Stressful life events promote the manifestation of asthma and atopic diseases

BACKGROUND: Psychosocial stress is known to aggravate asthma. Less is known about the impact of stressful life events on the expression of asthma and atopic disorders. OBJECTIVE: To determine whether the onset of asthma, allergic rhinitis or conjunctivitis, and atopic dermatitis, are associated with stressful life events. METHODS: A postal survey on risk factors for asthma and atopic diseases was carried out among 10 667 Finnish first-year university students aged 18-25 years. Stressful life events, (i) severe disease or death of a family member, and (ii) parental or personal conflicts, were retrospectively recorded during the preceding year, 1-5 years, 6-10 years, and more than 10 years prior to the survey response. In a case-control setting, conditional multiple logistic regression analysis was used to assess the temporal association between major stressful life events occurring during a period either preceding, concomitant or subsequent with subject's diagnoses. RESULTS: Concomitant parental and personal conflicts increased the risk of asthma (OR 1.72, 95% CI 1.10-2.69) when adjusted by parental asthma, education and passive smoking at early age. Concomitant severe disease or death of mother, father or spouse (OR 1.52, 95% CI 1.09-2.16) and precedent parental and personal conflicts (OR 1.75, 95% CI 1.15-2.77) increased the risk of manifestation of allergic rhinoconjunctivitis when adjusted for parental atopic disease, education and passive smoking. Subjects' asthma and atopic dermatitis, but not allergic rhinoconjunctivitis, were related to excess of subsequent stressful life events. CONCLUSION: An association between stressful life events and subjects' asthma, allergic rhinoconjunctivitis and atopic dermatitis is suggested.     

Stressful life events among adolescents in Wuhan, China: Associations with smoking, alcohol use, and depressive symptoms

The associations among stress and adolescent smoking, alcohol use, and depression have been well documented in the United States, but few studies have evaluated the evidence for these associations in Asian cultures. This study developed a scale of stressful life events among 7th-grade adolescents in Wuhan, China. The events reported as most frequent involved bad grades or punishment at school, and the events reported as most severe involved disruptions in family life, such as death, divorce, or disability of parents. Associations were observed between life events (especially negative school-related events) and smoking, alcohol use, and depressive symptoms. Results indicate that school-related stress may lead to substance use and mental health problems among Chinese adolescents.     

Epicutaneous sensitization in the development of food allergy: What is the evidence and how can this be prevented?

There is increasing evidence regarding the importance of allergic sensitization through the skin. In this review, we provide an overview of the atopic march and immune mechanism underlying the sensitization and effector phase of food allergy. We present experimental models and human data that support the concept of epicutaneous sensitization and how this forms one half of the dual-allergen exposure hypothesis. We discuss specific important elements in the skin (FLG and other skin barrier gene mutations, Langerhans cells, type 2 innate lymphoid cells, IL-33, TSLP) that have important roles in the development of allergic responses as well as the body of evidence on environmental allergen exposure and how this can sensitize an individual. Given the link between skin barrier impairment, atopic dermatitis, food allergy, allergic asthma, and allergic rhinitis, it is logical that restoring the skin barrier and prevention or treating atopic dermatitis would have beneficial effects on prevention of related allergic diseases, particularly food allergy. We present the experimental and human studies that have evaluated this approach and discuss various factors which may influence the success of these approaches, such as the type of emollient chosen for the intervention, the role of managing skin inflammation, and differences between primary and secondary prevention of atopic dermatitis to achieve the desired outcome.     

Atopic dermatitis and skin allergies – update and outlook

During the last few years, an impressive amount of experimental studies and clinical trials have dealt with a variety of distinct topics in allergic skin diseases – especially atopic dermatitis. In this update, we discuss selected recent data that provide relevant insights into clinical and pathophysiological aspects of allergic skin diseases or discuss promising targets and strategies for the future treatment of skin allergy. This includes aspects of barrier malfunction and inflammation as well as the interaction of the cutaneous immune system with the skin microbiome and diagnostic procedures for working up atopic dermatitis patients. Additionally, contact dermatitis, urticaria, and drug reactions are addressed in this review. This update summarizes novel evidence, highlighting current areas of uncertainties and debates that will stimulate scientific discussions and research activities in the field of atopic dermatitis and skin allergies in the future.     

