Anti-cytomegalovirus antibody levels stratify human immune profiles across the lifespan.

Human cytomegalovirus (hCMV) is a ubiquitous latent persistent herpesvirus infecting 60-90% of the population worldwide. hCMV carriage in immunocompetent people is asymptomatic; thus, hCMV can be considered a component of normative aging. However, hCMV powerfully modulates many features of the immune, and likely other, systems and organs. Questions remain as to how hCMV carriage affects the human host. We used anti-CMV antibody titers as a stratifying criterion to examine the impact of "intensity" of hCMV infection as a potential biomarker of aging, inflammation, and immune homeostasis in a cohort of 247 participants stratified into younger (21-40 years) and older (> 65 years of age) groups. We showed that anti-CMV antibody titers increased with age and directly correlated to increased levels of soluble tumor necrosis factor (sTNFR) I in younger but not older participants. CD8 + cell numbers were reduced in the older group due to the loss in CD8 + T naïve (Tn) cells. In CMV carriers and, in particular, in anti-CMV Ab-high participants, this loss was mitigated or reversed by an increase in the numbers of CD8 + T effector memory (Tem) and T effector memory reexpressing CD45RA (Temra) cells. Analysis of CD38, HLA-DR, and CD57 expression revealed subset (CD4 or CD8)-specific changes that correlated with anti-CMV Ab levels. In addition, anti-CMV Ab levels predicted anti-CMV CD8 T cell responsiveness to different CMV open reading frames (ORFs) selectively in older participants, which correlated to the transcriptional order of expression of specific CMV ORFs. Implications of these results for the potential predictive value of anti-CMV Ab titers during aging are discussed.

The mastery lifestyle intervention to reduce biopsychosocial risks for pregnant Latinas and African Americans and their infants: protocol for a randomized controlled trial.

BACKGROUND: Pregnant Mexican Americans (hereafter called Latinas) and Black/African American women are at increased risk for psychological distress, contributing to preterm birth and low birthweight; acculturative stress combined with perceived stress elevates depressive symptoms in Latinas. Based on our prior research using a psychoneuroimmunology framework, we identified psychological and neuroendocrine risk factors as predictors of preterm birth in Latina women that are also identified as risk factors for Black/African American women. METHODS/DESIGN: In this prospective, randomized controlled trial with parallel group design we will explore psychosocial, neuroendocrine, and birth outcome effects of the Mastery Lifestyle Intervention (MLI). The MLI is a culturally relevant, manualized, psychosocial, group intervention integrating two cognitive behavioral therapies for both pregnant Latinas and Black/African American women (total n = 221). Study inclusion criteria are: women with current pregnancy at 14-20 weeks gestation, ability to read and speak English or Spanish, self-identify as Latina of Mexican heritage or Black/African American, 18-45 years old, born in the US or Mexico, and currently living in the US. Participants must receive Medicaid or other government-supported insurance, and meet screening criteria for anxiety, depressive symptoms, or stress. Participants are randomly assigned to either the intervention (MLI) or usual care group (UCG) in groups of 6-8 participants that occur over 6 consecutive weeks. Data are collected at 3 time points: enrollment (14-20 weeks gestation), following treatment (20-26 weeks), and 6 weeks after treatment (32-36 weeks gestation). Additional outcome, mediating, and moderating data are collected from the electronic health record during pregnancy and at birth. Analyses will primarily use generalized linear mixed modeling (GLMM) to evaluate the relationships between predictors and outcomes. DISCUSSION: This RCT will test the efficacy of two combined third generation cognitive behavioral therapies (the MLI), given in a group format over 6 sessions, as compared to a usual prenatal care group, for both Latina and African American pregnant women. If efficacious, it may be provided as an adjunct to routine prenatal care and improve mental health, as well as babies being born too small and too soon. TRIAL REGISTRATION: The trial was retrospectively registered at ClinicalTrials.gov . Bethesda (MD): National Library of Medicine. Identifier NCT05012072 , Reducing Pregnancy Risks: The Mastery Lifestyle Intervention (MLI); August 19, 2021. The trial is currently recruiting participants.

Inflammatory and immune markers in HIV-infected older adults on long-term antiretroviral therapy: Persistent elevation of sCD14 and of proinflammatory effector memory T cells.

