Review article
HPA axis, respiration and the airways in stress—A review in search of intersections

https://doi.org/10.1016/j.biopsycho.2010.01.021Get rights and content

Abstract

Given clear connections between respiratory distress and subjective anxiety, it is not surprising that respiratory psychophysiologists have been interested in the psychobiology of anxiety. Given parallel links between anxiety and stress, it is not surprising that the hypothalamic-pituitary adrenal (HPA) stress system has also been a focus in anxiety research. However, despite extensive work in respiratory psychophysiology and stress neuroendocrinology – and evidence that these systems are jointly dysregulated in anxiety disorders – direct studies of their interactions are rare. This paper reviews evidence for scientific intersections, providing an overview of the HPA axis, its psychobiology, and shared neural substrates for HPA and respiratory control. We examine HPA hormone effects on respiration, immune/inflammatory mediators, and lung maturation. We also examine respiratory/dyspnea effects on HPA axis. There are clear points of intersection in the neuroscience of respiration and stress. Given the importance of both systems to an organism's ability to survive and adapt in challenging and changing environments, further study of their interactions is needed.

Introduction

Suffocation is among the most frightening experiences to which a human being can be exposed—witness the use of water boarding as torture and the outcry it has created. Being cut off from oxygen is an immediate and direct threat to life, but usually leaves the organism time to be aware of the threat and make efforts to escape, which is likely to generate intense emotional responses is humans. Given the intuitive connection between respiratory distress and fear, anxiety or the flight response, and the critical need for oxygen in stress adaptation, it is not surprising that the respiratory–anxiety link is of scientific interest (Wilhelm et al., 2006). Indeed, key theories of anxious psychopathology (e.g. panic disorder) have focused on respiratory control or monitoring systems (Klein, 1993); and the neurobiological relationships between critical emotion processes and respiratory control are now being characterized (Evans, 2009, Evans et al., 2009). If we all know what the acute distress of breath holding feels like, most of us also are familiar with the different set of feelings associated with prolonged stress—which is often subjectively characterized by anticipation of future calamity in the absence of an ability to control, shape or cope with the anticipated negative outcome. This is the quintessential type of situation that activates our central, neuroendocrine stress response system, the hypothalamic-pituitary adrenal (HPA) axis (Dickerson and Kemeny, 2004), leading to release of cortisol from the adrenal cortex. This stress system has been of central importance in the development of modern, biological psychiatry (Carroll et al., 1981). It is clearly critical for survival (McEwen, 1998), appears to suffer some degree of dysregulation across a wide range of psychiatric disorders (Khan et al., 2009) and plays a central role in the linkage between psychosocial stress and a wide range of general health problems (McEwen, 1998).

Though the psychophysiology of respiration and the neuroendocrinology of stress are both vibrant areas of research, there is little work done examining their intersections. This neglect may be partly due to lack of dialogue between the respective disciplines and a need to adequately develop each area separately before intelligently exploring intersections. However, given growing evidence linking neurobiological regions regulating emotional control with both respiratory phenomena and stress hormones (Jankord and Herman, 2008, Kristensen et al., 1997), and growing evidence that both systems are dysregulated in anxiety-related psychiatric disorders (Abelson et al., 2007, Wilhelm et al., 2001b, Young et al., 1994), further study of intersections may now be worthwhile.

To provide additional foundation for future attention to the intersections between respiratory psychophysiology and stress neuroendocrinology, we will provide an overview of the HPA axis and preliminary research from our group examining respiratory and neuroendocrine responses in panic disorder patients. We will then examine neuroanatomical intersections between HPA and respiratory control systems, physiological effects of HPA hormones on respiratory systems and development, and the impact of respiration on the HPA axis. Emerging themes suggest that the HPA axis and its end product cortisol play a major role in shaping biobehavioral capacities to adapt to changing and challenging environments, both through early programming of developing organ systems and through ongoing influences on acute and chronic responses to threats to survival; that a healthy and appropriately responsive respiratory system is equally critical to survival; and that these two systems have many points of intersection that warrant ongoing scientific attention.

Section snippets

Structure and function of the HPA axis

Stimulation of the hypothalamic-pituitary-adrenal (HPA) axis is precipitated by release of adrenocorticotrophic hormone (ACTH) from the anterior pituitary. In response to stress, this results from synergistic stimulation of the pituitary by corticotrophin-releasing hormone (CRH) and arginine vasopressin (AVP) from neurons originating from parvo- and magnocellular neurons in the peraventricular nucleus of the hypothalamus (PVN). CRH and AVP reach the pituitary through a circumscribed portal

Psychobiology of the HPA axis and intersections with respiratory control

Understanding of central control of the HPA axis has now expanded beyond the hypothalamus to include complex limbic and cortical inputs. Key additional brain regions of interest include those that subject sensory inputs to higher order processing involving memory, learning, emotion, cognition and their interactions (Herman et al., 2003). Given the fundamental importance of respiration to survival, and the critical need to efficiently match respiratory activity to immediate and anticipated

Inflammatory and immune effects

In addition to points of intersection between HPA axis and respiratory control systems within the brain (described above), there are also potential interactions in the periphery involving glucocorticoid effects on inflammatory and immune function. Cortisol produces specific anti-inflammatory effects and, through these mechanisms, could potentially mediate a relationship between stress and airway inflammation. This complex relationship is discussed in greater detail elsewhere in this issue, but

The influence of respiration on the HPA axis

In addition to the impact of HPA-mediated stress and immune processes on pulmonary function and health, there is also evidence that respiratory function per se can impact health and that HPA axis function may be an important mediator of these effects. The primary role of the respiratory system is the vital function of gas exchange with the external environment in order to supply oxygen to the body and remove carbon dioxide (Hlastala and Berger, 2001). Respiratory system dysfunction perturbs

Conclusions

Much remains to be learned about the complex interactions between stress response systems of the body involving hormonal, immunological, and physiological response channels. We have learned much from independent study of each of these systems, but the narrow focus required for deepened understanding of specific systems leaves us fairly ignorant of the interactions between systems. General systems theorists called on us decades ago to recognize the hierarchical organization of living systems,

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