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Chronic infections and the subsequent immune response have recently been shown to be risk factors for cognitive decline and Alzheimer disease and related dementias (ADRD). While some studies have shown an association between cytomegalovirus (CMV), a chronic and highly prevalent infection, and cognition and/or ADRD, these studies have been limited by nonrepresentative and small samples. Using 2016 data on 5,617 adults aged 65 years or more from the Health and Retirement Study, we investigated the cross-sectional associations of both CMV serostatus and immunoglobulin G (IgG) antibody response with cognitive function using linear regression models adjusting for age, sex, race/ethnicity, and educational attainment. We further investigated potential effect-measure modification by educational attainment. Overall, both CMV seropositivity and higher IgG antibody response were associated with lower cognitive function, though the relationship was not statistically significant in adjusted models. Among participants with less than a high school diploma, CMV seropositivity and being in the first tertile of IgG response, relative to seronegative persons, were associated with lower scores on the Telephone Interview for Cognitive Status (−0.56 points (95% confidence interval: −1.63, 0.52) and −0.89 points (95% confidence interval: −2.07, 0.29), respectively), and the relationship was attenuated among those with higher education. Our results suggest that CMV may be a risk factor for cognitive impairment, particularly among persons with fewer educational resources.

Telomere length, a biomarker of cell division and cellular aging, has been associated with multiple chronic disease endpoints. Experienced trauma over the life course may contribute to telomere shortening via mechanisms of stress embodiment. However, it is unclear how patterns of co-occurring trauma during sensitive periods (e.g., early life) throughout the life course may influence telomere shortening. We examine the relationship between co-occurring early life trauma on adult telomere length and the extent to which adulthood trauma, socioeconomic position, and health and lifestyle factors may mediate this relationship.We use data from a sample of participants in the Sister Study (N = 740, analytic sample: n = 602), a prospective cohort of U.S. self-identified females aged 35-74 years at enrollment (2003-2009) for whom leukocyte telomere length was measured in baseline blood samples. Participants reported their experience of 20 different types of trauma, from which we identified patterns of co-occurring early life trauma (before age 18) using latent class analysis. We estimated the direct and indirect effects of early life trauma on leukocyte telomere length using structural equation modeling, allowing for mediating adult pathways.Approximately 47 % of participants reported early life trauma. High early life trauma was associated with shorter telomere length compared to low early life trauma (β = -0.11; 95 % CI: -0.22, -0.004) after adjusting for age and childhood socioeconomic position. The inverse association between early life trauma and adult leukocyte telomere length was largely attributable to the direct effect of early life trauma on telomere length (β = -0.12; 95 %CI: -0.23, -0.01). Mediating indirect pathways via adult trauma, socioeconomic position, and health metrics did not substantively contribute the overall association.These findings highlight the role of patterns of co-occurring early life trauma on shortened telomere length independent of adult pathways.

The World Health Organization has identified excessive COVID-19 pandemic-related information as a public health crisis, calling it an "infodemic." Social media allows misinformation to spread quickly and outcompete scientifically grounded information delivered via other methods.

Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (Tmem). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of Tmem and/or other T-cell subsets. Methods: Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28null T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of Tmem, proportion of Tmem/cfPWV, CD28null T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required. Results: Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 Tmem in men (P ≤ 0.05) but not in women; proportions of CD4 Tmem/cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people. Conclusion: CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 Tmem, higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required. Published version This work was supported by The Dunhill Medical Trust, grant number R278/0213. AP is receiving funding from Miguel Servet CP19/00008, Instituto de Salud Carlos III & ERDF/ESF.

