Behavioral and psychosocial factors related to mental distress among medical students.

Introduction: Physicians die by suicide at rates higher than the general population, with the increased risk beginning in medical school. To better understand why, this study examined the prevalence of mental distress (e.g., depressive symptoms and suicide risk) and behavioral and psychosocial risk factors for distress, as well as the associations between mental distress and risk factors among a sample of medical students in a pre-COVID-19-era. Methods: Students enrolled in a large California medical school in 2018-2019 (N = 134; 52% female) completed questionnaires assessing sociodemographic characteristics, depression and suicide family history, health behaviors, and psychosocial wellbeing. Assessment scores indexing mental distress (e.g., depressive symptoms, thoughts of suicide in the past 12 months, suicide risk, and history of suicidality) and risk factors (e.g., stress, subjective sleep quality, alcohol use, impostor feelings, and bill payment difficulty) were compared across biological sex using chi-squared tests, and associations between mental distress and risk factors were determined through logistic regression. Results: Elevated mental distress indicators were observed relative to the general public (e.g., 16% positive depression screen, 17% thought about suicide in previous 12 months, 10% positive suicide risk screen, and 34% history of suicidality), as well as elevated risk factors [e.g., 55% moderate or high stress, 95% at least moderate impostor feelings, 59% poor sleep quality, 50% screened positive for hazardous drinking (more likely in females), and 25% difficulty paying bills]. A positive depression screen was associated with higher stress, higher impostor feelings, poorer sleep quality, and difficulty paying bills. Suicidal ideation in the previous 12 months, suicide risk, and a history of suicidality were independently associated with higher levels of impostor feelings. Discussion: Higher scores on assessments of depressive symptoms and suicidal thoughts and behaviors were related to several individual-level and potentially modifiable risk factors (e.g., stress, impostor feelings, sleep quality, and bill payment difficulties). Future research is needed to inform customized screening and resources for the wellbeing of the medical community. However, it is likely that the modification of individual-level risk factors is limited by the larger medical culture and systems, suggesting that successful interventions mitigate suicide risk for medical providers need to address multiple socio-ecological levels.

Oral microbial communities in children, caregivers, and associations with salivary biomeasures and environmental tobacco smoke exposure.

Human oral microbial communities are diverse, with implications for oral and systemic health. Oral microbial communities change over time; thus, it is important to understand how healthy versus dysbiotic oral microbiomes differ, especially within and between families. There is also a need to understand how the oral microbiome composition is changed within an individual including by factors such as environmental tobacco smoke (ETS) exposure, metabolic regulation, inflammation, and antioxidant potential. Using archived saliva samples collected from caregivers and children during a 90-month follow-up assessment in a longitudinal study of child development in the context of rural poverty, we used 16S rRNA gene sequencing to determine the salivary microbiome. A total of 724 saliva samples were available, 448 of which were from caregiver/child dyads, an additional 70 from children and 206 from adults. We compared children's and caregivers' oral microbiomes, performed "stomatotype" analyses, and examined microbial relations with concentrations of salivary markers associated with ETS exposure, metabolic regulation, inflammation, and antioxidant potential (i.e., salivary cotinine, adiponectin, C-reactive protein, and uric acid) assayed from the same biospecimens. Our results indicate that children and caregivers share much of their oral microbiome diversity, but there are distinct differences. Microbiomes from intrafamily individuals are more similar than microbiomes from nonfamily individuals, with child/caregiver dyad explaining 52% of overall microbial variation. Notably, children harbor fewer potential pathogens than caregivers, and participants' microbiomes clustered into two groups, with major differences being driven by Streptococcus spp. Differences in salivary microbiome composition associated with ETS exposure, and taxa associated with salivary analytes representing potential associations between antioxidant potential, metabolic regulation, and the oral microbiome. IMPORTANCE The human oral cavity is a multi-environment habitat that harbors a diversity of microorganisms. This oral microbiome is often transmitted between cohabitating individuals, which may associate oral and systemic health within family members. Furthermore, family social ecology plays a significant role in childhood development, which may be associated with lifelong health outcomes. In this study, we collected saliva from children and their caregivers and used 16S rRNA gene sequencing to characterize their oral microbiomes. We also analyzed salivary biomeasures of environmental tobacco smoke exposure, metabolic regulation, inflammation, and antioxidant potential. We show there are differences in individuals' oral microbiomes mainly due to Streptococcus spp. that family members share much of their microbes, and several bacterial taxa associate with the selected salivary biomeasures. Our results suggest there are large-scale oral microbiome patterns, and there are likely relationships between oral microbiomes and the social ecology of families.

