In cross-sectional studies of depressed patients, relationships between depression and levels of IL-8 are inconsistent, and have not been examined in relation to sex. Given identified sex differences ...in longitudinal data, it is important to evaluate sex-specific cross-sectional relationships between IL-8 and depressive symptoms, which may explain some inconsistency in the extant literature. It is further unknown whether IL-8 levels may relate to specific symptom profiles among depressed patients, with or without regard to sex.
Among 108 patients with treatment resistant depression (50 females), we evaluated cross-sectional relationships between IL-8 and depression severity, as measured by the Hamilton Depression Rating Scale HAM-D Score, and examined sex-specific relationships, as well as relationships with depressive symptom profiles. Other inflammatory markers (IL-6, IL-10, TNF-α, CRP) were also explored in relation to HAM-D.
Higher IL-8 was associated with lower total HAM-D score (standardized β = −0.19, p = 0.049). Sex-specific effects were identified (IL-8 x sex interaction: p = 0.03), in which higher IL-8 related to lower HAM-D score in females (standardized β = −0.41, p = 0.004, effect size (sr2) = 0.17), but not males (standardized β = 0.02, p = 0.91). Among a subset of 94 patients (41 females) who had individual HAM-D items available, we evaluated relationships between IL-8 and HAM-D factor subscores. Across sexes, higher IL-8 was associated with lower anxiety/hypochondriasis subscores (standardized β = −0.31, p = 0.002; sex interaction: p = 0.99). Sex differences were identified for relationships between IL-8 and two other HAM-D factor subscores.
IL-8 may be related to anxiety symptoms across sexes, but may have a sex-specific relationship with other depressive symptoms. Further evaluation of sex-specific relationships between IL-8, depression symptom profiles, treatment response, and potential neurobiological correlates, may inform mechanisms of depression pathophysiology and aid in development of precision medicine strategies.
•Among depressed females, but not males, higher IL-8 was associated with lower depression score.•Across sexes, higher IL-8 was associated with lower anxiety/hypochondriasis factor scores.•Plasma levels of other inflammatory markers (IL-6, IL-10, TNF-α, CRP) were not related to depression score.
Prenatal infection, particularly at mid-gestation, has been associated with various psychopathological outcomes in offspring; however, findings linking prenatal infection to offspring depression ...outcomes have been mixed. Previous research indicates that it may be the co-occurrence of prenatal adversities (e.g., infection and stress) that are associated with depression outcomes in offspring. Nevertheless, no study to date has investigated whether higher levels of biomarkers linked to prenatal stress (e.g., cortisol) in the presence of infection may account for these outcomes. Participants were drawn from the Child Health and Development Studies (CHDS), a prospective, longitudinal study of pregnant women and their offspring. The present study included mother-offspring dyads from the Adolescent Study, a subsample of the CHDS cohort, whose offspring were assessed in adolescence and whose mothers also provided sera to be assayed for cortisol (n = 695). Hierarchical multivariable regressions were conducted to examine whether maternal cortisol during the first and second trimesters of pregnancy interacted with maternal infection to predict increased risk for symptoms of depression in adolescent offspring. There was a significant interaction of second trimester infection and higher cortisol on offspring depression scores during adolescence, controlling for maternal education (p = 0.04). Findings suggest that higher maternal cortisol may sensitize mothers and their offspring to the disruptive influences of infection during mid-pregnancy, conferring greater risk of depressive symptomatology in offspring.
•Co-occurrence of higher cortisol with maternal infection associated with higher depressive symptoms in adolescent offspring.•This association is significant only in second trimester.•No direct association between higher cortisol or maternal infection with offspring symptoms.
Background
Cancer and its treatments may accelerate aging in survivors; however, research has not examined epigenetic markers of aging in longer term breast cancer survivors. This study examined ...whether older breast cancer survivors showed greater epigenetic aging than noncancer controls and whether epigenetic aging related to functional outcomes.
Methods
Nonmetastatic breast cancer survivors (n = 89) enrolled prior to systemic therapy and frequency‐matched controls (n = 101) ages 62 to 84 years provided two blood samples to derive epigenetic aging measures (Horvath, Extrinsic Epigenetic Age EEA, PhenoAge, GrimAge, Dunedin Pace of Aging) and completed cognitive (Functional Assessment of Cancer Therapy‐Cognitive Function) and physical (Medical Outcomes Study Short Form‐12) function assessments at approximately 24 to 36 and 60 months after enrollment. Mixed‐effects models tested survivor‐control differences in epigenetic aging, adjusting for age and comorbidities; models for functional outcomes also adjusted for racial group, site, and cognitive reserve.
