Linked emergence of racial disparities in mental health and epigenetic biological aging across childhood and adolescence.

Marginalization due to structural racism may confer an increased risk for aging-related diseases - in part - via effects on people's mental health. Here we leverage a prospective birth cohort study to examine whether the emergence of racial disparities in mental health and DNA-methylation measures of biological aging (i.e., DunedinPACE, GrimAge Acceleration, PhenoAge Acceleration) are linked across childhood and adolescence. We further consider to what extent racial disparities are statistically accounted for by perinatal and postnatal factors in preregistered analyses of N=4,898 participants from the Future of Families & Child Wellbeing Study, of which N=2,039 had repeated saliva DNA methylation at ages 9 and 15 years. We find that racially marginalized children had higher levels of externalizing and internalizing behaviors and diverging longitudinal internalizing slopes. Black compared to White identifying children, children living in more racially segregated neighborhoods, and racially marginalized children more affected by colorism tended to have higher age-9 levels of biological aging and more biological age acceleration over adolescence. Notably, longitudinal increases in internalizing and externalizing behavior were correlated with longitudinal increases in biological aging. While racial and ethnic disparities in mental health were largely statistically accounted for by socioeconomic variables, racial differences in biological aging were often still visible beyond covariate controls. Our findings indicate that racial disparities in mental health and biological aging are linked and emerge early in life. Programs promoting racial health equity must address the psychological and physical impacts of structural racism in children. Comprehensive measures of racism are lacking in current population cohorts.

Structural racism in primary schools and changes in epigenetic age acceleration among Black and White youth.

Structural racism generates racial inequities in U.S. primary education, including segregated schools, inequitable funding and resources, racial disparities in discipline and achievement, and hostile racial climates, which are risk factors for adverse youth health and development. Black youth are disproportionately exposed to adverse school contexts that may become biologically embedded via stress-mediated epigenetic pathways. This study examined whether childhood exposure to adverse school contexts is associated with changes in epigenetic aging during adolescent development. DNA methylation-based epigenetic clocks were calculated from saliva samples at ages 9 and 15 among Black (n = 774) and White (n = 287) youth in the Future of Families and Child Wellbeing Study (2009-2015). We performed latent class analyses to identify race-specific primary school contexts using administrative data on segregation, discipline, achievement, resources, economic disadvantage, and racial harassment. We then estimated change in epigenetic age acceleration from childhood to adolescence across school typologies using GrimAge, PhenoAge, and DunedinPACE epigenetic clocks. Three distinct school contexts were identified for Black youth: segregated and highly-disadvantaged (17.0%), segregated and moderately-disadvantaged (52.1%), and integrated and moderately-disadvantaged (30.8%). Two school contexts emerged for White youth: integrated and unequal (46.5%) and predominantly White & advantaged (53.5%). At age 15, Black youth who attended segregated and highly-disadvantaged primary schools experienced increases in their speed of epigenetic aging with GrimAge and DunedinPACE. Slowed epigenetic aging with GrimAge was observed for Black youth who attended integrated and moderately-disadvantaged schools. School contexts were not associated with changes in epigenetic age acceleration for White youth. Our findings suggest that manifestations of structural racism in primary school contexts are associated with early-life epigenetic age acceleration and may forecast future health inequities.

Mother adversity and co-residence time impact mother-child similarity in genome-wide and gene-specific methylation profiles.

