Early Childhood Socioeconomic Status Is Associated With Circulating Interleukin-6 Among Mid-Life Adults

It is proposed that socioeconomic conditions in early childhood effect immune programming, with poorer conditions resulting in adult phenotypes that are prone to inflammation. Recent evidence supports this possibility, showing an inverse association of childhood SES with adult markers of systemic inflammation. In this study, we further investigate this association, extending prior studies to include an examination of multiple indices of SES across distinct periods of childhood. Subjects were 112 men and women, 40–60 years of age (88.6% Caucasian). Childhood SES was indexed by a composite of three indicators of parental wealth (parental home and vehicle ownership, and number of bedrooms per child in the family home) averaged across 2 year periods of childhood between 1 and 18 years old. Higher adult serum concentrations of interleukin (IL)-6 were associated with lower SES in early childhood (years 1–2) (β = −.05, p < .05), associations that were independent of adult age, personal income, educational attainment, gender, race, body mass index, and physical activity. These associations support recent suggestions that the early environment may program immune phenotypes that contribute to disease risk.</p

Trait positive affect and antibody response to hepatitis B vaccination

Recent evidence suggests that dispositional positive affect may be associated with decreased vulnerability to upper respiratory infections. To explore a potential pathway of this relationship, we examined whether trait positive affect is related to an in vivo immune response relevant for host resistance to infection. Eighty-four healthy, graduate students who tested negative for prior expose to the hepatitis B virus were administered the standard hepatitis B vaccination series. Five months after the first dose, a blood sample was collected for the measurement of specific antibody response to the vaccine and subjects completed a battery of psychosocial questionnaires. Higher scores on a measure of dispositional positive affect were associated with a greater antibody response to hepatitis B vaccination. This relationship occurred after controlling for demographics and body mass and was largely independent of concomitant levels of dispositional negative affect, optimism, and extraversion. In the presence of dispositional positive affect, there was no independent effect of trait negative affect on antibody response. Physical activity played a protective role for individuals low in positive affect, being related to higher antibody responses. These data provide initial evidence that individual differences in dispositional positive affect may be of health significance, being related to an in vivo immune response relevant for protection against infection.</p

Associations Between Stress, Trait Negative Affect, Acute Immune Reactivity, and Antibody Response to Hepatitis B Injection in Healthy Young Adults

Eighty-four healthy graduate participants were administered the standard course of 3 hepatitis B vaccinations. Five months after the first dose (shortly after the second injection), each participant completed psychosocial measures, and a blood sample was drawn for determination of hepatitis B surface antibody titer. After completion of the vaccination series, participants performed an acute stress protocol, consisting of a 30-min adaptation period and a 5-min evaluative speech task. Blood was drawn at the end of the resting and task periods for assessment of cellular immune measures. Lower antibody response, as assessed after the second hepatitis B injection, was predicted independently by (a) high trait negative affect and (b) diminished T-cell proliferation in response to PHA. These data provide evidence that trait negative affect and the magnitude of stress-induced suppression of immune function may have clinical significance

Childhood environments and cytomegalovirus serostatus and reactivation in adults.

<p>Childhood adversity, defined in terms of material hardship or physical or emotional maltreatment has been associated with risk for infection with cytomegalovirus (CMV) among children and adolescents, and with CMV reactivation in children and adults. The present study examined whether different dimensions of childhood experience-those pertaining to socioeconomic status (SES), physical environment, or family relationships-relate differentially to CMV serostatus and reactivation during adulthood. Participants were 140 healthy adults, aged 18-55years (41% female; 64% white). Childhood environments were assessed retrospectively and included family SES (parental housing tenure); childhood neighborhood environment (urban residence; physical conditions; safety; and social atmosphere); residential exposures (parental smoking and physical condition of home); and family relationships (parental divorce; warmth; harmony; dysfunction; parental bonding). Approximately 39% (n=53) of participants were CMV+. In individual analyses controlling for age, sex, race, body mass, current adult SES and smoking status, fewer years of parental home ownership, having a parent who smoked, and living in a poorly maintained or unsafe neighborhood each were associated with greater odds of infection with CMV. By comparison, in individual analyses limited to CMV+ participants, less family warmth, less harmony, greater dysfunction, and suboptimal parental bonding each were related to higher antibody levels, independent of the aforementioned covariates. Findings were not attributable to current adult perceptions of psychological stress or relative levels of emotional stability. These results suggest that different types of childhood adversity may be associated with differential effects on CMV infection and latency.</p

Stress, immune reactivity and susceptibility to infectious disease

Psychological stress is known to affect immune function and to predict infectious disease susceptibility. However, not all individuals who are stressed develop disease. In the present article, we report on a series of studies from our laboratory describing interindividual variability of immune responses to psychological stress. In our initial series of experimental investigations, we demonstrated that acute laboratory stress alters both quantitative and functional components of cellular immunity. An examination of response variability revealed that individuals differ substantially in the magnitude of these immune responses. These differences were found to parallel (and be predicted by) interindividual variability in stress-induced sympathetic nervous system activation. Further investigation revealed that individuals vary consistently in the magnitude of their immune responses to stress, making it conceivable that individual differences in immune reactivity provide a vulnerability factor mediating relationships between stress and disease. In support of this possibility, we have recently reported initial evidence that individual differences in the magnitude of stress-induced reduction of immune function may be of clinical significance, being related to an immune response relevant for protection against infection, antibody response to hepatitis B vaccination.</p

Inflammatory pathways link socioeconomic inequalities to white matter architecture.

