Abstract Chronic stress is associated with morbidity and mortality from numerous conditions, many of whose pathogenesis involves persistent inflammation. Here, we examine how chronic stress ...influences signaling pathways that regulate inflammation in monocytes. The sample consisted of 33 adults caring for a family member with glioblastoma and 47 controls whose lives were free of major stressors. The subjects were assessed four times over eight months. Relative to controls, caregivers’ monocytes showed increased expression of genes bearing response elements for nuclear-factor kappa B, a key pro-inflammatory transcription factor. Simultaneously, caregivers showed reduced expression of genes with response elements for the glucocorticoid receptor, a transcription factor that conveys cortisol’s anti-inflammatory signals to monocytes. Transcript origin analyses revealed that CD14+/CD16− cells, a population of immature monocytes, were the predominate source of inflammatory gene expression among caregivers. We considered hormonal, molecular, and functional explanations for caregivers’ decreased glucocorticoid-mediated transcription. Across twelve days, the groups displayed similar diurnal cortisol profiles, suggesting that differential adrenocortical activity was not involved. Moreover, the groups’ monocytes expressed similar amounts of glucocorticoid receptor protein, suggesting that differential receptor availability was not involved. In ex vivo studies, subjects’ monocytes were stimulated with lipopolysaccharide, and caregivers showed greater production of the inflammatory cytokine interleukin-6 relative to controls. However, no group differences in functional glucocorticoid sensitivity were apparent; hydrocortisone was equally effective at inhibiting cytokine production in caregivers and controls. These findings may help shed light on the mechanisms through which caregiving increases vulnerability to inflammation-related diseases.
Interpersonal touch is emerging as an important topic in the study of adult relationships, with recent research showing that such behaviors can promote better relationship functioning and individual ...well-being. This investigation considers whether being hugged is associated with reduced conflict-related decreases in positive affect and increases in negative affect as well as whether these associations differ between women and men. A sample of 404 adults were interviewed every night for 14 consecutive days about their conflicts, hug receipt, and positive and negative affect. Results indicated that there was an interaction between hug receipt and conflict exposure such that receiving a hug was associated with a smaller conflict-related decrease in positive affect and a smaller conflict-related increase in negative affect when assessed concurrently. Hug receipt was also prospectively associated with a smaller conflict-related increase in next day negative affect but was not associated with next day positive affect. Associations between hug receipt and conflict-related changes in affect did not differ between women and men, between individuals who were married or in a marital-like relationship and those who were not, or as a function of individual differences in baseline perceived social support. While correlational, these results are consistent with the hypothesis that hugs buffer against deleterious changes in affect associated with experiencing interpersonal conflict. Possible mechanisms through which hugs facilitate positive adaptation to conflict are discussed.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary Background Indices of cortisol activity, including the cortisol awakening response (CAR), diurnal slope, and cortisol output across the day (total daily output), are often studied as ...mechanistic indicators that could link stress with health. Yet there is a paucity of data speaking to their temporal features, particularly whether they behave in a more state- or trait-like manner across time. Methods To address this issue, data from 3 studies were used to assess CAR, diurnal slope and total daily output stability over different age groups and time spans: 130 healthy children and adolescents collected salivary cortisol samples 5 times/day (1, 4, 9 and 11 h after wake) over 2 days at 5 visits spaced 6 months apart (Study 1); 147 adolescent girls collected saliva 6 times/day (wake, 1, 4, 9 and 14 h after wake) for 2 days at 3 visits, each a year apart (Study 2); and 47 healthy, primarily middle age adults collected saliva 6 times/day (wake, 1, 4, 9 and 14 h after wake) for 3 days at 4 visits spaced 2–3 months apart (Study 3). Stability was estimated by multilevel model-derived intraclass correlation coefficients ( ICC s). Results Across studies, approximately 50% of the variance in cortisol indices was attributable to day-to-day fluctuations, suggesting state-like properties. Of the indices, total daily output emerged as the most stable over time, followed by diurnal slope and CAR, but stability estimates were generally quite modest regardless of index and sample. Over time spans of >1 year, ICC s were ≤ .13. Conclusions Most of the variance in CAR, diurnal slope and total daily output reflects day-to-day fluctuation; there was little evidence for more stable trait-like influences. These findings suggest that future research should focus on short-term fluctuations in stress, cortisol and health, as opposed to lengthy disease processes.
Although responses to different stressors are sometimes assumed to be similar, recent research has demonstrated that certain types of stress, such as targeted rejection, are particularly potent. To ...test such associations in a chronic-disease model, we examined how noninterpersonal, interpersonal, and targeted-rejection major life events predicted changes in gene expression and symptom severity in 121 youths with asthma who were assessed every 6 months for 2 years. Youths who had recently experienced targeted rejection had lower messenger RNA expression for signaling molecules that control airway inflammation and obstruction (specifically, the glucocorticoid receptor and β2-adrenergic receptor) than youths who had not experienced targeted rejection. These associations were specific to targeted rejection and stronger for youths higher in subjective social status. Higher-status youths exposed to targeted rejection (but not other types of stress) also reported more asthma symptoms. These data demonstrate stressor-specific associations with molecular-signaling pathways and the severity of asthma, and they suggest that threats to the social self may be particularly deleterious.
Highlights • Married have lower cortisol levels and steeper slopes than the unmarried. • Differences in cortisol output between groups were greatest during the afternoon. • Higher stress is related ...to higher cortisol only for the previously married.
•Psychosocial predictors explained 1%-3.6% of variance in CAR responses.•Depression was linked to higher AUCw and posttraumatic stress to lower AUCw.•Inconclusive results were obtained for ...predictor-specific effects on CARi.•Cross-sectional studies of CAR need Ns of 617–783 to detect effects with 80% power.•There were no indications of questionable research practices biasing the CAR literature.
