Incarceration Exposure, Biological Aging, and Depression Symptoms in an African American Sample of Older Adults.

Objectives: The study draws upon perspectives on life-course stressors and health to assess whether lifetime incarceration exposure is a determinant of biological aging and self-reported depression. Methods: Using data from a sample of 460 African American participants (average age= 57) in the Family and Community Health Study, the study examined two epigenetic indices of biological aging, DunedinPoAm and GrimAge, as well as a self-reported measure of depression symptoms. Estimates were derived from multivariate regression models with adjustments for selection on observables and confounding factors. Results: Exposure to incarceration was a significant determinant of accelerated biological aging (GrimAge) and the pace of aging (DunedinPoAm) and depressive symptoms. Discussion: Among formerly incarcerated older adults, past experiences with the stressors of incarceration predict key biomarkers of physiological deterioration and depressive symptoms. Incarceration contributes to the mental and physical health burden of older adults.

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.

RACIAL DISCRIMINATION AND THE WEATHERING OF NONMARITAL RELATIONSHIPS.

Objective: The purpose of this study was to assess the impact of perceived racial discrimination on the satisfaction and dissolution of different-gender, nonmarital relationships among African American young adults. Background: Racial discrimination has proven detrimental to relationship quality among married couples. Racial disparities in relationship processes begin long before marriages form, however. Racial discrimination may also weather and disrupt nonmarital relationships earlier in the life course. Method: Survey data from African American young adult couples (N = 407) from the Family and Community Health Study were used to assess the associations between each partner's experience of racial discrimination, relationship satisfaction, and relationship dissolution using structural equation modeling. Results: Results support a stress spillover perspective in that racial discrimination experienced by both men and women increased the likelihood of relationship dissolution through reduced satisfaction. No support was found for a stress buffering perspective. Conclusion: Racial discrimination appears to distress and, ultimately, disrupt nonmarital relationships among African American young adult couples. Implications: Given the role of relationship quality and stability in promoting health and well-being, understanding how discrimination impacts the unfolding of relationships, or linked lives, across the life course is essential to untangling and addressing the "chains of disadvantage" identified by Umberson et al. (2014) as central to racial disparities in health and well-being.

Changes in Loneliness, BDNF, and Biological Aging Predict Trajectories in a Blood-Based Epigenetic Measure of Cortical Aging: A Study of Older Black Americans.

A recent epigenetic measure of aging has developed based on human cortex tissue. This cortical clock (CC) dramatically outperformed extant blood-based epigenetic clocks in predicting brain age and neurological degeneration. Unfortunately, measures that require brain tissue are of limited utility to investigators striving to identify everyday risk factors for dementia. The present study investigated the utility of using the CpG sites included in the CC to formulate a peripheral blood-based cortical measure of brain age (CC-Bd). To establish the utility of CC-Bd, we used growth curves with individually varying time points and longitudinal data from a sample of 694 aging African Americans. We examined whether three risk factors that have been linked to cognitive decline-loneliness, depression, and BDNFm-predicted CC-Bd after controlling for several factors, including three new-generation epigenetic clocks. Our findings showed that two clocks-DunedinPACE and PoAm-predicted CC-BD, but that increases in loneliness and BDNFm continued to be robust predictors of accelerated CC-Bd even after taking these effects into account. This suggests that CC-Bd is assessing something more than the pan-tissue epigenetic clocks but that, at least in part, brain health is also associated with the general aging of the organism.

Direct and Indirect Effects of Socioeconomic Status and Discrimination on Subjective Cognitive Decline: A Longitudinal Study of African American Women.

OBJECTIVES: The present study builds on recent findings suggesting that the stress of institutional and interpersonal racism may contribute to African Americans' elevated risk for dementia. We investigated the extent to which 2 consequences of racism-low socioeconomic status (SES) and discrimination-predict self-reported cognitive decline (SCD) 19 years later. Further, we examined potential mediating pathways that might link SES and discrimination to cognitive decline. Potential mediators included depression, accelerated biological aging, and onset of chronic illnesses. METHODS: Hypotheses were tested using a sample of 293 African American women. SCD was assessed using the Everyday Cognition Scale. Structural equation modeling was used to assess the effects of SES and racial discrimination, both measured in 2002, on SCD reported in 2021. Turning to the mediators, midlife depression was assessed in 2002, accelerated aging in 2019, and chronic illness in 2019. Age and prodrome depression were included as covariates. RESULTS: There were direct effects of SES and discrimination on SCD. In addition, these 2 stressors showed a significant indirect effect on SCD through depression. Finally, there was evidence for a more complex pathway where SES and discrimination accelerate biological aging, with accelerated aging, in turn leading to chronic illness, which then predicted SCD. DISCUSSION: Results of the present study add to a growing literature indicating that living in a racialized society is a central factor in explaining the high risk for dementia among Black Americans. Future research should continue to emphasize the various ways that exposure to racism over the life course effects cognition.

