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Specific cognitive behavioural mechanisms related to selective attention, situational avoidance and physical appearance are implicated in the development and maintenance of insomnia and negative reinforcement of body image disturbances. Therefore, we examined whether these processes potentially mediate the relationship between insomnia and body image perception. N=728 participants completed self-reported measures of sleep associated monitoring, insomnia symptoms, body image disturbance, and coping with body image challenges. Symptoms of insomnia and sleep-associated monitoring behaviour were independently related to increased reports of body image disturbance, cognitive distortions of body image, appearance fixing (i.e. altering appearance by covering, camouflaging, or correcting the perceived defect), avoidance (i.e. attempt to escape or avert stressful body-image situations) and reduced levels of positive rationale acceptance (i.e. acceptance of the challenging event and positive self-care or rational self-talk about one's appearance). More crucially, sleep-related monitoring on awakening, cognitive distortion of body image and negative coping strategies related to body image (i.e., appearance fixing, avoidance, rationale acceptance), mediated the relationship between reports of body image disturbance and insomnia symptoms. The current findings expand upon previous research demonstrating consistent relationships between poor sleep and increased dissatisfaction with cutaneous features, by providing novel evidence that body image disturbances are associated with symptoms of insomnia. More crucially, we highlight the role of particular cognitive and behavioural mechanisms pertaining to sleep (i.e., selective attention for physical signs of poor sleep) and body image (i.e., avoidance and rational acceptance) which may be targeted as part of cognitive behavioural treatments.
Context:
Insufficient sleep is associated with increased cardiometabolic risk. Alterations in hypothalamic-pituitary-adrenal axis may underlie this link.
Objective:
Our objective was to examine the impact of restricted sleep on daytime profiles of ACTH and cortisol concentrations.
Methods:
Thirteen subjects participated in 2 laboratory sessions (2 nights of 10 hours in bed versus 2 nights of 4 hours in bed) in a randomized crossover design. Sleep was polygraphically recorded. After the second night of each session, blood was sampled at 20-minute intervals from 9:00 am to midnight to measure ACTH and total cortisol. Saliva was collected every 20 minutes from 2:00 pm to midnight to measure free cortisol. Perceived stress, hunger, and appetite were assessed at hourly intervals by validated scales.
Results:
Sleep restriction was associated with a 19% increase in overall ACTH levels (P < .03) that was correlated with the individual amount of sleep loss (rSp = 0.63, P < .02). Overall total cortisol levels were also elevated (+21%; P = .10). Pulse frequency was unchanged for both ACTH and cortisol. Morning levels of ACTH were higher after sleep restriction (P < .04) without concomitant elevation of cortisol. In contrast, evening ACTH levels were unchanged while total and free cortisol increased by, respectively, 30% (P < .03) and 200% (P < .04). Thus, the amplitude of the circadian cortisol decline was dampened by sleep restriction (-21%; P < .05). Sleep restriction was not associated with higher perceived stress but resulted in an increase in appetite that was correlated with the increase in total cortisol.
Conclusion:
The impact of sleep loss on hypothalamic-pituitary-adrenal activity is dependent on time of day. Insufficient sleep dampens the circadian rhythm of cortisol, a major internal synchronizer of central and peripheral clocks.
The Global Burden of Disease (GBD) Study 2010 estimated the global burden of disease attributable to 15 categories of skin disease from 1990 to 2010 for 187 countries. For each of the following diseases we performed systematic literature reviews and analyzed resulting data: eczema, psoriasis, acne vulgaris, pruritus, alopecia areata, decubitus ulcer, urticaria, scabies, fungal skin diseases, impetigo, abscess and other bacterial skin diseases, cellulitis, viral warts, molluscum contagiosum, and non-melanoma skin cancer. We used disability estimates to determine non-fatal burden. Three skin conditions, fungal skin diseases, other skin and subcutaneous diseases and acne were in the top 10 most prevalent diseases worldwide in 2010, and eight fell into the top 50; these additional five skin problems were pruritus, eczema, impetigo, scabies and molluscum contagiosum. Collectively, skin conditions ranged from 2nd to 11th leading cause of years lived with disability at the country level. At global level, skin conditions were the 4th leading cause of nonfatal disease burden. Using more data than has been utilized previously the burden due to these diseases is enormous in both high and low income countries. These results argue strongly to include skin disease prevention and treatment in future global health strategies as a matter of urgency.Journal of Investigative Dermatology accepted article preview online, 28 October 2013; doi:10.1038/jid.2013.446.
To investigate the facial cues by which one recognizes that someone is sleep deprived versus not sleep deprived.
Experimental laboratory study.
Karolinska Institutet, Stockholm, Sweden.
Forty observers (20 women, mean age 25 ± 5 y) rated 20 facial photographs with respect to fatigue, 10 facial cues, and sadness. The stimulus material consisted of 10 individuals (five women) photographed at 14:30 after normal sleep and after 31 h of sleep deprivation following a night with 5 h of sleep.
Ratings of fatigue, fatigue-related cues, and sadness in facial photographs.
The faces of sleep deprived individuals were perceived as having more hanging eyelids, redder eyes, more swollen eyes, darker circles under the eyes, paler skin, more wrinkles/fine lines, and more droopy corners of the mouth (effects ranging from b = +3 ± 1 to b = +15 ± 1 mm on 100-mm visual analog scales, P < 0.01). The ratings of fatigue were related to glazed eyes and to all the cues affected by sleep deprivation (P < 0.01). Ratings of rash/eczema or tense lips were not significantly affected by sleep deprivation, nor associated with judgements of fatigue. In addition, sleep-deprived individuals looked sadder than after normal sleep, and sadness was related to looking fatigued (P < 0.01).
The results show that sleep deprivation affects features relating to the eyes, mouth, and skin, and that these features function as cues of sleep loss to other people. Because these facial regions are important in the communication between humans, facial cues of sleep deprivation and fatigue may carry social consequences for the sleep deprived individual in everyday life.
Sundelin T; Lekander M; Kecklund G; Van Someren EJW; Olsson A; Axelsson J. Cues of fatigue: effects of sleep deprivation on facial appearance. SLEEP 2013;36(9):1355-1360.
Objective
To determine the incidence of depression, anxiety, and suicidality in patients with psoriasis compared with the general population.Design
A population-based cohort study using data collected as part of patient's electronic medical record from 1987 to 2002.Setting
General Practice Research Database.Patients
Analyses included 146 042 patients with mild psoriasis, 3956 patients with severe psoriasis, and 766 950 patients without psoriasis. Five controls without psoriasis were selected from the same practices and similar cohort entry dates as patients with psoriasis.Main Outcome Measure
Clinical diagnoses of depression, anxiety, and suicidality among patients.Results
The adjusted hazard ratios (HRs) for receiving a diagnosis of depression, anxiety, and suicidality in patients with psoriasis compared with controls were 1.39 (95% confidence interval [CI], 1.37-1.41), 1.31 (95% CI, 1.29-1.34), and 1.44 (95% CI, 1.32-1.57), respectively. The adjusted HR of depression was higher in severe (HR, 1.72; 95% CI, 1.57-1.88) compared with mild psoriasis (HR, 1.38; 95% CI, 1.35-1.40). Younger patients with psoriasis had elevated HRs of outcomes compared with older patients with psoriasis.Conclusions
Patients with psoriasis have an increased risk of depression, anxiety, and suicidality. We estimate that in the United Kingdom, in excess of 10 400 diagnoses of depression, 7100 diagnoses of anxiety, and 350 diagnoses of suicidality are attributable to psoriasis annually. It is important for clinicians to evaluate patients with psoriasis for these conditions to improve outcomes. Future investigation should determine the mechanisms by which psoriasis is associated with psychiatric outcomes as well as approaches for prevention.
