorticoid overexposure and reduced growth factors. Animal studies suggest a role for epigenetic processes in maintaining early-life effects into adulthood, but human relevance is unknown. We aimed to investigate relationships between an unbalanced maternal diet in pregnancy, neonatal and adult anthropometric variables with methylation at key genes controlling tissue glucocorticoid action and foetal growth. We studied 34 individuals aged 40 from the Motherwell cohort study whose mothers ate an unbalanced diet in pregnancy, previously linked with elevated blood pressure and cortisol in adult offspring. DNA methylation at 11β-hydroxysteroid dehydrogenase type 2 (HSD2), glucocorticoid receptor (GR) and insulin-like growth factor 2 (IGF2) was measured by pyrosequencing on buffy coat DNA. Methylation at specific CpGs in the HSD2 promoter and at one of the IGF2 differentially methylated regions (H19 ICR) correlated with neonatal anthropometric variables. CpG methylation within HSD2, GR and H19 ICR was positively associated with increased adiposity and blood pressure in adulthood. Methylation at GR (exon 1F) was increased in offspring of mothers with the most unbalanced diets in pregnancy. Alterations in DNA methylation at genes important in regulating circulating cortisol levels, tissue glucocorticoid action, blood pressure and foetal growth are present in adulthood in association with both early-life parameters and cardiometabolic risk factors. The data indicate a persisting epigenetic link between early-life maternal diet and/or foetal growth and cardiovascular disease risk in humans.

Gender differences in prevalence of diagnosed type 2 diabetes and patient’s body mass index in five Ukraine regions with diverse historical backgrounds

Abstract Analysis of territorial diabetes mellitus registers of 2 Western and 3 Eastern Ukraine regions with diverse historical backgrounds was performed. Two western regions (Kherson and Crimea) were severely affected by Famine of 1932-33, Chernihiv region was less severely affected area, and Western-Ukraine regions (Volyn and Rivne) were not affected. Prevalence rates of diagnosed type 2 diabetes mellitus (T2D) in women are higher than in men in all birth cohorts studied except for the oldest ones. The female-to-male predominance is more pronounced for people with T2D residing in Eastern Ukraine regions. Female (but not male) persons with T2D residing in Eastern Ukraine have higher body mass index than those residing in Western Ukraine. Female predominance among persons with T2D in Ukraine may be due to the fact that women are more likely than men to be influenced by adverse early-life conditions. Keywords: Body mass index; Developmental programming ; Gender differences ; Great Ukrainian Famine of 1932-33; Type 2 diabetes

Epigenetics of Early Child Development

Comprehensive clinical studies show that adverse conditions in early life can severely impact the developing brain and increase vulnerability to mood disorders later in life. During early postnatal life the brain exhibits high plasticity which allows environmental signals to alter the trajectories of rapidly developing circuits. Adversity in early life is able to shape the experience-dependent maturation of stress-regulating pathways underlying emotional functions and endocrine responses to stress, such as the hypothalamo–pituitary–adrenal (HPA) system, leading to long-lasting altered stress responsivity during adulthood. To date, the study of gene–environment interactions in the human population has been dominated by epidemiology. However, recent research in the neuroscience field is now advancing clinical studies by addressing specifically the mechanisms by which gene–environment interactions can predispose individuals toward psychopathology. To this end, appropriate animal models are being developed in which early environmental factors can be manipulated in a controlled manner. Here we will review recent studies performed with the common aim of understanding the effects of the early environment in shaping brain development and discuss the newly developing role of epigenetic mechanisms in translating early life conditions into long-lasting changes in gene expression underpinning brain functions. Particularly, we argue that epigenetic mechanisms can mediate the gene–environment dialog in early life and give rise to persistent epigenetic programming of adult physiology and dysfunction eventually resulting in disease. Understanding how early life experiences can give rise to lasting epigenetic marks conferring increased risk for mental disorders, how they are maintained and how they could be reversed, is increasingly becoming a focus of modern psychiatry and should pave new guidelines for timely therapeutic interventions.

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

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.

The effect of rainfall during gestation and early childhood on adult height in a foraging and horticultural society of the Bolivian Amazon

Recent research documents the effects of adverse conditions during gestation and early childhood on growth responses and health throughout life. Most research linking adverse conditions in early life with adult health comes from industrial nations. We know little about the plasticity of growth responses to environmental perturbations early in life among foragers and horticulturalists. Using 2005 data from 211 women and 215 men 20+ years of age from a foraging-horticultural society of native Amazonians in Bolivia (Tsimane'), we estimate the association between (a) adult height and (b) rainfall amount and variability during three stages in the life cycle: gestation (year 0), birth year (year 1), and years 2-5. We control for confounders such as height of the same-sex parent. Rainfall amount and variability during gestation and birth year bore weak associations with adult height, probably from the protective role of placental physiology and breastfeeding. However, rainfall variability during years 2-5 of life bore a negative association with adult female height. Among women, a 10% increase in the coefficient of variation of rainfall during years 2-5 was associated with 0.7-1.2% lower adult height (1.08-1.93 cm). Environmental perturbations that take place after the cessation of weaning seem to leave the strongest effect on adult height. We advance possible explanations for the absence of effects among males.

Developmental Programming Through Epigenetic Changes

See related article, pages 520–526 The last decade has seen an exponential number of scientific articles addressing the concept of fetal programming of adult onset diseases. Though it has long been known (as it is probably part of common knowledge in human history) that the environment and life events during the fetal period impact on the child’s development, the notion that intrauterine life can also impact on adult health and on the incidence of late onset diseases such as hypertension and type II diabetes is relatively more recent. In 1964, Rose reported the association of ischemic heart disease and infant mortality within the same families (reviewed by1). Then Forsdahl in 1977 showed that incidence of arteriosclerotic heart disease in a certain age group could be correlated with the infant mortality rate of that same population.1 Interest in these types of association rose dramatically following Professor Barker and collaborators’ extensive observations of a well documented population in England and Wales. The meticulous work of home health visitors in the early 20th century, which noted every child weight and length at birth and throughout the first year of life as well as other observations of the mother health and living milieu, generated data which clearly demonstrated an inverse relationship between birthweight and adult incidence of cardiovascular related mortality and morbidities as well as type II diabetes.1 We will focus here on hypertension and related complications. The association between birthweight and adult blood pressure was demonstrated in many parts of the world, in industrialized as well as in more developing countries, in both men and women.1 The association is first noted in early childhood (but not at birth) and seems to increase with age. Despite the significant number of studies published, which have examined to date tens …