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.

Do Loneliness and Per Capita Income Combine to Increase the Pace of Biological Aging for Black Adults across Late Middle Age?

In a sample of 685 late middle-aged Black adults (M age at 2019 = 57.17 years), we examined the effects of loneliness and per capita income on accelerated aging using a newly developed DNA-methylation based index: the DunedinPACE. First, using linear, mixed effects regression in a growth curve framework, we found that change in DunedinPACE was dependent on age, with a linear model best fitting the data (b = 0.004, p < 0.001), indicating that average pace of change increased among older participants. A quadratic effect was also tested, but was non-significant. Beyond the effect of age, both change in loneliness (b = 0.009, p < 0.05) and change in per capita income (b = -0.016, p < 0.001) were significantly associated with change in DunedinPACE across an 11-year period, accounting for significant between person variability observed in the unconditional model. Including non-self-report indices of smoking and alcohol use did not reduce the association of loneliness or per capita income with DunedinPACE. However, change in smoking was strongly associated with change in DunedinPACE such that those reducing their smoking aged less rapidly than those continuing to smoke. In addition, both loneliness and per capita income were associated with DunedinPACE after controlling for variation in cell-types.

School Disengagement Predicts Accelerated Aging among Black American Youth: Mediation by Psychological Maladjustment and Moderation by Supportive Parenting.

Early experiences of school disengagement may serve as a warning sign for later young adult adjustment difficulties and eventually contribute to accelerated aging among Black American youth. At the same time, supportive parenting may play a protective role. Using longitudinal data from the Family and Community Health Study (FACHS), we examined psychological maladjustment (comprising depression, lack of self-regulation, and low self-esteem) as a mediator of the relationship between school disengagement and accelerated aging. We also examined the effect of supportive parenting in buffering the impact of school disengagement on adulthood outcomes by controlling for covariates. Hypotheses were examined in a sample of 386 (Mean age = 28.68; Females = 62.7%; Males = 37.3%) Black American youth who were followed into young adulthood. Path modeling was used to test hypothesized relationships. We found school disengagement, i.e., problems with school attendance, performance, and engagement, reported across ages 10-18, predicted psychological maladjustment, which, in turn, predicted accelerated aging at age 29. We also found a buffering effect for supportive parenting. No significant gender difference in the indirect effect or buffering effect was found. This study highlights the potential importance of greater attention to school disengagement to identify and potentially influence long-term health trajectories and adult outcomes for Black American youth.

Childhood adversity and adult health: A dyadic analysis of Black American couples.

OBJECTIVE: The association between childhood adversity and adulthood health is well established, but few studies have examined potential effects of childhood adversity on partner health in couples. This study examined the long-term health impact of childhood adversity on individuals as well as their significant others. METHOD: The participants were 163 distinguishable dyads from the Family and Community Health Study. Health outcomes included both self-reported chronic illness and a messenger RNA index of accelerated aging. The actor-partner interdependence model with structural equation methods was used to test the hypothesis. RESULTS: Replicating prior research, childhood adversity was associated with more chronic illness and an accelerated speed of aging. Further, participants' health in adulthood was affected by both own and partner experiences of childhood adversity. There were no gender differences. CONCLUSION: Our findings replicate and extend prior research on the long-term impact of exposure to childhood adversity, suggesting that adverse childhood experiences are also harmful to romantic partners. Further studies are required to examine potential mechanisms. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Incarceration exposure and epigenetic aging in neighborhood context.