Environmental tobacco smoke exposure is associated with increased levels of metals in children's saliva.

BACKGROUND: Exposure to environmental tobacco smoke (ETS) has been associated with detectable levels of cotinine (a nicotine metabolite) in children's saliva. However, tobacco smoke also contains toxic and essential trace metals, including chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), nickel (Ni) and zinc (Zn). OBJECTIVE: The current study examines whether there is a relationship between ETS exposure, as gauged by salivary cotinine, and salivary levels of these metals in a subset (n = 238) of children from the Family Life Project. METHODS: Using inductively-coupled-plasma optical emission spectrophotometry, we measured levels of metals in saliva from children at ~90 months of age. Salivary cotinine was measured using a commercial immunoassay. RESULTS: We found that Cr, Cu, Mn, and Zn were detected in most samples (85-99%) with lower levels of detection for Pb and Ni (9.3% and 13.9% respectively). There were no significant differences in any of the metal concentrations between males and females, nor were levels associated with body mass index, although significant differences in salivary Cr and Mn by race, state and income-to-needs ratio were observed. Children with cotinine levels >1 ng/ml had higher levels of Zn (b = 0.401, 95% CI: 0.183 to 0.619; p = 0.0003) and Cu (b = 0.655, 95% CI: 0.206 to 1.104; p = 0.004) compared to children with levels <1 ng/ml, after controlling for multiple confounders, including sex, race, BMI and income-to-needs ratio. Further, we show that children whose cotinine levels were >1 µg/L were more likely to have detectable levels of Pb in their saliva (b = 1.40, 95% CI: 0.424 to 2.459; p = 0.006) compared to children with cotinine levels <1 ng/ml, also considering confounders. IMPACT STATEMENT: This is the first study to demonstrate significant associations between salivary cotinine and salivary levels of Cu, Zn and Pb, suggesting that environmental tobacco smoke exposure my be one source of increased children's exposure to heavy metals. This study also demonstrates that saliva samples can be used to measure heavy metal exposure, and thus serve as a non-invasive tool for assessing a broader range of risk indicators.

Associations between prenatal and postnatal substance exposure and salivary C-reactive protein in early childhood.

