Determining the relationship of p16INK4a and additional molecular markers of aging with clinical frailty in hematologic malignancy.

PURPOSE: Older adults with hematologic malignancies (HM) have unique challenges due to age and fitness. The primary aim of this pilot study was to benchmark the ability of multiple biomarkers of aging (p16, epigenetic clocks, T cell gene expression profiles, and T cell receptor excision circles (TREC) to identify frailty as measured by a clinical impairment index (I2) in patients with HM. METHODS: 70 patients newly diagnosed with HM had peripheral blood T lymphocytes (PBTL) analyzed for p16INK4a expression using the OSU_Senescence Nanostring CodeSet. PBTL epigenetic age was measured using 7 epigenetic clocks, and TREC were quantified by qRT-PCR. A composite clinical impairment index (I2) was generated by combining values from 11 geriatric metrics (Independent Activities of Daily Living (iADL), physical health score, Short Physical Performance Battery (SPPB), Body Mass Index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status, self-reported KPS, Blessed Orientation Memory Concentration (BOMC), polypharmacy, Mental Health Inventory (MHI)-17, Medical Outcomes Study (MOS) subscales). Clinical frailty was defined as a score of 7 or greater on the I2. RESULTS: Age-adjusted p16INK4a was similar in newly diagnosed patients and healthy controls (p > 0.1). PBTL p16INK4a levels correlated positively with the Hannum [r = 0.35, 95% CI (0.09-0.75); p adj. = 0.04] and PhenoAge [r = 0.37, 95% CI (0.11-0.59); p adj. = 0.04] epigenetic clocks. The discrimination ability of the I2 model was calculated using the area under the receiver operating characteristic curve (AUC). After adjusting for chronologic age and disease group, baseline p16INK4a [AUC = 0.76, 95% CI (0.56-0.98); p = 0.01], Hannum [AUC = 0.70, 95% CI (0.54-0.85); p = 0.01], PhenoAge [AUC = 0.71, 95% CI (0.55-0.86); p = 0.01], and DunedinPACE [AUC = 0.73, 95% CI (0.57-0.88); p = < 0.01] measures showed the greatest potential to identify clinical frailty using the I2. CONCLUSIONS: Our pilot data suggest that multiple blood-based aging biomarkers have potential to identify frailty in older adults with HM. IMPLICATIONS FOR CANCER SURVIVORS: We developed the I2 index to quantify impairments across geriatric domains and discovered that PBTL p16, Hannum, PhenoAge, and DunedinPACE are promising indicators of frailty in HM.

Psychoneuroimmunology in multiple myeloma and autologous hematopoietic stem cell transplant: Opportunities for research among patients and caregivers.

Multiple myeloma (MM) is an incurable cancer and is the leading indication for autologous hematopoietic stem cell transplantation (HSCT). To be eligible for HSCT, a patient must have a caregiver, as caregivers play a central role in HSCT preparation and recovery. MM patients remain on treatment indefinitely, and thus patients and their caregivers face long-term challenges including the intensity of HSCT and perpetual therapy after transplant. Importantly, both patients and their caregivers show heightened depressive and anxiety symptoms, with dyadic correspondence evidenced and caregivers' distress often exceeding that of patients. An extensive psychoneuroimmunology (PNI) literature links distress with health via immune and neuroendocrine dysregulation as well as biological aging. However, data on PNI in the context of multiple myeloma - in patients or caregivers - are remarkably limited. Distress in MM patients has been associated with poorer outcomes including higher inflammation, greater one year post-HSCT hospital readmissions, and worse overall survival. Further, anxiety and depression are linked to biological aging and may contribute to the poor long-term health of both patients and caregivers. Because MM generally affects older adults, individual differences in biological aging may represent an important modifier of MM biology and HSCT treatment outcomes. There are a number of clinical scenarios in which biologically younger people could be prescribed more intensive therapies, with potential for greater benefit, by using a personalized cancer therapy approach based on the quantification of physiologic reserve. Further, despite considerable psychological demands, the effects of distress on health among MM caregivers is largely unexamined. Within this context, the current critical review highlights gaps in knowledge at the intersection of HSCT, inflammation, and biological aging in the context of MM. Research in this area hold promise for opportunities for novel and impactful psychoneuroimmunology (PNI) research to enhance health outcomes, quality of life, and longevity among both MM patients and their caregivers.

