Brain–skin axis

There is varying degrees of evidence to support the relationship between stress and skin disease. For psoriasis and atopic eczema that evidence is well-established, it is less well so for urticaria, herpes simplex virus and vitiligo and only a weak association exists for lichen planus, pemphigus vulgaris and acne (Pavlovsky & Friedman, 2007). Whilst there is still much research needed to untangle the mechanisms that link the brain and skin with associated stress, current opinion suggests that there are three areas of interest: the hypothalamic–pituitary–adrenal axis (HPA), the peripheral nervous system (PNS) and biological barriers. The skin appears to have a dual role in relation to its response to stress. It is a target for key stress mediators (such as corticotrophin releasing hormone, adrenocorticotrophic hormone, cortisol, catecholamines, prolactin, substance P and nerve growth factor) but also a key source of these mediators of the stress response (Arck et al., 2006).

Hypothalamus–pituitary–adrenal axis
The interplay between these three glands describes the classic stress response. Following experience of a stressor, the hypothalamus releases corticotrophin-releasing hormone, this acts on the pituitary gland to release adrenocorticotrophic hormone which finally induces the adrenal gland to produce cortisol. It is thought that cortisol protects the body under stress, although the mechanism is not clear, and it has a well-known anti-inflammatory effect. What appears to happen in some chronic inflammatory disorders (particularly psoriasis and eczema) is that there is a muted HPA response with cortisol levels that are lower than those seen in a general population. Richards et al. (2005) demonstrated that patients with psoriasis had lower levels of serum cortisol following an experimentally induced emotional stress, than controls. More significantly, those who rated their psoriasis as stress-responsive had even lower serum cortisol levels than those who did not rate so. Thus psoriasis patients do not seem to show an appropriate response of the HPA axis (Richards et al., 2005). As a result of this reduced HPA reactivity, the body is not protected by the release of cortisol in response to stress.

Peripheral nervous system (PNS)
The PNS is all nervous tissue other than the brain and the spinal column (which are known as the central nervous system). Part of the PNS is not under voluntary control and as such is labelled the autonomic nervous system (ANS). The ANS can be divided further into the parasympathetic and sympathetic nervous systems. The parasympathetic system maintains the body in a normal resting state. Stimulation of the sympathetic nervous system occurs during times of stress. At a gross physiological level there are a number of changes that happen to the body in order to deal with that stress. These responses are based upon an innate ‘flight or fight’ response that were useful when stressors were large dangerous animals, threatening life and limb. Whilst humans rarely run away literally, or fight the stressors in their lives, the biological responses still prepare us to be able to do so (see Table 6.2).

Table 6.2 Changes in the sympathetic nervous system in response to stress.   Target organ Sympathetic effect   Brain Becomes alert and focused in order to prepare for finding safety   Circulatory system Heart beats faster Blood flow diverted to muscles ready for activity Blood flow away from skin leading to pallor (classic look of fear) Blood clotting ability increases, preparing for possible injury   Lungs Airways open up allowing for increased oxygenation Rate of breathing increases   Gut Less activity in digestion Vomiting may occur Constriction leads to feeling of butterflies or knot in the stomach   Liver Releases more sugar and blood sugar levels go up in order to provide more energy   Bladder and bowel Tend to be more irritable with decreased bladder capacity. May lead to involuntary emptying of either   Sexual organs Erectile dysfunction in men Loss of lubrication in women

Besides the more familiar role of the sympathetic nervous system in relation to stress, it also has a crucial immune-related role to play through the release of catecholamines. These appear to stimulate stress-induced lymphocytosis and lead to particular changes in lymphocyte trafficking, circulation, proliferation and cytokine production. Another neurohormone which has a crucial role to play is nerve growth factor (NGF), which is a potent immunomodulator, aiding cell communications and facilitating monocyte/ macrophage migration through vascular endothelium (Arck et al., 2006). NGF modulates the synthesis of substance P which probably has a role in the activation of mast cells to secrete specific cytokines, chemokines and tumour necrosis factor α (Pavlovsky & Friedman, 2007).


Biological barriers
Studies in both human and animal models suggest that psychological stress has a direct impact on skin barrier and the ability for it to repair. A study looking at two groups of women who were put under psychological stress in a laboratory, one group through interview stress and another through sleep deprivation, both experienced a delay in barrier function recovery (Altemus et al., 2001). Further work on mouse models suggest that this occurs because psychological stress leads to decreased epidermal proliferation, decreased epidermal differentiation and decreased the density and size of corneodesmosomes. Decreased production of lamellar bodies and decreased secretion from them leads to a lower level of natural lipid in the skin that affects barrier function (Choi et al., 2005).