Racial discrimination during middle age predicts higher serum phosphorylated tau and neurofilament light chain levels a decade later: A study of aging black Americans.

INTRODUCTION: Recent evidence suggests that exposure to the stress of racism may increase the risk of dementia for Black Americans. METHODS: The present study used 17 years of data from a sample of 255 Black Americans to investigate the extent to which exposure to racial discrimination predicts subsequent changes in serum Alzheimer's Disease Research Center (ADRC) biomarkers: serum phosphorylated tau181(p-tau181), neurofilament light (NfL), and glial fibrillary acidic protein (GFAP). We hypothesized that racial discrimination assessed during middle age would predict increases in these serum biomarkers as the participants aged into their 60s. RESULTS: Our findings indicate that exposure to various forms of racial discrimination during a person's 40s and early 50s predicts an 11-year increase in both serum p-tau181 and NfL. Racial discrimination was not associated with subsequent levels of GFAP. DISCUSSION: These findings suggest that racial discrimination in midlife may contribute to increased AD pathology and neurodegeneration later in life. HIGHLIGHTS: A 17-year longitudinal study of Black Americans. Assessments of change in serum p-tau181, neurofilament light, and glial fibrillary acidic protein. Exposure to racial discrimination during middle age predicted increases in p-tau181 and neurofilament light. Education was positively related to both p-tau181 and exposure to racial discrimination.

Specifying the psychosocial pathways whereby child and adolescent adversity shape adult health outcomes.

BACKGROUND: Social scientists generally agree that health disparities are produced, at least in part, by adverse social experiences, especially during childhood and adolescence. Building on this research, we use an innovative method to measure early adversity while drawing upon a biopsychosocial perspective on health to formulate a model that specifies indirect pathways whereby childhood and adolescent adversity become biologically embedded and influence adult health. METHOD: Using nearly 20 years of longitudinal data from 382 Black Americans, we use repeated-measures latent class analysis (RMLCA) to construct measures of childhood/adolescent adversities and their trajectories. Then, we employ structural equation modeling to examine the direct and indirect effects of childhood/adolescent adversity on health outcomes in adulthood through psychosocial maladjustment. RESULTS: RMLCA identified two classes for each component of childhood/adolescent adversity across the ages of 10 to 18, suggesting that childhood/adolescent social adversities exhibit a prolonged heterogeneous developmental trajectory. The models controlled for early and adult mental health, sociodemographic and health-related covariates. Psychosocial maladjustment, measured by low self-esteem, depressive and anxiety symptoms, and lack of self-control, mediated the relationship between childhood/adolescent adversity, especially parental hostility, racial discrimination, and socioeconomic class, and both self-reported illness and blood-based accelerated biological aging (with proportion mediation ranging from 8.22% to 79.03%). CONCLUSION: The results support a biopsychosocial model of health and provide further evidence that, among Black Americans, early life social environmental experiences, especially parenting, financial stress, and racial discrimination, are associated with adult health profiles, and furthermore, psychosocial mechanisms mediate this association.

Childhood adversity predicts black young adults' DNA methylation-based accelerated aging: A dual pathway model.

We expand upon prior work (Gibbons et al., ) relating childhood stressor effects, particularly harsh childhood environments, to risky behavior and ultimately physical health by adding longer-term outcomes - deoxyribonucleic acid (DNA) methylation-based measures of accelerated aging (DNAm-aging). Further, following work on the effects of early exposure to danger (McLaughlin et al., ), we also identify an additional pathway from harsh childhood environments to DNAm-aging that we label the danger/FKBP5 pathway, which includes early exposure to dangerous community conditions that are thought to impact glucocorticoid regulation and pro-inflammatory mechanisms. Because different DNAm-aging indices provide different windows on accelerated aging, we contrast effects on early indices of DNAm-aging based on chronological age with later indices that focused on predicting biological outcomes. We utilize data from Family and Community Health Study participants (N = 449) from age 10 to 29. We find that harshness influences parenting, which, in turn, influences accelerated DNAm-aging through the risky cognitions and substance use (i.e., behavioral) pathway outlined by Gibbons et al. (). Harshness is also associated with increased exposure to threat/danger, which, in turn, leads to accelerated DNAm-aging through effects on FKBP5 activity and enhanced pro-inflammatory tendencies (i.e., the danger/FKBP5 pathway).

