Psychosocial Stress and Mechanisms of Skin Health: A Comprehensive Update

January 2021 | Volume 20 | Issue 1 | Original Article | 62 | Copyright © January 2021


Published online December 22, 2020

Mary D Sun BA BSEa, Evan A Rieder MDb

aIcahn School of Medicine at Mount Sinai, New York, NY
bRonald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York, NY

Abstract
Although the relationship between psychosocial stress and skin health is commonly invoked in both the scientific and popular literature, its underlying mechanisms are still not well understood. In this review, we provide a comprehensive update on the pathophysiology of stress and its clinical impact on skin homeostasis. The recent characterization of a bidirectional HPA stress axis in the skin has illuminated peripheral stress pathways, with effects spanning inflammation, atopy, barrier function, dermal thinning, wound healing, and melanogenesis. Additionally, new research into the cutaneous microbiome suggests the development of stress-induced dysbiosis through the “gut-brain-skin” axis. These new findings help contextualize how lifestyle factors such as diet, personal care practices, and sleep patterns may mediate and sometimes amplify the cutaneous impacts of psychological stress. We aim to clarify these clinically important relationships and highlight areas of future study that have widespread academic, clinical, and commercial implications.

J Drugs Dermatol. 2021;20(1):62-29. doi:10.36849/JDD.2021.5608

INTRODUCTION

The dynamic relationship between psychosocial state and skin health is a growing area of research and interest in dermatology. Psychosocial stress increases levels of cortisol,1,2 known as the “fight-or-flight” hormone, and activates the neuroendocrine system via the hypothalamic-pituitary-adrenal (HPA) axis.3,4 Therefore, the HPA axis is commonly referred to as the central stress axis. Stimulation of the stress axis affects multiple organ and body systems, including the sympathetic nervous system,3,5 immune response,6,7 cholinergic response,8 and microbiome.9-11 Epidemiological evidence has established that stress and emotional states can predispose and/or exacerbate many skin conditions, including but not limited to acne vulgaris,12-14 chronic itch,15,16 urticaria (hives),17 atopic dermatitis,18-20 psoriasis,21-24 vitiligo,25 and alopecia areata.26,27 Furthermore, dermatologic diseases are often comorbid with worse mental health outcomes and reduced quality of life, suggesting a bi-directional link.28,29 Indeed, psychiatric disorders and psychosocial stress are estimated to occur with or worsen nearly one third of skin disorders.29

In this review, we provide a comprehensive update of the evidence linking stress and skin health. Psychosocial stress is induced by an environment of social threat that impairs the gratification of core psychological needs, including affiliation with others and the maintenance of social-self.30 Note that our discussion refers only to psychosocial stress and generally excludes other well-described stressors including chronological aging, photoaging, and physical shear stress, unless mediated or potentiated by emotional stress. We discuss advancements in our understanding of the stress response, including the discovery of a fully operational, cutaneous analog of the classic HPA axis,31 and examine the multifactorial ways psychosocial stress interacts with the neuroimmune system to impact the health and appearance of skin. Specific emphases include inflammation and atopy, dysfunction of the skin barrier, cutaneous infection, wound healing, melanogenesis, and the modulatory role of the cutaneous microbiome. While stress-induced events can accumulate over various timescales, we highlight the effects of chronic psychological stress given its strong link to dysfunction of the HPA axes. Additionally, research into the cutaneous microbiome suggests that stress induces dysbiosis through the “gut-brain-skin” axis.32 These findings provide additional insight into the effects of diet, hygiene practices, and sleep on the mediation of stress-induced effects in skin.

Foundations of the Cutaneous Stress Response
The central (systemic) neuro-immuno-endocrine stress axis
Psychological stress elicits an immune response mediated by the central nervous and sympathetic adrenal systems. Cytokine levels increase,33 activating the locus coeruleus–norepinephrine sympathetic adrenomedullary (LC-NE/SAM) stress-response system and the hypothalamic–pituitary–adrenal (HPA) axis.34 The LC-NE/SAM releases epinephrine and norepinephrine,34 catecholamines that innervate lymphoid organs and upregulate the immune response.35 In times of acute stress, this increased