Altered hypothalamus-pituitary-adrenal axis function: A relevant factor in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder?

Epidemiological data show a significant association between childhood atopic eczema (AE) and an increased risk to develop attention deficit/hyperactivity disorder (ADHD). However, the underlying mechanisms of the comorbidity of AE and ADHD are mostly unknown. We investigated whether alterations of hypothalamus-pituitary-adrenal (HPA) axis function represent a shared feature of AE and ADHD potentiating AE-ADHD comorbidity. Children aged 6-12 years with AE, ADHD, or comorbid AE + ADHD and healthy control (HC) children were examined cross-sectionally (N = 145). To evaluate HPA axis function, salivary cortisol in response to psychosocial stress (Trier Social Stress Test for Children, TSST-C), after awakening (cortisol awakening response, CAR), and throughout the day (short diurnal profile) and hair cortisol capturing long-term HPA axis activity were assessed. Quantile regression analyses showed an attenuated cortisol response (% maximum change) to the TSST-C in children with ADHD compared to HC. A diminished cortisol response to acute stress was also observed in the comorbid AE + ADHD group, in which the reduction was numerically even more pronounced. Contrary to our previous findings, no alteration of the cortisol response to the TSST-C was observed in children with AE. However, in children with AE, increased ADHD-like behavior (i.e., inattention, impulsivity, and overall ADHD symptom severity) was associated with a reduced HPA axis response to acute stress. No such associations were observed in children without AE. Groups did not differ in CAR, short diurnal profile, and hair cortisol. These findings underscore the potential relevance of HPA axis function in the pathophysiology of AE and ADHD with emphasis on stress reactivity. Additional studies are required to further explore the separate and joint role of the HPA axis in the pathophysiology of AE and ADHD.

Increased attention-deficit/hyperactivity symptoms in atopic dermatitis are associated with history of antihistamine use.

BACKGROUND: Epidemiologic evidence indicates a relevant association between atopic dermatitis (AD) and attention-deficit/hyperactivity disorder (ADHD). Underlying mechanisms and ways to best identify subgroups of AD patients at risk for ADHD are poorly understood. AIMS OF THE STUDY: To compare sociodemographic, clinical and psychosocial characteristics of children with AD, ADHD, comorbid AD/ADHD and age-matched healthy controls and to investigate aspects of AD related to ADHD symptoms. METHODS: Applying a factorial design, we investigated 4 groups of children aged 6-12 years: AD-only (ie, without ADHD), ADHD-only (ie, without AD), AD + ADHD and healthy controls (HC; ie, no AD/no ADHD). Using validated instruments, ADHD symptoms and other behavioural problems, quality of life, parenting stress and sleeping problems were compared between groups. In children with AD-only, clinical signs (objective SCORAD), symptoms (POEM, VAS pruritus, VAS sleeping problems) and previous treatment of AD were assessed to investigate disease patterns related to ADHD symptoms. RESULTS: Compared to HC (n = 47), children with AD-only (n = 42), ADHD-only (n = 34) and comorbid AD + ADHD (n = 31) had significantly increased behavioural problems and decreased quality of life. Children with AD-only had significantly higher levels of ADHD symptoms than HC. In children with AD-only, previous use of antihistamines was significantly associated with increased ADHD symptoms (OR 1.88; 95% CI 1.04-3.39). Current clinical signs and AD symptoms were unrelated to the level of ADHD symptoms. CONCLUSIONS: Even if the clinical diagnosis of ADHD is excluded, children with AD show increased levels of ADHD symptoms. Further investigations need to determine whether early antihistamine exposure is a major risk factor for ADHD or a surrogate for previous AD severity and/or associated sleeping problems.

Memory and multitasking performance during acute allergic inflammation in seasonal allergic rhinitis.

