Editorial [Hot Topic: Stress-Induced Deleterious Consequences in the Gastrointestinal Tract. (Guest Editors: Juan C. Leza and Luis Menchen)]

During the second half of the nineteenth and the first decades of the twentieth century the separation of medical and psychiatric disorders started to be reconsidered by a number of physicians and scientists, leaded by Ivan Pavlov and Walter Cannon that inherited the legacy of Hippocrates and Galen who, more than two thousand years ago support the notion that psychosomatic disorders were abnormal physical reactions to stressful emotions or situations. Soon after, Hans Selye defined the physiological responses to stressors and adapted the term stress from physics and engineering to introduce it in the medical vocabulary: “in the biological sense stress is the interaction between damage and defense, just as in physics tension or pressure represents the interplay between a force and the resistance offered to it”, [1]. Selye described a uniform array of sequential, adaptive responses - termed the “General Adaptation Syndrome” - that, through the years, have been universally accepted as direct consequences of stress exposure: enlargement of the adrenal glands, atrophy of immune organs such as thymus, spleen and lymph nodes, and gastrointestinal ulcers [2, 3]. Eighty years later, the definition of stress remains to be subject of debate. In biological systems, the classical definition is any condition that seriously perturbs the physiological/psychological homeostasis of an organism. Indeed, biological stress occurs every day to organisms in their relation with other organisms and also with themselves, provoking a double-faced response: it can be an adaptive mechanism, allowing the organism to survive or fight to the stressful experience, but stress have also a negative impact on the individual, mainly after very intense, long lasting stressful stimuli. Several decades after the seminal works cited above, McEwen extended the term of homeostasis to explain that these mechanisms of stability are continuously changing and called it allostasis [4]. The price the organisms pay to maintain (or try to maintain) the stability is called allostatic load, many times clear diseases. The development of possible permanent changes depends on factors such as chronicity, controllability, predictability and habituation, in part because they are influencing the way an organism can reduce the impact of stressors (coping strategies). The current terminology distinguishes between the stimulus (stressful stimulus or stressor), the state generated in the organism (stress) and the response to the situation (stress response) [5]. Nowadays physical and psychological stresses are widely accepted as triggers and / or modifiers of the clinical course of a variety of gastrointestinal diseases such as functional gastrointestinal disorders, peptic ulcers, and inflammatory bowel diseases [6]. It has been shown that patients with functional gastrointestinal disorders, gastroduodenal ulcers, and relapsing IBD are more frequently exposed to stressful stimuli [7]. On the other hand, stress is involved in the subjective perception of gastrointestinal symptoms - which is often a challenge for the specialist - by patients [8], and psychological factors could be related with the high rate of placebo responses observed in IBD and IBS clinical trials. But although the relationship is often recognized both by patients and physicians, obvious methodological pitfalls of clinical studies make the demonstration of a casual nexus difficult. During the last years, growing evidence from experimental studies supports the ability of psychosocial stress to induce a wide variety of disturbances on the gastrointestinal tract such as gastric erosions and ulcers, increased gastrointestinal motility, altered ion secretion, increased intestinal permeability and enteric neurons dysfunction, to increase the severity of experimental colitis, and even to reactivate a quiescent colitis [9]. In this volume of Current Molecular Medicine, several scientists from some of the most productive groups worldwide in this topic write theirs reflections on different aspects of the effects of stress on the gastrointestinal function. Throughout these pages the possibility that consequences of stress provoke or predispose to disease, and the molecular and cellular basis of gut damage will be reviewed. Maunder and Levenstein, from Toronto and Rome, systematically review the published epidemiological evidence about the role of stress in the development and clinical course of IBD. Interestingly, whereas evidence of a contribution of stress to the onset of the disease is very weak, longitudinal studies on stress or depression and IBD disease course (based on inflammatory parameters) showed a significant relationship between UC and stress and CD and depression. Although possible therapeutic benefits of psychological interventions are limited by methodological weaknesses in these studies, both psychological and pharmacological interventions may be taken into account in IBD patients.