Use of archived neonatal bloodspots for examining associations between prenatal exposure to potentially traumatic or stressful life events, maternal herpesvirus infection and lifetime history of generalized anxiety disorder in offspring

Background: Lifetime prevalence of anxiety disorders is over 30% among U.S. adolescents, warranting further investigation into early life risk factors for such conditions. We conducted a pilot study to examine the role that maternal herpesvirus infection may play in the pathway between maternal trauma and stress during pregnancy and offspring generalized anxiety disorder (GAD). Methods: Participants included 69 women in the Detroit Neighborhood Health Study with data on past exposure to 19 potentially traumatic (PTEs) and 9 stressful life events (SLEs). Lifetime history of GAD in the youngest biologic child between 6 and 17 years old born in Michigan (i.e., index child) of each woman was ascertained via the Diagnostic Interview Schedule for Children, 4th edition, parent version. We obtained written informed consent from participants for retrieval of archived neonatal bloodspot samples corresponding to their index child from the Michigan Neonatal Biobank (MNB) and testing of these samples for markers of maternal herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) seropositivity. Logistic regression was used to examine the association between maternal PTEs or SLEs during pregnancy and offspring GAD. Results: A total of 18.1 and 31.9% of women experienced =1 PTE or SLE during pregnancy, respectively, and 10.8% of offspring met the criteria for lifetime history of GAD. We obtained maternal consent for retrieval of and tested bloodspot samples corresponding to the index child of 22 women (38.0%), of which 4.5 and 40.9% were seropositive for HSV-1 and CMV, respectively. We observed positive, although not statistically significant associations between =1 PTE or SLE during pregnancy and offspring lifetime history of GAD. While a greater proportion of offspring with lifetime history of GAD were born to women seropositive for CMV and HSV-1, compared to those without lifetime history, these differences were not statistically significant and we did not further examine the mediating role of maternal herpesvirus seropositivity in this pathway.Conclusion: Findings from this study support the feasibility of utilizing neonatal bloodspots archived in the MNB to examine the role of herpesviruses as mediators between maternal trauma or stress during pregnancy and offspring anxiety disorders in larger Michigan cohorts. © 2016 Simanek, Uddin, Yolken and Aiello

A longitudinal study of the association between persistent pathogens and incident depression among older U.S. Latinos

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

Seropositivity to cytomegalovirus, inflammation, all-cause and cardiovascular disease-related mortality in the United States

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

The impact of pathogen burden on leukocyte telomere length in the Multi-Ethnic Study of Atherosclerosis

Several 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

Quantum superconductor-metal transition

We consider a system of superconducting grains embedded in a normal metal. At zero temperature this system exhibits a quantum superconductor-normal metal phase transition. This transition can take place at arbitrarily large conductance of the normal metal.Comment: 13 pages, 1 figure include