Childhood adversity is linked to adult health among African Americans via adolescent weight gain and effects are genetically moderated.

Identifying the mechanisms linking early experiences, genetic risk factors, and their interaction with later health consequences is central to the development of preventive interventions and identifying potential boundary conditions for their efficacy. In the current investigation of 412 African American adolescents followed across a 20-year period, we examined change in body mass index (BMI) across adolescence as one possible mechanism linking childhood adversity and adult health. We found associations of childhood adversity with objective indicators of young adult health, including a cardiometabolic risk index, a methylomic aging index, and a count of chronic health conditions. Childhood adversities were associated with objective indicators indirectly through their association with gains in BMI across adolescence and early adulthood. We also found evidence of an association of genetic risk with weight gain across adolescence and young adult health, as well as genetic moderation of childhood adversity's effect on gains in BMI, resulting in moderated mediation. These patterns indicated that genetic risk moderated the indirect pathways from childhood adversity to young adult health outcomes and childhood adversity moderated the indirect pathways from genetic risk to young adult health outcomes through effects on weight gain during adolescence and early adulthood.

Disentangling the Effects of Boys' Pubertal Timing: The Importance of Social Context.

Some prior studies have found that, for boys, earlier puberty is linked to higher crime and delinquency, while other studies have found that earlier puberty is associated with greater social competence and beneficial psychosocial development. The current study suggests that these seemingly contradictory results actually represent two divergent pathways by which earlier pubertal timing can affect adjustment. Which pathway boys take is highly dependent on psychosocial context. Using a sample of 310 African American boys and their primary caregivers tracked across three waves of data collection from ages 10.55-18.84 from the Family and Community Health Study (FACHS), the current study utilizes Latent Moderated Structural Equation Modeling (LMS) to analyze effects of interactions between pubertal timing and social contextual factors on criminal behavior and social competence. Results suggest that criminogenic effects of early puberty are contingent on deviant peer group, poor school experience, harsh parenting, and neighborhood disorganization, whereas the association between earlier puberty and social competence is attenuated by harsh parenting. Results suggest that modeling both positive and negative development outcomes together may give a clearer picture of the developmental consequences of pubertal timing for boys. In addition, this study shows the importance of social context in shaping the meaning and consequences of biological variables like pubertal timing.

Childhood Adversities as Determinants of Cardiovascular Disease Risk and Perceived Illness Burden in Adulthood: Comparing Retrospective and Prospective Self-Report Measures in a Longitudinal Sample of African Americans.

A large body of evidence suggests that exposure to childhood adversities increases risk for poor quality physical health in adulthood. Much of this evidence is based on retrospective measures which are believed to be contaminated by the limitations and biases of autobiographical memory. Using longitudinal data on 454 African Americans (61 percent female) this study examines the corroboration between prospective and retrospective measures of childhood adversities gathered approximately two decades apart, and the relative ability of the measures to predict self-reported illnesses and a biomarker of 30-year cardiovascular disease risk. Comparisons indicated that the retrospective and prospective measures demonstrated weak convergence and did not provide completely equivalent information about self-reported adverse childhood experiences. A series of regression models indicated that the two measures of adversities exhibited similar associations with the cardiovascular disease biomarker but divergent associations with self-reported illnesses. Furthermore, both the prospective and retrospective measures simultaneously predicted cardiovascular disease risk in adulthood. That the prospective measure did not significantly predict perceived illnesses after adjusting for the retrospective measure is evidence that childhood adversities predict self-reported health burden insofar as respondents remember those adversities as adults. The findings provide evidence that retrospective self-report measures of childhood adversities do not closely converge with prospective measures, and that retrospective measures may not provide valid estimates of the association between childhood adversities and perceived illnesses in adulthood.

Puberty and Girls' Delinquency: A Test of Competing Models Explaining the Relationship between Pubertal Development and Delinquent Behavior.