BACKGROUND: In previous research, patients with seasonal allergic rhinitis (SAR) showed poorer school and work performance during periods of acute allergic inflammation, supporting the idea of an impact of SAR on cognitive functions. However, the specific cognitive domains particularly vulnerable to inflammatory processes are unclear. OBJECTIVE: In this study, the influence of SAR on memory and multitasking performance, as two potentially vulnerable cognitive domains essential in everyday life functioning, was investigated in patients with SAR. METHODS: Non-medicated patients with SAR (n = 41) and healthy non-allergic controls (n = 42) performed a dual-task paradigm and a verbal learning and memory test during and out of symptomatic allergy periods (pollen vs. non-pollen season). Disease-related factors (e.g. symptom severity, duration of symptoms, duration of disease) and allergy-related quality of life were evaluated as potential influences of cognitive performance. RESULTS: During the symptomatic allergy period, patients showed (1) poorer performance in word list-based learning (P = 0.028) and (2) a general slowing in processing speed (P < 0.001) and a shift in processing strategy (P < 0.001) in multitasking. Yet, typical parameters indicating specific multitasking costs were not affected. A significant negative association was found between learning performance and duration of disease (r = -0.451, P = 0.004), whereas symptom severity (r = 0.326; P = 0.037) and quality of life (r = 0.379; P = 0.015) were positively associated with multitasking strategy. CONCLUSIONS: Our findings suggest that SAR has a differentiated and complex impact on cognitive functions, which should be considered in the management of SAR symptoms. They also call attention to the importance of selecting sensitive measures and carefully interpreting cognitive outcomes.

Altered performance in attention tasks in patients with seasonal allergic rhinitis: seasonal dependency and association with disease characteristics.

BACKGROUND: Seasonal allergic rhinitis (SAR) is a chronic disease affecting about 23% of the European population with increasing prevalence rates. Beside classical symptoms (i.e., sneezing, nasal congestion), patients frequently complain about subjective impairments in cognitive functioning during periods of acute allergic inflammation. However, objective evidence for such deficits or the role of potential modulators and underlying mechanisms is limited. The present study aimed to investigate the effect of SAR on attention-related cognitive processes. In addition, relationships between attention performance, sleep and mood disturbances as well as specific disease characteristics as potential modulators of this link were explored. METHOD: SAR patients (n = 41) and non-allergic healthy controls (n = 42) completed a set of attention tasks during a symptomatic allergy period and during a non-symptomatic period. Influences of sleep, mood, total immunoglobulin E (IgE) levels and individual allergy characteristics on cognitive performance were evaluated. RESULTS: Compared to healthy controls, SAR patients had a slower processing speed during both symptomatic and non-symptomatic allergy periods. Additionally, they showed a more flexible adjustment in attention control, which may serve as a compensatory strategy. Reduction in processing speed was positively associated with total IgE levels whereas flexible adjustment of attention was linked with anxious mood. No association was found between SAR-related attention deficits and allergy characteristics or sleep. CONCLUSIONS: SAR represents a state that is crucially linked to impairments in information processing and changes in attentional control adjustments. These cognitive alterations are more likely to be influenced by mood and basal inflammatory processes than sleep impairments or subjective symptom severity.

Psychoendocrine and psychoneuroimmunological mechanisms in the comorbidity of atopic eczema and attention deficit/hyperactivity disorder.

Epidemiological data indicate that atopic eczema (AE) in infancy significantly increases the risk for attention deficit/hyperactivity disorder (ADHD) in later life. The underlying pathophysiological mechanisms of this comorbidity are unknown. We propose that the release of inflammatory cytokines caused by the allergic inflammation and/or elevated levels of psychological stress as a result of the chronic disease interfere with the maturation of prefrontal cortex regions and neurotransmitter systems involved ADHD pathology. Alternatively, increased stress levels in ADHD patients may trigger AE via neuroimmunological mechanisms. In a third model, AE and ADHD may be viewed as two separate disorders with one or more shared risk factors (e.g., genetics, prenatal stress) that increase the susceptibility for both disorders leading to the co-occurrence of AE and ADHD. Future investigation of these three models may lead to a better understanding of the mechanisms underlying the observed comorbidity between AE and ADHD and further, to targeted interdisciplinary primary prevention and treatment strategies.

Is atopic disease a risk factor for attention-deficit/hyperactivity disorder? A systematic review.