OBJECTIVE: Research has implicated incarceration exposure as a social determinant of health, with recent work suggesting incarceration may trigger a stress response that accelerates physiological deterioration. The objective of the current study is to assess whether neighborhood stressors intensify the health consequences of incarceration exposure. METHODS: We test whether two neighborhood context measures - socioeconomic disadvantage and perceived crime - moderate the association between incarceration exposure and a measure of accelerated epigenetic aging based on the GrimAge index. Our sample included 408 African American young adults from the Family and Community Health study. RESULTS: Results from regression analyses with inverse probability of treatment weights suggest that incarceration exposure and neighborhood disadvantage are independently associated with accelerated biological aging. The results also show that the impact of incarceration exposure on accelerated aging is amplified for individuals in neighborhoods with higher levels of perceived crime. CONCLUSIONS: These findings indicate that the neighborhood contexts where formerly incarcerated individuals return have a substantial impact on their pace of biological aging. Policies aimed at reducing ambient stressors after release may promote healthy aging among formerly incarcerated African American adults.

Shifts in lifestyle and socioeconomic circumstances predict change-for better or worse-in speed of epigenetic aging: A study of middle-aged black women.

BACKGROUND: While numerous studies have documented the power of new generation epigenetic clocks to predict morbidity and mortality, research regarding the causes of variation in speed of epigenetic aging is in the early stages. To the extent that these epigenetic clocks are robust measures of biological aging, they should be sensitive to various nutritional, behavioral, ecological, and social factors that have been shown to affect health. OBJECTIVE: Investigate over an 11-year period the extent to which changes in socioeconomic stress and lifestyle predict changes in speed of epigenetic aging among a sample of middle-aged African American women. METHODS: Using data from the Family and Community Health Study, we investigated whether changes in socioeconomic stress, diet, smoking, exercise, alcohol consumption, and relationship status predict changes in speed of biological aging assessed with 3 s-generation epigenetic clocks: AccelGrimAge, DunedinPoAm, and AccelPhenoAge. The study was able to avoid the challenges associated with self-reports of diet and smoking by employing recently developed epigenetic measures. RESULTS: Changes in socioeconomic stress and diet were associated with changes in speed of biological aging as assessed by all three epigenetic clocks, and changes in smoking was related to changes in AccelGrimAge and DunedinPoAm. Analyses controlling for cell-type indicated that in large measure diet exerts its effect on aging through its impact on the immune system. CONCLUSIONS: These findings suggest that adoption of a healthy diet and reduction in the use of tobacco are related to a decrease in epigenetic aging, whereas increased pressure relating to income, housing and economic independence are associated with an increase in the speed of aging. These effects were especially strong for the two epigenetic clocks AccelGrimAge and DunedinPoAm. Overall, the results indicate that stress and lifestyle changes may, for better or worse, influence the "biological weathering" often experienced by middle-aged African American women.

Additive and Interactive Genetically Contextual Effects of HbA1c on cg19693031 Methylation in Type 2 Diabetes.

Type 2 diabetes mellitus (T2D) has a complex genetic and environmental architecture that underlies its development and clinical presentation. Despite the identification of well over a hundred genetic variants and CpG sites that associate with T2D, a robust biosignature that could be used to prevent or forestall clinical disease has not been developed. Based on the premise that underlying genetic variation influences DNA methylation (DNAm) independently of or in combination with environmental exposures, we assessed the ability of local and distal gene x methylation (GxMeth) interactive effects to improve cg19693031 models for predicting T2D status in an African American cohort. Using genome-wide genetic data from 506 subjects, we identified a total of 1476 GxMeth terms associated with HbA1c values. The GxMeth SNPs map to biological pathways associated with the development and complications of T2D, with genetically contextual differences in methylation observed only in diabetic subjects for two GxMeth SNPs (rs2390998 AG vs. GG, p = 4.63 × 10-11, Δß = 13%, effect size = 0.16 [95% CI = 0.05, 0.32]; rs1074390 AA vs. GG, p = 3.93 × 10-4, Δß = 9%, effect size = 0.38 [95% CI = 0.12, 0.56]. Using a repeated stratified k-fold cross-validation approach, a series of balanced random forest classifiers with random under-sampling were built to evaluate the addition of GxMeth terms to cg19693031 models to discriminate between normoglycemic controls versus T2D subjects. The results were compared to those obtained from models incorporating only the covariates (age, sex and BMI) and the addition of cg19693031. We found a post-pruned classifier incorporating 10 GxMeth SNPs and cg19693031 adjusted for covariates predicted the T2D status, with the AUC, sensitivity, specificity and precision of the positive target class being 0.76, 0.81, 0.70 and 0.63, respectively. Comparatively, the AUC, sensitivity, specificity and precision using the covariates and cg19693031 were only 0.71, 0.74, 0.67 and 0.59, respectively. Collectively, we demonstrate correcting for genetic confounding of cg19693031 improves its ability to detect type 2 diabetes. We conclude that an integrated genetic-epigenetic approach could inform personalized medicine programming for more effective prevention and treatment of T2D.