BACKGROUND: The effects of adverse life events on physical and psychological health, with DNA methylation (DNAm) as a critical underlying mechanism, have been extensively studied. However, the epigenetic resemblance between mother and child in the context of neglectful caregiving, and whether it may be shaped by the emotional impact of maternal stressful events and the duration of co-residence (indexed by child age), remains unknown. The present study examined mother-child similarity in methylation profiles, considering the potential effect of mother adversity, mother empathy, neglect-control group, child age (an index of years of mother-child co-residence), and mother age. Using Illumina Epic arrays, we quantified DNAm in 115 mother-child saliva samples. We obtained a methylation similarity index by computing correlation coefficients between methylation profiles within dyads, for the entire epigenome, and five specific genes related to stress and empathy: NR3C1, FKPB5, OXTR, SCL6A4, and BDNF. RESULTS: The methylation profiles of the mother-child familial pairs significantly correlated as compared to mother-child random pairs for the entire epigenome and NR3C1, FKBP5, OXTR and BDNF genes. Next, multiple linear regression models observed associations of mother adversity, child age, and neglect-control group on mother-child methylation similarity, only significant in mother-child familial pairs, after correcting for multiple comparisons. Higher mother adversity was associated with lower mother-child methylation similarity for the epigenome-wide analysis, for the BDNF gene, and in the neglect-control group for the OXTR gene. In turn, being an older child (longer co-residence) was associated with higher mother-child methylation similarity. CONCLUSIONS: Mother adversity and co-residence time are modulating factors in the intergenerational methylation process that offer a window into development-dependent adaptations that can be affected by both hereditary and environmental factors, significantly observed only in biological dyads. A twofold implication for child well-being emerges, one is positive in that children of mothers exposed to life adversity or neglect did not necessarily inherit their methylation patterns. The other is concerning due to the influence of time spent living together, which affects similarity with the mother and potentially increases the risk of inheriting an epigenetic profile associated with future dysfunctional parenting patterns. This underscores the importance of the 'the earlier, the better' recommendation by the Child Protection System, which is not always followed.

Biomarker adoption in developmental science: A data-driven modelling of trends from 90 biomarkers across 20 years.

Developmental scientists have adopted numerous biomarkers in their research to better understand the biological underpinnings of development, environmental exposures, and variation in long-term health. Yet, adoption patterns merit investigation given the substantial resources used to collect, analyse, and train to use biomarkers in research with infants and children. We document trends in use of 90 biomarkers between 2000 and 2020 from approximately 430,000 publications indexed by the Web of Science. We provide a tool for researchers to examine each of these biomarkers individually using a data-driven approach to estimate the biomarker growth trajectory based on yearly publication number, publication growth rate, number of author affiliations, National Institutes of Health dedicated funding resources, journal impact factor, and years since the first publication. Results indicate that most biomarkers fit a "learning curve" trajectory (i.e., experience rapid growth followed by a plateau), though a small subset decline in use over time.

Parent Mental Health Before and During the COVID-19 Pandemic.

Although extant cross-sectional data suggest that parents have experienced numerous challenges (e.g., homeschooling, caregiver burden) and mental health consequences during the COVID-19 pandemic, longitudinal data are needed to confirm mental health changes relative to pre-pandemic levels and identify which specific pandemic-related changes most highly predict mental health during the pandemic. In two longitudinal subsamples (N = 299 and N = 175), we assessed change in anxiety, depression, and stress before and during the pandemic and whether the accumulation of pandemic-related changes predicted observed mental health changes. On average, parents reported increased depression and anxiety, but no significant changes in reported stress. Moreover, increased interpersonal conflict, difficulty managing work and caregiving responsibilities, and increased economic challenges were the types of pandemic-related changes that most strongly predicted worse mental health, highlighting that juggling caregiving responsibilities and economic concerns, along with the pandemic's impact on interpersonal family relationships are key predictors of worsening parental mental illness symptoms.

Sensitive Periods for the Effect of Child Maltreatment on Psychopathology Symptoms in Adolescence.