The increase in prevalence and burden of atopic diseases, i.e. eczema, rhinitis, and asthma over the past decades was paralleled by a worldwide increase in attention-deficit/hyperactivity disorder (ADHD) diagnoses. We systematically reviewed epidemiologic studies investigating the relationship between atopic diseases and ADHD. Electronic literature search in PubMed and PsycINFO (until 02/2010) supplemented by handsearch yielded 20 relevant studies totaling 170,175 individuals. Relevant data were abstracted independently by two reviewers. Six studies consistently reported a positive association between eczema and ADHD with one study suggesting effect modification by sleeping problems. Twelve studies consistently found a positive association between asthma and ADHD, which, however, appeared to be at least partly explained (confounded) by concurrent or previous eczema. Rhinitis and serum-IgE level were not related to ADHD symptomatology. We conclude that not atopic disease in general, but rather that eczema appears to be independently related to ADHD. Conclusions about temporality and whether the observed association constitutes a causal relationship are impossible, as most studies were cross-sectional (n = 14; 70%) or case-control studies without incident exposure measurement (n = 5; 25%). Another methodological concern is that the criteria to define atopic disease and ADHD were inadequate in most studies. A failure to adjust for confounders in the majority of studies was an additional limitation so that meta-analysis was not indicated. Future interdisciplinary high-quality prospective research is needed to better understand the mechanisms underlying the relationship between eczema and ADHD and to eventually establish targeted preventive and treatment strategies.

Blunted HPA axis responsiveness to stress in atopic patients is associated with the acuity and severeness of allergic inflammation.

Previously we could demonstrate attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to stress in patients with chronic allergic inflammatory disease (i.e., atopic dermatitis, allergic asthma). The present study was designed to investigate HPA axis function in an acute manifestation of allergy. Patients with seasonal allergic rhinitis (SAR; n = 20) and non-atopic controls (n = 20) were exposed to a standardized laboratory stressor ('Trier Social Stress Test'; TSST). Cortisol responses to the TSST and cortisol awakening responses (CAR) were measured in SAR subjects while suffering from acute symptoms of SAR (pollen season), and during a non-active state of their disease (pollen-free season). To assess the acuity and severity of SAR, eosinophil and basophil numbers and SAR symptomatology were determined. Non-allergic control subjects were examined at identical times during the year. To control for possible sequence effects, a cross-over design was used. SAR patients showed significantly increased symptom severity (t = 9.4; p<.001) as well as eosinophil (F(1,31) = 9.8; p<.01) and basophil (F(1,38) = 6.4; p<.05) numbers during the pollen season when compared to a pollen-free period. When exposed to the TSST, significantly attenuated cortisol responses were found in SAR subjects during acute manifestation of the disease (pollen season) when compared to the pollen-free season (F(16,456) = 1.65; p<.05). In SAR patients, there was a significant negative correlation between symptom severity and the cortisol response to the stressor (r = .53; p<.05). No significant between-group or between-condition differences with respect to the CAR could be determined (all p>.05). These findings support previous data of attenuated HPA axis responsiveness to stress in atopic conditions and further, suggest that HPA axis hyporesponsiveness in atopy may be linked to the severity of the allergic inflammatory process.

Cortisol responses to stress in allergic children: interaction with the immune response.

Allergic manifestations are increasingly common in infants and children. Accumulating evidence suggests that the 'epidemic' increase of childhood allergy may be associated with environmental factors such as stress. Although the impact of stress on the manifestation and exacerbation of allergy has been demonstrated, the underlying mechanisms of stress-induced exacerbation are still obscure. A growing number of studies have suggested an altered hypothalamus-pituitary-adrenal (HPA) axis function to stress in allergic children. It is speculated that a dysfunctional HPA axis in response to stress may facilitate and/or consolidate immunological aberrations and thus, may increase the risk for allergic sensitization and exacerbation especially under stressful conditions. In the present review the potential impact of a hyporesponsive as well as a hyperresponsive HPA axis on the onset and chronification of childhood allergy is summarized. Moreover, potential factors that may contribute to the development of an aberrant HPA axis responsiveness in allergy are discussed.

Personality characteristics in chronic and non-chronic allergic conditions.