HIV-positive patients whose viral loads are successfully controlled by active antiretroviral therapy (ART) show no clinical signs of AIDS. However, their lifespan is shorter compared with individuals with no HIV infection and they prematurely exhibit a multitude of chronic diseases typically associated with advanced age. It was hypothesized that immune system aging may correlate with, and provide useful biomarkers for, this premature loss of healthspan in HIV-positive subjects. Here, we tested whether the immune correlates of aging, including cell numbers and phenotypes, inflammatory status, and control of human cytomegalovirus (hCMV) in HIV-positive subjects on long-term successful ART (HIV+) may reveal increased "immunological age" compared with HIV-negative, age-matched cohort (HIV-) in participants between 50 and 69 years of age. Specifically, we expected that younger HIV+ subjects may immunologically resemble older individuals without HIV. We found no evidence to support this hypothesis. While T cells from HIV+ participants displayed differential expression in several differentiation and/or inhibitory/exhaustion markers in different T cell subpopulations, aging by a decade did not pronounce these changes. Similarly, while the HIV+ participants exhibited higher T cell responses and elevated inflammatory marker levels in plasma, indicative of chronic inflammation, this trait was not age-sensitive. We did find differences in immune control of hCMV, and, more importantly, a sustained elevation of sCD14 and of proinflammatory CD4 and CD8 T cell responses across age groups, pointing towards uncontrolled inflammation as a factor in reduced healthspan in successfully treated older HIV+ patients.

Diminished Cellular Immunity and Executive Cognitive Functioning Among Middle-Aged and Elderly Adults.

OBJECTIVE: Within the field of psychoneuroimmunology, much attention has been given to immune dysregulation and its impact on cognitive functioning. Some of this work has focused on the association between high levels of basal proinflammatory cytokines and poorer performance on measures of executive functioning; however, effect sizes have been quite small in human studies. METHODS: We investigated whether Epstein-Barr virus (EBV) antibody titers, a marker of immune dysregulation related to cellular immunity, may be associated with executive functioning while also attempting to replicate prior studies using two markers of proinflammatory cytokine production (i.e., circulating and lipopolysaccharide [LPS]-stimulated cytokines [interleukin 6, interleukin 1ß, interferon-γ]). A total of 71 community-dwelling adults (mean [standard deviation] age = 60.87 [6.26] years) who were seropositive for EBV infection participated in the study. RESULTS: Findings indicated that greater EBV antibody titers were associated with poorer performance on measures of the executive functions of inhibition ( B = -2.36, standard error = 1.06, p = .028) and cognitive flexibility ( B = -2.89, standard error = 1.13, p = .013) when including circulating and LPS-stimulated cytokines and other relevant covariates (i.e., age, sex, and body mass index) in linear regression analyses. Neither circulating nor LPS-stimulated cytokines were associated with performance on the cognitive tasks in the regression analyses. CONCLUSIONS: These results suggest that EBV antibody titers may be an indicator of immune dysregulation that is more relevant to executive functioning performance than either circulating or stimulated proinflammatory cytokines among community-dwelling adults.

Human Health during Space Travel: State-of-the-Art Review.

The field of human space travel is in the midst of a dramatic revolution. Upcoming missions are looking to push the boundaries of space travel, with plans to travel for longer distances and durations than ever before. Both the National Aeronautics and Space Administration (NASA) and several commercial space companies (e.g., Blue Origin, SpaceX, Virgin Galactic) have already started the process of preparing for long-distance, long-duration space exploration and currently plan to explore inner solar planets (e.g., Mars) by the 2030s. With the emergence of space tourism, space travel has materialized as a potential new, exciting frontier of business, hospitality, medicine, and technology in the coming years. However, current evidence regarding human health in space is very limited, particularly pertaining to short-term and long-term space travel. This review synthesizes developments across the continuum of space health including prior studies and unpublished data from NASA related to each individual organ system, and medical screening prior to space travel. We categorized the extraterrestrial environment into exogenous (e.g., space radiation and microgravity) and endogenous processes (e.g., alteration of humans' natural circadian rhythm and mental health due to confinement, isolation, immobilization, and lack of social interaction) and their various effects on human health. The aim of this review is to explore the potential health challenges associated with space travel and how they may be overcome in order to enable new paradigms for space health, as well as the use of emerging Artificial Intelligence based (AI) technology to propel future space health research.

Psychosocial stressors predict lower cardiovascular disease risk among Mexican-American adults living in a high-risk community: Findings from the Texas City Stress and Health Study.

