A systematic review and meta-analysis of the stability of peripheral immune markers in healthy adults.

Peripheral immune markers are widely used to predict risk for inflammatory disease. However, whether single assessments of inflammatory biomarkers represent stable individual differences remains unclear. We reviewed 50 studies (N = 48,674; 57 % male; mean age 54 (range 13-79) years) that assessed markers of inflammation on >1 occasion, with time between measures ranging from 24 h to 7+ years. Separate random effects meta-analyses were conducted for each inflammatory marker and time interval. Markers that had broad coverage across most time intervals included C-reactive protein (CRP; k = 37), interleukin (IL)-6 (k = 22), TNF-α (k = 10), and fibrinogen (Fg; k = 9). For CRP, IL-6, and TNF-α, stability estimates generally decreased with time, with strong to moderate stability over intervals <6 months (r's = 0.80-0.61), modest to moderate stability over 6 months - 3 years (r's = 0.60-0.51), and low stability for >3 years (r's = 0.39-0.30). Estimates were less reliable for Fg for time intervals ≤ 3 years although they generally followed the same pattern; more reliable findings suggested greater stability for Fg than other markers for intervals >3 years (r = 0.53). These findings suggest that single measures of inflammatory biomarkers may be an adequate index of stable individual differences in the short term (<6 months), with repeated measures of inflammatory biomarkers recommended over intervals ≥ 6 months to 3 years, and absolutely necessary over intervals >3 years to reliably identify stable individual differences in health risk. These findings are consistent with stability estimates and clinical recommendations for repeated measurement of other cardiovascular measures of risk (e.g., blood lipids, blood pressure).

Stress-Related Inflammation and Social Withdrawal in Mothers of a Child With Cancer: A 1-Year Follow-Up Study.

OBJECTIVE: Acute inflammation-induced sickness behavior involves changes in social behavior that are believed to promote recovery. Whether chronic inflammation can influence social behaviors in ways that promote recovery is unknown. In a sample of mothers of a child with cancer, this report explores the relationship between inflammation that accompanies the stress of diagnosis and changes in social network, cancer-related stress, and inflammation across 1 year. Three hypotheses tested whether a) initial levels of stress associate with initial levels of inflammation, b) initial levels of inflammation predict social network changes over time, and c) social network changes over time buffer changes in stress and inflammation over time. METHODS: Cancer-related stress (Impact of Events Scale), social network (social roles and contacts from the Social Network Inventory), and systemic inflammation (circulating interleukin [IL]-6) were assessed in 120 mothers three times after their child's cancer diagnosis: after diagnosis (T1), 6-month follow-up (T2), and 12-month follow-up (T3). RESULTS: Consistent with predictions, greater cancer-related stress after diagnosis (T1) was associated with higher IL-6 after diagnosis (T1; b = 0.014, standard error [SE] = 0.01, p = .008). In turn, higher IL-6 after diagnosis (T1) was associated with a decrease in social roles over time (T1 ➔ T3; B = -0.030, SE = 0.01, p = .041). Finally, dropping social roles over time (T1 ➔ T3) was associated with decreases in cancer-related stress (B = 25.44, SE = 12.31, p = .039) and slower increases in IL-6 (B = 1.06, SE = 0.52, p = .040) over time. CONCLUSIONS: This study provides a first indication that chronic stress-related systemic inflammation may predict changes in social behavior that associate with stress recovery and slower increases in inflammation in the year after a major life stressor.

Mindfulness-Based Stress Reduction Buffers Glucocorticoid Resistance Among Older Adults: A Randomized Controlled Trial.

OBJECTIVE: Mindfulness interventions have been effective for improving a range of health outcomes; however, pathways underlying these effects remain unclear. Inflammatory processes may play a role, possibly through increased resistance of immune cells to the anti-inflammatory effects of glucocorticoids (i.e., glucocorticoid resistance, or GCR). Here, we conducted an initial examination of whether mindfulness training mitigates GCR among lonely older adults. METHODS: Lonely older adults (65-85 years; n = 190) were randomly assigned to an 8-week Mindfulness-Based Stress Reduction (MBSR) or a matched Health Enhancement Program (HEP). Whole blood drawn before and after the intervention and at 3-month follow-up was incubated with endotoxin and varying concentrations of dexamethasone, and interleukin-6 production was assessed using enzyme-linked immunosorbent assay. GCR was assessed as the concentration of dexamethasone required to decrease the stimulated interleukin-6 response by 50% (half maximal inhibitory concentration), with higher concentrations indicating greater GCR. Mixed-effects linear models tested time (pre, post, follow-up) by condition (MBSR versus HEP) effects. RESULTS: There was no overall time by condition effect on GCR across all time points. However, a significant time by condition effect was observed from preintervention to postintervention (d = 0.29), such that MBSR buffered increases in GCR observed in the HEP group. Although MBSR showed small, nonsignificant reductions in GCR from preintervention to 3-month follow-up, group differences were not maintained at the 3-month follow-up (d = 0.10). CONCLUSIONS: Results suggest that MBSR may protect against declines in the sensitivity of immune cells to the anti-inflammatory effects of glucocorticoids among at-risk lonely older adults and show value in studying this biological mechanism in future trials.Trial Registration: Clinical Trials identifier NCT02888600.