Results
Survivors were 1.04 to 2.22 years biologically older than controls on Horvath, EEA, GrimAge, and DunedinPACE measures (p = .001–.04) at approximately 24 to 36 months after enrollment. Survivors exposed to chemotherapy were 1.97 to 2.71 years older (p = .001–.04), and among this group, an older EEA related to worse self‐reported cognition (p = .047) relative to controls. An older epigenetic age related to worse physical function in all women (p < .001–.01). Survivors and controls showed similar epigenetic aging over time, but Black survivors showed accelerated aging over time relative to non‐Hispanic White survivors.
Conclusion
Older breast cancer survivors, particularly those exposed to chemotherapy, showed greater epigenetic aging than controls that may relate to worse outcomes. If replicated, measurement of biological aging could complement geriatric assessments to guide cancer care for older women.
Older breast cancer survivors were biologically older than matched noncancer controls across multiple epigenetic aging measures at 24 months or more after enrollment (which was presystemic therapy for survivors). Older breast cancer survivors who had received chemotherapy showed the greatest epigenetic aging, and among this group, an older epigenetic age was associated with worse self‐reported cognition relative to controls.
Highlights • Examines sensitivity to social disconnection (SD) in context of endotoxin. • Greater sensitivity to SD was related to more inflammation in response to endotoxin. • This was found for ...both proinflammatory cytokines and multiple gene transcripts. • May have implications for links between social isolation and health.
•SES is inversely associated with inflammation in women with early-stage breast cancer.•Lower education status predicts higher levels of CRP and sTNF-RII.•BMI mediates links between lower education ...status and higher inflammation.•SES should be considered in interventions targeting BMI and health outcomes.
Breast cancer is the most common cancer among women in the US, and women of low socioeconomic status (SES) show markedly poorer outcomes than those of high SES. SES may influence health through inflammation, although links between SES and inflammatory biomarkers have not been investigated in women with breast cancer. This study tested the hypothesis that breast cancer patients of lower SES would show higher levels of inflammation than those of higher SES. BMI was examined as a mediator of this association.
Women recently diagnosed with early-stage breast cancer (N = 194) were recruited before neoadjuvant or adjuvant therapy. Participants completed questionnaires and provided blood samples for immune assessment. SES was indexed by participants’ self-reported education and annual household income, BMI was determined by height and weight measurements, and blood was assayed for inflammatory biomarkers linked with cancer outcomes: IL-6, CRP, TNF-α, and sTNF-RII. General linear models tested associations between SES and inflammation, and mediation models examined indirect effects through BMI.
Consistent with hypotheses, education status was associated with CRP, (F(2,185) = 4.72, p = 0.001), and sTNF-RII, (F(2,185) = 4.19, p = 0.02), such that lower education was associated with higher levels of both biomarkers. Further, BMI mediated the associations between education and CRP, (95% CIs -0.62, −0.11; −0.76, −0.21), sTNF-RII, (95% CIs −0.09, −0.01; −0.10, −0.02), and IL-6, (95% CIs −0.32, −0.05; −0.38, −0.09). Annual household income was not significantly associated with inflammation (ps > 0.25), and indirect effects on inflammation through BMI were not significant.
Lower education was associated with higher levels of inflammation in this sample, which may presage poor breast cancer-related and clinical outcomes. SES should inform the development of interventions targeting BMI and inflammation in breast cancer.
Sleep disturbance and aging are associated with increases in inflammation, as well as increased risk of infectious disease. However, there is limited understanding of the role of sleep loss on ...age-related differences in immune responses. This study examines the effects of sleep deprivation on toll-like receptor activation of monocytic inflammation in younger compared to older adults.
Community-dwelling adults (n = 70) who were categorized as younger (25-39 y old, n = 21) and older (60-84 y old, n = 49) participants, underwent a sleep laboratory-based experimental partial sleep deprivation (PSD) protocol including adaptation, an uninterrupted night of sleep, sleep deprivation (sleep restricted to 03:00-07:00), and recovery.
Blood samples were obtained each morning to measure toll-like receptor-4 activation of monocyte intracellular production of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Partial sleep deprivation induced a significant increase in the production of IL-6 and/or TNF-α that persisted after a night of recovery sleep (F(2,121.2) = 3.8, P < 0.05). Age moderated the effects of sleep loss, such that younger adults had an increase in inflammatory cytokine production that was not present in older adults (F(2,121.2) = 4.0, P < 0.05).