The skin is the largest organ of the human body and builds a barrier to protect us from the harmful environment and also from unregulated loss of water. Keratinocytes form the skin barrier by undergoing a highly complex differentiation process that involves changing their morphology and structural integrity, a process referred to as cornification. Alterations in the epidermal cornification process affect the formation of the skin barrier. Typically, this results in a disturbed barrier, which allows the entry of substances into the skin that are immunologically reactive. This contributes to and promotes inflammatory processes in the skin but also affects other organs. In many common skin diseases, including atopic dermatitis and psoriasis, a defect in the formation of the skin barrier is observed. In these diseases the cytokine composition within the skin is different compared to normal human skin. This is the result of resident skin cells that produce cytokines, but also because additional immune cells are recruited. Many of the cytokines found in defective skin are able to influence various processes of differentiation and cornification. Here we summarize the current knowledge on cytokines and their functions in healthy skin and their contributions to inflammatory skin diseases.
Up to 80% of people develop a cutaneous condition closely connected to their exposure to stressful life events. Psoriasis is a chronic recurrent inflammatory skin disorder with multifactorial etiology, including genetic background, environmental factors, and immune system disturbances with a strong cytokine component. Moreover, psoriasis is variably associated with sleep disturbance and sleep deprivation. This study evaluated the influence of sleep loss in the context of an animal model of psoriasis by measuring cytokine and stress-related hormone levels. Male adult Balb/C mice with or without psoriasis were subjected to 48 h of selective paradoxical sleep deprivation (PSD). Sleep deprivation potentiated the activities of kallikrein-5 and kallikrein-7 in the skin of psoriatic groups. Also, mice with psoriasis had significant increases in specific pro-inflammatory cytokines (IL-1β, IL-6 and IL-12) and decreases in the anti-inflammatory cytokine (IL-10) after PSD, which were normalized after 48 h of sleep rebound. Linear regression showed that IL-2, IL-6 and IL-12 levels predicted 66% of corticosterone levels, which were selectively increased in psoriasis mice subject to PSD. Kallikrein-5 was also correlated with pro-inflammatory cytokines, explaining 58% of IL-6 and IL-12 variability. These data suggest that sleep deprivation plays an important role in the exacerbation of psoriasis through modulation of the immune system in the epidermal barrier. Thus, sleep loss should be considered a risk factor for the development of psoriasis.
Abbreviations: BMI, body mass index; CI, confidence interval; NHS II, Nurses’ Health Study II
Technological advances, constant pressure, increased qualified demand, and other daily activities present in modern society result in increasingly stressful living conditions for the population. In the short term, the release of stress-related hormones can play a key role in the survival of an organism. However, it is well known that chronic exposure to cortisol can lead to many adverse effects. Several findings show immunological changes in response to chronic exposure to cortisol, in particular in skin integrity, which may interfere with the healing process. Morphine is an immunosuppressive drug, and when it is used chronically, it can lead to an increased incidence of infections and a delay in the healing process. The importance of opiates as analgesics in the medical setting is indisputable. However, there are a limited number of studies in this field. These investigations can provide further understanding of the mechanisms involved in the healing process in morphine-dependent individuals under chronic stress, which is a common condition in modern society. Furthermore, medical prescriptions of opiates are common among terminal patients, who frequently develop decubitus ulcers and bacterial infections. This review is aimed to provide a concise analysis of effects of morphine and stress on the healing process.
Background
It is believed that psoriasis is a chronic systemic inflammatory disease. Obstructive sleep apnea syndrome (OSAS) is a disease influencing all systems and characterized by intermittent partial or complete obstruction of the upper respiratory tract during sleep. In our study, we aimed to investigate the frequency of OSAS in patients previously diagnosed with psoriasis in order to investigate a potential association between chronic inflammation psoriasis and OSAS.
Methods
Thirty-three patients diagnosed with psoriasis by biopsy were enrolled into the study. Demographics of patients, Psoriasis Area Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Epworth Sleepiness Scale were examined. All patients underwent polysomnography.
Results
OSAS was determined in 18 of 33 patients with psoriasis (54.5 %). Eleven of the 18 patients had mild, 2 had moderate, and 5 had severe OSAS. Mean age was significantly higher in the OSAS group in comparison with non-OSAS group (54.4 ± 15.5 vs 39.4 ± 11.8, respectively, p < 0.05). Mean PASI was higher in the OSAS group in comparison with that of non-OSAS group, and the difference was not significant, although mean DLQI was lower (p > 0.05). It is believed that this was caused by the small patient population.
Conclusion
We detected that the frequency of OSAS in patients with psoriasis was much higher than that in the normal population. Though OSAS is not easy to diagnose without detailed testing, it should be investigated in psoriatic patients with long disease duration and high PASI score, and patients refractory to conventional systemic treatment. Physicians treating patients with psoriatic disease should incorporate this life-altering comorbidity into their assessment of disease and selection of treatment.
To estimate the prevalence of the metabolic syndrome among individuals with psoriasis and to examine the association between these 2 conditions in the general US population.
Cross-sectional health survey of a nationally representative random sample of the noninstitutionalized civilian US population.
The National Health and Nutrition Examination Survey, 2003-2006.
The study included 6549 participants aged 20 to 59 years.
Prevalence of the metabolic syndrome defined by the revised National Cholesterol Education Program Adult Treatment Panel III definition and odds ratios for associations after adjustment for age, sex, race/ethnicity, smoking status, and C-reactive protein levels.
The prevalence of the metabolic syndrome was 40% among psoriasis cases and 23% among controls. According to 2008 US census data, the projected number of patients with psoriasis aged 20 to 59 years with the metabolic syndrome was 2.7 million. The univariate and multivariate odds ratios for patients with psoriasis and the metabolic syndrome were 2.16 (95% confidence interval, 1.16 to 4.03) and 1.96 (1.01 to 3.77), respectively. The most common feature of the metabolic syndrome among patients with psoriasis was abdominal obesity, followed by hypertriglyceridemia and low levels of high-density lipoprotein cholesterol.
The prevalence of the metabolic syndrome is high among individuals with psoriasis. Given the serious complications associated with the metabolic syndrome, this frequent comorbidity should be recognized and taken into account in the long-term treatment of individuals with psoriasis.