Understanding the health effects of caregiving stress: New directions in molecular aging.

Dementia caregiving has been linked to multiple health risks, including infectious illness, depression, anxiety, immune dysregulation, weakened vaccine responses, slow wound healing, hypertension, cardiovascular disease, metabolic syndrome, diabetes, frailty, cognitive decline, and reduced structural and functional integrity of the brain. The sustained overproduction of proinflammatory cytokines is a key pathway behind many of these risks. However, contrasting findings suggest that some forms of caregiving may have beneficial effects, such as maintaining caregivers' health and providing a sense of meaning and purpose which, in turn, may contribute to lower rates of functional decline and mortality. The current review synthesizes these disparate literatures, identifies methodological sources of discrepancy, and integrates caregiver research with work on aging biomarkers to propose a research agenda that traces the mechanistic pathways of caregivers' health trajectories with a focus on the unique stressors facing spousal caregivers as compared to other informal caregivers. Combined with a focus on psychosocial moderators and mechanisms, studies using state-of-the-art molecular aging biomarkers such as telomere length, p16INK4a, and epigenetic age could help to reconcile mixed literature on caregiving's sequelae by determining whether and under what conditions caregiving-related experiences contribute to faster aging, in part through inflammatory biology. The biomarkers predict morbidity and mortality, and each contributes non-redundant information about age-related molecular changes -together painting a more complete picture of biological aging. Indeed, assessing changes in these biopsychosocial mechanisms over time would help to clarify the dynamic relationships between caregiving experiences, psychological states, immune function, and aging.

Repetitive negative thinking during pregnancy and postpartum: Associations with mental health, inflammation, and breastfeeding.

INTRODUCTION: Repetitive negative thinking (RNT) is a transdiagnostic feature that predicts increased mental health risks, inflammation, and reduced engagement in health promoting behaviors. Depression, anxiety, stress, inflammation, higher body mass index (BMI), and low engagement in health behaviors are associated with adverse outcomes during pregnancy as well as postpartum. However, there is limited literature on the associations between RNT and these contributing factors in the perinatal period, an at-risk time during which women may benefit from clinical interventions directed at RNT. METHODS: This study examined the contribution of RNT to inflammation [interleukin (IL)-6] and breastfeeding duration through mediating indicators of mental health and BMI. Behavioral and biological assessments occurred during late pregnancy as well as at 4-6 weeks, 4 months, 8 months, and 12 months postpartum. RESULTS: RNT was positively associated with depressive symptoms, anxiety, and perceived stress (ps ≤ .001) at each assessment timepoint, with the strongest associations observed at the pregnancy assessment and significant, but attenuated, associations during postpartum (ps < .01). In modeling of the association between RNT and IL-6, the indirect effect of BMI was significant at each timepoint (95%CIs 0.0013, 0.0052). Women with lower RNT exhibited longer breastfeeding duration (p = .02). These effects were not significantly mediated by mental health indicators. CONCLUSIONS: Clinically meaningful relationships, in which RNT predicts mental health, inflammation, and health behavior engagement during pregnancy and postpartum were observed. Clinical interventions to reduce RNT may have unique benefits this time. LIMITATIONS: Further research is warranted to determine if therapies to reduce RNT confer unique benefits for maternal and child health.

Associations Between Gut Microbes and Social Behavior in Healthy 2-Year-Old Children.

OBJECTIVE: Emerging research has connected abundances of specific bacteria to differences in psychosocial behaviors in animals and adult humans. However, research assessing mind-microbiome associations in children is sparse with extant work primarily focused on populations with autism, making it unclear whether links are also present in typically developing children. The current study fills this gap by examining associations between prosocial-self-regulating temperaments (effortful control; EC) and the gut microbiome in typically developing children. METHODS: Maternal ratings of temperament were assessed in 77 toddlers 18 to 27 months of age (46.7% female, mean age = 23.14 months). Next-generation pyrosequencing of the V1-V3 region of the 16S rRNA gene was used to classify children's gut microbial composition from fecal samples. EC included the following subcategories: cuddliness, attentional focusing, attentional shifting, inhibitory control, and low-intensity pleasure. RESULTS: After adjusting for covariates, EC was positively associated with relative abundances of Akkermansia (Δ R2 = 0.117, b = 0.022, SE = 0.007, p = .002), with cuddliness (i.e., joy and ease of being held) driving the relation. Furthermore, attentional focusing was negatively associated with Alistipes (Δ R2 = 0.062, b = -0.011, SE = 0.005, p = .028). Permutational analysis of variance revealed no significant differences in community structure between high and low EC groups on the phylum level ( R2 = 0.00372, p = .745) or the genus level ( R2 = 0.01559, p = .276). CONCLUSIONS: Findings suggest that certain microbes may be linked to prosocial behaviors used to regulate emotion in typically developing children. Further research is needed to test whether these observations replicate in larger samples.