Introduction: Child maltreatment is among the strongest risk factors for mental disorders. However, little is known about whether there are ages when children may be especially vulnerable to its effects. We sought to identify potential sensitive periods when exposure to the 2 most common types of maltreatment (neglect and harsh physical discipline) had a particularly detrimental effect on youth mental health. Methods: Data came from the Future of Families and Child Wellbeing Study (FFCWS), a birth cohort oversampled from "fragile families" (n = 3,474). Maltreatment was assessed at 3, 5, and 9 years of age using an adapted version of the Parent-Child Conflict Tactics Scales (CTS-PC). Using least angle regression, we examined the relationship between repeated measures of exposure to maltreatment on psychopathology symptoms at age 15 years (Child Behavior Checklist; CBCL/6-18). For comparison, we evaluated the strength of evidence to support the existence of sensitive periods in relation to an accumulation of risk model. Results: We identified sensitive periods for harsh physical discipline, whereby psychopathology symptom scores were highest among girls exposed at age 9 years (r2 = 0.67 internalizing symptoms; r2 = 1% externalizing symptoms) and among boys exposed at age 5 years (r2 = 0.41%). However, for neglect, the accumulation of risk model explained more variability in psychopathology symptoms for both boys and girls. Conclusion: Child maltreatment may have differential effects based on the child's sex, type of exposure, and the age at which it occurs. These findings provide additional evidence for clinicians assessing the benefits and drawbacks of screening efforts and point toward possible mechanisms driving increased vulnerability to psychopathology.

Salivary Epigenetic Measures of Body Mass Index and Social Determinants of Health Across Childhood and Adolescence.

Importance: Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Objective: To examine whether epigenetic measures of BMI developed in adults are valid biomarkers of childhood BMI and if they are sensitive to early life social determinants of health. Design, Setting, and Participants: This population-based study of over 3200 children and adolescents aged 8 to 18 years included data from 2 demographically diverse US pediatric cohort studies that combine longitudinal and twin study designs. Analyses were conducted from 2021 to 2022. Exposures: Socioeconomic status, marginalized groups. Main Outcome and Measure: Salivary epigenetic BMI, BMI. Analyses were conducted to validate the use of saliva epigenetic BMI as a potential biomarker of child BMI and to examine associations between epigenetic BMI and social determinants of health. Results: Salivary epigenetic BMI was calculated from 2 cohorts: (1) 1183 individuals aged 8 to 18 years (609 female [51%]; mean age, 13.4 years) from the Texas Twin Project and (2) 2020 children (1011 female [50%]) measured at 9 years of age and 15 years of age from the Future of Families and Child Well-Being Study. Salivary epigenetic BMI was associated with children's BMI (r = 0.36; 95% CI, 0.31-0.40 to r = 0.50; 95% CI, 0.42-0.59). Longitudinal analysis found that epigenetic BMI was highly stable across adolescence but remained both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic BMI captured differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (b = -0.13 to -0.15 across samples) and marginalized racial and ethnic groups (b = 0.08-0.34 across samples) had higher epigenetic BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. Socioeconomic status at birth relative to concurrent socioeconomic status best predicted epigenetic BMI in childhood and adolescence (b = -0.15; 95% CI, -0.20 to -0.09). Conclusion and Relevance: This study demonstrated that epigenetic measures of BMI calculated from pediatric saliva samples were valid biomarkers of childhood BMI and may be associated with early-life social inequalities. The findings are in line with the hypothesis that early-life conditions are especially important factors in epigenetic regulation of later-life health. Research showing that health later in life is linked to early-life conditions has important implications for the development of early-life interventions that could significantly extend healthy life span.

Systemic inflammation and biological aging in the Health and Retirement Study.

Chronic, low-level systemic inflammation associated with aging, or inflammaging, is a risk factor for several chronic diseases and mortality. Using data from the Health and Retirement Study, we generated a continuous latent variable for systemic inflammation from seven measured indicators of inflammation and examined associations with another biomarker of biological aging, DNA methylation age acceleration measured by epigenetic clocks, and 4-year mortality (N = 3,113). We found that greater systemic inflammation was positively associated with DNA methylation age acceleration for 10 of the 13 epigenetic clocks, after adjustment for sociodemographics and chronic disease risk factors. The latent variable for systemic inflammation was associated with 4-year mortality independent of DNA methylation age acceleration and was a better predictor of 4-year mortality than any of the epigenetic clocks examined, as well as mortality risk factors, including obesity and multimorbidity. Inflammaging and DNA methylation age acceleration may represent different biological processes contributing to mortality risk. Leveraging multiple measured inflammation markers to capture inflammaging is important for biology of aging research.