Central or peripheral stress may induce the development of clinical inflammation in the pilosebaceous unit (PSU) leading to the development or to exacerbation of preexisting acne. The presence of a complete corticotropin-releasing hormone (CRH) system has been confirmed in human sebocytes in vitro. CRH is capable to induce lipid synthesis, steroidogenesis and interact with testosterone and growth hormone. alpha-Melanocyte-stimulating hormone (alpha-MSH) and its receptors can regulate melanogenesis as well as affect inflammation, apoptosis and sebogenesis.
The purpose of the study was to investigate by immunohistochemistry if changes of CRH/CRH-binding protein (CRHBP)/CRH receptors (CRHR) as well as melanocortin-1 receptor (MC-1R) expression are detectable in acne lesions vs. normal skin, especially in the sebaceous gland (SG).
Very strong expression of CRH was observed in acne-involved skin in SG cells comparing with weaker expression in non-involved and normal skin SG. The strongest reaction for CRHBP in acne-involved SG was in differentiating sebocytes. CRHR-1 and -2 exhibited the strongest expression in sweat glands and SG, respectively. Sebocytes and cells of the ductus seboglandularis (DSG) of acne-involved and non-involved skin showed very intense MC-1R expression in contrast to less intense scattered immunoreactivity in normal skin samples.
33 patients with acne vulgaris and 8 age-matched volunteers without acne participated in the study. Skin biopsies were taken from acne-involved face, the non-involved thigh skin of the same patients and from normal human skin.
These data suggest that NP, such as the complete CRH system and MC-1R, are involved in the pathogenesis of acne.
Sleep comprises approximately one-third of a person's lifetime, but its impact on health and medical conditions remains partially unrecognized. The prevalence of sleep disorders is increasing in modern societies, with significant repercussions on people's well-being. This article reviews past and current literature on the paradoxical sleep deprivation method as well as data on its consequences to animals, ranging from behavioral changes to alterations in the gene expression. More specifically, we highlight relevant experimental studies and our group's contribution over the last three decades.
Skin atrophy is part of the normal ageing process, but is accelerated by topical glucocorticoid (GC) treatments that are widely used in dermatology. Hyaluronan (HA) is one of the most abundant components of the cutaneous extracellular matrix and is involved in tissue homeostasis, hydration, and repair processes, but little is known about the effects of GCs on HA synthesis and stability. Here we examined the regulation of HA metabolism in human skin during GC therapy. Expression of the HA synthesizing enzymes hyaluronan synthase (HAS)-2 and HAS-3 and the HA degrading enzymes HYAL-1, HYAL-2, and HYAL-3 in response to GC treatment was evaluated. HAS-2 expression was markedly suppressed by dexamethasone treatment of cultured fibroblasts and HaCaT keratinocyte cells, and in human skin biopsies taken from volunteers treated with dexamethasone ointment. Consistently, the HA content of cell culture supernatants and in human skin was reduced after dexamethasone treatment. Hyaluronidase expression and activity, on the other hand, was not altered by dexamethasone treatment. These data show that the levels of skin HA rapidly decrease after short-term GC treatment due to a reduction in HA synthesis, while HA degradation is not changed. This may reflect an initiation of skin atrophy in response to topically applied GCs.
Stress, both acute and chronic, can impair cutaneous wound repair, which has previously been mechanistically ascribed to stress-induced elevations of cortisol. Here we aimed to examine an alternate explanation that the stress-induced hormone epinephrine directly impairs keratinocyte motility and wound re-epithelialization. Burn wounds are examined as a prototype of a high-stress, high-epinephrine, wound environment. Because keratinocytes express the beta2-adrenergic receptor (beta2AR), another study objective was to determine whether beta2AR antagonists could block epinephrine effects on healing and improve wound repair.
Migratory rates of normal human keratinocytes exposed to physiologically relevant levels of epinephrine were measured. To determine the role of the receptor, keratinocytes derived from animals in which the beta2AR had been genetically deleted were similarly examined. The rate of healing of burn wounds generated in excised human skin in high and low epinephrine environments was measured. We utilized an in vivo burn wound model in animals with implanted pumps to deliver beta2AR active drugs to study how these alter healing in vivo. Immunocytochemistry and immunoblotting were used to examine the up-regulation of catecholamine synthetic enzymes in burned tissue, and immunoassay for epinephrine determined the levels of this catecholamine in affected tissue and in the circulation. When epinephrine levels in the culture medium are elevated to the range found in burn-stressed animals, the migratory rate of both cultured human and murine keratinocytes is impaired (reduced by 76%, 95% confidence interval [CI] 56%-95% in humans, p < 0.001, and by 36%, 95% CI 24%-49% in mice, p = 0.001), and wound re-epithelialization in explanted burned human skin is delayed (by 23%, 95% CI 10%-36%, p = 0.001), as compared to cells or tissues incubated in medium without added epinephrine. This impairment is reversed by beta2AR antagonists, is absent in murine keratinocytes that are genetically depleted of the beta2AR, and is reproduced by incubation of keratinocytes with other beta2AR-specific agonists. Activation of the beta2AR in cultured keratinocytes signals the down-regulation of the AKT pathway, accompanied by a stabilization of the actin cytoskeleton and an increase in focal adhesion formation, resulting in a nonmigratory phenotype. Burn wound injury in excised human skin also rapidly up-regulates the intra-epithelial expression of the epinephrine synthesizing enzyme phenylethanolamine-N-methyltransferase, and tissue levels of epinephrine rise dramatically (15-fold) in the burn wounded tissue (values of epinephrine expressed as pg/ug protein +/- standard error of the mean: unburned control, 0.6 +/- 0.36; immediately postburn, 9.6 +/- 1.58; 2 h postburn, 3.1 +/- 1.08; 24 h post-burn, 6.7 +/- 0.94). Finally, using an animal burn wound model (20% body surface in mice), we found that systemic treatment with betaAR antagonists results in a significant increase (44%, 95% CI 27%-61%, p < 0.00000001) in the rate of burn wound re-epithelialization.
This work demonstrates an alternate pathway by which stress can impair healing: by stress-induced elevation of epinephrine levels resulting in activation of the keratinocyte beta2AR and the impairment of cell motility and wound re-epithelialization. Furthermore, since the burn wound locally generates epinephrine in response to wounding, epinephrine levels are locally, as well as systemically, elevated, and wound healing is impacted by these dual mechanisms. Treatment with beta adrenergic antagonists significantly improves the rate of burn wound re-epithelialization. This work suggests that specific beta2AR antagonists may be apt, near-term translational therapeutic targets for enhancing burn wound healing, and may provide a novel, low-cost, safe approach to improving skin wound repair in the stressed individual.