Efficacy of a Stress Management Intervention for Mothers of Children with Cancer.

OBJECTIVE: Mothers of children with cancer confront life stress that can impact their psychological and physical health and, in turn, the health of the family. Recommendations advocate preemptive stress-management interventions; however, few studies have investigated their efficacy. Here, we report results of a parallel randomized pilot trial examining health benefits of a stress management intervention designed to teach coping skills. METHODS: One hundred twenty mothers (age 36 ± 8 years) of children newly diagnosed with cancer were randomized to a 12-session stress management intervention (n = 60) or usual care (n = 60). Sessions took place in the inpatient or outpatient setting of a children's hospital. Primary outcome variables included psychological function and physical health assessed preintervention and postintervention and at 6-month follow-up (∼12 months postdiagnosis). RESULTS: Enrollment, retention, and satisfaction data supported feasibility and acceptability. Latent change score models showed the intervention reduced perceived stress (d = -0.37, p = 0.03), anxiety symptoms (ds = -0.38 and -0.56, ps < .03) and, a nonsignificant effect for depressive symptoms (d = -0.29, p = .11) across the 6 months following diagnosis. Intervention participants also endorsed fewer depressive symptoms than controls ∼12 months after diagnosis. The intervention improved stress management skills, which associated with the psychological benefits of participation. There were no intervention-related changes in perceived health or markers of inflammation. CONCLUSION: Intervention-related improvements in stress management skills may result in better psychological health in the face of caring for a child with cancer. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02022449.

Circulating Interleukin-6 concentration covaries inversely with self-reported sleep duration as a function of polymorphic variation in the glucocorticoid receptor.

Growing evidence links extremes of self-reported sleep duration with higher circulating markers of inflammatory disease risk, although not all findings are consistent. Extremes of sleep duration also associate with activation of the hypothalamic-pituitary-adrenocortical (HPA) system and the peripheral release of cortisol, a glucocorticoid (GC) important in downregulating transcription of pro-inflammatory molecules. Polymorphic variation in the gene encoding the GC receptor (GR; NR3C1) modulates cellular sensitivity to GC-mediated anti-inflammatory signaling, thereby affecting levels of pro-inflammatory molecules. Thus, we hypothesized that extremes of self-reported sleep duration may covary with circulating levels of inflammatory markers as a function of allelic variation in NR3C1. Specifically, we examine the possibility that a single nucleotide polymorphism of the GR gene-(rs6198), the minor (G) allele of which confers reduced GR sensitivity-moderates an association of sleep duration with interleukin (IL)-6 and C-reactive protein (CRP) among a large sample (IL-6: N = 857; CRP: N = 929) of midlife community volunteers of European ancestry. Findings showed that sleep duration varied inversely with IL-6 (ß = -0.087, p = .012), and this association was stronger among individuals homozygous for the rs6198 G-allele compared to alternate genotypes (ß = -0.071, p = .039). We also found that sleep duration showed a U-shaped association with CRP (polynomial term: ß = 0.093, p = .006), which was not moderated by rs6198 genotype. In conclusion, we show that a common genetic variant in the GR moderates an inverse association of self-reported sleep duration with circulating IL-6, possibly contributing to the increased disease risk observed among some short sleepers.

Development of glucocorticoid resistance over one year among mothers of children newly diagnosed with cancer.

