Our objective was to explore the utility of salivary telomere length (sTL) as an early indicator of neighborhood level social environmental risk during child development. We therefore tested the hypothesis that sTL would be associated with markers of social stress exposure in children. Children age 4–14 from 87 neighborhoods were recruited through five urban schools in New Orleans, Louisiana, U.S. Data were collected at the level of the child, family/household, and neighborhood. DNA was obtained from saliva using commercially available kits and sTL was determined for 104 children using quantitative PCR. Analysis was performed on 99 children who had complete data including sTL, social environmental stress, and additional covariates. The mean sTL value was 7.4 T/S (telomere signal/single copy signal) ratio units (± 2.4, range=2.5–18.0), and 4.7% of the variance in sTL was attributed to differences across neighborhoods. Children living in neighborhoods characterized by high disorder had an sTL value 3.2 units lower than children not living in high disordered environments (p<0.05) and their odds of having low relative sTL (defined as < 1 standard deviation below standardized z score mean) values was 3.43 times that of children not living in high disorder environments (adjusted OR=3.43, 95% CI=1.22, 9.62). Our findings are consistent with previous studies in adults demonstrating a strong link between psychosocial stress and sTL obtained from peripheral blood, consistent with previous studies in youth demonstrating an association between early life stress and sTL obtained from buccal cell DNA and offer increased support for the hypothesis that sTL represents a non-invasive biological indicator of psychosocial stress exposure (i.e., neighborhood disorder) able to reflect differences in stress exposure levels even in young children.

WHAT'S KNOWN ON THIS SUBJECT: Poor health in children is associated with exposure to family violence and disruption. Telomere length has been hypothesized to be a lasting biological indicator of exposure to early adversity and potentially predictive of negative health outcomes throughout the life course. WHAT THIS STUDY ADDS:Telomere length reflects exposure to family violence and disruption and may be an early indicator of the biological impact of early adversity. Children exposed to interpersonal violence and family disruptions had significantly shorter telomeres. Gender moderated these associations. abstract BACKGROUND: To enhance the understanding of biological mechanisms connecting early adversity and negative health, we examine the association between family interpersonal violence and disruption and telomere length in youth. These specific exposures were selected because of their established links with negative health consequences across the life-course.

Background Given the established relation between testosterone and aging in older adults, we tested whether buccal telomere length (TL), an established cellular biomarker of aging, was associated with testosterone levels in youth. Methods Children, mean age 10.2 years, were recruited from the greater New Orleans area and salivary testosterone was measured during both an acute stressor and diurnally. Buccal TL was measured using monochrome multiplex quantitative real-time PCR (MMQ-PCR). Testosterone and telomere length data was available on 77 individuals. The association between buccal TL and testosterone was tested using multivariate Generalized Estimating Equations (GEE) to account for clustering of children within families. Results Greater peak testosterone levels (β=-0.87, p < 0.01) and slower recovery (β=-0.56, p < 0.01) and reactivity (β = -1.22, p < 0.01) following a social stressor were significantly associated with shorter buccal TL after controlling for parental age at conception, child age, sex, sociodemographic factors and puberty. No association was initially present between diurnal measurements of testosterone or morning basal testosterone levels and buccal TL. Sex significantly moderated the relation between testosterone reactivity and buccal TL. Conclusions The association between testosterone and buccal TL supports gonadal maturation as a developmentally sensitive biomarker of aging within youth. As stress levels of testosterone were significantly associated with buccal TL, these findings are consistent with the growing literature linking stress exposure and accelerated maturation. The lack of association of diurnal testosterone or morning basal levels with buccal TL bolsters the notion of a shared stress-related maturational mechanism between cellular stress and the hypothalamic pituitary gonadal (HPG) axis. These data provide novel evidence supporting the interaction of aging, physiologic stress and cellular processes as an underlying mechanism linking negative health outcomes and early life stress.

We examined caregiver report of externalizing behavior from 12 to 54 months of age in 102 children randomized to care as usual in institutions or to newly-created high quality foster care. At baseline no differences by group or genotype in externalizing were found. However, changes in externalizing from baseline to 42 months of age were moderated by 5HTTLPR genotype and intervention group, where the slope for s/s individuals differed as a function of intervention group. The slope for individuals carrying the l allele did not significantly differ between groups. At 54 months of age, s/s children in the foster care group had the lowest levels of externalizing behavior, while children with the s/s genotype in the care as usual group demonstrated the highest rates of externalizing behavior. No intervention group differences were found in externalizing behavior among children who carried the l allele. These findings, within a randomized control trial of foster care compared to continued care as usual, indicate that 5HTTLPR genotype moderates the relation between early caregiving environments to predict externalizing behavior in children exposed to early institutional care in a manner most consistent with differential susceptibility.