A substantial amount of research indicates precocious pubertal development is associated with delinquent behavior in girls. However, no clear consensus on theoretical mechanisms underlying this association has been established. Using a prospective panel study of 480 African American girls, the current study uses latent growth curve analysis to compare two competing models-context of risk (CR) and life history (LH) theory-offering potential explanations of this phenomenon. The CR model suggests that early pubertal development substantially shapes girls' social worlds such that they are exposed to more risk factors for delinquency; whereas, LH theory argues environmental unpredictability and harshness in childhood cause accelerated physical development, which predicts risky behavior. Results indicate that girls with precocious pubertal timing have more deviant peers and are exposed to harsher parenting, and that risk factors do not predict pubertal timing, providing more support for the CR model. Implications and future directions for research are discussed.

Youth Adversities Amplify the Association between Adult Stressors and Chronic Inflammation in a Domain Specific Manner: Nuancing the Early Life Sensitivity Model.

There is strong evidence that chronic, systemic inflammation hastens onset of the diseases of old age that ultimately lead to death. Importantly, several studies suggest that childhood adversity predicts chronic inflammation. Unfortunately, this research has been plagued by retrospective reports of childhood adversity, an absence of controls for adult stressors, and a failure to investigate various competing models of the link between childhood adversity and chronic inflammation. The present study was designed to address these limitations. Using 18 years of data collected from 413 African Americans (58% female) included in the Family and Community Health Study, hierarchical regression analyses provided support for a nuanced early life sensitivity explanation for the link between early adversity and adult chronic inflammation. Controlling for health risk behaviors and adult SES, late childhood (ages 10-12) adversity amplified the association between adult adversity (age 29) and chronic inflammation. This interaction operated in a domain-specific fashion. Harsh parenting amplified the relation between intimate partner hostility and inflammation, whereas early discrimination amplified the relation between adult discrimination and inflammation. These findings suggest that individuals may be primed to respond physiologically to adverse adult circumstances that resemble those experienced earlier in life.

Evaluating Observer Ratings: The Case of Measuring Neighborhood Disorder.

The purpose of this study is to evaluate the quality of observer ratings of neighborhood disorder using a many-facet Rasch model (MFRM). Our goal is to investigate observer severity and observer consistency. Observers trained in the use of a systematic social observation visited and rated residential neighborhoods. Data for this study are drawn from the Family and Community Health Study (FACHS). The FACHS sample consisted of 673 neighborhoods. Two observers, out of a total of 67 observers used for this study, rated each residential neighborhood. The results of this study suggested that there were statistically significant differences in observer severity, even after observer training, and that the ratings of observers are not consistent. Therefore, more or better observer training is necessary. In addition, the interaction effect between observer and item was significant, indicating significant variance in observer severity across at least one item.

Reports of perceived racial discrimination among African American children predict negative affect and smoking behavior in adulthood: A sensitive period hypothesis.

We examined the prospective relations between a cultural risk factor, perceived racial discrimination (PRD), and subsequent negative affect and health behavior (smoking) in a panel of 889 African American children (part of the Family and Community Health Study). Cultural moderators (protective factors) of these relations were also examined. PRD was assessed six times from ages 10.5 (Wave 1) to 24.5 (Wave 6), and negative affect (anger and depressive symptoms) was assessed at Wave 2 (age 12.5) and Wave 6 (age 24.5). Results indicated that Wave 1 PRD predicted Wave 6 smoking, controlling for multiple factors related to smoking and/or PRD, including smoking at age 15.5. Structural equation models indicated that these relations between Wave 1 PRD and smoking were mediated by both early and later negative affect. The models also indicated that Wave 1 PRD had a direct impact on Wave 6 anger (assessed 14 years later), controlling for the effects of PRD on early affect. Cultural socialization was associated with lower rates of adolescent smoking, and it buffered the relation between PRD and Wave 6 anger. The impact of early PRD experiences along with suggestions for culturally informed interventions and preventive interventions that might buffer against early PRD effects are discussed.

Biological embedding of neighborhood disadvantage and collective efficacy: Influences on chronic illness via accelerated cardiometabolic age.

