The concept of mechanisms that protect people against the psychological risks associated with adversity is discussed in relation to four main processes: reduction of risk impact, reduction of negative chain reactions, establishment and maintenance of self-esteem and self-efficacy, and opening up of opportunities. The mechanisms operating at key turning points in people's lives must be given special attention.

Psychosocial Resilience and Protective Mechanisms

Here we report that increased pup licking and grooming (LG) and arched-back nursing (ABN) by rat mothers altered the offspring epigenome at a glucocorticoid receptor (GR) gene promoter in the hippocampus. Offspring of mothers that showed high levels of LG and ABN were found to have differences in DNA methylation, as compared to offspring of 'low-LG-ABN' mothers. These differences emerged over the first week of life, were reversed with cross-fostering, persisted into adulthood and were associated with altered histone acetylation and transcription factor (NGFI-A) binding to the GR promoter. Central infusion of a histone deacetylase inhibitor removed the group differences in histone acetylation, DNA methylation, NGFI-A binding, GR expression and hypothalamic-pituitary-adrenal (HPA) responses to stress, suggesting a causal relation among epigenomic state, GR expression and the maternal effect on stress responses in the offspring. Thus we show that an epigenomic state of a gene can be established through behavioral programming, and it is potentially reversible.

/pdf/epigenetic-programming-by-maternal-behavior-nhsklwyk7o.pdf

Epigenetic programming by maternal behavior.

Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat.

How we raise young children is one of today's most highly personalized and sharply politicized issues, in part because each of us can claim some level of "expertise." The debate has intensified as discoveries about our development-in the womb and in the first months and years-have reached the popular media. How can we use our burgeoning knowledge to assure the well-being of all young children, for their own sake as well as for the sake of our nation? Drawing from new findings, this book presents important conclusions about nature-versus-nurture, the impact of being born into a working family, the effect of politics on programs for children, the costs and benefits of intervention, and other issues. The committee issues a series of challenges to decision makers regarding the quality of child care, issues of racial and ethnic diversity, the integration of children's cognitive and emotional development, and more. Authoritative yet accessible, From Neurons to Neighborhoods presents the evidence about "brain wiring" and how kids learn to speak, think, and regulate their behavior. It examines the effect of the climate-family, child care, community-within which the child grows.

/pdf/from-neurons-to-neighborhoods-the-science-of-early-childhood-3bfl5g72ow.pdf

From Neurons to Neighborhoods: The Science of Early Childhood Development

Psychosocial resilience and protective mechanisms.

Fluorometric Determination of Corticosterone and Cortisol in 0.02–0.05 Milliliters of Plasma or Submilligram Samples of Adrenal Tissue1

Behavioral stress impairs long-term potentiation in rodent hippocampus

A group of rats was trained to escape low-intensity shock in a shuttle-box test, while another group of yoked controls could not escape but was exposed to the same amount and regime of shock. After 1 week of training, long-term potentiation (LTP) was measured in vitro in hippocampal slices. Exposure to uncontrollable shock massively impaired LTP relative to exposure to the same amount and regime of controllable shock. These results provide evidence that controllability modulates plasticity at the cellular-neuronal level.

https://science.sciencemag.org/content/sci/244/4901/224.full.pdf

Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus.

Coping and Health

In adult organisms, glucmrticoids (GCs) serve a wide variety of regulatory and permissive functions.’ These functions are aimed basically at controlling the organism’s response to stress and regulating certain circadian activities. Most of the effects of GCs, in the adult, are readily reversible. However, during development, GC administration has been demonstrated to have permanent effects on growth and differentiation in a number of systems, including the CNS. In rats, high doses of GCs administered neonatally cause decreased mitosis, myelination, and altered neuromorphogenesis? Animals treated neonatally with GCs show reduced DNA content and brain size, as well as impaired neuroendocrine function as adults3 as well as behavior: Conversely, the absence of GCs following adrenalectomy also affects CNS development? Thus, relatively constant low levels of GCs are indispensable for normal maturation. It appears that during development a delicate and critical balance of GCs is essential. The dynamics of the HPA system show a characteristic developmental pattern. During the final days of gestation and immediately after birth, basal levels of CORT in the rat are declining but are still high.6 However, during the first two postnatal days, CORT concentrations decrease dramatically and remain at low levels until approximately day 14. In addition, concentrations of pituitary A m and hypothalamic CRF are also low during the first two postnatal weeks.’ The system is further characterized in the neonatal period by the fact that stimuli which normally elicit CORT elevations in adults are unable to do so in the infant. This neonatal period which covers, in the rat, the period from postnatal day 4 to 14, has been referred to as the “stress hyporesponsive period” (SHRP). During the SHRP, there is also a diminution of adrenal sensitivity, evidenced by the fact that the infant fails to show a significant elevation of CORT following administration of high doses of exogenous ACTH.8 The HPA system does not develop uniformly; different components of the system have different ontogenetic patterns. Thus, although the infant rat is capable of responding to stressful stimuli by day 15, circadian rhythmicity and feedback regulation are not yet fully developed until much later in developmentP” One proposed mechanism for the suppression of the HPA system during this period of development is that most stressors are unable to evoke a sufficiently large CRF signal to overcome an “enhanced CORT feedback signal” at the brain and pituitary l e v e l ~ . ~ * J ~ There are several experiments which question the validity of this hypo the~ i s .~~ The overall picture that emerges, however, is that there are multiple differences in the neonatal neuroendocrine system that ensure that plasma CORT

Seymour Levine

Papers

Fluorometric Determination of Corticosterone and Cortisol in 0.02–0.05 Milliliters of Plasma or Submilligram Samples of Adrenal Tissue1

Behavioral stress impairs long-term potentiation in rodent hippocampus

Inescapable versus escapable shock modulates long-term potentiation in the rat hippocampus.

Coping and Health

The Ontogeny of the Hypothalamic-Pituitary-Adrenal Axis. The Influence of Maternal Factorsa