The objective of this study was to examine the link between systemic and general psychosocial stress and cardiovascular disease (CVD) risk in a group of U.S. Latinos as a function of acculturation and education within the blended guiding conceptual framework of the biopsychosocial model of the stress process plus the reserve capacity model. We analyzed data from self-identifying Mexican-origin adults (n = 396, 56.9% female, Mage = 58.2 years, 55.5% < 12 years of education, 79% U.S.-born) from the Texas City Stress and Health Study. We used established measures of perceived stress (general stress), neighborhood stress and discrimination (systemic stress) to capture psychosocial stress, our primary predictor. We used the atherosclerotic CVD calculator to assess 10-year CVD risk, our primary outcome. This calculator uses demographics, cholesterol, blood pressure, and history of hypertension, smoking, and diabetes to compute CVD risk in the next 10 years. We also created an acculturation index using English-language use, childhood interaction, and preservation of cultural values. Participants reported years of education. Contrary to expectations, findings showed that higher levels of all three forms of psychosocial stress, perceived stress, neighborhood stress, and perceived discrimination, predicted lower 10-year CVD risk. Acculturation and education did not moderate the effects of psychosocial stress on 10-year CVD risk. Contextualized within the biopsychosocial and reserve capacity framework, we interpret our findings such that participants who accurately reported their stressors may have turned to their social networks to handle the stress, thereby reducing their risk for CVD. We highlight the importance of examining strengths within the sociocultural environment when considering cardiovascular inequities among Latinos.

Perceived Social Support and Latent Herpesvirus Reactivation: Testing Main and Stress-Buffering Effects in an Ethnically Diverse Sample of Adults.

OBJECTIVE: Perceived social support is consistently associated with physical health outcomes, and one potential physiological mechanism underlying this association is immune function. In this study, we tested both the main and stress-buffering effects of perceived social support on cellular immunity measured via latent herpesvirus reactivation. METHODS: Data were collected from a community-based sample of 1443 ethnically diverse adults between the ages of 25 and 90 years. Participants self-reported measures of perceived social support, stressful life events, daily hassles, and perceived stress, and provided a blood sample to assess antibody titers to the herpes simplex virus type 1 and Epstein-Barr virus (EBV). RESULTS: In accordance with the main effect hypothesis, results indicated that perceived social support was directly associated with EBV viral capsid antigen antibody titers (ß = -0.06, 95% confidence interval = -0.12 to -0.01, p = .029). Perceived social support, however, did not interact with stressful life events, daily hassles, or perceived stress to influence latent herpesvirus reactivation (p values > .05). Neither race/ethnicity nor age moderated any of the interactions between perceived social support and the stress measures on latent herpesvirus reactivation (p values > .10). CONCLUSIONS: Overall, the current study supports the main effect hypothesis, according to which higher levels of perceived social support were associated with lower levels of herpesvirus antibody titers.

Pregnant Mexican American Biopsychosocial/Cultural risks for adverse infant outcomes.

AIMS: To test a model of psychosocial/cultural/biological risk factors for poor birth outcomes in Latina pregnant women. DESIGN: An observational study measuring acculturation, progesterone, cortisol, cotinine, age, marital status, income, stress, depressive symptoms and coping. We tested a structural equation model to predict risk. METHODS: We obtained a convenience sample (N = 515) of low medical risk pregnant Mexican American Hispanic women at 22-24 weeks of gestation. Bilingual research nurses collected data from blood, urine and questionnaires. Self-report measures were the Beck Depression Inventory-II, the Perceived Stress Scale, the Acculturation Rating Scale for Mexican Americans-II and the Brief Cope. We measured progesterone and cortisol in plasma and cotinine levels in urine by enzyme-linked immunoassays. RESULTS: A PLS-SEM model revealed that Mexican American Hispanic pregnant women who were younger, single, lower income, more acculturated and who had greater negative coping, stress and depression were most at risk for having earlier and smaller babies.

Countermeasures-based Improvements in Stress, Immune System Dysregulation and Latent Herpesvirus Reactivation onboard the International Space Station - Relevance for Deep Space Missions and Terrestrial Medicine.

The International Space Station (ISS) has continued to evolve from an operational perspective and multiple studies have monitored both stress and the immune system of ISS astronauts. Alterations were ascribed to a potentially synergistic array of factors, including microgravity, radiation, psychological stress, and circadian misalignment. Comparing similar data across 12 years of ISS construction and operations, we report that immunity, stress, and the reactivation of latent herpesviruses have all improved in ISS astronauts. Major physiological improvements seem to have initiated approximately 2012, a period coinciding with improvements onboard ISS including cargo delivery and resupply frequency, personal communication, exercise equipment and protocols, food quality and variety, nutritional supplementation, and schedule management. We conclude that spaceflight associated immune dysregulation has been positively influenced by operational improvements and biomedical countermeasures onboard ISS. Although an operational challenge, agencies should therefore incorporate, within vehicle design limitations, these dietary, operational, and stress-relieving countermeasures into deep space mission planning. Specific countermeasures that have benefited astronauts could serve as a therapy augment for terrestrial acquired immunodeficiency patients.