Cortisol levels rise immediately after awakening and peak approximately 30–45min thereafter. Psychosocial functioning influences this cortisol awakening response (CAR), but there is considerable heterogeneity in the literature. The current study used p-curve and meta-analysis on 709 findings from 212 studies to test the evidential value and estimate effect sizes of four sets of findings: those associating worse psychosocial functioning with higher or lower cortisol increase relative to the waking period (CARi) and to the output of the waking period (AUCw). All four sets of findings demonstrated evidential value. Psychosocial predictors explained 1%-3.6% of variance in CARi and AUCw responses. Based on these effect sizes, cross-sectional studies assessing CAR would need a minimum sample size of 617–783 to detect true effects with 80% power. Depression was linked to higher AUCw and posttraumatic stress to lower AUCw, whereas inconclusive results were obtained for predictor-specific effects on CARi. Suggestions for future CAR research are discussed.
We report a new series of homoleptic Ni(I) bis-N-heterocyclic carbene complexes with a range of torsion angles between the two ligands from 68° to 90°. Electron paramagnetic resonance measurements ...revealed a strongly anisotropic g-tensor in all complexes with a small variation in g ∥ ∼ 5.7–5.9 and g ⊥ ∼ 0.6. The energy of the first excited state identified by variable-field far-infrared magnetic spectroscopy and SOC-CASSCF/NEVPT2 calculations is in the range 270–650 cm–1. Magnetic relaxation measured by alternating current susceptibility up to 10 K is dominated by Raman and direct processes. Ab initio ligand-field analysis reveals that a torsion angle of <90° causes the splitting between doubly occupied d xz and d yz orbitals, which has little effect on the magnetic properties, while the temperature dependence of the magnetic relaxation appears to have no correlation with the torsion angle.
Observational studies have given conflicting results about the effect of statins in preventing dementia and cognitive decline. Moreover, observational studies are subject to prescription bias, making ...it hard to draw definite conclusions from them. Randomized controlled trials are therefore the preferred study design to investigate the association between statins and cognition. Here we present detailed cognitive outcomes from the randomized placebo-controlled PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). Cognitive function was assessed repeatedly in all 5,804 PROSPER participants at six different time points during the study using four neuropsychological performance tests. After a mean follow-up period of 42 months, no difference in cognitive decline at any of the cognitive domains was found in subjects treated with pravastatin compared to placebo (all
p
> 0.05). Pravastatin treatment in old age did not affect cognitive decline during a 3 year follow-up period. Employing statin therapy in the elderly in an attempt to prevent cognitive decline therefore seems to be futile.
•Greater social integration associated with lower cortisol AUC for those over 35.•Social integration and cortisol AUC not associated for those under 35.•Greater social integration associated with ...steeper diurnal slopes overall.•Social integration and diurnal slopes more strongly associated for those over 35.
Social integration is defined as the degree to which an individual participates in a broad range of social relationships. Although measures of social integration vary across studies, it is often assessed as the number of social roles (e.g., parent, friend, student, volunteer) that an individual reports actively participating in. More socially integrated individuals tend to be healthier than those less socially integrated, but the biological mechanisms through which this occurs remain unclear. One possibility is that social integration might alter the function of the hypothalamic-pituitary-adrenal axis, of which cortisol is a key product, and in turn influence a broad range of health outcomes. This study examined the association between social integration and two indices of cortisol in a community sample of 680 healthy men and women aged 18–55. Because the social roles held by younger individuals may be more numerous yet superficial than those held by older individuals, this study also tested the hypothesis that these associations could be moderated by age such that lower levels of integration would be associated with cortisol dysregulation for older but not younger individuals in our sample. Participants provided salivary cortisol samples during waking hours on three days that were used to calculate diurnal cortisol levels and slopes. Increased social integration was associated with lower cortisol AUC among older (ages 35–55) but not younger (ages 18–34) individuals in our sample. Moreover, while increased social integration was associated with steeper diurnal cortisol slopes regardless of age, this association was strongest among older individuals. Differences in health behaviors, affect, and psychological stress did not mediate these associations. The results of this study support cortisol as a candidate biological mechanism through which increased social integration is associated with better physical health among older individuals.
ABSTRACT Objective Neighborhood risk in childhood is associated with poor health across the life span. However, many people who are reared in risky neighborhoods remain healthy in adulthood. In the ...context of high-risk neighborhoods, parenting practices that are controlling might promote better physical health outcomes later in life. The current study used a viral challenge paradigm to examine whether parental control throughout childhood moderated the association between recalled neighborhood risk and cytokine-mediated cold susceptibility. Methods A sample of 209 healthy adults completed questionnaires to assess recalled neighborhood risk and parental control over the first 15 years of life, were exposed to a common cold virus, and were quarantined for 6 days. Researchers assessed nasal proinflammatory cytokine production and objective markers of illness. Participants were diagnosed with a clinical cold if they met the infection and objective illness criteria. Results A significant Neighborhood Risk by Parental Control interaction emerged to predict proinflammatory cytokine production. Furthermore, parental control moderated the cytokine-mediated association between neighborhood risk and cold diagnosis (index = −0.073, 95% confidence interval CI = −0.170 to −0.016), likelihood of infection (index = −0.071, 95% CI = −0.172 to −0.015), and meeting the objective symptom criteria (index = −0.074, 95% CI = −0.195 to −0.005). Specifically, there was a negative association between neighborhood risk and objective cold diagnosis and infection status at higher levels of parental control, but a nonsignificant association at lower levels of parental control. Conclusions Findings suggest that the degree to which recalled neighborhood risk is related to adult health varies as a function of parental control throughout childhood.
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