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).

Socioeconomic disparities of depressive symptoms and cytokines in hepatocellular carcinoma.

OBJECTIVE: To examine the associations among socioeconomic factors, depressive symptoms, and cytokines in patients diagnosed with hepatocellular carcinoma (HCC). METHODS: A total of 266 patients diagnosed with HCC were administered a battery of questionnaires including a sociodemographic questionnaire and the Center for Epidemiologic StudiesDepression (CES-D) scale. Blood samples were collected to assess serum levels of cytokines using Luminex. Descriptive statistics, Mann-Whitney U, Kruskal-Wallis, linear regression, and Bonferroni corrections were performed to test the hypotheses. RESULTS: Of the 266 patients, 24% reported depressive symptoms in the clinical range (CES-D ≥ 22). Females had higher CES-D score than males (Mann-Whitney U = 7135, P = .014, Padj  = .028). Being unemployed/disabled (Kruskal-Wallis = 14.732, P = .001, Padj  = .005) was found to be associated with higher depressive symptoms in males but not in females. Serum level of IL-2 (Kruskal-Wallis = 17.261, P = .001, Padj  = .005) were found to be negatively associated with education level. Gender (ß = .177, P = .035), income (ß = -.252, P = .004), whether the patient's income met their basic needs (ß = .180, P = .035), and IL-1ß (ß = -.165, P = .045) independently predicted depressive symptoms and together explained 19.4% of variance associated with depressive symptoms. CONCLUSIONS: Sociodemographic and socioeconomic factors were predictive of inflammation and depressive symptoms. Recommendations include the development of gender-targeted interventions for patients diagnosed with HCC who have low socioeconomic status (SES) and may suffer from depressive symptoms.

Sleep duration partially accounts for race differences in diurnal cortisol dynamics.

OBJECTIVE: Emerging research demonstrates race differences in diurnal cortisol slope, an indicator of hypothalamic-pituitary-adrenocortical (HPA)-axis functioning associated with morbidity and mortality, with African Americans showing flatter diurnal slopes than their White counterparts. Sleep characteristics are associated with both race and with HPA-axis functioning. The present report examines whether sleep duration may account for race differences in cortisol dynamics. METHOD: Participants were 424 employed African American and White adults (mean age = 42.8 years, 84.2% White, 53.6% female) with no cardiovascular disease (Adult Health and Behavior Project-Phase 2 [AHAB-II] cohort, University of Pittsburgh). Cortisol slope was calculated using 4 salivary cortisol readings, averaged over each of 4 days. Demographic (age, sex), psychosocial (socioeconomic status [SES], affect, discrimination), and health behaviors (smoking, alcohol use, physical activity) variables were used as covariates, and sleep (self-report and accelerometry) was also assessed. RESULTS: African Americans had flatter slopes than Whites (F(1, 411) = 10.45, B = .02, p = .001) in models adjusting for demographic, psychosocial, and health behavior covariates. Shorter actigraphy-assessed total sleep time was a second significant predictor of flatter cortisol slopes (F(1, 411) = 25.27, B = -.0002, p < .0001). Total sleep time partially accounted for the relationship between race and diurnal slope [confidence interval = .05 (lower = .014, upper .04)]. CONCLUSIONS: African Americans have flatter diurnal cortisol slopes than their White counterparts, an effect that may be partially attributable to race differences in nightly sleep duration. Sleep parameters should be considered in further research on race and cortisol. (PsycINFO Database Record

Sleep duration is associated with survival in advanced cancer patients.

OBJECTIVE: Sleep problems have been linked to increased risk of mortality in the general population. Limited evidence suggests similar relationships among people diagnosed with cancer. The aims of the present study were to investigate the type and rates of sleep problems in advanced cancer patients and examine whether sleep problems are associated with survival. METHODS: A prospective study of 292 patients with advanced cancers affecting the hepatobiliary and pancreatic systems were administered a battery of questionnaires measuring sociodemographic information, sleep, and depression. Descriptive statistics, ANOVA, Chi-square, Kaplan-Meier survival, and Cox regression analyses were performed to test the aims. RESULTS: The majority of patients were male (64%) and the mean age was 62 years (SD = 11). Fifty-nine percent of patients reported poor sleep quality; 43% reported sleeping ≤6 h and 2% ≥10 h; 40% reported sleep latency of 30 min or greater; average sleep efficiency was 80%. Of the 292 patients, 58% reported clinically levels of depression and depressive symptoms were related to shorter sleep duration (p = 0.02). After adjusting for factors known to contribute to survival, a curvilinear relationship was observed between sleep duration and mortality: short and long sleep duration were associated with increased mortality [linear term: hazard ratio (HR) = 0.485, 95% confidence interval (CI) = 0.275-0.857; quadratic term: HR = 1.064, 95% CI = 1.015-1.115]. CONCLUSIONS: Consistent with findings in the general population, a curvilinear relationship between sleep duration and mortality was observed in advanced cancer patients. The high prevalence of sleep problems and link with mortality warrants routine screening and development of evidence-based treatments for sleep problems in the oncology setting.