Relationship satisfaction determines the association between Epstein-Barr virus latency and somatic symptoms after the loss of a spouse.

The loss of a spouse is associated with a host of negative health outcomes. While bereaved individuals commonly report somatic symptoms, no investigations exist of the association between reactivation of latent Epstein-Barr virus (EBV) and somatic symptoms among this population. Further, how an individual perceives the quality of their lost relationship in retrospect may impact loss outcomes. Among 99 bereaved spouses, elevated EBV antibody titers were associated with somatic symptoms for those who retrospectively reported high or mean levels of relationship satisfaction (RS), but not among those less satisfied. Further, higher RS was associated with greater grief symptoms. This study identifies higher retrospective RS as a possible risk factor for negative physical and mental health outcomes during bereavement.

Pilot Study of the Mastery Lifestyle Intervention.

BACKGROUND: Recognizing the effects of acculturation on quality of life and emotional health, especially during pregnancy, we developed an intervention that would target these factors in order to improve maternal well-being during the prenatal period and potentially improve infant outcomes, particularly preterm birth for Mexican-American women (Latinas). OBJECTIVE: The purpose of these pilot studies was to test the acceptability, feasibility, and preliminary efficacy of the mastery lifestyle intervention (MLI) to decrease depressive and anxiety symptoms and improve coping as implemented in prenatal clinics with culturally homogenous groups of Latinas. METHODS: The MLI was tested in three small pilot studies (n = 15), one in El Paso, Texas (an urban area), and two in Bastrop, Texas (a rural area outside Austin), for acceptability and feasibility. A pretest/posttest, quasi-experimental design was used with pregnant self-identified Mexican-American Latinas at 14-20 weeks' gestation. Measures of anxiety, depressive symptoms, and positive and negative coping were used. RESULTS: Feasibility was a success in terms of implementation of the MLI in an active prenatal clinic setting and the use of electronic tablets for data collection and entry of data into REDcap. Satisfaction was high, with the location of the MLI being at their primary OB/GYN clinic. Participants reported that six intervention sessions appear to be ideal as was the class length of 1.5 to 2 hours. On Cohen's d, there were medium to large effect size decreases in depressive and anxiety symptoms and small to medium effect size decreases in the use of negative coping strategies and small effect sizes for increases in positive coping strategies. DISCUSSION: Pilot testing of the MLI indicated that it was well accepted from the participants and feasible as a culturally tailored behavioral therapy administered in a group setting by nurse practitioners. Our initial pilot results also suggest preliminary efficacy as indicated by moderate to large Cohen's d effect sizes for depression and anxiety.

Church Attendance and CMV Herpes Virus Latency Among Bereaved and Non-Bereaved Adults.

OBJECTIVE: There is widespread literature linking church attendance to physical health. However, little is known about the association of church attendance and the immune system, particularly during difficult life transitions. This study investigated the association between church attendance and CMV herpes-virus latency by assessing Cytomegalovirus (CMV) IgG antibody titers among bereaved and non-bereaved individuals. METHODS: Participants included 44 bereaved individuals and 44 controls with a mean age of 68 (SD=12.84). CMV herpes-virus latency was measured using CMV IgG antibody titers. Church attendance was measured using three items from the Community Healthy Activities Model Program for Seniors (CHAMPS) Questionnaire. RESULTS: After adjusting for participant's age, gender, education, minority status, weekly alcohol consumption, smoking, depression, body mass index (BMI) and comorbidities, church attendance was associated with lower CMV IgG antibody titers among bereaved and control participants. Further, there was a significant moderating effect of church attendance in the association between bereavement status and CMV IgG antibody titers, so that bereaved individuals attending church were found to have less herpes-virus reactivation (lower CMV IgG antibody titers) when compared to their bereaved counterparts that do not attend church. CONCLUSION: This study demonstrated that church attendance is associated with less herpes-virus reactivation as indexed by lower levels of CMV IgG antibody titers, particularly among the bereaved. Future studies should focus on further understanding the pathways by which church attendance impacts CMV herpes-virus latency during stressful life events, such as bereavement.

