Sleep disturbances in major depressive and burnout syndrome: A longitudinal analysis.

Sleep quality (SQ) is considered to be a critical variable in major depressive syndrome (MD) as well as in burnout syndrome (B). Thus far, no study examined the differential influence of these syndromes on SQ. MD and B have been assessed in 4,415 participants at baseline and in 1,396 participants at follow-up based on the Patient Health Questionnaire-9 (PHQ-9) and the Maslach Burnout Inventory-General Survey (MBI-GS). The Pittsburgh Sleep Quality Index was used to measure SQ. Based on the PHQ-9 and MBI-GS at baseline assessment, participants were divided into four groups: a control group, a MD group, a B group, and a comorbid group suffering from MD and B. Multiple regression analyses showed that all groups demonstrate significantly worse SQ than the control group, while individuals with MD showed a lower SQ compared to individuals with B. The comorbid group showed the lowest SQ. Longitudinal analyses showed a significant bidirectional association between major depressive symptoms and SQ, whereas burnout symptoms were predictive for SQ but not vice versa. The study indicates differences between MD and B with regard to SQ, suggesting worse SQ in more severely burdened groups. Major depressive symptoms are bidirectionally linked to SQ, whereas burnout symptoms are only suggested a risk factor for impaired SQ.

Phenotype, Function, and Mobilization of 6-Sulfo LacNAc-Expressing Monocytes in Atopic Dermatitis.

Mononuclear phagocytes (MPs) are important immune regulatory cells in atopic dermatitis (AD). We previously identified 6-sulfo LacNAc-expressing monocytes (slanMo) as TNF-α- and IL-23-producing cells in psoriatic skin lesions and as inducers of IFN-γ-, IL-17-, and IL-22-producing T cells. These cytokines are also upregulated in AD and normalize with treatment, as recently shown for dupilumab-treated patients. We here asked for the role of slanMo in AD. Increased numbers of slanMo were found in AD skin lesions. In difference to other MPs in AD, slanMo lacked expression of FcɛRI, CD1a, CD14, and CD163. slanMo from blood of patients with AD expressed increased levels of CD86 and produced IL-12 and TNF-α at higher amounts than CD14+ monocytes and myeloid dendritic cells. While CD14+ monocytes from patients with AD revealed a reduced IL-12 production, we observed no difference in the cytokine production comparing slanMo in AD and healthy controls. Interestingly, experimentally induced mental stress, a common trigger of flares in patients with AD, rapidly mobilized slanMo which retained their high TNF-α-producing capacity. This study identifies slanMo as a distinct population of inflammatory cells in skin lesions and as proinflammatory blood cells in patients with AD. slanMo may, therefore, represent a potent future target for treatment of AD.

Stressful life events predict one-year change of leukocyte composition in peripheral blood.

A plethora of cross-sectional studies suggest that psychological stress resulting from experiencing stressful life events (SLE) can result in an altered immune response. Potential maladaptive immune changes may outlast the event and affect the organism long after stress cessation. As a consequence, an increased vulnerability for immune-mediated pathologies (e.g. arthritis, diabetes) may develop over the life span. The objective of the present study was to monitor the longitudinal kinetics of peripheral white blood cells (WBCs; neutrophils, lymphocytes, and monocytes) in response to SLE. Here we present blood, hair, and behavioural measures obtained in the Dresden Burnout Study, at first visit (T1; N = 446) and one year later (T2; N = 173). Cumulative impact of SLE was assessed at T1 with the Life Stressor Checklist (LSC-R). Results indicate a significant increase in neutrophils (+2.8% per each 10 LSC-R points) between T1 and T2 in association with reported SLE. The change in neutrophils tended to correlate with the change in hair cortisol (Cohens f = 0.6). We propose that SLE trigger immunological alterations that persist across time and thereby promote a continuous effect on WBC distribution. Such an effect might advance subclinical inflammatory processes, reduce an individuals immune defence, and promote a link between psychological stress and physical disease.

"Allergic mood" - Depressive and anxiety symptoms in patients with seasonal allergic rhinitis (SAR) and their association to inflammatory, endocrine, and allergic markers.