Perceived social support predicts self-reported and objective health and health behaviors among pregnant women.

Perinatal health and health behaviors play a crucial role in maternal and neonatal health. Data examining psychosocial factors which predict self-reported health and health behaviors as well as objective indicators downstream of health behaviors among pregnant women are lacking. In this longitudinal study design with 131 pregnant women, perceived social support was examined as a predictor of self-rated health and average levels of sleep quality, health-promoting and health-impairing behaviors, and red blood cell (RBC) polyunsaturated fatty acids across early, mid, and late pregnancy. Participants provided a blood sample and fatty acid methyl esters were analyzed by gas chromatography. Measures included the Multidimensional Scale of Perceived Social Support, Pittsburgh Sleep Quality Index, and Prenatal Health Behavior Scale. Regression models demonstrated that, after adjustment for income, race/ethnicity, age, relationship status, pre-pregnancy body mass index, greater social support was associated with better self-rated health (p = 0.001), greater sleep quality (p = 0.001), fewer health-impairing behaviors (p = 0.02), and higher RBC omega-3 fatty acids (p = 0.003). Associations among social support with health-promoting behaviors, RBC omega-6 fatty acids, or gestational weight gain were not significant. Findings underscore the benefits of perceived social support in the context of pregnancy. Examination of pathways that link social support with these outcomes will be meaningful in determining the ways in which perinatal psychosocial interventions may promote health.

Lifetime stressor exposure, systemic inflammation during pregnancy, and preterm birth among Black American women.

Although Black American mothers and infants are at higher risk for morbidity and mortality than their White counterparts, the biological mechanisms underlying these phenomena remain largely unknown. To investigate the role that lifetime stressor exposure, perceived stressor severity, and systemic inflammatory markers might play, we studied how these factors were interrelated in 92 pregnant Black American women. We also compared inflammatory marker levels for women who did versus did not go on to give birth preterm. During the early third trimester, women completed the Stress and Adversity Inventory for Adults to assess the stressors they experienced over their lifetime. Women also provided blood samples for plasma interleukin (IL)-6, IL-8, IL-1ß, and tumor necrosis factor (TNF)-α quantification. Preterm births were identified by medical record review. Controlling for relevant covariates, there were significant positive associations between average levels of both overall and acute perceived stressor severity and plasma IL-1ß levels. Controlling for perceived stress at assessment and exposure to racial discrimination did not affect these results. Mediation models revealed that exposure to more chronic stressors was related to higher plasma IL-1ß levels, as mediated by higher average levels of overall perceived stressor severity. Exposure to fewer acute stressors was related to higher plasma IL-1ß levels, as mediated by higher average levels of acute perceived stressor severity. Finally, women who went on to give birth preterm had higher levels of plasma IL-6. These data thus highlight the potential importance of assessing and addressing lifetime stressor exposure among mothers before and during maternal-infant care.

Immune and Epigenetic Pathways Linking Childhood Adversity and Health Across the Lifespan.

Childhood adversity is associated with a host of mental and physical health problems across the lifespan. Individuals who have experienced childhood adversity (e.g., child abuse and neglect, family conflict, poor parent/child relationships, low socioeconomic status or extreme poverty) are at a greater risk for morbidity and premature mortality than those not exposed to childhood adversity. Several mechanisms likely contribute to the relationship between childhood adversity and health across the lifespan (e.g., health behaviors, cardiovascular reactivity). In this paper, we review a large body of research within the field of psychoneuroimmunology, demonstrating the relationship between early life stress and alterations of the immune system. We first review the literature demonstrating that childhood adversity is associated with immune dysregulation across different indices, including proinflammatory cytokine production (and its impact on telomere length), illness and infection susceptibility, latent herpesvirus reactivation, and immune response to a tumor. We then summarize the growing literature on how childhood adversity may alter epigenetic processes. Finally, we propose future directions related to this work that have basic and applied implications.