Sex-specific DNA methylation in saliva from the multi-ethnic Future of Families and Child Wellbeing Study.

The prevalence and severity of many diseases differs by sex, potentially due to sex-specific patterns in DNA methylation. Autosomal sex-specific differences in DNA methylation have been observed in cord blood and placental tissue but are not well studied in saliva or in diverse populations. We sought to characterize sex-specific DNA methylation on autosomal chromosomes in saliva samples from children in the Future of Families and Child Wellbeing Study, a multi-ethnic prospective birth cohort containing an oversampling of Black, Hispanic and low-income families. DNA methylation from saliva samples was analysed on 796 children (50.6% male) at both ages 9 and 15 with DNA methylation measured using the Illumina HumanMethylation 450k array. An epigenome-wide association analysis of the age 9 samples identified 8,430 sex-differentiated autosomal DNA methylation sites (P < 2.4 × 10-7), of which 76.2% had higher DNA methylation in female children. The strongest sex-difference was in the cg26921482 probe, in the AMDHD2 gene, with 30.6% higher DNA methylation in female compared to male children (P < 1 × 10-300). Treating the age 15 samples as an internal replication set, we observed highly consistent results between the ages 9 and 15 measurements, indicating stable and replicable sex-differentiation. Further, we directly compared our results to previously published DNA methylation sex differences in both cord blood and saliva and again found strong consistency. Our findings support widespread and robust sex-differential DNA methylation across age, human tissues, and populations. These findings help inform our understanding of potential biological processes contributing to sex differences in human physiology and disease.

Association between the timing of childhood adversity and epigenetic patterns across childhood and adolescence: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort.

BACKGROUND: Childhood adversity is a potent determinant of health across development and is associated with altered DNA methylation signatures, which might be more common in children exposed during sensitive periods in development. However, it remains unclear whether adversity has persistent epigenetic associations across childhood and adolescence. We aimed to examine the relationship between time-varying adversity (defined through sensitive period, accumulation of risk, and recency life course hypotheses) and genome-wide DNA methylation, measured three times from birth to adolescence, using data from a prospective, longitudinal cohort study. METHODS: We first investigated the relationship between the timing of exposure to childhood adversity between birth and 11 years and blood DNA methylation at age 15 years in the Avon Longitudinal Study of Parents and Children (ALSPAC) prospective cohort study. Our analytic sample included ALSPAC participants with DNA methylation data and complete childhood adversity data between birth and 11 years. We analysed seven types of adversity (caregiver physical or emotional abuse, sexual or physical abuse [by anyone], maternal psychopathology, one-adult households, family instability, financial hardship, and neighbourhood disadvantage) reported by mothers five to eight times between birth and 11 years. We used the structured life course modelling approach (SLCMA) to identify time-varying associations between childhood adversity and adolescent DNA methylation. Top loci were identified using an R2 threshold of 0·035 (ie, ≥3·5% of DNA methylation variance explained by adversity). We attempted to replicate these associations using data from the Raine Study and Future of Families and Child Wellbeing Study (FFCWS). We also assessed the persistence of adversity-DNA methylation associations we previously identified from age 7 blood DNA methylation into adolescence and the influence of adversity on DNA methylation trajectories from ages 0-15 years. FINDINGS: Of 13 988 children in the ALSPAC cohort, 609-665 children (311-337 [50-51%] boys and 298-332 [49-50%] girls) had complete data available for at least one of the seven childhood adversities and DNA methylation at 15 years. Exposure to adversity was associated with differences in DNA methylation at 15 years for 41 loci (R2 ≥0·035). Sensitive periods were the most often selected life course hypothesis by the SLCMA. 20 (49%) of 41 loci were associated with adversities occurring between age 3 and 5 years. Exposure to one-adult households was associated with differences in DNA methylation at 20 [49%] of 41 loci, exposure to financial hardship was associated with changes at nine (22%) loci, and physical or sexual abuse was associated with changes at four (10%) loci. We replicated the direction of associations for 18 (90%) of 20 loci associated with exposure to one-adult household using adolescent blood DNA methylation from the Raine Study and 18 (64%) of 28 loci using saliva DNA methylation from the FFCWS. The directions of effects for 11 one-adult household loci were replicated in both cohorts. Differences in DNA methylation at 15 years were not present at 7 years and differences identified at 7 years were no longer apparent by 15 years. We also identified six distinct DNA methylation trajectories from these patterns of stability and persistence. INTERPRETATION: These findings highlight the time-varying effect of childhood adversity on DNA methylation profiles across development, which might link exposure to adversity to potential adverse health outcomes in children and adolescents. If replicated, these epigenetic signatures could ultimately serve as biological indicators or early warning signs of initiated disease processes, helping identify people at greater risk for the adverse health consequences of childhood adversity. FUNDING: Canadian Institutes of Health Research, Cohort and Longitudinal Studies Enhancement Resources, EU's Horizon 2020, US National Institute of Mental Health.