A growing number of studies show an association between seasonal allergic rhinitis (SAR) with depression and anxiety. The underlying mechanisms of a link between SAR and affect, however, are still unclear. The objective of the present study was to investigate depressive symptoms and anxiety in SAR patients and their association to inflammatory and endocrine parameters. SAR patients (n=41) and non-allergic, healthy controls (n=42) were assessed during (pollen season) and out of symptomatic periods (non-pollen season). Inflammatory cytokine profile (Interleukin [IL]-2, IL-4, IL-6, IL-8, IL-10, IL-17, IFN-γ, TNF-α), Immunoglobulin-E (IgE), hair cortisol concentrations (HCC), as well as sleep quality were measured. The present data show that during acute allergic inflammation SAR patients experienced a significant increase in Beck Depression Inventory (BDI-) II scores when (a) compared to the asymptomatic period and (b) when compared to the non-allergic controls, while no differences in anxiety were observed. Increased BDI-II scores in SAR patients were significantly associated with levels of IL-6 as well as IL-6/IL-10 and IFN-γ/IL-10 ratios and further, to an early age at manifestation of SAR and poor sleep quality. These findings support a close relationship between acute allergic processes and affective states, with inflammatory cytokines, sleep, and age of manifestation as potentially relevant mediators.

Positive life events predict salivary cortisol in pregnant women.

Maternal stress during pregnancy has been repeatedly associated with problematic child development. According to the fetal programming hypothesis adverse experiences during pregnancy increase maternal cortisol, which is then assumed to exert a negative effect on fetal development. Recent studies in non-pregnant women report significant associations between positive emotionality and low cortisol levels. We tested in a sample of 60 pregnant women whether both negative and positive life events independently predicted third-trimester baseline awakening cortisol levels. While the effect of negative life events proved unrelated positive life events significantly predicted lower cortisol levels. These findings suggest that positive experiences are of relevance regarding maternal morning cortisol levels in pregnancy reflecting a resource with potentially beneficial effects for the mother and the developing fetus. It might be promising for psychological intervention programs to focus on increasing positive experiences of the expecting mother rather than exclusively trying to reduce maternal stress during pregnancy.

Cortisol levels in pregnancy as a psychobiological predictor for birth weight.

Antenatal maternal stress is thought to negatively affect fetal development, birth outcomes, and infant's development. Glucocorticoids are suggested to be a common link between prenatal stressors and infant's health. However, data on these mechanisms are rare and sometimes conflicting. The objective of this study was to examine the effects of maternal distress during pregnancy on fetal development and birth weight in humans prospectively. This study focuses on cortisol as one mediating the mechanism of the association between maternal distress and birth outcomes. Pregnancy-related and general distress was measured in 81 women with uncomplicated, singleton pregnancies. The rise of salivary cortisol on awakening (CAR) was assessed in weeks 13-18 and 35-37 postmenstrual age of pregnancy. Mothers completed a structured interview, the perceived stress scale, a widely used psychological instrument that provided a global measure of perceived stress, as well as the Prenatal Distress Questionnaire, a self-report questionnaire designed to assess worries and anxiety in pregnancy. Pre-, peri-, and postnatal medical risk factors as well as birth characteristics were extracted from medical records routinely kept by the attending obstetricians. Hierarchical multiple regressions indicate that maternal cortisol levels explained 19.8% of the variance in birth weight and 9% of the variance in body length at birth, even after controlling for gestational age, parity, pre-pregnancy BMI, smoking, and infant's sex. Newborns of mothers with higher cortisol levels in pregnancy had lower birth weights and were shorter at birth. An ANCOVA for repeated measures indicated that, after controlling for covariates, pregnancy-related as well as general distress in pregnancy did not influence cortisol levels after awakening (area under the curve). No significant associations between perceived stress and anthrometric measures at birth were found. In conclusion, maternal cortisol levels in pregnancy influence intrauterine growth and may be a better predictor for birth outcome than perceived stress.

Association between life stress during pregnancy and infant crying in the first six months postpartum: a prospective longitudinal study.

OBJECTIVE: To examine prospectively the relationship between prenatal life stress and infant crying/fussing during the first 6 months of postnatal life, taking into account an array of confounders suggested in the literature. DESIGN: Prospective longitudinal study of a convenient sample, with data points in pregnancy and at about 6 weeks, 3, and 6 months postpartum. METHODS: The study included 86 pregnant women who completed a standardized, validated and widely used questionnaire on negative life changes experienced in the preceding 12 months. Women were grouped by median split on the impact score of negative life changes. Demographic, obstetric and lifestyle variables were obtained from pre- and postnatal interviews and from medical records in order to be taken into account as possible confounders. At all three postnatal data points, mothers kept a validated 5-day 24-h behavior diary to assess durations of infant crying/fussing. RESULTS: Infants of mothers with high scores of negative life changes exhibited more crying/fussing than infants born to mothers with low negative change scores, throughout the first half year postpartum, but particularly at ages 3 and 6 months. These results do not seem to be spurious due to the confounders considered in this report or to recording bias. CONCLUSION: Prenatal life stress is associated with infant crying/fussing in the first half year after delivery. To prevent or reduce infant crying and to foster a well-adapted parent-infant relationship, professionals attending expectant mothers should consider their emotional condition. If required, support should be provided already in pregnancy.