Mast cells are involved in atopic disorders, often exacerbated by stress, and are located perivascularly close to sympathetic and sensory nerve endings. Mast cells are activated by electrical nerve stimulation and millimolar concentrations of neuropeptides, such as substance P (SP). Moreover, acute psychological stress induces CRH-dependent mast cell degranulation. Intradermal administration of rat/human CRH (0.1-10 microM) in the rat induced mast cell degranulation and increased capillary permeability in a dose-dependent fashion. The effect of CRH on Evans blue extravasation was stronger than equimolar concentrations of the mast cell secretagogue compound 48/80 or SP. The free acid analog of CRH, which does not interact with its receptors (CRHR), had no biological activity. Moreover, systemic administration of antalarmin, a nonpeptide CRHR1 antagonist, prevented vascular permeability only by CRH and not by compound 48/80 or SP. CRHR1 was also identified in cultured leukemic human mast cells using RT-PCR. The stimulatory effect of CRH, like that of compound 48/80 on skin vasodilation, could not be elicited in the mast cell deficient W/Wv mice but was present in their +/+ controls, as well as in C57BL/6J mice; histamine could still induce vasodilation in the W/Wv mice. Treatment of rats neonatally with capsaicin had no effect on either Evans blue extravasation or mast cell degranulation, indicating that the effect of exogenous CRH in the skin was not secondary to or dependent on the release of neuropeptides from sensory nerve endings. The effect of CRH on Evans blue extravasation and mast cell degranulation was inhibited by the mast cell stabilizer disodium cromoglycate (cromolyn), but not by the antisecretory molecule somatostatin. To investigate which vasodilatory molecules might be involved in the increase in vascular permeability, the CRH injection site was pretreated with the H1-receptor antagonist diphenhydramine, which largely inhibited the CRH effect, suggesting that histamine was involved in the CRH-induced vasodilation. The possibility that nitric oxide might also be involved was tested using pretreatment with a nitric oxide synthase inhibitor that, however, increased the effect of CRH. These findings indicate that CRH activates skin mast cells at least via a CRHR1-dependent mechanism leading to vasodilation and increased vascular permeability. The present results have implications for the pathophysiology and possible therapy of skin disorders, such as atopic dermatitis, eczema, psoriasis, and urticaria, which are exacerbated or precipitated by stress.
Psoriasis is a chronic inflammatory skin disorder which can impair general routine activities and has been closely related to poor quality of life. Pruritus and scratching are frequently observed, occurring mainly during sleep and precipitating nighttime arousals. Indeed, sleep quality has been shown to be negatively affected in psoriatic patients, in a close relationship with stress exposure and immune response. Although psoriasis is known to impair sleep, leading to insomnia, its association with obstructive sleep apnea (OSA) is controversial. Similarly, OSA is considered a multifactorial inflammatory disease, characterized by intermittent hypoxia, sleep fragmentation and autonomic dysfunction, with important outcomes on the cardiovascular and metabolic systems. Importantly, immunological activities and pro-inflammatory cytokines play a prominent role in both OSA and psoriasis. Currently it is not clear whether OSA is a risk factor for psoriasis development or if psoriasis is a possible predictor of OSA. Thus, our main purpose is to provide an overview of this intriguing relationship and show the current link between psoriasis and OSA in a bidirectional relationship.
© 2015 The International Society of Dermatology.
Acne is estimated to affect 9.4% of the global population, making it the eighth most prevalent disease worldwide. Epidemiological studies have demonstrated that acne is most common in postpubescent teens, with boys most frequently affected particularly with more severe forms of the disease. This paper aims to provide an update on the epidemiology of acne worldwide. Recent general and institutional studies from around the world have shown that the prevalence of acne is broadly consistent globally (with the exception of specific populations, which are discussed). However, this review highlights that there is a wide range of disparate outcome measures being applied in epidemiology studies, and we emphasize the need to develop a widely accepted, credible, standard assessment scale to address this in the future. In addition we discuss special populations, such as those devoid of acne, as well as the impact of potential determinants of acne on disease epidemiology.This article is protected by copyright. All rights reserved.
In recent years, the prevalence of adult female acne has increased, but the reason for this increase remains unclear. Acne is one of the most common skin disorders. It can be triggered or worsened by endogenous and exogenous factors, including genetic predisposition, hormone concentrations, diet, smoke and stress; although the interaction with this last factor is not well understood. Modern life presents many stresses including urban noises, socioeconomic pressures and light stimuli. Women are especially affected by stress during daily routine. The recent insertion in the labor market is added to the duties of the mother and wife. Women also have a higher risk of developing psychiatric disorders such as depression and anxiety. Sleep restriction is added to these factors, with several negative consequences on health, including on hormonal secretion and the immune system. This is further complicated by the natural variation in sleep architecture across the menstrual cycle. Recent studies have brought new data about the mechanisms and possible factors involved. This review aims to establish a connection between stress, sleep deprivation and adult female acne.
Background:
Numerous studies have analyzed the influence of psoriasis on the quality of life and psychosocial health of patients. However, few studies have addressed the effect of this disease on individuals living with these patients (cohabitants).
Objective:
To analyze the influence of psoriasis on the levels of anxiety, depression, and quality of life of the cohabitants of psoriatic patients.
Methods:
The study included patients, cohabitants, and controls, a total of 130 participants. Their quality of life was measured with the Dermatology Life Quality Index (DLQI) and Family Dermatology Life Quality Index (FDLQI), and their psychological state with the Hospital Anxiety and Depression Scale (HADS). Demographic data of participants and clinical characteristics of patients were also gathered.
Results:
The presence of psoriasis impaired the quality of life of 87.8% of the cohabitants. FDLQI scores of cohabitants were significantly associated with the DLQI scores of the patients (rs = 0.554; P < .001). Anxiety and depression levels did not differ between patients and cohabitants, but were significantly higher than in the controls (P < .001).
Limitations:
Additional studies with larger numbers of patients and cohabitants are required to analyze differences between groups according to psoriasis severity.
Conclusion:
Psoriasis markedly worsens the global well-being of patients and their cohabitants, who experienced an impairment of their quality of life and higher levels of anxiety and depression.
Psoriasis is a multifactorial chronic inflammatory skin disease that often occurs in patients who are overweight or obese. In literature the connections between obesity and eating disorders are well known, but few studies have investigated the link between eating disorders and psoriasis. We hypothesized that Eating Disorders (ED) can be considered a psychogenic cofactors, which contribute to the development of obesity and metabolic syndrome in psoriatic patients, who are frequently prone to psychiatric comorbidity.
From January to April 2011 we enrolled 100 consecutive psoriatic outpatients and a control group of 100 selected non-psoriatic outpatients, matched by age, gender, and BMI to the study group. The assessment battery was composed by the Psoriasis Area Severity Index (PASI) score, the Eating Disorder Inventory (EDI) and the Symptom Checklist-90 Revised (SCL-90-R®).
Our data showed that most of EDI and SCL-90R subscales was mostly altered in psoriatic population compared to patients without psoriasis. Moreover, we noticed in patients with psoriasis an association between the progressive weight increase and an impairment on most of EDI subscales.