Antisocial behavior is associated with reduced frontoparietal network efficiency in youth.

Youth antisocial behavior (AB) is associated with deficits in socioemotional processing, reward and threat processing and executive functioning. These deficits are thought to emerge from differences in neural structure, functioning and connectivity, particularly within the default, salience and frontoparietal networks. However, the relationship between AB and the organization of these networks remains unclear. To address this gap, the current study applied unweighted, undirected graph analyses to resting-state functional magnetic resonance imaging data in a cohort of 161 adolescents (95 female) enriched for exposure to poverty, a risk factor for AB. As prior work indicates that callous-unemotional (CU) traits may moderate the neurocognitive profile of youth AB, we examined CU traits as a moderator. Using multi-informant latent factors, AB was found to be associated with less efficient frontoparietal network topology, a network associated with executive functioning. However, this effect was limited to youth at low or mean levels of CU traits, indicating that these neural differences were specific to those high on AB but not CU traits. Neither AB, CU traits nor their interaction was significantly related to default or salience network topologies. Results suggest that AB, specifically, may be linked with shifts in the architecture of the frontoparietal network.

Early childhood household instability, adolescent structural neural network architecture, and young adulthood depression: A 21-year longitudinal study.

Unstable and unpredictable environments are linked to risk for psychopathology, but the underlying neural mechanisms that explain how instability relate to subsequent mental health concerns remain unclear. In particular, few studies have focused on the association between instability and white matter structures despite white matter playing a crucial role for neural development. In a longitudinal sample recruited from a population-based study (N = 237), household instability (residential moves, changes in household composition, caregiver transitions in the first 5 years) was examined in association with adolescent structural network organization (network integration, segregation, and robustness of white matter connectomes; Mage = 15.87) and young adulthood anxiety and depression (six years later). Results indicate that greater instability related to greater global network efficiency, and this association remained after accounting for other types of adversity (e.g., harsh parenting, neglect, food insecurity). Moreover, instability predicted increased depressive symptoms via increased network efficiency even after controlling for previous levels of symptoms. Exploratory analyses showed that structural connectivity involving the left fronto-lateral and temporal regions were most strongly related to instability. Findings suggest that structural network efficiency relating to household instability may be a neural mechanism of risk for later depression and highlight the ways in which instability modulates neural development.

Feasibility of mailed biomarker data collection among U.S. young adults: Saliva-based cotinine and self-reported nicotine use.