A biopsychosocial framework for understanding sexual and gender minority health: A call for action.

The number of US adults identifying as lesbian, gay, bisexual, transgender, or a different sexual identity has doubled since 2008, and about 40 % of the sexual and gender minority population identify as people of color. Minority stress theory posits that sexual and gender minorities are at particular risk for stress via stigma and discrimination at the structural, interpersonal, and individual levels. This stress, in turn, elevates the risk of adverse health outcomes across several domains. However, there remains a conspicuously limited amount of research on the psychoneuroimmunology of stress among sexual and gender minorities. We developed the Biopsychosocial Minority Stress Framework which posits that sexual minority status leads to unique experiences of minority stress which results in adverse health behavioral factors, elevated psychological distress and sleep disturbance, and immune dysregulation. Moderators in the model include both individual differences and intersectional identities. There is a crucial need to understand the biological-psychological axis of stress among the increasingly visible sexual and gender minority population to increase their health, longevity, and quality of life.

Racial Discrimination and Stress Across the Life Course: Associations With Prenatal Inflammation, Perceived Stress, and Depressive Symptoms.

BACKGROUND: Among Black Americans, interpersonal racial discrimination is common. Stress, including following discrimination, contributes to pregnancy complications. In this secondary analysis, we provide data on associations among discrimination, stress, and their interaction across the life course and inflammation, perceived stress, and depressive symptoms during pregnancy. METHODS: During the early third trimester, Black American women (n = 93) completed the Experiences of Discrimination Scale, the Stress and Adversity Inventory, the Perceived Stress Scale, and the Center for Epidemiological Studies Depression Inventory. Plasma interleukin-6 (IL-6), IL-8, tumor necrosis factor-α (TNF-α), and IL-ß levels were quantified. Associations were examined by linear regression, controlling for demographic, behavioral, and clinical covariates. RESULTS: Associations among racial discrimination and plasma IL-8, TNF-α, and IL-ß levels depended upon average ratings of life course stress. When stress was low, discrimination in the mid tertile was associated with the highest levels of IL-8, TNF-α, and IL-ß. Subscale analyses suggested that findings related to IL-8 were driven by chronic stress whereas findings related to TNF-α and IL-ß were driven by acute stress. When examined together, greater discrimination but not greater life course stress was associated with higher prenatal perceived stress. In subscale analyses, the association between discrimination and prenatal perceived stress depended upon average ratings of life course acute stress. When acute stress was low, discrimination in the midtertile was associated with the highest levels of prenatal perceived stress. When acute stress was high, discrimination in the high tertile was associated with the highest levels of prenatal perceived stress. There were also direct associations among greater life course chronic stress, prenatal perceived stress, and prenatal depressive symptoms. Associations were attenuated when discrimination was included as a covariate. CONCLUSIONS: The current analyses suggest that, among Black Americans, prenatal inflammation, perceived stress, and depressive symptoms may be shaped by racial discrimination and stress across the life course. In many cases, associations among discrimination and prenatal parameters depended upon how stressful exposures to life course stressors had been rated. The data suggest the potential for adaptive plasticity under some stress and highlight the deleterious nature of compounding stress.

Predictors of Human Papillomavirus Seropositivity in Appalachian Women Aged 18 to 26 Years.

BACKGROUND: Key informants of the Appalachian community questioned whether their unique environmental stressors would alter their immune response to human papillomavirus (HPV) infections. The primary aim of this study is to determine predictors of HPV seroprevalence to at least 1 of the 4 vaccine-related HPV types before vaccination using a psychoneuroimmunologic model in Appalachian women. METHOD: Women aged 18 to 26 years (n = 185) who had not received HPV vaccination provided cervical HPV DNA and blood samples. Human papillomavirus DNA was identified through Hybrid Capture 2 assay and then genotyped for HPV types 6, 11, 16, and 18 by Roche Linear Array. Competitive Luminex Immunoassay measured the type-specific antibodies to HPV types 6, 11, 16, and 18 in milli-Merck units per milliliter. Nine psychoneuroimmunology scales measuring attributes of stress were self-completed. RESULTS: Human papillomavirus DNA was detected in 50% (92/183) of participants, with only 14% (26/183) positive for HPV-6/11/16/18 DNA. Seropositivity for at least one anti-HPV-6/11/16 or 18, on the other hand, was present in 35% (64/183) of women, with only 10% (19/183) concomitantly infected and seropositive for the vaccine-related types. The Perceived Stress Scale was not a strong predictor of HPV seropositivity. CONCLUSIONS: Both HPV infection and vaccine-related HPV type seropositivity is common among Appalachian women aged 18 to 26 years. The anticipated effect of environmental stressors on HPV seropositivity was not seen when multiple predictors were considered.