BACKGROUND: Exposure to tobacco and cannabis during developmental periods of enhanced vulnerability (e.g., in utero and early childhood) may have long-lasting effects on child health. One potential mechanism underlying these associations is the alteration of inflammatory pathways. Using data from a longitudinal study of mother/child dyads, we examined the adjusted and combined associations of prenatal and postnatal tobacco and cannabis exposure with inflammation in early childhood. Furthermore, we explored the relations between different measures of exposure, partly reflecting differences in timing, dose, and level of fetal exposure (e.g., self-report vs. biomarker), and inflammation. Finally, we explored child sex as a moderator of prenatal and postnatal tobacco and cannabis exposure and inflammation. METHOD: Women were recruited from a local hospital during their first prenatal appointment. Repeated assessments were conducted at each trimester, at birth, and when children were 2, 9, 16, 24, 36, and 60 months old (N = 215; 112 female children). To evaluate associations with different measurement approaches, prenatal tobacco and cannabis exposure were assessed using: 1) continuous dose-response variables of maternal self-reported tobacco and cannabis use during each trimester to assess associations with timing and severity of exposure, 2) categorization of children into exposure groups based on drugs and metabolites present in infant meconium reflecting later pregnancy fetal exposure, and 3) categorization into exposure groups using a combination of maternal self-report data and biomarker data derived from maternal saliva samples and infant meconium taking advantage of multiple methods of assessment to examine group differences. Postnatal exposure to tobacco (assessed using child salivary cotinine) and cannabis (assessed using maternal self-reported average joints smoked per day) was measured at each infancy/early childhood assessment. Adjusted pre- and postnatal exposure associations with child inflammation were assessed by including both measures as predictor variables in linear regression models predicting child salivary C-reactive protein (CRP) concentrations at 60 months. Interactions between pre- and postnatal exposure variables were then modeled to investigate the combined relations between pre- and postnatal substance exposure with child salivary CRP concentrations at 60 months. RESULTS: Adjusting for postnatal exposure variables, there was a significant interaction between the average daily cigarettes and the average daily cannabis joints smoked during the third trimester predicting salivary CRP concentrations in early childhood. At high tobacco exposure, the effect of cannabis on CRP concentrations was negligible, whereas at low tobacco exposure, the effect of cannabis exposure on CRP concentrations was positive. Adjusting for postnatal tobacco and cannabis exposure, children for whom meconium data indicated co-exposure to tobacco and cannabis showed approximately 43% lower CRP concentrations at age 60 months compared to children with no exposure. However, when mother/child dyads were categorized based on a combination of maternal self-report data and biomarker data from saliva samples and infant meconium, there were no differences in salivary CRP concentrations at age 60 months across the three groups (no prenatal exposure, prenatal tobacco exposure only, prenatal co-exposure to tobacco and cannabis), controlling for postnatal associations. Regardless of the measurement method used to assess prenatal exposures in adjusted analyses, prenatal tobacco exposure alone did not predict CRP concentrations in early childhood, nor did postnatal tobacco exposure. Among boys, postnatal cannabis exposure was associated with higher concentrations of CRP at age 60 months, controlling for prenatal exposure relations. There were no significant combined associations of pre- and postnatal exposure with CRP concentrations. CONCLUSION: This study expands upon known relations between prenatal and postnatal substance exposure and immunological outcomes in early childhood, underscoring the importance of assessing cannabis exposure during gestation and early life in combination with tobacco exposure.

Hypothalamic-pituitary-adrenal and sympathetic nervous system responses to social evaluative stress in chronic cannabis users and non-users.

BACKGROUND: To advance our understanding of the health-related consequences of chronic cannabis use, this study examined hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) reactivity and regulation in response to a well-characterized, acute, social evaluative stress task among cannabis users and non-users. We also explored differences in HPA-SNS coordination across the stress task in cannabis users and non-users. METHOD: Participants were 75 adults (53% female) who reported no use of tobacco/nicotine products. Cannabis use was measured using self-report and salivary/urinary THC levels. Participants were classified as cannabis users (n = 33) if they reported using cannabis at least twice per week in the prior year and had a positive salivary/urinary THC test or as non-users (n = 42) if they reported no use in the prior year and had a negative THC test. During a laboratory visit, participants completed the standard Trier Social Stress Test (TSST) and provided saliva samples before, and 5, 20, and 40 min after the task. Samples were assayed for salivary cortisol and alpha-amylase (sAA) as indices of HPA axis and SNS activity, respectively. RESULTS: Multilevel piecewise growth models revealed that, relative to non-users, cannabis users showed (a) blunted cortisol reactivity and recovery to the TSST, and (b) greater reductions in sAA concentrations following the TSST. Chronic cannabis users may exhibit blunted HPA axis responses and greater SNS recovery to acute psychosocial stress. Implications of individual differences in stress reactivity and regulation for the biobehavioral health of chronic cannabis users are discussed.

Characterizing and Evaluating Diurnal Salivary Uric Acid Across Pregnancy Among Healthy Women.