Background Prior studies in humans have suggested that telomere shortening may be accelerated by infection, but research on multiple pathogens and use of large population-based study samples has been limited. We estimated cross-sectional associations between seropositivity to five persistent pathogens (Herpes Simplex Virus Type-1 (HSV-1), Herpes Simplex Virus Type-2 (HSV-2), cytomegalovirus (CMV), Helicobacter pylori (H.pylori), and Hepatitis B) as well as total pathogen burden and leukocyte telomere length. Data were derived from the National Health and Nutrition Examination Survey (1999–2000) for individuals 20–49 years of age, N = 1708. We analyzed the influence of each pathogen separately, a pathogen count score and a latent class model of pathogen burden on log telomere length using linear regression models, adjusted for covariates. Results Individuals in a latent pathogen burden class characterized by high probabilities of infection with HSV-1, CMV, and H. pylori, had significantly decreased log telomere length (− 0.30 [95% CI: − 0.36, − 0.24]) compared to those in a latent class characterized by low probabilities of all five infections. There were limited significant associations using other pathogen measures. Conclusions These results suggest that infection with specific combinations of pathogens may be one mechanism contributing to accelerated cellular senescence with possible origins early in the life course.

Understanding of the role of objective versus subjective childhood socioeconomic disadvantage (SD) in depression onset in adulthood among women, independent of later life SD, and across birth cohorts, is limited. We examined the association between objective (i.e., household education level) and subjective (i.e., rank of family income and report of not enough food to eat) SD during childhood and diagnosis of clinical depression after age 30 among 47,055 women in the Sister Study. We used Cox proportional hazard models adjusting for women’s race/ethnicity, childhood household composition, mother’s age at her birth adulthood educational attainment, and calendar year of birth. Analyses were repeated stratified by 10-year birth group. A total of 8036 (17.1%) women were diagnosed with clinical depression over a mean follow-up of 24.0 (± 9.9) years. Those reporting being poor (versus well-off) or not having enough food to eat in childhood had a 1.28 (95% confidence interval (CI) 1.13, 1.44) and 1.30 (95% CI 1.21, 1.41) times higher rate of depression diagnosis, respectively, with consistent associations observed across birth year groups. An inverse association between low household education level and incident depression was observed at baseline (i.e., age 30) becoming positive over time in the total sample but only among women born between 1935–1954 in analyses stratified by 10-year birth group. Our findings suggest that subjective SD in childhood is a largely consistent predictor of depression onset among women in adulthood whereas the effects of household education level in childhood may vary across women born into different birth cohorts, and for some, across the lifecourse.

A growing body of literature suggests that early life socioeconomic disadvantage (SD) may play a key role in shaping a pro-inflammatory phenotype hypothesized to result from programming of cells of the innate immune system (i.e., monocytes and macrophages) for desensitization to glucocorticoid signaling and exacerbated inflammatory response to immune stimuli, yet understanding of the biologic pathways by which such programming may occur remains limited. The purpose of this review is to discuss the current research supporting the hypothesis that early life SD is associated with a pro-inflammatory phenotype beginning in childhood and highlight recent findings regarding the role that epigenetic programming via DNA methylation (DNAm) specifically, may serve as a biologic mediator of these associations. Gaps in knowledge and recommendations for future research are also discussed. Findings regarding the association between early life SD and DNAm of genes that may be involved in shaping a pro-inflammatory phenotype are mixed, but lend some support for epigenetic alterations to genes regulating inflammatory processes as a mediator of this association. Studies which integrate data on DNAm, gene expression, and markers of a pro-inflammatory phenotype beginning early in life and over time are ultimately needed to fully understand the role of epigenetic programming in shaping this adverse immune phenotype in those born into socioeconomically disadvantaged environments. Epigenetic programming of a pro-inflammatory phenotype represents a plausible and understudied pathway by which socioeconomic disparities in chronic disease develop across the lifecourse and are perpetuated across generations.

