Kharah M. Ross

How stable are diurnal cortisol activity indices in healthy individuals? Evidence from three multi-wave studies.

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 11h 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 (ICCs). 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, ICCs 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.

Social encounters in daily life and 2-year changes in metabolic risk factors in young women

Research shows that poor social ties increase risks of morbidity and mortality from cardiovascular disease (CVD). However, little is known about the nature of everyday social encounters that give rise to this association, or when in the course of development they begin to shape disease-relevant biological processes. In this study, 122 adolescent females recorded the qualities of their everyday social interactions using electronic diaries. At the same time we measured components of the metabolic syndrome, a precursor to CVD that includes central adiposity, high blood pressure, insulin resistance, and lipid dysregulation. Metabolic symptoms were reassessed 12 and 24 months later. Hierarchical linear modeling revealed an association between negative social interactions and metabolic symptom trajectories. To the extent that participants had more intense negative social encounters in daily life, they showed increasing scores on a composite indicator of metabolic risk over 2 years. This association was independent of a variety of potential confounders, and persisted when symptoms of depression and broader personality traits were controlled. There was no association between positive social encounters and metabolic risk trajectories. These findings suggest that even in otherwise healthy adolescents, abrasive social encounters may accelerate the progression of early stages of CVD.

Modeling the Association between Lifecourse Socioeconomic Disadvantage and Systemic Inflammation in Healthy Adults: The Role of Self-Control

OBJECTIVE We sought to identify pathways connecting lifecourse socioeconomic status (SES) with chronic, low-grade inflammation, focusing on the explanatory roles of self-control, abdominal adiposity, and health practices. METHODS Participants were 360 adults aged 15-55 who were free of chronic medical conditions. They were roughly equally divided between low and high current SES, with each group further divided between low and high early-life SES. Structural equation modeling (SEM) was used to identify direct and indirect pathways linking early-life and current SES with low-grade, chronic inflammation in adulthood, as manifest by serum interleukin-6 and C-reactive protein. Low SES was hypothesized to relate to inflammation by reducing self-control, which in turn was hypothesized to facilitate lifestyle factors that potentiate inflammation (smoking, alcohol use, sedentary behavior, and weight gain). RESULTS Analyses revealed that self-control was pivotal in linking both early-life and current SES to inflammation. Low early-life SES was related to a harsher family climate, and in turn lower adult self-control, over and above the effects of current SES. Controlling for early-life SES, low current SES was associated with perceived stress and, in turn, diminished self-control. Results showed that lower self-control primarily operated through higher abdominal adiposity to associate with greater inflammation. CONCLUSIONS The findings suggest a mechanistic scenario wherein low SES in early life or adulthood depletes self-control and, in turn, fosters adiposity and inflammation. These pathways should be studied longitudinally to elucidate and potentially ameliorate socioeconomic disparities in health.

Oxytocin does not attenuate the ex vivo production of inflammatory cytokines by lipopolysaccharide-activated monocytes and macrophages from healthy male and female donors.

Background: Oxytocin (OT) is a neuropeptide shown to attenuate inflammatory responses in both humans and animals, but the specific mechanism underlying these actions has not yet been identified. Preliminary research in humans suggests that monocytes (MOs) and macrophages (MPs) could be the target of anti-inflammatory actions of OT. Here, we present a series of ex vivo experiments in human MOs and MPs, testing whether OT attenuates the cytokine responses of these cells to a common bacterial product, lipopolysaccharide (LPS). Methods: MO experiments were conducted using blood samples taken from healthy volunteers after obtaining informed consent. MPs were purchased frozen from a cell supplier. All samples were cultured under standard conditions: for 6 h at 37°C in a 5% CO2 atmosphere. A number of variables were considered: volunteer sex, method of MO isolation, LPS concentration, OT concentration, preincubation with OT, cytokines measured, and method of cytokine measurement. Results: Regardless of the specific conditions, no attenuation of LPS-stimulated cytokine production by OT was observed in either MOs or MPs. Conclusion: OT does not attenuate MO or MP inflammatory cytokine production following LPS stimulation. The previously observed anti-inflammatory properties of OT may be attributable to effects on other classes of immune cells or actions in other lymphoid compartments. Alternatively, the effects of OT on inflammation could be secondary to other neurohormonal changes it elicits.