Uric acid levels during pregnancy have been examined as a potential indicator of risk for gestational diabetes mellites, hypertension, and related adverse birth outcomes. However, evidence supporting the utility of serum uric acid levels in predicting poor maternal and fetal health has been mixed. The lack of consistent findings may be due to limitations inherent in serum-based biomeasure evaluations, such as minimal repeated assessments and variability in the timing of these assessments. To address these gaps, we examined repeated measurements of diurnal salivary uric acid (sUA) levels in a sample of 44 healthy women across early-mid and late pregnancy. We assessed potential covariates and confounds of sUA levels and diurnal trajectories, as well as associations between maternal weight gain and blood pressure during pregnancy and sUA concentrations. Using multilevel linear models, we found sUA increased across pregnancy and displayed a robust diurnal pattern with the highest concentrations at waking, a steep decline in the early morning, and decreasing levels across the day. Maternal pre-pregnancy BMI, age, prior-night sleep duration, and fetal sex were associated with sUA levels and/or diurnal slopes. Maternal blood pressure and gestational weight gain also showed significant associations with sUA levels across pregnancy. Our results expand upon those found with serum UA measurements. Further, they demonstrate the feasibility of using at-home, minimally-invasive saliva sampling procedures to track UA levels across pregnancy with potential applications for the long-term monitoring of maternal cardiometabolic risk.

Censored data considerations and analytical approaches for salivary bioscience data.

Left censoring in salivary bioscience data occurs when salivary analyte determinations fall below the lower limit of an assay's measurement range. Conventional statistical approaches for addressing censored values (i.e., recoding as missing, substituting or extrapolating values) may introduce systematic bias. While specialized censored data statistical approaches (i.e., Maximum Likelihood Estimation, Regression on Ordered Statistics, Kaplan-Meier, and general Tobit regression) are available, these methods are rarely implemented in biobehavioral studies that examine salivary biomeasures, and their application to salivary data analysis may be hindered by their sensitivity to skewed data distributions, outliers, and sample size. This study compares descriptive statistics, correlation coefficients, and regression parameter estimates generated via conventional and specialized censored data approaches using salivary C-reactive protein data. We assess differences in statistical estimates across approach and across two levels of censoring (9% and 15%) and examine the sensitivity of our results to sample size. Overall, findings were similar across conventional and censored data approaches, but the implementation of specialized censored data approaches was more efficient (i.e., required little manipulations to the raw analyte data) and appropriate. Based on our review of the findings, we outline preliminary recommendations to enable investigators to more efficiently and effectively reduce statistical bias when working with left-censored salivary biomeasure data.

The case for the repeatability intra-class correlation as a metric of precision for salivary bioscience data: Justification, assessment, application, and implications.

Best practice standards for measuring analyte levels in saliva recommend that all biospecimens be tested in replicate with mean concentrations used in statistical analyses. This approach prioritizes minimizing laboratory-based measurement error but, in the process, expends considerable resources. We explore the possibility that, due to advances in salivary assay precision, the contribution of laboratory-based measurement error in salivary analyte data is very small relative to more important and meaningful variability in analyte levels across biological replicates (i.e., between different specimens). To evaluate this possibility, we examine the utility of the repeatability intra-class correlation (rICC) as an additional index of salivary analyte data precision. Using randomly selected subsamples (Ns=200 and 60) of salivary analyte data collected as part of a larger epidemiologic study, we compute the rICCs for seven commonly assayed salivary measures in biobehavioral research - cortisol, alpha-amylase, c-reactive protein, interlekin-6, uric acid, secretory immunoglobulin A, and testosterone. We assess the sensitivity of rICC estimates to assay type and the unique distributions of the underlying analyte data. We also use simulations to examine the bias, precision, and coverage probability of rICC estimates calculated for small to large sample sizes. For each analyte, the rICCs revealed that less than 5% of variation in analyte levels was attributable to laboratory-based measurement error. rICC estimates were similar across all analytes despite differences in analyte levels, average intra-assay coefficients of variation, and in the distributional properties of the data. Guidelines for calculating rICC are provided to enable investigators and laboratory staff to apply this metric and more accurately quantify, and communicate, the magnitude of laboratory-based measurement error in their data. By helping investigators scale measurement error relative to more scientifically meaningful variability between biological replicates, the application of the rICC has the potential to influence research strategies and tactics such that resources (e.g., finances, effort, number/volume of biospecimens) are allocated more efficiently and effectively.