Background: A growing literature supports the role of immune system alterations in the etiology of mood regulation, yet there is little population-based evidence regarding the association between persistent pathogens, inflammation and mood disorders among younger women and men in the U.S. Methods: We used data from the National Health and Nutrition Examination Survey III on individuals 15-39 years of age assessed for major depression, dysthymia, and/or bipolar disorder I and tested for cytomegalovirus (N=6825), herpes simplex virus (HSV)-1 (N=5618) and/or Helicobacter pylori (H. pylori) (N=3167) seropositivity as well as C-reactive protein (CRP) level (N=6788). CMV immunoglobulin G (IgG) antibody level was also available for a subset of women (N=3358). We utilized logistic regression to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between pathogens, CRP levels and each mood disorder overall and among women and men, separately. Results: H. pylori seropositivity was associated with increased odds of dysthymia (OR 2.37, 95% confidence interval (CI): 1.07, 5.24) among women, but decreased odds among men (OR 0.51, 95% CI: 0.28, 0.92). CMV seropositivity was also associated with lower odds of depression (OR 0.54, 95% CI: 0.32, 0.91) among men, while elevated CMV IgG level was marginally associated with increased odds of mood disorders among women. Associations were not mediated by CRP level. Conclusions: Our findings suggest that persistent pathogens such as CMV and H. pylori may differentially influence mood disorders among women and men, warranting further investigation into biological and/or sociocultural explanations for the contrasting associations observed.

Depression is estimated to affect more than 6.5 million Americans 65 years of age and older and compared with non-Latino whites older U.S. Latinos have a greater incidence and severity of depression, warranting further investigation of novel risk factors for depression onset among this population. We used data on 771/1,789 individuals ≥60 years of age from the Sacramento Area Latino Study on Aging (1998–2008) who were tested for cytomegalovirus (CMV), herpes simplex virus, varicella zoster, Helicobacter pylori, Toxoplasma gondii, and C-reactive protein (CRP) and interleukin-6 (IL-6) level. Among those without elevated depressive symptoms at baseline, we examined the association between each pathogen, inflammatory markers and incident depression over up to nearly 10 years of follow-up using discrete-time logistic regression. We found that only CMV seropositivity was statistically significantly associated with increased odds of incident depression (odds ratio [OR]: 1.38, 95% confidence interval [CI]: 1.00–1.90) in the total sample as well as among women only (OR: 1.70, 95% CI: 1.01–2.86). These associations were not mediated by CRP or IL-6 levels. Our findings suggest that CMV seropositivity may serve as an important risk factor for the onset of depression among older U.S. Latinos, but act outside of inflammatory pathways.

Background:The pathophysiology of preeclampsia remains unclear. The disorder is heterogeneous, and the pathophysiology may vary by subtype. Identification of relevant biomarkers will help to better elucidate the pathophysiologic basis of each preeclampsia subtype. Blood type may be a biomarker that allows risk identification for preeclampsia.Objective:The purpose of this study was to investigate the associations among maternal ABO blood type and preeclampsia subtype and fetal growth restriction (FGR).Method:Medical records of 126 women with early-onset preeclampsia (≤33 6/7 weeks’ gestation), 126 women with late-onset preeclampsia (≥34 0/7 weeks’ gestation), and 259 controls who gave birth between January 2012 and June 2016 were retrospectively abstracted from a large suburban tertiary referral center in South Central Pennsylvania for this hospital-based case–control study.Results:Women with AB blood type had >3 times the odds of late-onset preeclampsia (odds ratio [ OR] = 3.35, 95% confidence interval (CI) = [1.02, 11.05]) compared to those with O blood type. Among women with early-onset preeclampsia, those with B blood type had 5 times the odds of having a growth-restricted fetus than did women with O blood type ( OR = 5.44, 95% CI [1.65, 17.94]).Discussion:Our findings suggest that AB blood type may be an important risk factor for late-onset preeclampsia and that among women with early-onset preeclampsia, those with B blood type have increased odds of FGR. These findings warrant further study in women and their offspring to identify the pathophysiologic processes that may link ABO blood type, preeclampsia subtype, and FGR.

Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E/N ratio) and the CD4/CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E/N ratios and lower CD4/CD8 ratios compared with participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T cells.Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a $10,000 decrease in income and each ratio outcome.After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09-0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02-0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G antibody level partially mediated these associations.Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E/N ratio and that impaired immune control of CMV may partially mediate these associations.