Daily social interactions, close relationships, and systemic inflammation in two samples: Healthy middle-aged and older adults.

OBJECTIVE: Systemic inflammation is thought to be a biological mediator between social relationship quality and premature mortality. Empirical work has yielded mixed support for an association of social relationship variables with systemic inflammation, perhaps due to methodological limitations. To date, research in this literature has focused on global perceptions of social relationships, with limited attention to the covariance of characteristics of daily social interactions with inflammation. Here, we examine whether daily interactions, as assessed by ecological momentary assessment (EMA), associate with peripheral markers of inflammation among midlife and older adults. METHODS: Global social support and integration were measured using the Interpersonal Support Evaluation List (ISEL) and the Social Network Index (SNI), respectively, in older adults from the Pittsburgh Healthy Heart Project (PHHP), and in middle-aged adults from the Adult Health and Behavior Project-II (AHAB-II). Using time-sampled EMA, we assessed the proportion of the day spent in positive and negative social interactions. Systemic markers of inflammation were interleukin (IL)-6 and C-reactive protein (CRP). RESULTS: Global measures of support and integration did not associate with inflammation in either sample. In older adults, relative frequency of total positive interactions, those with close others (i.e. spouse, friends, family), and those with coworkers predicted lower concentrations of IL-6 in fully adjusted models, accounting for age, sex, race, education, BMI, smoking and alcohol. In middle-aged adults, relative frequency of positive interactions with close others was also inversely associated with IL-6 level and relative frequency of negative marital interactions was unexpectedly inversely associated with CRP level. CONCLUSIONS: Characteristics of daily social interactions among midlife and older adults associate with markers of systemic inflammation that are known to predict risk for cardiovascular disease. Ambulatory measures may better capture health-relevant social processes in daily life than retrospective, global self-report measures.

Childhood Socioeconomic Status and the Occurrence of Recent Negative Life Events as Predictors of Circulating and Stimulated Levels of Interleukin-6.

OBJECTIVES: Evidence supports an inverse association of childhood socioeconomic status (SES) with systemic inflammation in adulthood. However, it remains to be determined whether this association is dependent on exposure to stressful life experiences. METHODS: We predicted that the combination of a high number of recent negative life events and low childhood SES would be associated with the highest levels of both circulating interleukin (IL)-6 and lipopolysaccharide-stimulated production of IL-6. We tested this prediction among a community sample of 459 adults (47% male, mean [standard deviation] age = 42.8 [7.3] years). RESULTS: Inverse associations were found between childhood and adult SES indices with circulating IL-6 levels (r values between -0.07 and -0.16, p < .05) but not stimulated IL-6 levels (r values between -0.007 and 0.07, p > .05). The number of recent negative life events (mean [standard deviation] = 2.43 [2.34]) was not significantly related to subjective childhood SES and other SES indices (r values < 0.06, p > .10). Multivariate linear regression analyses revealed a significant association between the interaction of subjective childhood SES and recent negative life events and circulating IL-6 (ß = -0.09, t(404) = -1.98, p = .049) and a marginally significant association with stimulated levels of IL-6 (ß = -0.10, t(365) = -1.94, p = .054), whereas these covariate-adjusted models revealed no main effects for subjective SES or recent negative life events. CONCLUSIONS: The relationship between childhood SES and IL-6 seems to be moderated by recent life events, such that individuals with a relatively low childhood SES exhibit an inflammatory phenotype in the context of a high number of recent negative life events.

Daily marital interaction quality and carotid artery intima-medial thickness in healthy middle-aged adults.