In psycho-allergological research, the potential relevance of personality factors in the maintenance and exacerbation of atopic symptoms is still a matter of debate. The present study aimed to assess personality dimensions in chronic atopic disease, i.e. atopic dermatitis (AD) and in acute manifestation of atopy (seasonal allergic rhinitis, SAR). Further, the association of a potentially atopy-specific personality profile with atopy-relevant biological stress responses should be evaluated. Subjects suffering from AD (n=36), or SAR (n=20) and non-atopic controls (n=37) were investigated. To determine different personality domains, Spielberger's State-Trait Anxiety Inventory (STAI), the Questionnaire for Competence and Control (FKK) and the Questionnaire for Stress Vulnerability (MESA) were administered. To assess the relation between these personality dimensions and biological stress responses, atopics and non-atopic controls were exposed to a standardized laboratory stressor (Trier Social Stress Test, TSST). Endocrine (cortisol, ACTH), immune (total IgE, leukocyte subsets) and physiological (heart rates) measures were recorded before and after the stress test. When compared to healthy controls, AD and SAR patients showed significantly higher trait anxiety (STAI) and stress vulnerability in situations characterized by failure, job overload and social conflicts (MESA). Moreover, AD subjects scored significantly lower in self-competence and self-efficacy (FKK) as well as in recreation ability (MESA). No difference trait anxiety and stress vulnerability could be detected between AD and SAR subjects. Pearson correlational analyses yielded no significant correlation between the different personality domains and the endocrine, physiological and immunological stress responses. However, stress-induced increase in eosinophil number was significantly correlated with the perceived self-competence/self-efficacy in SAR patients.

Hypothalamic-pituitary-adrenal axis function and the cellular immune response in former preterm children.

CONTEXT: Animal data suggest that adverse early experiences may affect endocrine and immune functioning in later life. OBJECTIVE: Our objective was to assess the impact of preterm delivery on hypothalamus-pituitary-adrenal axis functioning, heart rate responses, and immune function. PARTICIPANTS: Former preterm children [aged 8-14 yr (n = 18)], sex and age-matched full-term born control children (n = 18), data on birth weight, gestational age, birth weight for gestational age (in sd units), actual body weight, height, and body mass index were assessed. DESIGN AND OUTCOME MEASURES: Subjects were exposed to a standardized laboratory stressor ("Trier Social Stress Test for Children"). Cortisol in saliva was determined in 10-min intervals before and after the stress test; heart rates were obtained continuously during the stress test. Additional assessment of saliva cortisol was performed: 1) on 3 consecutive days after awakening and at +10, +20, and +30 min (morning cortisol); and 2) at 0800, 1400, 1600, and 1900 h (short diurnal profile). Measurement of the delayed type hypersensitivity reaction to seven recall antigens [Multitest cellular mediated immunity (Multitest-Immignost, Biosyn, Fellbach, Germany)]. RESULTS: Exposure to the Trier Social Stress Test for Children yielded significantly increased cortisol levels [F (8, 232) = 19.86; P < 0.001] and heart rates [F (38, 988) = 10.46; P < 0.001], however, no difference between former preterms and full-terms could be observed. No between-group differences were found in the short diurnal cortisol profile. Former preterms showed significantly higher cortisol levels after awakening [F (3, 102) = 3.14; P < 0.05]. In addition, a significantly suppressed delayed type hypersensitivity response [reduced number of positive antigens (t = -2.64, P < 0.05); induration (t = -2.4, P < 0.05)] was found in former preterms. CONCLUSION: The data suggest that preterm delivery may be associated with altered endocrine and immune functions well into late childhood.

Altered distribution of leukocyte subsets and cytokine production in response to acute psychosocial stress in patients with psoriasis vulgaris.