Objectives Allostatic load (AL) represents cumulative biological "wear and tear" that results from chronic stress exposure over time, ultimately increasing risk for chronic disease. A consensus is lacking regarding the best operationalization of AL, particularly for younger, less studied populations. The purpose of this study was to test multiple hypothesized factor structures for AL to determine the best measurement approach for adolescents. Methods We analyzed biologic data for 1900 adolescents aged 12-18 from four waves (2003-2010) of the National Health and Nutrition Examination Survey. AL indicator variables included cardiovascular (systolic BP, creatinine), metabolic (HDL, LDL, triglycerides, insulin, fasting glucose, HA1C, body mass index [BMI], waist circumference), and immune (albumin, CRP, WBC, EBV) biomarkers. Structural equation modeling was used to test the fit of five hypothesized AL factor structures. Results The data best supported a unidimensional factor structure, where the AL construct directly influenced each of the indicator variables. All but two of the indicators (HDL and albumin) had positive factor loadings, thus, as AL increases the values for those indicators also increase. The best indicators for AL were those measuring metabolic dysregulation, with BMI and waist circumference having the highest factor loadings (0.95 and 0.982, respectively). Conclusions BMI and waist circumference may be some of the earliest clinical signs of elevated AL that manifest among adolescents. Future research should aim to include neuroendocrine biomarkers in their AL measures to have a more robust estimation of AL in younger populations.

Summary Background Depression is predicted to become the leading cause of disability worldwide by 2030 and moreover, socioeconomic inequalities in depression persist. Herpesviruses, which are more prevalent among socioeconomically disadvantaged populations, subject to stress-induced reactivation and are associated with increased levels of pro-inflammatory cytokines implicated in the etiology of depression, may serve as novel risk factors for depression onset. Methods Data are from individuals in the Detroit Neighborhood Health Study tested for herpes simplex virus-1 (HSV-1) and cytomegalovirus (CMV) seropositivity/immunoglobulin G (IgG) antibody levels ( N = 263) as well as interleukin-6 (IL-6) ( N = 245) and C-reactive protein (CRP) ( N = 236) levels and assessed for incident depression via the Patient Health Questionnaire-9. Linear and logistic regression models were used to examine associations between pathogen seropositivity/IgG antibody levels, pro-inflammatory markers and incident depression over approximately one-year of follow-up. Results For every one unit increase in CMV IgG antibody level, the odds of incident depression increased by 26% and individuals with IgG antibody levels in the highest quartile had over three times greater odds of incident depression (odds ratio 3.87, 95% confidence interval 1.47, 10.19), compared to those in the lower three quartiles. Neither CMV or HSV-1 seropositivity nor HSV-1 IgG antibody level were associated with IL-6 or CRP levels at Wave 1, nor were IL-6 or CRP levels associated with incident depression at Wave 2. Conclusions Further examination of the biological pathways linking CMV and depression are warranted.

SUMMARYSeveral infections have been linked to telomere shortening and in some cases these associations have varied by sex. We assessed the association between seropositivity to four persistent pathogens (cytomegalovirus (CMV), herpes simplex virus-1,Helicobacter pylori,Chlamydia pneumoniae), and total pathogen burden on leukocyte telomere length in a diverse US sample. Data came from the Multi-Ethnic Study of Atherosclerosis, a population-based cohort study. We utilized cross-sectional survey data, and biological samples from participants tested for pathogens and telomere length (N= 163). Linear regression was used to examine the association between seropositivity for individual pathogens as well as total pathogen burden and telomere length, adjusting for various confounders. CMV seropositivity and increased total pathogen burden level were significantly associated with shorter telomere length among females (β= −0·1204 (standard error (s.e.) 0·06),P= 0·044) and (β= −0·1057 (s.e.= 0·05),P= 0·033), respectively. There was no statistically significant association among males. Our findings suggest that prevention or treatment of persistent pathogens, in particular CMV, may play an important role in reducing telomere shortening over the life course among women. Future research is needed to confirm these novel findings in larger longitudinal samples.