BACKGROUND: Nationally representative self-report studies are the standard for data on the prevalence of substance use. Newly emerging biomarker assessments can add objective measurements of exposure. However, biomarker assessment has typically depended on in-person sample collection. The current study examined whether young adults in a national sample would be willing and able to provide a saliva sample via mail, and the correspondence of cotinine in the saliva sample with self-reported vaping and smoking. METHODS: Data collection for the Monitoring the Future (MTF) Vaping Supplement was from September to November 2020. Eligible participants (N = 4358) were selected from a nationally-representative sample of US 12th-grade students in MTF in spring 2019. The MTF Vaping Supplement surveyed individuals nationally about one year after the 12th grade MTF survey (in 2020, mean age = 19.6 years; N = 1244). Survey weights accounted for design and attrition. RESULTS: Of those surveyed, 66.2% consented to provide a saliva sample and, of those, 73.8% mailed a sample. There were no significant differences in providing a saliva sample across any demographic characteristic, but those who reported nicotine use were less likely to provide a sample. Cotinine cut-off measures of > 3 ng/mL and > 10 ng/mL had good correspondence with self-reported measures. CONCLUSIONS: Results support the feasibility of collecting saliva via the mail in a national sample and the validity of data collected in this way. These findings support future research innovations to expand existing survey research protocols to include biomarker data collection in representative samples of young adults.

Why weight? Analytic approaches for large-scale population neuroscience data.

Population-based neuroimaging studies that feature complex sampling designs enable researchers to generalize their results more widely. However, several theoretical and analytical questions pose challenges to researchers interested in these data. The following is a resource for researchers interested in using population-based neuroimaging data. We provide an overview of sampling designs and describe the differences between traditional model-based analyses and survey-oriented design-based analyses. To elucidate key concepts, we leverage data from the Adolescent Brain Cognitive Development℠ Study (ABCD Study®), a population-based sample of 11,878 9-10-year-olds in the United States. Analyses revealed modest sociodemographic discrepancies between the target population of 9-10-year-olds in the U.S. and both the recruited ABCD sample and the analytic sample with usable structural and functional imaging data. In evaluating the associations between socioeconomic resources (i.e., constructs that are tightly linked to recruitment biases) and several metrics of brain development, we show that model-based approaches over-estimated the associations of household income and under-estimated the associations of caregiver education with total cortical volume and surface area. Comparable results were found in models predicting neural function during two fMRI task paradigms. We conclude with recommendations for ABCD Study® users and users of population-based neuroimaging cohorts more broadly.

Measuring the long arm of childhood in real-time: Epigenetic predictors of BMI and social determinants of health across childhood and adolescence.

Children who are socioeconomically disadvantaged are at increased risk for high body mass index (BMI) and multiple diseases in adulthood. The developmental origins of health and disease hypothesis proposes that early life conditions affect later-life health in a manner that is only partially modifiable by later-life experiences. Epigenetic mechanisms may regulate the influence of early life conditions on later life health. Recent epigenetic studies of adult blood samples have identified DNA-methylation sites associated with higher BMI and worse health (epigenetic-BMI). Here, we used longitudinal and twin study designs to examine whether epigenetic predictors of BMI developed in adults are valid biomarkers of child BMI and are sensitive to early life social determinants of health. Salivary epigenetic-BMI was calculated from two samples: (1) N=1,183 8-to-19-year-olds (609 female, mean age=13.4) from the Texas Twin Project (TTP), and (2) N=2,020 children (1,011 female) measured at 9 and 15 years from the Future of Families and Child Well-Being Study (FFCWS). We found that salivary epigenetic-BMI is robustly associated with children's BMI (r=0.36 to r=0.50). Longitudinal analysis suggested that epigenetic-BMI is highly stable across adolescence, but remains both a leading and lagging indicator of BMI change. Twin analyses showed that epigenetic-BMI captures differences in BMI between monozygotic twins. Moreover, children from more disadvantaged socioeconomic status (SES) and marginalized race/ethnic groups had higher epigenetic-BMI, even when controlling for concurrent BMI, pubertal development, and tobacco exposure. SES at birth relative to concurrent SES best predicted epigenetic-BMI in childhood and adolescence. We show for the first time that epigenetic predictors of BMI calculated from pediatric saliva samples are valid biomarkers of childhood BMI that are sensitive to social inequalities. Our findings are in line with the hypothesis that early life conditions are especially important factors in epigenetic regulation of later life health. Research showing that health later in life is linked to early life conditions have important implications for the development of early-life interventions that could significantly extend healthy life span.