Psoriasis (PSO) is a mainly T helper-type 1 (TH(1)) cell mediated chronic inflammatory skin disease characterized by epidermal hyperproliferation and psoriatic plaques. There is ample evidence that stress may trigger psoriatic eruption, however, the underlying mechanisms of stress-induced exacerbation of PSO are poorly understood. The specific goal of the present study was to investigate the impact of acute stress on pathologically relevant immune functions in PSO patients. PSO patients (n=23) and healthy controls (n=25) were exposed to a standardized laboratory stressor ("Trier Social Stress Test", TSST) including a free speech and mental arithmetics in front of an audience. Blood samples were collected 10min before and 1, 10, 20, and 60min after the TSST as well as 24h after the experiment at identical time points under resting conditions. Analyses of leukocyte subsets indicated a significantly increased number of leukocyte subpopulations (lymphocytes, granulocytes, CD3(+), CD8(+), CD16(+)/CD56(+), and CD3(+)/HLA-DR(+)) after the TSST (all p<.01) with no significant between-group differences. However, monocyte number (F(3,120)=2.7; p<.01) and number of CD4(+)cells (F(3,120)=3.09; p<.05) were found to be significantly higher in PSO sufferers than in controls. Moreover, a significant decrease of CD3(+)/CD25(+)cells was observed in the PSO, but not in the control group (F(3,120)=3.46; p<.05). After exposure to the TSST, stimulation of peripheral blood mononuclear cells (PBMCs) with phytohemagglutinin (PHA) resulted in elevated production of IFN-gamma (F(3,126)=6.9; p<.001) and IL-2 (F(3,123)=6.6; p<.001), and moreover, a decreased production of IL-10 (F(3,132)=5.22; p<.01) and IL-4 (F(3,129)=3.9; p<.01). No difference in stress-induced changes of cytokine production to PHA could be identified between the two experimental groups (all p>.05). The present findings suggest that acute psychosocial stress is associated with changes of immune functions known to be involved in PSO which may be one potential explanation of how stress may trigger psoriatic eruption.

Endocrine stress responses in TH1-mediated chronic inflammatory skin disease (psoriasis vulgaris)--do they parallel stress-induced endocrine changes in TH2-mediated inflammatory dermatoses (atopic dermatitis)?

In previous research we reported attenuated responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis and further, an increased reactivity of the sympathetic adrenomedullary (SAM) system to stress in patients suffering from atopic dermatitis (AD). AD is a chronic inflammatory skin disease mainly triggered by TH(2)-dependent inflammatory processes. The specific goal of the present study was to investigate whether altered HPA axis and SAM system responsiveness to stress can also be found in TH(1)-mediated inflammatory conditions. Patients with psoriasis (PSO; n=23), a TH(1)-mediated inflammatory (autoimmune) skin disease and healthy controls (n=25) were exposed to a standardized laboratory stressor (TSST) which mainly consists of a free speech and a mental arithmetic task in front of an audience. To investigate HPA axis and SAM system responsiveness, cortisol, ACTH, and catecholamines were determined before and after the stress test. In addition, cortisol levels after awakening and cortisol levels during the day (short diurnal profile) were determined. In order to test feedback sensitivity of the HPA axis, a dexamethasone (DEX) suppression test (0.5 mg) was performed. Analysis of cortisol and ACTH levels after the stress test yielded no significant differences between PSO subjects and controls indicating no altered HPA axis function in this patient group. Further, no between-group differences were found in cortisol levels after awakening or during the day (short diurnal profile). Additionally, no difference between PSO and healthy subjects in the feedback sensitivity of the system could be found (DEX test). However, PSO patients showed elevated epinephrine (F(3,102)=4.7; p<0.005) and norepinephrine (F(3,135)=2.7; p<0.05) levels in response to the stress test when compared to the controls. These findings suggest no altered HPA axis responsiveness, but increased reactivity of the SAM system in TH(1)-mediated chronic inflammatory skin disease.

HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender.

