Elsevier

Metabolism

Volume 57, Supplement 2, October 2008, Pages S11-S15
Metabolism

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

https://doi.org/10.1016/j.metabol.2008.07.006Get rights and content

Abstract

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.

Introduction

Early life adversity has widespread effects on both brain and body. For example, early life physical and sexual abuse carry with it a life-long burden of behavioral and pathophysiologic problems [1], [2]. Moreover, cold and uncaring families, as well as chaos in the home environment, produce long-lasting emotional problems in children [3], [4]. Some of these effects are seen on brain structure and function and in the risk for later depression and posttraumatic stress disorder [5], [6], [7]. Other manifestations include increased risk for obesity and cardiovascular disease [8], [9].

Recent progress in neuroscience and biomedicine is providing a better understanding of mechanisms and pathways for these effects. This article will provide an overview by discussing 3 aspects. The first concerns animal models of early life adversity that provide mechanistic insights, including glimpses into the fascinating world that is now called “epigenetics.” Second, the translation of animal studies to understand and investigate the impact of early life adversity in humans will be discussed. Finally, the types of interventions that are likely to be most effective in early life will be considered. They will also be compared with the relative merits of pharmaceutical, medical, and psychosocial interventions to deal with the effects of early life adversity.

Section snippets

The long-lasting influence of early life experiences: contributions of animal models

The aging process begins at conception, and experiences early in life have a profound influence on the quality and length of life. Animal models have provided important insights. In rodents, early life maternal care is a powerful determinant of life-long emotional reactivity and stress hormone reactivity, and increases in both are associated with earlier cognitive decline and a shorter life span [10], [11]. Strong maternal behavior, involving licking and grooming of the offspring, produces a

Translation to understanding early life influences on human physiology and behavior

The animal models are very useful in helping to understand how early life experiences affect human physiology and behavior. Early life physical and sexual abuse carry with it a life-long burden of behavioral and pathophysiologic problems [1], [2], including an increased proinflammatory tone 20 years later [25]. Moreover, cold and uncaring families produce long-lasting emotional problems in children [3]. Some of these effects are seen on brain structure and function and in the risk for later

Importance of gene-environment interactions

In addition to the effects of experiences, genetic differences also play an important role as part of the nature-nurture interaction. This is a vast and growing topic, and only some examples will be noted here. For example, alleles of the glucocorticoid receptor gene found in the normal population confer a higher sensitivity to glucocorticoids for both negative feedback and insulin reponsiveness [33] or glucocorticoid resistance [34]; moreover, there is evidence of increased likelihood of

Epigenetic regulation

As evidence accumulates for the complex interactions between genes and environment, there is a new chapter opening up dealing with the molecular basis of gene regulation. This is catalyzed by recasting of an older term with new molecular meaning. “Epigenetics,” meaning “above the genome,” was originally defined to mean the gene-environment interactions that bring about the phenotype of an individual. Now, “epigenetics” means something more specific in molecular terms, namely, the methylation of

Interventions

We have seen that experiences have profound and long-lasting influences on the body and brain both during adult life and during development, when the effects of stressful events may have even a more profound and lasting influence on what happens during the life course. The lasting effects manifest themselves in the wear and tear referred to as allostatic overload [53].

What is the best approach to reducing the burden of allostatic overload? Clearly, interventions early in life that promote

Conclusions

Early life experiences are particularly important in determining how the individual responds over the life course. Genetic variants of an increasing variety of genes are recognized as contributing to the vulnerability or resilience in the face of stressors. At the same time, the new science of “epigenetics” is revealing ways in which the genome is regulated and modified in either a metastable or transgenerational manner, which alters the expression of certain genes. Some of these modifiable

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    STATEMENT OF CONFLICT OF INTEREST: The author is a member of the Scientific Committee of the Collège International de Recherche Servier (CIRS).

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