Chronic distress associates with peripheral release of cortisol and a parallel upregulation of innate inflammation. Typically, cortisol functions to down-regulate inflammatory processes. However, in the context of chronic stress, it is hypothesized that glucocorticoid receptors within immune cells become less sensitive to the anti-inflammatory effects of cortisol, resulting in increased systemic inflammation. Caring for a child newly diagnosed with cancer is a particularly provocative chronic stressor. Here, we examine evidence for the development of cellular resistance to glucocorticoids among 120 mothers (Aged 18-56 years; 86% Caucasian) across the 12 months following their child's new diagnosis with cancer. Measures of psychological distress, interleukin (IL)-6, and glucocorticoid resistance (GCR) were assessed 1, 6, and 12 months after the diagnosis. A latent factor for distress was derived from the covariation among symptoms of anxiety, depression, and post-traumatic stress. Latent change score models revealed a significant positive association between change in distress and change in GCR from 0 to 6 months, and 6 months-1 year. This finding provides initial evidence for a longitudinal association between change in maternal distress and change in GCR from the onset of a chronic stressor through one year. Although levels of IL-6 increased during the first six months after the child's diagnosis, the magnitude of this change was not related to change in distress or change in GCR. Given the possible health consequences of reduced immune sensitivity to glucocorticoids, future work should further explore this stress response and its clinical significance.

Sex-specific associations between childhood trauma and adult systemic inflammation in daily life.

OBJECTIVE: Childhood trauma may contribute to lifelong health through chronic systemic inflammation. However, associations between childhood trauma and inflammation are mixed, indicating that distinct types of childhood trauma may relate to inflammation differently. Moreover, most studies use a single assessment of inflammatory markers that may not reliably estimate stable interindividual differences. The current study is the first to examine relationships between childhood trauma and an ecologically valid measure of inflammation derived from repeated assessments of interleukin (IL)-6 in daily life. We also examine the possibility that glucocorticoid sensitivity and patterns of daily cortisol may contribute to observed associations. Finally, we explore whether biological sex moderates relationships between childhood trauma and IL-6. METHOD: Participants were 283 healthy adults aged 40-64 (57% female, 23% Black, Indigenous, and People of Color) who completed the Childhood Trauma Questionnaire and self-collected dried blood spots at home on 4 days to measure IL-6. Measures of salivary cortisol and blood-based glucocorticoid sensitivity were also assessed. RESULTS: Childhood trauma was not associated with IL-6 in the sample as a whole. However, exploratory analyses showed that childhood trauma related to IL-6 differently for males and females, such that total trauma and emotional neglect predicted higher IL-6 for males but not females. Results persisted after adjustment for covariates. There was no evidence for indirect effects via cortisol or glucocorticoid sensitivity. CONCLUSIONS: Childhood trauma and, specifically, emotional neglect were associated with IL-6 in daily life among middle-aged males. Additional research is needed to elucidate biological and behavioral pathways underlying these associations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Childhood trauma and hair cortisol response over the year following onset of a chronic life event stressor.

OBJECTIVE: Childhood trauma may contribute to poor lifelong health in part through programming of the HPA-axis response to future life stressors. To date, empirical evidence shows an association of childhood trauma with dysregulation of the HPA-axis and blunted cortisol reactivity to acute stressors. Here, we conduct an initial examination of childhood trauma as a moderator of changes over time in perceived stress levels and HPA-axis response to a major chronic stressor in adulthood. METHODS: Participants were 83 maternal caregivers of children newly diagnosed with cancer who completed the Childhood Trauma Questionnaire (CTQ), and who, over the year following their child's cancer diagnosis, had hair samples collected up to 7 times for the assessment of cortisol and completed monthly measures of perceived stress. RESULTS: CTQ scores were in the expected range for a community sample and associated with changes in perceived stress and cortisol concentration over time (γ =.003, p =.002; γ = -.0004, p =.008, respectively) independently of age, education, treatment intensity and randomization to stress management intervention. Maternal caregivers who endorsed lower childhood trauma showed a steeper decline in perceived stress and a larger increase in cortisol levels across the year than caregivers who recalled more childhood trauma. CONCLUSIONS: Findings extend animal models and studies that examine cortisol reactivity to acute stressors and suggest that childhood trauma may program a phenotype that is more psychologically reactive but shows a blunted HPA-axis response to chronic stress. While adaptive in the short-term, this early life programming may incur long-term costs for health. Further work is warranted to examine this possibility.

Glucocorticoid resistance and ß2-adrenergic receptor signaling pathways promote peripheral pro-inflammatory conditions associated with chronic psychological stress: A systematic review across species.