Adolescent functional network connectivity prospectively predicts adult anxiety symptoms related to perceived COVID-19 economic adversity.

BACKGROUND: Stressful events, such as the COVID-19 pandemic, are major contributors to anxiety and depression, but only a subset of individuals develop psychopathology. In a population-based sample (N = 174) with a high representation of marginalized individuals, this study examined adolescent functional network connectivity as a marker of susceptibility to anxiety and depression in the context of adverse experiences. METHODS: Data-driven network-based subgroups were identified using an unsupervised community detection algorithm within functional neural connectivity. Neuroimaging data collected during emotion processing (age 15) were extracted from a priori regions of interest linked to anxiety and depression. Symptoms were self-reported at ages 15, 17, and 21 (during COVID-19). During COVID-19, participants reported on pandemic-related economic adversity. Differences across subgroup networks were first examined, then subgroup membership and subgroup-adversity interaction were tested to predict change in symptoms over time. RESULTS: Two subgroups were identified: Subgroup A, characterized by relatively greater neural network variation (i.e., heterogeneity) and density with more connections involving the amygdala, subgenual cingulate, and ventral striatum; and the more homogenous Subgroup B, with more connections involving the insula and dorsal anterior cingulate. Accounting for initial symptoms, subgroup A individuals had greater increases in symptoms across time (ß = .138, p = .042), and this result remained after adjusting for additional covariates (ß = .194, p = .023). Furthermore, there was a subgroup-adversity interaction: compared with Subgroup B, Subgroup A reported greater anxiety during the pandemic in response to reported economic adversity (ß = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (ß = .237, p = .021). CONCLUSIONS: A subgrouping algorithm identified young adults who were susceptible to adversity using their personalized functional network profiles derived from a priori brain regions. These results highlight potential prospective neural signatures involving heterogeneous emotion networks that predict individuals at the greatest risk for anxiety when experiencing adverse events.

School connectedness as a protective factor against childhood exposure to violence and social deprivation: A longitudinal study of adaptive and maladaptive outcomes.

School connectedness, a construct indexing supportive school relationships, has been posited to promote resilience to environmental adversity. Consistent with prominent calls in the field, we examined the protective nature of school connectedness against two dimensions of early adversity that index multiple levels of environmental exposure (violence exposure, social deprivation) when predicting both positive and negative outcomes in longitudinal data from 3,246 youth in the Fragile Families and Child Wellbeing Study (48% female, 49% African American). Child and adolescent school connectedness were promotive, even when accounting for the detrimental effects of early adversity. Additionally, childhood school connectedness had a protective but reactive association with social deprivation, but not violence exposure, when predicting externalizing symptoms and positive function. Specifically, school connectedness was protective against the negative effects of social deprivation, but the effect diminished as social deprivation became more extreme. These results suggest that social relationships at school may compensate for low levels of social support in the home and neighborhood. Our results highlight the important role that the school environment can play for youth who have been exposed to adversity in other areas of their lives and suggest specific groups that may especially benefit from interventions that boost school connectedness.

Antisocial behavior is associated with reduced frontoparietal activity to loss in a population-based sample of adolescents.