Longitudinal changes in HRV across pregnancy and postpartum: Effect of negative partner relationship qualities.

During pregnancy, there are significant physiological changes to support a healthy fetus. Parasympathetic activity normatively decreases across pregnancy, and psychological stress can promote even further decreased heart rate variability (HRV). This study evaluated (1) changes in vagally-mediated HRV from pregnancy to postpartum, (2) changes in vagally-mediated HRV from pregnancy to postpartum based on negative partner relationship qualities, and (3) changes in depressive symptoms from pregnancy to postpartum based on negative partner relationship qualities. 78 participants in their 3rd trimester self-reported their relationship quality with their partner at the first visit. Depressive symptoms and vagally-mediated HRV were evaluated at rest at five time points from 3rd trimester to 12 months postpartum. On average, the only significant increase in vagally-mediated HRV occurred between the 3rd trimester and 4-6 weeks postpartum. However, those who reported more negative partner relationship qualities during their 3rd trimester of pregnancy maintained lower vagally-mediated HRV levels across all of the first year postpartum and significantly lower vagally-mediated HRV at both 4 and 8 months postpartum as compared to people who reported fewer negative partner relationship qualities. Across the first year postpartum, people reporting more negative partner relationship qualities experienced more severe depressive symptoms than their counterparts with fewer negative partner relationship qualities; however, there was no difference in the rate of change of depressive symptoms across the first year postpartum based on negative partner relationship qualities. Because lower vagally-mediated HRV is associated with depressive symptoms, future work should explore the temporal relationship between vagally-mediated HRV and depressive symptoms in the postpartum period.

Maternal depressive symptoms, sleep, and odds of spontaneous early birth: implications for racial inequities in birth outcomes.

STUDY OBJECTIVES: Delivery prior to full term affects 37% of US births, including ~400,000 preterm births (<37 weeks) and >1,000,000 early term births (37-38 weeks). Approximately 70% of cases of shortened gestation are spontaneous-without medically-indicated cause. Elucidation of modifiable behavioral factors would have considerable clinical impact. METHODS: This study examined the role of depressive symptoms and sleep quality in predicting the odds of spontaneous shortened gestation among 317 women (135 black, 182 white) who completed psychosocial assessment in mid-pregnancy. RESULTS: Adjusting for key covariates, black women had 1.89 times higher odds of spontaneous shortened gestation compared to White women (OR [95% CI] = 1.89 [1.01, 3.53], p = 0.046). Women who reported only poor subjective sleep quality (PSQI > 6) or only elevated depressive symptoms (CES-D ≥ 16) exhibited no statistically significant differences in odds of spontaneous shortened gestation compared to those with neither risk factor. However, women with comorbid poor sleep and depressive symptoms exhibited markedly higher odds of spontaneous shortened gestation than those with neither risk factor (39.2% versus 15.7% [OR (95% CI) = 2.69 (1.27, 5.70)], p = 0.01). A higher proportion of black women met criteria for both risk factors (23% of black women versus 11% of white women; p = 0.004), with a lower proportion experiencing neither risk factor (40.7% of black versus 64.3% of white women; p < 0.001). CONCLUSIONS: Additive effects of poor subjective sleep quality and depressive symptoms were observed with markedly higher odds of spontaneous shortened gestation among women with both risk factors. Racial inequities in rates of comorbid exposure corresponded with inequities in shortened gestation. Future empirical studies and intervention efforts should consider the interactive effects of these commonly co-morbid exposures.

Impaired vasodilation in pregnant African Americans: Preliminary evidence of potential antecedents and consequences.

