Understanding associations of early-life adversities with mid-life inflammatory profiles: Evidence from the UK and USA.

OBJECTIVES: In two cohorts, we aimed to establish associations between early-life adversities and adult inflammation, and whether adult (a) adiposity or (b) socioeconomic disadvantage are key intermediaries. METHODS: In both cohorts (N = 7661, 1958 British birth cohort; N = 1255, MIDUS), information was used on adult inflammatory markers (C-reactive protein (CRP), fibrinogen and (MIDUS only) interleukin-6 (IL-6)), adiposity and socioeconomic disadvantage, and early-life adversities (neglect, emotional neglect, physical, psychological, sexual abuse and childhood disadvantage). RESULTS: Early-life adversities varied from 1.6% (sexual abuse, 1958 cohort) to 14.3% (socioeconomic disadvantage, MIDUS). Across the two cohorts, associations were consistent for physical abuse, e.g. 16.3%(3.01,29.7) and 17.0%(-16.4,50.3) higher CRP in the 1958 cohort and MIDUS respectively. Associations attenuated after accounting for adult adiposity, e.g. physical abuse (1958 cohort) and sexual abuse (MIDUS, non-white participants) associations were abolished. Some associations attenuated after adjustment for adult socioeconomic disadvantage; e.g. 1958 cohort neglect-CRP associations reduced from 23.2%(13.7,32.6) to 17.7%(8.18,27.2). Across the cohorts, no associations were found for psychological abuse or emotional neglect; associations for childhood socioeconomic disadvantage were inconsistent. CONCLUSIONS: Specific early-life adversities are associated with adult inflammation; adiposity is a likely intermediary factor. Weight reduction and obesity prevention may offset pro-inflammatory related adult disease among those who experienced early-life adversities.

Examining the cross-sectional and longitudinal association between diurnal cortisol and neighborhood characteristics: Evidence from the multi-ethnic study of atherosclerosis.

We examined cross-sectional and longitudinal associations between neighborhood socioeconomic status, social cohesion and safety and features of the diurnal cortisol curve including: area under the curve (AUC), wake-to-bed slope, wake-up, cortisol awakening response (CAR, wake-up to 30 min post-awakening), early decline (30 min to 2 h post-awakening) and late decline (2 h post-awakening to bed time). In cross-sectional analyses, higher neighborhood poverty was associated with a flatter early decline and a flatter wake-to-bed slope. Higher social cohesion and safety were associated with higher wake-up cortisol, steeper early decline and steeper wake-to-bed slope. Over 5 years, wake-up cortisol increased, CAR, early decline, late decline and wake-to-bed slope became flatter and AUC became larger. Higher poverty was associated with less pronounced increases in wake-up and AUC, while higher social cohesion was associated with greater increases in wake-up and AUC. Adverse neighborhood environments were cross-sectionally associated with flatter cortisol profiles, but associations with changes in cortisol were weak and not in the expected direction.

Sleep and multisystem biological risk: a population-based study.

BACKGROUND: Short sleep and poor sleep quality are associated with risk of cardiovascular disease, diabetes, cancer, and mortality. This study examines the contribution of sleep duration and sleep quality on a multisystem biological risk index that is known to be associated with morbidity and mortality. METHODS: Analyses include a population-based sample from the Midlife Development in the United States survey recruited to the Biomarker substudy. A total of 1,023 participants aged 54.5 years (SD = 11.8), 56% female and 77.6% white, were included in the analyses. A multisystem biological risk index was derived from 22 biomarkers capturing cardiovascular, immune, lipid-metabolic, glucose-metabolic, sympathetic, parasympathetic, and hypothalamic-pituitary-adrenal systems. Self-reported average sleep duration was categorized as short (<5 hrs), below normal (5 to <6.5 hrs), normal (6.5 to <8.5 hrs), and long sleepers (8.5+ hrs). Sleep quality was determined using the Pittsburgh Sleep Quality Index categorized as normal (≤5) and poor quality (>5) sleep. FINDINGS: Linear mixed effect models adjusting for age, gender, race, education, income, BMI, and health status were performed. As compared to normal sleepers, multisystem biological risk in both short (B(SE) = .38(.15), p<.01) and long sleepers (B(SE) = .28(.11), p<.01) were elevated. Poor quality sleep alone was associated with elevated multisystem biological risk (B(SE) = .15(.06), p = .01), but was not significant after adjustment for health status. All short sleepers reported poor sleep quality. However in the long sleepers, only those who reported poor sleep quality exhibited elevated multisystem biological risk (B(SE) = .93(.3), p = .002). CONCLUSIONS: Self-reported poor sleep quality with either short or long sleep duration is associated with dysregulation in physiological set points across regulatory systems, leading to elevated multisystem biological risk. Physicians should inquire about sleep health in the assessment of lifestyle factors related to disease risk, with evidence that healthy sleep is associated with lower multisystem biological risk.