In the oral epithelium, peripheral stores of Epstein-Barr virus (EBV) are transmitted from infiltrating B cells to epithelial cells. Once the virus is transmitted to epithelial cells, the highly permissive nature of this cell type for lytic replication allows virus amplification and exchange to other hosts. Since the initial transfer of EBV from B cells to epithelial cells requires transitioning of the B-cell to a state that induces virus reactivation, we hypothesized that there might be epithelium-specific signals that allow the infiltrating B cells to sense the appropriate environment to initiate reactivation and begin this exchange process. We previously found that the epithelium-specific miR- IMPORTANCE Epstein-Barr virus (EBV) is an important human pathogen that is causally associated with several lymphomas and carcinomas.The switch from latency to the lytic cycle is critical for successful host infection and for EBV pathogenesis. Although the EBV lytic cycle can be triggered by certain agents in vitro, the mechanisms that signal reactivation in vivo are poorly understood. We previously reported that endogenously expressed miR-200 family members likely play a role in facilitating the lytic tendencies of EBV in epithelial cells. Here we show that membrane vesicles secreted from oral epithelial cells contain miR-200 family members and that they can be transmitted to proximal EBV-positive B cells, where they trigger reactivation. We propose that this intercellular communication pathway may serve as a sensor mechanism for infiltrating B cells to recognize an appropriate environment to initiate reactivation, thereby allowing the exchange of virus to the oral epithelium. M embrane vesicles (MVs), such as exosomes and microvesicles, can be actively released by cells into the extracellular environment, where they can facilitate intercellular communication. Exosomes are a class of small membrane vesicles (30 to 150 nm in diameter) of endocytic origin that are secreted from most cell types, including epithelial cells and lymphocytes, under both physiological and pathological conditions (1-8). Exosomes are composed of proteins, lipids, and nucleic acids that are derived from their cells of origin. Through the delivery of biologically active components from the cells of origin to neighboring and/or distant cells, exosomes are able to modulate many biological activities, such as tumorigenesis, immunosurveillance, cell proliferation, and angiogenesis (1, 9-12). MicroRNAs (miRNAs) are important exosomal cargo that facilitate signaling pathway alterations in recipient cells (2,(13)(14)(15)(16)(17). EBV-encoded BART miRNAs are selectively enriched in EBV-positive B-cell-derived exosomes (13,14) and have been shown to inhibit NLRP3 inflammasome-mediated interleukin 1␤ (IL-1␤) production (14) and to suppress the expression of the CXCL11 gene (13), an immunoregulatory gene involved in antiviral activity and lymphomagenesis.Epstein-Barr virus (EBV) causes a lifelong infection, with more than 90% of the adult population...

Building upon the transactional model of brain development, we explore the impact of early maternal deprivation on neural development and plasticity in three neural systems: hyperactivity/impulsivity, executive function, and hypothalamic–pituitary–adrenal axis functioning across rodent, nonhuman primate, and human studies. Recognizing the complexity of early maternal–infant interactions, we limit our cross-species comparisons to data from rodent models of artificial rearing, nonhuman primate studies of peer rearing, and the relations between these two experimental approaches and human studies of children exposed to the early severe psychosocial deprivation associated with institutional care. In addition to discussing the strengths and limitations of these paradigms, we present the current state of research on the neurobiological impact of early maternal deprivation and the evidence of sensitive periods, noting methodological challenges. Integrating data across preclinical animal models and human studies, we speculate about the underlying biological mechanisms; the differential impact of deprivation due to temporal factors including onset, offset, and duration of the exposure; and the possibility and consequences of reopening of sensitive periods during adolescence.

These findings extend previous findings associating genetic variation in the DAT with PTSD. The association of a haplotype in DAT with PTSD provides incremental traction for a model of genetic vulnerability to PTSD, a specific underlying mechanism implicating striatal dopamine regulation, and insight into potential future personalized interventions.

An individual's neurodevelopmental and cognitive sequelae to negative early experiences may, in part, be explained by genetic susceptibility. We examined whether extreme differences in the early caregiving environment, defined as exposure to severe psychosocial deprivation associated with institutional care compared to normative rearing, interacted with a biologically informed genoset comprising BDNF (rs6265), COMT (rs4680), and SIRT1 (rs3758391) to predict distinct outcomes of neurodevelopment at age 8 (N = 193, 97 males and 96 females). Ethnicity was categorized as Romanian (71%), Roma (21%), unknown (7%), or other (1%). We identified a significant interaction between early caregiving environment (i.e., institutionalized versus never institutionalized children) and the a priori defined genoset for full-scale IQ, two spatial working memory tasks, and prefrontal cortex gray matter volume. Model validation was performed using a bootstrap resampling procedure. Although we hypothesized that the effect of this genoset would operate in a manner consistent with differential susceptibility, our results demonstrate a complex interaction where vantage susceptibility, diathesis stress, and differential susceptibility are implicated.