Stress and the Skin
The skin is the interface between an organism and the outside world. External factors, such as cold, dryness, air pollution and UV radiation impact the skin in predictable ways. However, while psychological stress long has been recognized as an exacerbating factor in many skin conditions, we now are just beginning to understand possible mechanisms that may underlie this process. Psychological stress appears to act through the glucocorticoid portion of the HPA axis to modulate keratinocyte, nerve and immune cell responses. Effects of psychological stress on the keratinocyte epidermal permeability barrier are best understood; however, psychological stress notably also affects hair follicles, mast cells, and acute and chronic immune responses. Skin conditions known to be initiated or exacerbated by stress include atopic dermatitis, psoriasis, urticaria, acne, effluvium (hair loss), alopecia areata and vitiligo.
In humans, psychological stress is known to initiate or exacerbate many skin conditions, most notably atopic dermatitis, psoriasis, acne, non-immune mediated hair loss (effluvium), immune-mediated hair loss (alopecia areata), and vitiligo (reviewed in Alexopoulos and Chrousos, 2016). The epidermal permeability barrier was the first aspect of the skin to be successfully probed for mechanisms by which psychological stress might modulate skin function. The epidermal permeability barrier is composed of lipids that are processed between the uppermost cells of the epidermis (stratum corneum), thus keeping water and ions within the epidermis, and toxins out. An antimicrobial barrier also is contained within this permeability barrier, as the lipid bilayers contain antimicrobial peptides, and the stratum corneum is acidified. A variety of psychological stressors such as exams (Garg et al 2001) or divorce (Muizzuddin et al 2003) have been shown to decrease epidermal barrier function in humans. Further studies in mice also show that skin infections (Aberg 2007) are worsened by psychological stress. The best characterized pathophysiologic mechanism to explain the effects of psychological stress on skin function is that of the hypothalamic-pituitary-adrenocortical (HPA) axis (reviewed in Maarouf et al 2019). Psychological stress has been shown to increase glucocorticoid production, and blocking its effects, by preadministering either RU-486, a glucocorticoid receptor antagonist, or antalarmin, a corticotropin-releasing hormone (CRH) receptor antagonist that prevents increased GC production, rescues the epidermal barrier from the deleterious effects of psychological stress (Choi et al 2006, Choe et al 2018).
Psychological stress also is known to mediate skin nerve activity. The HPA axis also controls some aspects of this modulation, although additional downstream modulators from nerves, keratinocytes, fibroblasts and mast cells also likely play a role (reviewed in Alexopoulos and Chrousos 2016). These downstream mechanisms are much less studied than the HPA axis detailed above. While most animal and human studies have concentrated on acute psychological stress, it’s clear that chronic psychological stress also plays a role in skin disease. The immune system, in particular, plays a larger pathologic role in skin conditions associated with chronic stress (reviewed in Dhabhar 2009). Finally, psychological stress has been associated with defects in wound healing (reviewed in Walburn 2009).
Collection and Measurement
Epidermal barrier function can be measured in a variety of ways. Baseline transepidermal water loss (TEWL) is the easiest measure. However, numerous studies show that 24-hour recovery after standardized barrier perturbation (tape stripping) is a more accurate measure of epidermal barrier function. Other standard measures on people include stratum corneum pH and barrier integrity (number of tape strips it takes to break the barrier). On experimental preparations, transepidermal resistance (TER), permeation to dyes and immunostaining for antimicrobial peptides and circulating immune cells also are used (Alexander et al 2018).
Author and Reviewer(s):
This summary was prepared by Dr. Theodora Mauro and reviewed by Drs. Peter Elias, Katrina Abuabara, and Jan Kiecolt Glaser. Please direct any questions or feedback to Dr. Mauro ().
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