Older adults exhibit reduced toll-like receptor 4 stimulated cellular inflammation that, unlike in younger adults, is not activated after a night of partial sleep loss. Whereas sleep loss increases cellular inflammation in younger adults and may contribute to inflammatory disorders, blunted toll-like receptor activation in older adults may increase the risk of infectious disease seen with aging.
•Sleep disturbance and inflammation impair emotion perception in older adults.•Inflammation moderates the link between sleep disturbance and impaired FEP.•Sleep disturbance and inflammation serve as ...two “hits” to increase depression risk.
Facial emotion perception (FEP) is pivotal for discriminating salient emotional information. Accumulating data indicate that FEP responses, particularly to sad emotional stimuli, are impaired in depression. This study tests whether sleep disturbance and inflammation, two risk factors for depression, contribute to impaired FEP to sad emotional stimuli.
In older adults (n = 40, 71.7 ± 6.8y, 56.4% female), disturbance of sleep maintenance (i.e., wake time after sleep onset WASO) was evaluated by polysomnography. In the morning, plasma concentrations of two markers of systemic inflammation were evaluated (i.e., interleukin IL-6, tumor necrosis factor TNF-α), followed by two FEP tasks, which assessed delays in emotion recognition (ER) and ratings of perceived emotion intensity (EI) in response to sad facial emotional stimuli, with exploration of FEP responses to happiness and anger. Linear regression models tested whether WASO, IL-6, and TNF-α would be associated with impaired FEP to sad emotional stimuli. In addition, moderation tests examined whether inflammation would moderate the link between sleep disturbance and impaired FEP to sad emotional stimuli.
Longer WASO predicted longer ER delays (p < 0.05) and lower EI ratings in response to sad faces (p < 0.01). Further, higher TNF-α (p < 0.05) but not IL-6 predicted longer ER delays for sad faces, whereas higher IL-6 (p < 0.01) but not TNF-α predicted lower EI ratings for sad faces. Finally, TNF-α moderated the relationship between longer WASO and longer ER delays to sad faces (p < 0.001), while IL-6 moderated the relationship between longer WASO and lower EI ratings to sad faces (p < 0.01). Neither sleep nor inflammatory measures were associated with FEP responses to happiness or anger.
In older adults, disturbance of sleep maintenance is associated with impaired FEP to sad emotion, a relationship that appears to be moderated by inflammation. These data indicate that sleep disturbance and inflammation converge and contribute to impaired FEP with implications for risk for late-life depression.
Nonoperative management (NOM) of locally advanced rectal cancer was described as early as 2004. Initial national data demonstrated increase in utilization of NOM from 1998 to 2010, but newer national ...utilization data are not available.
We performed a retrospective cohort study using the National Cancer Database to assess utilization and 5-y overall survival (OS) of NOM of locally advanced rectal cancer. All patients had American Joint Committee on Cancer stage 2 or 3 rectal cancer, were over 40 y old, received both chemotherapy and radiation therapy, and were not being treated with palliative intent.
74,780 patients were analyzed. 64,540 (86.2%) underwent a definitive resection, 10,330 (13.8%) had NOM. Utilization of NOM steadily increased from 11.3% in 2010 to 18.6% in 2018. Multivariate regression identified the highest predictors of utilization of NOM to be uninsured status, government insurance, Black race, and treatment at a community cancer center. Multivariate regression identified NOM as the highest hazard for mortality (hazard ratio = 2.286, confidence interval 2.209-2.366). After propensity score matching, the mean estimated 5-y OS was 52.0% for those managed operatively compared to 39.8% for those managed nonoperatively.
From 2004 to 2018, the utilization of NOM of locally advanced rectal cancer significantly increased. However, there was a significant discrepancy in OS in comparison to surgical resection for these patients. Further study is needed to determine the long-term oncologic safety of NOM.
It has been established that inflammation leads to a variety of changes in social experience, but one area of social experience that has been overlooked is subjective social status. Furthermore, ...given sex differences in the relationship between inflammation and social status, males may be more sensitive to inflammation-induced changes in social status. However, no previous studies in humans have examined this possibility. In the present study, healthy young participants (
n
= 115) were randomly assigned to receive either endotoxin, an experimental inflammatory challenge, or placebo. Participants reported their subjective social status at baseline (prior to injection), and approximately 2 h later (time of peak inflammatory response for the endotoxin group). Results, using ANCOVA analyses, indicated that males exposed to endotoxin, but not females, reported lower levels of subjective social status at the peak of inflammatory response (vs. placebo). These results suggest that males may be more sensitive to the effects of inflammation in certain social domains, such as perceived social status.
Clinical Trial Registration:
www.ClinicalTrials.gov
, identifier NCT01671150.
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