miércoles, 28 de noviembre de 2012

En efecto biológico de la adversidad en los primeros momentos

Hace ya tiempo escribí sobre el efecto del cuidado y contacto directo en recién nacidos, sobre todo basado en el experimento de René Splitz en los años 40.

Hace un mes, PNAS publicó de forma abierta una serie de artículos muy interesantes sobre los efectos biológicos del estrés en edades tempranas en el coloquio titulado Biological Embedding of Early Social Adversity: From Fruit Flies to Kindergartners. A continuación copio titulo y abstract de algunos artículos que me parecen interesantes. Podéis encontrar todos ellos de forma gratuita y abierta en el link anterior:

Social stratification, classroom climate, and the behavioral adaptation of kindergarten childrenSocioeconomic status (SES) is the single most potent determinant of health within human populations, from infancy through old age. Although the social stratification of health is nearly universal, there is persistent uncertainty regarding the dimensions of SES that effect such inequalities and thus little clarity about the principles of intervention by which inequalities might be abated. Guided by animal models of hierarchical organization and the health correlates of subordination, this prospective study examined the partitioning of children's adaptive behavioral development by their positions within kindergarten classroom hierarchies. A sample of 338 5-y-old children was recruited from 29 Berkeley, California public school classrooms. A naturalistic observational measure of social position, parent-reported family SES, and child-reported classroom climate were used in estimating multilevel, random-effects models of children's adaptive behavior at the end of the kindergarten year. Children occupying subordinate positions had significantly more maladaptive behavioral outcomes than their dominant peers. Further, interaction terms revealed that low family SES and female sex magnified, and teachers’ child-centered pedagogical practices diminished, the adverse influences of social subordination. Taken together, results suggest that, even within early childhood groups, social stratification is associated with a partitioning of adaptive behavioral outcomes and that the character of larger societal and school structures in which such groups are nested can moderate rank–behavior associations.

Brain on stress: How the social environment gets under the skin
Stress is a state of the mind, involving both brain and body as well as their interactions; it differs among individuals and reflects not only major life events but also the conflicts and pressures of daily life that alter physiological systems to produce a chronic stress burden that, in turn, is a factor in the expression of disease. This burden reflects the impact of not only life experiences but also genetic variations and individual health behaviors such as diet, physical activity, sleep, and substance abuse; it also reflects stable epigenetic modifications in development that set lifelong patterns of physiological reactivity and behavior through biological embedding of early environments interacting with cumulative change from experiences over the lifespan. Hormones associated with the chronic stress burden protect the body in the short run and promote adaptation (allostasis), but in the long run, the burden of chronic stress causes changes in the brain and body that can lead to disease (allostatic load and overload). Brain circuits are plastic and remodeled by stress to change the balance between anxiety, mood control, memory, and decision making. Such changes may have adaptive value in particular contexts, but their persistence and lack of reversibility can be maladaptive. However, the capacity of brain plasticity to effects of stressful experiences in adult life has only begun to be explored along with the efficacy of top-down strategies for helping the brain change itself, sometimes aided by pharmaceutical agents and other treatments.

Experience and the developing prefrontal cortex
The prefrontal cortex (PFC) receives input from all other cortical regions and functions to plan and direct motor, cognitive, affective, and social behavior across time. It has a prolonged development, which allows the acquisition of complex cognitive abilities through experience but makes it susceptible to factors that can lead to abnormal functioning, which is often manifested in neuropsychiatric disorders. When the PFC is exposed to different environmental events during development, such as sensory stimuli, stress, drugs, hormones, and social experiences (including both parental and peer interactions), the developing PFC may develop in different ways. The goal of the current review is to illustrate how the circuitry of the developing PFC can be sculpted by a wide range of pre- and postnatal factors. We begin with an overview of prefrontal functioning and development, and we conclude with a consideration of how early experiences influence prefrontal development and behavior.