Racial discrimination and health among two generations of African American couples.

The current study extends research on the detrimental health implications of racial discrimination by examining how these implications reverberate across romantic relationships. Using two generations of different-gender romantic couples from the Family and Community Health Study, we examined how racial discrimination experienced by a romantic partner was associated with poor health among Black adults, independent of one's own level of racial discrimination. Results from the actor-partner interdependence model showed that beyond the effects of socioeconomic status, health behavior, relationship satisfaction, and own experiences of racial discrimination, a romantic partner's experiences of discrimination were associated with increased psychological distress for both the middle/older-age generation and the young-adult generation. Further, in the middle/older-age generation, partners' experiences of racial discrimination were associated with increased cardiovascular disease risk, particularly for men. These results reiterate recent findings that researchers may underestimate the impact of racial discrimination on health when we fail to consider linked lives. Further, they indicate that there may be gender and generational differences in the individual and relational implications of racial discrimination on health.

Romantic Relationship Status, Quality, and Depressive Symptoms Among Middle-Aged and Older Black Women.

OBJECTIVES: Past research has established a link between romantic relationships and depressive symptoms among adults, including those in later life. There is, however, still a lack of evidence regarding whether romantic relationship status or relationship quality is a better predictor of psychological well-being among middle-aged and older Black adult women. METHODS: The present study draws on data from the Family and Community Health Study, a multisite, longitudinal survey of health and psychosocial experiences of Black families, to examine how relationship status and quality relate to depressive symptoms among middle-aged and older Black adult women (N = 571). A series of negative binomial regression models, with 95% confidence intervals and internal moderators, were used to assess the research questions. RESULTS: Middle-aged and older Black women in married, cohabiting, and dating relationships who reported higher levels of relationship quality had a lower likelihood of depressive symptoms than those who reported lower levels of relationship quality or who did not report being in any romantic relationship when controlling for baseline depressive symptoms. The findings from our study indicate that relationship quality is a better predictor of depressive symptoms than relationship status. DISCUSSION: Our findings extend the body of literature on the impact of romantic relationships on individual well-being and provide compelling evidence that such relationships, particularly those of high quality, are significantly associated with lower depressive symptoms among middle-aged and older Black women.

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).

Neighborhood structural disadvantage and biological aging in a sample of Black middle age and young adults.

OBJECTIVES: Research on the social determinants of health has suggested that neighborhood disadvantage may undermine healthy aging and is particularly relevant for understanding health disparities. Recently, this work has examined deoxyribonucleic acid methylation (DNAm)-based measures of biological aging to understand the risk factors for morbidity and mortality. However, it is unknown whether neighborhood disadvantage is related to different indices of DNAm-based aging among Black Americans and whether such neighborhood effects vary as a function of age or gender. METHODS: Our analyses of a Black American sample included 448 young adults and 493 middle-aged adults. We measured neighborhood disadvantage using the Area Deprivation Index at the census block group level. DNAm-based accelerated aging indices were measured using established procedures. Regressions with clustered standard errors were used for the analysis. RESULTS: Neighborhood disadvantage was independently associated with acceleration in PhenoAge, GrimAge, and DunedinPoAm, among young and middle-aged adults. Further, there was no evidence that gender conditioned the effects of neighborhood disadvantage on the aging indices. CONCLUSIONS: Regardless of age groups or gender, accelerated biological aging among Black Americans is partly rooted in differences in neighborhood disadvantage. From a policy standpoint, our findings suggest that programs that decrease neighborhood disadvantage are likely to increase healthy aging, especially among Black Americans.

Life course trajectories of chronic financial strain and acute stress reactivity: Steeling in response to recovery from strain.

The steeling hypothesis suggests experiencing moderate strain may improve an individual's ability to cope with future strain, whereas crisis theory suggests that experiencing temporary strain will reduce the effect of future strain. The current study improves on past research by utilizing data from two independent prospective panel studies (one of 553 white rural Midwesterner women and 451 men and one of 624 African American women) spanning 26 and 22 years, respectively. We utilize growth mixture modeling to identify latent groups based on trajectories of financial strain and test interactions between class membership and later acute stressful events on chronic illness and physical health using three subscales from the RAND SF-12. We find being a group that experienced a period of temporary strain weakened the effect of later acute stressors on physical health for both samples and chronic illness for the African American sample. Results support crisis theory and highlight the importance of considering chronic strain as a life course process.