Neuroimmunological findings in allergic skin diseases

PURPOSE OF REVIEW: Recent studies have gained widespread information about the complex regulation of genetic, environmental, immunologic, and pharmacologic factors that contribute to the development of allergic inflammatory skin diseases such as atopic dermatitis. Neuroimmune mechanisms, however, still remain to be elucidated. This review will focus on the interaction between the cutaneous immune and peripheral nervous system in allergic inflammatory skin such as atopic dermatitis. RECENT FINDINGS: Neuropeptides and neuropeptide-positive nerve fibres are prominently increased in lesions of atopic dermatitis. The density of nerve fibres is increased while peripheral nerve endings are in an active state of excitation. In this regard, neurotrophins particularly described for their functional role on nerve cells are also expressed in atopic dermatitis skin. In addition, neurotrophins modulate the functional role of eosinophils as main target effector cells in atopic dermatitis, as described recently. Interestingly, eosinophils are capable of neurotrophin as well as neuropeptide production itself, pointing to a bidirectional communication between neuronal cell populations and main target effector cells. SUMMARY: Neurotrophins and neuropeptides modulate both the functional activity of sensory neurons and immune cells. We have therefore developed the concept of a neuroimmune network between target effector cells and sensory nerves that links pathogenic events to dysfunctions of the cutaneous immune and peripheral nervous system in allergic inflammatory skin diseases.     

The interaction of social network size and stressful life events predict delayed-type hypersensitivity among women with metastatic breast cancer.

This study examined relationships between social support, stressful life events and antigen-specific cell-mediated immunity. Participants were 72 women with documented metastatic breast carcinoma, who completed self-report measures of social support and life stress. Immune response was assessed using the delayed type hypersensitivity (DTH) skin test. Number of positive antigens was significantly related to the interaction of social network size and stressful life events (p<0.05). Number of positive antigens was greater for women who had experienced a high frequency of stressful life events but who reported a larger network of support. However, social network size was inversely related to DTH response among women who had experienced fewer stressful life events. Average induration size was not significantly related to the quality of social support, life stress per se, or their interactions. The relationship between social network size and immune response in women with metastatic breast cancer depends on prior stressful life experience.     

Atopic eczema in children: another harmful sequel of divorce

BACKGROUND: Different lifestyle factors seem to be associated with the risk for atopic diseases and some studies suggest that stress increases the risk of allergic sensitization, asthma and atopic eczema. Only few studies have investigated the association of early stressful life events and atopic eczema (AE) in children. SUBJECTS AND METHODS: Parents of participants of the ongoing LISA birth cohort study were asked to give information on life events, such as severe disease or death of a family member, unemployment, or divorce of the parents. Lifetime prevalence of AE and incidence after the assessment period for life events were compared. RESULTS: Prevalence of AE until the age of 4 years was 21.4%. Reported life events within the first 2 years were: severe disease (17.5%) or death (8.4%) of a family member, divorce/separation (3.4%), and unemployment (2.7%). Divorce/separation was associated with a significantly [odds ratio (OR) 3.59, 95% confidence interval (CI) 1.69-7.66] increased and disease with a significantly (OR 0.29, 95% CI 0.13-0.68) decreased incidence of AE for the subsequent 2 years of life. No effect was seen for unemployment. CONCLUSIONS: Divorce/separation of the parents and severe disease of a family member influence the risk of developing AE.     

Predicting Injury Risk in Adolescent Football Players: The Importance of Psychological Variables

Explored the relationship of anger/aggression, attention, andstressful life events to injury while addressing the methodologicallimitations of prior studies. An additional objective was todetermine whether the relationship of stressful life eventsto injury is mediated either by anger (directed either inwardor outward) or by impaired attention, either vigilant (broad,external) or focused (narrow, internal). At the beginning ofsummer practice, 120 first-string high school football playerscompleted measures of anger (Framingham Anger Scale), vigilantattention (Symbol Digit Modalities test), focused attention(Pursuit sub test, MacQuarrie Test of Mechanical Ability), andstressful life events (abbreviated form of the Social ReadjustmentRating Scale as modified for use with adolescents by Coddington,1972). Players were then followed through one season to identifythose injured. Logistic regression indicated that high angerdirected outward (p <.05) and low focused attention (p <.01) increased injury risk, while stressful life events andvigilant attention interacted. Injury risk was elevated whenrecent stress was present (p < .05), and increased as vigilancedecreased, suggesting that stressful life events elevate injuryrisk by reducing vigilance.     