Social information changes the brain
Social animals live in complex physical and social environments requiring them to attend and rapidly respond to social and environmental information by changing their behavior. A key social influence is rank or status, a ubiquitous element in animal societies. Rank typically regulates access to reproduction and other resources, among other consequences for individuals. Because reproduction is arguably the most important event in any animals’ life, understanding how reproduction is regulated by social status and related physiological factors can instruct our understanding of evolutionary change. This article reviews evidence from a model social system in which reproduction is tightly controlled by social status. Surprisingly, changes in social status have rapid and profound effects over very short time scales and radically alter overt behavior, as well as physiological, cellular, and molecular factors that regulate reproductive capacity.

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

Prenatal exposure to antidepressants and depressed maternal mood alter trajectory of infant speech perception
Language acquisition reflects a complex interplay between biology and early experience. Psychotropic medication exposure has been shown to alter neural plasticity and shift sensitive periods in perceptual development. Notably, serotonin reuptake inhibitors (SRIs) are antidepressant agents increasingly prescribed to manage antenatal mood disorders, and depressed maternal mood per se during pregnancy impacts infant behavior, also raising concerns about long-term consequences following such developmental exposure. We studied whether infants’ language development is altered by prenatal exposure to SRIs and whether such effects differ from exposure to maternal mood disturbances. Infants from non–SRI-treated mothers with little or no depression (control), depressed but non–SRI-treated (depressed-only), and depressed and treated with an SRI (SRI-exposed) were studied at 36 wk gestation (while still in utero) on a consonant and vowel discrimination task and at 6 and 10 mo of age on a nonnative speech and visual language discrimination task. Whereas the control infants responded as expected (success at 6 mo and failure at 10 mo) the SRI-exposed infants failed to discriminate the language differences at either age and the depressed-only infants succeeded at 10 mo instead of 6 mo. Fetuses at 36 wk gestation in the control condition performed as expected, with a response on vowel but not consonant discrimination, whereas the SRI-exposed fetuses showed accelerated perceptual development by discriminating both vowels and consonants. Thus, prenatal depressed maternal mood and SRI exposure were found to shift developmental milestones bidirectionally on infant speech perception tasks.

Effects of early intervention and the moderating effects of brain activity on institutionalized children's social skills at age 8
The present study examined the social skills of previously institutionalized, 8-y-old Romanian children from the Bucharest Early Intervention Project and the influence of attachment security and brain electrical activity (alpha power) on these skills. Participants included children randomized to an intervention involving foster care [Foster Care Group (FCG)], children randomized to remain in institutions [Care As Usual Group (CAUG)], and never-institutionalized children living with their families in the Bucharest community [Never-Institutionalized Group (NIG)]. A continuous rating of children’s attachment security to their primary caregiver was assessed at 42 mo of age. When children were 8 y old, teachers rated their social skills, and the children’s resting electroencephalogram alpha power was recorded. Teachers rated social skills of FCG children who were placed into foster care before 20 mo of age as no different from NIG children, and both of these groups were higher than CAUG children and FCG children placed after 20 mo. Electroencephalogram alpha power at age 8 significantly moderated the relations between attachment security and social skills. These findings characterize institutionalized children’s social skills in middle childhood within the context of a randomized intervention while highlighting the roles of both relational and biological factors in these developmental trajectories.

Conserved epigenetic sensitivity to early life experience in the rat and human hippocampus
Early life experience is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. However, it is unlikely that such effects completely capture the evolutionarily conserved epigenetic mechanisms of early adaptation to environment. Here we present DNA methylation profiles spanning 6.5 million base pairs centered at the NR3C1 gene in the hippocampus of humans who experienced abuse as children and nonabused controls. We compare these profiles to corresponding DNA methylation profiles in rats that received differential levels of maternal care. The profiles of both species reveal hundreds of DNA methylation differences associated with early life experience distributed across the entire region in nonrandom patterns. For instance, methylation differences tend to cluster by genomic location, forming clusters covering as many as 1 million bases. Even more surprisingly, these differences seem to specifically target regulatory regions such as gene promoters, particularly those of the protocadherin α, β, and γ gene families. Beyond these high-level similarities, more detailed analyses reveal methylation differences likely stemming from the significant biological and environmental differences between species. These results provide support for an analogous cross-species epigenetic regulatory response at the level of the genomic region to early life experience.

