Stress: an historical perspective

Seymour Levine*    Department of Psychiatry, Center for Neuroscience, University of California, Davis, California 95616, USA
* Tel.: + 1530 752 1887; Fax: + 1530 757 8827; email address: slevine@ucdavis.edu

Introduction

During the course of my career, which now spans over five decades, I could not begin to count the number of conferences, workshops, and symposia related to stress that I have attended. I will not attempt to describe the number of times during these meeting that at least one, if not several, of the participants had championed the notion that we discard the concept for a more precise definition. The absolute failure of these attempts is attested to by my most recent visit to one of my favorite biomedical computer searches. As of this moment Pub–Med listed 209,744 references that in one way or another had some reference to the term stress. It would be difficult to predict what this number will be at the time this chapter is published. These staggering figures are at best an underestimate since computer searches rarely go beyond the late 1970s and publications in this field began long before this time. Further, the particular search that was used lists mostly articles and ignores the extensive list of books dedicated to this subject. What is also evident from the information obtained from the computer is that the number of publications is accelerating. Over 60,000 papers have been published since the beginning of the new millennium. A close examination of only a small sample of these references made it abundantly clear that the term stress was used in so many different ways that it would be necessary to determine, for each article listed, the precise manner the term was used and in what context. It would be further difficult to specify all the different disciplines that have in some way found the concept of stress useful, though each discipline will define stress in its own idiosyncratic manner.

Defining stress

After the completion of my last effort to define stress (Levine and Ursin, 1991), I made myself the promise that I would never again engage in what I consider a futile exercise. One of the more recent definitions was presented by McEwen (2000). “Stress may be defined as a real or interpreted threat to the physiological or psychological integrity of an individual that results in physiological and/or behavioral responses. In biomedicine, stress often refers to situations in which adrenal glucocorticoids (GCs) and catecholamines are elevated because of an experience.” Chrousos and Gold (1992) state “we define stress as state of disharmony, or threatened homeostasis. The adaptive response can be specific or can be generalized and non specific.” At the core of these definitions is the concept of homeostasis. Thus, some disturbance of homeostasis results in a cascade of physiological and/or behavioral responses that presumably are required to reinstate the ideal homeostatic balance.

However, these definitions as well as most others are problematic. As stated by Levine and Ursin (1991) “The major problem with the concept of stress is that we are confronted with a composite, multidimensional concept. All existing definitions include some components. We can identify three main subclasses. These subclasses can be identified as the input (stress stimuli), the processing systems, including the subjective experience of stress and the output (stress responses). One basic difficulty is that these subclasses interact. The essential picture we want to convey is one of a complex system with feedback and control loops, no less but no more complicated than any other of the body’s self-regulated systems. This system affects many other biological processes and may function as a common alarm and drive system, whenever there is a real or apparent challenge to the self-regulating systems of the organism.”

Steptoe (2000) has suggested that “the effects of stress are manifest in four distinct domains; physiology, behavior, subjective experience, and cognitive function. The physiological effects of stress include alterations in neuroendocrine, autonomic nervous system and immune function.” If one were to isolate only the physiological effects of stress, the history of three major areas of investigation would need to be covered and this would not include the relationships or lack of relationship among these systems. This historical perspective will focus primarily on the neuroendocrine system and more specifically with the hypothalamic–pituitary–adrenal (HPA) axis. For this discussion we will use the more traditional designation HPA, although more recently we have seen a trend to label the axis as LHPA. The “L” stands for limbic system and is intended to indicate that the regulation of the hormonal cascade caused by exposure to stress involves extrahypothalamic structures. The aim of this chapter is to provide a glimpse into the historical events that have provided the framework, the insights, and the theories that in many ways still guide our current research.

Insofar as several papers will appear in subsequent volumes that deal extensively with many different aspects of the HPA axis, I will provide only a very simple description of some of the key elements in the neuroendocrine cascade that results in an increased secretion of adrenocorticotropic hormone (ACTH), and that ultimately results in elevations of the levels of GCs. Some environmental event which involves either physical demands or is psychologically challenging or a combination of both, induces an increase in the release of corticotrophin–releasing factor (CRF) and arginine vasopressin (AVP) into the portal circulation. CRF/AVP then activates the corticotrophs in the pituitary to release ACTH into the general circulation. ACTH acts upon the adrenal cortex to induce synthesis and increased secretion of the GCs. Under normal circumstances these elevated levels of GC activate the GC receptors which serve to terminate the release of CRF and ACTH, thus returning the organism to its basal state.

Traditionally, a discourse on the history of this or any other field would trace the evolution of the critical components along some time dimension. If I were to take this approach the result would simply be a compilation of the information contained in many other sources. Since history does unfold through time it is difficult to avoid using a temporal framework. However, I intend to trace this history as it unfolded in my academic lifetime and how it influenced and shaped the field as we know it today. This will be an historical perspective, but the perspective will be autobiographical.

Not so ancient history

As was stated earlier I will not attempt to present all the details of the variety of thought and experimental evidence that eventually leads us to the 21st century views of stress. The earliest references to the concept of homeostasis come from the Greek philosophers and physicians, in particular, Hippocrates. This is best summarized by Chrousos et al. (1988). What is important is that the concepts of harmony and disharmony (homeostasis?) of man and animals with both the external and internal environment have long been a concern of serious thinkers. The concept of stress was originally taken from the dynamics of physics to describe the relationship between stress and strain in an elastic body. “The term stress is applied to the mutual actions which take place across any section of a body to which a system of forces is applied. The term strain is applied to any changes occurring in the dimension or shape of a body when forces are applied” (Duncan and Starling, 1959).

However, our current interest in and views on the physiology and psychology of stress are of more recent vintage and can be traced primarily to the contributions of Walter B. Cannon (1914, 1915, 1932) and Hans Selye (1950, 1956). The overarching principles that emerged from the studies by Cannon and Selye were: (1) there was a physiology that was specific to stress and (2) that an integral part of this physiology was related to some function of the adrenal. Although both emphasized the role of the adrenal, there was a clear distinction between them. (1) Cannon focused primarily on the sympathetic nervous system, including the adrenal medulla, and the role of the...