γδ T cells and inflammatory skin diseases

Approximately 25% of the population suffers from skin diseases. The most common forms of skin diseases are the inflammatory skin diseases such as allergic contact dermatitis, psoriasis, and atopic dermatitis. These diseases are described as T cell–mediated diseases induced by either allergens or autoantigens. Classically, the focus has been on the role of αβ T cells, but it is becoming increasingly clear that γδ T cells play a central role in inflammatory skin diseases. In particular, an important role of IL-17A–producing γδ T cells in these inflammatory skin diseases has been shown in various disease models in mice. Interestingly, various epidermal proteins, which appear to be linked to inflammatory conditions in the skin by yet undescribed mechanisms, are expressed by specific subsets of thymic epithelial cells and mutations in these proteins seem to affect γδ T cell development. The focus of this review is how mutations in epidermal proteins affect γδ T cell development and how γδ T cells, and in particular of IL-17A–producing γδ T cells, contribute to inflammatory skin diseases such as allergic contact dermatitis, psoriasis, and atopic dermatitis.     

The relationship between racial identity, income, stress and C-reactive protein among parous women: implications for preterm birth disparity research

The persistent racial disparity in preterm birth (PTB)remains one of the most obvious yet poorly understood health disparities in the United States, and current evidence suggests that maternal stress, infection and inflammation may play an important role in the etiology of PTB. In this context, we assessed the complex relationships among racial identity; socioeconomic status (SES); psychosocial factors; and serum C-reactive protein (CRP), an inflammatory biomarker, among parous women in King County, WA. African-American women consistently reported a higher number of stressful life events than white American women (4.6 vs. 2.9, p < 0.001), as well as slightly higher levels of perceived stress and lower social support (24.7 vs. 22.2, p = 0.011, and 3.4 vs. 3.6, p = 0.06, respectively). In the multivariate analysis, African-American race, low-income status and their interaction were all independently associated with CRP; when further adjusted for proximal psychosocial, behavioral and infectious factors, race and income associations were significantly reduced. Stressful life events score was the single best proximal predictor of CRP levels (beta = 0.07 per event,p < 0.001), while perceived stress and social support were not significantly related to CRP. These results support the hypothesis that differences in CRP by racial identity and income may be mediated by differences in proximal risk factors, including stressful life events and health behaviors such as smoking. Objective life event stressors may be important to consider in future studies investigating a potential inflammatory etiology for preterm birth.     

Stress and life events during childhood and adolescence

Research concerned with life events and stress during childhood and adolescence is reviewed. Models of stress and life events and measures of stressful events during childhood and adolescence are described. Although problems in each of these areas are noted, recent progress in measurement is encouraging. Cross-sectional studies have found a consistent, although modest, correlation of stressful events with psychological, behavioral, and somatic problems. However, recent prospective studies provide greater support for the role of chronic strains and daily Stressors than major life events in the development of psychological and behavioral difficulties during adolescence. Directions for future research are outlined.     

Daily hassles, cortisol, and the pathogenesis of depression

Daily hassles and/or ongoing stress are associated with increased cortisol secretion in healthy individuals. Hassles are also associated with increased cortisol levels in depressed patients. Considerable evidence suggests that hypercortisolism is involved in the pathogenesis of depressive disorders. Over the past decade, there has been a shift from viewing excessive hypothalamic-pituitary-adrenal (HPA) activity in depression as an epiphenomenon to its having specific effects on symptom formation. The author suggests that increased cortisol secretion caused by daily hassles and/or ongoing stress contributes to the development of depressive disorders. Minor stressful events may lead to depression in vulnerable individuals. Genetic factors interact with environmental factors to influence the vulnerability to stress and mood disorders. The author also proposes that elevated cortisol levels associated with stressful daily events may worsen the condition of depressed patients. The author notes that one of the goals of prevention of stress-related disorders is to help individuals be more competent in managing their behavior and emotions in reaction to negative aspects of their environment, and briefly discusses stress management methods and techniques. The risk of developing depression is determined by a complex interplay between genetic susceptibility, environmental exposures, and aging. These influences also account for long term changes in the regulation of HPA function. Further studies of HPA function may not only advance our understanding of the role of the HPA system in the etiology and pathogenesis of psychiatric disorders, but also be useful in refining conceptions of psychiatric disorders themselves and possible approaches to the treatment of these conditions.     