Differential heart rate reactivity and recovery after psychosocial stress (TSST) in healthy children, younger adults, and elderly adults: the impact of age and gender.

In addition to numerous reports about psychophysiological stress responses to acute stressors, there are few data available on gender differences of stress-induced heart rate responses in multiple age groups applying the same psychological stressor. Second, the assessment of poststress recovery appears to be neglected in the empirical literature. For this study, data from 5 independent studies were reanalyzed to investigate the impact of age and gender on heart rate responses and poststress recovery to a standardized psychosocial stress task (Trier Social Stress Test; TSST) in 28 children, 34 younger adults, and 26 older adults. As expected, prestressor baselines correlated significantly with chronological age (r = -.27, p =.01). There was a marked age-related decrease in the heart rate stress response (p =.0003) with children and younger adults showing significantly higher increases than elderly persons. The analysis of gender effects showed that girls had higher heart rate increases during the stress exposure than boys (p =.03). In younger adults, stress responsivity was also higher in women (p =.03). Peak heart rate responses were comparable in older men and women, with only men returning to prestressor baselines during the observation period. In sum, this reanalysis revealed differential heart rate responses and recovery after exposition to the TSST in healthy children, younger adults, and elderly adults.

Increased responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to stress in newborns with atopic disposition.

In previous studies, atopic patients showed attenuated cortisol responses to psychosocial stress which is suggestive of a hyporeactive hypothalamus-pituitary-adrenal (HPA) axis in this patient group. Regarding the anti-inflammatory role of glucocorticoids, reduced responsiveness of the HPA axis under stress may be one potential explanation of stress-induced exacerbation of atopic symptoms. The present study evaluated whether hyporeactivity of the HPA axis is a feature related to the disposition of atopy rather than a consequence of an ongoing chronic allergic inflammatory process. Newborns with an atopic disposition (parental atopy; n=31) and without atopic disposition (no parental atopy; n=20) were recruited. To further assess atopic disposition, total IgE levels were determined in the cord blood of the neonates. Three days after birth, a blood sample was obtained by a heel prick which is part of a standard pediatric examination. Blood sampling by heel prick is well known to be a significant stressor resulting in activation of the HPA axis in newborns. Analysis of salivary cortisol indicated a significant increase of cortisol levels in the newborns after the stressor with a trend towards an elevated cortisol response in babies with a family history of atopy or with elevated levels of cord IgE (> or = 0.5 kU/l). Neonates with a positive parental atopic heritage and elevated cord IgE were found to show significantly elevated cortisol responses to the heel prick stress when compared to newborns without a parental atopic history and normal cord IgE values. Moreover, cord IgE levels were significantly correlated with basal cortisol levels and the cortisol response to the stressor. These findings suggest that atopic disposition in neonates is associated with altered responsiveness of the HPA axis to stress which may increase the vulnerability to develop manifestation of atopy in later life.

Influence of stress during pregnancy on HPA activity and neonatal behavior.

Prenatal maternal stress has been shown to impair birth outcome and behavioral functioning in nonhuman primate offspring. Little is known about the effects of prenatal stress on behavioral development in humans. We assessed the effect of self-reported prenatal stress on behavioral characteristics of 81 newborns using the Neonatal Behavioral Assessment Scale (NBAS). We suspected that high levels of perceived chronic stress during pregnancy may negatively affect the brain development of the fetus, reflected in poorer behavioral maturity and higher irritability. We found a poorer performance of newborns from high stressed mothers in the NBAS.

Blunted cortisol responses to psychosocial stress in asthmatic children: a general feature of atopic disease?