The present study extends prior research on the link between neighborhood disadvantage and chronic illness by testing an integrated model in which neighborhood characteristics exert effects on health conditions through accelerated cardiometabolic aging. Hypotheses were tested using a sample of 408 African Americans from the Family and Community Health Study. Using four waves of data spanning young adulthood (ages 18-29), we first found durable effects of neighborhood disadvantage on accelerated cardiometabolic aging and chronic illness. Then, we used marginal structural modeling to adjust for potential neighborhood selection effects. As expected, accelerated cardiometabolic aging was the biopsychosocial mechanism that mediated much of the association between neighborhood disadvantage and chronic illness. This finding provides additional support for the view that neighborhood disadvantage can influence morbidity and mortality by creating social contexts that becomes biologically embedded. Perceived neighborhood collective efficacy served to buffer the relationship between neighborhood disadvantage and biological aging, identifying neighborhood-level resilience factor. Overall, our results indicate that neighborhood context serves as a fundamental cause of weathering and accelerated biological aging. Residing in a disadvantaged neighborhood increases biological wear and tear that ultimately leads to onset of chronic illness, but access to perceived collective efficacy buffers the impact of these neighborhood effects. From an intervention standpoint, identifying such an integrated model may help inform future health-promoting interventions.

Sharing the Burden of the Transition to Adulthood: African American Young Adults' Transition Challenges and Their Mothers' Health Risk.

For many African American youth, the joint influences of economic and racial marginalization render the transition to stable adult roles challenging. We have gained much insight into how these challenges affect future life chances, yet we lack an understanding of what these challenges mean in the context of linked lives. Drawing on a life course framework, this study examines how young African Americans' experiences across a variety of salient domains during the transition to adulthood affect their mothers' health. Results suggest that stressors experienced by African Americans during the transition to adulthood (e.g., unemployment, troubled romantic relationships, arrest) heighten their mothers' cumulative biological risk for chronic diseases, or allostatic load, and reduce subjective health. These results suggest that the toll of an increasingly tenuous and uncertain transition to adulthood extends beyond young people to their parents. Hence, increased public investments during this transition may not only reduce inequality and improve life chances for young people themselves, but may also enhance healthy aging by relieving the heavy burden on parents to help their children navigate this transition.

A Droplet Digital PCR Assay for Smoking Predicts All-Cause Mortality.

OBJECTIVES: -Determine whether an epigenetic assay for smoking predicts all-cause mortality in adults participating in a longitudinal study of Iowa adoptees. BACKGROUND: -Improved biomarkers for smoking are needed given its large public health impact and significant limitations of both self-report and current biomarkers, such as cotinine in detecting smoking. In the past 5 years, multiple epigenome-wide association studies of smoking have identified loci suitable for translation as epigenetic biomarkers for smoking, in particular the CpG cg05575921. Digital polymerase chain reaction methods hold promise for the development of this and other epigenetic biomarkers. METHODS: -Participants in the Iowa Adoption Studies were interviewed regarding their smoking habits. DNA was prepared from whole blood and bisulfite-converted for methylation analysis and digital droplet polymerase chain reaction assay of methylation at cg05575921 was performed. National Death Index records were requested for 584 study participants, resulting in 24 complete matches, 210 partial matches and 350 non-matching records. Complete matches were coded as deceased while the remainder were coded as alive (ie, censored). In total, methylation data and vital status information were available for a total of N = 193 subjects, including 15 deceased and 178 non-deceased. Cox regression was used to examine the ability of cg05575921 methylation as a continuous value to predict the timing of mortality with and without the inclusion of age, sex, race, BMI, marital status, educational status, socioeconomic status, cardiovascular risk factors, and a history of cancer as covariates. RESULTS: -Methylation at cg05575921 predicted the hazard of mortality as the sole predictor and after accounting for major demographic and clinical risk factors. The fitted model showed the hazard ratio increased by 3.5% for every 1% decrease in methylation. CONCLUSIONS: -Decreased methylation at cg05575921, an emerging epigenetic biomarker for smoking, was associated with early mortality in a longitudinal study of adults after accounting for the impact of major demographic and clinical risk factors for all-cause mortality. This approach may be useful in clinical research or actuarial assessments.

Methylation of the oxytocin receptor gene mediates the effect of adversity on negative schemas and depression.