Life problems,social supports,and psychological functioning of emotionally disturbed and well low-income women

The relationship between stressful life events, social supports, and psychological functioning was examined in a low-income population of schizophrenic, depressed, and well mothers of young children. It was expected that the disturbed populations and those rated lowest on psychological functioning would have the most problems and the fewest resources. A buffering effect was hypothesized such that for the individuals with many problems, those with many resources would show better functioning than those with few resources. The results indicated that neither number of problems nor number of resources was related significantly to levels of psychological functioning. For disturbed women, having fewer problems may be associated with higher functioning. Both schizophrenic and depressed women reported more problems, but also more resources, than well women. Finally, having many resources did not affect the level of functioning of those with many stressful life events. Results were interpreted as failing to support the buffering hypothesis. Alternative explanations are proposed in terms of factors predisposing to vulnerability (e.g., low self-esteem) and alternative conceptualizations of social support.     

Psychobiological aspects of atopic dermatitis: an overview

Atopic dermatitis (AD) is a chronic, pruritic inflammatory skin disease with increasing incidence characterized by eczematous inflammation of the skin, a chronically relapsing course and severe pruritus. In the last decade, there has been growing evidence indicating that psychological factors such as personality and stress may play an important role in the pathogenesis of AD. While there is only little consensus on an AD-specific personality profile and its etiological significance, a growing number of reports support the role of psychosocial stress in the onset and the course of AD symptomatology. However, although a close association between psychosocial stress and skin condition in AD patients has been demonstrated by several investigators, pathological models that integrate stress and its effect on atopy-relevant biological processes, e.g. immune processes, are still missing. This overview summarizes the role of immunological and psychological factors in AD pathogenesis and discusses potential psychobiological pathways of stress-related modulation of AD symptoms.     

Major and minor life events as predictors of psychological distress: Further issues and findings

Current trends in research on stressful life events and disease have been to focus upon other psychosocial factors that may be associated with stress and illness relationships. Recently, the study of relatively minor life events or situations (e.g., daily hassles) has provided a promising alternative avenue of inquiry into basic stress measurement and the relationship of stress to disorder. While initial findings in this area of research appear encouraging, several methodological and procedural issues currently preclude definitive conclusions. The present paper outlines several of the most important limitations of existing research on this topic and provides further data taking these limitations into account for the role of minor life events as predictors of psychological distress. The results of the present prospective study indicate that undesirable minor events (e.g., hassles) significantly predict psychological symptoms, even once initial symptom status is controlled for statistically. Additionally, hassles were uniformly better predictors of subsequent psychological symptoms than were major life event categories; potentially important interactive effects (e.g., hassles x prior symptoms; hassles x prior major events) were also tested and their implications are discussed. Finally, basic associations between major and minor events were examined. The findings are discussed specifically in the context of recent advances in this area and more generally in relation to clarifying our understanding of psychosocial predictors of disorder.     

Stress and psychosis: towards the development of new models of investigation

The experience of stress is commonly implicated in the onset and maintenance of psychotic disorders such as schizophrenia. Previous studies that have addressed this relationship have had mixed results and serious methodological flaws associated with study design are common. One central limitation is the over-reliance on the experience of life events as a measure of the experience of stress. Research in the general stress literature suggest that attention also needs to be paid to the experience of other types of stressful events (such as 'hassles') as well as qualitative appraisals of events to fully understand the relationship between stressful experiences and mental health problems such as psychosis. Investigation of the experiences of stress by young people who are identified as being at heightened risk of developing a psychotic disorder would also result in a more complete understanding of the relationship between the experience of stress and the onset of psychotic disorder.     