Data from five independent studies were reanalyzed in order to investigate the impact of age and gender on HPA axis responses to an acute psychosocial laboratory stress task. The total sample consisted of 102 healthy subjects with 30 older adults (mean age: 67.3 y), 41 young adults (mean age: 23.5 y), and 31 children (mean age: 12.1 y). All participants were exposed to the Trier Social Stress Test (TSST). The stress protocol caused highly significant ACTH and total plasma cortisol responses in older and younger male and female adults (all p<0.0001) as well as salivary free cortisol responses in all six age and gender groups (all p<0.0001). Three-way ANOVAs for repeated measurement were applied to investigate the impact of age and gender on ACTH and cortisol responses. Results showed that the ACTH response to stress was higher in younger adults compared to older adults (main effect: p=0.009, interaction: p=0.06). Post hoc analyses revealed that there was no age effect in the subgroup of women (p=n.s.), while younger men had higher ACTH responses compared to older men (p=0.01). For total plasma cortisol, ANOVA results showed that the pattern of reactivity did not differ between age and gender groups (all interactional effects p=n.s.), although older females had hightened overall cortisol levels compared to the other groups, as proofed in post hoc analyses (all p<0.05). For free salivary cortisol, a significant main effect of gender (p=0.05) and an almost significant three-way-interaction (p=0.09) emerged. Post hoc analyses showed an elevated overall free salivary cortisol response in elderly men compared to elderly women (p=0.006), while no gender differences emerged in neither young adults nor children (both p=n.s.). In sum, the stressor induced significant HPA axis responses in all age and gender groups. The observed ACTH response patterns in young and elderly adults may suggest that a heightened hypothalamic drive in young men decreases with age, resulting in similar ACTH responses in elderly men and women. Alternative interpretations are also discussed. The data also supports the idea of a greater adrenal cortex sensitivity to ACTH signals in young females. Free salivary cortisol responses were elevated in elderly men compared to elderly women, an effect which cannot be explained by gender differences in perceived stress responses to the TSST. It can be speculated if corticosteroid binding globulin (CBG) and/or sex steroids are important modulators of these effects.

Stress-induced immunomodulation is altered in patients with atopic dermatitis.

Atopic dermatitis (AD) is a chronically relapsing inflammatory skin disease with main symptoms such as eczematous skin lesions and severe pruritus. Although the relevance of stress in the pathology of AD is widely accepted, the underlying biological mechanisms of stress-induced exacerbation of AD symptoms are not fully understood. The specific goal of the present study was to investigate the impact of acute psychosocial stress on atopy-relevant immune functions in AD sufferers. AD patients (n=36) and nonatopic controls (n=37) were exposed to a laboratory stressor including a free speech and mental arithmetic tasks in front of an audience ("Trier Social Stress Test," TSST). Blood samples were collected 10 min before and 1, 10 and 60 min after the stress test as well as 24 h after the experiment at identical time points under resting conditions. Analyses of leukocyte subsets indicated significantly elevated lymphocyte, monocyte, neutrophil and basophil numbers 10 min after the TSST (all p's<0.001) with no significant differences between the two groups. In contrast, eosinophil number was found to be significantly elevated only in AD sufferers, but not subjects (F(3,213)=4.8; p<0.01). Moreover, AD patients but not the control group showed increased IgE levels (F(1,71)=4.4; p<0.05) 24 h after the stress test. Exposure to the TSST resulted in elevation of interferon-gamma (IFN-gamma; F(3,207)=19.55; p<0.001) and, further, in attenuation of interleukin-4 (IL-4; F(3,207)=187.46; p<0.001) concentrations with no significant differences between both groups (all p's>0.05). The present findings suggest that stress may be associated with atopy-relevant immunological changes in AD sufferers, which may be one explanation of the common observation of stress-induced aggravation of symptomatology in this patient group.

Preliminary evidence for Herpes labialis recurrence following experimentally induced disgust.

BACKGROUND: After primary orofacial infection with the herpes simplex virus (type 1, HSV-1), up to 40% of HSV seropositive subjects suffer recurrent herpes infections which are characterized by painful erosions of the involved skin mainly around the lips (herpes labialis). Besides various other factors, there is growing evidence suggesting that psychosocial factors might trigger HSV. The present study was designed to investigate modulation of recurrent HSV infection by experimentally induced emotional distress. METHODS: Among patients with herpes labialis (n = 91), subjects who showed recurrent HSV infection (>5 acute infections/year) and who reported to suffer from HSV symptoms exclusively after confrontation with dirty dishes, i.e. dirty plates or dirty glasses were selected by standardized interview. Subjects (n = 20) were randomly assigned to two treatment groups. The experimental group (n = 10) was first exposed to 5 slides showing dirty glasses and subsequently to the glasses previously presented on the slides in vivo. The control group (n = 10) was exposed to neutral slides and neutral objects. In order to determine the proportion of leukocyte subpopulations and concentrations of tumor necrosis factor alpha (TNF-alpha), blood samples were collected 15 min before as well as 40 min and 48 h after stimulus presentation. Saliva cortisol was obtained 45, 20, 15 and 1 min before and 1, 10, 20 and 30 min after stimulus confrontation. RESULTS: Medical examination of the volunteers 48 h after the experiment indicated that four experimental subjects showed HSV-1 symptoms while not a single herpetic infection could be determined in the control subjects (p = 0.033). Moreover, significantly elevated concentrations of TNF-alpha were observed in the experimental, but not in the control group. No significant alterations of the number of leukocyte subpopulations were found 30 min or 48 h after stimulus presentation. Further, cortisol concentrations were found to be unchanged after the treatment. CONCLUSIONS: The present findings suggest that experimentally induced emotional stress such as disgust may be associated with reactivation of HSV.