Building upon various lines of research, we posited that methylation of the oxytocin receptor gene (OXTR) would mediate the effect of adult adversity on increased commitment to negative schemas and in turn the development of depression. We tested our model using structural equation modeling and longitudinal data from a sample of 100 middle-aged, African American women. The results provided strong support for the model. Analysis of the 12 CpG sites available for the promoter region of the OXTR gene identified four factors. One of these factors was related to the study variables, whereas the others were not. This factor mediated the effect of adult adversity on schemas relating to pessimism and distrust, and these schemas, in turn, mediated the impact of OXTR methylation on depression. All indirect effects were statistically significant, and they remained significant after controlling for childhood trauma, age, romantic relationship status, individual differences in cell types, and average level of genome-wide methylation. These finding suggest that epigenetic regulation of the oxytocin system may be a mechanism whereby the negative cognitions central to depression become biologically embedded.

When inflammation and depression go together: The longitudinal effects of parent-child relationships.

Parent-child relationships have long-term effects on health, particularly later inflammation and depression. We hypothesized that these effects would be mediated by later romantic partner relationships and elevated stressors in young adulthood, helping promote chronic, low grade, inflammation as well as depressive symptoms, and driving their covariation. It has been proposed recently that youth experiencing harsher parenting may also develop a stronger association between inflammation and depressive symptoms in adulthood and altered effects of stressors on outcomes. In the current investigation, we test these ideas using an 18-year longitudinal study of N = 413 African American youth that provides assessment of the parent-child relationship (at age 10), pro-inflammatory cytokine profile and depressive symptoms (at age 28), and potential mediators in early young adulthood (assessed at ages 21 and 24). As predicted, the effect of harsher parent-child relationships (age 10) on pro-inflammatory state and increased depressive symptoms at age 28 were fully mediated through young adult stress and romantic partner relationships. In addition, beyond these mediated effects, parent-child relationships at age 10 moderated the concurrent association between inflammation and depressive symptoms, as well as the prospective association between romantic partner relationships and inflammation, and resulted in substantially different patterns of indirect effects from young adult mediators to outcomes. The results support theorizing that the association of depression and inflammation in young adulthood is conditional on earlier parenting, and suggest incorporating this perspective into models predicting long-term health outcomes.

Accuracy and utility of an epigenetic biomarker for smoking in populations with varying rates of false self-report.

Better biomarkers to detect smoking are needed given the tremendous public health burden caused by smoking. Current biomarkers to detect smoking have significant limitations, notably a short half-life for detection and lack of sensitivity for light smokers. These limitations may be particularly problematic in populations with less accurate self-reporting. Prior epigenome-wide association studies indicate that methylation status at cg05575921, a CpG residue located in the aryl hydrocarbon receptor repressor (AHRR) gene, may be a robust indicator of smoking status in individuals with as little as half of a pack-year of smoking. In this study, we show that a novel droplet digital PCR assay for measuring methylation at cg05575921 can reliably detect smoking status, as confirmed by serum cotinine, in populations with different demographic characteristics, smoking histories, and rates of false-negative self-report of smoking behavior. Using logistic regression models, we show that obtaining maximum accuracy in predicting smoking status depends on appropriately weighting self-report and cg05575921 methylation according to the characteristics of the sample being tested. Furthermore, models using only cg05575921 methylation to predict smoking perform nearly as well as those also including self-report across populations. In conclusion, cg05575921 has significant potential as a clinical biomarker to detect smoking in populations with varying rates of accuracy in self-report of smoking behavior.

Factors that Influence Trajectories of Delinquency Throughout Adolescence.

Given that one of the most powerful predictors of adult crime is the presence of behavior problems in childhood and adolescence, there is a need to further understand factors that determine behavior patterns during this developmental stage. This study focuses on stressful life experiences such as exposure to delinquent peers, racial discrimination, as well as family characteristics such as parenting style and family transitions. Data come from four waves of the Family and Community Health Survey, an African-American sample. The present study investigates 354 males from this dataset. We utilize a group-based trajectory model to estimate the number and type of trajectories of delinquency. We then estimate multinomial regression models to predict trajectory group membership. The results indicated that there were four distinct groups of offenders (negligible delinquents; early starter/declining; late starter; and early starter/chronic offenders). We predicted group membership using both early predictors and measures of change in these predictors across the study period. The results indicated that individuals who experience greater racial discrimination (both early in childhood and throughout adolescence) are more likely to be in trajectory groups that begin offending early and persist through adolescence. Additionally, those respondents who reported having friends with greater delinquent behavior were more likely to be in groups that began their offending early in life and persisted when compared to groups who started later or desisted as they entered adulthood. The results contribute to developmental research and provide information that may be helpful in preventing adolescents from persisting in antisocial behavior as they enter adulthood.