Psoriasis is associated with psychopathological traits, which are frequently found in EDs. Since obesity makes psoriasis less susceptible to therapy and weight loss improves drug response, dermatologists should be alert to suspect the presence of this condition.
The skin is the primary barrier from the outside environment, protecting the host from injury, infectious pathogens, water loss and solar ultraviolet radiation. In this role, it is supported by a highly organized system comprising elements of innate and adaptive immunity, responsive to inflammatory stimuli. The cutaneous immune system is regulated by mediators such as cytokines and bioactive lipids that can initiate rapid immune responses with controlled inflammation, followed by efficient resolution. However, when immune responses are inadequate or mounted against non-infectious agents, these mediators contribute to skin pathologies involving unresolved or chronic inflammation. Skin is characterized by active lipid metabolism and fatty acids play crucial roles both in terms of structural integrity and functionality, in particular when transformed to bioactive mediators. Eicosanoids, endocannabinoids and sphingolipids are such key bioactive lipids, intimately involved in skin biology, inflammation and immunity. We discuss their origins, role and influence over various cells of the epidermis, dermis and cutaneous immune system and examine their function in examples of inflammatory skin conditions. We focus on psoriasis, atopic and contact dermatitis, acne vulgaris, wound healing and photodermatology that demonstrate dysregulation of bioactive lipid metabolism and examine ways of using this insight to inform novel therapeutics.
Glucocorticoids are effective for the treatment of various inflammatory skin diseases, but their long-term use may lead to serious side-effects such as osteoporosis and skin atrophy. The incidence of skin atrophy following application of potent corticosteroids is especially high among children and the elderly. During recent years the effects of glucocorticoids on connective tissue have been elucidated, and it is evident that skin atrophy is mostly due to a decrease in collagen synthesis. Since collagen is the most abundant protein in the skin, the inhibition of its synthesis leads to atrophy. This review discusses the molecular mechanisms of glucocorticosteroid-induced skin atrophy and therapeutic possibilities.
In general, stress has been regarded as immunosuppressive. Recent evidence, however, indicates that acute, subacute or chronic stress might suppress cellular immunity but boost humoral immunity. This is mediated by a differential effect of stress hormones, the glucocorticoids and catecholamines, on T helper 1 (Th1)/Th2 cells and type 1/type 2 cytokine production. Furthermore, acute stress might induce pro-inflammatory activities in certain tissues through neural activation of the peripheral corticotropin-releasing hormone–mast cell–histamine axis. Through the above mechanisms, stress might influence the onset and/or course of infectious, autoimmune/inflammatory, allergic and neoplastic diseases.
This study aims to investigate the risk of psoriasis or psoriatic arthritis in patients with obstructive sleep apnea (OSA) compared with age- and gender-matched unaffected individuals, using a nationally representative population-based dataset.
We used data from the Taiwan "Longitudinal Health Insurance Database 2000." The study consisted of 2258 patients with OSA and 11,255 matched comparison patients as the study cohort. Each selected subject (n=13,513) in this study was individually traced for a three-year period from their index ambulatory care visits to identify patients who had been diagnosed with psoriasis during the follow-up period. A stratified Cox proportional hazard regression was used to compute the risk of psoriasis between patients with and without OSA.
It showed that, of 13,513 sampled subjects, 0.27% (n=36) had psoriasis during the three-year follow-up period; the percentage was 0.49% and 0.22% for sampled subjects with and without OSA, respectively. After adjusting for the patients' monthly incomes, geographic location, urbanization level, and obesity, the hazard of psoriasis during the three-year follow-up period was 2.30 (95% CI=1.13-4.69, p=0.022) times greater for patients with OSA than for comparison patients.
Our results suggest that OSA is associated with an increased risk of subsequent psoriasis or psoriatic arthritis.
Symptoms of psoriasis can be embarrassing and distressing, and may increase risk of developing psychiatric disorders in young people.
We sought to compare incidences of psychiatric disorders between pediatric patients with psoriasis and psoriasis-free control subjects.
Patients (<18 years) with continuous health plan enrollment 6 months before and after first psoriasis diagnosis (index date) were selected (Thomson Reuters MarketScan database, 2000-2006 [Thomson Reuters, New York, NY]). Patients with psoriasis (N = 7404) were matched 1:5 on age and sex to psoriasis-free control subjects (N = 37,020). Patients were followed from index date to first diagnosis of a psychiatric disorder (ie, alcohol/drug abuse, depression, anxiety disorder, bipolar disorder, suicidal ideation, eating disorder), end of data availability, or disenrollment. Patients with psychiatric diagnoses or psychotropic medication use before the index date were excluded. Cox proportional hazard models controlling for age, sex, and comorbidities were used to estimate the effect of psoriasis on risks of developing psychiatric disorders.
Patients with psoriasis were significantly more at risk of developing psychiatric disorders versus control subjects (5.13% vs 4.07%; P = .0001; hazard ratio = 1.25; P = .0001), especially depression (3.01% vs 2.42%; P = .0036; hazard ratio = 1.25; P = .0053) and anxiety (1.81% vs 1.35%; P = .0048; hazard ratio = 1.32; P = .0045).
Retrospective, observational studies of medical claims data are typically limited by overall quality and completeness of data and accuracy of coding for diagnoses and procedures.
Pediatric patients with psoriasis had an increased risk of developing psychiatric disorders, including depression and anxiety, compared with psoriasis-free control subjects.
Information about the relationship between psoriasis and psychiatric morbidity and quality of life in children and adolescents is limited. We aimed to examine the symptoms of depression and anxiety and health-related quality of life levels in children and adolescents with psoriasis. Forty-eight outpatients with psoriasis aged 8 to 18 years are included in this study. Child Depression Inventory (CDI), State-Trait Anxiety Inventories for Children (STAI-C) and Pediatric Quality of Life Inventory Parent and Child Versions (PedQL-P and C) were applied to both patient and control groups. Psoriasis symptom severity was measured by the Psoriasis Area Severity Index (PASI). Both study and control groups were divided into two age groups, child (8-12 yrs) and adolescent (13-18 yrs), to exclude the effect of puberty on psychological condition. The mean CDI score was higher, and PedQL-C psychosocial and total scores were lower in the children compared with controls. Duration of psoriasis had an increasing effect on physical-health and total scores of PedQL-C in the child group and all PedQL-C scores in the entire sample. Psoriasis severity showed a negative correlation with psychosocial and total scores of PedQL-P in the adolescent group and PedQL-P physical-health scores in the entire sample. Psoriasis is related to depression and impaired quality of life in children. The depressive symptoms in children with psoriasis should not be overlooked and psychiatric assessment of these children should be provided.
