Stress Resilience

Molecular and Behavioral Aspects

Alon Chen

• Publisher: Academic Press
• Year: 2019
• ISBN:
  9780128139844
• Topic: Psychologie
• Subtopic: Neuropsychologie

Stress Resilience: Molecular and Behavioral Aspects presents the first reference available on the full-breadth of cutting-edge research being carried out in this field. It includes a wide range of basic molecular knowledge on the potential associations between resilience phenomenon and biochemical balance, but also focuses on the molecular and cellular mechanisms underlying stress resilience. World-renowned experts provide chapters that cover everything from the neural circuits of resilience, the effects of early-life adversity, and the transgenerational inheritance of resilience.

This unique and timely book will be a go-to resource for neuroscientists and biological psychiatrists who want to improve their understanding of the consequences of stress and on how some people are able to avoid it.

• Approaches resilience as a process rather than as a static trait
• Provides basic molecular knowledge on the potential associations between resilience phenomenon and biochemical balance
• Presents thorough coverage of both the genetic and environmental factors that contribute to resilience

Chapter 1

A life-course, epigenetic perspective on resilience in brain and body

Bruce S. McEwen Alfred E. Mirsky Professor Head, Harold and Margaret Milliken Hatch, Laboratory of Neuroendocrinology, The Rockefeller University, New York, NY, United States

Abstract

The brain is the central organ of stress and adaptation to stress because it perceives and determines what is threatening, as well as the behavioral and physiological responses to the stressor, which promote adaptation (“allostasis”) and also contribute to pathophysiology (“allostatic load/overload”) when overused and dysregulated. The adult, as well as developing brain, possesses a remarkable ability to show structural and functional plasticity in response to experiences, including neuronal replacement, dendritic remodeling, and synapse turnover. The hippocampus shows all three types of structural plasticity that have been recognized. The amygdala and prefrontal cortex show dendritic remodeling and spine synapse turnover. Acute stress and chronic stress cause an imbalance of neural activity that, in turn, affects systemic physiology. In the short term, these changes may be adaptive; however, if the danger passes and the behavioral state persists along with altered neural circuitry, such maladaptation may need intervention with a combination of pharmacological and behavioral therapies.

Keywords

Adverse childhood experiences; Allostasis; Allostatic load/overload; Amygdala; Epigenetics; Excitatory amino acids; Glucocorticoids; Hippocampus; Life course; Neuroplasticity; Prefrontal cortex; Toxic stress

Introduction

Resilience can be defined as “the ability to achieve a successful outcome in the face of adversity.” Understanding what this means in biological terms requires an understanding of “epigenetics,” as it is now applied to gene-environment interactions as well as the realization that the brain and body are continually changing as the life course proceeds and that one cannot simply “roll back the clock.” Moreover, positive and negative events during the life course, including events before conception and during gestation, can have long-term effects. Furthermore, the plasticity of the adult as well as developing brain provides the ability of experiences to change trajectories in a positive or negative direction. The mediators of this plasticity include not only endogenous neurotransmitters and neuromodulators but also mechanisms involving the cell surface, the cell nucleus, and mitochondria, along with circulating steroid and metabolic hormones. Two-way interactions between brain and body are of paramount significance, and the concepts of allostasis and allostatic load emphasize that the same mediators that promote adaptation in a biphasic and nonlinear manner can also promote pathophysiology when they are overused or dysregulated among themselves.

We begin by considering the meaning of “stress” and the concepts of allostasis and allostatic load before introducing brain adaptive plasticity and epigenetics and how they produce adaptive as well as maladaptive plasticity. Studies of gene expression show that the brain is continually changing and that one cannot “roll back the clock.” Moreover, experiences can have lasting positive influences as in successful attachment or lasting negative influences as in early life abuse and neglect or traumatic events that cause PTSD. This raises the issue of interventions where we now must refer to “resilience” rather than “reversal” in describing what appears to be “recovery” and must therefore think about the process as a “redirection” of a trajectory in more positive direction.

What is stress?

“Stress” is a widely used and ambiguous word and so this chapter will use the following classifications of types of stress: good stress, tolerable stress, and toxic stress.

See http://developingchild.harvard.edu/library/reports_and_working_papers/policy_framework/ for paper related to toxic stress.

"Good stress" is a term used in popular language to refer to the experience of rising to a challenge, taking a risk, and feeling rewarded by an often-positive outcome. A related term is “eustress.” Good self-esteem and good impulse control and decision-making capability, all functions of a healthy architecture of the brain, are important here! Even adverse outcomes can be “growth experiences” for individuals with such positive, adaptive characteristics that promote resilience in the face of adversity.

“Tolerable stress” refers to those situations where bad things happen, but the individual with healthy brain architecture is able to cope, often with the aid of family, friends, and other individuals who provide support. These adverse outcomes can be “growth experiences” for individuals with such positive, adaptive characteristics and support systems that promote resilience. Here, “distress” refers to the uncomfortable feeling related to the nature of the stressor and the degree to which the individual feels a lack of ability to influence or control the stressor (Lazarus and Folkman, 1984; Diez Roux and Mair, 2010; Theall et al., 2013).

Finally, “toxic stress” refers to the situation in which bad things happen to an individual who has limited support and who may also have brain architecture that reflects effects of adverse early life events that have impaired the development of good impulse control and judgment and adequate self-esteem. Here, the degree and/or duration of “distress” may be greater. With toxic stress, the inability to cope is likely to have adverse effects on behavior and physiology, and this will result in a higher degree of allostatic overload, as will be explained later in this chapter.

Definition of stress, allostasis, and allostatic load

In spite of the further definitions of types of stress, the word “stress” is still an ambiguous term and has connotations that make it less useful in understanding how the body handles events that are stressful. Insight into these processes can lead to a better understanding of how best to intervene, a topic that will be discussed at the end of this chapter. There are two sides to this story: on the one hand, the body responds to almost any event or challenge, whether or not we call it “stress,” by releasing chemical mediators—for example, catecholamines that increase heart rate and blood pressure—and helps us cope with the situation; on the other hand, chronic elevation of these same mediators—for example, chronically increased heart rate and blood pressure—produces a chronic wear and tear on the cardiovascular system that can result, over time, in disorders such as strokes and heart attacks. For this reason, the term “allostasis” was introduced by Sterling and Eyer in 1988 to refer to the active process by which the body responds to daily events and maintains homeostasis (allostasis literally means “achieving stability through change”). Since chronically increased allostasis can lead to disease, we introduced the term “allostatic load or overload” to refer to the wear and tear that results from either too much stress or the inefficient management of allostasis, for example, not turning off the response when it is no longer needed. Other forms of allostatic load involve not turning on an adequate response in the first place or not habituating to the recurrence of the same stressor and thus dampening the allostatic response (McEwen, 1998). See Fig. 1.1.

Figure 1.1 Central role of the brain in allostasis and the behavioral and physiological response to stressors.
Modified from McEwen, B.S. 1998. Protective and damaging effects of stress mediators. The New England Journal of Medicine 338, 171–179, with permission.

Protection and damage as the two sides of the response to experiences

Protection via allostasis and wear and tear on the body and brain via allostatic load/overload are the two contrasting sides of the physiology involved in defending the body against the challenges of daily life. Besides adrenalin and noradrenalin, there are many mediators that participate in allostasis, and they are linked together in a network of regulation that is n...