Activation of the HPA-axis and SNS are widely accepted to link chronic stress with elevated levels of peripheral pro-inflammatory markers in blood. Yet, empirical evidence showing that peripheral levels of glucocorticoids and/or catecholamines mediate this effect is equivocal. Recent attention has turned to the possibility that cellular sensitivity to these ligands may contribute to inflammatory mediators that accompany chronic stress. We review current evidence for the association of chronic stress with glucocorticoid receptor (GR) and ß-adrenergic receptor (ß-AR) signaling sensitivity. Across 15 mouse, 7 primate, and 19 human studies, we found that chronic stress reliably associates with downregulation in cellular GR sensitivity, alterations in intracellular ß-AR signaling, and upregulation in pro-inflammatory biomarkers in peripheral blood. We also present evidence that alterations in GR and ß-AR signaling may be specific to myeloid progenitor cells such that stress-related signaling promotes release of cells that are inherently less sensitive to glucocorticoids and differentially sensitive to catecholamines. Our findings have broad implications for understanding mechanisms by which chronic stress may contribute to pro-inflammatory phenotypes.

Breast ptosis: causes and cure.

Breast ptosis is one of the most common conditions treated by plastic surgeons, but the causes are not clearly defined. A review was conducted of 132 consecutive patients presenting for breast augmentation or mastopexy. Information was obtained by chart review and telephone interview. Standardized photographs were examined to determine degree of ptosis by the Regnault classification. Of patients who had at least one pregnancy, 85% reported adverse changes in breast shape following pregnancy, 35% reported a reduction in breast size, and 30% reported an increase in size. Upon logistic regression, age, history of significant (>50 lbs) weight loss, higher body mass index, larger bra cup size, number of pregnancies, and smoking history were found to be significant risk factors for breast ptosis (P < 0.05). History of breast-feeding, weight gain during pregnancy, and lack of participation in regular upper body exercise were not found to be significant risk factors for ptosis.

Mindfulness training and systemic low-grade inflammation in stressed community adults: Evidence from two randomized controlled trials.

Mindfulness interventions have garnered significant attention as a complementary health treatment for many physical and psychological conditions. While some research has shown that mindfulness training can decrease psychological and physiological stress responses, it remains unclear whether mindfulness training impacts inflammation-a predictor of poor health outcomes. In addition, little research has examined the active components of mindfulness that may drive health-related improvements. Here, we provide data from two 3-arm randomized controlled trials that examined the effect of mindfulness training on inflammation in stressed community adults. Specifically, we examined whether training individuals to have an accepting attitude towards present moment experiences is a key emotion regulation skill that can lead to decreases in inflammation. Both studies randomly assigned participants to one of three conditions: mindfulness training that taught both attention monitoring and acceptance skills (Monitor+Accept); mindfulness training teaching monitoring without the acceptance component (Monitor Only); or a control condition. Study 1 employed a novel 2-week smartphone-based intervention and Study 2 employed a standard 8-week Mindfulness-Based Stress Reduction (MBSR) intervention. We hypothesized that Monitor+Accept training would lead to reductions in the inflammatory biomarker C-Reactive Protein (CRP) compared to Monitor Only training and control groups. Contrary to this hypothesis, we found that Monitor+Accept mindfulness training did not lead to reductions in CRP. Exploratory analyses combining study subsamples, however, suggest that both mindfulness interventions may reduce CRP in populations at risk for systemic inflammation-midlife-to-older adults and individuals with high BMI. Overall, the present studies contribute significantly to the question of whether mindfulness interventions can reduce systemic markers of low-grade inflammation.

The effect of breastfeeding on breast aesthetics.

BACKGROUND: The health benefits of breast milk for infants are well documented, but breastfeeding is avoided by many women because of concerns about a negative effect upon breast appearance. However, there is very little objective data to either support or refute this view. OBJECTIVE: The purpose of this study is to identify risk factors for the development of breast ptosis after pregnancy and to determine whether breastfeeding has an adverse effect on breast shape. METHODS: Charts were reviewed of all patients seeking consultation for aesthetic breast surgery between 1998 and 2006. History of pregnancies, breastfeeding, and weight gain were obtained via telephone interview. Degree of breast ptosis was determined from preoperative photos. Nulliparous women were excluded. Logistic regression analysis was performed to identify independent predictors of postpregnancy breast ptosis. RESULTS: Ninety-three patients met the study criteria. Fifty-four patients (58%) reported a history of breastfeeding. The mean age at surgery in the breastfeeding group was 41 years, compared to 37 years in the nonbreastfeeding group. An adverse change in breast shape following pregnancy was described by 51 respondents (55%). Greater age, higher body mass index, greater number of pregnancies, larger prepregnancy bra size, and smoking were identified as significant independent risk factors for postpregnancy breast ptosis (P < .05). Breastfeeding was not found to be an independent risk factor for ptosis. CONCLUSIONS: The risk of breast ptosis increases with each pregnancy, but breastfeeding does not seem to worsen these effects. Expectant mothers should be reassured that breastfeeding does not appear to have an adverse effect upon breast appearance.