Unstable Childhood, Adult Adversity, and Smoking Accelerate Biological Aging Among Middle-Age African Americans: Similar Findings for GrimAge and PoAm.

Objectives: The recent biological clocks GrimAge and PoAm are robust predictors of morbidity and mortality. Little research, however, has investigated the factors that influence their ticking speed. No study has used multivariate analyses to examine whether childhood adversity, adult hardship, lifestyle practices, or some combination of these factors best explains acceleration of these indices. Methods: Using a sample of 506 middle-age African Americans, the present study investigated the extent to which childhood instability, adult adversity, and lifestyle predict accelerated GrimAge and PoAm. Results: The two clocks were highly correlated and the pattern of findings was very similar for the two measures. Childhood instability, adult financial hardship, and smoking were significant predictors of both clocks. Discussion: The findings support a life course perspective where both the long arm of childhood as well as later life conditions influence speed of aging. Similar results across the two clocks enhance confidence in the findings.

Methylation of FKBP5 is associated with accelerated DNA methylation ageing and cardiometabolic risk: replication in young-adult and middle-aged Black Americans.

Methylation of FKBP5 is involved in the regulation of the stress response and is influenced by early stress exposure. Two CpG sites, cg20813374 and cg00130530, have been identified as potential reporters of early stress. We examined whether FKBP5 methylation was associated with accelerated DNA methylation ageing and indirectly predicted poorer cardiovascular health among both young adult and middle-aged Black Americans. Four hundred and forty-nine young adults, with a mean age of 28.67 and N = 469 middle-age parents and their current partners with a mean age of 57.21, provided self-reports, biometric assessments, and blood draws. Methylation values were obtained using the Illumina Epic Array. Cardiometabolic risk was calculated by summing the standardized log-transformed scores for the body mass index, mean arterial blood pressure, and HbA1c. We also used a more standard index of risk, the Framingham 10-year cardiometabolic risk index, as an alternative measure of cardiometabolic risk. To measure accelerated ageing, four widely used indices of accelerated, DNA methylation-based ageing were used controlling sex, age, other variation in FKBP5, and cell-type. Exposure to community danger was associated with demethylation of FKBP5. FKBP5 methylation was significantly associated with accelerated ageing for both young-adult and middle-aged samples, with significant indirect effects from FKBP5 methylation to cardiometabolic risk through accelerated ageing for both. Early exposure to danger may influence FKBP5 methylation. In turn, FKBP5 methylation may help explain intrinsic accelerated ageing and elevated cardiometabolic risk in adulthood for Black Americans.

The Impact of Harsh Parenting on the Development of Obesity in Adulthood: An Examination of Epigenetic/Gene Expression Mediators Among African American Youth.

Objective: We examined the association of prospectively assessed harsh parenting during adolescence with body mass index (BMI) in young adulthood among African American youth. We also assessed the role of methylation of obesity-related genes and gene expression markers of obesity as mediators of this association, providing a pathway for the biological embedding of early harsh parenting and its long-term impact on young adult health. Methods: Hypotheses were tested with a sample of 362 African American youth for whom harsh parenting was assessed at ages 10-15, BMI was assessed at age 10 and 29, and both DNA methylation (DNAm) and gene expression of obesity genes were assessed at age 29. Mediational analyses were conducted using bootstrap methods to generate confidence intervals. Results: Controlling for genetic risk for obesity and health-related covariates, harsh parenting across childhood and adolescence was associated with change in BMI (Δ BMI) from ages 10-29. In addition, we found that the indirect effect of harsh parenting on Δ BMI was mediated through obesity-related DNAm and accounted for 45.3% of the total effect. Further, obesity-related DNAm mediated the effect of harsh parenting on gene expression of obesity-related genes (GEOG), and GEOG, in turn, mediated the impact of obesity-related DNAm on ΔBMI. This pathway accounted for 3.4% of the total effect. There were no gender differences in the magnitude of this indirect effect. Conclusions: The results suggest that alterations in methylation and gene expression mediate the impact of harsh parenting on change in obesity from childhood to young adulthood, illustrating plausible biological pathways from harsh parenting to obesity and bolstering the hypothesis that harsh parenting in childhood and adolescence can become biologically embedded and contribute to obesity.