OBJECTIVE: To examine the association between marital interaction quality during daily life and subclinical cardiovascular disease (CVD). Studies have shown that marital status and quality of marriage are associated with cardiovascular health. However, little is known about the role of marital interaction quality during daily life in contributing to these effects. METHODS: The sample consisted of 281 healthy, employed middle-aged adults who were married or living with a partner in a marital-like relationship (mean age = 42.0 years, 88% white, 52% men). Marital interaction quality was assessed using hourly real-time ecological momentary assessments for 4 days, with participants rating their current or recent partner interactions on positive and negative characteristics (e.g., agreeableness and conflict). Carotid artery intima-medial thickness (IMT) was assessed using ultrasound imaging. RESULTS: Adjusting for demographics, positive marital interaction was inversely associated with IMT (b = -0.02, F(1,275) = 9.18, p = .002), and negative marital interaction was positively associated with IMT (b = 0.02 F(1,275) = 10.29, p = .001). These associations were not accounted for by behavioral and biological CVD risk factors and were consistent across age, sex, race, and education. The associations were also independent of marital interaction frequency, nonmarital social interaction quality, and personality factors. Global reports of marital quality, in contrast, were not associated with IMT. CONCLUSIONS: Marital quality as measured during real-time interactions between partners was associated with subclinical CVD in healthy middle-aged adults. This study supports the use of real-time social interaction assessment for characterizing links between social relationships and cardiovascular health.

Depressive symptom clusters as predictors of 6-year increases in insulin resistance: data from the Pittsburgh Healthy Heart Project.

OBJECTIVE: To examine longitudinal bidirectional associations between two depressive symptom clusters-the cognitive-affective and somatic-vegetative clusters--and insulin resistance, a marker of prediabetes. METHODS: Participants were 269 adults aged 50 to 70 years without diabetes enrolled in the Pittsburgh Healthy Heart Project, a prospective cohort study. At baseline and 6-year visits, participants completed the Beck Depression Inventory-II (BDI-II) and underwent a blood draw to quantify fasting insulin and glucose. We examined baseline BDI-II total, cognitive-affective, and somatic-vegetative scores as predictors of 6-year change in the homeostatic model of assessment (HOMA) score, an estimate of insulin resistance computed from fasting insulin and glucose. We also examined baseline HOMA score as a predictor of 6-year change in BDI-II total and subscale scores. RESULTS: Regression analyses, adjusted for demographic factors and baseline HOMA score, revealed that the baseline BDI-II somatic-vegetative score (ß = 0.14, p = .025), but not the cognitive-affective (ß = 0.001, p = .98) or total (ß = 0.10, p = .11) scores, predicted 6-year HOMA change. This result persisted in models controlling for anxiety symptoms and hostility. Several factors were examined as candidate mediators; however, only change in body mass index was a significant mediator (p = .042), accounting for 23% of the observed association. Baseline HOMA score did not predict 6-year change in BDI-II total or subscale scores (all p values >.56). CONCLUSIONS: Among adults aged 50 to 70 years, the somatic-vegetative symptoms of depression (e.g., fatigue, sleep disturbance, and appetite changes) may worsen insulin resistance and increase diabetes risk, partly, by increasing body mass index.

Sleep duration and cardiovascular responses to stress in undergraduate men.

Short sleep has been related to incident cardiovascular disease, but physiological mechanisms accounting for this relationship are largely unknown. This study examines sleep duration and cardiovascular stress responses in 79 healthy, young men. Sleep duration was assessed by wrist actigraphy for seven nights. Participants then completed a series of laboratory stress tasks while heart rate and blood pressure were monitored. Shorter total sleep time was related to a greater reduction in high-frequency heart rate variability during stress tasks, and to prolonged elevations in heart rate and diastolic pressure following tasks. Associations were independent of age, race, body mass index, caffeine intake, and smoking status. In sum, healthy young men with shorter actigraphy-assessed sleep exhibit less cardiac vagal activity, and poorer heart rate and diastolic blood pressure recovery, upon encountering stressful stimuli, than those with longer sleep.

Hostility, cigarette smoking, and responses to a lab-based social stressor.