Socioeconomic gradients in child development in very young children: Evidence from India, Indonesia, Peru, and Senegal
Gradients across socio-economic position exist for many measures of children's health and development in higher-income countries. These associations may not be consistent, however, among the millions of children living in lower- and middle-income countries. Our objective was to examine child development and growth in young children across socio-economic position in four developing countries. We used cross-sectional surveys, child development assessments, measures of length (LAZ), and home stimulation (Family Care Index) of children in India, Indonesia, Peru, and Senegal. The Extended Ages and Stages Questionnaire (EASQ) was administered to parents of all children ages 3–23 mo in the household (n =8,727), and length measurements were taken for all children 0–23 mo (n = 11,102). Household wealth and maternal education contributed significantly and independently to the variance in EASQ and LAZ scores in all countries, while controlling for child's age and sex, mother's age and marital status, and household size. Being in the fifth wealth quintile in comparison with the first quintile was associated with significantly higher EASQ scores (0.27 to 0.48 of a standardized score) and higher LAZ scores (0.37 to 0.65 of a standardized score) in each country, while controlling for maternal education and covariates. Wealth and education gradients increased over the first two years in most countries for both EASQ and LAZ scores, with larger gradients seen in 16–23-mo-olds than in 0–7mo-olds. Mediation analyses revealed that parental home stimulation activities and LAZ were significant mediating variables and explained up to 50% of the wealth effects on the EASQ.

Early environments and the ecology of inflammation
Recent research has implicated inflammatory processes in the pathophysiology of a wide range of chronic degenerative diseases, although inflammation has long been recognized as a critical line of defense against infectious disease. However, current scientific understandings of the links between chronic low-grade inflammation and diseases of aging are based primarily on research in high-income nations with low levels of infectious disease and high levels of overweight/obesity. From a comparative and historical point of view, this epidemiological situation is relatively unique, and it may not capture the full range of ecological variation necessary to understand the processes that shape the development of inflammatory phenotypes. The human immune system is characterized by substantial developmental plasticity, and a comparative, developmental, ecological framework is proposed to cast light on the complex associations among early environments, regulation of inflammation, and disease. Recent studies in the Philippines and lowland Ecuador reveal low levels of chronic inflammation, despite higher burdens of infectious disease, and point to nutritional and microbial exposures in infancy as important determinants of inflammation in adulthood. By shaping the regulation of inflammation, early environments moderate responses to inflammatory stimuli later in life, with implications for the association between inflammation and chronic diseases. Attention to the eco-logics of inflammation may point to promising directions for future research, enriching our understanding of this important physiological system and informing approaches to the prevention and treatment of disease.

Early childhood poverty, immune-mediated disease processes, and adult productivity
This study seeks to understand whether poverty very early in life is associated with early-onset adult conditions related to immune-mediated chronic diseases. It also tests the role that these immune-mediated chronic diseases may play in accounting for the associations between early poverty and adult productivity. Data (n = 1,070) come from the US Panel Study of Income Dynamics and include economic conditions in utero and throughout childhood and adolescence coupled with adult (age 30–41 y) self-reports of health and economic productivity. Results show that low income, particularly in very early childhood (between the prenatal and second year of life), is associated with increases in early-adult hypertension, arthritis, and limitations on activities of daily living. Moreover, these relationships and particularly arthritis partially account for the associations between early childhood poverty and adult productivity as measured by adult work hours and earnings. The results suggest that the associations between early childhood poverty and these adult disease states may be immune-mediated.

Leveraging the biology of adversity to address the roots of disparities in health and development
Extensive evidence that personal experiences and environmental exposures are embedded biologically (for better or for worse) and the cumulative knowledge of more than four decades of intervention research provide a promising opportunity to mobilize evolving scientific insights to catalyze a new era of more effective early childhood policy and practice. Drawing on emerging hypotheses about causal mechanisms that link early adversity with lifelong impairments in learning, behavior, and health, this paper proposes an enhanced theory of change to promote better outcomes for vulnerable, young children by strengthening caregiver and community capacities to reduce or mitigate the impacts of toxic stress, rather than simply providing developmental enrichment for the children and parenting education for their mothers.

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