In this community-based cross-sectional study, 1443 Japanese adolescents aged 13-19 years participated from two schools in Kagawa Prefecture. Students completed a self-administered questionnaire to assess the prevalence of acne, knowledge about acne, self-management of acne and emotional well-being. A five-item version of the Mental Health Inventory (MHI) subscale of the Short Form 36 was used to assess psychological health and depression status. Among respondents, 859 (59.5%) said they had acne (51.6% of the boys and 64.8% of the girls). A majority (56.8%) of those who said they had acne also reported a family history of acne. Of the 555 female respondents with acne, 39.1% reported experiencing acne flares in temporal proximity to menstruation. Less than half (38.8%) of respondents with acne had sought or were seeking treatment. The three most common factors believed to trigger or exacerbate acne were stress, lack of sleep and sweat. The mean MHI score of 847 students with acne was significantly lower than 475 students without acne. The mean MHI score of female students with acne was significantly lower than male students with acne. Students with acne were also significantly more depressed than those without acne and female students were significantly more depressed than male students. Acne is a common problem for Japanese teenagers and causes personal and social difficulties. Our results suggest the necessity of educational programs in school or public to ensure that adolescents are aware of acne and to encourage young people to improve their mental health through better acne treatment.
The skin is the largest organ of the human body and plays a major role in maintaining homeostasis and protection. As the main component of skin, collagen has a key role in providing integrity and elasticity to this organ. Several factors, including autoimmune disease, aging, and stress, can change the quantity and integrity of skin collagen. These factors impair collagen quality and consequently affect skin function. Stress seems to affect the integrity of skin collagen through glucocorticoid-mediated processes that alter its synthesis and degradation. Glucocorticoids also affect skin quality through modulation of the immune system. This review will briefly present comprehensive data from both animal and human studies delineating processes that modulate alterations in collagen in general, and will treat in more detail the consequences of stress on skin collagen.
Please cite this paper as: The skin: an indispensable barrier. Experimental Dermatology 2008.Abstract: The skin forms an effective barrier between the organism and the environment preventing invasion of pathogens and fending off chemical and physical assaults, as well as the unregulated loss of water and solutes. In this review we provide an overview of several components of the physical barrier, explaining how barrier function is regulated and altered in dermatoses. The physical barrier is mainly localized in the stratum corneum (SC) and consists of protein-enriched cells (corneocytes with cornified envelope and cytoskeletal elements, as well as corneodesmosomes) and lipid-enriched intercellular domains. The nucleated epidermis also contributes to the barrier through tight, gap and adherens junctions, as well as through desmosomes and cytoskeletal elements. During epidermal differentiation lipids are synthesized in the keratinocytes and extruded into the extracellular domains, where they form extracellular lipid-enriched layers. The cornified cell envelope, a tough protein/lipid polymer structure, resides below the cytoplasmic membrane on the exterior of the corneocytes. Ceramides A and B are covalently bound to cornified envelope proteins and form the backbone for the subsequent addition of free ceramides, free fatty acids and cholesterol in the SC. Filaggrin is cross-linked to the cornified envelope and aggregates keratin filaments into macrofibrils. Formation and maintenance of barrier function is influenced by cytokines, 3',5'-cyclic adenosine monophosphate and calcium. Changes in epidermal differentiation and lipid composition lead to a disturbed skin barrier, which allows the entry of environmental allergens, immunological reaction and inflammation in atopic dermatitis. A disturbed skin barrier is important for the pathogenesis of contact dermatitis, ichthyosis, psoriasis and atopic dermatitis.
Collagen is synthesized as procollagen and large extra domains known as propeptides are cleaved off enzymatically. In the present study we have measured the carboxyterminal propeptide of type I collagen (PICP) and the aminoterminal propeptide of type III collagen (PIIINP) in blister fluids of human skin. High concentrations of PICP were found in the spontaneous blisters of patients with bullous pemphigoid, erysipelas, or erytherna multiforme. Detectable amounts were also found in suction blisters induced on healthy skin. Because the concentrations in suction blisters were several times higher than in corresponding serum, most of PICP and PIIINP was derived from the underlying dermis.
This method was used for assessing type I and type III collagen synthesis after topical glucocorticoid treatment. Clobetasol-17-propionate (CP) decreased the concentrations of PICP by 75% after 1 d of treatment, the maximum inhibition (92%) being found after 2 d treatment. PIIINP was also affected. Hydrocortisone and hydrocortisone-17-butyrate also decreased the concentrations of PICP and PIIINP, but less markedly than CP. Partial recovery was seen 3 d after stopping the treatment. Thus measurement of collagen type specific propeptides in suction blisters can be used as an estimate of collagen synthesis in vivo, avoiding both local anesthesia and skin biopsing. With radioimmunoassays for PICP and PIIINP a large number of samples can also be processed simultaneously.
This study of the relationship between nocturnal scratching and sleep is based on an analysis of 17 overnight polygraphic records of the scratch bouts and EEG of severely itchy patients. Our patients spent little time in deep orthodox sleep (stages 3 and 4), which was absent from 7 of the 17 records. Bouts of scratching were found to occur in all stages of sleep but were most numerous in stage 1 (light orthodox sleep). Sleep tended to remain stable, i.e. in a single sleep stage, for the 40 s immediately before a bout of scratching but had often changed to a more superficial stage by the time the bout had ceased, implying perhaps that scratching itself was the event linked most closely with arousal.
The effects of systemic glucocorticoid and isotretinoin treatments on type I and type III collagen synthesis in intact skin were investigated by measuring the carboxyterminal and aminoterminal propeptides of type I procollagen, and the aminoterminal propeptide of type III procollagen, in suction blister fluid (SBF), in a study of 27 patients. All three parameters were significantly lower in the SBF of glucocorticoid-treated patients than in controls or patients undergoing treatment with isotretinoin, whereas the latter two groups did not differ significantly from each other. During glucocorticoid treatment, the concentrations of the procollagen propeptides were only about 20% of the corresponding control values, indicating that systemic therapy with prednisone at a dose of 0.48 mg/kg per day almost totally abolishes collagen synthesis in the skin. These results indicate that systemic glucocorticoid treatment suppresses the synthesis of both type I and type III collagen in the dermis, and suggest that many side-effects of these drugs, such as atrophy of the skin, are due to this inhibition. Systemic isotretinoin treatment did not stimulate skin collagen synthesis. Thus, its regenerative effect on connective tissue may be mediated by mechanisms other than direct stimulation of collagen synthesis.
Regulation of elastin gene expression by dexamethasone was examined in cultured human skin fibroblasts at mRNA and promoter level. Dexamethasone markedly suppressed elastin mRNA levels, maximally down to 30% of the levels noted in control cells. Dexamethasone had minimal effect on the activity of two human elastin promoter/CAT constructs in transiently transfected human skin fibroblasts and rat aortic smooth muscle cells. The results indicate that glucocorticoids potently suppress elastin gene expression by skin fibroblasts, and suggest that reduced elastin deposition may also play a role in glucocorticoid induced dermal atrophy.