Sex differences in executive functioning and latent herpesvirus reactivation among bereaved and nonbereaved individuals.

The death of a spouse is a highly stressful event. Better executive functioning has been shown to benefit men to a greater degree than women during stress. We evaluated potential sex differences in stress and immune dysregulation among control and bereaved participants who completed a self-report measure of perceived stress, neuropsychological measures of inhibition and updating/monitoring of information in working memory, and a blood draw to measure Epstein-Barr virus (EBV) antibody titres. Moderation analyses were conducted to test the hypothesis that better inhibition would be associated with less stress and immune dysregulation among male bereaved participants compared with female bereaved participants. Bereaved females demonstrated greater EBV antibody titres than bereaved males. Male bereaved participants benefited from better inhibition, as evidenced by fewer EBV antibody titres, whereas bereaved female participants did not. In the control group, males with high inhibition reported lower stress than males with low inhibition. Present study results are an important step towards identifying those at greatest risk of stress and poor health.

Psychological and Biological Pathways Linking Perceived Neighborhood Characteristics and Body Mass Index.

BACKGROUND: Perceived neighborhood characteristics are linked to obesity, however, the mechanisms linking these two factors remain unknown. PURPOSE: This study aimed to examine associations between perceived neighborhood characteristics and body mass index (BMI), establish whether indirect pathways through psychological distress and inflammation are important, and determine whether these associations vary by race/ethnicity. METHODS: Participants were 1,112 adults enrolled in the Texas City Stress and Health Study. Perceived neighborhood characteristics were measured using the Perceived Neighborhood Scale. Psychological distress was measured with the Center for Epidemiological Studies Depression Scale, Perceived Stress Scale and mental health subscale of the Short Form Health Survey-36. Markers of inflammation included C-reactive protein, interleukin-6, and tumor necrosis factor receptor-1. Associations were examined with Structural Equation Modeling. RESULTS: A model linking neighborhood characteristics with BMI through direct and indirect (i.e., psychological distress and inflammation) paths demonstrated good fit with the data. Less favorable perceived neighborhood characteristics were associated with greater psychological distress (B = -0.87, ß = -0.31, p < .001) and inflammation (B = -0.02, ß = -0.10, p = .035). Psychological distress and inflammation were also significantly associated with BMI (Bdistress = 0.06, ß = 0.08, p = .006; Binflammation = 4.65, ß = 0.41, p < .001). Indirect paths from neighborhood characteristics to BMI via psychological distress (B = -0.05, ß = -0.03, p = .004) and inflammation (B = -0.08, ß = -0.04, p = .045) were significant. In multiple group analysis, a model with parameters constrained equal across race/ethnicity showed adequate fit suggesting associations were comparable across groups. CONCLUSION: Our study extends the literature by demonstrating the importance of neighborhood perceptions as correlates of BMI across race/ethnicity, and highlights the role of psychological and physiological pathways.

Micro RNA clusters in maternal plasma are associated with preterm birth and infant outcomes.

The current study examined micro RNA (miRNAs) clusters from the maternal plasma to determine their association with preterm birth (PTB) and infant birth outcomes. A subsample of 42 participants who spontaneously delivered either preterm (≤37 weeks) or term was selected from a parent sample of 515 pregnant Mexican American women. Plasma samples and prenatal data were collected at a single mid-gestation time point (22-24 weeks' gestation) and birth outcomes were obtained from medical records after delivery. Circulating miRNAs were analyzed by qPCR. When miRNAs were grouped according to chromosomal cluster rather than expression level, individual miRNAs correlated strongly with other individual miRNAs within their respective genomic locus. miRNAs from the c19mc cluster negatively correlated with c14mc miRNAs, and this relationship was more pronounced in PTB. Clusters c14mc was negatively associated with length of gestation; while the c19mc was positively associated with length of gestation and infant head circumference. Together, these findings suggest that groups of miRNAs from common chromosomal clusters, rather than individual miRNAs, operate as co-regulated groups of signaling molecules to coordinate length of gestation and infant outcomes. From this evidence, differences in cluster-wide expression of miRNAs are involved in spontaneous PTB.

Objectively Measured Social Integration Is Associated With an Immune Risk Phenotype Following Marital Separation.