Maternal socioeconomic disadvantage is associated with transcriptional indications of greater immune activation and slower tissue maturation in placental biopsies and newborn cord blood

Children from economically disadvantaged families experience worse cognitive, psychiatric, and medical outcomes compared to more affluent youth. Preclinical models suggest some of the adverse influence of disadvantage could be transmitted during gestation via maternal immune activation, but this hypothesis has not been tested in humans. It also remains unclear whether prenatal interventions can mitigate such effects. To fill these gaps, we conducted two studies. Study 1 characterized the socioeconomic conditions of 79 women during pregnancy. At delivery, placenta biopsies and umbilical blood were collected for transcriptional profiling. Maternal disadvantage was associated with a transcriptional profile indicative of higher immune activation and slower fetal maturation, particularly in pathways related to brain, heart, and immune development. Cord blood cells of disadvantaged newborns also showed indications of immaturity, as reflected in down-regulation of pathways that coordinate myeloid cell development. These associations were independent of fetal sex, and characteristics of mothers (age, race, adiposity, diabetes, pre-eclampsia) and babies (delivery method, gestational age). Study 2 performed the same transcriptional analyses in specimens from 20 women participating in CenteringPregnancy, a group-based psychosocial intervention, and 20 women in traditional prenatal care. In both placenta biopsies and cord blood, women in CenteringPregnancy showed up-regulation of transcripts found in Study 1 to be most down-regulated in conjunction with disadvantage. Collectively, these results suggest socioeconomic disparities in placental biology are evident at birth, and provide clues about the mechanistic origins of health disparities. They also suggest the possibility that psychosocial interventions could have mitigating influences.

Genome-Wide Profiling of RNA from Dried Blood Spots: Convergence with Bioinformatic Results Derived from Whole Venous Blood and Peripheral Blood Mononuclear Cells.

ABSTRACT Genome-wide transcriptional profiling has emerged as a powerful tool for analyzing biological mechanisms underlying social gradients in health, but utilization in population-based studies has been hampered by logistical constraints and costs associated with venipuncture blood sampling. Dried blood spots (DBS) provide a minimally invasive, low-cost alternative to venipuncture, and in this article we evaluate how closely the substantive results from DBS transcriptional profiling correspond to those derived from parallel analyses of gold-standard venous blood samples (PAXgene whole blood and peripheral blood mononuclear cells [PBMC]). Analyses focused on differences in gene expression between African-Americans and Caucasians in a community sample of 82 healthy adults (age 18–70 years; mean 35). Across 19,679 named gene transcripts, DBS-derived values correlated r = .85 with both PAXgene and PBMC values. Results from bioinformatics analyses of gene expression derived from DBS samples were concordant with PAXgene and PBMC samples in identifying increased Type I interferon signaling and up-regulated activity of monocytes and natural killer (NK) cells in African-Americans compared to Caucasian participants. These findings demonstrate the feasibility of DBS in field-based studies of gene expression and encourage future studies of human transcriptome dynamics in larger, more representative samples than are possible with clinic- or lab-based research designs.

Patterns of peripheral cytokine expression during pregnancy in two cohorts and associations with inflammatory markers in cord blood.

Maternal inflammation undergoes adaptations during pregnancy, and excessive inflammation has been associated with adverse outcomes. One mechanism may be maternal inflammation transmission to the fetal compartment. Links between maternal pregnancy inflammation and fetal inflammation are poorly characterized.

Early-life socioeconomic disadvantage and metabolic health disparities

Objective A quarter of the worlds population have metabolic syndrome (MetS). MetS prevalence is stratified by socioeconomic status (SES), such that low SES is associated with higher MetS risk. The present study examined the relative roles of early-life SES and current SES in explaining MetS risk. Methods Participants (N = 354; ages = 15–55 years, M [SD] = 36.5 [10.7] years; 55% female; 72.9% white, 16.9% Asian, 10.2% others) were evaluated for SES and MetS. All were in good health, defined as free of chronic medical illness and acute infectious disease. Using occupational status as a proxy for SES, we recruited roughly equal numbers of participants with low-low, low-high, high-low, and high-high combinations of early-life and current SES. We used the International Diabetes Federation definition for MetS using race- and sex-specific cutoffs for waist circumference, triglyceride levels, high-density lipoprotein cholesterol, blood pressure, and glycosylated hemoglobin levels. Results Analyses revealed a main effect of low early-life SES on increased MetS risk according to the three separate definitions. They included the traditional MetS diagnosis (odds ratio [OR] = 1.53, confidence interval [CI] = 1.01–2.33, p = .044), the number of MetS components for which diagnostic thresholds were met (OR = 1.61, CI = 1.10–2.38, p = .015), and a continuous indicator of metabolic risk based on factor analysis (F(1,350) = 6.71, p = .010, partial &eegr;2 = .019). There was also a significant interaction of early-life SES and current SES in predicting MetS diagnosis (OR = 1.54, CI = 1.02–2.34). The main effects of current SES were nonsignificant in all analyses. Conclusions These findings suggest that MetS health disparities originate in childhood, which may be an opportune period for interventions.