Best practice recommendations for the measurement and interpretation of salivary proinflammatory cytokines in biobehavioral research.

Despite the integration of salivary inflammatory cytokines into research across the biobehavioral, psychological, clinical, and health-related disciplines, there is little guidance regarding the biospecimen collection, handling, and storage practices that maximize the quality and validity of salivary cytokine data. Furthermore, associations between salivary cytokines and measures related to oral health are rarely assessed and accounted for in studies outside the oral health fields. To address these gaps, we examine the sensitivity of salivary interleukin-1ß (IL-1ß), IL-6, IL-8, and tumor necrosis factor-α (TNF-α) to changes in saliva sample collection technique and cold chain management procedures. Using subsets of saliva samples collected from 150 healthy adults, we measure salivary IL-1ß, IL-6, IL-8, TNF-α, and other oral health-related indices (i.e., blood contamination [transferrin], and salivary matrixmallotprotienase-8). In addition to examining changes in cytokine levels associated with sample collection technique and cold chain management procedures, we assess relations between cytokine concentrations and levels of other oral health-related measures. We found that IL-1ß, IL-6, and IL-8 were more robust to changes in sample collection and cold chain management procedures than TNF-α, and all cytokines were positively associated with other oral health-related measures. Based on our findings, we recommend analyte-specific guidance for measuring and interpreting salivary cytokine concentrations.

Correspondence Between Cytomegalovirus Immunoglobulin-G Levels Measured in Saliva and Serum.

Human cytomegalovirus (HCMV) infects more than 80% of the global population. While mostly asymptomatic, HCMV infection can be serious among the immunocompromised, and it is implicated in chronic disease pathophysiology in adulthood. Large-scale minimally invasive HCMV screening could advance research and public health efforts to monitor infection prevalence and prevent or mitigate downstream risks associated with infection. We examine the utility of measuring HCMV immunoglobulin-G (IgG) levels in saliva as an index of serum levels. Matched serum and saliva samples from healthy adults (N = 98; 44% female; 51% white) were assayed for HCMV IgG, total salivary protein, and salivary markers related to oral inflammation, blood, and tissue integrity. We examine the serum-saliva association for HCMV IgG and assess the influence of participant characteristics and factors specific to the oral compartment (e.g., oral inflammation) on HCMV IgG levels and cross-specimen relations. We found a robust serum-saliva association for HCMV IgG with serum antibody levels accounting for >60% of the variance in salivary levels. This relation remained after adjusting for key demographic and oral immune-related variables. Compared to the serum test, the salivary HCMV IgG test had 51% sensitivity and 97% specificity. With improvements in assay performance and sample optimization, HCMV antibody levels in oral fluids may be a useful proxy for serum levels.

Reactivity of salivary uric acid in response to social evaluative stress in African Americans.

High uric acid (UA) is associated with hypertension and cardiovascular disease (CVD), both of which occur disproportionately among African Americans. High UA also predicts greater blood pressure reactivity responses to acute social stress. However, whether UA itself shows reactivity in response to stress is unknown. We evaluated salivary uric acid (sUA) and blood pressure reactivity in response to acute social stress. Healthy African Americans (N = 103; 32 % male; M age = 31.36 years), completed the Trier Social Stress Test. sUA and blood pressure measurements were taken before, during and after the stressor task. sUA showed significant reactivity and recovery, especially among older African Americans. Total sUA activation was also associated with systolic and diastolic blood pressure total activation. Findings illuminate that acute stress may be a way in which UA is implicated in hypertension and CVD, suggesting a critical need to explore UA reactivity as a novel parameter of the acute stress response.

Salivary total Immunoglobulin G as a surrogate marker of oral immune activity in salivary bioscience research.