Significant health disparities exist between African Americans (AA) and European Americans (EA) in hypertension and hypertension-related disorders. Evidence suggests that this is due to impaired vasodilation in AAs. Pregnancy is a potent systemic vasodilatory state. However, differences in vasodilation between AAs and EAs have not been investigated in pregnancy. We sought to examine the effects of pregnancy on vasodilation in AA and EA women and how this might be related to discrimination and low birth weight in their offspring. Hemodynamics [blood pressure (MAP), cardiac output (CO), total peripheral resistance (TPR)] and heart rate variability (HF-HRV) were examined at baseline in 40 pregnant AAs (n = 20) and EAs (n = 20) and matched nonpregnant women (n = 40). The Experiences of Discrimination scale and birth weight were also measured in the offspring of the pregnant participants. Whereas pregnancy was associated with decreased MAP independent of race, AAs showed impaired vasodilation independent of pregnancy status as indicated by greater TPR despite greater HF-HRV. In AAs, but not EAs, reports of fewer incidences of discrimination were associated with greater TPR. Finally, the HF-HRV of EA mothers was inversely related to the birth weight of their offspring but was uncorrelated in AAs. We report novel evidence of impaired vasodilation to an endogenous vasodilatory stimulus in AAs. Higher TPR was related to discrimination in AAs and higher HF-HRV was related to low birth weight in EAs. These findings have implications for understanding the intergenerational transmission of impaired vasodilation in AAs.

Sleep disturbances and inflammatory gene expression among pregnant women: Differential responses by race.

Excessive inflammation in pregnancy predicts adverse birth outcomes, including shortened gestational length and lower birthweight, with African American women at greater risk. As substantial racial disparities in sleep quality, and evidence that African Americans have increased vulnerability for sleep-induced inflammatory dysregulation, sleep may be a critical, modifiable health behavior that contributes to racial disparities in birth outcomes. The present study examined sleep disturbance as a predictor of genome-wide transcriptome profiles of peripheral blood samples from 103 pregnant women (33 African American, 70 white) assessed at 18.7 ± 7.2 weeks gestation. We hypothesized that pregnant women with significant sleep disturbances would have gene expression profiles indicating over-expression of inflammatory pathways, with greater effects among African American compared to white women. Promoter-based bioinformatics analyses of differentially expressed genes indicated greater activation of NF-кB, AP1, and CREB transcription factors among African American women with sleep disturbances (all p < 0.05), and enhanced activation of AP1, but not NF-кB and reduced CREB activity among white women with sleep disturbances (p < 0.05). Differences in glucocorticoid receptor (GR) activity were also observed, in which African American women with sleep disturbances had reduced GR activity (p < 0.05), but white women with sleep disturbances showed a trend for enhanced GR activity (p = 0.11). Similarly, Interferon Response Factor (IRF) activity was reduced in African American women while increased in white women with sleep disturbances (p < 0.05). The current study provides novel evidence for gene expression related to inflammation, glucocorticoids, and anti-viral immunity among pregnant women with sleep disturbances, with differential effects by race. African Americans showed greater breadth and magnitude in these proinflammatory and anti-viral pathways than whites, with divergence in anti-inflammatory glucocorticoid, proinflammatory adrenergic-mediated cAMP, and anti-viral interferon responses. These data elucidate the role of sleep disturbances in intracellular inflammatory and anti-viral immunity in pregnancy and provide a potential target for intervention.

The association of maternal obesity and race with serum adipokines in pregnancy and postpartum: Implications for gestational weight gain and infant birth weight.