Social status and biological dysregulation: the "status syndrome" and allostatic load.

Data from a national sample of 1255 adults who were part of the MIDUS (Mid-life in the U.S.) follow-up study and agreed to participate in a clinic-based in-depth assessment of their health status were used to test the hypothesis that, quite part from income or educational status, perceptions of lower achieved rank relative to others and of relative inequality in key life domains would be associated with greater evidence of biological health risks (i.e., higher allostatic load). Results indicate that over a variety of status indices (including, for example, the person's sense of control, placement in the community rank hierarchy, perception of inequality in the workplace) a syndrome of perceived relative deprivation is associated with higher levels of biological dysregulation. The evidence is interpreted in light of the well-established associations between lower socio-economic status and various clinically identified health morbidities. The present evidence serves, in effect, both as a part of the explanation of how socio-economic disparities produce downstream morbidity, and as an early warning system regarding the ultimate health effects of currently increasing status inequalities.

History of socioeconomic disadvantage and allostatic load in later life.

There is a growing interest in understanding how the experience of socioeconomic status (SES) adversity across the life course may accumulate to negatively affect the functioning of biological regulatory systems important to functioning and health in later adulthood. The goal of the present analyses was to examine whether greater life course SES adversity experience would be associated with higher scores on a multi-system allostatic load (AL) index of physiological function in adulthood. Data for these analyses are from 1008 participants (92.2% White) from the Biomarker Substudy of the Study of Midlife in the US (MIDUS). Multiple indicators of SES adversity in childhood (parent educational attainment, welfare status, financial situation) and two points in adulthood (educational attainment, household income, difficulty paying bills, availability of money to meet basic needs, current financial situation) were used to construct SES adversity measures for each life course phase. An AL score was constructed using information on 24 biomarkers from 7 different physiological systems (sympathetic and parasympathetic nervous systems, hypothalamic-pituitary-adrenal axis, cardiovascular, lipid metabolism, glucose metabolism, inflammatory immune activity). Analyses indicate higher AL as a function of greater SES adversity at each phase of, and cumulatively across, the life course. Associations were only moderately attenuated when accounting for a wide array of health status, behavioral and psychosocial factors. Findings suggest that SES adversity experience may cumulate across the life course to have a negative impact on multiple biological systems in adulthood. An important aim of future research is the replication of current findings in this predominantly White sample in more ethnically diverse populations.

Neighborhood disadvantage and ischemic stroke: the Cardiovascular Health Study (CHS).

BACKGROUND AND PURPOSE: Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status and incident ischemic stroke and examine potential mediators of these associations. METHODS: We analyzed data from 3834 whites and 785 blacks enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages≥65 years from 4 US counties. The primary outcome was adjudicated incident ischemic stroke. Neighborhood socioeconomic status was measured using a composite of 6 census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed adjusted for sociodemographic, behavioral, and biological risk factors. RESULTS: Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared with the highest neighborhood socioeconomic status quartile (hazard ratio, 1.32; 95% CI, 1.01-1.72) with greater attenuation of the hazard ratio after adjustment for biological risk factors (hazard ratio, 1.16; 0.88-1.52) than for behavioral risk factors (hazard ratio, 1.30; 0.99-1.70). Among blacks, we found no significant associations between neighborhood socioeconomic status and ischemic stroke. CONCLUSIONS: Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among blacks. The relationship between neighborhood socioeconomic status and stroke among whites appears to be mediated more strongly by biological than behavioral risk factors.

Histories of social engagement and adult cognition: midlife in the U.S. study.

OBJECTIVES: To evaluate whether social contacts, support, and social strain/conflict are related to executive function and memory abilities in middle-age and older adults. METHODS: Longitudinal data on social contacts, support, and strain/conflict were examined in relation to executive function and memory at ages 35-85 years using data from the national Midlife in the U.S. (MIDUS) study. Age-related differences in patterns of association were also examined. RESULTS: Regression analyses, controlling for age, sex, race, education, chronic health conditions, and health behaviors, revealed significant positive associations between histories of greater social contacts and support and both executive function and episodic memory, whereas declines in social contacts were negatively associated with both outcomes. Greater average reported frequency of social exchanges characterized by strain or conflict was negatively associated with executive function but not episodic memory. Patterns were generally consistent across different age groups; where differences were seen, associations were stronger in younger age group. DISCUSSION: Positive and negative aspects of social relationships are related to cognition throughout adulthood, consistent with the hypothesis that social factors have life-long influences on cognition. Positive and negative aspects of social engagement may thus be important factors to consider in relation to efforts to promote optimal cognitive development and cognitive aging.