Persistent infections, such as cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), Helicobacter pylori (H. pylori), and Toxoplasma gondii (T. gondii), are common in the U.S. but their prevalence varies by socioeconomic status. It is unclear if early or later life socioeconomic position (SEP) is a more salient driver of disparities in immune control of these infections. Using data from the Sacramento Area Latino Study on Aging, we examined whether early or later life SEP was the strongest predictor of immune control later in life by contrasting two life course models, the critical period model and the chain of risk model. Early life SEP was measured as a latent variable, derived from parental education and occupation, and food availability. Indicators for SEP in later life included education level and occupation. Individuals were categorized by immune response to each pathogen (seronegative, low, medium and high) with increasing immune response representing poorer immune control. Cumulative immune response was estimated using a latent profile analysis with higher total immune response representing poorer immune control. Structural equation models were used to examine direct, indirect and total effects of early life SEP on each infection and cumulative immune response, controlling for age and gender. The direct effect of early life SEP on immune response was not statistically significant for the infections or cumulative immune response. Higher early life SEP was associated with lower immune response for T.gondii, H.pylori and cumulative immune response through pathways mediated by later life SEP. For CMV, higher early life SEP was both directly associated and partially mediated by later life SEP. No association was found between SEP and HSV-1. Findings from this study support a chain of risk model, whereby early life SEP acts through later life SEP to affect immune response to persistent infections in older age.

The social patterning of cytomegalovirus (CMV) and its implication in aging suggest that the virus may partially contribute to socioeconomic disparities in mortality. We used Cox regression and inverse odds ratio weighting to quantify the proportion of the association between socioeconomic status (SES) and all-cause mortality that was attributable to mediation by CMV seropositivity. Data were from the National Health and Nutrition Examination Survey (NHANES) III (1988–1994), with mortality follow-up through December 2011. SES was assessed as household income (income-to-poverty ratio ≤1.30; >1.30 to ≤1.85; >1.85 to ≤3.50; >3.50) and education (high school). We found strong associations between low SES and increased mortality: hazard ratio (HR) 1.80; 95% confidence interval (CI): 1.57, 2.06 comparing the lowest versus highest income groups and HR 1.29; 95% CI: 1.13, 1.48 comparing high school education. 65% of individuals were CMV seropositive, accounting for 6–15% of the SES-mortality associations. Age modified the associations between SES, CMV, and mortality, with CMV more strongly associated with mortality in older individuals. Our findings suggest that cytomegalovirus may partially contribute to persistent socioeconomic disparities in mortality, particularly among older individuals.

Background Social networks are increasingly recognized as important points of intervention, yet relatively few intervention studies of respiratory infection transmission have utilized a network design. Here we describe the design, methods, and social network structure of a randomized intervention for isolating respiratory infection cases in a university setting over a 10-week period. Methodology/principal findings 590 students in six residence halls enrolled in the eX-FLU study during a chain-referral recruitment process from September 2012–January 2013. Of these, 262 joined as “seed” participants, who nominated their social contacts to join the study, of which 328 “nominees” enrolled. Participants were cluster-randomized by 117 residence halls. Participants were asked to respond to weekly surveys on health behaviors, social interactions, and influenza-like illness (ILI) symptoms. Participants were randomized to either a 3-Day dorm room isolation intervention or a control group (no isolation) upon illness onset. ILI cases reported on their isolation behavior during illness and provided throat and nasal swab specimens at onset, day-three, and day-six of illness. A subsample of individuals (N = 103) participated in a sub-study using a novel smartphone application, iEpi, which collected sensor and contextually-dependent survey data on social interactions. Within the social network, participants were significantly positively assortative by intervention group, enrollment type, residence hall, iEpi participation, age, gender, race, and alcohol use (all P Conclusions/significance We identified a feasible study design for testing the impact of isolation from social networks in a university setting. These data provide an unparalleled opportunity to address questions about isolation and infection transmission, as well as insights into social networks and behaviors among college-aged students. Several important lessons were learned over the course of this project, including feasible isolation durations, the need for extensive organizational efforts, as well as the need for specialized programmers and server space for managing survey and smartphone data.