Adiponectin and leptin are hormones known to play roles in maternal metabolism during pregnancy. Levels of these hormones have been demonstrated to vary based on adiposity and race. However, there is a lack of data concerning the relationship between race and the change of adiponectin and leptin throughout pregnancy. The purpose of this study was to examine serum levels of adiponectin, leptin, and leptin-to-adiponectin ratio (LAR) throughout pregnancy and to assess their association with gestational weight gain (GWG) and infant birth weight while considering the effects of race and pre-pregnancy body mass index (BMI). Serum levels of adiponectin, leptin, gestational weight gain, and infant birth weight were measured in 80 pregnant women at early (12.4 â€‹± â€‹1.3 weeks gestation), mid (20.6 â€‹± â€‹1.3 weeks gestation), late pregnancy (29.2 â€‹± â€‹1.4 weeks gestation), and 7-11 weeks postpartum (8.8 â€‹± â€‹0.8 weeks). In women overall, serum adiponectin decreased across pregnancy and increased at postpartum (p â€‹= â€‹0.17.) At each prenatal timepoint, both black race and obesity were associated with lower adiponectin (ps â€‹< â€‹0.05). In women overall, serum leptin increased across pregnancy, and declined at postpartum. At every assessment, a stepwise increase in leptin was observed in relation to BMI class. Black women with obesity had markedly higher LAR in mid- and late pregnancy and postpartum than all other groups (p â€‹< â€‹0.05). Serum leptin during pregnancy was significantly associated with total GWG in both black and white women (ps â€‹< â€‹0.005). Neither adiponectin, leptin, nor LAR were associated with infant birth weight. Race and BMI both have significant effects on serum adiponectin, leptin, and LAR levels in pregnancy and postpartum. Notably, the combined effects of race and BMI result in markedly higher LAR among black women with obesity. Implications for racial disparities in metabolic syndrome and postpartum weight retention remain to be explicated.

At the forefront of psychoneuroimmunology in pregnancy: Implications for racial disparities in birth outcomes: PART 2: Biological mechanisms.

As reviewed in Part 1 of this two part review, birth prior to full term is a substantial public health issue. In the US, ˜400,000 babies per year are born preterm (< 37 weeks), while>1 million are early term (37-386/7 weeks) and remarkable racial disparities in shortened gestation are observed among African Americans as compared to Whites. Biomechanisms linking stressor exposures with birth outcomes are increasingly being explicated. The current paper reviews the mechanistic role of maternal biological functioning in the link between behavioral exposures and birth outcomes. These include the inter-related roles of neuroendocrine function, inflammatory regulation, biological aging, and the microbiome. An integrative approach which addresses both behavioral and biological factors within the same study, carefully considers the role of race/ethnicity, and rigorously defines birth outcomes (e.g., spontaneous versus medically-indicated and inclusive of early term birth) is needed to move research in this field toward better mechanistic understanding and clinical application.

At the forefront of psychoneuroimmunology in pregnancy: Implications for racial disparities in birth outcomes PART 1: Behavioral risks factors.

Birth prior to full term is a substantial public health issue. In the US, ˜400,000 babies per year are born preterm (<37 weeks), while>1 million are early term (37-386/7 weeks). Birth prior to full term confers risk both immediate and long term, including neonatal intensive care, decrements in school performance, and increased mortality risk from infancy through young adulthood. Risk for low birth weight and preterm birth are 1.5-2 times greater among African Americans versus Whites. Psychosocial stress related to being a member of a discriminated racial minority group contributes substantially to these racial disparities. Providing promising targets for intervention, depressed mood, anxiety, and poor sleep are each linked with exposure to chronic stress, including racial discrimination. A rigorous transdisciplinary approach addressing these gaps holds great promise for clinical impact in addressing racial disparities as well as ameliorating effects of stress on perinatal health more broadly. As will be reviewed in a companion paper, the mechanistic roles of physiological sequelae to stress - including neuroendocrine, inflammatory regulation, biological aging, and the microbiome - also require delineation.

Early adversity and the regulation of gene expression: Implications for prenatal health.

Early life, including prenatal development and childhood, is a period of sensitivity, with potential for developmental programming under conditions of adversity. The intergenerational effects of early adversity have received attention, most often studied in relation to fetal development according to maternal exposures. Less often considered but critically important is the effect of early adversity on future prenatal risk (e.g., risk for preeclampsia, preterm birth), which threatens the health of mother and infant. The body's ability to turn collections of genes "on" or "off" across a range of tissues via receptor-driven transcription factors and epigenetic mechanisms (i.e., chemical modifications to the genome) in response to the perceived environment may help to explain such associations. This review aims to summarize discoveries surrounding the effects of early adversity on gene expression, emphasizing prenatal populations. First, we review findings from gene expression studies examining the effects of early adversity on various tissues known to contribute to prenatal health in adulthood. Next, we review several gene regulatory mechanisms thought to underlie differences in gene expression. Finally, we discuss potential implications for prenatal risk among early adversity-exposed mothers according to our current understanding of the biology that contributes to the development of prenatal syndromes.