Social rearing effects on HPA axis activity over early development and in response to stress in rhesus monkeys

Previous studies have found evidence of behavioral and psychophysiological differences between nonhuman primates reared in different social environments, however, few of these have employed longitudinal study of the animals over early development. In this study, HPA axis activity was assessed via measurement of ACTH and cortisol values over the first 6 months of life and in response to two stressful housing transitions in 48 infant rhesus monkeys that were either mother- or peer-reared. ACTH and cortisol values declined over the first 6 months in both rearing groups. Peer-reared monkeys showed lower levels of ACTH over the first 6 months of life than mother-reared, but the rearing groups did not differ in basal cortisol values over this period. Mother-reared animals showed a greater ACTH response to the mild stress of being moved to a new cage, and male monkeys showed higher values than females. Mother-reared animals showed the largest cortisol increase in response to the caging transition. Both groups showed increases in ACTH and cortisol in response to the more severe stress of separation from their rearing partners and housing with unfamiliar agemates. Mother-reared animals again showed the largest increase in ACTH in response to these events, but increases in cortisol were similar among both sexes and rearing groups. These results suggest an interaction of sex and rearing history in response to stressful events. © 1993 John Wiley & Sons Inc.     

Stress during development: Impact on neuroplasticity and relevance to psychopathology

Development represents a critical moment for shaping adult behavior and may set the stage to disease vulnerability later in life. There is now compelling evidence that stressful experiences during gestation or early in life can lead to enhanced susceptibility for mental illness. In this paper we review the data from experimental studies aimed at investigating behavioral, hormonal, functional and molecular consequences of exposure to stressful events during prenatal or early postnatal life that might contribute to later psychopathology. The use of the newest methodology in the field and the intensive efforts produced by researchers have opened the possibility to reveal the complex, finely tuned and previously unappreciated sets of molecular interactions between different factors that are critical for neurodevelopment thus leading to important discoveries regarding perinatal life. The major focus of our work has been to revise and discuss data from animal studies supporting the role of neuronal plasticity in the long-term effects produced by developmental adversities on brain function as well as the possible implications for disease vulnerability. We believe these studies might prove useful for the identification of novel targets for more effective pharmacological treatments of mental illnesses.     

Association analyses of the serotonin transporter gene with lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism (COGA) sample

The objective of this study was to analyze association of the serotonin transporter gene 5-HTTLPR polymorphism on lifetime depression and alcohol dependence in the Collaborative Study on the Genetics of Alcoholism sample. We conducted family-based association analyses in 1913 Caucasians genotyped for the 5-HTTLPR polymorphism. We found evidence for association of the short allele with depression, but no evidence of association with alcohol dependence. On the basis of the evidence that the effect of this polymorphism may be moderated by stressful life events, we classified individuals for the presence and/or absence of stress, as defined by unemployment, relationship problems, or poor health. The evidence for the association with lifetime depression was limited to the group of individuals who had experienced stress, paralleling the direction of effects originally reported by Caspi and colleagues. No evidence was found for the association with alcohol dependence in either the stress or the no-stress groups.     

A review on heme oxygenase-1 induction: is it a necessary evil

Heme oxygenase-1 (HO-1) is considered to be the main protein in diseases arising as a result of oxidative and inflammatory insults. Tremendous research has been carried out on HO-1 since years, pertaining its cytoprotective effect against oxidative injury and other cellular stresses. HO-1, by regulating intracellular levels of pro-oxidant heme, or by other benefits of its by-products such as carbon monoxide (CO) and biliverdin (BV) had become an important candidate protein to be up-regulated to combat diverse stressful events. Although the beneficial effects of HO-1 induction have been reported in a number of cells and tissues, a growing body of evidence indicates that this increased HO-1 expression may lead to the progression of several diseases such as neurodegeneration, carcinogenesis. But it is not clear, what accounts for the increased expression of HO-1 in cells and tissues. The observed friendly role of HO-1 in a wide range of stress conditions since times is now doubtful. Therefore, more studies are needed to elucidate the exact role of HO-1 in various stressful events. Being more concise, elucidating the effect of HO-1 up-regulation on critical genes involved in particular diseases such as cancer will help to a larger extent to comprehend the exact role of HO-1. This review will assist in understanding the dual role (protective and detrimental) of HO-1 and the signaling pathway involved and will help in unraveling the doubtful role of HO-1 induction.