Background Psychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging. Methods Data were from 85 individuals who participated in the community-based Detroit Neighborhood Health Study. Immune markers assessed included the CD4:CD8 ratio, the ratio of late-differentiated effector (CCR7-CD45RA+CD27-CD28-) to naive (CCR7+CD45RA+CD27+CD28+) T cells, the percentage of KLRG1-expressing cells, and the percentage of CD57-expressing cells. Results In models adjusted for age, gender, race/ethnicity, education, smoking status, and medication use, we found that past-year PTSD was associated with statistically significant differences in the CD8+ T cell population, including a higher ratio of late-differentiated effector to naive T cells, a higher percentage of KLRG1+ cells, and a higher percentage of CD57+ cells. The percentage of CD57+ cells in the CD4 subset was also significantly higher and the CD4:CD8 ratio significantly lower among individuals who had experienced past-year PTSD. Lifetime PTSD was also associated with differences in several parameters of immune aging. Conclusions PTSD is associated with an aged immune phenotype and should be evaluated as a potential catalyzer of accelerated immunological aging in future studies.

The notion that chronic stress contributes to health inequalities by socio-economic status (SES) through physiological wear and tear has received widespread attention. This article reviews the literature testing associations between SES and cortisol, an important biomarker of stress, as well as the summary index of allostatic load (AL).A search of all published literature on the PubMed and ISI Web of Knowledge literature search engines was conducted using broad search terms. The authors reviewed abstracts and selected articles that met the inclusion criteria. A total of 26 published studies were included in the review.Overall, SES was not consistently related to cortisol. Although several studies found an association between lower SES and higher levels of cortisol, many found no association, with some finding the opposite relationship. Lower SES was more consistently related to a blunted pattern of diurnal cortisol secretion, but whether this corresponded to higher or lower overall cortisol exposure varied by study. Approaches to collecting and analysing cortisol varied widely, likely contributing to inconsistent results. Lower SES was more consistently related to higher levels of AL, but primarily via the cardiovascular and metabolic components of AL rather than the neuroendocrine markers.Current empirical evidence linking SES to cortisol and AL is weak. Future work should standardize approaches to measuring SES, chronic stress and cortisol to better understand these relationships.

Background Numerous studies have documented a strong inverse association between cardiovascular disease and socioeconomic position (SEP). Several infections are associated with both cardiovascular disease and SEP; hence infection may form an important link between SEP and cardiovascular disease. This study examines whether seropositivity to cytomegalovirus (CMV), to herpes simplex virus type-1 (HSV-1), and/or to both pathogens mediates the relationship between SEP and cardiovascular disease history in a nationally representative sample of the United States. Methods We conducted a cross-sectional study of subjects 545 years of age, who were tested for seropositivity to CMV, HSV-1 or both pathogens and assessed for cardiovascular disease history in the National Health and Nutrition Examination Survey III. Cardiovascular disease history was defined as history of stroke, heart attack and/or congestive heart failure and SEP as education level. Results SEP was associated with CMV, HSV-1 and seropositivity to both pathogens. CMV seropositivity was associated with cardiovascular disease history even after adjusting for confounders as well as SEP. The odds of reporting a history of cardiovascular disease for those with less than a high school education compared with those with more than a high school education decreased by 7.7% after adjusting for CMV (Sobel mediation test for CMV, P ¼ 0.0006). In contrast, neither seropositivity to HSV-1 nor to both pathogens was associated with cardiovascular disease history after adjusting for SEP. Conclusions Persistent pathogens such as CMV infection may explain a portion of the relationship between SEP and cardiovascular disease in the United States. Further studies examining additional pathogens and sociobiological mechanisms are warranted.