The integration of salivary biomeasures in biobehavioral, psychophysiological, and clinical research has greatly expanded our ability to study the biopsychosocial processes underlying health. Much of this research, however, has failed to adequately assess and adjust for the impact of oral immune activity on salivary biomeasure concentrations and associations with serum levels. Aiming to improve the validity and reliability of salivary biomeasure data, we examine salivary total Immunoglobulin G (IgG) as a potential surrogate marker of oral inflammation and immune activity. During a single study visit in Baltimore, Maryland, healthy young adult participants provided matched blood and saliva samples (N=99; age 18-37 years, 42% female) and completed an oral health questionnaire. Biospecimens were assayed for total IgG and immune markers related to inflammation (cytokines), blood in saliva (transferrin), and tissue remodeling (matrix metalloproteinase-8). Total IgG (µg/mL) concentrations were higher in serum than saliva. Salivary total IgG was associated with some self-reported oral health measures, and strongly positively associated with all salivary immune markers. Controlling for salivary total IgG may be a feasible, affordable approach to adjusting salivary biomeasure findings for the influence of the oral immune environment when it is not possible or practical to obtain clinical oral health data.

Long-Term Associations Between Prenatal Maternal Cortisol and Child Neuroendocrine-Immune Regulation.

BACKGROUND: Advancing understanding of the developmental origins of neuroendocrine-immune (NEI) functioning is key to elucidating the biological mechanisms involved in health and disease risk across the lifespan. This study examined whether prenatal maternal hypothalamic-pituitary-adrenal (HPA) activity moderates child NEI relations and explored the consistency of this moderating effect across gestation. METHODS: Pregnant women participated in five prenatal study visits from 24 to 38 weeks gestation. At each visit, women provided a saliva sample. In a 5-year follow-up study, children (nfemale = 25, nmale=20) provided four saliva samples and participated in behavioral assessments and challenge tasks. Prenatal maternal saliva samples were assayed for cortisol. Child saliva samples were assayed for cortisol and cytokines (IL-1ß, IL-6, IL-8, TNFα) as indices of HPA and inflammatory activity. Multilevel mixed-effects models examined the moderation of child NEI relations by prenatal maternal cortisol. RESULTS: Among males, average prenatal maternal cortisol did not moderate child NEI relations. Among females, average prenatal maternal cortisol moderated some child NEI relations with higher prenatal cortisol associated with more positive cortisol-cytokine relations at age five. When examined by gestational time point, there were more significant NEI moderation effects by maternal cortisol from later gestation (≥ 30 weeks) than earlier. CONCLUSIONS: The findings suggest prenatal maternal HPA activity may moderate child NEI functioning. Additional research conducted with more heterogeneous and larger samples is needed to fully understand these relations. Furthering our knowledge of NEI development has important research and clinical implications, particularly for understanding and addressing conditions with inflammatory pathophysiologies, such as depression and cardiovascular disease.

Salivary uric acid: Associations with resting and reactive blood pressure response to social evaluative stress in healthy African Americans.

High levels of uric acid are associated with greater risk of stress-related cardiovascular illnesses that occur disproportionately among African Americans. Whether hyperuricemia affects biological response to acute stress remains largely unknown, suggesting a need to clarify this potential connection. The current study examined how salivary uric acid (sUA) is associated with resting and reactive blood pressure - two robust predictors of hypertension and related cardiovascular disease and disparity. Healthy African Americans (N = 107; 32% male; M age = 31.74 years), completed the Trier Social Stress Test to induce social-evaluative stress. Systolic and diastolic blood pressure readings were recorded before, during, and after the task to assess resting and reactive change in blood pressure. Participants also provided a saliva sample at baseline that was assayed for sUA. At rest, and controlling for age, sUA was modestly associated with higher systolic (r = .201, p = .044), but not diastolic (r = .100, p = .319) blood pressure. In response to the stressor task, and once again controlling for age, sUA was also associated with higher total activation of both systolic (r = .219, p = .025) and diastolic blood pressure (r = .198, p < .044). A subsequent moderation analysis showed that associations between sUA and BP measures were significant for females, but not for males. Findings suggest that uric acid may be implicated in hypertension and cardiovascular health disparities through associations with elevated blood pressure responses to acute social stress, and that low levels of uric acid might be protective, particularly for females.

The validity, stability, and utility of measuring uric acid in saliva.