Mechanisms That Link Parenting Practices to Adolescents' Risky Sexual Behavior: A Test of Six Competing Theories.

Risky sexual behavior, particularly among adolescents, continues to be a major source of concern. In order to develop effective education and prevention programs, there is a need for research that identifies the antecedents of such behavior. This study investigated the mediators that link parenting experiences during early adolescence to subsequent risky sexual behaviors among a diverse sample of African American youth (N = 629, 55 % female). While there is ample evidence that parenting practices (e.g., supportive parenting, harsh parenting, parental management) are antecedent to risky sexual behavior, few studies have examined whether one approach to parenting is more strongly related to risky sex than others. Using a developmental approach, the current study focused on factors associated with six theories of risky sexual behavior. While past research has provided support for all of the theories, few studies have assessed the relative contribution of each while controlling for the processes proposed by the others. The current study addresses these gaps in the literature and reports results separately by gender. Longitudinal analyses using structural equation modeling revealed that the mediating mechanisms associated with social learning and attachment theories were significantly related to the risky sexual behavior of males and females. Additionally, there was support for social control and self-control theories only for females and for life history theory only for males. We did not find support for problem behavior theory, a perspective that dominates the risky sex literature, after controlling for the factors associated with the other theories. Finally, supportive parenting emerged as the parenting behavior most influential with regard to adolescents' risky sexual behavior. These results provide insight regarding efficacious approaches to education and preventative programs designed to reduce risky sexual behaviors among adolescents.

Pubertal timing and sexual risk behaviors among rural African American male youth: testing a model based on life history theory.

Life History Theory (LHT), a branch of evolutionary biology, describes how organisms maximize their reproductive success in response to environmental conditions. This theory suggests that challenging environmental conditions will lead to early pubertal maturation, which in turn predicts heightened risky sexual behavior. Although largely confirmed among female adolescents, results with male youth are inconsistent. We tested a set of predictions based on LHT with a sample of 375 African American male youth assessed three times from age 11 to age 16. Harsh, unpredictable community environments and harsh, inconsistent, or unregulated parenting at age 11 were hypothesized to predict pubertal maturation at age 13; pubertal maturation was hypothesized to forecast risky sexual behavior, including early onset of intercourse, substance use during sexual activity, and lifetime numbers of sexual partners. Results were consistent with our hypotheses. Among African American male youth, community environments were a modest but significant predictor of pubertal timing. Among those youth with high negative emotionality, both parenting and community factors predicted pubertal timing. Pubertal timing at age 13 forecast risky sexual behavior at age 16. Results of analyses conducted to determine whether environmental effects on sexual risk behavior were mediated by pubertal timing were not significant. This suggests that, although evolutionary mechanisms may affect pubertal development via contextual influences for sensitive youth, the factors that predict sexual risk behavior depend less on pubertal maturation than LHT suggests.

Invited address: "The times they are a-changin'" gene expression, neuroplasticity, and developmental research.

For good reason, social scientists have a long history of being suspicious of biological explanations of human behavior. Importantly, however, recent paradigmatic shifts in the life sciences have largely obviated these longstanding concerns. We highlight the changes that have occurred in genetics with its movement away from genetic determinism to an emphasis on epigenetics and in neuroscience with its switch from a fixed to a neuroplastic view of the brain. We describe these new developments noting the way they recognize, indeed place a premium upon, the role of the environment. The remainder of the paper focuses upon the challenges and opportunities for social scientists, especially those involved in developmental work, proffered by these paradigmatic shifts. The evidence clearly shows that nature and nurture are inextricably interlinked. Importantly, however, it also indicates that they are connected in a manner that honors the priority that the social sciences place upon the environment. We contend that incorporating biological processes into our developmental work will sharpen our theories and enhance their significance. We argue that such biologically integrated models will provide a clearer and more comprehensive understanding of how nurture influences behavior across the life course.