The purpose of this article is to provide a systematic review of studies that have examined the association between prenatal exposure to maternal infection and development of mood disorders across the life course. Drawing from both human- and animal-based studies, we give an overview of hypothesized biological mechanisms by which exposure to maternal infection during critical periods of gestation may contribute to fetal programming of mood disorders in offspring. We discuss studies examining the association between prenatal exposure to maternal infection with pathogens including influenza as well as other respiratory viruses, herpesviruses, hepatitis viruses, and Toxoplasma gondii and mood disorders in human populations. Moreover, we outline strengths and limitations of the current body of evidence and make recommendations for future research. We also discuss findings in the context of well-documented gender and socioeconomic disparities in the prevalence and severity of mood disorders, particularly major depression, and the role that early exposure to infection may play in explaining the perpetuation of such disparities across generations. Overall, this review of the current knowledge on this topic has important implications for determining future research directions, designing interventions as well as prenatal care guidelines targeted at prevention or treatment of infection during pregnancy, and clinical practice for the identification of individuals that may be at increased risk for mood disorders beginning early in life. Importantly, such efforts may not only lower the overall burden of mood disorders but also serve to address social disparities in these adverse mental health conditions in the U.S.

SUMMARYA ‘black box’ paradigm has prevailed in which researchers have focused on the association between the total number of pathogens for which individuals are seropositive (i.e. total pathogen burden) and various chronic diseases, while largely ignoring the role that seropositivity for specific combinations of pathogens may play in the aetiology of such outcomes and consequently mortality. We examined the association between total pathogen burden as well as specific pathogen combinations and all-cause mortality in the United States. Data were from individuals aged ⩾25 years tested for cytomegalovirus (CMV), herpes simplex virus (HSV)-1, HSV-2 andHelicobacter pylori, with mortality follow-up to 31 December 2006 in the National Health and Nutrition Examination Survey (NHANES) III (N= 6522). We did not observe a statistically significant graded relationship between total pathogen burden level and all-cause mortality. Furthermore, compared to those seronegative for all four pathogens, the greatest statistically significant rate of all-cause mortality was for those CMV+/HSV-2+ (hazard ratio 1·95, 95% confidence interval 1·13–3·35) adjusting for age, gender, race/ethnicity, education level, body mass index (kg/m2) and smoking status. Interventions targeting prevention or treatment of particular pathogens may be more effective for reducing mortality than those focused solely on reducing overall pathogen burden.

HIV Study, Parrinello et al. [7] found that higher CMV immunoglobulin G (IgG) levels were not associated with markers of subclinical atherosclerosis among HIV-uninfected women, suggesting that increased antibody levels did not increase the risk of atherosclerosis in their HIV-uninfected subsample. In contrast, HIV-positive women with increased CMV IgG levels were more likely to have carotid artery stiffness. These same individuals did not show greater intima-media thickness nor presence of carotid lesions, indicating that the relationship between CMV IgG levels and markers of cardiovascular disease was specific for carotid artery stiffness in HIV-positive subjects. The relation between increased CMV IgG levels and carotid artery stiffness was consistentacrosstreated/aviremic,treated/ viremic, and untreated HIV-infected groups. However, when examining the association between CMV IgG levels and presence of carotid lesions by treatment/ viremia status groups, Parrinello and colleagues found that CMV IgG levels were associated with presence of carotid artery lesions only among HIV-infected persons who were receiving antiretroviral treatment and were aviremic, after adjustment for age, race, and smoking history. These results suggest that treatment/viremia status modifies the impact of CMV IgG level on carotid lesions.

Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and with several age-related diseases. However, current evidence on whether and how human CMV (HCMV) infection is implicated in immunosenescence and in age-related diseases remains incomplete and many aspects of CMV involvement in immune aging remain controversial. The attendees of the 4th International Workshop on "CMV & Immunosenescence", held in Parma, Italy, 25-27th March, 2013, presented and discussed data related to these open questions, which are reported in this commentary., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Background Studies have suggested that CMV infection may influence cardiovascular disease (CVD) risk and mortality. However, there have been no large-scale examinations of these relationships among demographically diverse populations. The inflammatory marker C-reactive protein (CRP) is also linked with CVD outcomes and mortality and may play an important role in the pathway between CMV and mortality. We utilized a U.S. nationally representative study to examine whether CMV infection is associated with all-cause and CVD-related mortality. We also assessed whether CRP level mediated or modified these relationships. Methodology/Principal Findings Data come from subjects ≥25 years of age who were tested for CMV and CRP level and were eligible for mortality follow-up on December 31st, 2006 (N = 14153) in the National Health and Nutrition Examination Survey (NHANES) III (1988–1994). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for all-cause and CVD-related mortality by CMV serostatus. After adjusting for multiple confounders, CMV seropositivity remained statistically significantly associated with all-cause mortality (HR 1.19, 95% CI: 1.01, 1.41). The association between CMV and CVD-related mortality did not achieve statistical significance after confounder adjustment. CRP did not mediate these associations. However, CMV seropositive individuals with high CRP levels showed a 30.1% higher risk for all-cause mortality and 29.5% higher risk for CVD-related mortality compared to CMV seropositive individuals with low CRP levels. Conclusions/Significance CMV was associated with a significant increased risk for all-cause mortality and CMV seropositive subjects who also had high CRP levels were at substantially higher risk for both for all-cause and CVD-related mortality than subjects with low CRP levels. Future work should target the mechanisms by which CMV infection and low-level inflammation interact to yield significant impact on mortality.

Background. The objective of this study was to examine whether cytomegalovirus (CMV), herpes simplex virus type-1 (HSV-1), and C-reactive protein (CRP) are associated with functional impairment in older Latinos. Methods. A cross-sectional analysis of a cohort study was conducted with a community-dwelling elderly population. The sample was a subset (N ¼ 1559/1789) of participants in the Sacramento Area Latino Study on Aging (SALSA) ages 60‐101 with available serum samples and functional impairment measures. Baseline serum samples were assayed for levels of immunoglobulin G antibodies to CMV and HSV-1 and for levels of CRP. Several measures were used to assess functional impairment, including activities of daily living (ADL), instrumental activities of daily living (IADL), and walking pace. Results. CMV and CRP showed statistically significant graded associations with ADL functional impairment, even after controlling for age and gender. The relationship between CMV and ADL was slightly attenuated, and the confidence interval contained the null value when adjusted for total number of health conditions, body mass index, and household income. Only high levels of CRP were significantly related to ADL and IADL impairment even after adjusting for all other covariates. Conclusion. Inflammation is clearly linked to physical functioning among aging Latinos. This study also suggests a role for CMV infection in relation to ADL impairment. Further research examining the influence of infection, immune response, and inflammation on longitudinal trajectories of physical functioning is warranted.

A growing body of literature suggests that exposure to the neurotropic parasite Toxoplasma gondii (T. gondii) is associated with increased risk of mental disorders, particularly schizophrenia. However, a potential association between T. gondii exposure and anxiety disorders has not been rigorously explored. Here, we examine the association of T. gondii infection with both anxiety and mood disorders. Participants (n=484) were drawn from the Detroit Neighborhood Health Study, a population-representative sample of Detroit residents. Logistic regression was used to examine the associations between T. gondii exposure (defined by seropositivity and IgG antibody levels) and three mental disorders: generalized anxiety disorder (GAD), posttraumatic stress disorder (PTSD) and depression. We found that T. gondii seropositivity was associated with a 2 times greater odds of GAD (odds ratio (OR), 2.25; 95% confidence interval (CI), 1.11–4.53) after adjusting for age, gender, race, income, marital status, and medication. Individuals in the highest antibody level category had more than 3 times higher odds of GAD (OR, 3.35; 95% CI, 1.41–7.97). Neither T. gondii seropositivity nor IgG antibody levels was significantly associated with PTSD or depression. Our findings indicate that T. gondii infection is strongly and significantly associated with GAD. While prospective confirmation is needed, T. gondii infection may play a role in the development of GAD.