Anxiety and helplessness in the face of stress predisposes, precipitates, and sustains gastric ulceration

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Abstract

When an organism is subjected to stress, gastric ulcers or ulcerations commonly develop but the vulnerability to and amount of pathology induced varies considerably between individuals. The role of psychological factors in determining the occurrence and severity of these ulcerations is amply demonstrated in the studies reviewed here. The present paper (a) gives a brief history of the search for the causes of gastric ulcer, (b) provides a review of our own research which reveals that vulnerability to gastric ulceration is modulated by psychologically meaningful experiences, and (c) offers a multifactorial perspective on the causes of gastric ulceration and the future of research on it.

Introduction

That emotions influence the digestive system has been known scientifically for at least two centuries [116]. At the end of the last century, Pavlov discovered that the digestive system was also influenced by prior conditioning and learning-a fact that proved a foundation for much of psychology in this century. Selye [95] promoted gastric ulcer as the prototypic disease of ‘stress’-both mental and physical-a view fostered by a number of classic observations on the interaction of emotion and gastric functions [117]. The present paper (a) gives a brief history of the search for the ‘causes’ of gastric ulcer, (b) provides a review of our own research which reveals that vulnerability to gastric ulceration is modulated by psychologically meaningful experiences, and (c) offers a multifactorial perspective on the causes of gastric ulceration and the future of research on it. Although many distinguished researchers have contributed to this field and guided our thinking, limitations of space in this review allow us to cite only a few. The interested reader is directed also to broader reviews [28], [108].

Section snippets

Animal models, causality, and mechanisms

Much of the research on causes has used animal models because they provide an opportunity to demonstrate causality and mechanisms [108]. The primary animal for this research has been the rat, although, in light of more recent interests in bacterial factors, it could be argued that the pig [23] or other species might be useful [35]. Stress-ulcers in rats are different from those in humans in that they are most commonly gastric rather than duodenal, and they are generally transient, healing over

Traditional single factor causal models

‘Stress’ is a concept central to research on gastric ulceration, yet it is a concept that has challenged researchers ever since (e.g. [41]). It is not surprising then, that, researchers studying stress and gastric ulceration have employed a variety of instantiations of ‘stress’. Most early research was based upon the hope of finding a single causal factor for ulcerations. In these, stress was induced by either a physiological or a psychological stress challenge.

Newer concepts

Diathesis-stress models seem to be popular now as accounts of all pathologies. And, indeed, bases for this abound in the literature. We have already noted several factors predisposing to gastric ulceration when stressed. How these influence gastric vulnerability is neither always readily apparent nor direct. For example, Ader et al. [7] early showed that rats weaned early were more vulnerable to ulcerations. Some initially attributed this increased vulnerability to social-psychological trauma.

Strategy

Our own research strategy has been guided by Weiner’s perspective on ulcerogenicity and Selye’s notion of ‘pluricausality’. We have adopted a strategy of using a known ulcerogenic physical challenge and exploring how past experiences and psychologically important variations in those past experiences can be shown to predispose to increased or decreased vulnerability to the physical challenge. We have also sought to show that one can take signal elements from those past events and reinstate

Mechanisms

We have shown that the ulceration processes can be modulated by treatments that access psychological processes in all three of the ulcerative stages, predisposing, precipitating, and sustaining. It would be of interest to know the mechanisms through which these psychological processes effected their modulation. Unfortunately the mechanisms of the ulcerative process itself are not yet understood. Several of these have been explored by others and also by ourselves, and we shall only briefly

Predicting vulnerability

One challenge that has faced us is the enormous differences between individuals in vulnerability to RIW. It would be useful to find ways to either constrain this variability or to predict in advance the individual vulnerability [57]. Such prediction itself could, perhaps through genetic analysis, allow isolation of the variables critical in ulcerogenesis. Individual rats differ in a number of other behavioral and physiological variables — aggressive behaviors, defensive behaviors, sensitivity

Bacterial infection and the future

We have presented a series of studies showing that psychological factors modulate gastric erosions in rats and there are reasons to believe that these factors operate in humans as well. The general implication is that these experiments which explore the psychological manipulations that are effective modulators of gastric vulnerability can, when combined with physiological assays, give insights into the proximal mechanisms that might otherwise be overlooked or misinterpreted. This implies that

Future research

Something is modulating vulnerability to Hp and/or Hp related pathology. Among these, certainly past life stress events are important risk factors — as well as a number of social and behavioral factors [40]. Thus, any future research strategy for animal models that seeks to link our past research program to contemporary human disease process must study the interaction of (a) psychological modulators of the type we have validated as relevant, (b) immunological status and bacterial exposure, and

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