OBJECTIVE: Atopy is defined by the individual predisposition to develop a group of inflammatory disorders in response to certain food or environmental substances that are otherwise innocuous for the host. In previous studies we could demonstrate a reduced responsiveness of the hypothalamus-pituitary-adrenal (HPA) axis to psychosocial stress in young and adult patients with atopic dermatitis (AD), a chronic atopic skin disorder. With respect to the important immunoregulatory role of the HPA axis, especially under stress, this observation could be of clinical relevance and may at least partly explain stress-induced exacerbation of AD. The present study was designed to investigate whether attenuated responsiveness of the HPA axis to stress represents a characteristic feature of AD or whether it can also be found in other chronic manifestations of atopy. METHODS: Children (aged 7-12) with allergic asthma (AA; N = 17) and age- and sex-matched healthy controls (N = 18) were exposed to the "Trier Social Stress Test for Children"(TSST-C), which mainly consists of a free speech and mental arithmetic tasks in front of an audience. Salivary cortisol was measured in ten-minute intervals before and after the TSST-C, while heart rate was monitored continuously. In addition, early morning cortisol levels (after awakening, +10, +20, +30 minutes) were assessed on three consecutive days. RESULTS: Data analysis yielded a significant increase of cortisol concentrations (F (9297)= 16.79; p <.001) and heart rates (F(32,992)= 9.16; p <.001) after the stressor with no between-group difference in heart rate responses. However, AA children showed a significantly blunted cortisol response to the TSST-C when compared with the control group (F(9297)= 2.95; p <.01). Awakening in the morning was accompanied by a significant rise of cortisol levels on all three experimental days in AA and control subjects (all p <.001) that was not different between the two groups. CONCLUSIONS: These findings suggest that a blunted adrenocortical response to stress may represent a common feature of chronic allergic inflammatory processes that may be relevant in different forms of chronic manifestation of atopy.

Endocrine and immune responses to stress in chronic inflammatory skin disorders.

Atopy is a genetically and environmentally determined condition predisposing to different forms such as atopic dermatitis (AD) or allergic asthma (AA). Both AD and AA are considered to be multifactorial diseases; however, distinct immunologic abnormalities have been described that play a crucial role. There is growing evidence that immunoglobulin-E hypersecretion and activation of the predominantly T-helper-2 (TH2)-like T cell subset trigger allergic inflammatory processes and cause the disease to become chronic. In the present paper, data suggesting reduced hypothalamic-pituitary-adrenal (HPA) axis responsiveness in patients with AD and AA are summarized, and the potential etiologic significance of a hyporeactive HPA axis is discussed. We propose that because of defective HPA axis, immunoregulation under stressful conditions is ineffective in patients with atopic conditions, leading to aberrant immune responses and subsequent exacerbation of the disease. Further research into the role of the HPA axis in atopy may elucidate the cause of stress-induced exacerbation of atopic symptoms and may be of clinical relevance.

Altered responsiveness of the hypothalamus-pituitary-adrenal axis and the sympathetic adrenomedullary system to stress in patients with atopic dermatitis.

A growing number of animal data strongly suggest that a hyporeactive hypothalamus-pituitary adrenal (HPA) axis may be pathologically significant by increasing the susceptibility to chronic inflammation. Following this line of evidence, the specific goal of the present study was to investigate the HPA axis in patients with atopic dermatitis (AD), a chronic allergic inflammatory disease. In addition, the sympathetic adrenomedullary (SAM) system as a second potent immunoregulatory and anti-inflammatory stress-response system has been examined. AD patients (n = 36) and nonatopic control subjects (n = 37) were exposed to a standardized laboratory stressor consisting of a free speech and mental arithmetic task in front of an audience. Cortisol, ACTH, and catecholamine concentrations were assessed before and after the stressor. To investigate feedback sensitivity of the HPA axis, a low dose (0.5 mg) dexamethasone suppression test was also performed. AD patients showed significantly attenuated cortisol and ACTH responses to the stressor, whereas catecholamine levels were significantly elevated in atopic patients. No difference between the experimental groups was found in basal cortisol and ACTH concentrations, whereas basal catecholamine levels were significantly elevated. Analysis of cortisol levels after dexamethasone treatment suggested an intact feedback sensitivity in AD sufferers at the pituitary level. The present findings suggest that patients with AD demonstrate a blunted HPA axis responsiveness with a concurrent overreactivity of the SAM system to psychosocial stress. Considering the important immunoregulatory role of the HPA axis and the SAM system, especially under stressful conditions, an aberrant responsiveness of these neuroendocrine systems may increase the susceptibility to (allergic) inflammation and may be one psychobiological mechanism of stress-related aggravation of the disease.