It has been shown previously that topical corticosteroid treatment decreases collagen synthesis in human skin in vivo and that the adverse effects are due to reduced collagen synthesis. The aim of the present study was to evaluate the effect of hydrocortisone, hydrocortisone-17-butyrate and betamethasone on collagen synthesis in human skin in vivo. Fourteen healthy male volunteers applied hydrocortisone, hydrocortisone-17-butyrate, betamethasone and vehicle twice a day for one week to four separate areas marked on their abdominal skin. The collagen synthesis rate in the skin was measured by assaying collagen propeptides from the suction blisters induced on the treated areas. Aminoterminal propeptide of type I procollagen (PINP) and aminoterminal propeptide of type III procollagen (PIIINP) were measured from skin blister fluid using radioimmunoassays. Skin thickness was measured with ultrasound. Hydrocortisone decreased the two propeptides studied in the suction blister fluids less than did hydrocortisone-17-butyrate and betamethasone, but the interindividual variation was great. Hydrocortisone-17-butyrate and betamethasone had almost similar decreasing effects on the propeptides in the suction blister fluid. Hydrocortisone decreased the concentrations of PINP and PIIINP by about 35%. In some subjects (4/14) the decline of the collagen propeptide levels was over 50%. The decline in the concentration of PINP was 63% by hydrocortisone-17-butyrate and 69% by betamethasone, while the decrease in PIIINP was 55% by hydrocortisone-17-butyrate and 62% by betamethasone. None of the treatments had any effect on skin thickness within one week. In conclusion, it seems that hydrocortisone is less atrophogenic than hydrocortisone-17-butyrate and betamethasone, as shown by radioimmunoassays for collagen propeptides. The order of inhibitory potency of the three glucocorticoids on collagen synthesis was hydrocortisone < hydrocortisone-17-butyrate < betamethasone. Thus, assay of collagen propeptides from suction blisters can be used to screen various steroids with respect to their action on collagen synthesis.
Acne is usually recognized as a disorder of adolescence. However, the referral of patients over the age of 25 years with acne has significantly increased over the past 10 years. The clinical features of 200 patients over the age of 25 years, referred to our department for treatment of acne. were evaluated with a view to establishing possible aetiological factors. There were 152 (76%) women and 48 (24%) men. The mean age of the patients was 35.5 years (range 25-55 years). The acne was mild or moderate in severity, consisting principlly of inflammatory lesion, with mean total acne grade (Leeds Grading Scale) of 1.125 for men and 0.75 for women. Most patients had persistent acne; but true late-onset acne (onset after the age of 25 years) was seen in 28 (18.4%) of women and four (8.3%) of men. Thirty-seven per cent of women had features of hyperandrogenicity. One hundred and sixty-four patients (82%) had failed to respond to multiple courses of antibiotics, and 64 (32%) had relapsed after treatment with one or more courses of isotretinoin. External factors, such as cosmetics. drugs and occupation, were not found to be significant aetiological factor. A family history revealed that 100 (50%) of patients had a first-degree relative with post-adolescent acne.
Patients with post-adolescent acne appear to represent an increasingly important population of acne sufferers. External factors do not seem to have a significant aetiological role. Two main clinical groups were identified: those with persistent acne and those with late-onset acne. A minority of women also had features of hyperandrogenicity. These patients, and those with late-onset acne, may represent a subgroup who have underlying abnormalities of ovarian, adrenal or local androgen metabolism, and require separate investigation.
The effects of topical betamethasone-17-valerate on collagen propeptide levels, collagen mRNA level, lysyl oxidase mRNA and matrix metalloproteinase (MMP)-1 and MMP-2 mRNA levels were studied in human skin. Three days' treatment of healthy skin with topical betamethasone caused a 70-80% decrease in type I and III collagen propeptides in suction blister fluid. A similar decrease was found in type I collagen mRNA when assayed by either slot-blot hybridization or a quantitative polymerase chain reaction method, indicating that the decrease in collagen synthesis after topical glucocorticoid treatment is apparently due to a decrease in corresponding mRNA. mRNA of lysyl oxidase, which is an important enzyme catalysing the cross-linking of collagen chains, and collagen-degrading enzyme MMP-1 and MMP-2 mRNAs were not decreased in the same skin samples. This suggests that in vivo, glucocorticoids modulate variably the genes involved in collagen synthesis and degradation. Our study provides a solid molecular basis for glucocorticoid-induced dermal atrophy, which results from the decrease in functional collagen mRNA in the skin.
Despite clear exacerbation of several skin disorders by stress, the effect of psychologic or exertional stress on human skin has not been well studied. We investigated the effect of three different stressors, psychologic interview stress, sleep deprivation, and exercise, on several dermatologic measures: transepidermal water loss, recovery of skin barrier function after tape stripping, and stratum corneum water content (skin conductance). We simultaneously measured the effects of stress on plasma levels of several stress-response hormones and cytokines, natural killer cell activity, and absolute numbers of peripheral blood leukocytes. Twenty-five women participated in a laboratory psychologic interview stress, 11 women participated in one night of sleep deprivation, and 10 women participated in a 3 d exercise protocol. The interview stress caused a delay in the recovery of skin barrier function, as well as increases in plasma cortisol, norepinephrine, interleukin-1beta and interleukin-10, tumor necrosis factor-alpha, and an increase in circulating natural killer cell activity and natural killer cell number. Sleep deprivation also decreased skin barrier function recovery and increased plasma interleukin-1beta, tumor necrosis factor-alpha, and natural killer cell activity. The exercise stress did not affect skin barrier function recovery, but caused an increase in natural killer cell activity and circulating numbers of both cytolytic T lymphocytes and helper T cells. In addition, cytokine responses to the interview stress were inversely correlated with changes in barrier function recovery. These results suggest that acute psychosocial and sleep deprivation stress disrupts skin barrier function homeostasis in women, and that this disruption may be related to stress-induced changes in cytokine secretion.
Acne is usually perceived as a disease of teenagers, and most epidemiological studies have focused on adolescents.
The primary objective was to investigate the prevalence of acne in a representative sample of French females. Information about skin type, life-style factors influencing acne and quality of life were also recorded.
A self-administered questionnaire was sent to 4,000 adult women aged 25-40 years, after a validation test by three dermatologists. A definition of acne severity, according to questionnaire answers, was established before the questionnaire was sent out.
A total of 3394 women completed the questionnaire of which 3,305 were useable. The data showed a prevalence of acne in 17% of the population, and physiological acne in 24%. Thus, the total acne prevalence was 41%. Forty-nine per cent of the acne patients had acne sequelae (scars and/or pigmented macules). Forty-one per cent of adult acne patients had not experienced acne during their adolescence. A premenstrual flare and stress was recorded as causing acne in 78% and 50%, respectively. Twenty-two per cent of acne subjects were currently receiving therapy. For most patients, acne did not severely impair their quality of life.
This study shows a prevalence of acne in 41% of women in the general population. A high proportion of these acne cases are late onset acne.
Although emotional stress has long been suspected to exacerbate acne vulgaris, previous reports addressing its influence on acne severity have been mainly anecdotal.
To elucidate the possible relationship between stress and acne exacerbation by evaluating changes in acne severity during nonexamination and examination periods and to assess the possible relationship of these changes in severity with perceived examination stress by using previously validated scales measuring acne severity and perceived stress.