Background: Close relationships play an integral role in human development, and robust evidence links marital separation and divorce to poor health outcomes. Social integration may play a key role in this association. In many ways, the study of marital separation and divorce provides an ideal model system for a more complete understanding of the association between life stress and physical health. Purpose: The current study investigated associations among objectively measured social integration, psychological distress, and biomarkers of immune health in recently separated adults (N = 49). Methods: We collected four measures of immune functioning-interleukin-6, C-reactive protein, and antibody titers to latent cytomegalovirus and Epstein-Barr virus-that were combined to yield a viral-Immune Risk Profile. To assess how variability in social integration is associated with immunological correlates following the end of a marriage, we incorporated observational ecological momentary assessment data using a novel methodology (the Electronically Activated Recorder). Results: We found that objectively measured social behaviors are associated with concurrent viral-Immune Risk Profile scores over and above the effects of psychological distress and that psychological distress may be linked to biomarkers of immune health through social integration. Conclusions: This research expands current knowledge of biomarkers of immune health after divorce and separation and includes a new methodology for objective measures of social engagement.

An Evaluation of Perceived Health Risk and Depressive Symptoms Before a Disaster in Predicting Postdisaster Inflammation.

OBJECTIVE: Exposure to major life stressors is associated with subsequent enhanced inflammation-related disease processes. Depressive symptoms exacerbate stress-induced inflammatory responses. Moreover, those who report a high degree of perceived health risk before being exposed to a major life stressor such as a disaster are at risk for poor health outcomes. The present study examined whether perceived health risk and depressive symptoms before a disaster were associated with postdisaster inflammation markers. METHODS: The sample included 124 participants (mean [standard deviation] age = 55 [16] years; 69% women). At a baseline visit, participants completed self-report measures of perceived health risk and depressive symptoms (Center for Epidemiologic Studies Depression Scale) in addition to a blood draw for the assessment of inflammation markers (C-reactive protein, tumor necrosis factor receptor 1, and interleukin 6). All participants lived near a large petrochemical complex where an unexpected explosion occurred. A second blood sample was obtained 2 to 6 months after the explosion. RESULTS: No significant differences in inflammation markers were found between predisaster and postdisaster assessment (p > .21). An interaction between predisaster perceived health risk and depressive symptoms in predicting postdisaster circulating inflammation markers was identified (Cohen f = 0.051). Specifically, predisaster perceived health risk was associated with postdisaster circulating inflammation markers if predisaster depressive symptoms were greater than 8.10 on the Center for Epidemiologic Studies Depression Scale. CONCLUSIONS: These findings add to our understanding of the complex interactions between stress, depression, and immune responses. Indeed, findings provide a potential mechanism (i.e., inflammation) explaining the association between exposure to major life stressors and negative mental and physical health outcomes.

Depressive symptoms are associated with salivary shedding of Epstein-Barr virus in female adolescents: The role of sex differences.

BACKGROUND: Adolescent females have a higher prevalence of depression in comparison to their male peers - a disparity that has been increasing over the past decade. Depression is of concern as it is associated with chronic disease and to immune dysregulation, which may be one mechanism linking depression to future pathology. This study examined the extent to which sex moderated the association between depressive symptoms and immune dysregulation during adolescence using Epstein-Barr virus (EBV) reactivation, a biomarker of cellular immune response, as a model. METHODS: A representative community sample of 259 female and 279 male adolescents aged 11-17 years who were EBV IgG positive were examined. Trained interviewers collected the data during two home visits, one week apart. Depressive symptoms were measured at the first visit using the 9 item short-form of the Center for Epidemiologic Studies-Depression scale. EBV biomarkers were collected via saliva at the second visit and included a qualitative measure of EBV viral capsid antigen immunoglobulin G to assess prior EBV infection and a quantitative measure of EBV DNA to assess the number of viral copies shed in the saliva. RESULTS: In multivariable logistic regression analyses, increasing depressive symptoms were significantly associated with salivary shedding of EBV DNA for adolescent females only (logit=0.66, se=0.30, p<0.05), and the interaction between sex and depressive symptoms on salivary shedding of EBV DNA was statistically significant (logit=-1.19, se=0.42, p<0.01). Sensitivity analyses were conducted in which sex was examined as a moderator in the relationship between depressive symptoms and salivary EBV DNA quantitative copies via Tobit regression; results were consistent with the presented findings. CONCLUSIONS: Depressive symptoms are associated with EBV reactivation among EBV positive female adolescents, but not males. Future research is needed to examine EBV reactivation in female adolescents as a mechanism linking depression to future chronic disease and the role of sex hormones in explaining sex differences in the relationship between depressive symptoms and EBV reactivation.