High-trait hostility is associated with persistent cigarette smoking. To better understand mechanisms that may account for this association, we examined the effects of acute smoking abstinence and delayed versus immediate smoking reinstatement on responses to a social stressor among 48 low hostile (LH) and 48 high hostile (HH) smokers. Participants completed two laboratory sessions, one before which they had smoked ad lib and one before which they had abstained for the prior 12 hr. During each session, participants completed a stressful speaking task and then smoked immediately after the stressor or after a 15-min delay. The effect of immediate versus delayed smoking reinstatement on recovery in negative mood was significantly moderated by hostility. When reinstatement was delayed, HH participants showed significant increases in negative mood over time, whereas LH participants showed little change. When reinstatement was immediate, HH and LH smokers showed similar significant decreases in negative mood. Smoking abstinence did not moderate hostility effects. Cigarette smoking may prevent continuing increases in negative mood after social stress in HH smokers, which may partially explain their low rates of quitting.

A prospective evaluation of the directionality of the depression-inflammation relationship.

Cross-sectional studies have found that individuals with depressive disorders or symptoms have elevated levels of inflammatory markers predictive of coronary artery disease, including interleukin-6 (IL-6) and C-reactive protein (CRP). Due to the paucity of prospective studies, however, the directionality of the depression-inflammation relationship is unclear. We evaluated the longitudinal associations between depressive symptoms and both IL-6 and CRP among 263 healthy, older men and women enrolled in the Pittsburgh Healthy Heart Project, a 6-year prospective cohort study. During the baseline and follow-up visits, participants completed the Beck Depression Inventory-II (BDI-II) to assess depressive symptoms and underwent blood draws to quantify serum IL-6 and CRP. Path analyses revealed that baseline BDI-II (beta=0.18, p=0.01, DeltaR(2)=0.02) was a predictor of 6-year change in IL-6, even after adjustment for demographic, biomedical, and behavioral factors as well as other negative emotions. Of all the factors examined, only body-mass index was a stronger predictor of IL-6 change than depressive symptoms. In contrast to these results, baseline IL-6 did not predict 6-year change in BDI-II. Evidence of a weak bidirectional relationship between BDI-II and CRP was also observed; however, neither of these longitudinal associations was significant. The present findings indicate that depressive symptoms may precede and augment some inflammatory processes relevant to coronary artery disease among healthy, older adults. Therefore, our results imply that depression may lead to inflammation and that inflammation may be one of the mechanisms through which depression contributes to cardiovascular risk.

Depressive symptoms moderate the influence of hostility on serum interleukin-6 and C-reactive protein.

OBJECTIVE: Recent evidence suggests that depressive symptoms and hostility may act together, as interacting factors, to have an effect on the circulating levels of inflammatory markers relevant to coronary artery disease. Further research, however, is needed to clarify the nature of this interaction and to determine whether previous findings extend to older adults. In this report we examined the cross-sectional associations of depressive symptoms, hostility, and their interaction with circulating levels of two such inflammatory markers-interleukin-6 (IL-6) and C-reactive protein (CRP). METHODS: A total of 316 healthy, older adults underwent a blood draw for the assessment of serum IL-6 and CRP and completed the Beck Depression Inventory-II and the Cook-Medley Hostility Scale. Regression analyses were performed to examine depressive symptoms, hostility, and their interaction as predictors of serum IL-6 and CRP. RESULTS: After adjustment for demographic factors, cardiovascular risk factors, and health behaviors, we detected depressive symptoms x hostility interactions for serum IL-6 (DeltaR(2) = .027, p < .01) and CRP (DeltaR(2) = .015, p < .05). Simple slope analyses revealed that hostility was positively related to serum IL-6 only among individuals with higher depressive symptoms. The pattern of results was similar for serum CRP, although none of the simple slopes was significant. CONCLUSIONS: Our findings suggest that depressive symptoms may moderate the hostility-inflammation relationship such that hostility may augment inflammatory processes relevant to coronary artery disease only in the presence of depressive symptoms. Our results also extend previous findings from younger adults to older adults from the general community.

Depressive symptomatology and coronary heart disease in Type I diabetes mellitus: a study of possible mechanisms.

Recent evidence has suggested that depressive symptomatology is a risk factor for the development of coronary heart disease (CHD) in patients with diabetes mellitus, although little is understood about mechanisms that may explain this association. The Pittsburgh Epidemiology of Diabetes Complications (EDC) Study is a natural history study of 658 men and women with childhood-onset Type I diabetes. Participants from the EDC Study who reported the fewest depressive symptoms on the Beck Depression Inventory at baseline examination were least likely to develop CHD over 10 years. Differences in insulin resistance, autonomic dysregulation, inflammation, smoking, and complications associated with Type I diabetes appear to help explain this relationship. Future research should clarify causal pathways between depressive symptomatology, behavioral and physiological processes, and CHD.