Close relationship qualities and maternal peripheral inflammation during pregnancy

OBJECTIVE Close relationships are associated with pregnancy outcomes, but little is known about the mechanisms involved. This paper examines whether quality of womens close relationships, specifically with romantic partner (RP) and closest friend or family member (CF), is associated with inflammatory biomarkers during the third trimester of pregnancy. METHODS 90 pregnant women were assessed during the second and third trimester. At both visits they completed self-reports describing the positive and negative aspects of their RP and CF relationships. Peripheral blood was collected during these visits, and used to measure systemic levels of cytokines, including IFNγ, IL10, IL6, IL8 and IL13. An index of inflammatory regulation, as reflected by the ratio of IL6:IL10, was also computed. RESULTS Positive (e.g. support, intimacy) and negative (e.g. conflict) aspects of the RP relationship interacted to predict third trimester cytokine values. Specifically, RP relationships relatively low in both positive and negative aspects were associated with lower third trimester anti-inflammatory (IL10, IL13) and anti-viral (IFNγ) cytokines, and a higher IL6:IL10 ratio, controlling for second trimester levels. These associations were independent of demographics, gestational age, weeks between assessment, parity, pre-pregnancy body mass index, maternal stress, distress, depressed mood and RP cohabitation. CF relationship aspects were not associated with inflammatory markers. CONCLUSIONS RP relationships relatively low in both positive, e.g. support and intimacy, and negative, e.g. conflict, aspects were associated with a less anti- and more pro-inflammatory cytokine profile during the third trimester. These findings have implications for understanding the associations amongst close relationships, inflammation, and potentially pregnancy outcomes.

Interactions between race/ethnicity, poverty status, and pregnancy cardio-metabolic diseases in prediction of postpartum cardio-metabolic health

ABSTRACT Background: Prenatal health disparities exist for African Americans and low socioeconomic status (SES) individuals when compared to non-Hispanic Whites and people of higher SES, particularly in cardio-metabolic diseases. Furthermore, having had a pregnancy-specific cardio-metabolic disease, e.g. preeclampsia, increases risk for future cardio-metabolic disease. Although these factors (race, SES and pregnancy cardio-metabolic disease) are interrelated, studies have rarely considered their combined effect on postpartum cardio-metabolic risk. The purpose of this study was to assess whether SES, race/ethnicity, and prenatal cardio-metabolic disease interact in the prediction of postpartum cardio-metabolic risk. Methods: A sample of 1,753 low-income women of African American, Latina, non-Hispanic White race/ethnicity was recruited after a birth in 5 US sites. Household income was used to categorize poverty status as Poor (< Federal Poverty Level; FPL), near poor (100–200% FPL), or low/middle income (> 200% FPL). Three prenatal cardio-metabolic disease diagnoses (preeclampsia, gestational hypertension, gestational diabetes) were identified from medical records. Four biomarkers (mean arterial pressure, glycosylated haemoglobin, total cholesterol:HDL ratio, and waist-hip ratio) were collected at 6 and 12 months postpartum, and combined into an average postpartum cardio-metabolic risk index. Maternal age, pre-pregnancy body mass index, parity, health behaviors and employment status were covariates. Results: Analyses revealed interactions of race/ethnicity, poverty status, and prenatal cardio-metabolic diseases in the prediction of postpartum cardio-metabolic risk. African American women had higher postpartum cardio-metabolic risk, which was exacerbated following a prenatal cardio-metabolic disease. Low/middle income African American women had higher cardio-metabolic risk compared to poor African American, and all Latina and White women. Conclusions: African American women, and especially those who experienced pregnancy complications, emerged as vulnerable, and greater household income did not appear to confer protection against worse postpartum cardio-metabolic risk for this group. These results highlight the complex interplay between socioeconomic status and race/ethnicity with respect to understanding health disparities.