<p>Socioeconomic disadvantage confers risk for aspects of ill health that may be mediated by systemic inflammatory influences on the integrity of distributed brain networks. Following this hypothesis, we tested whether socioeconomic disadvantage related to the structural integrity of white matter tracts connecting brain regions of distributed networks, and whether such a relationship would be mediated by anthropometric, behavioral, and molecular risk factors associated with systemic inflammation. Otherwise healthy adults (N= 155, aged 30-50 years, 78 men) completed protocols assessing multilevel indicators of socioeconomic position (SEP), anthropometric and behavioral measures of adiposity and cigarette smoking, circulating levels of C-reactive protein (CRP), and white matter integrity by diffusion tensor imaging. Mediation modeling was used to test associations between SEP indicators and measures of white matter tract integrity, as well as indirect mediating paths. Measures of tract integrity followed a socioeconomic gradient: individuals completing more schooling, earning higher incomes, and residing in advantaged neighborhoods exhibited increases in white matter fractional anisotropy and decreases in radial diffusivity, relative to disadvantaged individuals. Moreover, analysis of indirect paths showed that adiposity, cigarette smoking, and CRP partially mediated these effects. Socioeconomic inequalities may relate to diverse health disparities via inflammatory pathways impacting the structural integrity of brain networks.</p

β2-Adrenergic receptor density and cardiovascular response to mental stress

In this study we evaluated effects of an acute experimental stressor on β2-adrenoceptor density and examined the relationships of baseline receptor density to cardiovascular reactions induced by stress. In addition, we investigated whether any observed alterations in receptor density were associated with concomitant redistribution of circulating lymphocyte populations. Receptor density and lymphocyte subsets were determined before and immediately following performance of a frustrating laboratory task in 22 male volunteers. Blood pressure, heart rate (HR), and plasma catecholamine concentrations were also assessed at baseline and during task performance. Parallel measurements were obtained among 11 unstressed control subjects. Receptor density increased significantly between baseline and posttask measurements, but equally so in experimental and control subjects. Numbers of T suppressor/cytotoxic and natural killer cells increased selectively among subjects assigned to the experimental (stress) condition. However, there was no association between lymphocyte subset distribution and receptor density. Interindividual variability in pretask receptor density correlated significantly with heart rate and systolic blood pressure (SBP) reactivity during the initial 3 min of mental stress, but not over the entire task period. In addition, baseline receptor density correlated with SBP (but not HR) reactivity after covariance adjustment for the concomitant change in plasma catecholamine concentrations.</p

Competing physiological pathways link individual differences in weight and abdominal adiposity to white matter microstructure.

<p>Being overweight or obese is associated with reduced white matter integrity throughout the brain. It is not yet clear which physiological systems mediate the association between inter-individual variation in adiposity and white matter. We tested whether composite indicators of cardiovascular, lipid, glucose, and inflammatory factors would mediate the adiposity-related variation in white matter microstructure, measured with diffusion tensor imaging on a group of neurologically healthy adults (N=155). A composite factor representing adiposity (comprised of body mass index and waist circumference) was associated with smaller fractional anisotropy and greater radial diffusivity throughout the brain, a pattern previously linked to myelin structure changes in non-human animal models. A similar global negative association was found for factors representing inflammation and, to a lesser extent, glucose regulation. In contrast, factors for blood pressure and dyslipidemia had positive associations with white matter in isolated brain regions. Taken together, these competing influences on the diffusion signal were significant mediators linking adiposity to white matter and explained up to fifty-percent of the adiposity-white matter variance. These results provide the first evidence for contrasting physiological pathways, a globally distributed immunity-linked negative component and a more localized vascular-linked positive component, that associate adiposity to individual differences in the microstructure of white matter tracts in otherwise healthy adults.</p

Negative emotions and acute physiological responses to stress

One pathway through which stressors are thought to influence physiology is through their effects on emotion. We used meta-analytic statisitical techniques with data from nine studies to test the effects of acute laboratory stressors (speech, star mirror-image tracing, handgrip) on emotional (undifferentiated negative emotion, anger, anxiety) and cardiovascular (CV) response. In all of the studies, participants responded to stressors with both increased CV response and increased negative emotion. Increases in negative emotion were associated with increases in CV response across tasks, however, these associations were small. The range of variance accounted for was between 2% and 12%. Thus, the contribution of negative emotion, as assessed in these studies, to physiological responses to acute laboratory stressors was limited. Although these results raise questions about the role of emotion in mediating stress-elicited physiological responses, the nature of the acute laboratory stress paradigm may contribute to the lack of a strong association

Cardiovascular Reactivity and the Course of Immune Response to an Acute Psychological Stressor

This study evaluated the temporal nature of cellular immune responses, as well as the effects of cardiovascular reactivity on immune responses after exposure to an acute psychological stressor. Lymphocyte subsets and lymphocyte proliferative response to phytohemagglutinin were assessed at baseline and at 5 and 21 minutes after stressor onset in the experimental group and at the same time points in a nonstressor control group. By 5 minutes after stressor onset, the number of CD8 suppressor/cytotoxic T and CD16/56 natural killer cells increased and proliferative response to phytohemagglutinin decreased. These changes were maintained at 21 minutes. Those subjects showing the greatest cardiovascular reactivity had the largest immune alterations. These data did not indicate that gender significantly moderated immune responses. Results are consistent with the hypothesis that sympathetic activation mediates stressor-induced quantitative alterations of peripheral blood lymphocyte subpopulations and nonspecific mitogen stimulated proliferation.</p