BACKGROUND: Adolescent antisocial behavior (AB) is a public health concern due to the high financial and social costs of AB on victims and perpetrators. Neural systems involved in reward and loss processing are thought to contribute to AB. However, investigations into these processes are limited: few have considered anticipatory and consummatory components of reward, response to loss, nor whether associations with AB may vary by level of callous-unemotional (CU) traits. METHODS: A population-based community sample of 128 predominantly low-income youth (mean age = 15.9 years; 42% male) completed a monetary incentive delay task during fMRI. A multi-informant, multi-method latent variable approach was used to test associations between AB and neural response to reward and loss anticipation and outcome and whether CU traits moderated these associations. RESULTS: AB was not associated with neural response to reward but was associated with reduced frontoparietal activity during loss outcomes. This association was moderated by CU traits such that individuals with higher levels of AB and CU traits had the largest reductions in frontoparietal activity. Co-occurring AB and CU traits were also associated with increased precuneus response during loss anticipation. CONCLUSIONS: Findings indicate that AB is associated with reduced activity in brain regions involved in cognitive control, attention, and behavior modification during negative outcomes. Moreover, these reductions are most pronounced in youth with co-occurring CU traits. These findings have implications for understanding why adolescents involved in AB continue these behaviors despite severe negative consequences (e.g. incarceration).

The shared mother-child epigenetic signature of neglect is related to maternal adverse events.

Studies of DNA methylation have revealed the biological mechanisms by which life adversity confers risk for later physical and mental health problems. What remains unknown is the "biologically embedding" of maternal adverse experiences resulting in maladaptive parenting and whether these epigenetic effects are transmitted to the next generation. This study focuses on neglectful mothering indexed by a severe disregard for the basic and psychological needs of the child. Using the Illumina Human Methylation EPIC BeadChip in saliva samples, we identified genes with differentially methylated regions (DMRs) in those mothers with (n = 51), versus those without (n = 87), neglectful behavior that present similar DMRs patterns in their children being neglected versus non-neglected (n = 40 vs. 75). Mothers reported the emotional intensity of adverse life events. After covariate adjustment and multiple testing corrections, we identified 69 DMRs in the mother epigenome and 42 DMRs in the child epigenome that were simultaneously above the α = 0.01 threshold. The common set of nine DMRs contained genes related to childhood adversity, neonatal and infant diabetes, child neurobehavioral development and other health problems such as obesity, hypertension, cancer, posttraumatic stress, and the Alzheimer's disease; four of the genes were associated with maternal life adversity. Identifying a shared epigenetic signature of neglect linked to maternal life adversity is an essential step in breaking the intergenerational transmission of one of the most common forms of childhood maltreatment.

Polymethylation scores for prenatal maternal smoke exposure persist until age 15 and are detected in saliva in the Fragile Families and Child Wellbeing cohort.

Prenatal maternal smoking is associated with low birthweight, neurological disorders, and asthma in exposed children. DNA methylation signatures can function as biomarkers of prenatal smoke exposure. However, the robustness of DNA methylation signatures across child ages, genetic ancestry groups, or tissues is not clear. Using coefficients from a meta-analysis of prenatal smoke exposure and DNA methylation in newborn cord blood, we created polymethylation scores of saliva DNA methylation from children at ages 9 and 15 in the Fragile Families and Child Wellbeing study. In the full sample at age 9 (n = 753), prenatal smoke exposure was associated with a 0.51 (95%CI: 0.35, 0.66) standard deviation higher polymethylation score. The direction and magnitude of the association was consistent in European and African genetic ancestry samples. In the full sample at age 15 (n = 747), prenatal smoke exposure was associated with a 0.48 (95%CI: 0.32, 0.63) standard deviation higher polymethylation score, and the association was attenuated among the European and Admixed-Latin genetic ancestry samples. The polymethylation score classified prenatal smoke exposure accurately (AUC age 9 = 0.77, age 15 = 0.76). Including the polymethylation score increased the AUC of base model covariates by 5 (95% CI: (2.1, 7.2)) percentage points, while including a single candidate site in the AHRR gene did not (P-value = 0.19). Polymethylation scores for prenatal smoking were portable across genetic ancestries and more accurate than an individual DNA methylation site. Polymethylation scores from saliva samples could serve as robust and practical biomarkers of prenatal smoke exposure.