Prospective cohort study.
General university community.
A volunteer sample of 22 university students (15 women and 7 men) with a minimum acne vulgaris severity of 0.5 on the photonumeric Leeds acne scale (baseline scores, 0.50-1.75).
Participants were graded on their acne severity using the Leeds acne scale, and had their subjective stress levels assessed with the Perceived Stress Scale questionnaire during both nonexamination and examination periods.
Subjects had a higher mean grade of acne severity and mean perceived stress score (P<.01 for both) during examinations. Using regression analysis and adjusting for the effects of confounding variables, such as changes in sleep hours, sleep quality, diet quality, and number of meals per day, increased acne severity was significantly associated with increased stress levels (r = 0.61, P<.01), while self-assessed change in diet quality was the only other significant association (P =.02).
Patients with acne may experience worsening of the disease during examinations. Furthermore, changes in acne severity correlate highly with increasing stress, suggesting that emotional stress from external sources may have a significant influence on acne.
A causative link between emotional stress and acne has long been postulated. There is mounting evidence that the molecular mechanism underlying this observation is related to the expression of receptors for several neuroendocrine mediators by the sebaceous gland. Recent and ongoing studies have indicated that human sebocytes express functional receptors for corticotropin-releasing hormone, melanocortins, beta-endorphin, vasoactive intestinal polypeptide, neuropeptide Y and calcitonin gene-related peptide. After ligand binding, these receptors modulate the production of inflammatory cytokines, proliferation, differentiation, lipogenesis and androgen metabolism in sebocytes. By means of their autocrine, paracrine and endocrine actions, these neuroendocrine factors appear to mediate centrally and topically induced stress towards the sebaceous gland, ultimately affecting the clinical course of acne.
Numerous studies demonstrate links between chronic stress and indices of poor health, including risk factors for cardiovascular disease and poorer immune function. Nevertheless, the exact mechanisms of how stress gets “under the skin” remain elusive. We investigated the hypothesis that stress impacts health by modulating the rate of cellular aging. Here we provide evidence that psychological stress— both perceived stress and chronicity of stress—is significantly associated with higher oxidative stress, lower telomerase activity, and shorter telomere length, which are known determinants of cell senescence and longevity, in peripheral blood mononuclear cells from healthy premenopausal women. Women with the highest levels of perceived stress have telomeres shorter on average by the equivalent of at least one decade of additional aging compared to low stress women. These findings have implications for understanding how, at the cellular level, stress may promote earlier onset of age-related diseases.
• psychological stress
• telomere length
• telomerase
• oxidative stress
Although many skin disorders, including psoriasis and atopic dermatitis, are adversely affected by psychologic stress (PS), the pathophysiologic link between PS and disease expression remains unclear. Recent studies demonstrated PS-induced alterations in permeability barrier homeostasis, mediated by increased endogenous glucocorticoids. Here, we assessed the mechanisms by which PS alters stratum corneum (SC) function. Insomniac psychologic stress (IPS) altered both barrier homeostasis and SC integrity. IPS decreased epidermal cell proliferation, impaired epidermal differentiation, and decreased the density and size of corneodesmosomes (CD), which was linked to degradation of CD proteins (e.g., desmoglein1). Barrier compromise was linked to decreased production and secretion of lamellar bodies (LB), which in turn could be attributed to a decrease in de novo synthesis of epidermal lipids. Topical physiologic lipids (equimolar cholesterol, ceramides, and free fatty acids) normalized both barrier homeostasis and SC integrity in IPS mice, further evidence that lipid deficiency accounted for these functional abnormalities. Thus, PS inhibition of epidermal lipid synthesis results in decreased LB formation and secretion, as well as decreased CD, compromising both permeability barrier homeostasis and SC integrity. These studies suggest that topical treatment with epidermal physiologic lipids could be beneficial in stress-induced, barrier-associated dermatoses, such as psoriasis and atopic dermatitis.
Since previous data of our group showed increased concentrations in HPA axis hormones in sleep deprived rats, we hypothesized that this augmentation could produce effects in other hormonal systems, particularly in the sexual system. Considering that little is known about how the hormonal system changes during the recovery period after sleep deprivation (SD), our objective was to examine from what point SD alters sexual and stress-related hormones along with plasma catecholamine concentrations during 4 days. We also sought to verify the time course of their recovery after an equivalent period of recovery sleep. Rats were deprived of sleep by the platform technique for 1-4 days and were allowed to recover for the same period. Plasma catecholamines [dopamine (DA) and noradrenaline (NOR)], testosterone, estrone, progesterone, prolactin, corticosterone and adrenocorticotropic hormone (ACTH) concentrations were measured. Comparisons between groups showed that the SD procedure used in the present study produced marked alterations in almost all studied hormones from 24 h of SD, except for estrone and prolactin (which required 96 h of SD to become altered). Testosterone and estrone decreased, whereas progesterone, prolactin, corticosterone, ACTH, DA and NOR increased. During recovery period, progesterone, prolactin and corticosterone concentrations returned to control levels, whereas testosterone, estrone, NOR and DA did not. In addition, after 48 h of recovery ACTH and NOR decreased below control concentrations, remaining low until 96 h of sleep recovery. Thus, SD showed long lasting, differential effects upon these neurochemicals suggesting that each has its own pattern of responses to SD as well as variable periods of recovery.
Topical glucocorticoids have always been considered first-line drugs for inflammatory diseases of the skin and bronchial system. Applied systemically, glucocorticoids are used for severe inflammatory and immunological diseases and the inhibition of transplant rejection. Owing to the progress in molecular pharmacology, the knowledge of the mechanism of action has increased during the last years. Besides distinct genomic targets, which are due to the activation of specific cytoplasmatic receptors resulting in the (trans-) activation or (trans-) repression of target genes, there are non-genomic effects on the basis of the interference with membrane-associated receptors as well as with membrane lipids. In fact, various glucocorticoids appear to differ with respect to the relative influence on these targets. Thus, the extended knowledge of glucocorticoid-induced cellular signalling should allow the design and development of even more specifically acting drugs - as it has been obtained with other steroids, e.g. estrogens for osteoporosis prevention.
Glucocorticoids (GCs) are highly effective for the topical treatment of inflammatory skin diseases. Their long-term use, however, is often accompanied by severe and partially irreversible adverse effects, with atrophy being the most prominent limitation. Progress in the understanding of GC-mediated molecular action as well as some advances in technologies to determine the atrophogenic potential of compounds has been made recently. It is likely that the detailed mechanisms of GC-induced skin atrophy will be discovered and in vitro models for the reliable prediction of atrophy will be established in the foreseeable future. This knowledge will not only facilitate safety profiling of established drugs but will also foster further drug discovery by improving compound characterization processes. New insights into GC modes of action will guide optimization strategies aiming at novel GC receptor ligands with improved effect/side effect profile.
Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organ-cultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus, differential, CRH-driven responses of defined cutaneous cell populations reproduce key features of the central HPA axis at the tissue/single cell levels.