Of body and mind: if breathing helps cope with stress, does impaired breathing promote anxiety?

Abstract

Stress is part of modern life. Whether real or perceived, challenging situations trigger brilliantly orchestrated neuroendocrine responses aiming to prepare the organism to face (or escape) the threat. In the short term, the release of stress hormones is a highly adaptive response that helps maintain homeostasis. Cortisol (in humans) or corticosterone (in rodents) are key effectors in this process owing to their ability to elicit rapid responses (via membrane receptors) or act as potent transcription factors capable of modulating gene expression. As such, these hormones can induce plasticity and thus alter physiology in many ways. When stress persists, however, chronic elevation of these steroids can have encompassing and deleterious effects on health. Neuroscientists have explored this notion for decades (Lupien et al. 2009), and we now know that chronic elevation of cortisol is closely associated with major depression (Zunszain et al. 2011). Previously in Experimental Physiology, Scheuer (2010) had discussed how stress hormones can interfere with the neural circuits regulating blood pressure and increase the incidence of hypertension and other manifestations of cardiovascular disease. On occasion, respiratory physiologists highlight the significance of their research to their audience (and funding agencies) by rightfully stating a wise (and famous) quote from Mr Miyagi: ‘no breathe, no life’. Consistent with the vital necessity to ensure gas exchange during challenging times, an increase in breathing is an important part of the response to stress. As a result, the neural circuits that co-ordinate the stress response evolved smartly; they are anatomically and functionally interlinked with those that regulate breathing (Kc & Dick, 2010; Behan & Kinkead, 2011). Consequently, most conditions that interfere with the act of breathing or compromise homeostasis of arterial blood gases consistently trigger powerful behavioural, emotional and physiological responses. Despite their appreciation of wisdom in certain contexts, respiratory physiologists too frequently dismiss or ignore the potential impact that stress can have on respiratory regulation. Though rarely measured, the possibility that stress hormones are released in response to an experimental treatment that mimics specific aspects of a respiratory disease is more frequently considered as an inconvenient confounding variable rather than being viewed as mechanism that can alter a phenotype and thus contribute to the pathophysiology of interest. Conversely, the fact that respiratory dysfunction and dyspnoea are stressors that could (at least in part) explain affective disorders is not a prominent notion in this sphere of biomedical research. In their article, in this edition of Experimental Physiology, Pate & Davenport (2013) did not embrace these common views; instead, they chose an alternate and innovative tack as they aimed to determine whether chronic respiratory obstruction can stimulate the release of stress hormone (corticosterone) and promote anxiety in rats. For their study, these authors developed a clever experimental approach to perform tracheal occlusion in awake animals over 10 consecutive days to mimic the recurrent airway obstructions experienced by patients suffering from respiratory disease. By measuring indicators of anxiety and activation of the stress response, as well as neuronal activation in selected brain regions before and after exposure to the protocol, they showed that tracheal occlusion causes anxiety and augments the basal level of stress and activity in brainstem regions influencing cardiorespiratory function and affective sensory processing. In pulmonary diseases, such as chronic obstructive pulmonary disease and asthma, experiencing the respiratory load associated with increased airway resistance constitutes both a psychological and a systemic stress. For most clinical studies, the presence of confounding factors related to disease and co-morbidity makes it difficult to draw clear conclusions on the impact of stress on disease state. By performing experiments on otherwise healthy animals, the results of Pate & Davenport (2013) indicate that recurrent airway obstruction is sufficient to cause anxiety. Their work therefore provides valuable insight into the pathophysiology of complex, yet interrelated diseases affecting both the body and mind. Knowing that stress increases vulnerability to disease, their work also raises important questions regarding the impact of a tensed mind on the emergence of respiratory disease. Readers are invited to give their opinion on this article. To submit a comment, go to: http://ep.physoc.org/letters/submit/expphysiol;98/3/652