AIM: Serum uric acid (UA) is associated with many health conditions, including kidney, cardiovascular, and metabolic disorders. We examined the validity and stability of salivary UA as a noninvasive measure of serum UA. MATERIALS & METHODS: Using serum and salivary UA data from healthy adults (n = 99), we examined the UA serum-saliva correlation, and UA associations with adiponectin and C-reactive protein. Using longitudinal data from young adults (n = 182), we examined salivary UA stability. RESULTS: We found robust positive serum-saliva correlations for UA. UA and adiponectin were inversely related in serum and saliva. Salivary UA was relatively stable; 62-66% of variance could be attributed to a latent trait-like component. CONCLUSION: Salivary UA may be an important biomarker indexing health and disease risk.

Adiponectin: Serum-saliva associations and relations with oral and systemic markers of inflammation.

This study addresses gaps in our understanding about the validity and utility of using salivary adiponectin to index serum adiponectin levels. Matched blood and saliva samples were collected on a single occasion from healthy adults (n=99; age 18-36 years, 53% male). Serum and saliva was assayed for adiponectin and inflammatory cytokines (IL-1ß, IL-6, IL-8, TNFα), and saliva was also assayed for markers of blood contamination (transferrin), total protein (salivary flow rate) and matrix metalloproteinase-8 (MMP-8). We examined the extent to which salivary adiponectin was associated with serum adiponectin, and the influence of potential confounders on the serum-saliva correlation, including age, sex, body mass index, and markers of inflammation, oral health, salivary blood contamination, and flow rate. Findings revealed a modest serum-saliva association for adiponectin, and strong positive associations between salivary adiponectin and salivary levels of inflammatory cytokines, MMP-8, transferrin, and total protein. By contrast, salivary adiponectin was not related to serum levels of inflammatory activity. The magnitude of the serum-saliva association was strengthened when controlling for total protein in saliva, blood leakage into oral fluid, salivary inflammatory cytokines, and MMP-8. The pattern of findings extends our understanding of salivary adiponectin and its potential use as an index of circulating adiponectin levels.

Income, Family Context, and Self-Regulation in 5-Year-Old Children.

OBJECTIVE: Self-regulation (SR) is a core aspect of child development with enduring effects on health and wellbeing across the lifespan. Early childhood poverty may shape SR development. This study examined the cross-sectional relationship among family income, family context, and SR in 5-year-old children. METHODS: A total of 140 five-year-old children and their mothers participated in the study. Children completed a battery of SR tasks; mothers completed questionnaires. Cognitive and emotional SR composite scores were generated based on a principal component analysis of the SR tasks. The SR scores were first regressed on family income (in 10 levels ranging from <5000 to 150,000+) adjusting for age, sex, and race of the child; family context variables were subsequently added to the models. RESULTS: Controlling for age, sex, and race, each level increase in family income was associated with 0.04 SD increase in emotional SR (p = .32) and 0.08 SD increase in cognitive SR (p = .01). In fully adjusted models, exposure to household instability and experiencing 10 or more negative life events was associated with worse emotional SR; exposure to mother's depressive symptoms was associated with worse cognitive SR. Higher income buffered children's SR from some contextual risk factors. Family contextual variables explained 62% of the correlation between higher income and better cognitive SR scores. CONCLUSION: Income-based cognitive SR disparities were associated with family contextual factors. Screening for family adversity in pediatric care and linking families to needed resources may protect children's developing SR capacities, with benefits to health and well-being.

Subjective Social Status and Psychological Distress in Mothers of Young Children.