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.

Tissue specificity of glucocorticoid sensitivity in healthy adults.

Contradicting data exist as to whether interindividual patterns in glucocorticoid (GC) sensitivity vary between different target tissues in humans. This study therefore measured GC sensitivity in 36 healthy subjects in three target tissues: the immune system; the cardiovascular system, and the hypothalamus-pituitary-adrenal axis. For this purpose, dexamethasone inhibition of lipopolysaccharide-induced interleukin-6 and tumor necrosis factor-alpha production in peripheral leukocytes, beclomethasone dipropionate-induced skin blanching, and suppression of cortisol levels after low-dose (0.5 mg) dexamethasone suppression test were determined in each subject. The results showed the expected glucocorticoid-induced suppression of interleukin-6 and tumor necrosis factor-alpha production (both P < 0.001), dose-dependent skin blanching (P < 0.001), and suppression of salivary cortisol response to awakening (P < 0.001). However, neither simple correlations nor cluster analysis revealed a significant association among the three bioassays for GC sensitivity. In contrast to the idea that interindividual variation in GC sensitivity is an intrinsic trait affecting all tissues, these results suggest that this variability is target tissue specific in healthy subjects.

Pavlovian conditioning of immune function: animal investigation and the challenge of human application.

Pavlovian conditioning of immune functions provided early impetus to the rapidly expanding knowledge of bi-directional communication among the immune, endocrine, and central nervous systems. Since these early investigations, the phenomenology of this response has been well characterized. However the neural mechanisms and biological relevance of conditioned immunomodulation remain unclear. To this end, we present here data from our laboratories that have: (1) revealed some of the neural mechanisms and biological relevance of an animal model of conditioned immunomodulation; (2) demonstrated the conditionability and potential mechanisms of conditioned immune responses in healthy humans, and (3) investigated conditioned immunomodulation in a clinical sample. Together, these data demonstrate that animal models provide a basis for investigating mechanisms whereby conditioned changes in immune function may modulate health status in a clinical realm.

Skin surgery under local anesthesia leads to stress-induced alterations of psychological, physical, and immune functions.

BACKGROUND: Although excision of nevi under local anesthesia is a frequent and harmless operation, it apparently causes increased stress in many patients. However, thus far no studies have focused on the question of whether there are measurable effects on psychological, physiological, and immunological parameters. OBJECTIVE: To assess the perioperative stress reactions of patients undergoing skin surgery under local anesthesia for nevocellular nevi. METHODS: Fifty consecutive patients with pigmented nevi were examined at five points of measurement: 1 week and 30 minutes before the operation, during the operation, 30 minutes and 1 week after the operation. Somatic parameters included blood pressure, pulse, respiratory rate, and the level of pain. Lymphocyte subpopulations, white blood cell count, and cortisol in saliva were determined. Anxiety and general psychological distress were evaluated with validated questionnaires. RESULTS: There was a significant increase in anxiety at the time of surgery. In parallel, the physiological parameters as well as the CD56+ lymphocytes changed significantly. Preoperation anxiety and intraoperation pain were significantly higher in women (P <.001), but did not depend on age. CONCLUSION: There appears to be an interaction between physiological and emotional components in the operative stress reaction under local anesthesia. In patients with skin cancer, the perioperative stress may lead to transient impairment of immune function.