Introduction Perceptions of social standing have increasingly well-documented relationships with health. Higher subjective social status (SSS) is associated with better psychological well-being among women, and mothers of newborns. The relationship between SSS and psychological distress among mothers of young children, however, is largely unknown. SSS may provide insight into aspects of maternal functioning that are relevant to parenting capacity, as well as insight into future health; in addition, SSS is brief, and may be perceived as less intrusive than other measures of socioeconomic status or mental health. We evaluated the relationship between SSS and psychological distress among mothers of 5-year-old children from diverse socioeconomic backgrounds. Methods One hundred and sixty-two mothers of 5-year old children, who participated in a study of child self-regulation, completed surveys that assessed sociodemographics, mental health, and perceived social support. The MacArthur Scale of SSS used pictures of ten-rung ladders to assess respondents' social position in relation to the US (SES ladder) and their community (community ladder). Quantile regression models were used to assess the relationship between maternal psychological distress (perceived social support, depressive symptoms, anxiety) and the ladders (individually and together), adjusting for maternal age, race, education, and number of children. To examine whether the SSS-health relationships differed by race, the models were also stratified by race. Results Community ladder ranking was positively associated with social support (ß = 1.34, SE = 0.33, p < .001), and negatively associated with depressive symptoms (ß = -1.34, SE = 0.52, p < .05). SES ladder ranking was positively associated with social support (ß = 1.17, SE = 0.52, p < .05). Findings in the full sample were driven by more robust relationships between psychological distress and community SSS among Black/African-American mothers. Discussion The findings suggest that perceived social standing in one's community is associated with maternal psychological well-being. Community SSS may be particularly influential for Black/African-American mothers' well-being.

State of the Art Review: Poverty and the Developing Brain.

In the United States, >40% of children are either poor or near-poor. As a group, children in poverty are more likely to experience worse health and more developmental delay, lower achievement, and more behavioral and emotional problems than their more advantaged peers; however, there is broad variability in outcomes among children exposed to similar conditions. Building on a robust literature from animal models showing that environmental deprivation or enrichment shapes the brain, there has been increasing interest in understanding how the experience of poverty may shape the brain in humans. In this review, we summarize research on the relationship between socioeconomic status and brain development, focusing on studies published in the last 5 years. Drawing on a conceptual framework informed by animal models, we highlight neural plasticity, epigenetics, material deprivation (eg, cognitive stimulation, nutrient deficiencies), stress (eg, negative parenting behaviors), and environmental toxins as factors that may shape the developing brain. We then summarize the existing evidence for the relationship between child poverty and brain structure and function, focusing on brain areas that support memory, emotion regulation, and higher-order cognitive functioning (ie, hippocampus, amygdala, prefrontal cortex) and regions that support language and literacy (ie, cortical areas of the left hemisphere). We then consider some limitations of the current literature and discuss the implications of neuroscience concepts and methods for interventions in the pediatric medical home.

Maternal distress and child neuroendocrine and immune regulation.

RATIONALE: Neuroendocrine-immune regulation is essential for maintaining health. Early-life adversity may cause dysregulation in the neuroendocrine-immune network through repeated activation of the stress response, thereby increasing disease risk. OBJECTIVE: This paper examined the extent to which maternal psychological well-being moderates neuroendocrine-immune relations in children. METHODS: We used data from a laboratory-based study of mothers and their five-year old children (n = 125 mother-child pairs) conducted from 2011 to 2013 in Baltimore, Maryland. Child saliva was assayed for markers of immune function (i.e., cytokines: interleukin [IL]-1ß, IL-6, IL-8, tumor necrosis factor alpha [TNF-α]) and hypothalamic-pituitary-adrenal activity (i.e., cortisol). A composite score for depressive symptoms, anxiety, and parenting stress characterized maternal psychological distress. Multilevel mixed models examined the relationship between maternal psychological well-being and child neuroendocrine-immune relations. RESULTS: Significant cytokine × maternal distress interactions indicated that as maternal distress increased, expected inverse cytokine-cortisol relations within children became weaker for IL-1ß, IL-6, and TNF-α. Sex-stratified models revealed that these interactions were only significant among girls. Among boys, there were inverse cytokine-cortisol relations for all cytokines, and, while in the same direction as observed among girls, the cytokine × maternal distress interactions were non-significant. CONCLUSION: The findings suggest that maternal distress is associated with child neuroendocrine-immune relations in saliva and may alter the sensitivity of inflammatory immune processes to cortisol's inhibitory effects. This desensitization may place the child at risk for inflammatory diseases. The findings support efforts for the early detection and treatment of at-risk mothers to protect maternal and child health and well-being.